High-density optical tomography of cerebral blood flow and metabolism in small animals

小动物脑血流和代谢的高密度光学断层扫描

• 批准号: 10323090
• 负责人: Guoqiang Yu
• 金额: $ 34.12万
• 依托单位: BIOPTICSTECHNOLOGY, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10323090
• 关键词: 3-Dimensional; Acute; Aging; Algorithmic Software; Algorithms; Animal Experimentation; Animal Model; Animals; Biological Markers; Biomedical Research; Brain; Brain Neoplasms; Brain imaging; Calibration; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Chronic; Clinical; Collaborations; Computer software; Development; Devices; Diffuse; Dyes; Evaluation; Feedback; Fluorescence; Functional Imaging; Funding; Future; Head; Histologic; Homeostasis; Human; Hypoxia; Image; Imaging Device; Imaging technology; Industrialization; Infant; Intervention; Investigation; Kentucky; Laboratories; Legal patent; Magnetic Resonance Imaging; Measurement; Measures; Medical; Metabolic; Metabolism; Methodology; Monitor; Mus; Neonatal; Neonatal Brain Injury; Neurologic; Neurons; Neurosciences; Neurosciences Research; Noise; Optical Tomography; Optics; Outcome; Oxygen; Oxygen Consumption; Pathologic; Pathology; Penetration; Performance; Perfusion; Phase; Positron-Emission Tomography; Property; Rattus; Recovery; Research Personnel; Resolution; Rodent; Rodent Model; Signal Transduction; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Stress; Stroke; System; Techniques; Technology; Testing; Therapeutic Intervention; Three-Dimensional Imaging; Time; Tissues; Ultrasonics; United States National Institutes of Health; Universities; Variant; Work; base; brain health; clinical application; commercialization; cost; density; design; effective intervention; experience; hemodynamics; human imaging; human subject; imager; imaging modality; in vivo; innovation; instrument; instrumentation; light weight; metabolic rate; multimodality; neonatal brain development; neonate; nervous system disorder; non-invasive imaging; phase 1 study; phase 2 study; portability; pre-clinical; relating to nervous system; response; serial imaging; stress disorder; stroke model; therapeutically effective; tissue oxygenation; tissue phantom; tomography; tool; user-friendly

ABSTRACT Many clinical situations, including stroke, expose the brain to insufficient cerebral blood flow (CBF) that cannot maintain normal cerebral metabolic rate of oxygen consumption (CMRO2) requirements, thereby leading to cerebral ischemic/hypoxic stresses and neurological disorders. Effective interventions are dependent on the findings of CBF/CMRO2 improvement and eventually neural recovery. Rodents (mice and rats) make up 95% of research animals. However, one major limitation with neuroscience research in rodent models is lack of affordable noninvasive imaging technologies for continuous and longitudinal monitoring of CBF and CMRO2 variations. Large imaging modalities (e.g., CT, PET, and MRI) require expensive instrumentation, and are difficult to use for longitudinal monitoring. Portable, inexpensive optical/ultrasonic technologies greatly expand choices for continuous cerebral monitoring although most systems lack the combination of high tempo-spatial resolution, wide field-of-view, and proper penetration depth into deep brains. Moreover, none of currently available techniques enable simultaneous imaging of CBF, cerebral tissue oxygen saturation (StO2), and CMRO2. To overcome these limitations, researchers at University of Kentucky (UK) have developed an innovative CCD/CMOS based speckle contrast diffuse correlation tomography (scDCT: US Patent #9861319) technique to accommodate noninvasive, noncontact, fast, high-density 3D imaging of CBF distributions in mice, rats, piglets, and human neonates. While effective, scDCT has not been optimized for dissemination and commercialization in terms of imaging performance (signal-to-noise ratio, temporal-spatial resolution, accuracy, easy-to-use), and instrument cost and portability. In collaboration with UK, Bioptics Technology LLC (BOT) proposes to develop, optimize, validate, and commercialize an affordable, portable, easy-to-use, multi-wavelength scDCT (MW- scDCT) technique for repeated, longitudinal imaging of CBF, StO2, and CMRO2 distributions in rodents. New methodologies and algorithms will be developed to achieve a nearly real-time, high-density, 3D imaging of cerebral function. The MW-scDCT will be rigorously tested and optimized using head-simulating phantoms with known optical and hemodynamic properties (Aim 1). In vivo calibration and evaluation of absolute measurements with MW-scDCT will be conducted against standard perfusion MRI and histological examination in rats with or without stroke (Aim 2). Finally, optimized MW-scDCT devices will be disseminated to several neuroscience researchers inside and outside UK to collect feedback regarding instrument applicability and user experience. With preliminary feedback from these selected end-users, we expect to identify refinements and improvements needed for the MW-scDCT in a continued Phase-II study to produce an optimal product-level device for commercialization. The ultimate use will be expanded to larger animal models and human subjects. However, this Phase-I project will begin with rodents as using small animals is easier, more economical and efficient for commercializing the device, thereby paving the way for future commercialization of clinical-level devices.

