VASCULAR BUBBLE GENERATION FOR DIAGNOSIS AND THERAPY

这是一个修订后的提案，旨在开发和评估受控发电 使用高强度聚焦超声脉冲的动脉微泡 可能的诊断和治疗用途。自上次提交以来， 在体外流动的全血中已经产生了动脉微泡 用725千赫的超声波通过犬类组织模拟人类 经皮生成。在血液中观察到的阈值强度是 比之前的1.8 MHz低2.3倍，温度上升 实际放置的椎骨是可以接受的。短丸给药 超声成像，小于40微米的气泡，产生于 选定的动脉，应可用于诊断和监测 目前评估较多的血管和血流灌注异常 缓慢且昂贵，而且可能更具侵入性，使用MRI或 需要动脉插管的血管造影术。20的稀疏分布 应使用40微米至40微米的气泡来重新聚焦超声束 通过像差覆盖的组织进行分辨率成像，甚至用于成像 穿过头骨。丸剂的第一个也是最确定的医学用途 预计生成的供血动脉将识别为 治疗靶点，如肿瘤和动静脉畸形。 供血动脉的凝结，或由重复的， 更广泛的推注，将遮挡目标，使其更安全、更有效 超声波或化学疗法或外科手术。超声场知识 它产生的血管微泡对血管的损害可以忽略不计 闭塞将有助于改进安全诊断和治疗指南 超音波。 气泡将在不同的条件下产生和表征 旨在实现上述目标。研究将包括气泡大小 有无造影剂的分布、成分和寿命 播种和在两个或更多个超声频率下，脉冲幅度和 持续时间和血流速度。目前在团剂生产方面取得了成功 动脉壁损伤最小的暴露动脉显然是由于 在血管内聚焦。更低的频率和其他技术将 用于所需的气泡生成，具有较低的热能和空化能力 损坏，甚至可能是在更小、更深的容器中 遏制焦点是不可能的。体内研究将是 最初在脑血管系统进行，因为有很好的机会 大脑是最敏感、最有研究价值的专业 动脉气体损伤的器官，尽管体积是最小体积的750,000倍 超声可成像的体积。神经学诊断和治疗正在进行中 需要更好的技术，最后，需要经皮动脉生成 在颈动脉是最容易的。生成两种类型的诊断 颈动脉栓剂计划在动物模型中用于验证 颅内影像的阈值、演示和初步评估 由光学组织学证明的可能的不良反应，彩色 微球和放射自显影。动脉供血动脉的显示 将进行血管闭塞治疗病变的勾画 在犬的甲状腺血管系统中。

This is a revised proposal to develop and evaluate controlled generation of arterial microbubbles using intense, focused ultrasound pulses for possible diagnostic and therapeutic use. Since the previous submission, arterial microbubbles have been generated in flowing whole blood in vitro with 725 kHz ultrasound passing through canine tissues simulating human transcutaneous generation. Threshold intensities observed in blood were 2.3 times less than at the previous 1.8 MHz and temperature rise on realistically-placed vertebral bone was acceptable. Short boluses of ultrasonically imageable, less than 40 micron bubbles, generated in selected arteries, should be usable for diagnosis and monitoring of those vascular and perfusion abnormalities which currently are evaluated more slowly and expensively, and probably more invasively, with MRI or with angiography requiring arterial catheterization. Sparse distributions of 20 to 40 micron bubbles should be usable to refocus ultrasound beams for high resolution imaging through aberrating overlying tissues, even for imaging through the skull. The first and most certain medical use of bolus generation is expected to be identification of feeder arteries to therapeutic targets such as tumors and arterio-venous malformations. Coagulation of the feeder arteries, or thrombus generated by repeated, more extensive boluses, will occlude the target for safer, more effective ultrasound or chemical therapy or surgery. Knowledge of ultrasonic fields which produce vascular microbubbles of negligible damage up to vascular occlusion will help improve guidelines for safe diagnostic and therapeutic ultrasound. Bubbles will be produced and characterized under various conditions directed to the above goals. Studies will include bubble size distributions, constituents and longevity with and without contrast agent seeding and at two or more ultrasound frequencies, pulse amplitudes and durations and blood velocities. Current success at bolus production in exposed arteries with minimal arterial wall damage apparently is due to focusing within the vessel. Lower frequencies and other techniques will be utilized for desired bubble generation with lower thermal and cavitational damage, even, possibly, in smaller, deeper vessels where luminal containment of the focus is not possible. In vivo studies will be performed initially on the cerebral vasculature, as there is a good chance of success and the brain is the most sensitive and best studied major organ for arterial gas damage, albeit at volumes 750,000 times the minimum ultrasonically imageable volume. Neurologic diagnosis and treatment is in need of better techniques and, finally, transcutaneous arterial generation will be easiest in the carotid. Generation of the two types of diagnostic carotid boluses is planned in animal models for verification of thresholds, demonstration of intracranial imaging and initial evaluation of possible adverse effects demonstrable by optical histology, colored microspheres and autoradiography. Demonstration of feeder artery delineation for lesion treatment by vascular occlusion will be performed in the canine thyroid vasculature.