@article{czernuszewicz_aji_moore_montgomery_velasco_torres_anand_johnson_deal_zuki_et al._2022, title={Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models}, ISSN={["2471-254X"]}, DOI={10.1002/hep4.1912}, abstractNote={Shear wave elastography (SWE) is an ultrasound‐based stiffness quantification technology that is used for noninvasive liver fibrosis assessment. However, despite widescale clinical adoption, SWE is largely unused by preclinical researchers and drug developers for studies of liver disease progression in small animal models due to significant experimental, technical, and reproducibility challenges. Therefore, the aim of this work was to develop a tool designed specifically for assessing liver stiffness and echogenicity in small animals to better enable longitudinal preclinical studies. A high‐frequency linear array transducer (12‐24 MHz) was integrated into a robotic small animal ultrasound system (Vega; SonoVol, Inc., Durham, NC) to perform liver stiffness and echogenicity measurements in three dimensions. The instrument was validated with tissue‐mimicking phantoms and a mouse model of nonalcoholic steatohepatitis. Female C57BL/6J mice (n = 40) were placed on choline‐deficient, L‐amino acid‐defined, high‐fat diet and imaged longitudinally for 15 weeks. A subset was sacrificed after each imaging timepoint (n = 5) for histological validation, and analyses of receiver operating characteristic (ROC) curves were performed. Results demonstrated that robotic measurements of echogenicity and stiffness were most strongly correlated with macrovesicular steatosis (R2 = 0.891) and fibrosis (R2 = 0.839), respectively. For diagnostic classification of fibrosis (Ishak score), areas under ROC (AUROCs) curves were 0.969 for ≥Ishak1, 0.984 for ≥Ishak2, 0.980 for ≥Ishak3, and 0.969 for ≥Ishak4. For classification of macrovesicular steatosis (S‐score), AUROCs were 1.00 for ≥S2 and 0.997 for ≥S3. Average scanning and analysis time was <5 minutes/liver. Conclusion: Robotic SWE in small animals is feasible and sensitive to small changes in liver disease state, facilitating in vivo staging of rodent liver disease with minimal sonographic expertise.}, journal={HEPATOLOGY COMMUNICATIONS}, author={Czernuszewicz, Tomasz J. and Aji, Adam M. and Moore, Christopher J. and Montgomery, Stephanie A. and Velasco, Brian and Torres, Gabriela and Anand, Keerthi S. and Johnson, Kennita A. and Deal, Allison M. and Zuki, Dzenan and et al.}, year={2022}, month={Feb} }
 @article{rojas_joiner_velasco_bautista_aji_moore_beaumont_pylayeva-gupta_dayton_gessner_et al._2022, title={Validation of a combined ultrasound and bioluminescence imaging system with magnetic resonance imaging in orthotopic pancreatic murine tumors}, volume={12}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-021-03684-z}, abstractNote={Preclinical mouse solid tumor models are widely used to evaluate efficacy of novel cancer therapeutics. Recent reports have highlighted the need for utilizing orthotopic implantation to represent clinical disease more accurately, however the deep tissue location of these tumors makes longitudinal assessment challenging without the use of imaging techniques. The purpose of this study was to evaluate the performance of a new multi-modality high-throughput in vivo imaging system that combines bioluminescence imaging (BLI) with robotic, hands-free ultrasound (US) for evaluating orthotopic mouse models. Long utilized in cancer research as independent modalities, we hypothesized that the combination of BLI and US would offer complementary advantages of detection sensitivity and quantification accuracy, while mitigating individual technological weaknesses. Bioluminescent pancreatic tumor cells were injected into the pancreas tail of C57BL/6 mice and imaged weekly with the combination system and magnetic resonance imaging (MRI) to serve as a gold standard. BLI photon flux was quantified to assess tumor activity and distribution, and US and MRI datasets were manually segmented for gross tumor volume. Robotic US and MRI demonstrated a strong agreement (R2 = 0.94) for tumor volume measurement. BLI showed a weak overall agreement with MRI (R2 = 0.21), however, it offered the greatest sensitivity to detecting the presence of tumors. We conclude that combining BLI with robotic US offers an efficient screening tool for orthotopic tumor models.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Rojas, Juan D. and Joiner, Jordan B. and Velasco, Brian and Bautista, Kathlyne Jayne B. and Aji, Adam M. and Moore, Christopher J. and Beaumont, Nathan J. and Pylayeva-Gupta, Yuliya and Dayton, Paul A. and Gessner, Ryan C. and et al.}, year={2022}, month={Jan} }
