Non-invasive optical imaging of neuropathology in vivo

描述(申请人提供)：非侵入性光学成像利用近红外光谱的传输特性，是一种快速发展的分子成像方法，是对MRI、PET或SPECT的补充。光学成像是廉价的，可以对完整的动物进行空间分辨率低于1毫米的活体成像。最近，在动物模型和人类中，在肿瘤结构检测和血流、代谢和蛋白酶活性的功能成像方面取得了重大进展。下一代光学成像方法将依赖于专门识别完整动物体内结构或功能的新型造影剂。我们建议加快光学成像技术的发展，以及开发用于近红外分子成像的新型光学对比剂。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，并在硬件和软件方面取得进展，对完整的小鼠进行颅内成像。我们还将开发一套分子成像探针，针对特定的颅内结构，应用于广泛的神经疾病的体内成像。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不仅将有助于描述各种动物模型中大脑结构变化的自然历史，而且将成为评估和筛选旨在改善动物模型中疾病进展的治疗方法的量化终点。这项提议汇集了一支拥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、神经病理活体检测和生物医学工程方面拥有丰富的经验。多学科团队包括麻省理工学院化学家蒂莫西·斯瓦格、匹兹堡大学精神病学家兼化学家威廉·克伦克、麻省理工学院光学工程师大卫·博阿斯、麻省理工学院神经解剖学家布拉德·海曼和麻省理工学院神经学家史蒂文·里夫斯。该项目的共同努力将导致一个新的分子成像工具武器库，以利用新出现的近红外光谱技术。

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.