The investigator's plan to study a new perfluorocarbon stabilized microbubble (PFH stabilized uB) as a vascular imaging agent and tissue profusion agent in conjunction with standard gray scale ultrasound imaging and Doppler flow imaging. Newer ultrasound techniques such as power Doppler and second harmonic imaging will also be employed. The agent has both PFC vapor and nitrogen gas within its microbubbles. It has previously been shown by the principle investigator and others that a combination of air or nitrogen together with PFC vapor serves to stabilize microbubbles in vivo and can increase the intravascular dwell time to 8 10 minutes, which is substantionally longer that previous microbubble agents. The agent has been shown to produce a triphasic enhancement pattern in liver tumors (arterial, portal venous and entrapment phase) on standard gray scale imaging which increases tumor conspicuity and possibly specificity by displaying abnormal tumor vessels during the arterial and portal venous phases. Further, the agent is highly efficient in second harmonic imaging which can produce a tissue specific contrast enhancement compared to a background when no contrast media is present. The investigators are aware that increased backscatter also increases attenuation and the impact of attenuation on lesion detection will be explored. The investigators hope that they can come up with an optimal imaging strategy which will increase tumor conspicuity in both the near and far field. They will evaluate the effect of attenuation and describe the tumor enhancement pattern as a function of lesion depth, transmit frequency and imaging technique (standard versus second harmonic) over time. They will also test their hypothesis that since pressure decreases the longevity of the agent that the near field lesions will be better imaged early while far field lesions will be better imaged late. Testing of this hypothesis and determining if it is true is crucial to any human clinical trial since the time of imaging will be important so that lesions will not be missed by imaging at the wrong time post administration of the agent. In addition to these fundamental studies, additional biological studies such as trying to define the mechanism of liver entrapment and determine on a cellular or subcellular level the biodistribution of the microbubbles (sinusoidal versus intracellular) will also be carried out. In vitro studies will explore in both stationary and flowing blood variables that can effect echogenicity and backscatter such as the velocity to assess shear effects, ambient and insonation pressure, interrogating frequency and imaging technique, vessel size and angle of incidence and concentration. Phantom studies will also be conducted using reference standard materials as a control and reference to in vivo measurements.
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