SBIR Phase I: Transcranial Dynamic Focused Ultrasound for the Non-Invasive Opening of the Blood-Brain Barrier (BBB)

这个SBIR一期项目旨在开发技术，旨在为医生提供一种新的能力来管理脑癌、阿尔茨海默氏症或帕金森氏症等脑部疾病患者。脑部疾病难以治疗的一个原因是血脑屏障（BBB）的存在，它阻止了几乎所有的治疗药物从血液到达患病组织。所提出的技术可以通过便携式系统以非侵入性方式打开血脑屏障，并且可以部署在门诊或诊所环境中。这一系统可能会影响管理脑部疾病患者的成本负担，并提供更好的生活质量。该项目开发了一种方法，通过一组超声换能器，将聚焦的超声光束精确地引导到患者大脑内的治疗目标，这些传感器嵌入在一个与患者头部舒适匹配的帽状装置中。在过去的几年里，微泡聚焦超声（FDA批准的超声造影剂）已被用于短暂打开血脑屏障，以给药或提供治疗。所提出的帽状装置包括符合患者头部和测量结果与患者解剖结构对齐的机制。设想的方法是提前获取帽的位置信息以及特定患者的MR和CT图像，以便治疗超声可以准确地定向到患者大脑内的目标。提出的工作包括a)开发适用于一系列患者头部尺寸的波束形成算法，传感器元件安装在符合的帽上；(b)了解和减轻限制性能的潜在错误来源。该项目将使用从美国国家医学图书馆可见人体项目获得的真实患者的MR和CT图像进行模拟和分析，从而得出适合构建实验室设备进行验证和确认的规格。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This SBIR Phase I project aims to develop technology designed to provide physicians with a new capability to manage patients with brain diseases such as brain cancers, Alzheimer’s or Parkinson’s. One reason brain disease is difficult to treat is the existence of the blood-brain barrier (BBB) that prevents almost all therapeutic agents from reaching diseased tissue from blood. The proposed technology enables opening the BBB in a non-invasive manner with a system that is portable and may be deployed in an out-patient or a clinic setting. This system could impact the cost burden of managing patients with brain diseases and provide better quality of life. The proposed project develops methods to accurately direct focused beams of ultrasound to therapy targets within the patient’s brain from an array of ultrasound transducers embedded in a cap-like device conformed comfortably to a patient’s head. In the last several years, focused ultrasound with microbubbles (an FDA approved ultrasound contrast agent) has been used to transiently open the BBB to administer drugs or provide therapy. The proposed cap-like device includes mechanisms both to conform to the patient head and to measure the resulting alignment to the patient anatomy. The envisioned method is to acquire information on cap placement and MR and CT images of the specific patient in advance so that the therapeutic ultrasound can then be directed accurately to targets within the patient's brain. The proposed work includes a) developing beamforming algorithms applicable to a range of patient head sizes, with transducer elements arranged on the conforming cap; and (b) understanding and mitigating potential sources of errors limiting the performance. The project will conduct simulation and analysis using MR and CT images from real patients, obtained from the U.S. National Library of Medicine Visible Human Project, resulting in specifications suitable for construction of a laboratory device for verification and validation.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.