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

通过暴露于高强度聚焦超声来闭塞喂养血管治疗子宫肌瘤的无创治疗装置和临床技术的开发

基本信息

批准号：
15200042
负责人：
OKAI Takashi
金额：
$ 26.79万
依托单位：
Showa Unviersity School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

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

本研究的最终目的是开发一种使用高强度聚焦超声(HIFU)闭塞供血血管的非侵入性治疗妇科肿瘤，特别是子宫肌瘤的方法。以下基础研究是我们迈向这一目标的第一步。首先，我们构建了一个共振频率为3.2 MHz的HIFU换能器原型，并结合一个提供彩色多普勒成像和多普勒测速的成像探头。将HIFU经皮照射至SD大鼠左大腿股深动脉，用彩色血流图像对准HIFU束。峰值强度分别为530、1080、2750和4300W/cm2。每次HIFU照射的持续时间为5秒。HIFU以4300W/cm2的强度完成血流阻断，但以较低的强度继续血流。用多普勒测速仪测量的血流峰值收缩速度(PSV)在接受…治疗的动脉中增加。在1080W/cm2和2750W/cm2时，d值较大。这种增加与HIFU强度相对应。照射功率为530W/cm2的HIFU对血流速度无明显影响。组织学研究表明，2750和4300W/cm2的HIFU照射可导致动脉中膜的空泡变性和弹力纤维破坏。1080W/cm2照射可导致PSV增加，但未引起血管壁的组织学改变。这些结果表明，动脉对HIFU的反应因强度不同而不同。低强度时血管收缩，但无组织变性；随着强度的增加，组织学上可检测到的组织变性缩小了血管直径，最终在高强度时，血流被闭塞。在第二项研究中，我们假设向血流中注入超声造影剂可能会降低闭塞的最小HIFU强度。本研究旨在探讨造影剂对高强度聚焦超声(HIFU)照射后动脉血流和形态变化的影响。其中5只大鼠注射60 mg左氧氟沙星，另5只大鼠注射生理盐水0.5ml作为对照。HIFU强度为530、870、1550和2750W/cm2时，分别有0%(0/5)、60%(3/5)、100%(5/5)和100%(5/5)的大鼠血流闭塞。对照组各强度HIFU血流阻断成功率分别为0%(0/5)、0%(0/5)、0%(0/5)和80%(4/5)。H-E染色显示Levovist组大鼠中膜有明显的空泡变性，内皮细胞脱落。这些结果表明，HIFU照射下造影剂的空化对血管内皮细胞有明显的影响，因此，注射造影剂提示有可能降低HIFU的强度以达到阻断靶动脉的目的。综上所述，临床适用强度的HIFU在阻断供血动脉以非侵入性治疗肿瘤方面可能被证明是有用的。较少

项目成果

期刊论文数量（33）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Functional and histological changes in rat femoral arteries by HIFU exposure

DOI：
10.1016/s0301-5629(03)00951-7
发表时间：
2003-10-01
期刊：
ULTRASOUND IN MEDICINE AND BIOLOGY
影响因子：
2.9
作者：
Ishikawa, T;Okai, T;Ichizuka, K
通讯作者：
Ichizuka, K

Effect of simultaneous application of ultrasound contrast agents and HIFU on occlusion of arteries

超声造影剂与HIFU同时应用对动脉闭塞的影响

DOI：
发表时间：
期刊：
J Urtrasonics. (in press)
影响因子：
0
作者：
Uchiyama N;Okai T;Kasuaki S;Shinichiro U;Ishikawa T;Kushima M;Ando S;Ichihara M;Matsuoka R;Ichizuka K.
通讯作者：
Ichizuka K.

EFFECT OF CONTRAST AGENTS ON ARTERIES OCCLUDED BY EXPOSURE TO HIFU

造影剂对 HIFU 暴露引起的闭塞动脉的影响