Multi-probe minimally invasive endomicroscope

项目总结 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 在目前无法接触到的大脑区域内的多个位置进行光刺激。仪器将会是 服从于模型动物的科学研究，是未来有针对性的医疗器械的垫脚石 在人类的诊断和疾病治疗方面。 该公司满足了科学和医疗领域对内窥镜的最低限度的迫切需求 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，并同时处理穿透组织的多个探头 损坏。目标应用是在多个区域同时进行脑深部成像和光刺激 大脑的一部分。该系统将能够对难以触及的大脑区域进行成像，如脑干或嗅觉 球茎，对动物的创伤可以忽略不计。插入多个成像探针以关联刺激的可能性 而大脑不同区域的活动可以提供对连接体的新理解，并有助于观察 健康的大脑和患病的大脑之间的区别。 目前的内窥镜解决方案适合于在大型空洞中插入，但它们会产生过大的损害 在深部脑成像等应用中。该项目将创建一种微创、健壮、灵活和 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了从根本上最薄的 实时传输高信息量图像并将其并行到多个大脑站点的机制。 单个探测器的横截面积比现有最薄的内窥镜小10倍。此外，每个 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，以及用于光刺激和消融的激光图案生成。 该成像方法在各种多模光纤探头中同时实现波前整形，使用 先进的机器学习和信号处理方法，可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，然后扫描 高速照明，补偿固有的模式色散和模式间耦合。 通过多模光纤演示了第一个活体成像和光遗传学实验，展示了 在深层单独成像的神经元群体，具有亚细胞分辨率，组织损伤最小， 为扩展和发展多探头多模式系统提供了令人兴奋的机会。这个 该公司最初的重点是降低风险并验证多模光纤探头在动物功能中的使用 神经成像。长期的愿景是将这项技术转化为医疗应用。

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.