 @article{torres_czernuszewicz_homeister_farber_caughey_gallippi_2020, title={Carotid Plaque Fibrous Cap Thickness Measurement by ARFI Variance of Acceleration: In Vivo Human Results}, volume={39}, ISSN={["1558-254X"]}, DOI={10.1109/TMI.2020.3019184}, abstractNote={This study evaluates the performance of an acoustic radiation force impulse (ARFI)-based outcome parameter, the decadic logarithm of the variance of acceleration, or log(VoA), for measuring carotid fibrous cap thickness. Carotid plaque fibrous cap thickness measurement by log(VoA) was compared to that by ARFI peak displacement (PD) in patients undergoing clinically indicated carotid endarterectomy using a spatially-matched histological validation standard. Fibrous caps in parametric log(VoA) and PD images were automatically segmented using a custom clustering algorithm, and a pathologist with expertise in atherosclerosis hand-delineated fibrous caps in histology. Over 10 fibrous caps, log(VoA)-derived thickness was more strongly correlated to histological thickness than PD-derived thickness, with Pearson correlation values of 0.98 for log(VoA) compared to 0.89 for PD. The log(VoA)-derived cap thickness also had better agreement with histology-measured thickness, as assessed by the concordance correlation coefficient (0.95 versus 0.62), and, by Bland-Altman analysis, was more consistent than PD-derived fibrous cap thickness. These results suggest that ARFI log(VoA) enables improved discrimination of fibrous cap thickness relative to ARFI PD and further contributes to the growing body of evidence demonstrating ARFI’s overall relevance to delineating the structure and composition of carotid atherosclerotic plaque for stroke risk prediction.}, number={12}, journal={IEEE TRANSACTIONS ON MEDICAL IMAGING}, author={Torres, Gabriela and Czernuszewicz, Tomasz J. and Homeister, Jonathon W. and Farber, Mark A. and Caughey, Melissa C. and Gallippi, Caterina M.}, year={2020}, month={Dec}, pages={4383–4390} }
 @article{czernuszewicz_papadopoulou_rojas_rajamahendiran_perdomo_butler_harlacher_o'connell_zukic_dayton_et al._2019, title={A preclinical ultrasound platform for widefield 3D imaging of rodent tumors}, volume={79}, ISSN={["1538-7445"]}, DOI={10.1158/1538-7445.AM2019-1955}, abstractNote={Background: Preclinical ultrasound (US) and contrast-enhanced ultrasound (CEUS) imaging have long been used in oncology to noninvasively measure tumor volume and vascularity. While the value of preclinical US has been repeatedly demonstrated, these modalities are not without several key limitations that make them unattractive to cancer researchers, including: high user-variability, low throughput, and limited imaging field-of-view (FOV). Herein, we present a novel robotic preclinical US/CEUS system that addresses these limitations and demonstrates its use in evaluating tumors in 3D in a rodent model. Methods: The imaging system was designed to allow seamless whole-body 3D imaging, which requires rodents to be imaged without physical contact between the US transducer and the animal. To achieve this, a custom dual-element transducer was mounted on a robotic carriage, submerged in a hydrocarbon fluid, and the reservoir sealed with an acoustically transmissive top platform. Eight NOD/scid/gamma (NSG) female mice were injected subcutaneously in the flank with 8×109 786-O human clear-cell renal cell carcinoma (ccRCC) cells. Weekly imaging commenced after tumors reached a size of 150 mm3 and continued until tumors reached a maximum size of 1 cm3 (∼4-5 