Abstract
ObjectivesTo assess the changes in phosphodiester (PDE)-levels, detected by 31P magnetic resonance spectroscopy (MRS), over 24-months to determine the potential of PDE as marker for muscle tissue changes in Duchenne Muscular Dystrophy (DMD) patients.MethodsSpatially resolved phosphorous datasets were acquired in the right lower leg of 18 DMD patients (range: 5–15.4 years) and 12 age-matched healthy controls (range: 5–14 years) at three time-points (baseline, 12-months, and 24-months) using a 7T MR-System (Philips Achieva). 3-point Dixon images were acquired at 3T (Philips Ingenia) to determine muscle fat fraction. Analyses were done for six muscles that represent different stages of muscle wasting. Differences between groups and time-points were assessed with non-parametric tests with correction for multiple comparisons. Coefficient of variance (CV) were determined for PDE in four healthy adult volunteers in high and low signal-to-noise ratio (SNR) datasets.ResultsPDE-levels were significantly higher (two-fold) in DMD patients compared to controls in all analyzed muscles at almost every time point and did not change over the study period. Fat fraction was significantly elevated in all muscles at all time points compared to healthy controls, and increased significantly over time, except in the tibialis posterior muscle. The mean within subject CV for PDE-levels was 4.3% in datasets with high SNR (>10:1) and 5.7% in datasets with low SNR.Discussion and conclusionThe stable two-fold increase in PDE-levels found in DMD patients in muscles with different levels of muscle wasting over 2-year time, including DMD patients as young as 5.5 years-old, suggests that PDE-levels may increase very rapidly early in the disease process and remain elevated thereafter. The low CV values in high and low SNR datasets show that PDE-levels can be accurately and reproducibly quantified in all conditions. Our data confirms the great potential of PDE as a marker for muscle tissue changes in DMD patients.
Highlights
Duchenne Muscular Dystrophy (DMD) is an X-linked disease caused by a mutation in the DMD gene which codes for the protein dystrophin
PDE-levels were significantly higher in DMD patients compared to controls in all analyzed muscles at almost every time point and did not change over the study period
While %fat correlates well with function, it reflects the replacement of muscle by fat and does not allow any statement on muscle tissue itself. [4,5,6] Water T2 has a closer relation with muscle, as it reflects inflammation and/or edema-like processes in this tissue
Summary
Duchenne Muscular Dystrophy (DMD) is an X-linked disease caused by a mutation in the DMD gene which codes for the protein dystrophin. [4,5,6] