# In Vivo Imaging of Cortical Glial Activation Using Advanced Diffusion Magnetic Resonance Imaging

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $479,639

## Abstract

Project Summary
 Neuroinflammation by means of glial (microglia and astrocytes) activation is thought to
play a key role in the pathogenesis of several psychiatric and neurodegenerative
disorders of different etiology including depression, schizophrenia, Alzheimer’s disease
and multiple sclerosis (MS). Still, current noninvasive methods to detect and
characterize neuroinflammation in vivo are limited. Positron emission tomography (PET)-
based targeting of the 18kDa translocator protein (TSPO), which is overexpressed in
activated glial cells but otherwise present at very low levels in the healthy brain, is the
current gold-standard for imaging in vivo glial activation in the human brain. PET
imaging, however, is associated with radiation exposure, which limits its use in children
and child-bearing women, and over time.
 Microglia and astrocytes are dynamic cells able to change morphology and function
following “activation” from a variety of pathological insults. Advanced magnetic
resonance (MR) diffusion weighted imaging (DWI) is a sensitive approach for non-
invasive measurement of intra- and extra-cellular microstructural changes associated
with glial activation. We have developed a novel DWI multi-compartment microstructural
model (MCM) for imaging microglia and astrocyte activation, which we validated in an
experimental rat model of grey matter (GM) inflammation.
 Here, we propose to translate this model to the study of cortical glial activation in
healthy controls and patients with MS, and to validate in vivo findings in post-mortem MS
brain tissue. MS is a chronic inflammatory and neurodegenerative disorder of the central
nervous system that represents the leading cause of non-traumatic neurological
disability in young adults in the US. There is solid evidence that extensive microglia
activation is a main pathological feature of cortical pathology in MS.
 Our overall hypothesis is that MCM-derived indices are sensitive to cortical
microstructural changes related to glial activation as evidenced by a strong correlation
with TSPO levels on PET with 11C-PBR28, a second generation TSPO radioligand, and
by neuropathological verification. A non-invasive methodology that allows investigating
and characterizing the contribution of neuroinflammation in the GM will have a
tremendous impact in clarifying disease mechanisms in MS, as well as in a wide-
spectrum of neurological and psychiatric conditions.

## Key facts

- **NIH application ID:** 10288188
- **Project number:** 1R21NS123419-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Caterina Mainero
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $479,639
- **Award type:** 1
- **Project period:** 2021-07-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10288188

## Citation

> US National Institutes of Health, RePORTER application 10288188, In Vivo Imaging of Cortical Glial Activation Using Advanced Diffusion Magnetic Resonance Imaging (1R21NS123419-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10288188. Licensed CC0.

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