weeks). An additional six nude athymic female mice were injected subcutaneously in the flank with 7 × 105 SVR angiosarcoma cells to perform an inter-operator variability study. Imaging consisted of 3D B-mode (conventional ultrasound) of the whole abdomen ( Results: Wide-field US images reconstructed from 3D volumetric data showed superior FOV over conventional US. Several anatomical landmarks could be identified within each image surrounding the tumor, including the liver, small intestines, bladder, and inguinal lymph nodes. Tumor boundaries were clearly delineated in both B-mode and BVD images, with BVD images showing heterogeneous microvessel density at later timepoints suggesting tumor necrosis. Excellent agreement was measured for both inter-reader and inter-operator experiments, with alpha coefficients of 0.914 (95% CI: 0.824-0.948) and 0.959 (0.911-0.981), respectively. Conclusion: We have demonstrated a novel preclinical US imaging system that can accurately and consistently evaluate tumors in rodent models. The system leverages cost-effective robotic technology, and a new scanning paradigm that allows for easy and reproducible data acquisition to enable wide-field, 3D, multi-parametric ultrasound imaging. Note: This abstract was not presented at the meeting. Citation Format: Tomasz Czernuszewicz, Virginie Papadopoulou, Juan D. Rojas, Rajalekha Rajamahendiran, Jonathan Perdomo, James Butler, Max Harlacher, Graeme O9Connell, Dzenan Zukic, Paul A. Dayton, Stephen Aylward, Ryan C. Gessner. A preclinical ultrasound platform for widefield 3D imaging of rodent tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1955.}, number={13}, journal={CANCER RESEARCH}, author={Czernuszewicz, Tomasz and Papadopoulou, Virginie and Rojas, Juan D. and Rajamahendiran, Rajalekha and Perdomo, Jonathan and Butler, James and Harlacher, Max and O'Connell, Graeme and Zukic, Dzenan and Dayton, Paul A. and et al.}, year={2019}, month={Jul} }
 @article{torres_czernuszewicz_homeister_caughey_huang_lee_zamora_farber_marston_huang_et al._2019, title={Delineation of Human Carotid Plaque Features In Vivo by Exploiting Displacement Variance}, volume={66}, ISSN={["1525-8955"]}, DOI={10.1109/TUFFC.2019.2898628}, abstractNote={While in vivo acoustic radiation force impulse (ARFI)-induced peak displacement (PD) has been demonstrated to have high sensitivity and specificity for differentiating soft from stiff plaque components in patients with carotid plaque, the parameter exhibits poorer performance for distinguishing between plaque features with similar stiffness. To improve discrimination of carotid plaque features relative to PD, we hypothesize that signal correlation and signal-to-noise ratio (SNR) can be combined, outright or via displacement variance. Plaque feature detection by displacement variance, evaluated as the decadic logarithm of the variance of acceleration and termed “log(VoA),” was compared to that achieved by exploiting SNR, cross correlation coefficient, and ARFI-induced PD outcome metrics. Parametric images were rendered for 25 patients undergoing carotid endarterectomy, with spatially matched histology confirming plaque composition and structure. On average, across all plaques, log(VoA) was the only outcome metric with values that statistically differed between regions of lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), collagen (COL), and calcium (CAL). Further, log(VoA) achieved the highest contrast-to-noise ratio (CNR) for discriminating between LRNC and IPH, COL and CAL, and grouped soft (LRNC and IPH) and stiff (COL and CAL) plaque components. More specifically, relative to the previously demonstrated ARFI PD parameter, log(VoA) achieved 73% higher CNR between LRNC and IPH and 59% higher CNR between COL and CAL. These results suggest that log(VoA) enhances the differentiation of LRNC, IPH, COL, and CAL in human carotid plaques, in vivo, which is clinically relevant to improving stroke risk prediction and medical management.}, number={3}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Torres, Gabriela and Czernuszewicz, Tomasz J. and Homeister, Jonathon W. and Caughey, Melissa C. and Huang, Benjamin Y. and Lee, Ellie R. and Zamora, Carlos A. and Farber, Mark A. and Marston, William A. and Huang, David Y. and et al.}, year={2019}, month={Mar}, pages={481–492} }
