Anatomical Grading for Metabolic Activity of Brown Adipose Tissue

Abstract

Background: Recent advances in obesity research suggest that BAT activity, or absence thereof, may be an important factor in the growing epidemic of obesity and its manifold complications. It is thus important to assess larger populations for BAT-activating and deactivating factors. 18FDG-PET/CT is the standard method to detect and quantify metabolic BAT activity, however, the manual measurement is not suitable for large studies due to its time-consuming nature and poor reproducibility across different software and devices.

Methodology/main findings: In a retrospective study, 1060 consecutive scans of 1031 patients receiving a diagnostic 18FDG-PET/CT were examined for the presence of active BAT. Patients were classified according to a 3-tier system (supraclavicular, mediastinal, infradiaphragmatic) depending on the anatomical location of their active BAT depots, with the most caudal location being the decisive factor. The metabolic parameters (maximum activity, total volume and total glycolysis) were measured on a standard PET/CT workstation. Mean age of the population was 60±14.6y. 41.61% of patients were female. Metabolically active BAT was found in 53 patients (5.1%). Female, younger and leaner patients tended to have more active BAT, higher metabolic activity and more caudally active BAT. In total, 15 patients showed only supraclavicular, 27 additional mediastinal, and 11 infradiaphragmal activity. Interestingly, the activation of BAT always followed a cranio-caudal gradient. This anatomical pattern correlated with age and BMI as well as with all metabolic parameters, including maximum and total glycolysis (p<0.001).

Conclusion: Based on our data we propose a simple method to grade or quantify the degree of BAT amount/activity in patients based on the most caudally activated depot. As new modalities for BAT visualization may arise in the future, this system would allow direct comparability with other modalities, in contrary to the PET-metrics, which are restricted to 18FDG-PET/CT.

Fig 1. Differences between the two cohorts.

a) Sex difference: Stacked bar plot depicting the top 15% percent of the overall population, showing the higher incidence (OR = 3.62) of positive BAT in females compared to males. b) Age and c) BMI difference of the BAT-positive cohort. Density plots showing the shift of age and BMI from the overall population to the BAT-positive cohort (blue), who were found to be significantly younger and lighter.

Fig 2. Morphologic Patterns of BAT.

a) Schematic drawing of the different depots, some of which were summarized as indicated by the coloration into the three categories c) supraclavicular d) mediastinal and e) infradiaphragmatic. b) Showing the total number of BAT-positive subjects grouped by the most caudally active depot of either supraclavicular (including axillary and nuchal), mediastinal or infadiaphragmal BAT. c-e) Coronal MIP PET images (left) and fused PET/CT slices (right) of representative subjects in the according category. All pictures also show variable glucose uptake of the liver, intestines and myocardium as well as strong emissions from the renal pelvis, the latter being concentrated ¹⁸FDG breakdown products excreted through the urine. This can be appreciated in the fused d) image, where the true BAT activity is located in a fat depot on the patient’s left side (right side on the picture) adjacent to the first lumbar vertebra.

Fig 3. Quantification of glycolysis in the different depots.

A clear increase of all three metabolic PET-parameters MFV, TFG and SUV_max, from the supraclavicular depots to the more caudally located infradiaphragmatic depots can be appreciated.

Fig 4. Differences in BAT activation between individuals and categories.

The first column depicts the total fat glycolysis (TFG) in relation to BMI (a), age (b) and external temperature (c). As can be guessed by the visual impression of the scatter plots, no clear correlation between either of the factors and the TFG could be established. In the second column however, the same data is shown and instead of using the metabolic activity, it is simply ordered by the morphological type of activation, showing clearly more activated depots with lower BMI, age and temperature. The dashed lines in (a) and (b) represent the significant linear correlation (p > 0.05), the asterisk (*) in (c) marks the only statistically significant difference (p<0.0125) in absence of a linear correlation.