Unique Instrument Significantly Advances the Ability to Study Neurodegenerative Diseases
Scientists and engineers at the Synchrotron Radiation Center (SRC), led by SRC User Carol Hirschmugl (UW-Milwaukee), have designed and built an instrument that greatly increases the ability of researchers to study individual cells. The development of this instrument, as shown in a paper published in NeuroImage, brings an unprecedented tool to bear in the study of neurodegenerative diseases such as Alzheimer’s.
The scientific process is based on creative ideas, independent measurements, and objective conclusions. While advances in science depend on following these precepts, they also depend on building increasingly more sensitive tools. This unique advance in instrumentation represents a 100-fold leap forward in the ability to study the changes that happen to individual neurons as diseases such as Alzheimer’s progress.
Traditional methods for identifying specific chemical components in the study of neurodegenerative diseases involve the use of stains. Specific stains highlight structures in molecules or cells for viewing with microscopes. These methods are limited because they are unable to reliably provide specific chemical information, are mostly non-quantitative, can interact with cell components, and are relatively specific to the one molecule or cell that the stain was designed to enhance.
With the InfraRed Environmental Imaging (IRENI) instrument, it is now possible to study changes in individual neurons in situ and to characterize their surroundings using only the bio-chemical signatures of naturally-occurring components in unstained tissue. This is demonstrated in the study of mouse hippocampal tissue comparing a stained sample and the corresponding IRENI data (see figure). IRENI not only provides a high-resolution image of the tissue but, for each pixel, spectral information can be extracted to identify specific chemical components, for example, lipid concentrations. Lipids are naturally occurring molecules whose many biological functions range from energy storage and use as structural components of cell membranes to important tasks as signaling molecules. The role that lipids play in Alzheimer’s Disease tissue is not fully characterized, but their presence could be related to chronic inflammation and they may also participate in plaque formation and dissolution.
Caption: Image of a mouse hippocampal tissue showing a photomicrograph of neurons with stained nuclei (A), and the same region imaged with IRENI (B) prior to the stain procedure. The IRENI image has been processed to show concentrations of lipids from low concentration (blue) to high concentration (red). The white boxed area includes a nucleus, cytoplasm and white matter which has been expanded in (C) to show raw IRENI pixels. Spectra (graph in C) from three pixels show differences between nuclear (blue), cytoplasmic (green), and white matter (red) regions.
IRENI has also allowed scientists to examine the biochemical composition of retinal layers that can be used to study changes related to the Alzheimer’s disease process and results of dietary modification. On the order of minutes IRENI provided a never-before-seen wealth of data that included not only spatially-resolved data with unprecedented clarity but also distinct spectral variation, from sub-regions including photoreceptors, other neuronal cell bodies and synapse in sections of mouse retinal tissue.
This best-in-the-world, and currently one-of-a-kind, instrument should find wide application as a tool for research in neuroscience, providing unprecedented spatial resolution as well as spectrochemical information. IRENI will positively affect this field for years to come.
IRENI was funded by a grant from the National Science Foundation (PI: C. Hirschmugl). The study demonstrating the advances in the field of neural degeneration using IRENI was supported by grants from the Canadian Institutes of Health Research, the Manitoba Health Research Council, and NSERC Canada (PI: K. Gough).
M.Z. Kastyak-Ibrahim, M.J. Nasse, M. Rak, C. Hirschmugl, M.R. Del Bigio, B.C. Albensi, K.M. Gough, “Biochemical label-free tissue imaging with subcellular-resolution synchrotron FTIR with focal plane array detector,” NeuroImage, 60 (1), pp. 376-383 (2012).
C.J. Hirschmugl, K.M. Gough, “Fourier Transform Infrared Spectrochemical Imaging: Review of Design and Applications with a Focal Plane Array and Multiple Beam Synchrotron Radiation Source,” Applied Spectroscopy, 66 (5), pp. 475-491 (2012).
Link to paper
Michael J Nasse, Michael J Walsh, Eric C Mattson, Ruben Reininger, André Kajdacsy-Balla, Virgilia Macias, Rohit Bhargava, & Carol J Hirschmugl, "High-resolution Fourier-transform infrared chemical imaging with multiple synchrotron beams," Nature Methods, 8, 413-416 (2011)
The author file from Nature Methods for Rohit Bhargava and Carol Hirschmugl