 @article{rojas_rajamahendiran_czernuszewicz_velasco_perdomo_harlacher_o'connell_butler_damania_dayton_et al._2019, title={Tracking angiogenesis induced microvascular changes in a lymphoma model via a new high throughput non-invasive dual modality imaging platform}, volume={79}, ISSN={["1538-7445"]}, DOI={10.1158/1538-7445.AM2019-1935}, abstractNote={This study presents a novel dual-modality imaging system for assessing cancer progression in rodents. The system incorporates bioluminescence imaging (BLI), used to assess tumor growth, and contrast-enhanced ultrasound (CEUS), used to assess anatomical information and map microvasculature. The combination of the two modalities has previously been shown to reduce inter-user variability of BLI quantification, and in this work, we demonstrate that a dual BLI/US system can provide a more holistic assessment of disease. NSG (NOD/scid/gamma) female mice were implanted with luc-tagged lymphoma cells (BCBL-1, RRID: CVCL_0165, 1x105 cells, intraperitoneal (IP) injection, N = 8 mice) and imaged using the US and BLI hybrid modality system (SonoVol, Inc.), and a BLI-alone system (Perkin Elmer, Inc.) for comparison to a widely available commercial BLI system. BLI sensitivity was evaluated using a weakly luminescent tritium phantom to find the shortest exposure required to detect signal. In vivo studies consisted of an IP injection of D-luciferin (250 µL at 15 mg/mL) and serial captures of images with exposure times of 60 s every 3 min. Acoustic Angiography (AA), a high-resolution CEUS technique, was used to acquire 3D volumes in the abdomen surrounding the tumor site to assess angiogenesis-induced vascular remodeling associated with tumor growth. In vitro BLI sensitivity experiments showed that the dual-modality system required an exposure of 3 sec to detect signal (p This work demonstrates that non-invasive measurements of in vivo microvascular remodeling can be precisely mapped to changes in tumor growth with a hybrid modality system. The system has comparable sensitivity to a BLI-alone system and provides similar assessments of longitudinal tumor growth. Adding quantitative metrics for vascular remodeling to the widely used luminescent imaging could provide a more comprehensive assessment for tumor functional status than either modality could individually. This should prove valuable when using antiangiogenic therapies because changes in vasculature will precede cell death, and the ability to monitor both the cells and their blood supply might help to elucidate underlying biological processes. Citation Format: Juan D. Rojas, Rajalekha Rajamahendiran, Tomasz J. Czernuszewicz, Brian Velasco, Jonathan Perdomo, Max Harlacher, Graeme O9Connell, James Butler, Blossom Damania, Paul A. Dayton, Ryan C. Gessner. Tracking angiogenesis induced microvascular changes in a lymphoma model via a new high throughput non-invasive dual modality imaging platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1935.}, number={13}, journal={CANCER RESEARCH}, author={Rojas, Juan D. and Rajamahendiran, Rajalekha and Czernuszewicz, Tomasz J. and Velasco, Brian and Perdomo, Jonathan and Harlacher, Max and O'Connell, Graeme and Butler, James and Damania, Blossom and Dayton, Paul A. and et al.}, year={2019}, month={Jul} }
 @article{rojas_papadopoulou_czernuszewicz_rajamahendiran_chytil_chiang_chong_bautch_rathmell_aylward_et al._2019, title={Ultrasound Measurement of Vascular Density to Evaluate Response to Anti-Angiogenic Therapy in Renal Cell Carcinoma}, volume={66}, ISSN={["1558-2531"]}, DOI={10.1109/TBME.2018.2860932}, abstractNote={<italic>Background:</italic> Functional and molecular changes often precede gross anatomical changes, so early assessment of a tumor's functional and molecular response to therapy can help reduce a patient's exposure to the side effects of ineffective chemotherapeutics or other treatment