@article{oura_young_keene_robertson_jennings_thrall_2015, title={A VALENTINE-SHAPED CARDIAC SILHOUETTE IN FELINE THORACIC RADIOGRAPHS IS PRIMARILY DUE TO LEFT ATRIAL ENLARGEMENT}, volume={56}, ISSN={["1740-8261"]}, DOI={10.1111/vru.12221}, abstractNote={Conflicting information has been published regarding the cause of a valentine-shaped cardiac silhouette in dorsoventral or ventrodorsal thoracic radiographs in cats. The purpose of this retrospective, cross-sectional study was to test the hypothesis that the valentine shape is primarily due to left atrial enlargement. Images for cats with a radiographic valentine-shaped cardiac silhouette and full echocardiography examination were retrieved and independently reviewed. A subjective scoring system was used to record severity of radiographic valentine shape. Subjective radiographic evidence of left atrial enlargement in a radiographic lateral projection and a final diagnosis based on medical records were also recorded. A total of 81 cats met inclusion criteria. There was a strong positive correlation (P < 0.001) between echocardiographic left atrial size and severity of radiographic valentine shape. There was no effect of echocardiographic right atrial size on the severity of valentine shape, except when concurrent with severe left atrial enlargement. In this situation, right atrial enlargement increased the likelihood of observing a severe valentine shape. There was no effect of right atrial enlargement on the shape of the cardiac silhouette when left atrial enlargement was absent or only mild to moderate. There was no correlation between the category of final diagnosis of cardiac disease and the severity of valentine shape. Findings from this study supported the hypothesis that a valentine-shaped cardiac silhouette in radiographs is due primarily to left atrial enlargement in cats, with right atrial enlargement only impacting the shape if concurrent with severe left atrial enlargement.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Oura, Trisha J. and Young, Aisha N. and Keene, Bruce W. and Robertson, Ian D. and Jennings, Dennis E. and Thrall, Donald E.}, year={2015}, pages={245–250} }
 @article{specchi_pey_ledda_lustgarten_thrall_bertolini_2015, title={COMPUTED TOMOGRAPHIC AND ULTRASONOGRAPHIC CHARACTERISTICS OF CAVERNOUS TRANSFORMATION OF THE OBSTRUCTED PORTAL VEIN IN SMALL ANIMALS}, volume={56}, ISSN={["1740-8261"]}, DOI={10.1111/vru.12265}, abstractNote={In humans, the process of development of collateral vessels with hepatopetal flow around the portal vein in order to bypass an obstruction is called “cavernous transformation of the portal vein.” The purpose of this retrospective, cross-sectional, multicentric study was to describe presumed cavernous transformation of the portal vein in small animals with portal vein obstruction using ultrasound and multidetector-row computed tomography (MDCT). Databases from three different institutions were searched for patients with an imaging diagnosis of cavernous transformation of the portal vein secondary to portal vein obstruction of any cause. Images were retrieved and reanalyzed. With MDCT-angiography, two main portoportal collateral pathways were identified: short tortuous portoportal veins around/inside the thrombus and long portoportal collaterals bypassing the site of portal obstruction. Three subtypes of the long collaterals, often coexisting, were identified. Branches of the hepatic artery where involved in collateral circulation in nine cases. Concomitant acquired portosystemic shunts were identified in six patients. With ultrasound, cavernous transformation of the portal vein was suspected in three dogs and one cat based on visualization of multiple and tortuous vascular structures corresponding to periportal collaterals. In conclusion, the current study provided descriptive MDCT and ultrasonographic characteristics of presumed cavernous transformation of the portal vein in a sample of small animals. Cavernous transformation of the portal vein could occur as a single condition or could be concurrent with acquired portosystemic shunts.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Specchi, Swan and Pey, Pascaline and Ledda, Gianluca and Lustgarten, Meghann and Thrall, Donald and Bertolini, Giovanna}, year={2015}, pages={511–519} }
 @article{jones_rawlins_arauz_thrall_plessis_thrall_2015, title={What Is Your Diagnosis?}, volume={247}, ISSN={["1943-569X"]}, DOI={10.2460/javma.247.11.1237}, number={11}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Jones, Sarah A. and Rawlins, Gilda and Arauz, Maziel and Thrall, Mary-Anna and Plessis, Wencke M. and Thrall, Donald E.}, year={2015}, month={Dec}, pages={1237–1239} }
 @article{boss_muradyan_thrall_2013, title={DCE-MRI: a review and applications in veterinary oncology}, volume={11}, ISSN={["1476-5829"]}, DOI={10.1111/j.1476-5829.2011.00305.x}, abstractNote={Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is a functional imaging technique that assesses the physiology of tumour tissue by exploiting abnormal tumour microvasculature. Advances made through DCE-MRI include improvement in the diagnosis of cancer, optimization of treatment choices, assessment of treatment efficacy and non-invasive identification of prognostic information. DCE-MRI enables quantitative assessment of tissue vessel density, integrity, and permeability, and this information can be applied to study of angiogenesis, hypoxia and the evaluation of various biomarkers. Reproducibility of DCE-MRI results is important in determining the significance of observed changes in the parameters. As improvements are made towards the utility of DCE-MRI and interpreting biologic associations, the technique will be applied more frequently in the study of cancer in animals. Given the importance of tumour perfusion with respect to tumour oxygenation and drug delivery, the use of DCE-MRI is a convenient and powerful way to gain basic information about a tumour.}, number={2}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Boss, M. Keara and Muradyan, N. and Thrall, D. E.}, year={2013}, month={Jun}, pages={87–100} }
 @article{copple_robertson_thrall_samei_2013, title={EVALUATION OF TWO OBJECTIVE METHODS TO OPTIMIZE KVP AND PERSONNEL EXPOSURE USING A DIGITAL INDIRECT FLAT PANEL DETECTOR AND SIMULATED VETERINARY PATIENTS}, volume={54}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2012.01989.x}, abstractNote={It is important to optimize digital radiographic technique settings for small animal imaging in order to maximize image quality while minimizing radiation exposure to personnel. The purpose of this study was to evaluate two objective methods for determining optimal kVp values for an indirect flat panel digital detector. One method considered both image quality and personnel exposure as endpoints and one considered only image quality. Phantoms simulated veterinary patients of varying thicknesses with lesions of varying sizes. Phantoms were exposed to a range of kVp values (60, 81, 100, and 121), using different mAs settings for each phantom. Additionally, all phantoms were exposed to a standard test exposure of 100 kVp/2.5 mAs. Scattered radiation was recorded and used as a measure of personnel exposure. When personnel exposure was considered, a figure of merit was calculated as an endpoint of optimization. The optimal kVp value for each phantom was determined based on the highest signal difference-to-noise ratio with or without inclusion of the figure of merit. When personnel exposure was not considered, increasing kVp resulted in higher signal difference-to-noise ratios and personnel exposure increased when both patient thickness and kVp increased. Findings indicated that a single standard technique of 100 kVp/2.5 mAs was only optimal for most medium-sized patients. Images of thinner patients should be made with a lower kVp. Very large patients require a higher kVp than 100 regardless of the optimization method used. Personnel exposure from optimized techniques was low and not expected to exceed annual occupational dose limits.}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Copple, Christina and Robertson, Ian D. and Thrall, Donald E. and Samei, Ehsan}, year={2013}, pages={9–16} }
 @book{textbook of veterinary diagnostic radiology_2013, publisher={St. Louis: Saunders Elsevier}, year={2013} }
 @article{sunico_hamel_styner_robertson_kornegay_bettini_parks_wilber_smallwood_thrall_2012, title={TWO ANATOMIC RESOURCES OF CANINE PELVIC LIMB MUSCLES BASED ON CT AND MRI}, volume={53}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2012.01926.x}, abstractNote={Advances in magnetic resonance (MR) imaging and three-dimensional (3D) modeling software provide the tools necessary to create sophisticated, interactive anatomic resources that can assist in the interpretation of MR images of extremities, and learning the structure and function of limb musculature. Modeling provides advantages over dissection or consultation of print atlases because of the associated speed, flexibility, 3D nature, and elimination of superimposed arrows and labels. Our goals were to create a diagnostic atlas of pelvic limb muscles that will facilitate interpretation of MR images of patients with muscle injury and to create a 3D model of the canine pelvic limb musculature to facilitate anatomic learning. To create these resources, we used structural segmentation of MR images, a process that groups image pixels into anatomically meaningful regions. The Diagnostic Atlas is an interactive, multiplanar, web-based MR atlas of the canine pelvic limb musculature that was created by manually segmenting clinically analogous MR sequences. Higher resolution volumetric MR and computed tomography (CT) data were segmented into separately labeled volumes of data and then transformed into a multilayered 3D computer model. The 3D Model serves as a resource for students of gross anatomy, encouraging integrative learning with its highly interactive and selective display capabilities. For clinicians, the 3D Model also serves to bridge the gap between topographic and tomographic anatomy, displaying both formats alongside, or even superimposed over each other. Both projects are hosted on an open-access website, http://3dvetanatomy.ncsu.edu/}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Sunico, Sarena K. and Hamel, Corentin and Styner, Martin and Robertson, Ian D. and Kornegay, Joe N. and Bettini, Chris and Parks, Jerry and Wilber, Kathy and Smallwood, J. Edgar and Thrall, Donald E.}, year={2012}, pages={266–272} }
 @article{thrall_maccarini_stauffer_macfall_hauck_snyder_case_linder_lan_mccall_et al._2012, title={Thermal dose fractionation affects tumour physiological response}, volume={28}, ISSN={["0265-6736"]}, DOI={10.3109/02656736.2012.689087}, abstractNote={Purpose: It is unknown whether a thermal dose should be administered using a few large fractions with higher temperatures or a larger number of fractions with lower temperatures. To evaluate this we assessed the effect of administering the same total thermal dose, approximately 30 CEM43T90, in one versus three to four fractions per week, over 5 weeks.Materials and methods: Canine sarcomas were randomised to receive one of the hyperthermia fractionation schemes along with fractionated radiotherapy. Tumour response was based on changes in tumour volume, oxygenation, water diffusion quantified using MRI, and a panel of histological and immunohistochemical end points.Results: There was a greater reduction in tumour volume and water diffusion at the end of therapy in tumours receiving one hyperthermia fraction per week. There was a weak but significant association between improved tumour oxygenation 24 h after the first hyperthermia treatment and extent of volume reduction at the end of therapy. Finally, the direction of change of HIF-1α and CA-IX immunoreactivity after the first hyperthermia fraction was similar and there was an inverse relationship between temperature and the direction of change of CA-IX. There were no significant changes in interstitial fluid pressure, VEGF, vWF, apoptosis or necrosis as a function of treatment group or temperature.Conclusions: We did not identify an advantage to a three to four per week hyperthermia prescription, and response data pointed to a one per week prescription being superior.}, number={5}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Thrall, Donald E. and Maccarini, Paolo and Stauffer, Paul and Macfall, James and Hauck, Marlene and Snyder, Stacey and Case, Beth and Linder, Keith and Lan, Lan and Mccall, Linda and et al.}, year={2012}, pages={431–440} }
 @article{seiler_robertson_mai_widmer_suran_nemanic_lamb_lang_johnson_thrall_2012, title={USEFULNESS OF A HALF-FOURIER ACQUISITION SINGLE-SHOT TURBO SPIN-ECHO PULSE SEQUENCE IN IDENTIFYING ARACHNOID DIVERTICULA IN DOGS}, volume={53}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2011.01893.x}, abstractNote={Single-shot turbo spin-echo sequences are heavily T2-weighted sequences that are exceptionally well suited to evaluate the subarachnoid space. In the T2-weighted fast spin-echo sequences that are used routinely in spinal magnetic resonance (MR) imaging, the subarachnoid space is not well differentiated from the surrounding epidural fat, which could lead to decreased detection of lesions of the subarachnoid space such as arachnoid diverticula. Our purpose was to determine the added value of a single-shot turbo spin-echo sequence in identifying cystic lesions of the subarachnoid space in dogs. MR images of six dogs with a confirmed arachnoid diverticulum and 24 dogs with other spinal disease were included. Six observers were asked to interpret only T2-weighted images initially, and in a second session, T2-weighted and half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences. The MR images were anonymized, and no signalment, history, or clinical information was provided. Without the HASTE sequences, 25% of arachnoid diverticula were identified. Adding the HASTE sequence increased the diagnosis of arachnoid diverticulum to 52.8%. The resulting difference, after adding the HASTE sequence, of 27.8% was statistically significant (P = 0.002). No false-positive diagnoses of arachnoid diverticulum were made with either sequence. Although sensitivity in this study was likely artificially low, the significantly increased detection rate of arachnoid diverticula when using HASTE imaging indicates that this sequence is a valuable addition to MR imaging protocols for the canine spine.}, number={2}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Seiler, Gabriela S. and Robertson, Ian D. and Mai, Wilfried and Widmer, William R. and Suran, Jantra and Nemanic, Sarah and Lamb, Christopher R. and Lang, Johann and Johnson, Jeffrey L. and Thrall, Donald E.}, year={2012}, pages={157–161} }
 @article{chi_thrall_jiang_snyder_fels_landon_mccall_lan_hauck_macfall_et al._2011, title={Comparison of Genomics and Functional Imaging from Canine Sarcomas Treated with Thermoradiotherapy Predicts Therapeutic Response and Identifies Combination Therapeutics}, volume={17}, ISSN={["1557-3265"]}, DOI={10.1158/1078-0432.ccr-10-2583}, abstractNote={While hyperthermia is an effective adjuvant treatment to radiotherapy, we do not completely understand the nature of the response heterogeneity.We performed gene expression analysis of 22 spontaneous canine sarcomas before and after the first hyperthermia treatment administered as an adjuvant to radiotherapy. In parallel, diffusion-weighted MRI (DWI) was done prior to the treatment course and at the end of therapy.From the integrative analysis of gene expression and DWI, we identified significant correlation between tumor responses with genes involved in VEGF signaling, telomerase, DNA repair, and inflammation. The treatment-induced changes in gene expression identified 2 distinct tumor subtypes with significant differences in their gene expression and treatment response, as defined by changes in DWI. The 2 tumor subtypes could also be readily identified by pretreatment gene expression. The tumor subtypes, with stronger expression response and DWI increase, had higher levels of HSP70, POT1, and centrosomal proteins, and lower levels of CD31, vWF, and transferrin. Such differential gene expression between the 2 subtypes was used to interrogate connectivity map and identify linkages to an HSP90 inhibitor, geldanamycin. We further validated the ability of geldanamycin to enhance cell killing of human tumor cells with hyperthermia and radiotherapy in clonogenic assays.To our knowledge, this is one of the first successful attempts to link changes in gene expression and functional imaging to understand the response heterogeneity and identify compounds enhancing thermoradiotherapy. This study also demonstrates the value of canine tumors to provide information generalizable to human tumors.}, number={8}, journal={CLINICAL CANCER RESEARCH}, author={Chi, Jen-Tsan and Thrall, Donald E. and Jiang, Chen and Snyder, Stacey and Fels, Diane and Landon, Chelsea and McCall, Linda and Lan, Lan and Hauck, Marlene and MacFall, James R. and et al.}, year={2011}, month={Apr}, pages={2549–2560} }
 @article{seiler_robertson_mukundan_thrall_2011, title={IMAGING DIAGNOSIS-MAGNETIC RESONANCE IMAGING PULSATILITY ARTIFACT IN THE CANINE CERVICAL SPINE}, volume={52}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2010.01769.x}, abstractNote={Pulsatile venous flow in the internal vertebral venous plexus of the cervical spine can lead to vertical, linear T2-hyperintensities in the spinal cord at the cranial aspect of C3 and C4 in transverse T2-weighted images in large breed dogs that are not accompanied by ghosting. The artifact is more conspicuous in pre- and postcontrast transverse T1-weighted images and is accompanied by ghosting in that sequence, typical of a pulsatility artifact. A flow-related artifact was confirmed as the cause for this appearance by noting its absence after either exchange of phase and frequency encoding direction or by flow compensation. Care should be exercised to avoid misdiagnosing this pulsatility artifact seen in transverse T2-weighted images of the midcervical spine in large dogs as an intramedullary lesion when T1-images or phase-swap images are not available to confirm its artifactual origin.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Seiler, Gabriela S. and Robertson, Ian D. and Mukundan, Srinivasan and Thrall, Donald E.}, year={2011}, pages={313–316} }
 @article{robertson_thrall_2011, title={IMAGING DOGS WITH SUSPECTED DISC HERNIATION: PROS AND CONS OF MYELOGRAPHY, COMPUTED TOMOGRAPHY, AND MAGNETIC RESONANCE}, volume={52}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2010.01788.x}, abstractNote={Myelography, computed tomography (CT), and magnetic resonance (MR) imaging are the diagnostic modalities currently used in the evaluation of dogs with suspected disc herniation. Where high-field MR imaging is available, it is considered the optimal modality for any myelopathy in dogs, including those with disc disease. CT myelography may be the next best option, particularly in nonchondrodystrophoid dogs. In chondrodystrophoid dogs, in which extrusion of mineralized disc material is common, plain CT will enable diagnosis in most cases. Myelography is still considered adequate for diagnosis of disc herniation when MR and CT are unavailable.}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Robertson, Ian and Thrall, Donald E.}, year={2011}, pages={S81–S84} }
