Second and third generation ultrasonic contrast agents have created an exciting new opportunity to image local microvascular perfusion. Physicians and physiologists have long recognized the significance of tissue perfusion, however, important questions remain unanswered due to the lack of assessment tools. Our initial observations show promise for a new family of diagnostic tools that could be applied to assess cancer, cardiovascular disease, glaucoma and wound healing. The techniques described in this proposal could provide the opportunity to map microvascular density and heterogeneity at the correct scale for the detection of tumors and to assess the maximum local microvascular transit time. Using a unique new experimental system, we have established that a set of physical phenomena affect the scattered signal from ultrasound contrast agents, and provide significant opportunities for new tools for the assessment of vascular function as well as structure. In this application, we propose to extend these studies to evaluate these effects through intravital microscopy, and to take advantage of these phenomena to tailor a new imaging mode to assess vascular density and microvascular transit time. Due to our expertise in tumor vascularity, we propose to focus our investigations on applications in this area. However, the proposed techniques could have far wider clinical application. We propose to map vascular density and transit time. A new mode called recovery imaging will be employed in which microbubbles are destroyed in a local region and the timing for echo restoration determined. These new methods will be evaluated in phantoms, through intravital microscopy in an ischemic rat model, and in a final comparative study of four mouse tumor cell lines and a benign fibroadenoma model.
| Hu, Xiaowen; Zheng, Hairong; Kruse, Dustin E et al. (2010) A sensitive TLRH targeted imaging technique for ultrasonic molecular imaging. IEEE Trans Ultrason Ferroelectr Freq Control 57:305-16 |
| Pollard, Rachel E; Dayton, Paul A; Watson, Katherine D et al. (2009) Motion corrected cadence CPS ultrasound for quantifying response to vasoactive drugs in a rat kidney model. Urology 74:675-81 |
| Qin, Shengping; Kruse, Dustin E; Ferrara, Katherine W (2008) Transmitted ultrasound pressure variation in micro blood vessel phantoms. Ultrasound Med Biol 34:1014-20 |
| Zheng, Hairong; Dayton, Paul A; Caskey, Charles et al. (2007) Ultrasound-driven microbubble oscillation and translation within small phantom vessels. Ultrasound Med Biol 33:1978-87 |
| Pollard, Rachel E; Broumas, Amy R; Wisner, Erik R et al. (2007) Quantitative contrast enhanced ultrasound and CT assessment of tumor response to antiangiogenic therapy in rats. Ultrasound Med Biol 33:235-45 |
| Sun, Yang; Kruse, Dustin E; Ferrara, Katherine W (2007) Contrast imaging with chirped excitation. IEEE Trans Ultrason Ferroelectr Freq Control 54:520-9 |
| Qin, Shengping; Ferrara, Katherine W (2007) The natural frequency of nonlinear oscillation of ultrasound contrast agents in microvessels. Ultrasound Med Biol 33:1140-8 |
| Borden, Mark A; Martinez, Gary V; Ricker, Josette et al. (2006) Lateral phase separation in lipid-coated microbubbles. Langmuir 22:4291-7 |
| Sun, Yang; Zhao, Shukui; Dayton, Paul A et al. (2006) Observation of contrast agent response to chirp insonation with a simultaneous optical-acoustical system. IEEE Trans Ultrason Ferroelectr Freq Control 53:1130-7 |
| Qin, Shengping; Ferrara, Katherine W (2006) Acoustic response of compliable microvessels containing ultrasound contrast agents. Phys Med Biol 51:5065-88 |
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