Non-invasive optical imaging of neuropathology in vivo

体内神经病理学的无创光学成像

• 批准号: 7903375
• 负责人: Brian J Bacskai
• 金额: $ 84.22万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7903375
• 关键词: 3-Dimensional; Age; Algorithms; Alzheimer' s Disease; Amyloid beta-Protein; Angiography; Animal Model; Animals; Antibodies; Area; Arts; Binding; Biology; Biomedical Engineering; Blood - brain barrier anatomy; Blood flow; Boa; Brain; Brain imaging; Cerebrum; Chemistry; Computer software; Deposition; Detection; Development; Disease Progression; Dyes; Emerging Technologies; Engineering; Evaluation; Fluorescence; Fluorescent Probes; Functional Imaging; Goals; Head; Human; Image; Imaging Device; Imaging Techniques; Label; Lead; Life; Light; Magnetic Resonance Imaging; Measurement; Metabolism; Modeling; Mus; Natural History; Near-Infrared Spectroscopy; Neuroanatomy; Neurology; Non-Invasive Cancer Detection; Optical Tomography; Optics; Outcome Measure; Pathology; Peptide Hydrolases; Positron-Emission Tomography; Principal Investigator; Property; Proteins; Psychiatrist; Reagent; Reporter; Research Personnel; Resolution; Screening procedure; Senile Plaques; Sensitivity and Specificity; Signal Transduction; Staining method; Stains; Structure; System; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Transgenic Mice; experience; fluorescence imaging; fluorophore; gray matter; imaging probe; in vivo; instrumentation; molecular imaging; mouse model; multidisciplinary; nervous system disorder; neuropathology; next generation; novel; optical imaging; optical switch; programs; protein aggregate; reconstruction; single photon emission computed tomography; software development; tumor; white matter

DESCRIPTION (provided by applicant): Non-invasive optical imaging capitalizing on the transmissive properties of the near-infrared spectrum is a rapidly evolving molecular imaging approach complementary to MRI, PET, or SPECT. Optical imaging is inexpensive and allows in vivo imaging of intact animals with spatial resolutions less than 1 mm. Significant strides in structural detection of tumors and functional imaging of blood flow, metabolism, and protease activities have recently been accomplished in both animal models and humans. The next generation of optical imaging approaches will depend on novel contrast reagents that specifically identify structures or functions within intact animals. We propose to accelerate the development of optical imaging techniques, as well as to generate novel optical contrast reagents for near infrared molecular imaging. We will modify an existing optical imaging system to optimize the sensitivity and spatial resolution with advances in both hardware and software for intracranial imaging of intact mice. We will also develop a suite of molecular imaging probes that will target specific intracranial structures, with applications for in vivo imaging for a broad range of neurological diseases. We will develop fluorescent probes for non-invasive measurement of grey matter, white matter, cerebral vasculature, and the pathological protein aggregates found in Alzheimer's disease. Successful implementation of these techniques will not only aid in the characterization of the natural history of structural alterations in the brain in a variety of animal models, but will serve as a quantitative end-point for evaluation and screening of therapeutics aimed at ameliorating the progression of disease in animal models. This proposal brings together a multidisciplinary team with a broad range of experience. Principal investigator Brian Bacskai at MGH has extensive experience in optical imaging, in vivo detection of neuropathology and biomedical engineering. The multidisciplinary team includes MIT chemist Timothy Swager, U. Pittsburgh Psychiatrist/Chemist William Klunk, MGH optical engineer David Boas, MGH Neuroanatomist Brad Hyman, and MGH Neuroscientist Steven Reeves. The combined efforts from this project will lead to a new arsenal of molecular imaging tools to exploit the newly emerging technology of NIR spectroscopy.

描述（由申请人提供）：利用近红外光谱的透射特性的非侵入性光学成像是一种快速发展的分子成像方法，与MRI、PET或SPECT互补。光学成像是廉价的，并允许在体内成像的完整的动物与空间分辨率小于1毫米。重大的进步，肿瘤的结构检测和功能成像的血流，代谢和蛋白酶活性最近已经完成了在动物模型和人类。下一代光学成像方法将依赖于新型造影剂，这些造影剂可以特异性地识别完整动物体内的结构或功能。我们建议加快光学成像技术的发展，以及产生新的光学造影剂的近红外分子成像。我们将修改现有的光学成像系统，以优化灵敏度和空间分辨率的硬件和软件的进步，完整的小鼠颅内成像。我们还将开发一套针对特定颅内结构的分子成像探针，用于广泛的神经系统疾病的体内成像。我们将开发荧光探针，用于非侵入性测量灰质、白色物质、脑血管和阿尔茨海默病中发现的病理性蛋白质聚集体。这些技术的成功实施将不仅有助于表征各种动物模型中脑结构改变的自然史，而且将作为评价和筛选旨在改善动物模型中疾病进展的治疗剂的定量终点。该提案汇集了一个具有广泛经验的多学科团队。MGH的首席研究员Brian Bacskai在光学成像，神经病理学和生物医学工程的体内检测方面拥有丰富的经验。这个多学科的研究小组包括麻省理工学院的化学家蒂莫西·斯瓦格、美国大学的化学家、美国科学院的化学家。匹兹堡精神病学家/化学家William Klunk，MGH光学工程师大卫博厄斯，MGH神经解剖学家布拉德海曼和MGH神经科学家史蒂文里夫斯。该项目的共同努力将导致一个新的分子成像工具库，以利用新兴的近红外光谱技术。

项目成果

Fluorescence lifetime-based optical molecular imaging.

基于荧光寿命的光学分子成像。

• DOI: 10.1007/978-1-60761-901-7_12
• 发表时间: 2011
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Kumar,AnandTN