 @article{williams_pruitt_thrall_2010, title={CHEMOTHERAPY FOLLOWED BY ABDOMINAL CAVITY IRRADIATION FOR FELINE LYMPHOBLASTIC LYMPHOMA}, volume={51}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2010.01723.x}, abstractNote={Combination chemotherapy is standard care for feline lymphoma, although clinically relevant improvements in remission duration are unlikely to result from manipulations of chemotherapy agents alone. Lymphopoietic tissues generally are sensitive to radiation, and support for chemoradiotherapy as a treatment for lymphoma is found in both humans and dogs. The goal of this prospective pilot study was to determine the normal tissue tolerance to 15 Gy total abdomen fractionated radiation therapy following induction chemotherapy in cats with lymphoblastic lymphoma. Eight cats with lymphoblastic gastrointestinal or multicentric lymphoma confined to the abdominal cavity were treated with a 6-week combination chemotherapy protocol followed 2 weeks later by whole-abdomen radiation therapy consisting of 10 daily fractions of 1.5 Gy. Treatment was well tolerated; renal insufficiency documented in one cat at the start of radiation therapy progressed to stable chronic renal failure. One cat not in complete remission at the time of radiation therapy relapsed 2 weeks later, one cat with multicentric lymphoma relapsed with hepatic large granular lymphoma, and one cat was euthanatized 3 weeks following completion of radiation therapy for other reasons; no evidence of lymphoma or radiation toxicoses was identified on post mortem evaluation. The remaining five cats remain in remission at least 266 days after starting therapy; median remission duration has not been reached (range, > 266 to > 1332 days). Results of this study suggest that 15 Gy total abdomen fractionated radiation therapy after induction chemotherapy is tolerated satisfactorily. This protocol is suitable for further testing to quantify efficacy.}, number={6}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Williams, Laurel E. and Pruitt, Amy F. and Thrall, Donald E.}, year={2010}, pages={681–687} }
 @article{labens_schramme_robertson_thrall_redding_2010, title={CLINICAL, MAGNETIC RESONANCE, AND SONOGRAPHIC IMAGING FINDINGS IN HORSES WITH PROXIMAL PLANTAR METATARSAL PAIN}, volume={51}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2009.01614.x}, abstractNote={Sonography is commonly used for diagnosis of desmopathy of the proximal part of the suspensory ligament in horses. However, magnetic resonance (MR) imaging has been stated to be superior for detecting disease and localizing lesions. In this retrospective study of 39 horses or 46 hind limbs with lameness due to proximal plantar metatarsal pain, the clinical and diagnostic findings are discussed and sonography and MR imaging compared for examination of the proximal part of the suspensory ligament. With MR imaging interpreted as the clinical gold standard, desmopathy of the proximal part of the suspensory ligament was diagnosed in 21 hind limbs, proximal plantar metatarsal pain of unknown cause in 12, an osseous injury at the origin of the suspensory ligament in four and a condition unrelated to the suspensory ligament in nine. Based on these findings, sonography had a sensitivity of 0.77 and 0.66 and specificity of 0.33 and 0.31 for diagnosing proximal suspensory desmopathy and for accurately localizing lesions, respectively. MR imaging changes consistent with proximal suspensory desmopathy were signal hyperintensities and an increase in cross-sectional area compared with the contralateral limb. Anesthesia of the deep branch of the lateral plantar nerve is not specific neither for proximal suspensory desmopathy, as conditions unrelated to the suspensory ligament were diagnosed, nor for diagnosis of proximal plantar metatarsal pain, as conditions outside the proximal plantar metatarsal region were also diagnosed.}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Labens, Raphael and Schramme, Michael C. and Robertson, Ian D. and Thrall, Donald E. and Redding, W. Rich}, year={2010}, pages={11–18} }
 @article{gonzalez_schramme_robertson_thrall_redding_2010, title={MRI FEATURES OF METACARPO(TARSO)PHALANGEAL REGION LAMENESS IN 40 HORSES}, volume={51}, ISSN={1058-8183 1740-8261}, url={http://dx.doi.org/10.1111/j.1740-8261.2010.01676.x}, DOI={10.1111/j.1740-8261.2010.01676.x}, abstractNote={Lameness originating from the metacarpo(tarso)phalangeal (MP) joint has a significant effect on the use and athletic competitiveness of a horse. The identification of the cause of lameness originating from the MP joint can be challenging, given the limitations of radiography, ultrasonography, and nuclear scintigraphy. Our purpose was to describe the injury types and incidence in magnetic resonance imaging (MRI) studies from 40 horses with lameness attributable to the MP joint region where it was not possible to reach a clinically plausible diagnosis using other imaging modalities. Horses were examined in a 1.5 T magnet (Siemens Medical Solutions) under general anesthesia. The frequency of occurrence of MR lesions was subchondral bone injury (19), straight or oblique distal sesamoidean desmitis (13), articular cartilage injury and osteoarthritis (eight), suspensory branch desmitis (seven), osteochondral fragmentation (seven), proximal sesamoid bone injury (seven), inter-sesamoidean desmitis (four), deep digital flexor tendonitis (four), collateral desmitis (three), superficial digital flexor tendonitis (two), enostosis-like lesions of the proximal phalanx or MCIII (two), desmitis of the palmar annular ligament (one), desmitis of the proximal digital annular ligament (one), and dystrophic calcification of the lateral digital extensor tendon (one). Twenty-five horses had multiple MR abnormalities. MRI provided information that was complementary to radiography, ultrasonography, and nuclear scintigraphy and that allowed for a comprehensive evaluation of all structures in the MP joint region and a diagnosis in all 40 horses.}, number={4}, journal={Veterinary Radiology & Ultrasound}, publisher={Wiley}, author={Gonzalez, Liara M. and Schramme, Michael C. and Robertson, Ian D. and Thrall, Donald E. and Redding, Rich W.}, year={2010}, month={Apr}, pages={404–414} }
 @misc{craciunescu_thrall_vujaskovic_dewhirst_2010, title={Magnetic resonance imaging: A potential tool in assessing the addition of hyperthermia to neoadjuvant therapy in patients with locally advanced breast cancer}, volume={26}, ISSN={["1464-5157"]}, DOI={10.3109/02656736.2010.499526}, abstractNote={The poor overall survival for patients with locally advanced breast cancers has led over the past decade to the introduction of numerous neoadjuvant combined therapy regimens to down-stage the disease before surgery. At the same time, more evidence suggests the need for treatment individualisation with a wide variety of new targets for cancer therapeutics and also multi modality therapies. In this context, early determination of whether the patient will fail to respond can enable the use of alternative therapies that can be more beneficial. The purpose of this review is to examine the potential role of magnetic resonance imaging (MRI) in early prediction of treatment response and prognosis of overall survival in locally advanced breast cancer patients enrolled on multi modality therapy trials that include hyperthermia. The material is organised with a review of dynamic contrast (DCE)-MRI and diffusion weighted (DW)-MRI for characterisation of phenomenological parameters of tumour physiology and their potential role in estimating therapy response. Most of the work published in this field has focused on responses to neoadjuvant chemotherapy regimens alone, so the emphasis will be there, however the available data that involves the addition of hyperthermia to the regimen will be discussed The review will also include future directions that include the potential use of MRI imaging techniques in establishing the role of hyperthermia alone in modifying breast tumour microenvironment, together with specific challenges related to performing such studies.}, number={7}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Craciunescu, Oana I. and Thrall, Donald E. and Vujaskovic, Zeljko and Dewhirst, Mark W.}, year={2010}, pages={625–637} }
 @article{gerard_pruitt_thrall_2010, title={RADIATION THERAPY COMMUNICATION: NASAL PASSAGE AND PARANASAL SINUS LYMPHOMA IN A PONY}, volume={51}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2009.01630.x}, abstractNote={An aged pony with extensive paranasal sinus and nasal passage B-cell lymphoma was treated with palliative radiation therapy. Sixteen gray were administered in two fractions, 7 days apart. A lateral field was used for the first fraction and a dorsal field for the second. Because of tumor being present in the left frontal sinus, gross tumor was knowingly excluded from the treated volume in the lateral field. The tumor regressed within 2 months and the pony remained free of clinical disease for 2.5 years. Acute, temporary blindness developed shortly after the second radiation fraction, but a direct causal relationship with the radiation therapy was not confirmed. The only radiation side effect was leukotrichia. Palliative treatment was successful in improving and prolonging the quality of life. These results suggest that localized equine B-cell lymphoma is radiosensitive, and that palliative radiation therapy is a reasonable consideration for large tumors, even when tumor volume prevents all gross tumor from being irradiated.}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Gerard, Mathew and Pruitt, Amy and Thrall, Donald E.}, year={2010}, pages={97–101} }
 @article{dewhirst_thrall_palmer_schroeder_vujaskovic_charles_macfall_wong_2010, title={Utility of functional imaging in prediction or assessment of treatment response and prognosis following thermotherapy}, volume={26}, ISSN={["1464-5157"]}, DOI={10.3109/02656730903286214}, abstractNote={The purpose of this review is to examine the roles that functional imaging may play in prediction of treatment response and determination of overall prognosis in patients who are enrolled in thermotherapy trials, either in combination with radiotherapy, chemotherapy or both. Most of the historical work that has been done in this field has focused on magnetic resonance imaging/magnetic resonance spectroscopy (MRI/MRS) methods, so the emphasis will be there, although some discussion of the role that positron emission tomography (PET) might play will also be examined. New optical technologies also hold promise for obtaining low cost, yet valuable physiological data from optically accessible sites. The review is organised by traditional outcome parameters: local response, local control and progression-free or overall survival. Included in the review is a discussion of future directions for this type of translational work.}, number={3}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Dewhirst, Mark W. and Thrall, Donald E. and Palmer, Gregory and Schroeder, Thies and Vujaskovic, Zeljko and Charles, H. Cecil and Macfall, James and Wong, Terence}, year={2010}, pages={283–293} }
 @article{viglianti_lora-michiels_poulson_lan_yu_sanders_craciunescu_vujaskovic_thrall_macfall_et al._2009, title={Dynamic Contrast-enhanced Magnetic Resonance Imaging as a Predictor of Clinical Outcome in Canine Spontaneous Soft Tissue Sarcomas Treated with Thermoradiotherapy}, volume={15}, ISSN={["1557-3265"]}, DOI={10.1158/1078-0432.CCR-08-2222}, abstractNote={This study tests whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters obtained from canine patients with soft tissue sarcomas, treated with hyperthermia and radiotherapy, are predictive of therapeutic outcome.Thirty-seven dogs with soft tissue sarcomas had DCE-MRI done before and following the first hyperthermia. Signal enhancement for tumor and reference muscle were fitted empirically, yielding a washin/washout rate for the contrast agent and tumor area under the signal enhancement curve (AUC) calculated from 0 to 60 seconds, 90 seconds, and the time of maximal enhancement in the reference muscle. These parameters were then compared with local tumor control, metastasis-free survival, and overall survival.Pretherapy rate of contrast agent washout was positively predictive of improved overall and metastasis-free survival with hazard ratio of 0.67 (P = 0.015) and 0.68 (P = 0.012), respectively. After the first hyperthermia washin rate, AUC60, AUC90, and AUCt-max were predictive of improved overall and metastasis-free survival with hazard ratio ranging from 0.46 to 0.53 (P < 0.002) and 0.44 to 0.55 (P < 0.004), respectively. DCE-MRI parameters were compared with extracellular pH and (31)P MR spectroscopy results (previously published) in the same patients showing a correlation. This suggested that an increase in perfusion after therapy was effective in eliminating excess acid from the tumor.This study shows that DCE-MRI has utility predicting overall and metastasis-free survival in canine patients with soft tissue sarcomas. To our knowledge, this is the first time that DCE-MRI parameters are predictive of clinical outcome for soft tissue sarcomas.}, number={15}, journal={CLINICAL CANCER RESEARCH}, author={Viglianti, Benjamin L. and Lora-Michiels, Michael and Poulson, Jeanie M. and Lan, Lan and Yu, Dahio and Sanders, Linda and Craciunescu, Oana and Vujaskovic, Zeljko and Thrall, Donald E. and Macfall, James and et al.}, year={2009}, month={Aug}, pages={4993–5001} }
 @article{benoit_pruitt_thrall_2009, title={EFFECT OF WETNESS LEVEL ON THE SUITABILITY OF WET GAUZE AS A SUBSTITUTE FOR SUPERFLAB((R)) AS A BOLUS MATERIAL FOR USE WITH 6 MV PHOTONS}, volume={50}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2009.01573.x}, abstractNote={Despite the availability of commercial tissue equivalent bolus material, wet gauze has an application in radiation therapy to provide superior conformance to irregular contours. Wet gauze bolus has the potential to reduce air gaps between the bolus and surface, which could decrease surface dose if sufficiently large to disrupt electronic equilibrium. Wet gauze bolus is often fabricated and wetness judged qualitatively. We assessed the effect of specific gauze wetness levels, quantified in terms of physical density, at various field sizes with respect to their effectiveness as bolus material compared with Superflab. For large fields, > 7 x 7 cm2 in this study, wet gauze sponges with a physical density of 1.02 g/cm3 performed essentially identical to Superflab; at a smaller field size the wet gauze was slightly less effective, likely due to the heterogeneity of the gauze-water matrix. Gauze that was wetter, with a physical density of 1.2 g/cm3, or less wet, with a physical density of 0.75 g/cm3 was not as effective either due to enhanced photon absorption in the wetter sponges, or less effective establishment of electronic equilibrium in the less wet sponges. The presence of an air gap under Superflab led to reduced surface dose, especially for small fields and large air gaps. Thus, if Superflab use leads to poor contact with the skin, wet gauze having a physical density of 1.02 g/cm3 can be used as a substitute. Judging the water content of wet gauze subjectively is not acceptable as over- or under wetness can lead to decreased effectiveness of the bolus material.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Benoit, Jerome and Pruitt, Amy F. and Thrall, Donald E.}, year={2009}, pages={555–559} }
 @article{shiomitsu_johnson_malarkey_pruitt_thrall_2009, title={Expression of epidermal growth factor receptor and vascular endothelial growth factor in malignant canine epithelial nasal tumours}, volume={7}, ISSN={["1476-5829"]}, DOI={10.1111/j.1476-5829.2009.00178.x}, abstractNote={Epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) signalling pathways play a role in carcinogenesis. Inhibition of EGF receptor (EGFR) and of VEGF is effective in increasing the radiation responsiveness of neoplastic cells both in vitro and in human trials. In this study, immunohistochemical evaluation was employed to determine and characterize the potential protein expression levels and patterns of EGFR and VEGF in a variety of canine malignant epithelial nasal tumours. Of 24 malignant canine nasal tumours, 13 (54.2%) were positive for EGFR staining and 22 (91.7%) were positive for VEGF staining. The intensity and percentage of immunohistochemically positive neoplastic cells for EGFR varied. These findings indicate that EGFR and VEGF proteins were present in some malignant epithelial nasal tumours in the dogs, and therefore, it may be beneficial to treat canine patients with tumours that overexpress EGFR and VEGF with specific inhibitors in conjunction with radiation.}, number={2}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Shiomitsu, K. and Johnson, C. L. and Malarkey, D. E. and Pruitt, A. F. and Thrall, D. E.}, year={2009}, month={Jun}, pages={106–114} }
 @article{adams_kleiter_thrall_klauer_forrest_la due_havighurst_2009, title={PROGNOSTIC SIGNIFICANCE OF TUMOR HISTOLOGY AND COMPUTED TOMOGRAPHIC STAGING FOR RADIATION TREATMENT RESPONSE OF CANINE NASAL TUMORS}, volume={50}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2009.01545.x}, abstractNote={Prognostic significance of tumor histology and four computed tomography (CT) staging methods was tested retrospectively in dogs from three treatment centers that underwent intent-to-cure-radiotherapy for intranasal neoplasia. Disease-free and overall survival times were available for 94 dogs. A grouping of anaplastic, squamous cell, and undifferentiated carcinomas had a significantly shorter median disease-free survival (4.4 mo) than a grouping of all sarcomas (10.6 months). Disease-free survivals were not significantly different, when all carcinomas were compared with all sarcomas. The published original and modified WHO staging methods did not significantly relate to either survival endpoint. A modified human maxillary tumor staging system previously applied to canine nasal tumors was prognostically significant for both survival endpoints; a further modified version of that CT-based staging system resulted in improved significance for both survival endpoints. Dogs with unilateral intranasal involvement without bone destruction beyond the turbinates on CT, had longest median survival (23.4 months); CT evidence of cribriform plate involvement was associated with shortest median survival (6.7 months). Combining CT and histology statistically improved prognostic significance for both survival endpoints over the proposed CT staging method alone. Significance was lost when CT stages were collapsed to <four categories or histopathology groupings were collapsed to <three categories.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Adams, William M. and Kleiter, Miriam M. and Thrall, Donald E. and Klauer, Julia M. and Forrest, Lisa J. and La Due, Tracy A. and Havighurst, Thomas C.}, year={2009}, pages={330–335} }
 @article{arthur_kleiter_thrall_pruitt_2008, title={Characterization of normal tissue complications in 51 dogs undergoing definitive pelvic region irradiation}, volume={49}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2007.00322.x}, abstractNote={Our objective was to further characterize the late normal tissue complications developing after definitive irradiation of pelvic region tumors in dogs, and to search for prognostic factors. The medical records of dogs receiving definitive irradiation of the pelvic region between 1987 and 2005 were reviewed. The following criteria were established for inclusion: total dose > or =45 Gy, a portion of colon in the primary field, and a minimum of 6 months follow-up. Fifty-one dogs were identified. Prognostic factors evaluated included multiple descriptors of the patient, tumor and radiation treatment. One or more late complications were documented in 20 of 51 patients (39%). Complications were necrotic drainage/ulceration in the skin and subcutaneous tissues within the radiation field (n=7), chronic colitis (n=4), strictures (n=4), osteopenia (n=2), and one each rectal perforation, urinary bladder thickening, iliosacral osteosarcoma, pelvic limb edema, and perianal pain. Two prognostic factors were identified. There was an increase in complications in dogs with perineal tumors compared with other pelvic region sites (P = 0.04), and also in dogs with larger radiation fields (P = 0.04). The finding of an association of tumor site to complications may be a spurious finding and the association between field size and complications is not unexpected although absolute difference in field size between dogs with and without complications was small. There was no association between development of complications and survival. Based on the observed complication rate, consideration can be given to reducing dose per fraction in dogs receiving definitive pelvic region irradiation to <3 Gy.}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Arthur, Jennifer J. and Kleiter, Miriam M. and Thrall, Donald E. and Pruitt, Amy F.}, year={2008}, pages={85–89} }