strategies. <italic>Objective:</italic> Our intent was to test the hypothesis that an ultrasound microvascular imaging approach might provide indications of response to therapy prior to assessment of tumor size. <italic>Methods:</italic> Mice bearing clear-cell renal cell carcinoma xenograft tumors were treated with antiangiogenic and Notch inhibition therapies. An ultrasound measurement of microvascular density was used to serially track the tumor response to therapy. <italic>Results:</italic> Data indicated that ultrasound-derived microvascular density can indicate response to therapy a week prior to changes in tumor volume and is strongly correlated with physiological characteristics of the tumors as measured by histology (<inline-formula><tex-math notation="LaTeX">$\rho = {\text{0.75}}$</tex-math></inline-formula>). Furthermore, data demonstrated that ultrasound measurements of vascular density can determine response to therapy and classify between-treatment groups with high sensitivity and specificity. <italic>Conclusion/Significance:</italic> Results suggests that future applications utilizing ultrasound imaging to monitor tumor response to therapy may be able to provide earlier insight into tumor behavior from metrics of microvascular density rather than anatomical tumor size measurements.}, number={3}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Rojas, Juan D. and Papadopoulou, Virginie and Czernuszewicz, Tomasz J. and Rajamahendiran, Rajalekha M. and Chytil, Anna and Chiang, Yun-Chen and Chong, Diana C. and Bautch, Victoria L. and Rathmell, W. Kimryn and Aylward, Stephen and et al.}, year={2019}, month={Mar}, pages={873–880} }
 @article{czernuszewicz_homeister_caughey_wang_zhu_huang_lee_zamora_farber_fulton_et al._2017, title={Performance of acoustic radiation force impulse ultrasound imaging for carotid plaque characterization with histologic validation}, volume={66}, ISSN={["0741-5214"]}, DOI={10.1016/j.jvs.2017.04.043}, abstractNote={Stroke is commonly caused by thromboembolic events originating from ruptured carotid plaque with vulnerable composition. This study assessed the performance of acoustic radiation force impulse (ARFI) imaging, a noninvasive ultrasound elasticity imaging method, for delineating the composition of human carotid plaque in vivo with histologic validation.Carotid ARFI images were captured before surgery in 25 patients undergoing clinically indicated carotid endarterectomy. The surgical specimens were histologically processed with sectioning matched to the ultrasound imaging plane. Three radiologists, blinded to histology, evaluated parametric images of ARFI-induced peak displacement to identify plaque features such as necrotic core (NC), intraplaque hemorrhage (IPH), collagen (COL), calcium (CAL), and fibrous cap (FC) thickness. Reader performance was measured against the histologic standard using receiver operating characteristic curve analysis, linear regression, Spearman correlation (ρ), and Bland-Altman analysis.ARFI peak displacement was two-to-four-times larger in regions of NC and IPH relative to regions of COL or CAL. Readers detected soft plaque features (NC/IPH) with a median area under the curve of 0.887 (range, 0.867-0.924) and stiff plaque features (COL/CAL) with median area under the curve of 0.859 (range, 0.771-0.929). FC thickness measurements of two of the three readers correlated with histology (reader 1: R2 = 0.64, ρ = 0.81; reader 2: R2 = 0.89, ρ = 0.75).This study suggests that ARFI is capable of distinguishing soft from stiff atherosclerotic plaque components and delineating FC thickness.}, number={6}, journal={JOURNAL OF VASCULAR SURGERY}, author={Czernuszewicz, Tomasz J. and Homeister, Jonathon W. and Caughey, Melissa C. and Wang, Yue and Zhu, Hongtu and Huang, Benjamin Y. and Lee, Ellie R. and Zamora, Carlos A. and Farber, Mark A. and Fulton, Joseph J. and et al.}, year={2017}, month={Dec}, pages={1749-+} }
