Multi-probe minimally invasive endomicroscope

多探头微创内窥镜

基本信息

批准号：
10709909
负责人：
Antonio Miguel Caravaca Aguirre
金额：
$ 23.88万
依托单位：
MODENDO INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-23 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10709909
关键词：
3-Dimensional Ablation Address Algorithms Amygdaloid structure Anatomy Animal Model Animals Area Assessment tool Behavior Brain Brain Diseases Brain Stem Brain imaging Brain region Calibration Cell Nucleus Collection Communities Compensation Computer software Coupling Development Diagnosis Diameter Disease Distal Electronics Endoscopes Environment Epilepsy Fiber Fiber Optics Fluorescence Food Future Generations Head Human Image Imaging Device Individual Lasers Light Location Machine Learning Medical Mental disorders Methods Modality Modeling Monitor Mus Neurons Neurosciences Neurosciences Research Noise Optics Parkinson Disease Pattern Penetration Performance Phase Population Research Resolution Response to stimulus physiology Scanning Schizophrenia Scientist Shapes Signal Transduction Site Speed Spottings Surveys System Taste Perception Technology Temperature Testing Three-Dimensional Image Three-Dimensional Imaging Time Tissues Translating Trauma Validation confocal imaging connectome design digital experimental study flexibility fluorescence imaging high resolution imaging image reconstruction imaging approach imaging capabilities imaging modality imaging probe in vivo in vivo imaging innovation instrument instrumentation lens meter microendoscopy minimally invasive multimodality nervous system disorder neural neuroimaging olfactory bulb optical fiber optogenetics parallelization prototype restraint scale up signal processing spectrograph temporal measurement transmission process

项目摘要

PROJECT SUMMARY This project seeks to develop a multi-probe ultrathin endomicroscope to enable high-resolution imaging and photo-stimulation at multiple sites within currently inaccessible regions of the brain. The instrument will be amenable to scientific studies in model animals and a stepping stone for future medical instrumentation targeted at diagnosis and disease treatment in humans. The company addresses the critical need in the scientific and medical fields for endoscopes that are minimally invasive, with a cross section in the order of 100μm. The proposed system prototype will be digitally programmed, contain no moving parts, and simultaneously address multiple probes that penetrate tissue with negligible damage. The target application is deep brain imaging and photo-stimulation simultaneously in multiple regions of the brain. The system will enable imaging difficult-to-reach brain areas, such as the brain stem or the olfactory bulb, with negligible trauma to the animal. The possibility of inserting multiple imaging probes to correlate stimulation and activity in different regions of the brain could provide new understanding of the connectome and help observe differences between healthy and diseased brains. Current endoscopic solutions are appropriate for insertion in large cavities but they produce excessive damage in applications such as deep brain imaging. This project will create a minimally–invasive, robust, flexible, and compact prototype for multi-probe endomicroscopy. The key innovation is in achieving the fundamentally thinnest mechanism to transmit a high information content image in real time and in parallelizing it to multiple brain sites. The individual probes have a cross-area 10 times smaller than the thinnest existing endoscopes. Further, each of the probes will be able to deliver multiple functions: 3D imaging with micrometer resolution, fluorescence and reflection imaging, as well as laser pattern generation for photo-stimulation and ablation. The imaging approach implements wavefront shaping in various multimode fiber probes simultaneously, using advanced machine learning and signal processing methods, to generate arbitrary digitally-reprogrammable light patterns and 3D images. The system uses a spatial light modulator to first calibrate each fiber and then scan light at high speed, compensating for the inherent modal dispersion and intermodal coupling. The demonstration of the first in-vivo imaging and optogenetics experiments through a multimode fiber, showing populations of neurons individually imaged at depth, with subcellular resolution, and with minimal tissue damage, opens exciting opportunities for expansion and development into mullti-probe multi-modality systems. The company’s initial focus is on de-risking and validating the use of multimode fiber probes in animal functional neuro-imaging. The long-term vision is to translate the technology towards medical applications.

项目概要该项目旨在开发一种多探头超薄内窥镜，以实现高分辨率成像和该仪器将在目前无法到达的大脑区域的多个部位进行光刺激。适合对模型动物进行科学研究，并为未来目标医疗仪器奠定基础用于人类的诊断和疾病治疗。该公司满足科学和医疗领域对内窥镜的迫切需求侵入式，横截面约为 100μm 所提出的系统原型将进行数字编程，不包含移动部件，并同时处理多个探针，这些探针可忽略不计地穿透组织目标应用是在多个区域同时进行深部脑成像和光刺激该系统将能够对难以到达的大脑区域进行成像，例如脑干或嗅觉。灯泡，对动物的创伤可以忽略不计，可以插入多个成像探针来关联刺激。大脑不同区域的活动可以提供对连接组的新理解并帮助观察健康大脑和患病大脑之间的差异。目前的内窥镜解决方案适合插入大腔内，但会产生过度损坏该项目将创建一种微创、强大、灵活且灵活的应用。用于多探头内窥镜检查的紧凑型原型，关键的创新在于实现最薄的设计。实时传输高信息内容图像并将其并行化到多个大脑部位的机制。此外，每个探头的横截面积比现有最薄内窥镜小 10 倍。的探针将能够提供多种功能：具有微米分辨率的 3D 成像、荧光和反射成像，以及用于光刺激和消融的激光图案生成。该成像方法同时在各种多模光纤探头中实现波前整形，使用先进的机器学习和信号处理方法，生成任意数字可重新编程的光该系统使用空间光调制器首先校准每根光纤，然后进行扫描。高速光，补偿固有的模色散和模间耦合。通过多模光纤演示首次体内成像和光遗传学实验，显示神经元群在深度上单独成像，具有亚细胞分辨率，并且组织损伤最小，为多探针多模态系统的扩展和发展提供了令人兴奋的机会。该公司最初的重点是降低和验证多模光纤探头在动物功能研究中的使用神经成像的长期愿景是将这项技术转化为医学应用。