Image-Guided Deep Brain Microscopy for Neurosurgical Intervention

描述（由申请人提供）：本研究提出了用于图像引导的脑深部光学活检和脑深部刺激电极精确放置的微创显微镜的发展。该系统将允许实时组织评估和干预措施的准确放置。使用梯度指数（GRIN）透镜的微创多光子荧光显微镜可以提供高质量的亚细胞分辨率图像，用于评估脑表面以下的病理。这项工作的总体目标是开发一个精确定位的显微镜系统，并在幻影中测试和验证该系统。为了使这项技术对神经外科干预有用，需要常规的术中计算机断层扫描（CT）来定位和定位神经外科环境中的显微镜。此外，精确定位需要补偿由于脑移位和插入显微镜而引起的脑变形。因此，这项工作需要显微镜的发展，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。显微镜系统必须设计一个足够窄和长的GRIN镜头，以达到潜在的目标区域，最小的组织损伤。配准方法必须对术中CT成像所提供的较低图像质量和覆盖范围具有鲁棒性。变形方法必须提供精确的生物力学模型，而不需要过多的计算。植入粒子的凝胶幻影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输送放置。脑深部显微镜的发展有可能彻底改变神经外科手术的干预措施，如活检和电极放置，使它们更加准确和有效，以提高癌症、帕金森病和癫痫等疾病的治疗效果。这一发展将解决当前成像技术的关键局限性，如缺乏分辨正常组织和癌组织的分辨率或特异性，或精确确定帕金森病电极植入所需的不同细胞层的位置。

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.