 @inproceedings{czernuszewicz_homeister_caughey_huang_lee_zamora_farber_fulton_ford_marston_et al._2016, title={Carotid plaque characterization with ARFI imaging: Blinded reader study}, DOI={10.1109/ultsym.2016.7728873}, abstractNote={Stroke is commonly caused by thromboembolic events originating from vulnerable atherosclerotic plaque in the carotid vasculature. The purpose of this study was to evaluate the ability of acoustic radiation force impulse (ARFI) imaging, a noninvasive elastography imaging technique, to assess the composition of carotid artery plaques using histologic examination as the gold standard. Twenty-five patients undergoing carotid endarterectomy (CEA) were enrolled and imaged with ARFI. After surgery, extracted specimens were histologically processed and matched to the ultrasound imaging plane. Parametric 2D ARFI images of peak displacement (PD) were evaluated by three radiologists blinded to the histology result. Receiver operating characteristic (ROC) curve analysis was performed, and area under the ROC curve (AUC) was taken as a metric of performance for detecting plaque features such as necrotic core (NC), intraplaque hemorrhage (IPH), collagen (COL), and calcium (CAL). Additionally, linear regression was performed on fibrous cap (FC) thickness measurements. Areas of plaque with NC and IPH were observed to have substantially increased ARFI PD (2× to 4×) compared to areas of plaque with COL or CAL. Median AUC for detecting soft plaque features (NC/IPH) was 0.887 (range: 0.867 - 0.924) and stiff plaque features (COL/CAL) was 0.859 (range: 0.771 - 0.929). FC thickness measured by two of the three radiologists matched closely with histology (reader 1: R2 = 0.64; reader 2: R2 = 0.89). This study suggests that ARFI is capable of distinguishing soft from stiff compositional elements of atherosclerotic plaques and may be relevant to improving plaque risk assessment.}, booktitle={2016 ieee international ultrasonics symposium (ius)}, author={Czernuszewicz, T. J. and Homeister, J. W. and Caughey, M. C. and Huang, B. Y. and Lee, E. R. and Zamora, C. A. and Farber, M. A. and Fulton, J. J. and Ford, P. F. and Marston, W. A. and et al.}, year={2016} }
 @article{wang_li_czernuszewicz_gallippi_liu_geng_jiang_2016, title={Design, Fabrication, and Characterization of a Bifrequency Colinear Array}, volume={63}, ISSN={["1525-8955"]}, DOI={10.1109/tuffc.2015.2506000}, abstractNote={Ultrasound imaging with high resolution and large penetration depth has been increasingly adopted in medical diagnosis, surgery guidance, and treatment assessment. Conventional ultrasound works at a particular frequency, with a - 6-dB fractional bandwidth of ~ 70% , limiting the imaging resolution or depth of field. In this paper, a bifrequency colinear array with resonant frequencies of 8 and 20 MHz was investigated to meet the requirements of resolution and penetration depth for a broad range of ultrasound imaging applications. Specifically, a 32-element bifrequency colinear array was designed and fabricated, followed by element characterization and real-time sectorial scan (S-scan) phantom imaging using a Verasonics system. The bifrequency colinear array was tested in four different modes by switching between low and high frequencies on transmit and receive. The four modes included the following: 1) transmit low, receive low; 2) transmit low, receive high; 3) transmit high, receive low; and 4) transmit high, receive high. After testing, the axial and lateral resolutions of all modes were calculated and compared. The results of this study suggest that bifrequency colinear arrays are potential aids for wideband fundamental imaging and harmonic/subharmonic imaging.}, number={2}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Wang, Zhuochen and Li, Sibo and Czernuszewicz, Tomasz J. and Gallippi, Caterina M. and Liu, Ruibin and Geng, Xuecang and Jiang, Xiaoning}, year={2016}, month={Feb}, pages={266–274} }
