Daniela Franz1, Dominik Weidlich1, Friedemann Freitag1, Christina Holzapfel2, Thomas Baum1, Holger Eggers3, Ernst J. Rummeny1, Hans Hauner2, and Dimitrios C. Karampinos1
1Department of Diagnostic and Interventional Radiology, Technical University of Munich, Munich, Germany, 2Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich, Munich, Germany, 3Philips Research Laboratory, Hamburg, Germany
Synopsis
Proton density fat fraction (PDFF) mapping has been
emerging as important metabolic phenotyping parameter in obesity enabling spatially-resolved
fat quantification in multiple organs. PDFF of adipose tissue has also recently
gained significant attention due to the interest in developing biomarkers of
brown fat which is assumed to be present in the adult supraclavicular fossa.
However, it remains unknown how adipose tissue PDFF relates to other fat depots
and anthropometric parameters. The present study aims to investigate the
relationship of the supraclavicular and gluteal fat PDFF with SAT and VAT
volumes and anthropometric obesity markers.
Purpose:
The selection of optimal treatment and lifestyle
interventions in patients with metabolic diseases is in tremendous need for
better risk stratification strategies. MRI-based metabolic phenotyping
quantifying different fat depots has been proposed as a methodology to improve risk
stratification in obesity and diabetes [1]. MRI has been traditionally used to
quantify the subcutaneous adipose tissue (SAT) volume and the visceral adipose
tissue (VAT) volume [2]. Proton density fat fraction (PDFF) mapping based on a
multi-echo gradient echo acquisition has also recently enabled
spatially-resolved fat quantification in multiple organs and liver PDFF has
been emerging as an important metabolic phenotyping parameter [3]. In addition,
recent reports have suggested that PDFF values in the supraclavicular fossa can
be indicative of the presence of brown fat even in adults [4,5]. However, it
remains unknown how the PDFF of adipose tissue relates to other fat depots and
anthropometric parameters. Therefore, the purpose of the present study was to investigate
the relationship of the PDFF of supraclavicular and gluteal fat with SAT and
VAT volumes and anthropometric obesity markers.Methods:
Subjects & measurements: For this prospective study, 30 healthy subjects (20
females and 10 males; median BMI 22.7 kg/m2, range 17.4-39.1 kg/m2;
median age 29 years, range 22-68 years) were recruited. Subjects underwent an
MRI of the neck and the abdomen/ pelvis on a 3T scanner (Ingenia, Philips
Healthcare). In order to measure the supraclavicular and gluteal PDFF, a
six-echo multi-echo gradient echo sequence with bipolar gradients was used: TR
= 12 ms, TE1 = 1.24 ms, ΔTE = 1.0, flip angle = 5°, bandwidth = 1413
Hz/pixel, 268x200x93 acquisition matrix size, FOV = 400x300x140 mm3,
1.5 mm isotropic voxel size, SENSE with R = 2.5. For the abdomen and pelvis, a
two-point Dixon sequence with two stacks was used: TR = 4.0 ms, TE1/TE2 =
1.32/2.6 ms, flip angle = 10°, bandwidth = 1004 Hz/pixel, 332x220 acquisition
matrix size, FOV = 500x446 mm2, acquisition voxel = 1.5x2.0x5.0 mm3,
44 slices, SENSE with R = 2.5.
Data analysis: PDFF maps were generated using the online complex-based
fat quantification algorithm, accounting for known confounding factors
including the presence of multiple fat peaks, a single T2* correction and phase
errors. In order to determine volumes of SAT and VAT, a custom-built post-processing
algorithm was used for automatic classification of the different abdominal
tissue compartments based on the water-separated and fat-separated images from
the 2-point Dixon scan [6]. VAT and SAT volumes were normalized by height
(ml/cm). For segmentation of the supraclavicular and subcutaneous fat, a custom-built
MATLAB-algorithm was used, delineating the deep supraclavicular and gluteal
subcutaneous fat pockets bilaterally. BMI, waist circumference and
waist-to-height-ratio were recorded as anthropomorphic obesity markers.
Results:
PDFF in the supraclavicular fossa was 74.1% ±4.5 (65.4-83.8) and the PDFF of subcutaneous
gluteal fat was 89.1% ±3.2 (82.2-94), resulting in in a highly significant
difference in PDFF between the supraclavicular fat and subcutaneous gluteal fat
(p < 0.0001) (Fig.1). Fig. 2 shows the SAT/VAT segmented regions and the PDFF
maps of supraclavicular and gluteal region in a low and a high BMI subject. The
subject with high BMI has higher SAT/VAT volume, and higher supraclavicular and
gluteal PDFF than the low BMI subject. PDFF in supraclavicular as well as
gluteal fat was positively associated with VAT volume (r=0.67, p=0.0001;
r=0.56, p=0.0013 respectively) and SAT volume (r=0.64, p=0.0001; r=0.53,
p=0.0024, respectively). Correlations with anthropometric obesity markers are
listed in Table 1.Discussion & Conclusion:
The present study shows a highly significant difference
between the PDFF in different fat regions, pointing towards brown fat being
present in the supraclavicular adipose tissue in adults. Furthermore, PDFF of
the analyzed adipose tissue depots is correlated to both MR-based and
anthropometric markers of obesity. The correlation of supraclavicular PDFF with
obesity markers is consistent with the assumed relationship between brown fat
and obesity. To the best of our knowledge the correlation of the gluteal PDFF
with SAT and VAT volumes has never been reported before. The above association
is also consistent with previous findings relating CT-based SAT attenuation to
obesity markers [7]. Therefore, the presents findings suggest that adipose
tissue PDFF can not only identify the presence of brown fat in the
supraclavicular adipose tissue, but might also serve as new biomarker in subcutaneous
adipose tissue for improving the characterization of the obese phenotype, risk
stratification and selection of appropriate treatment and lifestyle
interventions options in clinical routine.Acknowledgements
The
present work was supported by the European Research Council (grant agreement
No 677661, ProFatMRI) and Philips Healthcare.References
[1] Thomas, Obesity 20:76, 2012
[2] Machann, Radiology 257:353, 2010
[3] Hu, NMR Biomed 26:1609, 2013
[4] Fransssens, NMR Biomed 29:48, 2016
[5] Franz, J Nucl Med 56:1742, 2015
[6] Cordes, J Magn Reson Imaging 42:1272, 2015
[7] Rosenquist, J. Am. Coll. Cardiol 6:762, 2013