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Biomedical Imaging and Instrumentation

Biomedical Imaging and Instrumentation - Poster Session E

Poster R4 - Biorthogonal metabolic imaging of brain during aging and diseases

Saturday, October 26, 2024

10:00 AM - 11:00 AM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

YL

Yajuan Li

Postdoctoral Researcher
University of California, San Diego, United States

Last Author(s)

Lingyan Shi, PhD (she/her/hers)

Associate Professor
University of California, San Diego
La Jolla, California, United States

Introduction: Understanding brain lipid metabolism is vital for unraveling brain aging and neurodegeneration mechanisms. Traditional imaging methods lack chemical specificity and resolution. Stimulated Raman scattering (SRS) imaging provides high specificity, resolution, and deep penetration. We utilize a multimodal imaging platform integrating deuterium isotope probed SRS microscopy (DO-SRS), multiphoton fluorescence (MPF), and second harmonic generation (SHG) to visualize lipid dynamics in animal brains. Deuterium incorporation generates detectable carbon-deuterium bonds in lipids, revealing turnover. We find decreased lipid activity during aging and neurodegeneration in Drosophila brains, with interventions like dietary restriction and pathway modulation enhancing turnover. Our advanced imaging and analysis methods offer high-resolution insights applicable to diverse biomedical studies.

Materials and

Methods: Understanding the dynamics of lipid metabolism in brain is essential to unraveling the mechanistic basis of brain aging and neurodegeneration. Traditional imaging methods such as MRI, PET, Fluorescence, and Mass Spectrometry have fundamental limitations including low chemical specificity and low spatial resolution. As an emerging non-linear vibrational imaging technique, stimulated Raman scattering (SRS) imaging offers high chemical specificity, high resolution, deep penetration, and quantitative capability. We apply a multimodal imaging platform that integrates deuterium isotope probed SRS microscopy (DO-SRS), multiphoton fluorescence (MPF), and second harmonic generation (SHG) together to visualize lipid metabolic dynamics in animal brains. The enzymatic incorporation of deuterium (D) will generate carbon-deuterium (C-D) bonds in newly-synthesized lipids. The vibrational signals of these C-D bonds can be detected by SRS in the spectral cell-silence region (wavenumber 1800 – 2800 cm-1).

Results, Conclusions, and Discussions: By leveraging this cutting-edge imaging technique, we reveal that lipid metabolic activity in Drosophila brain decreased during aging and neurodegeneration. Dietary restriction (DR), downregulation of insulin/IGF-1 signaling (IIS) pathway, and overexpression of AMPK signalling pathway all lead to significant enhancements of brain lipid turnover. In addition, under DR treatment and downregulation of IIS pathway, the brain uses acetate as a major carbon source for lipid synthesis. Combined with our advanced deconvolution method (Adam optimization-based Pointillism Deconvolution) and penalized reference matching (PRM) algorithm, this non-invasive, universally applicable technology platform enables the detection of macromolecular with high fidelity and resolution and can be adapted to a broad range of biomedical studies including development, aging, metabolism, tumor progression, neuronal degeneration and more.

Acknowledgements (Optional):