Table 1.

Strengths and limitations of commonly-used techniques to measure neuroinflammation in humans in the context of HIV.

Technique	Example studies	Strengths	Limitations
Neuropathology	Smith et al. [26] Anthony et al. [223]	Cellular and molecular features of neuroinflammation such as microglial ramification or activation may be observed and quantified directly	Limited availability of post-mortem human brain tissue
Cerebrospinal fluid markers	Cheng et al. [224] Guha et al. [225]	Concentrations of inflammatory cytokines circulating in the central nervous system may be determined directly	High variability; lumbar puncture is an invasive and painful procedure
Blood biomarkers	Lyons et al. [226] Wada et al. [227]	Venepuncture for sample collection is a routine procedure; levels of some blood biomarkers are correlated with CSF levels	Less direct measure of CNS inflammation as there is limited exchange of molecules across the blood–brain barrier
PET Imaging	Garvey et al. [228] Vera et al. [97]	In vivo measurement of microglial and/or astroglial activation in the brain	Heterogeneity in choice of radioligands and analysis; invasive and with potential risks with injection of radioactive tracers
MRS Imaging	Graham et al. [69] Cysique et al. [229]	Non-invasive, relatively straightforward to administer; can detect changes in a range of neurometabolites in localised brain regions	Low signal-to-noise ration; requires pre-specific Regions of Interest (ROIs)

Studies employing these techniques to assess neuroinflammation in HIV are included as examples.