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

这个SBIR第一阶段项目旨在开发一种技术，旨在为医生提供一种新的能力来管理患有脑癌、阿尔茨海默氏症或帕金森氏症等脑部疾病的患者。脑部疾病难以治疗的一个原因是血脑屏障(BBB)的存在，该屏障阻止几乎所有治疗剂从血液到达病变组织。建议的技术能够以非侵入性的方式利用便携式系统打开血脑屏障，并且可以部署在门诊或诊所环境中。这个系统可以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。拟议的项目开发了一种方法，从嵌入在舒适地贴合患者头部的帽状设备中的一系列超声换能器中，将聚焦的超声波波束准确地引导到患者大脑中的治疗目标。在过去的几年里，带有微泡的聚焦超声(FDA批准的超声造影剂)已被用于瞬时打开血脑屏障，以给药或提供治疗。所提出的帽状装置包括既符合患者头部又测量结果与患者解剖对齐的机构。设想的方法是事先获取有关特定患者的盖子放置和MR和CT图像的信息，以便治疗性超声波可以准确地定向到患者大脑内的目标。建议的工作包括a)开发适用于一定范围的患者头部大小的波束形成算法，其中换能器元件布置在符合帽上；以及(B)了解和减轻限制性能的潜在误差源。该项目将使用来自真实患者的MR和CT图像进行模拟和分析，这些图像来自美国国家医学图书馆可见人项目，从而产生适合于构建用于验证和验证的实验室设备的规范。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.