Beyond mean value analysis - a voxel-based analysis of the quantitative MR biomarker water T2 in the presence of fatty infiltration in skeletal muscle tissue of patients with neuromuscular diseases

Abstract

The main pathologies in the muscles of patients with neuromuscular diseases (NMD) are fatty infiltration and edema. Recently, quantitative magnetic resonance (MR) imaging for determination of the MR biomarkers proton density fat fraction (PDFF) and water T₂ (T_2w ) has been advanced. Biophysical effects or pathology can have different effects on MR biomarkers. Thus, for heterogeneously affected muscles, the routinely performed mean or median value analyses of MR biomarkers are questionable. Our work presents a voxel-based histogram analysis of PDFF and T_2w images to point out potential quantification errors. In 12 patients with NMD, chemical-shift encoding-based water-fat imaging for PDFF and T₂ mapping with spectral adiabatic inversion recovery (SPAIR) for T_2w determination was performed. Segmentation of nine thigh muscles was performed bilaterally (n = 216). PDFF and T₂ maps were coregistered. A voxel-based comparison of PDFF and T_2w showed a decreased T_2w with increasing PDFF. Mean T_2w and mean T_2w ^{without fatty voxels} (PDFF < 10%) show good agreement, whereas standard deviation (σ) T_2w and σ T_2w ^{without fatty voxels} show increasing difference with increasing values of σ. Thereby two subgroups can be observed, referring to muscles in which the exclusion of fatty voxels has a negligible influence versus muscles in which a strong dependency of the T_2w value distribution on the exclusion of fatty voxels is present. Because of the two opposite effects that influence T_2w in a voxel, namely, (i) a pathophysiologically increased water mobility leading to T_2w elevation, and (ii) a dependency of T_2w on the PDFF leading to decreased T_2w , the T_2w distribution within a muscle might be heterogenous and the routine mean or median analysis can lead to a misinterpretation of the muscle health. It was concluded that muscle T_2w mean values can wrongly suggest healthy muscle tissue. A deeper analysis of the underlying value distribution is necessary. Therefore, a quantitative analysis of T_2w histograms is a potential alternative.

Keywords: MR biomarker; NMD; PDFF; edema; fatty infiltration; histogram; skeletal muscle; water T2.