Multiexponential Analysis of the WaterT2-Relaxation in the Skeletal Muscle Provides Distinct Markers of Disease Activity Between Inflammatory and Dystrophic Myopathies

Background The monoexponential water T-2(T2-mono) is a proven biomarker of disease activity in neuromuscular disorders (NMDs). However, it lacks specificity, being elevated in the presence of several pathological processes and pathomorphological alterations in the muscle tissue. Purpose To investigate the multiexponential behavior of the water T-2-relaxation in the skeletal muscle of NMD patients, aiming to identify more sensitive and specific biomarkers of disease activity. Study Type Retrospective case-control. Population Thirty Duchenne muscular dystrophy and 114 inclusion body myositis patients and 55 control subjects. Field Strength/Sequence 3T/Single-voxel proton spectroscopy (H-1-MRS) and multispin-echo (MSE) imaging. Assessment Water T-2-decay curves generated from(1)H-MRS data acquired at 14 echo-times were fitted to mono- and biexponential models and the adjusted R(2)of each fit was computed. Additionally, T(2)spectra were generated from a regularized inverse Laplace transform. For comparison, water T(2)maps were generated from the MSE data. The performances of the different variables at identifying patients were assessed via receiver operating characteristic (ROC)-curve analysis. Statistical Tests Chi-square, Kruskal-Wallis, and Mann-Whitney with Bonferroni correction for multiple comparisons. Results T(2-mono)was elevated in patients (P<0.05), but could not distinguish inclusion body myositis (IBM) from Duchenne muscular dystrophy (DMD). While 79% of IBM data presented a biexponential behavior, this was only 16% and 10% for DMD and control data, respectively (P<0.05). All T(2)spectra presented an intermediate-T(2)peak characterized by an elevated T(2)in patients (P<0.05) and by a relative fraction that was abnormally smaller in IBM patients (P<0.05). Also, a long-T(2)peak was exclusively observed in IBM patients. A combination of T-2-spectrum variables performed best at identifying patients. Data Conclusion T(2)spectra not only provided more sensitive and specific markers of disease presence than the T2-mono, but also allowed distinguishing IBM from DMD patients. This must reflect distinct predominant pathological alterations between these diseases, suggesting that these markers provide additional pathophysiological/histopathological information that are missing from T2-mono. Level of Evidence 3 Technical Efficacy Stage 3

Automated summary

The study aimed to investigate the multiexponential behavior of water T2-relaxation in the skeletal muscle of NMD patients to identify more sensitive and specific biomarkers of disease activity. Results showed that T2-spectra provided more sensitive and specific markers of disease presence compared to T2-mono, allowing for distinguishing between different types of NMD patients.