Time-resolved laser speckle contrast imaging of resting-state functional connectivity in neonatal brain

新生儿大脑静息态功能连接的时间分辨激光散斑对比成像

基本信息

批准号：
10760193
负责人：
Guoqiang Yu
金额：
$ 28.91万
依托单位：
BIOPTICSTECHNOLOGY, LLC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10760193
关键词：
3-Dimensional Affect Algorithms Animal Model Biological Markers Brain Brain Injuries Brain imaging Brain region Calibration Cerebrovascular Circulation Clinical Collaborations Complex Consumption Development Diffuse Diffusion Disease Early Diagnosis Electroencephalography Functional Magnetic Resonance Imaging Future Head Health Healthcare Human Image Imaging Device Imaging technology Infant Investigation Kentucky Laboratories Laser Speckle Imaging Light Magnetic Resonance Imaging Maps Methods Modality Modeling Monitor Near-Infrared Spectroscopy Neonatal Neonatal Brain Injury Neonatal Intensive Care Units Neurodevelopmental Problem Neurosciences Research Noise Operating System Outcome Pathology Perinatal anoxic ischemic brain injury Phase Photons Physiologic pulse Positron-Emission Tomography Property Rattus Resolution Rest Risk Rodent Scalp structure Signal Transduction Small Business Technology Transfer Research Statistical Models System Technology Term Birth Testing Time Tissues Universities Variant biomarker identification brain abnormalities care burden care costs cerebral hemodynamics clinical application clinical development commercialization cost cranium denoising design diffuse optical tomography experimental study feasibility testing high resolution imaging imager improved in vivo lens mortality neonatal brain neonatal brain development neonatal hypoxic-ischemic brain injury neonate neuroimaging neurovascular operation porcine model portability pre-clinical prevent prototype reconstruction tomography user-friendly

项目摘要

ABSTRACT Continuous monitoring of neonatal brain development is crucial for effective management of brain injury and associated complications, thus reducing healthcare burden and costs. One rapidly developing method for early characterization of abnormal brain development is to map resting-state functional connectivity (rs-FC) across distinct regions of the brain. However, currently available neuroimaging technologies are either expensive and difficult to use continuously (fMRI and PET) or lack the combination of temporal-spatial resolution and large field- of-view (FOV) to image distributed rs-FC (EEG and near-infrared spectroscopy and tomography). In collaboration with University of Kentucky inventors, Bioptics Technology is developing, validating, and commercializing a revolutionary time-resolved laser speckle contrast imaging (TR-LSCI) technology that enables noncontact, fast, high-resolution imaging of cerebral blood flow (CBF) over a large FOV. TR-LSCI illuminates picosecond-pulsed, widefield, coherent, near-infrared light onto the brain and synchronizes a newly developed, picosecond-gated, high-resolution, single-photon avalanche diode (SPAD) camera for 2D mapping of cerebral blood flow (CBF) at different depths into the head. By applying the time-gated strategy, TR-LSCI differentiates short and long photon paths through the layered head tissues at different depths, thus eliminating the need for time-consuming complex 3D reconstruction in near-infrared diffuse optical tomography technologies. In preliminary studies, continuous mapping of CBF at different depths has been demonstrated by a lab-made benchtop TR-LSCI prototype in flow- simulating phantoms and in vivo rodents. In this Fast Track STTR proposal through two phases, we will develop, optimize, validate, and commercialize a user-friendly portable TR-LSCI device for fast, high-solution, and multiscale imaging of CBF and rs-FC in neonatal rodents (Phase 1) and neonatal piglets (Phase 2). Specifically, Phase 1 will optimize and assess the benchtop TR-LSCI prototype for imaging CBF and extracting rs-FC (derived from time-course CBF images) in neonatal rodents with perinatal hypoxic-ischemic encephalopathy (HIE). Neonatal rats are used in this Phase 1 feasibility test to de-risk the TR-LSCI before its full-scale development in neonatal piglets during Phase 2. HIE is selected to study as it affects 2-9 babies per 1000 term births and is associated with severe neurodevelopmental problems and mortality. Phase 2 will develop, optimize, and assess a user-friendly portable TR-LSCI device for continuous imaging of CBF and rs-FC in neonatal piglets with HIE. Neonatal piglets are selected to study as their head size and post-HIE pathology are analogous to human neonates. TR-LSCI results will be correlated with MRI results and clinical outcomes to identify biomarkers for assessing neonatal brain injury after HIE. While this proposal tests it on HIE models of neonatal rats and piglets as the first step for preclinical commercialization, the TR-LSCI device is broadly applicable to investigate many neurovascular diseases beyond HIE occurring in human neonates, thereby providing a significant opportunity for future clinical development and commercialization.

抽象的持续监测新生儿大脑发育对于有效管理脑损伤和相关并发症，从而减轻医疗负担和成本。一种快速发展的早期方法异常大脑发育的表征是绘制静息态功能连接（rs-FC）大脑的不同区域。然而，目前可用的神经影像技术要么价格昂贵，要么难以连续使用（fMRI 和 PET）或缺乏时空分辨率和大视场的结合视场 (FOV) 到图像分布式 rs-FC（脑电图、近红外光谱和断层扫描）。合作中 Bioptics Technology 与肯塔基大学的发明者一起开发、验证和商业化革命性的时间分辨激光散斑对比成像 (TR-LSCI) 技术，可实现非接触式、快速、大视场内脑血流 (CBF) 的高分辨率成像。 TR-LSCI 照亮皮秒脉冲，宽场、相干、近红外光照射到大脑上，并同步新开发的皮秒门控、高分辨率单光子雪崩二极管 (SPAD) 相机，用于绘制脑血流 (CBF) 的二维图进入头部的深度不同。通过应用时间选通策略，TR-LSCI 区分短光子和长光子通过不同深度的分层头部组织的路径，从而消除了耗时的复杂过程的需要近红外漫射光学断层扫描技术中的 3D 重建。在初步研究中，连续实验室制造的台式 TR-LSCI 原型在流- 模拟体模和活体啮齿动物。在这个分两个阶段的快速通道 STTR 提案中，我们将开发，优化、验证和商业化用户友好的便携式 TR-LSCI 设备，以实现快速、高解决方案和新生啮齿动物（第 1 阶段）和新生仔猪（第 2 阶段）的 CBF 和 rs-FC 多尺度成像。具体来说，第一阶段将优化和评估台式 TR-LSCI 原型，用于成像 CBF 和提取 rs-FC（衍生患有围产期缺氧缺血性脑病（HIE）的新生啮齿动物的时程CBF图像）。新生大鼠用于第一阶段可行性测试，以在 TR-LSCI 全面开发之前降低 TR-LSCI 的风险。第 2 阶段的新生仔猪。选择 HIE 进行研究是因为它影响每 1000 头足月分娩中的 2-9 名婴儿，并且与严重的神经发育问题和死亡有关。第二阶段将开发、优化和评估一种用户友好的便携式 TR-LSCI 设备，用于对患有 HIE 的新生仔猪进行 CBF 和 rs-FC 的连续成像。选择新生仔猪进行研究是因为它们的头部大小和 HIE 后的病理学与人类相似新生儿。 TR-LSCI 结果将与 MRI 结果和临床结果相关联，以确定生物标志物评估 HIE 后的新生儿脑损伤。该提案在新生大鼠和仔猪的 HIE 模型上进行了测试作为临床前商业化的第一步，TR-LSCI 设备广泛适用于研究许多人类新生儿中发生 HIE 以外的神经血管疾病，从而提供了重要的机会用于未来的临床开发和商业化。