 @article{blond_thrall_roe_chailleux_robertson_2008, title={Diagnostic accuracy of magnetic resonance imaging for meniscal tears in dogs affected with naturally occuring cranial cruciate ligament rupture}, volume={49}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2008.00401.x}, abstractNote={A stifle magnetic resonance (MR) imaging protocol was developed based on the appearance of the cruciate ligaments and menisci in normal dogs. Proton density images were subjectively considered to have the highest likelihood of detecting a meniscal lesion. Following this initial evaluation, the accuracy of high-field MR imaging to detect meniscal tears in dogs was evaluated in 11 dogs suffering from naturally occurring cranial cruciate ligament rupture. Dogs underwent MR imaging of the affected stifle before surgery. MR imaging and surgical findings were assessed independently, and then compared. Five tears of the medial meniscus were correctly diagnosed with MR imaging and 19 normal menisci were accurately characterized as such, based on MR images. In one medial meniscus, changes consistent with meniscal degeneration were seen on MR images but this was not seen at surgery. With regard to the lateral meniscus, one false positive diagnosis of a tear was made and this likely represented a normal variation. One other lateral meniscus had changes consistent with meniscal degeneration but, as with the similar lesion seen in the medial meniscus, this was not confirmed surgically. The global sensitivity of MR imaging for the diagnosis of a meniscal tear was 100% and the specificity was 94%. High-field MR imaging is a reliable method to diagnose meniscal tears preoperatively and this may be useful in selecting the surgical approach to clinically abnormal joints and may decrease the need for arthrotomy.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Blond, Laurent and Thrall, Donald E. and Roe, Simon C. and Chailleux, Nadege and Robertson, Ian D.}, year={2008}, pages={425–431} }
 @article{siddiqui_li_larue_poulson_avery_pruitt_zhang_ullrich_thrall_dewhirst_et al._2007, title={A phase I trial of hyperthermia-induced interleukin-12 gene therapy in spontaneously arising feline soft tissue sarcomas}, volume={6}, ISSN={["1535-7163"]}, DOI={10.1158/1535-7163.MCT-06-0342}, abstractNote={Abstract Interleukin-12 (IL-12), a proinflammatory cytokine, shows anticancer properties. Systemically administered IL-12 causes dose-dependent toxicity. To achieve localized intratumoral gene expression, an adenoviral gene therapy vector with IL-12 controlled by a heat-inducible promoter (heat shock promoter 70B) was developed and tested in a phase I clinical trial in cats with spontaneously arising soft tissue sarcoma. A feasibility study was done in 16 cats with soft tissue sarcoma using murine IL-12 and/or enhanced green fluorescent protein adenoviral vectors under cytomegalovirus or heat shock promoter 70 control. Subsequently, we conducted a phase I clinical trial using an adenoviral feline IL-12 construct in 13 cats with soft tissue sarcoma. The soft tissue sarcomas were irradiated (48 Gy/16 fractions) followed by intratumoral injection of adenovirus. Twenty-four hours postinjection, tumors were heated (41°C, 60 min). Tumor expression of feline IL-12 and IFN-γ was determined. Cats were monitored for systemic toxicity. For the murine IL-12 construct, an association was noted between viral dose and murine IL-12 levels within tumor, whereas serum levels were minimal. Mild toxicity was noted at 1011 plaque-forming units (pfu). With the feline IL-12 construct, high levels of feline IL-12 mRNA were detected in tumor biopsies with low or absent IFN-γ mRNA following gene therapy. Hematologic and hepatic toxicities were noted at the highest viral doses and were associated with detection of IFN-γ mRNA in tumor. It is possible to localize gene expression and limit systemic toxicity of IL-12 using the hyperthermia-induced gene therapy approach. The maximum tolerated dose of the feline IL-12 adenoviral vector was 1010 pfu/tumor as dose-limiting toxicities were noted at the 4 × 1010 pfu dose. [Mol Cancer Ther 2007;6(1):380–9]}, number={1}, journal={MOLECULAR CANCER THERAPEUTICS}, author={Siddiqui, Farzan and Li, Chuan-Yuan and LaRue, Susan M. and Poulson, Jean M. and Avery, Paul R. and Pruitt, Amy F. and Zhang, Xiuwu and Ullrich, Robert L. and Thrall, Donald E. and Dewhirst, Mark W. and et al.}, year={2007}, month={Jan}, pages={380–389} }
 @article{lyons_thrall_pruitt_2007, title={Comparison of isodose distributions in canine brain in heterogeneity-corrected versus uncorrected treatment plans using 6 MV photons}, volume={48}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2007.00245.x}, abstractNote={Magnetic resonance (MR) images may be useful for radiation planning due to greater contrast resolution. One disadvantage of MR images for radiation planning is the inability to incorporate electron density information into the dose calculation algorithm. To assess the magnitude of this problem, we evaluated radiation dose distribution in canine brain by comparing computed tomography (CT)-based radiotherapy plans with and without electron density correction. Computerized radiotherapy plans were generated for 13 dogs with brain tumors using 6 MV photons. A tissue-contouring program was used to outline the gross tumor volume (GTV) and the planning target volume (PTV) for each patient. Two treatment plans were generated for each dog. First, the plan was optimized without heterogeneity correction. Then the heterogeneity correction was implemented without changing any other plan parameters. Isodose distributions and dose volume histograms (DVHs) were used to compare the two plans. The D95 (dose delivered to 95% of the volume) within the PTV was calculated for each treatment plan and differences in the D95s were compared. The mean D95s without and with heterogeneity correction were 49.1±0.7 and 48.9±1.0Gy, respectively. The absolute mean percent dose difference without and with heterogeneity correction was 1.0±0.9% (−1.3–3.2%) and was not considered to be clinically significant. We found no clinically significant difference between CT-based radiotherapy plans without and with heterogeneity correction for brain tumors in small animals, which supports the use of MR-based treatment planning for radiotherapy of small animal brain tumors.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Lyons, J. and Thrall, D. E. and Pruitt, A. F.}, year={2007}, pages={292–296} }
 @article{mackillop_thrall_ranck_linder_munana_2007, title={Imaging diagnosis-synchronous primary brain tumors in a dog}, volume={48}, ISSN={["1058-8183"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-35448932842&partnerID=MN8TOARS}, DOI={10.1111/j.1740-8261.2007.00294.x}, abstractNote={Veterinary Radiology & UltrasoundVolume 48, Issue 6 p. 550-553 IMAGING DIAGNOSIS—SYNCHRONOUS PRIMARY BRAIN TUMORS IN A DOG EDWARD MacKILLOP, EDWARD MacKILLOP Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC 277606 1428,Search for more papers by this authorDONALD E. THRALL, DONALD E. THRALL Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC 277606 1428Search for more papers by this authorROSE S. RANCK, ROSE S. RANCK Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine, Raleigh, NC 277606 1428, andSearch for more papers by this authorKEITH E. LINDER, KEITH E. LINDER Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine, Raleigh, NC 277606 1428, andSearch for more papers by this authorKAREN R. MUNANA, KAREN R. MUNANA Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC 277606 1428,Search for more papers by this author EDWARD MacKILLOP, EDWARD MacKILLOP Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC 277606 1428,Search for more papers by this authorDONALD E. THRALL, DONALD E. THRALL Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC 277606 1428Search for more papers by this authorROSE S. RANCK, ROSE S. RANCK Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine, Raleigh, NC 277606 1428, andSearch for more papers by this authorKEITH E. LINDER, KEITH E. LINDER Department of Population Health and Pathobiology, North Carolina State University College of Veterinary Medicine, Raleigh, NC 277606 1428, andSearch for more papers by this authorKAREN R. MUNANA, KAREN R. MUNANA Department of Clinical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC 277606 1428,Search for more papers by this author First published: 22 October 2007 https://doi.org/10.1111/j.1740-8261.2007.00294.xCitations: 10 Address correspondence and reprint requests to Dr. Karen Munana at the above address. E-mail: karen_munana@ncsu.edu Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume48, Issue6November–December 2007Pages 550-553 RelatedInformation}, number={6}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={MacKillop, Edward and Thrall, Donald E. and Ranck, Rose S. and Linder, Keith E. and Munana, Karen R.}, year={2007}, pages={550–553} }
 @article{kleiter_thrall_malarkey_ji_lee_chou_raleigh_2006, title={A comparison of oral and intravenous pimonidazole in canine tumors using intravenous CCI-103F as a control hypoxia marker}, volume={64}, ISSN={["1879-355X"]}, DOI={10.1016/j.ijrobp.2005.09.010}, abstractNote={Pimonidazole HCl is widely used in immunohistochemical analyses of hypoxia in normal and malignant tissues. The present study investigates oral administration as a means of minimizing invasiveness.Twelve dogs with confirmed malignancy received 0.5 g/m2 of pimonidazole HCl: 6 by mouth and 6 by i.v. infusion. All dogs received i.v. CCI-103F as a control. Plasma levels of pimonidazole, pimonidazole N-oxide, and CCI-103F were measured. Tumor biopsies were formalin fixed, paraffin embedded, sectioned, immunostained, and analyzed for pimonidazole and CCI-103F binding. pH dependence for pimonidazole and CCI-103F binding was studied in vitro.Pimonidazole and CCI-103F binding in carcinomas and sarcomas was strongly correlated for both oral and i.v. pimonidazole HCl (r2=0.97). On average, the extent of pimonidazole binding exceeded that for CCI-103F by a factor of approximately 1.2, with the factor ranging from 1.0 to 1.65. Binding of both markers was pH dependent, but pimonidazole binding was greater at all values of pH.Oral pimonidazole HCl is effective as a hypoxia marker in spontaneously arising canine tumors. Selective cellular uptake and concomitant higher levels of binding in regions of hypoxia at the high end of pH gradients might account for the greater extent of pimonidazole binding.}, number={2}, journal={INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS}, author={Kleiter, MM and Thrall, DE and Malarkey, DE and Ji, XS and Lee, DYW and Chou, SC and Raleigh, JA}, year={2006}, month={Feb}, pages={592–602} }
 @article{kleiter_yu_mohammadian_niehaus_spasojevic_sanders_viglianti_yarmolenko_hauck_petry_et al._2006, title={A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral Doxil extravasation}, volume={12}, ISSN={["1078-0432"]}, DOI={10.1158/1078-0432.CCR-06-0839}, abstractNote={Abstract Purpose: A noninvasive method to monitor intratumoral Doxil delivery in individual patients during targeted tumor therapy is important to predict treatment response. The purpose of this study was to determine if a small tracer dose of technetium-99m (99mTc)–labeled liposomes could be used to quantify the effect of local hyperthermia on intratumoral Doxil extravasation. Experimental Design: Experiments were carried out in a rat fibrosarcoma model with transplanted thigh tumors. Liposomes of approximately same size and composition as Doxil were radiolabeled using [technetium-99m (99mTc)]exametazime. Eight treatment groups received either Doxil, a tracer dose or a large dose of 99mTc-labeled liposomes, or a combination of tracer and Doxil, with or without hyperthermia. This design was chosen to assure that coadministration of both liposomal formulations did not influence their intratumoral distribution. Hyperthermia was done for 45 minutes. Scintigraphic images were obtained at 5 and 18 hours. At 18 hours, tumors were removed and gamma counts as well as doxorubicin concentrations were measured. Results: Intratumoral extravasation of the 99mTc-labeled tracer could be imaged scintigraphically under normothermic and hyperthermic conditions. The thermal enhancement ratio was slightly higher for radiolabeled liposomes than for doxorubicin concentration. However, there was a significant positive correlation of intratumoral doxorubicin concentration and intratumoral uptake of the radiolabeled tracer (expressed as percentage of the injected dose per gram of tissue). Coadministration of radiolabeled liposomes did not negatively influence the amount of drug delivered with Doxil. Conclusions: The use of a radiolabeled tracer has potential value to monitor drug delivery and estimate the effect of an intervention aimed to increase liposomal accumulation, such as local hyperthermia.}, number={22}, journal={CLINICAL CANCER RESEARCH}, author={Kleiter, Miriam M. and Yu, Daohai and Mohammadian, Lenore A. and Niehaus, Nelsen and Spasojevic, Ivan and Sanders, Linda and Viglianti, Benjamin L. and Yarmolenko, Pavel S. and Hauck, Marlene and Petry, Neil A. and et al.}, year={2006}, month={Nov}, pages={6800–6807} }
 @article{thrall_larue_pruitt_case_dewhirst_2006, title={Changes in tumour oxygenation during fractionated hyperthermia and radiation therapy in spontaneous canine sarcomas}, volume={22}, ISSN={["0265-6736"]}, DOI={10.1080/02656730600836386}, abstractNote={Tumour oxygenation was measured in seven canine soft tissue sarcomas being treated with a fractionated course of radiation and hyperthermia. Measurements obtained during treatment were compared to pre-treatment measurements. The most important finding was an increase in oxygenation in tumours with low pre-treatment oxygenation that persisted throughout treatment. This is an advantageous hyperthermia effect as it may lead to increased radiation cell killing at each fraction. In other tumours, potentially less advantageous changes in oxygenation may be hyperthermia fractionation related and this deserves further investigation.}, number={5}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Thrall, D. E. and Larue, S. M. and Pruitt, A. F. and Case, B. and DeWhirst, M. W.}, year={2006}, month={Aug}, pages={365–373} }
 @article{looper_malarkey_ruslander_proulx_thrall_2006, title={Epidermal growth factor receptor expression in feline oral squamous cell carcinomas}, volume={4}, ISSN={["1476-5829"]}, DOI={10.1111/j.1476-5810.2006.00091.x}, abstractNote={Feline oral squamous cell carcinomas (SCC) have a poor prognosis despite aggressive treatment with surgery, radiation and anticancer drugs. Overexpression of the epidermal growth factor receptor (EGFR), a membrane-bound tyrosine kinase receptor, has been found in many human epithelial neoplasms, including oral SCC. EGFR overexpression has been associated with advanced disease and a poor prognosis. The purpose of this study was to determine whether feline oral SCC express EGFR. Thirteen formalin-fixed paraffin wax-embedded biopsy samples from feline oral SCC were analysed for EGFR expression using immunohistochemistry. Nine of 13 tumours (69%) were positive for EGFR expression, suggesting that altered EGFR expression plays a role in feline oral SCC and provides a rationale for a potential clinical benefit using EGFR inhibitors in combination with conventional treatments.}, number={1}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Looper, J. S. and Malarkey, D. E. and Ruslander, D. and Proulx, D. and Thrall, D. E.}, year={2006}, month={Mar}, pages={33–40} }
 @article{lora-michiels_yu_sanders_poulson_azuma_case_vujaskovic_thrall_charles_dewhirst_2006, title={Extracellular pH and P-31 magnetic resonance spectroscopic variables are related to outcome in canine soft tissue sarcomas treated with thermoradiotherapy}, volume={12}, ISSN={["1078-0432"]}, DOI={10.1158/1078-0432.CCR-05-2669}, abstractNote={Abstract Purpose: The objective was to test whether tumor pH and 31P magnetic resonance spectroscopic end points were related to treatment outcome in pet canine patients with spontaneous soft tissue sarcomas treated with thermoradiotherapy. Experimental Design: Forty-two dogs with evaluable 31P magnetic resonance spectroscopic end points and pH data were included in this study. Tumor variables (grade and volume), extracellular pH (pHe), T2 relaxation times, intracellular pH, and selected phosphometabolite ratios were examined for correlation with clinical outcome. Results: From 39 dogs, pHe was a predictor of metastasis-free survival (MFS), with hazard ratio (HR, 0.29; P = 0.005) and overall survival (OS) with (HR, 0.36; P = 0.013). Tumor volume (>19 cm3) was related to MFS (HR, 2.14; P = 0.04), time to local failure (HR, 3.4; P = 0.025), and OS (HR, 2.27; P = 0.03). There was no association between T2 or intracellular pH and clinical outcome. Tumor grade (high versus low/intermediate) and phosphodiester/βATP ratio were identified as significant predictors for MFS, with (HR, 2.66; P = 0.009) and (HR, 0.75; P = 0.027), respectively, and as predictors of OS with (HR, 2.66; P = 0.009) and (HR, 0.76; P = 0.03), respectively. The phosphodiester/phosphocreatinine ratio predicted time to local failure (HR, 1.24; P = 0.017). Conclusions: pHe was predictive of metastasis and OS in canine spontaneous sarcomas. To our knowledge, this is the first time that pHe has been shown to be predictive of clinical outcome. The results suggest that additional studies should be considered evaluating the prognostic significance of this variable. Phospholipid resonances, related to membrane metabolism, were related to clinical outcome, confirming recent results reported in human patients with soft tissue sarcomas treated with thermoradiotherapy.}, number={19}, journal={CLINICAL CANCER RESEARCH}, author={Lora-Michiels, Michael and Yu, Daohai and Sanders, Linda and Poulson, Jean M. and Azuma, Chieko and Case, Beth and Vujaskovic, Zeljko and Thrall, Donald E. and Charles, H. Cecil and Dewhirst, Mark W.}, year={2006}, month={Oct}, pages={5733–5740} }
 @article{brofman_thrall_2006, title={Magnetic resonance imaging findings in a dog with caudal aortic thromboembolism and ischemic myopathy}, volume={47}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2006.00149.x}, abstractNote={Veterinary Radiology & UltrasoundVolume 47, Issue 4 p. 334-338 MAGNETIC RESONANCE IMAGING FINDINGS IN A DOG WITH CAUDAL AORTIC THROMBOEMBOLISM AND ISCHEMIC MYOPATHY PETER J. BROFMAN, PETER J. BROFMAN Veterinary Specialty Hospital of the Carolinas, 6405 Tryon Rd., Cary, NC 27511,Search for more papers by this authorDONALD E. THRALL, DONALD E. THRALL College of Veterinary Medicine North Carolina State University, 4700 Hillsborough, St. Raleigh, NC 27606Search for more papers by this author PETER J. BROFMAN, PETER J. BROFMAN Veterinary Specialty Hospital of the Carolinas, 6405 Tryon Rd., Cary, NC 27511,Search for more papers by this authorDONALD E. THRALL, DONALD E. THRALL College of Veterinary Medicine North Carolina State University, 4700 Hillsborough, St. Raleigh, NC 27606Search for more papers by this author First published: 22 June 2006 https://doi.org/10.1111/j.1740-8261.2006.00149.xCitations: 7 Address correspondence and reprint requests to Dr. Peter J. Brofman, at the above address. E-mail: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume47, Issue4July–August 2006Pages 334-338 RelatedInformation}, number={4}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Brofman, Peter J. and Thrall, Donald E.}, year={2006}, pages={334–338} }
