Three-Photon Microscope for High-Resolution Deep Tissue Imaging

项目总结

Project Summary Three-photon microscopy (3PM) is an optical imaging technology that enables significantly deeper imaging in a scattering biological tissue than the current leading standard two-photon microscopy (2PM), while providing additional contrast mechanisms and enhancing spatial resolution. This technology is made possible by advances in long-wavelength, tunable, high-pulse-energy femtosecond lasers and corresponding modifications in 2PM setups to accommodate a novel excitation regime. As a direct result of these advancements, 3PM imaging depth in rodent brain is greatly extended with respect to 2PM imaging depth—from ~700 μm to more than 1,200 μm. Due to such a large improvement, we anticipate that 3PM will allow breakthrough studies of the structure (e.g., vascular, glial, and neural architecture) and function (e.g., oxygenation, calcium signaling, and cellular interactions) in preclinical in vivo studies, with cellular- size resolution in previously inaccessible tissue layers, such as the subcortical white matter and the hippocampus. The 11 NIH-funded projects listed in this proposal will significantly benefit from these imaging capabilities. These projects span a diverse range of research topics relevant to NIMH mission, including improvement of the quantitativeness of the clinical imaging modalities and better understanding of the mechanisms involved in development of various brain conditions. The Martinos Center for Biomedical Imaging and Massachusetts General Hospital constitute a diverse community of researchers, many of whom are funded with NIH support, performing cutting edge biomedical research that will further advance our fundamental understanding of human health and disease. This proposed 3PM imaging system will represent the first instrument of its kind in the Boston area (and probably Northeast US) that is available within an Imaging Core. This cutting-edge instrumentation will allow our research community to significantly enhance various research studies relevant to NIMH mission, and it will also allow the Martinos Center to continue prospering as a leader for advanced biomedical imaging.