@article{gessner_streeter_kothadia_feingold_dayton_2012, title={AN IN VIVO VALIDATION OF THE APPLICATION OF ACOUSTIC RADIATION FORCE TO ENHANCE THE DIAGNOSTIC UTILITY OF MOLECULAR IMAGING USING 3-D ULTRASOUND}, volume={38}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2011.12.005}, abstractNote={For more than a decade, the application of acoustic radiation force (ARF) has been proposed as a mechanism to increase ultrasonic molecular imaging (MI) sensitivity in vivo. Presented herein is the first noninvasive in vivo validation of ARF-enhanced MI with an unmodified clinical system. First, an in vitro optical-acoustical setup was used to optimize system parameters and ensure sufficient microbubble translation when exposed to ARF. 3-D ARF-enhanced MI was then performed on 7 rat fibrosarcoma tumors using microbubbles targeted to αvβ3 and nontargeted microbubbles. Low-amplitude (<25 kPa) 3-D ARF pulse sequences were tested and compared with passive targeting studies in the same animal. Our results demonstrate that a 78% increase in image intensity from targeted microbubbles can be achieved when using ARF relative to the passive targeting studies. Furthermore, ARF did not significantly increase image contrast when applied to nontargeted agents, suggesting that ARF did not increase nonspecific adhesion.}, number={4}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Gessner, Ryan C. and Streeter, Jason E. and Kothadia, Roshni and Feingold, Steven and Dayton, Paul A.}, year={2012}, month={Apr}, pages={651–660} }
 @article{gessner_kothadia_feingold_dayton_2011, title={3-D MICROVESSEL-MIMICKING ULTRASOUND PHANTOMS PRODUCED WITH A SCANNING MOTION SYSTEM}, volume={37}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2010.12.013}, abstractNote={Ultrasound techniques are currently being developed that can assess the vascularization of tissue as a marker for therapeutic response. Some of these ultrasound imaging techniques seek to extract quantitative features about vessel networks, whereas high-frequency imaging also allows individual vessels to be resolved. The development of these new techniques, and subsequent imaging analysis strategies, necessitates an understanding of their sensitivities to vessel and vessel network structural abnormalities. Constructing in-vitro flow phantoms for this purpose can be prohibitively challenging, because simulating precise flow environments with nontrivial structures is often impossible using conventional methods of construction for flow phantoms. Presented in this manuscript is a method to create predefined structures with <10 μm precision using a three-axis motion system. The application of this technique is demonstrated for the creation of individual vessel and vessel networks, which can easily be made to simulate the development of structural abnormalities typical of diseased vasculature in vivo. In addition, beyond facilitating the creation of phantoms that would otherwise be very challenging to construct, the method presented herein enables one to precisely simulate very slow blood flow and respiration artifacts, and to measure imaging resolution. (E-mail: [email protected])}, number={5}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Gessner, Ryan C. and Kothadia, Roshni and Feingold, Steven and Dayton, Paul A.}, year={2011}, month={May}, pages={827–833} }
 @article{sheeran_wong_luois_mcfarland_ross_feingold_matsunaga_dayton_2011, title={DECAFLUOROBUTANE AS A PHASE-CHANGE CONTRAST AGENT FOR LOW-ENERGY EXTRAVASCULAR ULTRASONIC IMAGING}, volume={37}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2011.05.021}, abstractNote={Currently available microbubbles used for ultrasound imaging and therapeutics are limited to intravascular space due to their size distribution in the micron range. Phase-change contrast agents (PCCAs) have been proposed as a means to overcome this limitation, since droplets formed in the hundred nanometer size range might be able to extravasate through leaky microvasculature, after which they could be activated to form larger highly echogenic microbubbles. Existing PCCAs in the sub-micron size range require substantial acoustic energy to be vaporized, increasing the likelihood of unwanted bioeffects. Thus, there exists a need for PCCAs with reduced acoustic activation energies for use in imaging studies. In this article, it is shown that decafluorobutane, which is normally a gas at room temperature, can be incorporated into metastable liquid sub-micron droplets with appropriate encapsulation methods. The resulting droplets are activatable with substantially less energy than other favored PCCA compounds. Decafluorobutane nanodroplets may present a new means to safely extend ultrasound imaging beyond the vascular space.}, number={9}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Sheeran, Paul S. and Wong, Vincent P. and Luois, Samantha and McFarland, Ryan J. and Ross, William D. and Feingold, Steven and Matsunaga, Terry O. and Dayton, Paul A.}, year={2011}, month={Sep}, pages={1518–1530} }
 @article{seiler_salmon_mantuo_feingold_dayton_gilger_2011, title={Effect and Distribution of Contrast Medium after Injection into the Anterior Suprachoroidal Space in Ex Vivo Eyes}, volume={52}, ISSN={1552-5783}, url={http://dx.doi.org/10.1167/iovs.11-7525}, DOI={10.1167/iovs.11-7525}, abstractNote={PURPOSE
To determine the effects and posterior distribution of injections made into the anterior suprachoroidal space (SCS).


