Image-Guided Deep Brain Microscopy for Neurosurgical Intervention

描述(申请人提供)：这项研究建议开发用于图像引导的脑深部光学活检的微创显微镜和用于脑深部刺激的电极的准确放置。该系统将允许实时组织评估和准确的介入放置。使用梯度折射率(GRIN)透镜的微创多光子荧光显微镜可以提供高质量的图像，具有亚细胞分辨率，用于评估脑表面下的病理。这项工作的总体目标是开发一种精确定位的显微镜系统，并在体模中测试和验证该系统。为了使这项技术用于神经外科治疗，需要常规术中计算机断层扫描(CT)来定位显微镜在神经外科环境中的位置。此外，精确定位需要补偿由于大脑移位和显微镜插入而导致的大脑变形。因此，这项工作需要开发显微镜、术中图像配准的图像分析方法、脑变形计算的生物力学建模以及集成到图像引导的神经外科系统中。显微镜系统的设计必须具有足够窄和长的GRIN透镜，以达到潜在的靶区，并将组织损伤降至最低。配准方法必须对术中CT成像提供的较低的图像质量和覆盖率具有健壮性。变形方法必须提供准确的生物力学模型，而不需要过多的计算。对植入颗粒的凝胶模体的研究将证明该系统的可行性、显微镜的质量以及放置和变形的准确性。在这项工作的下一阶段，患者研究将被设计用于光学活检和精确的生物传感器或治疗药物的放置。对公众健康而言，脑深部显微镜的发展有可能使活检和电极放置等神经外科干预措施发生革命性变化，使其更加准确和有效，目标是提高癌症、帕金森病和癫痫等疾病的治疗效果。这一进展将解决目前成像技术的关键局限性，例如缺乏分辨率或特异性来区分正常组织和癌症组织，或根据帕金森病电极植入所需精确确定不同细胞层的位置。

DESCRIPTION (provided by applicant): This study proposes the development of minimally-invasive microscopy for image guided deep brain optical biopsy and accurate placement of electrodes for deep brain stimulation. This system will allow real-time tissue evaluation and accurate placement for interventions. Minimally-invasive multiphoton fluorescence microscopy using gradient index (GRIN) lenses can provide high quality images with subcellular resolution for the evaluation of pathology below the brain surface. The overall objective of this work is to develop a microscope system with accurate positioning, and to test and validate the system in phantoms. In order to make this technology useful for neurosurgical intervention, conventional intraoperative computed tomography (CT) is needed in order to position and localize the microscope in the neurosurgical environment. In addition, precise localization requires compensation for brain deformation due to brain shift and the insertion of the microscope. This work therefore requires the development of the microscope, image analysis methods for registration of intraoperative images, biomechanical modeling for brain deformation computation and integration into an image-guided neurosurgical system. The microscopy system must be designed with a sufficiently narrow and long GRIN lens to reach potential target regions with minimal tissue damage. The registration methods must be robust to the lower image quality and coverage afforded by intra-operative CT imaging. The deformation methods must provide accurate biomechanical models without excessive computation. Studies of gel phantoms with implanted particles will demonstrate the feasibility of the system, the quality of the microscopy, and the accuracy of placement and deformation. In the next phase of this work, patient studies will be designed for optical biopsy and for precise biosensor or therapeutics delivery placement. to Public Health The development of deep brain microscopy has the potential to revolutionize neurosurgical interventions such as biopsy and electrode placement, making them more accurate and efficient with the goal of improving the efficacy of treatments for diseases such as cancer, Parkinson disease and epilepsy. This development will address key limitations of current imaging techniques such as the lack of resolution or specificity to distinguish normal tissue from cancerous tissue, or to precisely determine the location of different cell layers as needed in electrode implantation for Parkinson disease.