 @article{czernuszewicz_gallippi_2016, title={On the Feasibility of Quantifying Fibrous Cap Thickness With Acoustic Radiation Force Impulse (ARFI) Ultrasound}, volume={63}, ISSN={["1525-8955"]}, DOI={10.1109/tuffc.2016.2535440}, abstractNote={Acute cerebrovascular accidents are associated with the rupture of vulnerable atherosclerotic plaques in the carotid arteries. Fibrous cap (FC) thickness has been shown to be an important predictor of plaque rupture but has been challenging to measure accurately with clinical noninvasive imaging modalities. The goals of this investigation were first, to evaluate the feasibility of using transcutaneous acoustic radiation force impulse (ARFI) ultrasound to quantify FC thickness and second, to optimize both imaging and motion-tracking parameters to support such measurements. FCs with varying thickness (0.1-1.0 mm) were simulated using a simple-layered geometry, and their mechanical response to an impulse of radiation force was solved using finite-element method (FEM) modeling. Ultrasound tracking of FEM displacements was performed in Field II utilizing three center frequencies (6, 9, and 12 MHz) and eight motion-tracking kernel lengths (0.5λ - 4λ). Additionally, FC thickness in two carotid plaques imaged in vivo was measured with ARFI and compared to matched histology. The results of this study demonstrate that 1) tracking pulse frequencies around 12 MHz are necessary to resolve caps around 0.2 mm; 2) large motion-tracking kernel sizes introduce bias into thickness measurements and overestimate the true cap thickness; and 3) color saturation settings on ARFI peak displacement images can impact thickness measurement accuracy substantially.}, number={9}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Czernuszewicz, Tomasz J. and Gallippi, Caterina M.}, year={2016}, month={Sep}, pages={1262–1275} }
 @article{wang_jiang_czernuszewicz_gallippi_2015, title={Dual-frequency IVUS transducer for acoustic radiation force impulse (ARFI) imaging}, ISSN={["1948-5719"]}, DOI={10.1109/ultsym.2015.0119}, abstractNote={Coronary atherosclerotic disease is the major cause of mortality in the United States. Elasticity imaging techniques such as acoustic radiation force impulse (ARFI) imaging using intravascular ultrasound (IVUS) transducers can be used to characterize coronary plaque. Conventional IVUS transducers with frequencies of 20 MHz - 60 MHz are not optimized for high-voltage, long-duration pulses required for ARFI imaging. In this work, a dual-frequency IVUS transducer, consisting of a 6.5 MHz “pushing” element and a 26 MHz “tracking” element, was designed and fabricated for ARFI application. In ARFI testing with a 160 V, 1000-cycle burst excitation, a displacement of 12.3 μm was detected in a phantom with a Young's modulus of 10 kPa at an axial depth of 3.5 mm. The result of this study suggests great potential of this dual-frequency IVUS transducer for intravascular ARFI imaging.}, journal={2015 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)}, author={Wang, Zhuochen and Jiang, Xiaoning and Czernuszewicz, Tomasz J. and Gallippi, Caterina M.}, year={2015} }
 @article{czernuszcwicz_gallippi_wang_ma_jiang_2014, title={Acoustic radiation force (ARF) generation with a novel dual-frequency intravascular transducer.}, ISSN={["1948-5719"]}, DOI={10.1109/ultsym.2014.0569}, abstractNote={Atherosclerosis and coronary artery disease remain the leading cause of death in the US. Coronary plaque is visualized with intravascular ultrasound (IVUS) and is typically implemented with high center frequencies (>20 MHz) for superior spatial resolution. Coronary plaque characterization may be improved by implementing elasticity imaging techniques such as acoustic radiation force impulse (ARFI) imaging using IVUS transducers. In this work we propose to extend ARFI imaging to a novel, dual-frequency small-aperture transducer design that includes a low-frequency “pushing” element and a high-frequency “tracking” element. A 40 MHz element (0.6 mm × 0.6 mm) was integrated onto a 5 MHz element (0.6 mm × 3 mm). Both elements of the transducer were fabricated from single crystal PMN-PT and the whole transducer was mounted on a 20 gauge needle tip. ARF-induced motion from the low-frequency element was quantified using optical tracking methods in a translucent phantom (~8 kPa) containing embedded graphite microparticles. Displacements induced by ARF excitations with 300, 600, 900, and 1200 cycles (5 MHz, 190 V) were captured and compared to baseline. Median (inter-quartile range) peak displacements for 300, 600, 900, and 1200 cycles were 0.33 (0.27 - 0.39) μm, 0.72 (0.62 - 0.87) μm, 1.1 (1.0 - 1.3) μm, and 1.6 (1.43 - 1.75) μm, respectively. In another phantom, 40 MHz pulse/echo RF lines were captured to demonstrate backscatter sensitivity. The results of this study show that ARF generation and high-resolution tracking is feasible on a small-aperture transducer fit for IVUS implementation.