METHODS
The anterior SCS of adult porcine and canine ex vivo eyes was cannulated. Latex injections and high frequency ultrasound (50 MHz) was used to image the effect and distension of the SCS. Flow characteristics and percentage maximal distribution of microbubble contrast injection into the SCS were assessed by 2D and 3D ultrasound.


RESULTS
Mean (SD) distension of the SCS with PBS increased from 1.57 (0.48) mm after injection of 250 μL to 3.28 (0.57) mm with 1000 μL PBS. Eyes injected at physiologic IOP had no significant difference in SCS distension. In real-time 2D ultrasound, the contrast agent flowed from the injection site to the opposite ventral anterior SCS and the posterior SCS. Contrast arrived at the opposite and posterior SCS 7.8 (4.6) and 7.7 (4.6) seconds after injection, respectively. In sagittal images, contrast was visible in 24.0%to 27.2% of the SCS; in 10 of 12 eyes, contrast reached the posterior pole of the eye. In 3D images, contrast medium occupied 39.0% to 52.1% of the entire SCS.


CONCLUSIONS
These results suggest that the SCS can expand, in a dose-dependent manner, to accommodate various volumes of fluid and that it is possible to image the SCS with ultrasound contrast. The authors' hypothesis that a single anterior SCS injection can reach the ocular posterior segment was supported. Further development of SCS injections for treatment of the ocular posterior segment is warranted.}, number={8}, journal={Investigative Opthalmology & Visual Science}, publisher={Association for Research in Vision and Ophthalmology (ARVO)}, author={Seiler, Gabriela S. and Salmon, Jacklyn H. and Mantuo, Rebecca and Feingold, Steven and Dayton, Paul A. and Gilger, Brian C.}, year={2011}, month={Jul}, pages={5730} }
 @article{kogan_johnson_feingold_garrett_guracar_arendshorst_dayton_2011, title={VALIDATION OF DYNAMIC CONTRAST-ENHANCED ULTRASOUND IN RODENT KIDNEYS AS AN ABSOLUTE QUANTITATIVE METHOD FOR MEASURING BLOOD PERFUSION}, volume={37}, ISSN={["0301-5629"]}, DOI={10.1016/j.ultrasmedbio.2011.03.011}, abstractNote={Contrast-enhanced ultrasound (CEUS) has demonstrated utility in the monitoring of blood flow in tissues, organs and tumors. However, current CEUS methods typically provide only relative image-derived measurements, rather than quantitative values of blood flow in milliliters/minute per gram of tissue. In this study, CEUS derived parameters of blood flow are compared with absolute measurements of blood flow in rodent kidneys. Additionally, the effects of contrast agent infusion rate and transducer orientation on image-derived perfusion measurements are assessed. Both wash-in curve and time-to-refill algorithms are examined. Data illustrate that for all conditions, image-derived flow measurements were well-correlated with transit-time flow probe measurements (R > 0.9). However, we report differences in the sensitivity to flow across different transducer orientations as well as the contrast analysis algorithm utilized. Results also indicate that there exists a range of contrast agent flow rates for which image-derived estimates are consistent.}, number={6}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Kogan, Paul and Johnson, Kennita A. and Feingold, Steven and Garrett, Nicholas and Guracar, Ismayil and Arendshorst, William J. and Dayton, Paul A.}, year={2011}, month={Jun}, pages={900–908} }
