The overall goal of this proposal is to create a system and conduct the required studies to propel ultrasound contrast imaging into breast cancer management. Ultrasound contrast agents, which are shell-encapsulated microbubbles, are used to increase the acoustic backscatter from blood providing the opportunity for ultrasound molecular imaging and the detection of angiogenic tumor vasculature. Imaging modes, including phase-inversion and subharmonic modes, exploit nonlinear oscillation of these agents; however, these modes are most effective for a range of transmission frequencies below 6 MHz. When contrast imaging has been attempted with higher transmitted frequencies, poor depth of penetration, limited signal to noise ratio, and poor tissue/contrast echo separation have resulted. High resolution clinical systems operating near 15 MHz are becoming more available and are particularly important for cancer imaging, however, they lack sensitive harmonic imaging modes for contrast agent detection. We propose a new strategy to greatly increase the effective bandwidth utilizing transducers with widely separated center frequencies arranged confocally to simultaneously excite and receive echoes from contrast agent. In addition to a higher frame rate, experiments have been performed to demonstrate that the resulting new imaging mode shows similar resolution, higher echo amplitudes, and greatly reduced attenuation compared to transmission at a higher frequency, and superior resolution compared to transmission and reception at a lower frequency. The proposed method is shown to provide the opportunity to detect contrast agents in capillaries and resolve vessels on the order of 100 microns. The proposed high resolution system could have a substantial advantage in the diagnosis of small tumors, where the increased vascular density is limited to a region on the order of several millimeters. Our preliminary results demonstrate that it is possible to detect angiogenic regions in tumors with a diameter on the order of millimeters with ultrasound contrast imaging, however, the signal to noise ratio of this measurement would be greatly increased with the proposed system. The proposed system should allow reliable and quantitative mapping of the distribution of targeted contrast agents, and thus could have a very high significance for cancer imaging. We will test the performance and safety of the system for cancer imaging through in vitro and in vivo studies. ? ? ?
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