MR-based assessment of quadriceps muscle fat has been proposed as surrogate marker in sarcopenia, osteoarthritis, and neuromuscular disorders. Intermuscular fat (fat between muscles) and intramuscular fat (fat within muscles) constitute the intermuscular adipose tissue (IMAT). In contrast to T1-weighted imaging, chemical shift encoding-based water-fat MRI allows the separate assessment and quantification of inter- and intramuscular fat. Despite previous studies on investigating the relationship between IMAT, intramuscular proton density fat fraction (PDFF), and muscle strength in patients with neuromuscular diseases and knee osteoarthritis [1-3], little is known about the relationship between IMAT, intramuscular PDFF, and muscle strength in healthy volunteers. Therefore, we investigated the association of quadriceps muscle fat with isometric strength measurements in healthy males using chemical shift encoding-based water-fat MRI.

Subjects:

Nine, healthy men (age: 28±8 years, BMI: 28.1±3.9 kg/m²) were recruited for this study.

Physical Strength Measurements:

Right quadriceps muscle maximum isometric torque [Nm] produced by knee extension at 60° and 90° knee flexion angle was measured with a rotational dynamometer (Isomed 2000).

MR Imaging:

The whole thigh musculature of the subjects was scanned on a 3 T whole-body scanner (Ingenia, Philips Healthcare) using the built-in-the-table posterior coil (12-channel array) and the anterior coil (16-channel array). The MR exam consisted of two axial imaging stacks in feet-head direction in order to achieve whole thigh coverage. A six-echo 3D spoiled gradient echo sequence was used for chemical shift encoding-based water-fat separation. The sequence acquired the six echoes in a single TR using non-flyback (bipolar) read-out gradients and the following imaging parameters: TR/TE_min/ΔTE = 10/1.04/0.8 ms, FOV = 300x525 mm², acquisition matrix = 96x263, slice thickness = 4 mm, number of slices = 65, receiver bandwidth = 2345 Hz/pixel, frequency direction = A/P (to minimize breathing artifacts), SENSE in L/R direction with reduction factor R=2, N_avg = 1, scan time = 1min and 48 s per stack. A flip angle of 3° was used to minimize T1-bias effects [4].

Imaging-Based Fat Quantification:

The gradient echo imaging data were processed on-line using the mDIXON Quant method provided by the manufacturer. It performs a complex-based water-fat decomposition using a pre-calibrated seven-peak fat spectrum and a single T₂* to model the signal variation with echo time [5-7]. PDFF maps were then computed as the ratio of the fat signal over the sum of fat and water signals.

Segmentation of the right quadriceps muscle was performed on the PDFF maps by using the free open-source software Medical Imaging Interaction Toolkit (MITK). The quadriceps muscle region of interest (ROI) including all muscle components (i.e. Rectus femoris, Vastus medialis, Vastus intermedius, and Vastus lateralis), muscular fasciae, and the intermuscular fat were semi-automatically segmented from the insertion at the patella tendon upward in 40 consecutive slices in all subjects (ROI I in Figure 1). The ROI I including all quadriceps muscle components was used to measure the quadriceps muscle volume. The mean PDFF value over ROI I was defined as the IMAT fraction (i.e. IMAT = intermuscular fat + intramuscular fat). Quadriceps lean tissue volume was calculated by the equation: (100 – IMAT fraction) x quadriceps muscle volume. Furthermore, the four muscle components were separately segmented in the ten most proximal of the 40 above mentioned slices (ROIs II in Figure 1). Quadriceps intramuscular PDFF was determined by averaging the PDFF over all manually placed ROIs II.

Reproducibility:

Three subjects were scanned three times with repositioning to assess the reproducibility error of the MRI measurements. Precision errors of the IMAT fraction and intramuscular PDFF were expressed as root mean square error (RMSE) in [%] (absolute units) and as root mean square coefficients of variation (RMSCV) in [%] (relative units).

Quadriceps IMAT fraction and intramuscular PDFF correlated significantly (p<0.05) with physical strength (up to r=-0.83 and r=-0.87, p<0.05; Figure 2). A statistical trend (p<0.01) was observed for the association of quadriceps muscle volume and lean tissue volume with physical strength (up to r=0.65). Furthermore, a significant correlation was found between quadriceps IMAT fraction and intramuscular PDFF (r=0.98; p<0.05). The RMSE of the IMAT fraction and intramuscular PDFF amounted to 0.07% and 0.17% (absolute units), respectively. The RMSCV of the IMAT fraction and intramuscular PDFF was 1.5% and 5.7% (relative units), respectively.

The present study demonstrated that quadriceps inter- and intramuscular fat could be reliably quantified using chemical shift encoding-based water-fat MRI. Strong associations were observed between water-fat MRI derived quadriceps muscle fat parameters and corresponding physical strength measurements in healthy males. Thus, water-fat MRI could detect minor changes of intramuscular fat that correlate with muscle strength. This may help to initiate early, individualized therapy protocols in order to maintain or improve muscle function.

mDIXON Quant is not labeled for the use under discussion.