 @article{hauck_larue_petros_poulson_yu_spasojevic_pruitt_klein_case_thrall_et al._2006, title={Phase I trial of doxorubicin-containing low temperature sensitive liposomes in spontaneous canine tumors}, volume={12}, ISSN={["1078-0432"]}, DOI={10.1158/1078-0432.CCR-06-0226}, abstractNote={Abstract Purpose: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. Experimental Design: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. Results: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the dose-limiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received ≥2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 ± 6.17 ng/mg tissue. Conclusion: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted.}, number={13}, journal={CLINICAL CANCER RESEARCH}, author={Hauck, Marlene L. and LaRue, Susan M. and Petros, William P. and Poulson, Jean M. and Yu, Daohai and Spasojevic, Ivan and Pruitt, Amy F. and Klein, Allison and Case, Beth and Thrall, Donald E. and et al.}, year={2006}, month={Jul}, pages={4004–4010} }
 @article{pease_sullivan_olby_galano_cerda-gonzalez_robertson_gavin_thrall_2006, title={Value of a single-shot turbo spin-echo pulse sequence for assessing the architecture of the subarachnoid space and the constitutive nature of cerebrospinal fluid}, volume={47}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2006.00136.x}, abstractNote={Three case history reports are presented to illustrate the value of the single-shot turbo spin-echo pulse sequence for assessment of the subarachnoid space. The use of the single-shot turbo spin-echo pulse sequence, which is a heavily T2-weighted sequence, allows for a rapid, noninvasive evaluation of the subarachnoid space by using the high signal from cerebrospinal fluid. This sequence can be completed in seconds rather than the several minutes required for a T2-fast spin-echo sequence. Unlike the standard T2-fast spin-echo sequence, a single-shot turbo spin-echo pulse sequence also provides qualitative information about the protein and the cellular content of the cerebrospinal fluid, such as in patients with inflammatory debris or hemorrhage in the cerebrospinal fluid. Although the resolution of the single-shot turbo spin-echo pulse sequence images is relatively poor compared with more conventional sequences, the qualitative information about the subarachnoid space and cerebrospinal fluid and the rapid acquisition time, make it a useful sequence to include in standard protocols of spinal magnetic resonance imaging.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Pease, A and Sullivan, S and Olby, N and Galano, H and Cerda-Gonzalez, S and Robertson, ID and Gavin, P and Thrall, D}, year={2006}, pages={254–259} }
 @misc{thrall_2005, title={An  interview with... Dr. Donald E. Thrall}, volume={100}, number={9}, journal={Veterinary Medicine}, author={Thrall, D. E.}, year={2005}, pages={636–638} }
 @article{dewhirst_vujaskovic_jones_thrall_2005, title={Re-setting the biologic rationale for thermal therapy}, volume={21}, ISSN={["1464-5157"]}, DOI={10.1080/02656730500271668}, abstractNote={This review takes a retrospective look at how hyperthermia biology, as defined from studies emerging from the late 1970s and into the 1980s, mis-directed the clinical field of hyperthermia, by placing too much emphasis on the necessity of killing cells with hyperthermia in order to define success. The requirement that cell killing be achieved led to sub-optimal hyperthermia fractionation goals for combinations with radiotherapy, inappropriate sequencing between radiation and hyperthermia and goals for hyperthermia equipment performance that were neither achievable nor necessary. The review then considers the importance of the biologic effects of hyperthermia that occur in the temperature range that lies between that necessary to kill substantial proportions of cells and normothermia (e.g. 39–42°C for 1 h). The effects that occur in this temperature range are compelling including—inhibition of radiation-induced damage repair, changes in perfusion, re-oxygenation, effects on macromolecular and nanoparticle delivery, induction of the heat shock response and immunological stimulation, all of which can be exploited to improve tumour response to radiation and chemotherapy. This new knowledge about the biology of hyperthermia compels one to continue to move the field forward, but with thermal goals that are eminently achievable and tolerable by patients. The fact that lower temperatures are incorporated into thermal goals does not lessen the need for non-invasive thermometry or more sophisticated hyperthermia delivery systems, however. If anything, it further compels one to move the field forward on an integrated biological, engineering and clinical level.}, number={8}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Dewhirst, MW and Vujaskovic, Z and Jones, E and Thrall, D}, year={2005}, month={Dec}, pages={779–790} }
 @article{thrall_larue_yu_samulski_sanders_case_rosner_azuma_poulson_pruitt_et al._2005, title={Thermal dose is related to duration of local control in canine sarcomas treated with thermoradiotherapy}, volume={11}, number={14}, journal={Clinical Cancer Research}, author={Thrall, D. E. and Larue, S. M. and Yu, D. H. and Samulski, T. and Sanders, L. and Case, B. and Rosner, G. and Azuma, C. and Poulson, J. and Pruitt, A. F. and et al.}, year={2005}, pages={5206–5214} }
 @article{prather_berry_thrall_2005, title={Use of radiography in combination with computed tomography for the assessment of noncardiac thoracic disease in the dog and cat}, volume={46}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2005.00023.x}, abstractNote={Computed tomography (CT) of the thorax was performed in 28 dogs and five cats and findings were compared with previous thoracic radiographs. The sample population included all animals that had thoracic radiographs and a CT study within 5 days of each other, where the complete imaging studies were available for review. Thoracic radiographs were considered indeterminate in 31 patients and CT examinations were done to acquire additional information. The presence of additional information from CT relating to presence of pathology, location of pathology, extent of pathology, and involvement of mediastinal structures was recorded. Whether there was a change in diagnosis based on the CT findings was also recorded. In only 4/33 animals (all dogs) did CT fail to provide any new information for the parameters evaluated when compared with survey thoracic radiographs. Additional information about the pathology that was present was gained by CT in 5/5 cats and 21/28 dogs. New information on compartmental location of pathology was seen in 4/5 cats and 19/28 dogs. New information on pathology extent was noted in 5/5 cats and 20/28 dogs. Additional information regarding involvement of mediastinal structures was obtained in 2/5 cats and 10/28 dogs. A change in diagnosis was made in 3/5 cats and 13/28 dogs. In conclusion, CT is a valuable tool for evaluating intrathoracic disease. CT provides additional cross-sectional anatomic information that can aid in anatomic localization and evaluation of the extent of the pathology in question.}, number={2}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Prather, AB and Berry, CR and Thrall, DE}, year={2005}, pages={114–121} }
 @article{williams_johnson_hauck_ruslander_price_thrall_2004, title={Chemotherapy followed by half-body radiation therapy for canine lymphoma}, volume={18}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2004)18<703:CFBHRT>2.0.CO;2}, abstractNote={A protocol of induction chemotherapy followed by half-body radiation therapy for treatment of lymphoma was used in 94 dogs. Seventy-three (78%) dogs achieved complete remission. Substage (P = .011) and phenotype (P = .015) were identified as predictors of complete remission rate. Of these, 52 dogs received half-body irradiation. Cranial and caudal halves received a total dose of 8.0 Gy, given in 2 fractions of 4.0 Gy on consecutive days with cobalt-60 photons and a 3-week interval between halves. Median 1st remission for these dogs was 311 days. Anemia was identified as the only predictor for length of 1st remission (P = .024). Toxicoses after half-body irradiation generally were mild and infrequent and included myelosuppression and gastrointestinal signs. Thirty-one dogs relapsed and 20 resumed treatment with induction followed by maintenance chemotherapy. Seventeen (85%) dogs achieved a 2nd complete remission. Median overall remission for all 52 dogs was 486 days. Results of this study suggest that half-body radiation therapy after induction chemotherapy is well tolerated and might increase remission duration compared with conventional protocols that use chemotherapy alone, but this increase might not be long enough to be clinically relevant or to justify application of the method described herein.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Williams, LE and Johnson, JL and Hauck, ML and Ruslander, DM and Price, GS and Thrall, DE}, year={2004}, pages={703–709} }
 @article{poulson_vujaskovic_gaskin_larue_meyer_prescott_samulski_thrall_dewhirst_2004, title={Effect of calcitonin gene related peptide vs sodium nitroprusside to increase temperature in spontaneous canine tumours during local hyperthermia}, volume={20}, ISSN={["1464-5157"]}, DOI={10.1080/0265673032000173906}, abstractNote={The objectives of this study were to compare the effects of two vasodilators, sodium nitroprusside (SNP) and calcitonin gene-related peptide (CGRP) on mean arterial pressure (MAP), heart rate (HR) and temperatures in tumour and surrounding normal tissue during local hyperthermia treatment. Eleven tumour-bearing pet dogs with spontaneous soft tissue sarcomas were given SNP intravenously during local hyperthermia. The drug infusion rate was adjusted to maintain a 20% decrease in MAP. The median (95% CI) increase in the temperature distribution descriptors T90 and T50 was 0.2°C (0.0–0.4°C, p = 0.02) and 0.4°C (0.1–0.7°C, p = 0.02), respectively, in tumour. Normal subcutaneous tissue temperatures were mildly increased but remained below the threshold for thermal injury. The effects of CGRP were investigated in six tumour-bearing dogs following a protocol similar to that used for SNP. The median (interquartile (IQ) range) decrease in mean arterial pressure was 19% (15–26%) after CGRP administration and a significant increase was seen in tumour but not normal subcutaneous tissue temperatures. The median (95% CI) increase in the temperature distribution descriptors T90 and T50 was 0.5°C (0.1–1.6°C, p = 0.03) and 0.8°C (0.1–1.6°C, p = 0.13), respectively. Administration of SNP or CGRP did not result in local or systemic toxicity in tumour-bearing dogs. However, the magnitude of increase in tumour temperatures was not sufficient to improve the likelihood of increased response rates. Therefore, there is little justification for translation of this approach to human trials using conventional local hyperthermia.}, number={5}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Poulson, JM and Vujaskovic, Z and Gaskin, AA and Larue, SM and Meyer, RE and Prescott, DM and Samulski, TV and Thrall, DE and Dewhirst, MW}, year={2004}, month={Aug}, pages={477–489} }
 @article{kleiter_malarkey_ruslander_thrall_2004, title={Expression of cyclooxygenase-2 in canine epithelial nasal tumors}, volume={45}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2004.04046.x}, abstractNote={Cyclooxygenase-2 (COX-2) is an enzyme upregulated in some human and animal tumors. Enzymatic products are associated with tumorigenic activities. Given the poor response of canine nasal tumors to radiation, we considered the possibility that some of this resistance may be associated with COX-2 expression. To test this, 21 formalin-fixed, paraffin-embedded, and archived biopsy samples from canine epithelial nasal tumors were analyzed for COX-2 expression using immunohistochemistry. The biopsies were collected from dogs prior to radiation therapy. COX-2 expression was present in 17 of 21 (81%) tumors. The expression was observed in several different tumor types, including nasal carcinomas, adenocarcinomas, and squamous cell carcinomas. Samples from five control dogs without nasal neoplasia were also analyzed for COX-2 staining. These specimens were characterized by varying degrees of lymphoplasmacytic rhinitis with scattered regions of COX-2 positive respiratory epithelial and stromal cells. Whether the intensity and distribution of COX-2 expression in nasal tumors can be used as a prognostic marker requires further investigation. A combination therapy of irradiation and a selective COX-2 inhibitor appears worthy of clinical investigation in the treatment of canine epithelial nasal tumors.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Kleiter, M and Malarkey, DE and Ruslander, DE and Thrall, DE}, year={2004}, pages={255–260} }
 @article{mcentee_page_theon_erb_thrall_2004, title={Malignant tumor formation in dogs previously irradiated for acanthomatous epulis}, volume={45}, DOI={10.1111/j.1740-8261.2001.04067.x}, number={4}, journal={Veterinary Radiology & Ultrasound}, author={McEntee, M. C. and Page, R. L. and Theon, A. and Erb, H. N. and Thrall, D. E.}, year={2004}, pages={357–361} }
 @article{pruitt_thrall_2004, title={Use of photon fields with noncoincident isocenters to improve homogeneity of dose distribution}, volume={45}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2004.04081.x}, abstractNote={To compare changes in dose distribution in irregularly shaped volumes treated using fields with noncoincident isocenters compared with fields with coincident isocenters. The hypothesis was that use of fields with noncoincident isocenters would result in improved homogeneity of dose distribution. We chose to test the hypothesis in canine nasal tumors because of the increased dorsoventral thickness of the caudal compared with the rostral nasal cavity. Computed tomography images from eight dogs with nasal tumors were selected. A tissue-contouring program was used to outline contours, including the mandible as a normal tissue structure and the planning target volume (PTV), divided into a rostral and caudal volume. A traditional computerized treatment plan consisting of two parallel-opposed fields was constructed for each dog. A second treatment plan using a third caudally located field having a different isocenter was constructed for comparison. Dose–volume histograms were generated and compared for each contoured structure in both plans. In all dogs the use of noncoincident fields resulted in increased dose to the ethmoid region through the caudal field. Minimum dose in the caudal tumor PTV increased as well. At the same time, dose delivered to the mandible, prone to develop significant side effects, was lower in all dogs with the use of noncoincident fields, as it was possible to reduce the dose delivered from the ventral field. Use of photon fields with noncoincident isocenters can improve the dose distribution in irregularly shaped volumes in comparison with fields with coincident isocenters. Improved tumor dose distribution was achieved with the addition of a smaller field having a different isocenter.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Pruitt, AF and Thrall, DE}, year={2004}, pages={471–475} }
 @article{proulx_ruslander_dodge_hauck_williams_horn_price_thrall_2003, title={A retrospective analysis of 140 dogs with oral melanoma treated with external beam radiation}, volume={44}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2003.tb00468.x}, abstractNote={Despite the early notion that canine oral malignant melanoma is radioresistant, recent data suggest that external beam radiotherapy is effective in local tumor control. However, optimal fractionation schedules have not been established. The high rate of regional and distant metastasis is another problem that has hindered long-term control. The role of chemotherapy in the management of canine oral melanoma has also not been determined. In this study, data from 140 dogs irradiated at North Carolina State University were evaluated with the following objectives: (1) to compare the efficacy of three radiation therapy protocols (36 Gy, 9 Gy × 4 fractions; 30 Gy, 10 Gy × 3 fractions; or >45 Gy, 2–4 Gy × 12–19 fractions) for the treatment of dogs with oral malignant melanoma, (2) to identify any host or tumor factors influencing prognosis, and (3) to determine the impact of systemic chemotherapy on treatment outcome. Information regarding response to therapy, disease progression, and survival were determined from the medical records or from information obtained by telephone or mail survey. Relationships between host, tumor, and treatment variables and outcome measures (response, time to first event, and survival) were evaluated using Fisher's exact test (response) and the Cox regression model (time to first event and survival). The median time to first event for the 140 dogs was 5.0 months (95% C.I., 4–6 months) and the median survival was 7.0 months (95% C.I., 6–9 months). In the univariate analysis, the following variables were associated with increased time to first event and survival: (1) rostral tumor sublocation; (2) lack of bone lysis observed on skull imaging, and (3) microscopic tumor burden. In a multivariate analysis of 111 dogs with complete data for these variables, tumor sublocation, bone lysis, and tumor volume were identified as joint predictors of time to first event (p <.001, p <.001, and p= .04, respectively) and survival (p <.001, p <.001, and p= 05, respectively). There were no differences in response, time to first event and survival between the three radiation therapy protocols used. Systemic chemotherapy had no impact on the development of metastatic disease, time to first event, or survival, although the dosages used in this study were suboptimal. External beam radiation therapy is effective in local disease control of canine oral malignant melanoma; however, the optimal fractionation scheme has yet to be determined. The high metastatic rate observed with this disease and the inefficacy of systemic chemotherapy indicate that further investigation into novel therapies is warranted.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Proulx, DR and Ruslander, DM and Dodge, RK and Hauck, ML and Williams, LE and Horn, B and Price, GS and Thrall, DE}, year={2003}, pages={352–359} }
 @article{thrall_2003, title={Images from the 2002 ACVR Certification Examination: Small animal diagnosis elective}, volume={44}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2003.tb01458.x}, abstractNote={Veterinary Radiology & UltrasoundVolume 44, Issue 1 p. 118-121 IMAGES FROM THE 2002 ACVR CERTIFICATION EXAMINATION: SMALL ANIMAL DIAGNOSIS ELECTIVE Donald E. Thrall DVM, PHD, Donald E. Thrall DVM, PHD Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh NC 27606. Reprints not available.Search for more papers by this author Donald E. Thrall DVM, PHD, Donald E. Thrall DVM, PHD Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh NC 27606. Reprints not available.Search for more papers by this author First published: 19 May 2005 https://doi.org/10.1111/j.1740-8261.2003.tb01458.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Volume44, Issue1January 2003Pages 118-121 RelatedInformation}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Thrall, DE}, year={2003}, pages={118–121} }
