市塚 清健¹, 岡井 崇¹, 藤原 礼¹, 石川 哲也¹, 市原 三義¹, 梅村 晋一郎^{1, 2}, 佐々木 一昭², 川畑 健一², 馬場 一憲³

Kiyotake ICHIZUKA¹, Takashi OKAI¹, Rei FUJIWARA¹, Tetsuya ISHIKAWA¹, Mitsuyoshi ICHIHARA¹, Shinichiro UMEMURA^{1, 2}, Kazuaki SASAKI², Kenichi KAWABATA², Kazunori BABA³

¹昭和大学産婦人科, ²日立製作所中央研究所ライフサイエンス研究センター, ³埼玉医科大学総合医療センター総合周産期母子医療センター

¹Department of Obstetrics and Gynecology, Showa University School of Medicine, ²Medical Systems Research Department, Central Research Laboratory, Hitachi, Ltd., ³Center for Maternal, Fetal, and Neonatal Medicine, Saitama Medical School

キーワード : HIFU, vessel occlusion, blood flow, uterine fibroid

超音波は, レーザー等の電磁波に比べ体内深部への深達度およびエネルギー集束性に優れ, また人体への影響が少ないことから, 近年は診断のみならず治療へも応用され始めている. 我々は強出力集束超音波(High-intensity focused ultrasound; HIFU)の照射により子宮筋腫栄養血管の血流を遮断することによる低侵襲の治療法を考案し, その手技を確立するために基礎的検討を行った. 1) 血管の閉塞実験；SDラットの深部大腿動脈にHIFUを皮膚上より対象血管を横切るように5秒間照射した. 超音波強度は530, 1080, 2750, 4300 W/cm²とした. 4300 W/cm²の照射では血流遮断が可能であった. 1080, 2750 W/cm²照射後, 照射部位での収縮期最高速度は強度と共に増加した. 2750, 4300 W/cm²の照射後, 組織学的に血管中膜に空胞変性が認められた. 2) 子宮筋腫の組織血流量の検討；マイクロバブル溶液である超音波造影剤Levovist^®をインフォームドコンセントの得られた患者に静脈投与し, 0.5, 1, 3, 5秒間隔の超音波照射で得られるドプラシグナル強度をもとに相対的組織血流量を測定した. その結果, 子宮筋腫核は正常子宮筋層に比べ血流量の指数が低値であった. 我々の実験で, HIFU照射により深部小動脈の血流閉塞が可能であることが示され, また, 組織血液量が少ないという筋腫の血流特性などの検討からも, 本法を無侵襲の子宮筋腫治療へ発展させ得る可能性が示唆された. 本論文は日本超音波医学会研究開発班の研究の一環で行われた研究報告のレビューである.

The ultimate purpose of this study is to develop a noninvasive therapy for 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, high-intensity focused ultrasound was used in animal experiments on arterial occlusion to sonicate deep femoral arteries in the thighs of Sprague Dawley rats through the skin while visualizing blood flow with color imaging. Peak ultrasound intensities were 530, 1080, 2750, and 4300 W/cm², and high-intensity focused ultrasound sonication lasted 5 seconds. Blood flow was occluded by high-intensity focused ultrasound exposure of 4300 W/cm² but was preserved with intensities of 530, 1080, and 2750 W/cm². Peak systolic velocity of blood flow measured by Doppler velocimetry increased in arteries sonicated with high-intensity focused ultrasound of 1080 and 2750 W/cm² and correlated with high-intensity focused ultrasound intensity. Histologic studies have demonstrated vacuolar degeneration in the tunica media of vessels exposed to high-intensity focused ultrasound at 2750 and 4300 W/cm². In a second study, we measured blood flow to the uterine fibroids. After obtaining informed consent from all patients, we administered a microbubble solution of a galactose-based microbubble contrast agent (Levovist^®) to a patient with a uterine fibroid. Increase in the intensity of the signal returned from the tissue was measured by pulsing at intervals of 0.5, 1, 3, and 5 seconds, and blood-flow indices were calculated. The indices of tissue blood flow in uterine fibroids were compared with those of the myometrium. The result showed that blood flow was lower in the uterine fibroids than in the myometrium. We thus demonstrated that high-intensity focused ultrasound exposure can occlude deep arteries. Further, low blood flow in the uterine fibroids also supports the view that occlusion of tumor feeding arteries by high-intensity focused ultrasound may offer a noninvasive option for treating uterine fibroids. This paper forms part of a continuing study supported by the Research and Development Committee Program of The Japan Society of Ultrasonics in Medicine.