}, journal={2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)}, author={Czernuszcwicz, Tomasz J. and Gallippi, Caterina M. and Wang, Zhuochen and Ma, Jianguo and Jiang, Xiaoning}, year={2014}, pages={2284–2287} }
 @article{selzo_czernuszewicz_gallippi_2014, title={Displacement Underestimation Correction Using Shear Waves in VisR Ultrasound}, ISSN={["1948-5719"]}, DOI={10.1109/ultsym.2014.0261}, abstractNote={We have previously proposed an imaging technique called Viscoelastic Response (VisR) ultrasound that uses acoustic radiation force (ARF) impulses to assess the viscoelastic properties of tissue. Using two successive ARF impulses in the same region of excitation and monitoring the induced deformation, VisR fits displacements to the mass-spring-damper mechanical model to measure the relaxation time constant, τ. In this method, ARF pulses are generated by the same transducer that is used to track motion and thus, the tracked displacements are susceptible to underestimation. Displacement underestimation introduces error into measurement of τ. It is hypothesized that by utilizing shear waves to generate displacement and monitoring tissue displacement outside the region of excitation we can better estimate axial displacements and generate τ measurements that more closely represent the material. We demonstrate displacement underestimation in, versus outside of, the ROE and the associated impact on VisR-derived τ using FEM simulations and experimentally using optical tracking in a translucent tissue-mimicking phantom.}, journal={2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)}, author={Selzo, Mallory R. and Czernuszewicz, Tomasz J. and Gallippi, Caterina M.}, year={2014}, pages={1065–1068} }
 @article{behler_czernuszewicz_wu_nichols_zhu_homeister_merricks_gallippi_2013, title={Acoustic Radiation Force Beam Sequence Performance for Detection and Material Characterization of Atherosclerotic Plaques: Preclinical, Ex Vivo Results}, volume={60}, ISSN={["1525-8955"]}, DOI={10.1109/tuffc.2013.2847}, abstractNote={This work presents preclinical data demonstrating performance of acoustic radiation force (ARF)-based elasticity imaging with five different beam sequences for atherosclerotic plaque detection and material characterization. Twelve trained, blinded readers evaluated parametric images taken ex vivo under simulated in vivo conditions of 22 porcine femoral arterial segments. Receiver operating characteristic (ROC) curve analysis was carried out to quantify reader performance using spatially-matched immunohistochemistry for validation. The beam sequences employed had high sensitivity (sens) and specificity (spec) for detecting Type III+ plaques (sens: 85%, spec: 79%), lipid pools (sens: 80%, spec: 86%), fibrous caps (sens: 86%, spec: 82%), calcium (sens: 96%, spec: 85%), collagen (sens: 78%, spec: 77%), and disrupted internal elastic lamina (sens: 92%, spec: 75%). 1:1 single-receive tracking yielded the highest median areas under the ROC curve (AUC), but was not statistically significantly higher than 4:1 parallel-receive tracking. Excitation focal configuration did not result in statistically different AUCs. Overall, these results suggest ARF-based imaging is relevant to detecting and characterizing plaques and support its use for diagnosing and monitoring atherosclerosis.}, number={12}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Behler, Russell H. and Czernuszewicz, Tomasz J. and Wu, Chih-Da and Nichols, Timothy C. and Zhu, Hongtu and Homeister, Jonathon W. and Merricks, Elizabeth P. and Gallippi, Caterina M.}, year={2013}, month={Dec}, pages={2471–2487} }