This application proposes to develop an ultrasound technique that uses microbubble-based contrast agents to measure blood flow in mouse tumors. Towards this goal, the investigators have developed a multigating pulse sequence that allows acquisition of ultrasound images at a variable frame rate during bolus injection of the contrast agent. The rate at which the microbubbles are destroyed as a function of image acquisition is used to measure contrast flow. The overall goal is to validate this approach and to develop it to a form that can be used to measure flow on a routine basis. The proposed research has five specific aims involving (i) further refinement of the technique, (ii) its validation by comparison with true flow in phantoms and mouse tumors, (iii) establishing the influence of various imaging and contrast agent properties on the measurements, (iv) establishing the limits imposed by inter- and intra- subject variability in the measurements and (v) demonstrating the feasibility of the technique for measuring change in blood flow in response to physiological and therapeutic interventions. At the completion of this project the investigators anticipate having a thoroughly evaluated method for the assessment of blood flow using ultrasound contrast agents. With the approval of various contrast agents for use in clinics by the regulatory agencies impending, this technology is timely and is likely to useful in the diagnosis and treatment of many cancers and cardiovascular diseases.
