Near-Infrared Time-Resolved Spectroscopy for Assessing Brown Adipose Tissue Density in Humans: A Review

Brown adipose tissue (BAT) mediates adaptive thermogenesis upon food intake and cold exposure, thus potentially contributing to the prevention of lifestyle-related diseases. ¹⁸F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) with computed tomography (CT) (¹⁸FDG-PET/CT) is a standard method for assessing BAT activity and volume in humans. ¹⁸FDG-PET/CT has several limitations, including high device cost and ionizing radiation and acute cold exposure necessary to maximally stimulate BAT activity. In contrast, near-infrared spectroscopy (NIRS) has been used for measuring changes in O₂-dependent light absorption in the tissue in a non-invasive manner, without using radiation. Among NIRS, time-resolved NIRS (NIR_TRS) can quantify the concentrations of oxygenated and deoxygenated hemoglobin ([oxy-Hb] and [deoxy-Hb], respectively) by emitting ultrashort (100 ps) light pulses and counts photons, which are scattered and absorbed in the tissue. The basis for assessing BAT density (BAT-d) using NIR_TRS is that the vascular density in the supraclavicular region, as estimated using Hb concentration, is higher in BAT than in white adipose tissue. In contrast, relatively low-cost continuous wavelength NIRS (NIR_CWS) is employed for measuring relative changes in oxygenation in tissues. In this review, we provide evidence for the validity of NIR_TRS and NIR_CWS in estimating human BAT characteristics. The indicators (Ind_NIRS) examined were [oxy-Hb]_sup, [deoxy-Hb]_sup, total hemoglobin [total-Hb]_sup, Hb O₂ saturation (StO_2sup), and reduced scattering coefficient ( $$ ) in the supraclavicular region, as determined by NIR_TRS, and relative changes in corresponding parameters, as determined by NIR_CWS. The evidence comprises the relationships between the Ind_NIRS investigated and those determined by ¹⁸FDG-PET/CT; the correlation between the Ind_NIRS and cold-induced thermogenesis; the relationship of the Ind_NIRS to parameters measured by ¹⁸FDG-PET/CT, which responded to seasonal temperature fluctuations; the relationship of the Ind_NIRS and plasma lipid metabolites; the analogy of the Ind_NIRS to chronological and anthropometric data; and changes in the Ind_NIRS following thermogenic food supplementation. The [total-Hb]_sup and [oxy-Hb]_sup determined by NIR_TRS, but not parameters determined by NIR_CWS, exhibited significant correlations with cold-induced thermogenesis parameters and plasma androgens in men in winter or analogies to ¹⁸FDG-PET. We conclude that NIR_TRS can provide useful information for assessing BAT-d in a simple, rapid, non-invasive way, although further validation study is still needed.