Mapping microglia and astrocyte activation in vivo using diffusion MRI (Garcia-Hernandez et al, 2022)

[SNT Gatchaman]

Mapping microglia and astrocyte activation in vivo using diffusion MRI
Raquel Garcia-Hernandez, Antonio Cerdán Cerdá, Alejandro Trouve Carpena, Mark Drakesmith, Kristin Koller, Derek K Jones, Santiago Canals, Silvia De Santis

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.

Link | PDF | Supplementary Materials

 

[SNT Gatchaman]

They induced neuroinflammation in rats vs healthy controls to validate the findings, then did a "phase 1" style evaluation in healthy humans, to show a null result. Next step is to look at diseased human subjects. Hope they start looking at a few long COVID patients early to spark some interest our way.

The proposed MRI methodology was adapted to a human MRI scanner, and healthy subjects were recruited to perform a reproducibility study, demonstrating that the glia biomarkers are highly reproducible between different MRI sessions and in line with CoVs calculated for conventional MRI parameters routinely used in clinical settings.

In vivo variability of MRI-derived microglia biomarkers can explain known patterns of cell density measured postmortem in humans across several regions of the brain parenchyma. While further work is needed to test the model in the presence of, e.g., a neurodegenerative condition, the results establish the value of the developed MRI framework to quantify glial reactions noninvasively in humans.

To conclude, we proposed here a new generation of noninvasive glia-centric biomarkers, which are expected to transform the study of many diseases associated with a glial response: those where inflammation is as a known or possible cause, as well as those in which the glial reaction can serve as a powerful early diagnostic and/or prognostic marker.

 

[Pyrrhus]

I just read this study this morning. I also intend to look at references 12-15, which provide background information.

There have been a number of publications over the last couple years that have proposed ways to detect/measure neuroinflammation using MRI, but this approach is truly novel and, in my opinion, the most promising approach so far.

Whether their results can be replicated will probably depend upon the correctness of their mathematical model. Definitely something to watch.

 

[Pyrrhus]

Somewhat related discussions:

Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods (VanElzakker et al., 2019)
https://forums.phoenixrising.me/thr...-a-critical-review-of-research-methods.76890/

A systematic review of neurological impairments in myalgic encephalomyelitis/chronic fatigue syndrome using neuroimaging techniques (Maksoud et al., 2020)
https://forums.phoenixrising.me/thr...syndrome-using-neuroimaging-techniques.81884/