 @article{douglass_berry_thrall_malarkey_spaulding_2003, title={Radiographic features of aortic bulb/valve mineralization in 20 dogs}, volume={44}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2003.tb01443.x}, abstractNote={The radiographic features of aortic bulb/valve mineralization in 20 dogs were reviewed. Extent, shape, number, and location of mineralization were recorded. Five of the dogs had additional alternate imaging examinations, including bone scintigraphy, echocardiography, and thoracic computed tomography. A necropsy was done on one dog, and the area of mineralization was evaluated using routine histology. The median age was 10 (mean 9.7; SD +/- 2.7) years. There were five males, seven neutered males, one female, and seven neutered females. The breeds were: Irish setter (6); rottweiler (7); chow-chow (1); miniature dachshund (1); borzoi (1); English setter (1); English springer spaniel (1); great Dane (1); and greyhound (1). Dogs with both right and left lateral radiographs (n = 17) had mineralization visible on both views, more conspicuously on the right lateral radiograph (n = 12). Aortic bulb mineralization was identified on the ventrodorsal radiograph of only one dog. On lateral radiographs, the aortic bulb mineralization was localized within the 4th intercostal space and in the craniodorsal quadrant of the cardiac silhouette. In nine of the dogs, there were complex or multiple mineralizations and in 11 dogs, there was a single curvilinear mineral opacity oriented in a caudoventral to craniodorsal direction. In all radiographs, the mineralization was in the expected position of the aortic bulb, and echocardiography (n = 4), spiral computed tomography (n = 2), and necropsy (n = 1) confirmed that the mineralization was within the aortic bulb. Clinical pathologic data of the dogs suggested no reason for metastatic mineralization. Exact etiopathogenesis of the lesions were not determined in this study. Based on the histologic findings in one dog, the mineralization seen in the aortic root is similar to a form of dystrophic mineralization called Monckeberg's calcific arteriosclerosis in humans. No clinical signs attributable to the mineralization were observed.}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Douglass, JP and Berry, CR and Thrall, DE and Malarkey, DE and Spaulding, KA}, year={2003}, pages={20–27} }
 @article{saito_sharp_munana_troan_tokuriki_thrall_2002, title={CT findings of intracranial blastomycosis in a dog}, volume={43}, ISSN={["1058-8183"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036369393&partnerID=MN8TOARS}, DOI={10.1111/j.1740-8261.2002.tb00436.x}, abstractNote={Computed tomography (CT) findings in a dog with intracranial blastomycosis were marked periventricular contrast enhancement of the lateral ventricles, the 3rd ventricle, and the mesencephalic aqueduct. The CT appearance correlated with the histopathologic findings, where severe ependymitis was present throughout the ventricular system and there was stenosis of the mesencephalic aqueduct due to an inflammatory infiltrate. CT is therefore recommended as a screening test for intracranial blastomycosis in dogs and also as an imaging modality for follow-up evaluation after treatment. This is particularly true in dogs with systemic or ocular blastomycosis, which appear to be at higher risk of developing CNS involvement.}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Saito, M and Sharp, NJH and Munana, K and Troan, BV and Tokuriki, M and Thrall, DE}, year={2002}, pages={16–21} }
 @article{thrall_2002, title={Images from the 2001 ACVR Certifying Examination - CT/MR elective section}, volume={43}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2002.tb00447.x}, abstractNote={Veterinary Radiology & UltrasoundVolume 43, Issue 1 p. 68-70 IMAGES FROM THE 2001 ACVR CERTIFYING EXAMINATION CT/MR Elective Section DONALD E. THRALL, DONALD E. THRALL College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606. Reprints not available.Search for more papers by this author DONALD E. THRALL, DONALD E. THRALL College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606. Reprints not available.Search for more papers by this author First published: 19 May 2005 https://doi.org/10.1111/j.1740-8261.2002.tb00447.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume43, Issue1January 2002Pages 68-70 RelatedInformation}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Thrall, DE}, year={2002}, pages={68–69} }
 @article{saito_sharp_kortz_lahunta_leventer_tokuriki_thrall_2002, title={Magnetic resonance imaging features of lissencephaly in 2 Lhasa Apsos}, volume={43}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2002.tb01013.x}, abstractNote={Two Lhasa Apsos were diagnosed with lissencephaly based on MR imaging and clinical findings. Histologic confirmation of the diagnosis was obtained in one dog. The MR imaging appearance of the brain in 2 Lhasa Apsos with lissencephaly was of a smooth cerebral surface and a thick neocortex with an absence of the corona radiata. This correlated very well with the histopathologic findings in the dog. Our findings, together with the histopathologic features reported previously, are most consistent with Lhasa Apsos having the canine equivalent of human classical lissencephaly. MR is the imaging modality of choice for antemortem diagnosis of canine lissencephaly.}, number={4}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Saito, M and Sharp, NJH and Kortz, GD and Lahunta, A and Leventer, RJ and Tokuriki, M and Thrall, DE}, year={2002}, pages={331–337} }
 @article{kobayashi_hauck_dodge_page_price_williams_hardie_mathews_thrall_2002, title={Preoperative radiotherapy for vaccine associated sarcoma in 92 cats}, volume={43}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2002.tb01036.x}, abstractNote={Medical records for 92 cats with a vaccine associated sarcoma receiving preoperative irradiation, with or without chemotherapy, between December 1985 and September 1998 were reviewed. The purposes were to quantify response to treatment and to attempt identification of factors associated with favorable response. Variables evaluated for a relationship to outcome included signalment, tumor location, presence of gross vs. microscopic tumor, radiation field size, irradiation technique, type of surgical procedure, completeness of excision, and chemotherapy (none, carboplatin alone, and others). Time to first event was calculated for the first day of treatment until local tumor recurrence or metastasis, or the date of euthanasia or death. Median time to first event for all 92 cats was 584 days. Only completeness of surgical excision was related to the time to first event. Median time to first event in cats having complete surgical excision was 986 days compared to 292 days for cats with incomplete excision (P = 0.004). Cats requiring bone removal to effect tumor removal had earlier failure than cats having other types of surgery. There was not a significant relationship between administration of chemotherapy or chemotherapy type and time to first event although outcome in cats receiving carboplatin was better than all other treatment groups. Carboplatin addition to preoperative irradiation appears worthy of further study. Preoperative irradiation is an effective treatment for cats with vaccine associated sarcoma, especially if complete excision can be accomplished following irradiation.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Kobayashi, T and Hauck, ML and Dodge, R and Page, RL and Price, GS and Williams, LE and Hardie, EM and Mathews, KG and Thrall, DE}, year={2002}, pages={473–479} }
 @article{chaffin_thrall_2002, title={Results of radiation therapy in 19 dogs with cutaneous mast cell tumor and regional lymph node metastasis}, volume={43}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2002.tb01023.x}, abstractNote={The records of 19 dogs with cutaneous mast cell tumor and regional lymph node metastasis (WHO Stage 2) were reviewed to determine the efficacy of radiation therapy in this population. Dogs with grade I (n = 1), grade II (n = 16), and grade III (n = 2) cutaneous mast cell tumor were included in this study. All dogs were treated with a combination of pre-irradiation surgical cytoreduction of the primary tumor, irradiation of the primary tumor and regional lymph node, and oral prednisone. Total radiation dose to the primary tumor and regional lymph node ranged from 48 to 57 Gray (Gy). The medial iliac and hypogastric lymph nodes were irradiated prophylactically in 11 dogs with primary tumor of the pelvic limb and positive ipsilateral popliteal lymph node. Total radiation dose to these lymph nodes ranged from 48 to 57 Gy. For all radiation fields, dose per fraction was 3 Gy, and therapy was administered on a Monday through Friday schedule. Acute and late radiation side effects observed in this study were considered acceptable. The median disease-free survival was 1,240 days (95% confidence interval 256 to 2,391 days). The disease-free survival in dogs with stage 2 mast cell tumor suggests that the combination of surgery, irradiation, and prednisone for the primary tumor along with irradiation of the positive lymph node is effective.}, number={4}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Chaffin, K and Thrall, DE}, year={2002}, pages={392–395} }
 @book{thrall_2002, title={Textbook of veterinary diagnostic radiology}, ISBN={0721688209}, publisher={Philadelphia, Pa.: W.B. Saunders}, author={Thrall, D. E.}, year={2002} }
 @article{mcentee_thrall_2001, title={Computed tomographic imaging of infiltrative lipoma in 22 dogs}, volume={42}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2001.tb00928.x}, abstractNote={Twenty two dogs with an infiltrative lipoma had computed tomographic (CT) images acquired to evaluate the extent of local disease. Ten dogs had undergone at least one cytoreductive surgical procedure (range = 1-3; median = 2) prior to imaging. Twenty dogs had measurable disease on CT images; 2 dogs had diffuse disease at a previous surgical site that could not be measured. Tumor volume (n = 20) ranged from 20 to 5,632 cm3 (median = 345 cm3; mean = 996 cm3). None of the dogs had evidence of bone involvement on the CT images; 2 of the 22 dogs had tumors that did not come into direct contact with osseous structures. All dogs with measurable disease had evidence of a fat opacity mass with variable degrees of muscle infiltration. Eleven of 22 dogs were given intravenous contrast medium prior to image acquisition and there was not evidence of enhancement of the infiltrative lipoma in any dog. Based on CT images, tumors were classified as well-defined in 9 dogs, moderately well-defined in 4, not well-defined in 3 and a mix of well-defined and not well-defined in 6 dogs. Tumors tended to be less well-defined in regions where the infiltrative lipoma interdigitated with normal body fat. It appears CT imaging allows adequate discrimination of tumor with the caveat that differentiation of normal fat from infiltrative lipoma can be problematic.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={McEntee, MC and Thrall, DE}, year={2001}, pages={221–225} }
 @article{thrall_2001, title={Images from the 2001 ACVR certifying examination - CT/MR elective section}, volume={42}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2001.tb00990.x}, abstractNote={Veterinary Radiology & UltrasoundVolume 42, Issue 6 p. 594-594 IMAGES FROM THE 2001 ACVR CERTIFYING EXAMINATION CT/MR Elective Section Donald E. Thrall, Donald E. Thrall College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606. Reprints not available.Search for more papers by this author Donald E. Thrall, Donald E. Thrall College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606. Reprints not available.Search for more papers by this author First published: 19 May 2005 https://doi.org/10.1111/j.1740-8261.2001.tb00990.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume42, Issue6November 2001Pages 594-594 RelatedInformation}, number={6}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Thrall, DE}, year={2001}, pages={594–594} }
 @article{dickerson_page_ladue_hauck_thrall_stebbins_price_2001, title={Retrospective analysis of axial skeleton osteosarcoma in 22 large-breed dogs}, volume={15}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2001)015<0120:RAOASO>2.3.CO;2}, abstractNote={Medical-records of 22 large-breed dogs (>15 kg) with osteosarcoma (OSA) of the axial skeleton were reviewed to determine prevalence of metastasis and survival associated with this neoplasm. All dogs were treated with more than 1 mode of therapy including palliative radiation (n = 12), definitive radiation (n = 8), surgery (n = 7), chemotherapy (n = 12), or some combination of these therapies. Metastasis was documented in 10 of 22 dogs (46%), and the median survival for all dogs was 137 days. Primary cause of death was local tumor recurrence (54%). Breed (retriever versus purebred versus mixed-breed survival was 100, 182, and 264 days, respectively) and radiation therapy protocol (survival in dogs treated with palliative radiation therapy versus those treated with definitive radiation therapy was 79 and 265 days, respectively) were significantly related to survival (P < .05). Prevalence of metastasis and median survival for large-breed dogs with axial skeleton OSA seems to be similar to that reported for large-breed dogs with appendicular skeleton OSA. Definitive radiation therapy may have a role in the treatment of axial skeleton osteosarcoma.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Dickerson, ME and Page, RL and LaDue, TA and Hauck, ML and Thrall, DE and Stebbins, ME and Price, GS}, year={2001}, pages={120–124} }
 @article{raleigh_chou_bono_thrall_varia_2001, title={Semiquantitative immunohistochemical analysis for hypoxia in human tumors}, volume={49}, ISSN={["1879-355X"]}, DOI={10.1016/s0360-3016(00)01505-4}, abstractNote={Objective: The goal of this study was to develop a semiquantitative scoring system for measuring hypoxia in human tumors by an immunohistochemical marker approach. Methods and Materials: Eighteen patients diagnosed with squamous cell carcinoma of the uterine cervix or head and neck were infused intravenously with a solution of pimonidazole hydrochloride at a dose of 0.5 gm/m2. Twenty-four hours later, four biopsies on average from each tumor were fixed in formalin, processed into paraffin blocks, and sectioned. Tissue sections were immunostained for the presence of pimonidazole adducts. Microscopic images (×200) of immunostaining were captured and quantitated by standard image analysis. Images with known amounts of hypoxia spanning ranges of > 0% to 5%, > 5% to 15%, > 15% to 30%, and >30% were assigned scores of +1, +2, +3, and +4, respectively. Three observers then used this calibrated scoring system to analyze hypoxia in tumor sections in a blinded fashion. Results: Excellent interobserver reproducibility was obtained with the calibrated, semiquantitative, immunohistochemical assay for hypoxia in squamous cell carcinomas. Conclusion: The calibrated, semiquantitative assay shows promise as an approach to simplifying the quantitation of human tumor hypoxia by immunohistochemical techniques.}, number={2}, journal={INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS}, author={Raleigh, JA and Chou, SC and Bono, EL and Thrall, DE and Varia, MA}, year={2001}, month={Feb}, pages={569–574} }
 @article{poulson_dewhirst_gaskin_vujaskovic_samulski_prescott_meyer_page_thrall_2000, title={Acute pancreatitis associated with administration of a nitric oxide synthase inhibitor in tumor-bearing dogs}, volume={14}, number={6}, journal={In Vivo (Athens, Greece)}, author={Poulson, J. M. and Dewhirst, M. W. and Gaskin, A. A. and Vujaskovic, Z. and Samulski, T. V. and Prescott, D. M. and Meyer, R. E. and Page, R. L. and Thrall, D. E.}, year={2000}, pages={709–714} }
 @article{van camp_fisher_thrall_2000, title={Dynamic CT measurement of contrast medium washin kinetics in canine nasal tumors}, volume={41}, DOI={10.1111/j.1740-8261.2000.tb01861.x}, abstractNote={Tumor oxygenation affects the biologic behavior of a tumor and also its radiation response. Decreased tumor oxygenation has been associated with an aggressive phenotype and with decreased local tumor control following irradiation. Thus, measurement of oxygenation may be useful for pretreatment evaluation of a tumor. Many methods for assessing tumor oxygenation are available but most are invasive. There is a need for a non-invasive measure of oxygenation, or a surrogate for oxygenation. Measurement of perfusion has been suggested as a substitute for measurement of oxygenation. The use of washin kinetics of iodinated contrast medium to estimate perfusion has been shown to be related to radiation response of human carcinomas. We quantified the washin kinetics of iodinated contrast medium using dynamic CT in 9 dogs. All dogs had a malignant nasal tumor and perfusion was quantified at two sites in each tumor to evaluate intratumoral variation in perfusion. Dogs were given an intravenous bolus injection of contrast medium and arterial and tumor washin kinetics quantified using a helical CT scanner. Perfusion was estimated from these data using previously validated methods. Eight of the 9 dogs received definitive radiation therapy and perfusion was quantified a second time in these 8 dogs midway through irradiation. Pretreatment perfusion varied between dogs by a factor of 16.9. Between dog variation in perfusion was subjectively greater than within tumor variation based on comparison of two intratumoral regions. Changes in perfusion in individual dogs during irradiation were observed, but no identifiable pattern of perfusion alteration was detected. Measurement of perfusion in canine nasal tumors using dynamic CT is possible and further study of this parameter as it relates to radiation response is reasonable.}, number={5}, journal={Veterinary Radiology & Ultrasound}, author={Van Camp, S. and Fisher, P. and Thrall, D. E.}, year={2000}, pages={403–408} }
 @article{matteucci_anyarambhatla_rosner_azuma_fisher_dewhirst_needham_thrall_2000, title={Hyperthermia increases accumulation of technetium-99m-labeled liposomes in feline sarcomas}, volume={6}, number={9}, journal={Clinical Cancer Research}, author={Matteucci, M. L. and Anyarambhatla, G. and Rosner, G. and Azuma, C. and Fisher, P. E. and Dewhirst, M. W. and Needham, D. and Thrall, D. E.}, year={2000}, pages={3748–3755} }
 @article{spugnini_thrall_price_sharp_munana_page_2000, title={Primary irradiation of canine intracranial masses}, volume={41}, ISSN={["1740-8261"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034220024&partnerID=MN8TOARS}, DOI={10.1111/j.1740-8261.2000.tb02091.x}, abstractNote={Twenty-nine dogs received primary radiation therapy for intracranial lesions and clinical signs suggestive of neoplasia. Presumptive diagnosis and tumor categorization was based on computed tomographic or magnetic resonance images. Meningioma was the most likely tumor type in 22 dogs and glioma or choroid plexus tumors were tentatively identified in 4 and 3 dogs, respectively. Cobalt-60 radiation was delivered in 3 Gy fractions on a daily, Monday-through-Friday basis for a total dose of 48 Gy (16 fractions) in 28 dogs; one dog received 54 Gy. Two of 29 dogs died during treatment of signs suggestive of progressive tumor growth but were included in the overall evaluation of response to treatment. Median overall survival was 250 days (range 21-804). Mild acute radiation effects on normal tissue developed and did not influence outcome in any dog. Late radiation effects could not be evaluated in this study. No significant predictive indicators were identified from the clinical or imaging data. Radiation therapy is superior to medical treatment of brain tumors in dogs with steroids, is useful for tumors that are not currently operable and may be preferable to surgical resection in dogs if the mass appears infiltrative. However, 22/29 (76%) dogs died of recurrent progressive neuropathy suggestive of tumor regrowth or progression. Thus, alternative methods for delivery of radiation to dogs with brain tumors or novel combinations of therapy should continue to undergo evaluation.}, number={4}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Spugnini, EP and Thrall, DE and Price, GS and Sharp, NJ and Munana, K and Page, RL}, year={2000}, pages={377–380} }
