Multi-probe minimally invasive endomicroscope

多探头微创内窥镜

• 批准号: 10898521
• 负责人: Antonio Miguel Caravaca Aguirre
• 金额: $ 12.13万
• 依托单位: MODENDO INC.
• 依托单位国家: 美国
• 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/10898521
• 关键词: Ablation; Address; Animal Model; Animals; Area; Brain; Brain Diseases; Brain Stem; Brain imaging; Brain region; Calibration; Communities; Compensation; Coupling; Development; Diagnosis; Disease; Endoscopes; Fiber; Fluorescence; Future; Generations; Human; Image; Individual; Lasers; Light; Machine Learning; Medical; Methods; Modality; Neurons; Neurosciences; Pattern; Penetration; Population; Resolution; Scanning; Shapes; Site; Speed; System; Technology; Three-Dimensional Image; Three-Dimensional Imaging; Time; Tissues; Translating; Trauma; connectome; digital; experimental study; flexibility; high resolution imaging; imaging approach; imaging probe; in vivo imaging; innovation; instrument; instrumentation; meter; microendoscopy; minimally invasive; multimodality; neuroimaging; olfactory bulb; optogenetics; parallelization; prototype; signal processing; transmission process

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.

项目摘要 该项目旨在开发一种多探针显微镜，以实现高分辨率成像， 在大脑的当前不可接近区域内的多个部位进行光刺激。仪器将 适用于模型动物的科学研究，也是未来医疗仪器的垫脚石。 在人类疾病诊断和治疗方面的作用。 该公司解决了科学和医疗领域对内窥镜的迫切需求， 侵入性，横截面约为100μm。拟议的系统原型将进行数字编程， 不包含移动部件，并同时寻址多个穿透组织的探针， 损害目标应用是在多个区域同时进行脑深部成像和光刺激 大脑。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。插入多个成像探头以关联刺激的可能性 大脑不同区域的活动可以提供对连接体的新理解， 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用于插入大腔体，但会产生过度损伤 在诸如脑深部成像的应用中。该项目将创建一个微创，强大，灵活， 用于多探针显微内镜的紧凑型原型。关键的创新在于实现从根本上最薄的 在真实的时间内传输高信息量图像并将其并行化到多个大脑部位的机制。 单个探头的横截面积比现有最薄的内窥镜小10倍。此外，每个 的探针将能够提供多种功能：微米分辨率的3D成像，荧光和 反射成像以及用于光刺激和烧蚀的激光图案生成。 成像方法同时在各种多模光纤探头中实现波前整形， 先进的机器学习和信号处理方法，以生成任意数字可重新编程的光 图案和3D图像。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 光在高速，补偿固有的模式色散和模间耦合。 通过多模光纤进行的第一次体内成像和光遗传学实验的演示， 神经元群体在深度单独成像，具有亚细胞分辨率，并且具有最小的组织损伤， 为扩展和发展到多探头多模态系统提供了令人兴奋的机会。的 公司最初的重点是降低风险和验证多模光纤探头在动物功能中的使用 神经成像长期愿景是将该技术转化为医疗应用。