Non-invasive treatment of uterine fibroid by feeding vessel occlusion using HIFU sonication.

本研究的最终目的是利用高强度聚焦超声（HIFU）阻断子宫肌瘤的供血血管，实现对子宫肌瘤的无创治疗。作为该目标的一个步骤，已经进行了以下基础研究：1）测量子宫肌瘤的血流;将微泡溶液Levovist ® R施用给子宫肌瘤患者。通过脉冲间隔时间（0.5、1、3、5秒）测量来自组织的信号强度的增加，并计算血流指数。比较子宫肌瘤与子宫肌层的组织血流指标。2）动脉阻断动物实验：超声辐照Sprague道利大鼠股深动脉。超声处理的持续时间为5秒。通过4300 W/cm ^2的HIFU超声处理实现血流阻断，但在530、1080和2750 W/cm ^2的强度下保持血流。豌豆 ...更多信息 在1080和2750 W/cm^2的HIFU声处理动脉中，k收缩期血流速度增加，并与HIFU强度相关。组织学研究表明，暴露于2750和4300 W/cm ^2的HIFU的血管图尼卡中膜出现空泡变性。注射超声造影剂（Levovist^R）降低了动脉闭塞所需的HIFU强度，因为微泡在超声声处理下被破坏并对血管内皮产生空化效应，这将损伤血管。3）通过闭塞肿瘤供血动脉来降低肿瘤的效果，将VX 2（皮肤鳞状细胞癌细胞）植入日本白色兔的右股肌肉中。3周后，提供动物进行HIFU超声处理供血动脉的实验（峰值强度; 4kW/cm ^2）。对照组肿瘤体积较治疗前明显增大。另一方面，在研究组中，肿瘤体积显示出增加的趋势，但未认识到其显著性。HE染色显示动脉图尼卡中膜空泡变性，肿瘤变性坏死。4）人子宫肌瘤供血动脉闭塞;共有6例子宫肌瘤患者入选本研究。剖腹手术后应用HIFU。峰强度为2（n=4）和4（n=5）kW/cm ^2。在以2 kW/cm ^2的功率施加HIFU的纤维瘤动脉中，HE染色显示动脉中膜图尼卡出现空泡变性，但血流并未停止。4 kW/cm^2的高强度聚焦超声可成功阻断子宫肌瘤动脉。在这些病例中，HE染色显示图尼卡中膜和塌陷腔中有强烈的空泡变性。我们的研究已经证明，HIFU超声处理可以实现深动脉闭塞。除此之外，流向子宫肌瘤的低组织血流量也支持通过HIFU阻断肿瘤的供血可能是子宫肌瘤非侵入性治疗的一种选择。少

The final goal of our study is to develop the non-invasive therapy for uterine fibroid by feeding vessels occlusion using high intensity focused ultrasound (HIFU). As a step for the goal, following basic studies have been conducted.1) Measurement of blood flow to uterine fibroid; A micro bubble solution, Levovist^R, was administrated to the patient of uterine fibroid. Increases in the intensity of signal from the tissue were measured by pulsing interval times (0.5, 1, 3, 5 seconds) and blood flow indices were calculated. The indices of tissue blood flow of uterine fibroids were compared with those of the myometrium. The result showed lower tissue blood flow to uterine fibroid than myometrium.2) Animal experiments for artery occlusion; HIFU was sonicated to deep femoral arteries of Sprague Dawley rats. Duration of sonication was 5seconds. Blood flow occlusion was accomplished by HIFU sonication at 4300 W/cm^2, but the flow was preserved with intensities at 530, 1080 and 2750 W/cm^2. Pea … More k systolic velocity of blood flow increased in sonicated arteries with HIFU at 1080 and 2750 W/cm^2 and correlated with HIFU intensity. Histological studies have demonstrated vacuolar degeneration in tunica media of the vessels exposed to HIFU at 2750 and 4300 W/cm^2. Injecting ultrasound contrast agents (Levovist^R) decreased the HIFU intensity required for arterial occlusion, because microbubbles were destroyed under ultrasound sonication and exerted a cavitation effect on the vessel endothelium, which would damage blood vessels.3)Reducing effect of tumor by occlusion of the tumor feeding artery, VX2 (dermatological squamous cancer cell) was implanted in the right femoral muscles of Japanese White rabbits. After 3 weeks, animals were provided to experiment of HIFU sonication to feeding arteries (Peak intensity; 4kW/cm^2). In the control group, the tumor volume increased significantly in comparison with before HIFU sonication. On the other hand, in the study group, the tumor volume showed a tendency to increase, but the significance was not recognized. HE staining revealed vacuolar degeneration in the tunica media of the artery and degenerative necrosis in the tumor.4) Occlusion of the human uterine fibroid feeding artery; A total of 6 patients with uterine fibroids, who had been scheduled for hysterectomy were enrolled in this study. HIFU was applied after laparotomy. Peak intensities were 2 (n=4) and 4 (n=5) kW/cm^2. In those fibroid arteries to which HIFU had been applied at 2 kW/cm^2, the HE stain revealed a vacuolar degeneration in the tunica media of the artery, although cessation of blood flow was not accomplished. The uterine fibroids artery could be successfully occluded by HIFU at 4 kW/cm^2 in two cases out of five. In these cases, the HE stain revealed strong vacuolar degeneration in the tunica media and collapsed cavity. It has been demonstrated by our study that HIFU sonication can achieve the occlusion of deep arteries. Additionally to this fact, low tissue blood flow to uterine fibroid also support that, occlusion of tumors' feeding by HIFU may be an option for non-invasive therapy for uterine fibroid. Less