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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15200042/
• 关键词: HIFU; Rat femoral artery; ultrasound contrast media; feeding vessel occulusion; myoma uteri; non pregnant rabit; pregnant rabit; イヌ子宮動脈

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无创治疗妇科肿瘤，特别是子宫肌瘤，使用高强度聚焦超声（HIFU）闭塞供血血管。以下基础研究是我们实现这一目标的第一步。首先，我们构建了一个原型HIFU换能器，其具有3.2 MHz的谐振频率，结合提供彩色多普勒成像和多普勒测速的成像探头。通过皮肤将HIFU施加到Sprague-Dawley大鼠左大腿的股深动脉;血流的彩色图像用于瞄准HIFU束。使用的峰强度为530、1080、2750和4300 W/cm 2。每次HIFU暴露的持续时间为5秒。HIFU在4300 W/cm 2的强度下实现血流阻断，但在较低强度下血流继续。经HIFU治疗的动脉中，多普勒血流速度仪测量的血流收缩期峰值速度（PSV）增加。 ...更多信息 d在1080和2750 W/cm 2。增加与HIFU强度相对应。暴露于530 W/cm 2的HIFU不会改变血流速度。组织学研究表明，暴露于2750和4300 W/cm 2的HIFU导致动脉图尼卡中膜的空泡变性和弹性纤维破坏。1080 W/cm 2的暴露导致PSV增加，但未诱导血管壁的组织学变化。这些结果表明，动脉对HIFU的反应随强度而变化。在低强度下发生无组织变性的血管收缩;随着强度的增加，组织学中可检测到的组织变性使血管直径减小，最后，在高强度下，血流被阻塞。在第二项研究中，我们假设将超声造影剂注射到血流中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）照射下动脉血流和形态学变化的影响。5只大鼠注射利声显60 mg，另5只注射生理盐水0.5ml作为对照。在530、870、1550和2750 W/cm 2的HIFU照射强度下，分别在0%（0/5）、60%（3/5）、100%（5/5）和100%（5/5）的大鼠中实现了血流阻断。在对照组中，对于每种HIFU强度，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染色显示利声显组大鼠血管图尼卡中膜出现明显空泡变性，内皮细胞脱落。这些结果表明，在HIFU照射下，造影剂的空化作用对血管内皮产生了显著影响，因此，注射造影剂提示了降低HIFU强度以实现靶动脉闭塞的可能性。总之，在临床上适用的强度HIFU可能被证明是有用的闭塞供血动脉治疗肿瘤的非侵入性。少

项目成果

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

• 期刊: J Urtrasonics. (in press)
• 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

• 发表时间: 2005
• 期刊: J Showa Med Assoc 65(2)
• 作者: Uchiyama N;Ishikawa T;Ando S;Ichihara M;Matsuoka R;Ichizuka K;Okai T
• 通讯作者: Okai T

HIFU照射による動脈閉塞に対する超音波造影剤の効果及びそれによる血管内皮の組織学的変化

超声造影剂对HIFU照射引起的动脉闭塞的影响及血管内皮组织学变化

• 发表时间: 2005
• 期刊: 昭和医学会雑誌 65巻2号
• 作者: 内山心美;石川哲也;安藤智;市原三義;松岡隆;市塚清健;岡井崇;佐々木一昭;梅村晋一郎;九島巳樹
• 通讯作者: 九島巳樹

胎児病の低侵襲治療を目指した高出力集束超音波照射による動脈閉塞実験

高功率聚焦超声照射微创治疗胎儿疾病的动脉闭塞实验

• 发表时间: 2005
• 期刊: 日本周産期・新生児医学会雑誌 41(2)
• 作者: 市塚清健;石川哲也;松岡隆;長谷川潤一;関沢明彦;岡井崇
• 通讯作者: 岡井崇