Mapping microglia and astrocyte activation in vivo using diffusion MRI

Abstract

While glia are increasingly implicated in the pathophysiology of psychiatric and neurodegenerative disorders, available methods for imaging these cells in vivo involve either invasive procedures or positron emission tomography radiotracers, which afford low resolution and specificity. Here, we present a noninvasive diffusion-weighted magnetic resonance imaging (MRI) method to image changes in glia morphology. Using rat models of neuroinflammation, degeneration, and demyelination, we demonstrate that diffusion-weighted MRI carries a fingerprint of microglia and astrocyte activation and that specific signatures from each population can be quantified noninvasively. The method is sensitive to changes in glia morphology and proliferation, providing a quantitative account of neuroinflammation, regardless of the existence of a concomitant neuronal loss or demyelinating injury. We prove the translational value of the approach showing significant associations between MRI and histological microglia markers in humans. This framework holds the potential to transform basic and clinical research by clarifying the role of inflammation in health and disease.

Cross-Talk and Subset Control of Microglia and Associated Myeloid Cells in Neurological Disorders

“…TSPO is also expressed in blood-borne infiltrating monocytes/macrophages, suggesting that this radioligand target may be reflective of broad myeloid activation [ 142 ]. To mitigate this limitation of PET imaging, a recent pre-clinical study investigated the utility of diffusion-weighted MRI to map microglia activation [ 143 ]. This method is specific to microglia through the combination of three MRI parameters: the stick fraction, the stick dispersion, and the small sphere size.…”

A translational MRI approach to validate acute axonal damage detection

“…The ARRIVE 10 checklist was used. Animal preparation (n=9 rodents) was carried out as described here (Garcia-Hernandez et al, 2022). Briefly, axonal damage in the fimbria was achieved by injecting 1 μl of saline and ibotenic acid (a selective agonist of N-methyl-D-aspartate (NMDA) glutamate receptors that produces selective neurotoxicity (Zinkand et al, 1992)) at a concentration of 2.5 μg/μl in the right dorsal hippocampus (coordinates bregma -3.8 mm, supinf 3.0 mm, 2 mm from midline in the left hemisphere).…”

“…Indeed, MRI sensitivity to the loss axonal loss of axons has yet to be fully demonstrated to establish its clinical utility. Recently, we proposed an approach to selectively manipulate specific microstructural aspects of the parenchyma through targeted, unilateral injection of neurotoxic agents (Garcia-Hernandez et al, 2022).…”

“…Recently, we proposed an approach to selectively manipulate specific microstructural aspects of the parenchyma through targeted, unilateral injection of neurotoxic agents (Garcia-Hernandez et al, 2022).…”

Relationship between manual dexterity and left-right asymmetry of anatomical and functional properties of corticofugal tracts revealed by T2-weighted brain images

“…The health of cerebral white matter is affected by multiple factors, including axonal packing density, axonal caliber, myelination, microglia, and tissue structure [32][33][34] . The activation sensitive signal arising from diffusion MRI of glia is of interest as a marker in this context 35 . It may be of relevance to further test the reproducibility and reliability of the imaging and the CFT signal strength measurements by application of complementary multimodal imaging techniques.…”