 @article{mcentee_page_mauldin_thrall_2000, title={Results of irradiation of infiltrative lipoma in 13 dogs}, volume={41}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2000.tb01889.x}, abstractNote={Thirteen dogs with infiltrative lipomas were treated with cobalt 60 radiation. Four of the thirteen dogs also received either whole body (n = 2) or combination local/whole body (n = 2) hyperthermia in conjunction with radiation therapy. Cytoreductive surgery was performed prior to radiation in 10 dogs, although only 3 dogs had microscopic disease at the time of radiation therapy. Dogs received a total dose of 45.6 Gy-63 Gy in 2.5-4 Gy/fraction on either a Monday/Wednesday/Friday schedule or on a daily Monday through Friday schedule. Twelve of the 13 dogs had computed tomography (CT) images acquired prior to irradiation. Survival time was determined from the time of completion of radiation therapy. Survival ranged from 6 months to 94 months, with a median (95% confidence interval) of 40 (18.5-77) months and a mean of 46.4 months. Only one dog was euthanized due to persistent signs related to the infiltrative lipoma at 6 months after the end of radiation therapy. There was no apparent difference in response based on whether or not the dogs received hyperthermia in conjunction with irradiation, although the numbers were too small to make any significant conclusions. It appears that dogs with infiltrative lipomas can benefit from external beam irradiation alone or in combination with surgery to effect long-term local tumor control.}, number={6}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={McEntee, MC and Page, RL and Mauldin, GN and Thrall, DE}, year={2000}, pages={554–556} }
 @article{vujaskovic_poulson_gaskin_thrall_page_charles_macfall_brizel_meyer_prescott_et al._2000, title={Temperature-dependent changes in physiologic parameters of spontaneous canine soft tissue sarcomas after combined radiotherapy and hyperthermia treatment}, volume={46}, ISSN={["0360-3016"]}, DOI={10.1016/s0360-3016(99)00362-4}, abstractNote={The objectives of this study were to evaluate effects of hyperthermia on tumor oxygenation, extracellular pH (pHe), and blood flow in 13 dogs with spontaneous soft tissue sarcomas prior to and after local hyperthermia.Tumor pO2 was measured using an Eppendorf polarographic device, pHe using interstitial electrodes, and blood flow using contrast-enhanced magnetic resonance imaging (MRI).There was an overall improvement in tumor oxygenation observed as an increase in median pO2 and decrease in hypoxic fraction (% of pO2 measurements <5 mm Hg) at 24-h post hyperthermia. These changes were most pronounced when the median temperature (T50) during hyperthermia treatment was less than 44 degrees C. Tumors with T50 > 44 degrees C were characterized by a decrease in median PO2 and an increase in hypoxic fraction. Similar thermal dose-related changes were observed in tumor perfusion. Perfusion was significantly higher after hyperthermia. Increases in perfusion were most evident in tumors with T50 < 44 degrees C. With T50 > 44 degrees C, there was no change in perfusion after hyperthermia. On average, pHe values declined in all animals after hyperthermia, with the greatest reduction seen for larger T50 values.This study suggests that hyperthermia has biphasic effects on tumor physiologic parameters. Lower temperatures tend to favor improved perfusion and oxygenation, whereas higher temperatures are more likely to cause vascular damage, thus leading to greater hypoxia. While it has long been recognized that such effects occur in rodent tumors, this is the first report to tie such changes to temperatures achieved during hyperthermia in the clinical setting. Furthermore, it suggests that the thermal threshold for vascular damage is higher in spontaneous tumors than in more rapidly growing rodent tumors.}, number={1}, journal={INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS}, author={Vujaskovic, Z and Poulson, JM and Gaskin, AA and Thrall, DE and Page, RL and Charles, HC and MacFall, JR and Brizel, DM and Meyer, RE and Prescott, DM and et al.}, year={2000}, month={Jan}, pages={179–185} }
 @article{olby_muntana_sharp_thrall_2000, title={The computed tomographic appearance of acute thoracolumbar intervertebral disk herniations in dogs.}, volume={41}, ISSN={1058-8183 1740-8261}, url={http://dx.doi.org/10.1111/j.1740-8261.2000.tb01860.x}, DOI={10.1111/j.1740-8261.2000.tb01860.x}, abstractNote={The appearance of herniated intervertebral disc material in the thoracolumbar vertebral canal was evaluated in 23 dogs using computed tomography (CT). The images were then compared with the myelographic and surgical findings. The normal spinal cord, outlined by epidural fat over intervertebral disc spaces, was of intermediate attenuation on transverse CT images. Herniated disc material was identified in all animals as a heterogeneous hyperattenuating extradural mass. The attenuation of the disc material increased with the degree of mineralization. In seven dogs, the herniated material was only slightly more attenuating than the spinal cord. In these dogs, small fragments of mineralized disc material and significant hemorrhage were found in the epidural space at surgery. In dogs with a long standing history of disc herniations, disc material identified in the vertebral canal had a more hyperattenuating and homogeneous appearance than recently herniated disc material. We conclude that mineralized, herniated disc material and hemorrhage can be identified quickly and safely in dogs using CT.}, number={5}, journal={Veterinary Radiology Ultrasound}, publisher={Wiley}, author={Olby, Natasha J. and Muntana, Karen R. and Sharp, Nicholas J.H. and Thrall, Donald E.}, year={2000}, month={Sep}, pages={396–402} }
 @article{prescott_charles_poulson_page_thrall_vujaskovic_dewhirst_2000, title={The relationship between intracellular and extracellular pH in spontaneous canine tumors}, volume={6}, number={6}, journal={Clinical Cancer Research}, author={Prescott, D. M. and Charles, H. C. and Poulson, J. M. and Page, R. L. and Thrall, D. E. and Vujaskovic, Z. and Dewhirst, M. W.}, year={2000}, pages={2501–2505} }
 @misc{matteucci_thrall_2000, title={The role of liposomes in drug delivery and diagnostic imaging: A review}, volume={41}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2000.tb01462.x}, abstractNote={This manuscript is not intended as a comprehensive overview of the large filed of liposome technology and all its applications. However, our intent was to present current data, which are active, cutting-edge research. Because of their unique properties liposomes will continue to be investigated in drug delivery and imaging systems, and very likely will be incorporated into our discipline of veterinary medicine as the clinical applications of liposomes continue to expand.}, number={2}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Matteucci, ML and Thrall, DE}, year={2000}, pages={100–107} }
 @misc{thrall_2000, title={Untitled - Reply}, volume={16}, number={3}, journal={International Journal of Hyperthermia}, author={Thrall, D. E.}, year={2000}, pages={289–290} }
 @article{thrall_rosner_azuma_larue_case_samulski_dewhirst_2000, title={Using units of CEM 43 degrees C T-90, local hyperthermia thermal dose can be delivered as prescribed}, volume={16}, ISSN={["1464-5157"]}, DOI={10.1080/026567300416712}, abstractNote={A randomized study was designed in dogs with spontaneous soft tissue sarcomas to gain information about the relationship between hyperthermia dose and outcome. The study compared two levels of thermal dose applied to dogs with heatable tumours, so it was necessary to deliver either a low (2-5 CEM 43°C T90) or high (20-50 CEM 43°C T90) thermal dose as precisely as possible. It was also desirable to have similar numbers of hyperthermia treatments in each thermal dose group. Identification of heatable tumours and randomization to high or low heat dose group was done during the first hyperthermia treatment. This was readily accomplished using mapping of temperatures in thermometry catheters, manual recording of thermal data, and visual inspection of raw thermal data with subsequent adjustment of the duration of the hyperthermia treatment. An analysis of precision of thermal dose delivery was conducted after approximately 50% of projected accrual had been met in a randomized phase III assessment of thermal dose effect. Fifty-four dogs were eligible for randomization; in 48 dogs the tumour was deemed heatable according to predetermined temperature criteria applied during the first heat treatment. Twenty-four dogs were randomized to the high heat dose group, and 24 to the low heat dose group. Median (range) total thermal dose for dogs in the high dose group was 43.5 CEM 43°C T90 (16.4-66.6) compared to 3.2 CEM 43°C T90 (2.1-4.6) for dogs in the low dose group. There was no overlap of thermal doses between groups. Thus, thermal dose could be delivered accurately, being within the predetermined range in 47 of the 48 dogs. Thermal dose quantified as CEM 43°C T50, however, did overlap between groups and the clinical significance of this finding will not be known until outcome data are analysed. Most dogs in both groups received five hyperthermia treatments. Median (range) treatment duration for dogs in the high dose group was 300min (147-692) compared to 111min (51-381) for dogs in the low dose group. Relatively simple but accurate methods of delivering prescribed thermal dose as described herein will aid the translation of clinical hyperthermia from the research setting into more general practice once the characteristics of the relationship between hyperthermia dose and outcome are understood.}, number={5}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Thrall, DE and Rosner, GL and Azuma, C and Larue, SM and Case, BC and Samulski, T and Dewhirst, MW}, year={2000}, month={Sep}, pages={415–428} }
 @article{ladue_dodge_page_price_hauck_thrall_1999, title={Factors influencing survival after radiotherapy of nasal tumors in 130 dogs}, volume={40}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.1999.tb00367.x}, abstractNote={Improvements in survival of dogs with nasal tumors have been slow to develop throughout the past three decades. Despite multiple studies examining various radiation time-dose schema, the advancement of CT-based computerized treatment planning, and the evaluation of detailed staging systems, the optimal treatment regimen, and most important prognostic factors regarding survival remain unclear. In this study, data from four previous studies were combined with data from 44 additional dogs, and this population of 130 dogs was evaluated for factors which influenced survival. Twenty-one dogs were treated with orthovoltage at the University of Pennsylvania. One hundred nine dogs were treated with cobalt photons at North Carolina State University. Sixty-five of these 109 dogs had been previously described. Of the 44 dogs not previously described, 35 were treated with a shrinking field technique. Survival was determined from the medical record, or from information derived by telephone or mail survey. The univariate Cox regression model was used to examine for relationship between various patient, tumor, and treatment variables and survival. Significant relationships identified in the univariate analysis were further analyzed using the multivariate Cox regression model. Median survival of the 130 dogs was 8.9 months (95% C.I., 8-11 months). In the univariate analysis, the following variables were associated with decreased survival: 1) age >10 years old, 2) regional lymph node metastasis, 3) advanced tumor stage, 4) use of megavoltage radiation, 5) overall total dose >55 Gray, and 6) boost technique performed. In a multivariate analysis of 125 dogs with complete data for age, radiation type, and radiation dose, age (p < .001) and radiation type (p = .02) were identified as joint predictors of survival. After adjusting for age, the staging system lost prognostic significance (p = .06). In a subset of dogs that received cobalt radiation, after adjusting for age, dogs treated with a boost technique had decreased survival (p = .001). In general, local control of canine nasal tumors following aggressive radiation therapy is poor. Early diagnosis and selection of appropriate patients is warranted and palliative types of treatment should be considered in dogs with a poor chance of long term survival.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={LaDue, TA and Dodge, R and Page, RL and Price, GS and Hauck, ML and Thrall, DE}, year={1999}, pages={312–317} }
 @article{marcellin-little_deyoung_thrall_merrill_1999, title={Osteosarcoma at the site of bone infarction associated with total hip arthroplasty in a dog}, volume={28}, ISSN={["0161-3499"]}, DOI={10.1053/jvet.1999.0054}, abstractNote={Objective— To report the occurrence of medullary bone infarction in both femoral canals after bilateral total hip arthroplasty (THA) and the subsequent unilateral development of an osteosarcoma at the site of bone infarction. Study Design— Clinical report. Animal Population— An 8-month-old neutered male Samoyed dog. Methods— Serial physical and radiographic examinations performed at 1, 2, 3, and 5 years after THA. Bone biopsy specimens of the right distal femoral metaphysis were taken 5 years after THA, and a complete necropsy was performed at the time of euthanasia. Results— Bilateral medullary bone infarction was visible in the femoral canals 1 year after THA and remained visible on subsequent evaluations. An osteosarcoma developed in the right distal femoral metaphysis at the site of infarction, 5 years after THA, and was found to have metastasized widely throughout the body. Conclusion— Bone infarction may occur in the femoral canal after canine THA. Clinical Relevance— Bone infarction may be a predisposing factor for the development of osteosarcoma in the femora of dogs with THAs.}, number={1}, journal={VETERINARY SURGERY}, author={Marcellin-Little, DJ and DeYoung, DJ and Thrall, DE and Merrill, CL}, year={1999}, pages={54–60} }
 @article{ramirez_dodge_page_price_hauck_ladue_nutter_thrall_1999, title={Palliative radiotherapy of appendicular osteosarcoma in 95 dogs}, volume={40}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.1999.tb00385.x}, abstractNote={Ninety-five dogs with either a presumptive (n = 24) or biopsy confirmed diagnosis (n = 71) of osteosarcoma received palliative radiotherapy using 60Co photons. Parallel opposed beams were used with each dog receiving either 10 Gy on days 0, 7 and 21 (n = 58) or 8 Gy on days 0 and 7 (n = 37). The 8 Gy fractionation scheme was given with the intent of retreating upon relapse from pain relief. Only 9 of 37 (24%) dogs in the 8 Gy group returned for retreatment. Forty-seven of the 95 dogs (49%) received concurrent or sequential chemotherapy. Seventy of the 95 dogs (74%) experienced pain relief following treatment. In dogs experiencing pain relief the median duration of response was 73 days. Numerous clinical variables were evaluated as predictors of response. The only variable significantly related to achieving a response was the use of chemotherapy. The following variables were significantly related to the duration of response: extent of bone lysis, chemotherapy use, length of bone involved and tumor site (humerus). In a multivariate analysis (n = 73 dogs), after adjusting for chemotherapy use, extent of bone involvement (p = 0.01) and tumor site (p = 0.02) retained statistical significance, while degree of bone lysis did not (p = 0.11). No difference in response incidence or duration was found between 3 fractions of 10 Gy vs. 2 fractions of 8 Gy. Administration of a low initial dose with the intent of retreatment was not a successful strategy.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Ramirez, O and Dodge, RK and Page, RL and Price, GS and Hauck, ML and LaDue, TA and Nutter, F and Thrall, DE}, year={1999}, pages={517–522} }
 @article{matteucci_ramirez_thrall_1999, title={Radiographic diagnosis: Effect of right vs. left lateral recumbency on myelographic appearance of a lateralized extradural mass}, volume={40}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.1999.tb02123.x}, abstractNote={Veterinary Radiology & UltrasoundVolume 40, Issue 4 p. 351-352 RADIOGRAPHIC DIAGNOSIS: EFFECT OF RIGHT VS. LEFT LATERAL RECUMBENCY ON MYELOGRAPHIC APPEARANCE OF A LATERALIZED EXTRADURAL MASS Mark L. Matteucci DVM, Mark L. Matteucci DVM Department of Anatomy, Physiological Sciences and Radiology (MLM, OR, DET), College of Veterinary Medicine, North Carolina State University 4700, Hillsborough St. Raleigh, NC 27606.Search for more papers by this authorOscar III Ramirez DVM, Oscar III Ramirez DVM Department of Anatomy, Physiological Sciences and Radiology (MLM, OR, DET), College of Veterinary Medicine, North Carolina State University 4700, Hillsborough St. Raleigh, NC 27606.Search for more papers by this authorDonald E. Thrall DVM, PhD, Corresponding Author Donald E. Thrall DVM, PhD Department of Anatomy, Physiological Sciences and Radiology (MLM, OR, DET), College of Veterinary Medicine, North Carolina State University 4700, Hillsborough St. Raleigh, NC 27606.Address correspondence and reprint requests to Dr. Thrall.Search for more papers by this author Mark L. Matteucci DVM, Mark L. Matteucci DVM Department of Anatomy, Physiological Sciences and Radiology (MLM, OR, DET), College of Veterinary Medicine, North Carolina State University 4700, Hillsborough St. Raleigh, NC 27606.Search for more papers by this authorOscar III Ramirez DVM, Oscar III Ramirez DVM Department of Anatomy, Physiological Sciences and Radiology (MLM, OR, DET), College of Veterinary Medicine, North Carolina State University 4700, Hillsborough St. Raleigh, NC 27606.Search for more papers by this authorDonald E. Thrall DVM, PhD, Corresponding Author Donald E. Thrall DVM, PhD Department of Anatomy, Physiological Sciences and Radiology (MLM, OR, DET), College of Veterinary Medicine, North Carolina State University 4700, Hillsborough St. Raleigh, NC 27606.Address correspondence and reprint requests to Dr. Thrall.Search for more papers by this author First published: 23 May 2005 https://doi.org/10.1111/j.1740-8261.1999.tb02123.xCitations: 5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume40, Issue4July 1999Pages 351-352 RelatedInformation}, number={4}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Matteucci, ML and Ramirez, O and Thrall, DE}, year={1999}, pages={351–352} }
