# Imaging inflammation in the whole body and brain of ME/CFS patients

> **NIH NIH R21** · STANFORD UNIVERSITY · 2022 · $235,253

## Abstract

Project Summary
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a highly debilitating disease affecting millions
of people in the United States, yet very little is known about its underlying pathophysiology. The disease itself is
exceedingly complex and characterized by variable clusters of incapacitating symptoms, including extreme
fatigue, unrefreshing sleep, muscle pain, joint pain, headaches, and loss of memory or concentration. Preliminary
theories suggest that an initial trigger, possibly viral, results in inflammation that chronically affects several parts
the body, including the muscles, joints, lymphatic system, and central nervous system (CNS). Unfortunately,
current standard of care techniques for diagnosing suspected ME/CFS (i.e., blood tests and structural brain
imaging) do not provide direct measures of inflammation in the CNS or other organs and often afford results
within normal range. Hence, there is a critical unmet need to develop more sensitive and specific tests that not
only improve the accuracy of diagnosis but also provide a means to investigate specific immune responses and
their role in the initiation and progression of ME/CFS in the brain and periphery of ME/CFS.
Here, we propose for the first time to perform whole body position emission tomography (PET) imaging of
ME/CFS patients using [11C]DPA-713, a highly sensitive and specific radiotracer for the translocator protein 18
kDa (TSPO). TSPO is an established imaging biomarker of inflammation that is predominately upregulated in
activated innate immune cells including microglia in the CNS and other myeloid lineage cells (e.g., macrophages)
in the periphery. We hypothesize that chronic, unresolved inflammation driven by innate immune cells
underlies the central clinical problems of fatigue, pain, and cognitive dysfunction observed in ME/CFS.
Our encouraging preliminary data shows increased [11C]DPA-713-PET signal in multiple brain regions of severe
ME/CFS patients compared to healthy controls. We also demonstrate the feasibility of whole body PET/magnetic
resonance (PET/MR) imaging using [11C]DPA-713. In this proposal, we will expand on this data by investigating
the relationship between peripheral and central markers of inflammation, through the following aims: 1) Quantify
[11C]DPA-713 uptake in the CNS and whole body of ME/CFS patients compared to healthy asymptomatic
controls using PET/MRI, and 2) Correlate the extent and location of [11C]DPA-713-PET signal to clinical
measures of disease severity and peripheral fluid-based biomarkers of inflammation and infection. Additionally,
we will correlate PET findings with advanced multimodal MRI, including quantitative brain volumetry, diffusion
tensor imaging, and quantitative susceptibility mapping (QSM).
Completing these experiments will provide invaluable insights into the correspondence between myeloid cell
activation in the CNS and whole body, with that of plasma cytokine signatures, herpesvirus shedding,...

## Key facts

- **NIH application ID:** 10312128
- **Project number:** 5R21NS120087-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Michelle Louise James
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $235,253
- **Award type:** 5
- **Project period:** 2020-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312128

## Citation

> US National Institutes of Health, RePORTER application 10312128, Imaging inflammation in the whole body and brain of ME/CFS patients (5R21NS120087-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10312128. Licensed CC0.

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