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首页> 外文会议>International Conference on Biomedical Engineering >Multiple Low-Pressure Sonications to Improve Safety of Focused-Ultrasound Induced Blood-Brain Barrier Disruption: In a 1.5-MHz Transducer Setup
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Multiple Low-Pressure Sonications to Improve Safety of Focused-Ultrasound Induced Blood-Brain Barrier Disruption: In a 1.5-MHz Transducer Setup

机译：多次低压超声，提高重点 - 超声诱导的血脑屏障中断的安全性：在1.5MHz换能器设置中

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Burst-mode driven high intensity focused ultrasound (HIFU) with the presence of ultrasound micro bubbles has been proven to be capable of locally and reversibly increasing the permeability of blood-brain barrier (BBB). However, the use of excessive acoustic pressure usually accompanied with intracerebral hemorrhage, which is considered a deterred side effect, especially when in applications such as drug delivery. The purpose of the current study is to provide a secure protocol using multiple low-pressure sonications, to disrupt localized BBB and preserve sonicated area without producing intracerebral hemorrhage. The brains of 10 Sprague-Dawley rats were subjected to 16 sonications, either unilaterally or bilaterally. A 1.5-MHz spherically curved 1-3 composite transducer was used to deliver the burst-mode ultrasonic focal energy into the rat brain after both craniotomy and micro bubble injection. Electric powers from 1 to 10 W were tested and sonication mode was adjusted from single high-pressure sonication (2.45 MPa, 30s x1) to multiple shoots (1.1 MPa, 30s x6). The path of sonication could be either a row or a triangle, which depends on the treatment plan. Pathologic examination includes hematoxylin and cosin (H&E) and immuno-histochemistry (IHC) staining. It was used to quantify the damage in accompany with BBB disruption which includes hemorrhage and tissue necrosis. MR imaging was employed to evaluate the BBB disruption and brain tissue hemorrhage in vivo. Pathological examinations showed that the average hemorrhage score decreased from 2.3+/- std (severe) to 0.3+/- std (slight) by using the proposed protocol. The finding was confirmed by In vivo MRI examinations. Compared with single high-pressure sonication, multiple low-pressure sonication effectively reduced the occurrence of hemorrhage noticed in T2*-weighted images. The efficiency of BBB-disruption increased as observed in contrast-enhanced T1 weighted Turbo-spin-echo sequence. The current study provides an improved sonication protocol which could temporally and locally disrupt the Blood-Brain-Barrier. It therefore demonstrated the possibility of safe drug delivery into restricted brain regions in the future applications.
机译：突发模式驱动的高强度聚焦超声（HIFU）具有超声波微气泡的存在，已经证明能够在本地和可逆地增加血脑屏障（BBB）的渗透率。然而，使用过多的声压通常伴有脑内出血，这被认为是阻止副作用，特别是在药物递送等应用时。目前研究的目的是提供一种使用多个低压超声的安全协议，以破坏局部化BBB并保持超声处理区域而不产生脑出血。 10种Sprague-Dawley大鼠的大脑进行单侧或双侧进行16个超声处理。在Craniotomy和微气泡注射后，使用1.5MHz球形弯曲的1-3复合换能器将突发模式超声焦点输送到大鼠脑中。测试1至10W的电力，并从单一高压超声（2.45MPa，30s x1）调节超声模式，以多次芽（1.1MPa，30s x6）。超声处理的路径可以是行或三角形，这取决于治疗计划。病理检查包括苏木精和辛酸（H＆E）和免疫组织化学（IHC）染色。它用于量化伴随BBB破坏的损伤，包括出血和组织坏死。 MR成像用于评估体内BBB中断和脑组织出血。病理检查表明，通过使用所提出的方案，平均出血得分从2.3 +/- STD（严重）降低到0.3 +/- STD（轻微）。在体内MRI考试中确认了发现。与单一高压超声处理相比，多次低压超声处理有效地降低了T2 * - 重量的图像中注意到的出血。以对比度增强的T1加权涡轮旋转回波序列观察到的BBB破坏的效率增加。目前的研究提供了一种改进的超声处理协议，其可能在暂时和局部地破坏血脑屏障。因此，它证明了未来应用中安全药物的可能性。

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