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 该项目旨在开发多探针超大构成巨型显微镜，以实现高分辨率成像和 当前大脑中无法接近的区域内的多个地点的照片刺激。该仪器将是 适用于模型动物的科学研究和针对未来医疗仪器的垫脚石 在人类的诊断和疾病治疗方面。 该公司解决了最小的内窥镜科学和医学领域的关键需求 侵入性，横截面为100μm。提出的系统原型将通过数字编程， 不包含运动部件，同时解决了多种问题，这些问题可渗透到无忽略的组织 损害。目标应用仅在多个区域中进行深度脑成像和光刺激 大脑。该系统将启用成像难以到达的大脑区域，例如脑干或嗅觉 灯泡，对动物的创伤微不足道。插入多个成像问题以关联模拟的可能性 和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 健康和患病的大脑之间的差异。 当前的内窥镜解决方案适合在大型腔中插入，但它们会产生多余的损害 在诸如深脑成像之类的应用中。该项目将创建一个最小的 - 侵入性，健壮，灵活的，并且 多探针膜镜检查的紧凑原型。关键的创新是实现最稀薄的 实时传输高信息内容图像并将其并行将其与多个大脑位点并行的机制。 个体问题的跨区域比最薄的内窥镜小10倍。此外，每个 问题将能够提供多个功能：3D成像以微米分辨率，荧光和 反射成像以及用于光刺激和消融的激光图案生成。 成像方法简单地使用各种多模纤维问题实现波前形状 先进的机器学习和信号处理方法，以生成任意数字可编程的光 图案和3D图像。该系统使用空间光调节器首先校准每个光纤然后扫描 高速照明，以补偿固有的模态分散体和模式耦合。 通过多模纤维进行的第一个体内成像和光遗传学实验的演示，显示 神经元的群体单独成像，并具有亚细胞分辨率，并具有最小的组织损伤， 为Mullti-Probe多模式系统打开了令人兴奋的扩展和发展机会。这 公司最初的重点是降低风险和验证多模纤维问题在动物功能中的使用 神经成像。长期的愿景是将技术转化为医疗应用。