Collaborative Research: An implantable intracranial ultrasound stimulation for treating neurodiseases

合作研究:用于治疗神经疾病的植入式颅内超声刺激

基本信息

项目摘要

Ultrasound stimulation has been demonstrated to be an effective therapeutic tool for treating several brain related disorders in humans. Reducing the symptoms of chronic disorders such as migraine, epilepsy, neuropathic pain due to spinal cord damage, essential tremors and Parkinson’s disease can be accomplished through neuromodulation and targeted delivery of drugs to specific regions of the brain via temporary disruption of the blood- brain-barrier (BBB). However, current ultrasound neuromodulation technology uses a bulky arrangement of several single element ultrasonic transducers inside a helmet shaped device that require high voltage for operation. This limits its use to only clinical settings in hospitals. In contrast, minimally invasive, implantable intracranial ultrasonic stimulation microchips can help treat neurodiseases that require intermittent and chronic stimulation over prolonged periods. Towards this goal, this project will design, fabricate, and validate a low power and biocompatible intracranial micromachined ultrasound chip for temporary opening of the BBB. Such a chip will consume minimal power, operate at safe low voltage, and has the potential to treat chronic neural diseases requiring intermittent on-demand stimulation over periods of months to years. Beyond the application proposed here, successful demonstration of miniaturized ultrasonic chips could also find applications for non-invasive wearable imaging of arterial blood flow for diagnosing vascular diseases and inspection of critical fractures and material failures in aircraft and infrastructural constructions like bridges and pipelines. The multidisciplinary research will enable integration of new pedagogical materials on ultrasound neuromodulation and piezoelectric micromachined ultrasound transduces (PMUTs) design and development, into both undergraduate and graduate engineering curriculum and Senior Capstone Design projects. Outreach activities will target diverse middle and high school students, underrepresented in engineering, with the goal of raising interest and curiosity in ultrasound transduction and imaging methods.This project addresses the current need for implantable focused ultrasound (fUS) technology by leveraging a microelectromechanical systems (MEMS) approach to fabricate miniaturized curved 3D transducers in single and array formats and demonstrate their use for trans-BBB drug delivery. To suit implantable and wearable applications, low-voltage, scandium-doped aluminum nitride (Sc-AlN) MEMS approach will be used to realize the PMUTs. To achieve ultra-high electromechanical coupling coefficient, unique curved PMUT membrane shapes will be developed using chip-scale glass-blowing fabrication. The proposed curved PMUT arrays will use optimized Sc-AlN thin films for piezoelectric material, thus ensuring lead-free and biocompatible implants. Inherently curved 3D PMUTs are expected to reduce beam width in elevational direction and thus deliver ultrasound energy more efficiently to the neural target of interest. Overall, by using a set of innovations at material, structure, and system level, 8 x 8 PMUT arrays will be demonstrated to generate steerable focused ultrasound output at up to 2 cm depth in the brain tissue with 1 MPa pressure at the focal spot and 0.5 mm resolution. This approach will offer unique flexibility to cover a large region of interest in brain with high resolution for ultrasound stimulation applications. Further, the pressure output of the fabricated curved PMUT array device will be validated using experiments on brain tissue. BBB-opening capabilities will be tested using in vitro cell culture experiments.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.
超声刺激已被证明是治疗人类几种脑相关疾病的有效治疗工具。减轻慢性疾病如偏头痛、癫痫、由于脊髓损伤引起的神经性疼痛、原发性震颤和帕金森病的症状可以通过神经调节和经由暂时破坏血脑屏障(BBB)将药物靶向递送至脑的特定区域来实现。然而,当前的超声神经调节技术使用头盔形装置内的几个单元件超声换能器的庞大布置,其需要高电压来操作。这限制了其仅在医院的临床环境中使用。相比之下,微创、植入式颅内超声刺激微芯片可以帮助治疗需要长时间间歇性和慢性刺激的神经疾病。为了实现这一目标,本项目将设计,制造和验证一个低功耗和生物相容性的颅内微机械超声芯片暂时打开血脑屏障。这种芯片将消耗最小的功率,在安全的低电压下工作,并有可能治疗慢性神经疾病,需要在数月至数年的时间内进行间歇性按需刺激。除了这里提出的应用之外,小型化超声波芯片的成功演示还可以应用于动脉血流的非侵入性可穿戴成像,用于诊断血管疾病以及检查飞机和桥梁和管道等基础设施建设中的关键断裂和材料故障。多学科研究将使新的教学材料的超声神经调节和压电微机械超声传感器(PMUT)的设计和开发整合到本科和研究生工程课程和高级顶点设计项目。外联活动将针对不同的初中和高中学生,在工程,该项目通过利用微机电系统(MEMS)方法制造单个和阵列格式的小型化弯曲3D换能器,并展示其用于跨导超声成像的用途,以满足当前对植入式聚焦超声(fUS)技术的需求。BBB药物递送。为了适应可植入和可穿戴应用,低电压,掺钪氮化铝(Sc-AlN)MEMS方法将用于实现PMUT。为了实现超高机电耦合系数,将使用芯片级玻璃吹制制造来开发独特的弯曲PMUT膜形状。所提出的弯曲PMUT阵列将使用优化的Sc-AlN薄膜作为压电材料,从而确保无铅和生物相容性植入物。预期固有弯曲的3D PMUT将减小垂直方向上的波束宽度,从而更有效地将超声能量递送到感兴趣的神经目标。总的来说,通过在材料、结构和系统层面上使用一系列创新,8 x 8 PMUT阵列将被证明能够在脑组织中产生高达2 cm深度的可控聚焦超声输出,焦点处的压力为1 MPa,分辨率为0.5 mm。这种方法将提供独特的灵活性,以高分辨率覆盖大脑中的大区域,用于超声刺激应用。此外,所制造的弯曲PMUT阵列装置的压力输出将使用脑组织上的实验来验证。该奖项反映了NSF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。

项目成果

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Sri-Rajasekhar Kothapalli其他文献

Sri-Rajasekhar Kothapalli的其他文献

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{{ truncateString('Sri-Rajasekhar Kothapalli', 18)}}的其他基金

CAREER: Smart and scalable approaches for developing multimodal optical and acoustic imaging technologies
职业:开发多模态光学和声学成像技术的智能且可扩展的方法
  • 批准号:
    2238878
  • 财政年份:
    2023
  • 资助金额:
    $ 29万
  • 项目类别:
    Continuing Grant

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