Free-water (FW) is a diffusion MRI marker of freely diffusing water in the extracellular space, which is expected to increase in the presence of neuroinflammation. Here, we test associations between FW and positron emission tomography (PET) imaging of the translocator protein (TSPO), which is a putative neuroinflammatory marker. We show that increased FW relates to higher TSPO binding in the hippocampi of healthy controls, but not of individuals with sports-related, repetitive traumatic brain injury. Thus, while FW relates to TSPO under healthy conditions, pathological variance in TSPO may complicate associations between FW and TSPO-indexed neuroinflammation.
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