抽象的 许多临床情况，包括中风，都会使大脑暴露在脑血流量 (CBF) 不足的情况下，无法 维持正常的脑代谢耗氧率（CMRO2）需求，从而导致 脑缺血/缺氧应激和神经系统疾病。有效的干预措施取决于 CBF/CMRO2 改善和最终神经恢复的结果。啮齿类动物（小鼠和大鼠）占 95% 研究动物。然而，啮齿动物模型神经科学研究的一个主要限制是缺乏 用于连续和纵向监测 CBF 和 CMRO2 的经济实惠的无创成像技术 变化。大型成像模式（例如 CT、PET 和 MRI）需要昂贵的仪器，并且难度较大 用于纵向监测。便携式、廉价的光学/超声波技术极大地扩展了选择 尽管大多数系统缺乏高时空分辨率的结合，但用于连续脑监测， 广阔的视野和适当的深入大脑深处的深度。此外，目前还没有任何可用的 技术能够同时对 CBF、脑组织氧饱和度 (StO2) 和 CMRO2 进行成像。到 克服这些限制，肯塔基大学（英国）的研究人员开发了一种创新的 基于 CCD/CMOS 的散斑对比漫相关断层扫描（scDCT：美国专利号 #9861319）技术 用于对小鼠、大鼠、仔猪、 和人类新生儿。 scDCT 虽然有效，但尚未针对传播和商业化进行优化 在成像性能方面（信噪比、时空分辨率、准确性、易于使用），以及 仪器成本和便携性。 Bioptics Technology LLC (BOT) 与英国合作提议开发， 优化、验证和商业化一种经济实惠、便携、易于使用的多波长 SCDCT（MW- scDCT）技术，用于对啮齿类动物的 CBF、StO2 和 CMRO2 分布进行重复纵向成像。新的 将开发方法和算法来实现近乎实时、高密度的 3D 成像 脑功能。 MW-scDCT 将使用头部模拟模型进行严格测试和优化 已知的光学和血液动力学特性（目标 1）。绝对测量的体内校准和评估 MW-scDCT 将针对患有以下疾病的大鼠进行标准灌注 MRI 和组织学检查： 无中风（目标 2）。最后，优化的MW-scDCT设备将传播到多个神经科学领域 英国国内外的研究人员收集有关仪器适用性和用户体验的反馈。 根据这些选定的最终用户的初步反馈，我们希望确定改进和改进 MW-scDCT 在持续的 II 期研究中需要，以生产最佳的产品级设备 商业化。最终用途将扩展到更大的动物模型和人类受试者。然而， 该第一阶段项目将从啮齿类动物开始，因为使用小动物更容易、更经济、更高效。 该设备的商业化，从而为未来临床级设备的商业化铺平了道路。