Direct label-free imaging of brain tissue using synchrotron light: a review of new spectroscopic tools for the modern...

The incidence of brain disease and brain disorders is increasing on a global scale. Unfortunately, development of new therapeutic strategies has not increased at the same rate, and brain diseases and brain disorders now inflict substantial health and economic impacts. A greater understanding of the fundamental neurochemistry that underlies healthy brain function, and the chemical pathways that manifest in brain damage or malfunction, are required to enable and accelerate therapeutic development. A previous limitation to the study of brain function and malfunction has been the limited number of techniques that provide both a wealth of biochemical information, and spatially resolved information (i.e., there was a previous lack of techniques that provided direct biochemical or elemental imaging at the cellular level). In recent times, a suite of direct spectroscopic imaging techniques, such as Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence microscopy (XFM), and X-ray absorption spectroscopy (XAS) have been adapted, optimized and integrated into the field of neuroscience, to fill the above mentioned capability-gap. Advancements at synchrotron light sources, such as improved light intensity/flux, increased detector sensitivities and new capabilities of imaging/optics, has pushed the above suite of techniques beyond "proof-of-concept" studies, to routine application to study complex research problems in the field of neuroscience (and other scientific disciplines). This review examines several of the major advancements that have occurred over the last several years, with respect to FTIR, XFM and XAS capabilities at synchrotron facilities, and how the increases in technical capabilities have being integrated and used in the field of neuroscience.