 @article{larue_fox_ogilvie_page_getzy_thrall_johnson_dewhirst_gillette_1999, title={Tumour cell kinetics as predictors of response in canine lymphoma treated with chemotherapy alone or combined with whole body hyperthermia}, volume={15}, DOI={10.1080/026567399285477}, abstractNote={Kinetic parameters including potential doubling time (Tpot), duration of S phase (Ts), labelling index (LI), and DNA index (DI) were obtained from 42 dogs with previously untreated lymphoma. Standard flow cytometric techniques using BrdUrd were employed. All dogs were treated with L-asparaginase and remission was induced in 26 dogs, which were then randomized to receive chemotherapy only (doxorubicin [DOX] alone or with lonidamine) or chemotherapy plus whole body hyperthermia (WBH). Dogs were treated every 3 weeks for up to five treatments and evaluated every 3 weeks for evidence of tumour recurrence. Within this subset of animals there was no difference in outcome based on treatment group. Median values for Tpot, Ts and LI were 3.4 days, 7.23 h and 12.49%, respectively. Dogs that had tumours with LI > or = 20% had a shorter time until recurrence than dogs with tumours characterized by LI < 20%. In dogs treated only with chemotherapy, dogs bearing tumours with longer than median Tpot and Ts values and lower than median LI had significantly longer remission duration than dogs with more rapidly proliferating tumours. Dogs treated only with chemotherapy, which had longer than median Tpot and Ts values and lower than median LI, had significantly longer remission duration than all other dogs in the study. The mechanisms in which kinetics are associated with response to chemotherapy are not clear and vary depending on tumour type and treatment regimen. More work is needed to understand factors involved in cell killing during in vivo hyperthermia.}, number={6}, journal={International Journal of Hyperthermia}, author={Larue, S. M. and Fox, M. H. and Ogilvie, G. K. and Page, R. L. and Getzy, D. M. and Thrall, D. E. and Johnson, J. L. and Dewhirst, M. W. and Gillette, E. L.}, year={1999}, pages={475–486} }
 @article{thrall_larue_powers_page_johnson_george_kornegay_mcentee_levesque_smith_et al._1999, title={Use of whole body hyperthermia as a method to heat inaccessible tumours uniformly: a phase III trial in canine brain masses}, volume={15}, number={5}, journal={International Journal of Hyperthermia}, author={Thrall, D. E. and Larue, S. M. and Powers, B. E. and Page, R. L. and Johnson, J. and George, S. L. and Kornegay, J. N. and McEntee, M. C. and Levesque, D. C. and Smith, M. and et al.}, year={1999}, pages={383–398} }
 @article{ramirez_thrall_1998, title={A review of imaging techniques for canine cauda equina syndrome}, volume={39}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.1998.tb01608.x}, abstractNote={There are many imaging modalities available for evaluating the canine lumbosacral region. These include conventional radiography, stress radiography, myelography, epidurography, transosseous and intravenous venography, discography, linear tomography, computed tomography, and magnetic resonance imaging. Myelography, epidurography and discography are commonly used, but often lack sensitivity. Myelography is of little value when evaluating the cauda equina because the dural sac is elevated from the vertebral canal floor and frequently ends before the lumbosacral junction. Epidurography will identify a ventrally located compressive lesion and discography can delineate the dorsal extent of the diseased disc; however, both are sometimes difficult to interpret. Therefore, more than one of these imaging techniques must be used in order to make a diagnosis. Computed tomography and magnetic resonance imaging have become valuable in evaluating the lumbosacral region in dogs. These modalities have proven to be both sensitive and specific for determining cauda equina compression in both humans and in dogs.}, number={4}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Ramirez, O and Thrall, DE}, year={1998}, pages={283–296} }
 @inbook{thrall_1998, title={Biologic principles of radiation therapy}, booktitle={Cancer in dogs and cats: Medical and surgical management}, publisher={Baltimore: Williams & Wilkins}, author={Thrall, D. E.}, year={1998}, pages={399–413} }
 @article{mcgaughey_gould_gelernter_1998, title={Bt resistance management}, volume={16}, ISSN={["1087-0156"]}, DOI={10.1038/nbt0298-144}, number={2}, journal={NATURE BIOTECHNOLOGY}, author={McGaughey, WH and Gould, F and Gelernter, W}, year={1998}, month={Feb}, pages={144–146} }
 @article{spann_sellon_thrall_bostian_boston_1998, title={Computed tomographic diagnosis: Use of computed tomography to distinguish a pulmonary mass from alveolar disease}, volume={39}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.1998.tb01645.x}, abstractNote={Veterinary Radiology & UltrasoundVolume 39, Issue 6 p. 532-535 COMPUTED TOMOGRAPHIC DIAGNOSIS: USE OF COMPUTED TOMOGRAPHY TO DISTINGUISH A PULMONARY MASS FROM ALVEOLAR DISEASE Dennis R. Spann DVM, Corresponding Author Dennis R. Spann DVM Department of Companion Animal and Special Species, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606Address correspondence and reprint requests to Dennis R. Spann, DVM, Veterinary Medical Teaching Hospital Department of Small Animal Medicine, University of California-Davis, Davis, CA 95616.Search for more papers by this authorRance K. Sellon DVM PHD, Rance K. Sellon DVM PHD Department of Companion Animal and Special Species, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606Search for more papers by this authorDonald E. Thrall DVM, PHD, Donald E. Thrall DVM, PHD Department of Anatomy, Physiological Sciences, and Radiology, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606Search for more papers by this authorAudrey E. Bostian DVM, Audrey E. Bostian DVM Department of Companion Animal and Special Species, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606Search for more papers by this authorGary T. Boston DVM, Gary T. Boston DVM Department of Microbiology, Pathology, and Parasitology, Countryside Pet Hospital, 508-S 10th Street NW, Conover, NC 28613Search for more papers by this author Dennis R. Spann DVM, Corresponding Author Dennis R. Spann DVM Department of Companion Animal and Special Species, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606Address correspondence and reprint requests to Dennis R. Spann, DVM, Veterinary Medical Teaching Hospital Department of Small Animal Medicine, University of California-Davis, Davis, CA 95616.Search for more papers by this authorRance K. Sellon DVM PHD, Rance K. Sellon DVM PHD Department of Companion Animal and Special Species, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606Search for more papers by this authorDonald E. Thrall DVM, PHD, Donald E. Thrall DVM, PHD Department of Anatomy, Physiological Sciences, and Radiology, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606Search for more papers by this authorAudrey E. Bostian DVM, Audrey E. Bostian DVM Department of Companion Animal and Special Species, North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606Search for more papers by this authorGary T. Boston DVM, Gary T. Boston DVM Department of Microbiology, Pathology, and Parasitology, Countryside Pet Hospital, 508-S 10th Street NW, Conover, NC 28613Search for more papers by this author First published: 23 May 2005 https://doi.org/10.1111/j.1740-8261.1998.tb01645.xCitations: 15AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCE 1 Suter PF, Carrig C, O'Brien TR, Koller D. Radiographic recognition of primary and metastatic pulmonary neoplasia of dogs and cats. J Am Vet Radiol Soc 1974; 15: 3–24. 2 Lamb CR. The canine lung. In: DE Thrall. Textbook of veterinary diagnostic radiology, 2nd ed. Philadelphia : WB Saunders, 1994: 331–346. 3 Tidwell AS. Diagnostic pulmonary imaging. Problems Vet Med 1992; 4: 239–264. 4 Postorino NC, Wheeler SL, Park RD, et al. A syndrome resembling lymphomatoid granulomatosis in a dog. J Vet Int Med 1989; 3: 15–19. 5 Berry CR, Moore PF, Thomas WP, et al. Pulmonary lymphomatoic granulomatosis in seven dogs (1976–1987). J Vet Int Med 1990; 4: 157–166. 6 Calvert CA, Mahaffey MB, Lappin MR, Farrell RL. Pulmonary and disseminated eosinophilic granulomatosis in a dog. J Am Anim Hosp Assoc 1988; 24: 311–319. 7 Walker MA. Thoracic blastomycosis: A review of its radiographic manifestation in 40 dogs. Vet Radiol 1981; 22: 22–26. 8 Hawkins EC. Transtracheal wash and bronchoalveolar lavage in the management of respiratory disease. In: RW Kirk, JD Bonagura. Current veterinary therapy XI: Small animal practice. Philadelphia , WB Saunders Co, 1992: 795–800. 9 Hawkins EC, De Nicola DB, Plier ML. Cytologic analysis of bronchoalveolar lavage fluid in the diagnosis of spontaneous respiratory tract disease in dogs: A retrospective study. J Vet Intern Med 1995; 9: 386–392. 10 Teske E, Stokhof AA, van der Ingh TSGAM, et al. Transthoracic needle aspiration biopsy of the lung in dogs with pulmonic disease. J Am Anim Hosp Assoc 1991; 27: 289–294. 11 Turrel JM, Fike JR, LeCouter RA, Higgins RJ. Computed tomographic characteristics of primary brain tumors in 50 dogs. JAVMA 1986; 188: 851–856. 12 LeCouter RA, Fike JR, Scagliotti RH, Cann CE. Computed tomography of orbital tumors in the dog. JAVMA 1982; 180: 910–913. 13 Burk RL. Computed tomographic imaging of nasal disease in 100 dogs. Vet Radiol & Ultrasound 1992; 33: 170–176. 14 Drost WT, Love NE, Berry CR. Comparison of radiography, myelography, and computed tomography for the evaluation of canine vertebral and spinal cord tumors in sixteen dogs. Vet Radiol & Ultrasound 1996; 37: 28–33. 15 Jones JC, Sorjonen DC, Simpson ST, et al. Comparison between computed tomographic and surgical findings in nine large-breed dogs with lumbosacral stenosis. Vet Radiol & Ultrasound 1996; 37: 247–256. 16 Bailey MQ. Use of x-ray computed tomography as an aid in localization of adrenal masses in the dog. JAVMA 1986; 188: 1046–1049. 17 Smallwood JE, George TF. Anatomic atlas for computed tomography in the mesaticephalic dog: Thorax and cranial abdomen. Vet Radiol & Ultrasound 1993; 34: 65–84. 18 Chen QC, Klein JS, Gamsu G, Webb WR. High-resolution computed tomography of the mammalian lung. Am J Vet Res 1992; 53: 1218–1224. 19 Burk RL. Computed tomography of thoracic diseases in dogs. JAVMA 1991; 199: 617–621. Citing Literature Volume39, Issue6November 1998Pages 532-535 ReferencesRelatedInformation}, number={6}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Spann, DR and Sellon, RK and Thrall, DE and Bostian, AE and Boston, GT}, year={1998}, pages={532–535} }
 @misc{ramirez_jorgensen_thrall_1998, title={Imaging basilar skull fractures in the horse: A review}, volume={39}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.1998.tb01624.x}, abstractNote={Due to the complex nature of the anatomy of the equine head, superimposition of numerous structures, and poor soft tissue differentiation, radiography may be of limited value in the diagnosis of basilar skull fractures. However, in many horses radiographic changes such as soft tissue opacification of the guttural pouch region, irregular bone margination at the sphenoccipital line, attenuation of the nasopharynx, ventral displacement of the dorsal pharyngeal wall and the presence of irregularly shaped bone fragments in the region of the guttural pouches are suggestive of a fracture of the skull base. These findings in conjunction with physical examination findings and historical information may lead to a presumptive diagnosis of a fracture. When available and when the patient will accommodate the equipment, computed tomography may give a definitive diagnosis owing to its superior resolution and differentiation of soft tissue structures.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Ramirez, O and Jorgensen, JS and Thrall, DE}, year={1998}, pages={391–395} }
 @article{price_cline_page_riviere_thrall_1998, title={Potential complications associated with normothermic lonidamine infusion and with systemic acidosis in dogs receiving lonidamine during whole body hyperthermia (WBH)}, volume={14}, ISSN={["0265-6736"]}, DOI={10.3109/02656739809018232}, abstractNote={The vascular toxicosis of lonidamine (40mg/h) or vehicle infusion was investigated in six dogs. Vasculitis and thrombosis were observed in veins infused with lonidamine but not in veins infused with vehicle. This finding suggests that it may not be possible to use lonidamine infusion to circumvent therapeutic limitations associated with the oral lonidamine formulation currently used in patients. We also investigated the systemic toxicosis of lonidamine (400 mg/m2; rapid intravenous bolus) or vehicle in six other dogs that developed systemic acidosis (pH ≤ 7.0) during whole body hyperthermia (42d`C × 90min). Gross and histologic haemorrhage was observed in all dogs; however, haemorrhagic lesions in acidotic dogs receiving lonidamine + WBH were more severe than changes observed in acidotic dogs receiving vehicle + WBH. These observations confirm the results of in vitro studies which suggest that the combined effect of lonidamine and hyperthermia is enhanced under acidic conditions. Furthermore, these findings indicate that acid-base status of patients receiving lonidamine during WBH must be monitored carefully to avoid serious complications.}, number={3}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Price, GS and Cline, JM and Page, RL and Riviere, JE and Thrall, DE}, year={1998}, pages={271–283} }
 @article{ladue_price_dodge_page_thrall_1998, title={Radiation therapy for incompletely resected canine mast cell tumors}, volume={39}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.1998.tb00326.x}, abstractNote={The records of 56 dogs treated with megavoltage radiation for mast cell neoplasia were reviewed to determine the efficacy of this treatment modality. Total radiation dose ranged from 45 to 57 Gray (Gy), dose per fraction ranged from 3.0 to 4.0 Gy, and radiation treatment time ranged from 14–28 days. Median disease free interval (95% CI) was 32.7 (19–70) months. Median disease free interval for dogs older than 7.5 years was 15 (lower limit 7) months as compared to 62 (lower limit 20) for dogs younger than 7.5 years of age (p = 0.006). Median disease free interval for dogs with measurable disease was 12 (lower limit 5) months as compared to 54 (32–70) months for dogs with microscopic disease (p = 0.006). Radiation treatment time was also significantly related to disease free interval. Median disease free interval for dogs treated longer than 22 days was 12 (7–19) months as compared to greater than 50 (lower limit 20) months for dogs treated in 22 or fewer days (p < 0.001). This appeared to be due to more recurrences in dogs treated with 3-per-week fractionation and suggests that tumor proliferation in the interfraction interval may be important. Sex, tumor location, histologic grade, WHO clinical stage, number of radiation fractions, total radiation dose, and dose-per-fraction, as well as the following “yes/no” variables: steroids given, surgery prior to radiation, lymph nodes irradiated, and development of another mast cell tumor did not appear to influence median disease free interval or survival. Data presented herein support megavoltage radiation as an effective treatment for canine mast cell neoplasia, and suggest that disease free interval in dogs treated with daily fractions may be longer than that achieved with alternating day fractions.}, number={1}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={LaDue, T and Price, GS and Dodge, R and Page, RL and Thrall, DE}, year={1998}, pages={57–62} }
 @book{textbook of veterinary diagnostic radiology_1998, ISBN={0721650929}, publisher={Philadelphia: W. B. Saunders}, year={1998} }
 @article{thrall_1997, title={Biologic basis of radiation therapy}, volume={27}, ISSN={["0195-5616"]}, DOI={10.1016/S0195-5616(97)50003-9}, abstractNote={The biologic effects of ionizing radiation are well understood. The limitations of radiation therapy time-dose schemes typically used in veterinary medicine are also well understood. Before expensive and potentially toxic combinations of treatment, such as radiation combined with chemotherapy or radiation combined with hyperthermia, can be fully understood, the effect of optimizing the manner in which radiation itself is administered must first be defined. This will only occur after a sufficient period of observation after improvement of the radiation time-dose schemes in use today. Also, when evaluating historic data regarding the response of canine and feline tumors to irradiation, the time-dose scheme used must be considered. Many papers were published based on coarsely fractionated schemes using large doses per fraction and relatively low total doses. Thus, the response rates published must be tempered by the fact that it may be possible to obtain better tumor control rates using smaller doses per fraction and a larger total dose.}, number={1}, journal={VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE}, author={Thrall, DE}, year={1997}, month={Jan}, pages={21-&} }
 @article{starrak_berry_page_johnson_thrall_1997, title={Correlation between thoracic radiographic changes and remission/survival duration in 270 dogs with lymphosarcoma}, volume={38}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.1997.tb00863.x}, abstractNote={A retrospective study was undertaken wherein the medical records and thoracic radiographs of 270 dogs with lymphosarcoma were reviewed to determine the type and frequency of thoracic radiographic changes. Statistical evaluation of the relationship between radiographic, clinical and immunologic factors and the primary remission duration and survival times was performed using univariate and multivariate analysis. One hundred ninety-two dogs (71%) had some type of thoracic radiographic abnormality, including 80 dogs (29.6%) with pulmonary infiltrates and 164 dogs (64.4%) with thoracic lymphadenomegaly. Only T-cell phenotype (p = 0.0056 for survival, p = 0.0045 for remission) and the presence of cranial mediastinal lymphadenomegaly (p = 0.0005 for survival, p = 0.0129 for remission) were identified as having a significant negative correlation to both primary remission and survival duration by multivariate analysis.}, number={6}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Starrak, GS and Berry, CR and Page, RL and Johnson, JL and Thrall, DE}, year={1997}, pages={411–418} }
 @article{thrall_rosner_azuma_mcentee_raleigh_1997, title={Hypoxia marker labeling in tumor biopsies: quantification of labeling variation and criteria for biopsy sectioning}, volume={44}, ISSN={["0167-8140"]}, DOI={10.1016/s0167-8140(97)01931-2}, abstractNote={The error associated with using biopsy-based methods for assessing parameters reflective of the tumor microenvironment depends on the variability in distribution of the parameter throughout the tumor and the biopsy sample. Some attention has been given to intratumoral distribution of parameters, but little attention has been given to their intrabiopsy distribution. We evaluated the intrabiopsy distribution of CCI-103F, a 2-nitroimidazole hypoxia marker.The hypoxia marker CCI-103F was studied in dogs bearing spontaneous solid tumors. Two biopsies were taken from each of seven tumors, for a total of 14 biopsies. Biopsies were serially sectioned and four to six contiguous slides from each 100-150 microm of the biopsy were used to formulate the best estimate of CCI-103F labeled area throughout the biopsy sample. One, two or four slides were then randomly selected from each biopsy and the labeled area, based on this limited sample, was compared to the estimate obtained from counting all available slides. Random sampling of slides was repeated 1000 times for each biopsy sample.CCI-103F labeling variance throughout the biopsy decreased as the estimated overall labeled area in the biopsy decreased. The error associated with estimating the overall labeled area in a biopsy from a randomly selected subset of slides decreased as the number of slides increased, and as the overall labeled area in the biopsy decreased. No minimally labeled biopsy was classified as unlabeled based on limited sampling.With regard to CCI-103F labeling, quantification of the labeled area in four randomly selected slides from a biopsy can provide, in most biopsies, an estimate of the labeled area in the biopsy within an absolute range of +/-0.05.}, number={2}, journal={RADIOTHERAPY AND ONCOLOGY}, author={Thrall, DE and Rosner, GL and Azuma, C and McEntee, MC and Raleigh, JA}, year={1997}, month={Aug}, pages={171–176} }
