This subproject is one of many research subprojects utilizing the resources provided by a Shared Instrumentation Grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the grant, which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): Multi-photon microscopy is rapidly becoming one of the most versatile imaging modalities for biomedical research. The ability to image intact tissues to depths of over 500 microns constitutes one of the most groundbreaking developments in in-vivo functional imaging in recent years. At the Martinos Center for Biomedical Imaging, Massachusetts General Hospital (MGH), we strive to develop and utilize breakthrough approaches and our continuing success relies on the integration of new and emerging technologies into our research facility. New modalities enhance our ability to validate and interpret data from our existing imaging resources which include functional and high-resolution magnetic resonance imaging (fMRI and MRI), magnetoencephalography (MEG), positron emission tomography (PET) and functional optical imaging. We are proposing to purchase a state-of-the-art multi-photon microscopy system, with fluorescence lifetime imaging capabilities. The configuration of the microscope platform chosen is optimized for rapid in-vivo imaging, as well as for a spectrum of other microscopy functions. Two-photon microscopy provides unrivalled depth sensitivity and resolution in intact tissue, allowing structure and function to be imaged in- vivo on scales as small as a single dendrite. Fluorescence lifetime imaging (FLIM) exploits both intrinsic and exogenous contrast, and provides dramatic improvement to fluorescence resonance energy transfer (FRET) imaging, which can be used to reveal not only biomarkers, but also interactions between individual proteins. The new microscopy system will be an important resource for currently funded medical imaging research initiatives. Major projects include studies of: cortical neurovascular coupling using calcium sensitive dyes and dynamic blood flow microscopy, the morphological and functional effects of cocaine on the brain, mechanisms of cell death in stroke, and development of molecular probes for cancer and diabetes research. The system will allow versatile imaging of the structure and function of in-vivo, ex-vivo and in-vitro tissues. With the new multi-photon microscopy system and our existing imaging facilities under one roof, we can feasibly perform in-vivo experiments using multiple medical imaging modalities in succession or even in parallel. This system will be an invaluable resource for the many interdisciplinary research projects within the Martinos center, in the surrounding MGH community, and for many others in the greater Boston area.
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| Baraghis, Edward; Devor, Anna; Fang, Qianqian et al. (2011) Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response. J Biomed Opt 16:106003 |
