Development of Noninvasive Therapeutic Devices and Clinical Techniques for Treating Uterine Fibroid by Occluding Feeding Vessels Through Exposure to High Intensity Focused Ultrasound

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The ultimate purpose of this study is to develop a noninvasive therapy for gynecologic tumors, particularly uterine fibroid, using high intensity focused ultrasound (HIFU) to occlude the feeding vessels. The following basic studies comprise our first step toward that goal. First, we constructed a prototype HIFU transducer which has a resonant frequency of 3.2 MHz, in combination with an imaging probe that provides color Doppler imaging and Doppler velocimetry. HIFU was applied through the skin to deep femoral arteries in left thighs of Sprague-Dawley rats ; color images of the blood flow were used to aim the HIFU beam. Peak intensities used were 530, 1080, 2750 and 4300 W/cm2. The duration of each HIFU exposure was 5 seconds. Blood flow occlusion was accomplished by HIFU at an intensity of 4300 W/cm2, but the flow continued with the lower intensities. Peak systolic velocities (PSVs) of blood flow as measured by Doppler velocimetry increased in the arteries to which HIFU had been applie … More d at 1080 and 2750 W/cm2. The increase corresponded with HIFU intensity. Exposure to HIFU at 530 W/cm2 did not change the blood flow velocity. Histologic studies have demonstrated that exposure to HIFU at 2750 and 4300 W/cm2 leads to vacuolar degeneration and destruction of elastic fibers of the tunica media of the artery. Exposure at 1080 W/cm2 led to increased PSV, but did not induce histologic changes in the vessel wall. These results suggest that the response of the artery to HIFU varied with intensity. Vascular contraction without tissue degeneration occurred at low intensity; with increasing intensity, the tissue degeneration detectable in histology reduced the vascular diameter and, finally, at high intensity, the blood flow was occluded. In the second study, we hypothesized that the injection of ultrasound contrast agents into blood flow might decrease the minimal HIFU intensity for the occlusion. The study was conducted to investigate the effect of contrast agents on changes in blood flow and morphology of arteries by HIFU exposure. Five rats had injection of 60mg of Levovist, and other 5 had 0.5ml of saline as control. Blood flow occlusion was achieved in 0%(0/5), 60%(3/5), 100%(5/5) and 100%(5/5) of rats with administration of Levovist by HIFU exposure at the intensity of 530, 870, 1550 and 2750 W/cm2, respectively. In control rats, the rate of successful blood flow occlusion were 0%(0/5), 0%(0/5), 0%(0/5), and 80%(4/5), for each HIFU intensity. The H-E stain revealed a strong vacuolar degeneration in the tunica media and endothelium cells fall off the vessel wall in rats with Levovist. These results imply that the cavitation of contrast agents under HIFU exposure exerts significant effects on the endothelium of vessels, therefore, the, injection of contrast agents suggests the possibility for reduction of the intensity of HIFU to achieve the occlusion of targeting arteries. In conclusion, HIFU at clinically applicable intensity might prove useful in occluding feeding arteries for treating tumors non-invasively. Less