 @article{azuma_raleigh_thrall_1997, title={Longevity of pimonidazole adducts in spontaneous canine tumors as an estimate of hypoxic cell lifetime}, volume={148}, ISSN={["1938-5404"]}, DOI={10.2307/3579536}, abstractNote={The longevity of pimonidazole adducts in tumors was quantified as an estimate of the lifetime of hypoxic cells. Pimonidazole was given before irradiation to 12 dogs bearing spontaneous tumors, and tumors were biopsied 24, 48 and 72 h later. Pimonidazole antigen was quantified in the biopsies using ELISA and immunohistochemistry. Pimonidazole antigen was detectable in the initial biopsy in all dogs. In 5 dogs the amount of detectable antigen decreased to less than 50% of the initial amount, in 5 other dogs the amount of detectable antigen decreased to an amount between 50 and 100% of the initial amount, and in 2 dogs the amount of antigen appeared to increase relative to the initial amount. Tumors with high initial adduct concentration were characterized by greater decreases in adduct concentration than tumors with low initial adduct concentration. Immunohistochemically, labeled cells were present in 11 of 12 tumors. The geographic area in tumor biopsies labeled immunohistochemically with pimonidazole adducts (labeled area fraction) tended to decrease over time in 6 dogs, remain stable in 4 dogs and seemingly increase in 1 dog. There was no relationship in individual tumors between the relative change in antigen concentration and the relative change in labeled area fraction. Hypoxic cells which bind pimonidazole may persist for days during fractionated radiation therapy, and the potential exists for them to exert a negative effect on the host.}, number={1}, journal={RADIATION RESEARCH}, author={Azuma, C and Raleigh, JA and Thrall, DE}, year={1997}, month={Jul}, pages={35–42} }
 @article{kennedy_raleigh_perez_calkins_thrall_novotny_varia_1997, title={Proliferation and hypoxia in human squamous cell carcinoma of the cervix: First report of combined immunohistochemical assays}, volume={37}, ISSN={["0360-3016"]}, DOI={10.1016/S0360-3016(96)00539-1}, abstractNote={Preliminary data establishes pimonidazole as a useful probe for human tumor hypoxia. Although different in chemical structure and properties, pimonidazole is indistinguishable from other markers in its binding to hypoxic cells in human tumors. Pimonidazole hydrochloride is convenient to administer and is well tolerated when given as single intravenous infusion of 0.5 g/m2. Comparison of immunostaining for pimonidazole binding and for PCNA or MIB-1 shows an inverse relationship between proliferation and hypoxia.}, number={4}, journal={INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS}, author={Kennedy, AS and Raleigh, JA and Perez, GM and Calkins, DP and Thrall, DE and Novotny, DB and Varia, MA}, year={1997}, month={Mar}, pages={897–905} }
 @article{cline_rosner_raleigh_thrall_1997, title={Quantification of CCI-103F labeling heterogeneity in canine solid tumors}, volume={37}, ISSN={["0360-3016"]}, DOI={10.1016/S0360-3016(96)00559-7}, abstractNote={The purposes of this study were to assess sources of variation in the distribution of nitroimidazole-labeled hypoxic cells in canine tumors and to quantify the reliability of estimating overall nitroimidazole-labeled area fraction from biopsies.Hypoxic cells were labeled in 24 canine tumors by immunostaining of the nitroimidazole hypoxia marker CCI-103F. In tumors with a volume < 100 cm3, each cubic centimeter of tumor was examined; in larger tumors 100 randomly selected 1 cm3 samples were examined. These data were used to estimate the overall CCI-103F-labeled area fraction in the tumor. A variance components model was used to quantify intertumoral, intratumoral, and within slide (residual) sources of variation. The ability to estimate intratumoral CCI-103F-labeled area fraction based on information obtained from biopsies was assessed by randomly selecting two or four samples from the dataset for each tumor and comparing the mean CCI-103F-labeled area fraction from this limited sample to the labeled area fraction based on each cubic centimeter; this simulation process was repeated 1000 times.Intratumoral (27% of total) and intertumoral (30% of total) variation in CCI-103F-labeled area fraction were similar. Residual variation (variation at the microscopic level) accounted for 43% of total variation in CCI-103F labeling. Intratumoral variation in labeling decreased as the intratumoral CCI-103F mean labeled area fraction decreased. The accuracy of estimating the intratumoral CCI-103F-labeled area fraction in a tumor from limited sampling increased as the number of samples increased or the intratumoral labeled area fraction decreased. When four random samples were used to estimate overall CCI-103F-labeled area fraction in the tumor, estimates from approximately 90% of the 1000 simulations were within 0.10 of the intratumoral CCI-103F-labeled area fraction. Classifying a minimally labeled tumor as unlabeled based on limited sampling was unlikely.Despite intratumor variation, acceptable estimates of nitroimidazole-labeled cells in a tumor may be obtained from a clinically feasible number of biopsies.}, number={3}, journal={INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS}, author={Cline, JM and Rosner, GL and Raleigh, JA and Thrall, DE}, year={1997}, month={Feb}, pages={655–662} }
 @article{thrall_cline_mcentee_azuma_raleigh_1996, title={Hypoxia in canine tumors}, volume={20}, number={3}, journal={Veterinary Cancer Society Newsletter}, author={Thrall, D. E. and Cline, J. M. and McEntee, M. C. and Azuma, C. and Raleigh, J. A.}, year={1996}, pages={6} }
 @article{price_page_riviere_cline_thrall_1996, title={Pharmacokinetics and toxicity of oral and intravenous lonidamine in dogs}, volume={38}, ISSN={["0344-5704"]}, DOI={10.1007/s002800050460}, number={2}, journal={CANCER CHEMOTHERAPY AND PHARMACOLOGY}, author={Price, GS and Page, RL and Riviere, JE and Cline, JM and Thrall, DE}, year={1996}, month={Jun}, pages={129–135} }
 @article{hauck_price_ogilvie_johnson_gillette_thrall_dewhirst_page_1996, title={Phase I evaluation of mitoxantrone alone and combined with whole body hyperthermia in dogs with lymphoma}, volume={12}, ISSN={["0265-6736"]}, DOI={10.3109/02656739609022520}, abstractNote={The maximum tolerated dose of mitoxantrone (MX) administered alone or combined with whole body hyperthermia (WBH) was determined in this non-randomized, prospective study in dogs with lymphoma. MX was administered to 53 dogs every three weeks for a total of six treatments unless progressive disease or persistent, severe toxicity developed. Fifty dogs were evaluable (MX alone n = 30, MX/WBH n = 20). MX was administered as a 1 h infusion at the onset of the plateau phase of WBH in dogs treated with combined therapy. Dogs were evaluated weekly between treatments for the first four treatments with physical examination and complete blood counts to define acute and cumulative toxicity. Dogs were evaluated every three weeks for tumour response until relapse. The maximum tolerated dose (MTD) was defined as that dose in each group that resulted in a 50% incidence of moderate or severe toxicity as estimated from logistic regression analysis of the toxicity data. Myelosuppression was the only toxicity observed. Neutropenia was equal in frequency and severity between treatment groups. Thrombocytopenia was not observed in any dog receiving MX/WBH but occurred in 13% of dogs treated with MX alone. The MTD for MX ± WBH was 6·1 ± 0·6 and 6·5 ± 0·8mg/M2 respectively. A steeper dose-response relationship was observed in dogs receiving combined therapy compared to dogs treated with MX alone suggesting WBH may improve the uniformity of patient response to chemotherapy. We concluded that MX may be administered without dose reduction to dogs undergoing WBH and that MX should be evaluated more thoroughly in future thermochemotherapy studies.}, number={3}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Hauck, ML and Price, GS and Ogilvie, GK and Johnson, J and Gillette, EL and Thrall, DE and Dewhirst, MW and Page, RL}, year={1996}, pages={309–320} }
 @article{price_page_riviere_cline_frazier_thrall_1995, title={EFFECT OF WHOLE-BODY HYPERTHERMIA ON LONIDAMINE AND DOXORUBICIN PHARMACOKINETICS AND TOXICITY IN DOGS}, volume={11}, ISSN={["0265-6736"]}, DOI={10.3109/02656739509022489}, abstractNote={Six cycles of the maximum tolerable intravenous doses of lonidamine (400 mg/m2) and doxorubicin (30 mg/m2) were administered to three normothermic dogs and three dogs undergoing whole-body hyperthermia (WBH) (42°C × 90 min), at 3-week intervals. Lonidamine pharmacokinetics was unaltered by WBH. WBH increased doxorubicin clearance 1·6-fold, however this trend was not statistically significant. WBH resulted in a 2·4-fold increase in the volume of distribution (Vdss) of doxorubicin relative to dogs treated under euthermic conditions (p < 0·001). This finding suggests tissue extraction of doxorubicin was increased by WBH. The specific tissues in which this occurred is unknown, but myelosuppression and cardiotoxicity were only minimally increased. Therefore, doxorubicin uptake in critical normal tissues was probably unaffected. The biochemical and haematologic toxicities observed 6 h and 1 week after each treatment did not appear to differ in character or severity from that reported in dogs receiving lonidamine ± WBH or doxorubicin ± WBH. These results suggest WBH did not decrease the maximum tolerable dose of doxorubicin when given with lonidamine, and that the antitumour activity of this combination should be assessed.}, number={4}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={PRICE, GS and PAGE, RL and RIVIERE, JE and CLINE, JM and FRAZIER, DL and THRALL, DE}, year={1995}, pages={545–559} }
 @article{price_page_riviere_cline_thrall_1995, title={EFFECT OF WHOLE-BODY HYPERTHERMIA ON THE PHARMACOKINETICS AND TOXICITY OF LONIDAMINE IN DOGS}, volume={11}, ISSN={["0265-6736"]}, DOI={10.3109/02656739509022488}, abstractNote={The pharmacokinetics and toxicity of intravenous lonidamine were investigated in dogs receiving four cycles of lonidamine (400 or 800 mg/m2) ± whole-body hyperthermia (WBH). Clearance and volume of distribution in dogs receiving lonidamine during WBH increased 1·6–2·3 and 1·9–3·5-fold respectively, relative to dogs receiving lonidamine under euthermic conditions (p < 0·02). In dogs receiving lonidamine under euthermic conditions or 400 mg/m2 + WBH, the area under the lonidamine concentration versus time curve (AUC) measured during the fourth treatment was 21–58% lower than the first treatment AUC. However, in dogs receiving 800 mg/m2 + WBH, the fourth treatment AUC was four-fold higher than the first treatment AUC (p < 0·02). This suggests repeated exposure to 800 mg/m2 lonidamine and WBH impairs lonidamine metabolism. Weakness, hypoglycaemia, and elevations in amylase, alanine aminotransferase, alkaline phosphatase and bilirubin were more severe or occurred exclusively in dogs receiving 800 mg/m2 + WBH. Since these changes were attributable to marked AUC increases, which occurred secondary to repeated exposure to 800 mg/m2 lonidamine during WBH, 400 mg/m2 was identified as the maximum tolerable dose to be administered intravenously to dogs during WBH.}, number={4}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={PRICE, GS and PAGE, RL and RIVIERE, JE and CLINE, JM and THRALL, DE}, year={1995}, pages={531–544} }
 @article{thrall_larue_1995, title={Palliative radiation therapy}, volume={10}, number={3}, journal={Seminars in Veterinary Medicine and Surgery (small Animal)}, author={Thrall, D. E. and LaRue, S. M.}, year={1995}, pages={205} }
 @article{page_mcentee_williams_george_price_novotney_hauck_riviere_dewhirst_thrall_1994, title={EFFECT OF WHOLE-BODY HYPERTHERMIA ON CARBOPLATIN DISPOSITION AND TOXICITY IN DOGS}, volume={10}, ISSN={["0265-6736"]}, DOI={10.3109/02656739409012373}, abstractNote={Fifty dogs with refractory or disseminated spontaneous tumours were evaluated in two independent phase I studies using either carboplatin (CBDCA) alone or CBDCA plus whole body hyperthermia (WBH). CBDCA was administered as a 30 min infusion at the onset of the plateau phase of WBH in dogs receiving combined treatment. Serum samples were collected and drug disposition was determined in both treatment groups. The dose-effect relationship was mathematically described with a logistic regression model developed from categorical toxicity data accumulated throughout the first two treatment courses in all dogs. The maximum tolerated dose (MTD) was defined as that dose which resulted in a 50% probability of achieving moderate or severe toxicity. The only toxicities observed were neutropenia and thrombocytopenia, which were dose-dependent. The nadir occurred between 7 and 14 days following treatment. A significant decrease in the area under the serum CBDCA versus time curve for dogs undergoing WBH was consistent with increased tissue binding of the drug as well as increased urinary eliminations. Serum AUC values determined following the first course of treatment were predictive of subsequent toxicity in both treatment groups. The MTD (95%CI) for CBDCA and CBDCA/WBH were estimated to be 318(44) and 239(51) mg/M2 respectively (p = 0.08). A randomized phase II evaluation should be initiated to determine if a therapeutic gain can be achieved using combined CBDCA and WBH. Further refinement of the CBDCA dose in such a trial should be based on both pharmacokinetic parameters and normal tissue response.}, number={6}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={PAGE, RL and MCENTEE, MC and WILLIAMS, PL and GEORGE, SL and PRICE, GS and NOVOTNEY, CA and HAUCK, ML and RIVIERE, JE and DEWHIRST, MW and THRALL, DE}, year={1994}, pages={807–816} }
 @article{thrall_mcentee_novotney_hauck_page_1993, title={A BOOST TECHNIQUE FOR IRRADIATION OF MALIGNANT CANINE NASAL TUMORS}, volume={34}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.1993.tb01579.x}, abstractNote={Eighteen dogs with malignant nasal cavity tumors were treated with radiation therapy, including a boost technique. Three 3:0 Gy boost doses were added to a treatment protocol consisting of sixteen 3.0 Gy daily fractions, bringing the total dose to 57 Gy. This boost technique was implemented without an associated increase in overall treatment time by giving the boost doses on a twice-a-day basis. Boost doses were given during the first half of the radiation therapy period. The treatment was completed as planned in 16 of the 18 dogs; two dogs received lower doses (51 and 54 Gy). Median survival was 177 days, poorer than in some other reported studies of nasal tumor irradiation. Acute effects were unacceptable, with 11 of the 18 dogs developing severe mucositis, desquamation, edema, swelling, and pruritus. The extensive nature of the acute reactions compromised assessment of the effect of the increased radiation dose on the tumor. Although there is justification for assessing more aggressive radiation protocols in canine nasal tumor patients, total doses approximating 60 Gy can not be given as described because of the inability of acutely responding normal tissues to compensate.}, number={4}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={THRALL, DE and MCENTEE, MC and NOVOTNEY, C and HAUCK, ML and PAGE, RL}, year={1993}, pages={295–300} }
 @article{page_thrall_george_price_heidner_mcentee_novotney_hauck_dewhirst_1992, title={QUANTITATIVE ESTIMATION OF THE THERMAL DOSE-MODIFYING FACTOR FOR CIS-DIAMMINEDICHLOROPLATINUM (CDDP) IN TUMOR-BEARING DOGS}, volume={8}, ISSN={["0265-6736"]}, DOI={10.3109/02656739209005024}, abstractNote={A statistical method for estimating clinical toxicity was used to determine a theoretical isoeffect dose-modifying factor for dogs with disseminated or refractory neoplasia treated with cis-diammine dichloroplatinum (II) plus whole-body hyperthermia or CDDP alone. CDDP was administered every 3 weeks with vigorous saline hydration to 54 dogs (CDDP alone n = 21, CDDP/WBH n = 33) that were eligible for entry into this non-randomized study. CDDP was administered during the plateau phase of WBH in dogs receiving combined therapy. Acute toxicity included myelosuppression (CDDP n = 7; CDDP/WBH n = 5), nephrotoxicity (CDDP n = 1, CDDP/WBH n = 1) and respiratory distress (CDDP/WBH n = 2). Eight dogs experienced chronic renal dysfunction as a result of CDDP (n = 2) or CDDP/WBH (n = 6). A theoretical thermal dose-modifying factor was determined for both acute and cumulative toxicity by comparing the maximum tolerated dose of each treatment group. The maximum tolerated dose (MTD) of CDDP +/- WBH was defined as that dose producing a 50% incidence of moderate acute toxicity or acute plus mild chronic toxicity as estimated from logistic regression analysis of the toxicity data. The MTD (+/- .standard error) of CDDP/WBH for acute toxicity only was 54.6 (4.3) mg/M2 and for CDDP alone the MTD was 73.6 (40) mg/M2. Thus, the isoeffect dose-modifying factor for acute toxicity was 1.35 (0.12). The MTD (SE) of CDDP/WBH for cumulative toxicity (acute plus chronic toxicity) was 46.4 (2.7) mg/M2 and for CDDP alone waas 70.0 (2.9) mg/M2. The isoeffect dose-modifying factor for total cumulative toxicity was 1.5 (0.1).(ABSTRACT TRUNCATED AT 250 WORDS)}, number={6}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={PAGE, RL and THRALL, DE and GEORGE, SL and PRICE, GS and HEIDNER, GL and MCENTEE, MC and NOVOTNEY, CA and HAUCK, ML and DEWHIRST, MW}, year={1992}, pages={761–769} }
 @inproceedings{page_riviere_heidner_mcentee_thrall_1989, title={Effect of temperature on cisplatin (CDDP) and carboplatin (CBDCA) pharmacokinetic disposition in dogs}, volume={2}, booktitle={Conference Proceedings}, author={Page, R. L. and Riviere, J. E. and Heidner, G. L. and McEntee, M. C. and Thrall, D. E.}, year={1989}, pages={499–501} }
 @article{riviere_page_dewhirst_tyczkowska_thrall_1986, title={Effect of hyperthermia on cisplatin pharmacokinetics in normal dogs}, volume={2}, DOI={10.3109/02656738609004965}, abstractNote={In vitro and in vivo cisplatin pharmacokinetic studies were conducted at 37 degrees C and 42-43 degrees C in dogs. Cisplatin at 1, 2, 3, 4 and 5 micrograms/ml was incubated with canine serum at 37 degrees and 43 degrees C. Aliquots were processed immediately for atomic absorption spectrophotometry to determine total as well as free, ultrafilterable cisplatin concentrations. Thirteen healthy, average-sized mongrel dogs received 1 mg/kg cisplatin as an intravenous bolus. Four were maintained unanaesthetized at 37 degrees C, two were anaesthetized and maintained at 37 degrees C and seven were anaesthetized and maintained at a rectal temperature of 42 degrees C for 60 min. Serum samples were obtained and processed for free and total cisplatin. There were no detectable concentration effects present in either in vitro group. The rate constant reflecting the decay of free cisplatin at 37 degrees C was 0.0035 +/- 0.0007 min-1 and increased significantly (P less than 0.0001) to 0.0053 +/- 0.001 min-1 at 43 degrees C. In vivo pharmacokinetic analysis consisted of model-independent parameters (total body clearance, volume of distribution, half-life and mean residence time). A significant increase (P less than or equal to 0.05) in all parameters was observed with free-cisplatin at 42 degrees C. This data would indicate that at the elevated temperatures encountered in whole body hyperthermia, the rate of formation of reactive metabolites from parent cisplatin is increased.(ABSTRACT TRUNCATED AT 250 WORDS)}, journal={International Journal of Hyperthermia}, author={Riviere, J. E. and Page, R. L. and Dewhirst, M. W. and Tyczkowska, K. and Thrall, D. E.}, year={1986}, pages={351–358} }