Comparison of [18F]FDG PET/CT with magnetic resonance imaging for the assessment of human brown adipose tissue activity

Jonas Gabriel William Fischer, Claudia Irene Maushart, Anton S Becker, Julian Müller, Philipp Madoerin, Alin Chirindel, Damian Wild, Edwin E G W Ter Voert, Oliver Bieri, Irene Burger, Matthias Johannes Betz, Jonas Gabriel William Fischer, Claudia Irene Maushart, Anton S Becker, Julian Müller, Philipp Madoerin, Alin Chirindel, Damian Wild, Edwin E G W Ter Voert, Oliver Bieri, Irene Burger, Matthias Johannes Betz

Abstract

Background: Brown adipose tissue (BAT) is a thermogenic tissue which can generate heat in response to mild cold exposure. As it constitutes a promising target in the fight against obesity, we need reliable techniques to quantify its activity in response to therapeutic interventions. The current standard for the quantification of BAT activity is [18F]FDG PET/CT. Various sequences in magnetic resonance imaging (MRI), including those measuring its relative fat content (fat fraction), have been proposed and evaluated in small proof-of-principle studies, showing diverging results. Here, we systematically compare the predictive value of adipose tissue fat fraction measured by MRI to the results of [18F]FDG PET/CT.

Methods: We analyzed the diagnostic reliability of MRI measured fat fraction (FF) for the estimation of human BAT activity in two cohorts of healthy volunteers participating in two prospective clinical trials (NCT03189511, NCT03269747). In both cohorts, BAT activity was stimulated by mild cold exposure. In cohort 1, we performed [18F]FDG PET/MRI; in cohort 2, we used [18F]FDG PET/CT followed by MRI. Fat fraction was determined by 2-point Dixon and 6-point Dixon measurement, respectively. Fat fraction values were compared to SUVmean in the corresponding tissue depot by simple linear regression.

Results: In total, 33 male participants with a mean age of 23.9 years and a mean BMI of 22.8 kg/m2 were recruited. In 32 participants, active BAT was visible. On an intra-individual level, FF was significantly lower in high-SUV areas compared to low-SUV areas (cohort 1: p < 0.0001 and cohort 2: p = 0.0002). The FF of the supraclavicular adipose tissue depot was inversely related to its metabolic activity (SUVmean) in both cohorts (cohort 1: R2 = 0.18, p = 0.09 and cohort 2: R2 = 0.42, p = 0.009).

Conclusion: MRI FF explains only about 40% of the variation in BAT glucose uptake. Thus, it can currently not be used to substitute [18F] FDG PET-based imaging for quantification of BAT activity.

Trial registration: ClinicalTrials.gov. NCT03189511 , registered on June 17, 2017, actual study start date was on May 31, 2017, retrospectively registered. NCT03269747 , registered on September 01, 2017.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Schematic overview of study procedures in cohorts 1 and 2
Fig. 2
Fig. 2
Image processing workflow. a Segmentation based on a crude manual outline of the adipose tissue in the neck region. b Segmentation based on thresholding of the fat fraction volume selecting all voxels with a fat fraction between 400 and 1000 per mille. c Intersection of segmentations a and b leading to an exact representation of the adipose tissue in the neck region. d This segmentation was shrunk by one voxel in each dimension in order to reduce partial volume effects. e To reduce background noise the in-phase volume was thresholded in order to select the contours of the body and intersected with segmentation d resulting in a final segmentation f (overlay with PET data). This segmentation was again intersected with areas within the PET data volume exhibiting SUV values above 1.5 g/ml yielding a representation of the metabolically active supraclavicular adipose tissue
Fig. 3
Fig. 3
Comparison of the fat fraction in PET-negative and PET-positive areas within the supraclavicular adipose tissue depot. a Placement of spherical region of interest in PET-negative (turquois) and PET-positive (pink) area of supraclavicular adipose tissue. b Study cohort 1, p < 0.0001 and c study cohort 2, p = 0.0002 (paired t test).
Fig. 4
Fig. 4
Simple linear regression plots with SUVmean (g/ml) as dependent variable versus tissue fat fraction (‰) as the independent variable. Cohort 1, final segmentation (a) and the more restrictive optimized final segmentation (b). Cohort 2, final segmentation (c) and the more restrictive optimized final segmentation (d)
Fig. 5
Fig. 5
Simple linear regression plots with SUVmean (g/ml) as dependent variable versus tissue fat fraction (‰) as the independent variable
Fig. 6
Fig. 6
Linear regression of FDG uptake versus cold-induced thermogenesis (CIT) and fat fraction versus CIT in cohort 1 (a and b) and cohort 2 (c and d)

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