Non-invasive optical imaging of neuropathology in vivo

体内神经病理学的无创光学成像

基本信息

批准号：
7071532
负责人：
Brian J Bacskai
金额：
$ 86.68万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2011-07-31
项目状态：
已结题

项目摘要

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。光学成像价格低廉，并且可以对完整动物进行体内成像，空间分辨率小于 1 毫米。最近在动物模型和人类中，肿瘤的结构检测以及血流、代谢和蛋白酶活性的功能成像方面都取得了重大进展。下一代光学成像方法将依赖于特异性识别完整动物内的结构或功能的新型造影剂。我们建议加速光学成像技术的发展，以及生产用于近红外分子成像的新型光学对比试剂。我们将修改现有的光学成像系统，利用完整小鼠颅内成像的硬件和软件的进步来优化灵敏度和空间分辨率。我们还将开发一套针对特定颅内结构的分子成像探针，可应用于多种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、白质、脑血管系统以及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不仅有助于表征各种动物模型中大脑结构改变的自然史，而且将作为评估和筛选旨在改善疾病进展的治疗方法的定量终点。动物模型中的疾病。该提案汇集了一支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、神经病理学体内检测和生物医学工程方面拥有丰富的经验。该多学科团队包括麻省理工学院化学家 Timothy Swager、美国匹兹堡精神病学家/化学家 William Klunk、MGH 光学工程师 David Boas、MGH 神经解剖学家 Brad Hyman 和 MGH 神经科学家 Steven Reeves。该项目的共同努力将产生一个新的分子成像工具库，以利用新兴的近红外光谱技术。