 @article{feingold_gessner_guracar_dayton_2010, title={Quantitative Volumetric Perfusion Mapping of the Microvasculature Using Contrast Ultrasound}, volume={45}, ISSN={["1536-0210"]}, DOI={10.1097/rli.0b013e3181ef0a78}, abstractNote={Objectives:Contrast-enhanced ultrasound imaging has demonstrated significant potential as a noninvasive technology for monitoring blood flow in the microvasculature. With the application of nondestructive contrast imaging pulse sequences combined with a clearance-refill approach, it is possible to create quantitative time-to-refill maps of tissue correlating to blood perfusion rate. One limitation to standard two-dimensional (2D) perfusion imaging is that the narrow elevational beamwidth of 1- or 1.5-D ultrasound transducers provides information in only a single slice of tissue, and thus it is difficult to image exactly the same plane from study to study. We hypothesize that inhomogeneity in vascularization, such as that common in many types of tumors, makes serial perfusion estimates inconsistent unless the same region can be imaged repeatedly. Our objective was to evaluate error in 2D quantitative perfusion estimation in an in vivo sample volume because of differences in transducer positioning. To mitigate observed errors due to imaging plane misalignment, we propose and demonstrate the application of quantitative 3-dimensional (3D) perfusion imaging. We also evaluate the effect of contrast agent concentration and infusion rate on perfusion estimates. Materials and Methods:Contrast-enhanced destruction-reperfusion imaging was performed using parametric mapping of refill times and custom software for image alignment to compensate for tissue motion. Imaging was performed in rats using a Siemens Sequoia 512 imaging system with a 15L8 transducer. A custom 3D perfusion mapping system was designed by incorporating a computer-controlled positioning system to move the transducer in the elevational direction, and the Sequoia was interfaced to the motion system for timing of the destruction-reperfusion sequence and data acquisition. Perfusion estimates were acquired from rat kidneys as a function of imaging plane and in response to the vasoactive drug dopamine. Results:Our results indicate that perfusion estimates generated by 2D imaging in the rat kidney have mean standard deviations on the order of 10%, and as high as 22%, because of differences in initial transducer position. This difference was larger than changes in kidney perfusion induced by dopamine. With application of 3D perfusion mapping, repeatability in perfusion estimated in the kidney is reduced to a standard deviation of less than 3%, despite random initial transducer positioning. Varying contrast agent administration rate was also observed to bias measured perfusion time, especially at low concentrations; however, we observed that contrast administration rates between 2.7 × 108 and 3.9 × 108 bubbles/min provided results that were consistent within 3% for the contrast agent type evaluated. Conclusions:Three-dimensional perfusion imaging allows a significant reduction in the error caused by transducer positioning, and significantly improves the reliability of quantitative perfusion time estimates in a rat kidney model. When performing perfusion imaging, it is important to use appropriate and consistent contrast agent infusion rates to avoid bias.}, number={10}, journal={INVESTIGATIVE RADIOLOGY}, author={Feingold, Steven and Gessner, Ryan and Guracar, Ismayil M. and Dayton, Paul A.}, year={2010}, month={Oct}, pages={669–674} }
 @article{hettiarachchi_lee_zhang_feingold_dayton_2009, title={Controllable Microfluidic Synthesis of Multiphase Drug-Carrying Lipospheres for Site-Targeted Therapy}, volume={25}, ISSN={["1520-6033"]}, DOI={10.1002/btpr.214}, abstractNote={Abstract}, number={4}, journal={BIOTECHNOLOGY PROGRESS}, author={Hettiarachchi, Kanaka and Lee, Abraham P. and Zhang, Shirley and Feingold, Steven and Dayton, Paul A.}, year={2009}, pages={938–945} }
 @article{streeter_gessner_tsuruta_feingold_dayton, title={Assessment of molecular imaging of angiogenesis with three-dimensional ultrasonography}, volume={10}, number={6}, journal={Molecular Imaging}, author={Streeter, J. E. and Gessner, R. C. and Tsuruta, J. and Feingold, S. and Dayton, P. A.}, pages={460–468} }