Non-invasive optical imaging of neuropathology in vivo

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，并且允许完整动物的体内成像，空间分辨率小于1毫米。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，最近在动物模型和人类中都取得了重大进展。下一代光学成像方法将依赖于新型造影剂，专门识别完整动物的结构或功能。我们建议加速光学成像技术的发展，以及产生用于近红外分子成像的新型光学造影剂。我们将对现有的光学成像系统进行改进，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，用于完整小鼠的颅内成像。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。我们将开发用于无创测量灰质、白质、脑血管和阿尔茨海默病病理蛋白聚集体的荧光探针。这些技术的成功实施不仅有助于在各种动物模型中描述大脑结构改变的自然历史，而且将作为定量终点，用于评估和筛选旨在改善动物模型中疾病进展的治疗方法。该提案汇集了一个具有广泛经验的多学科团队。MGH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。多学科团队包括麻省理工学院化学家Timothy Swager，匹兹堡大学精神病学家/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。这个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。

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.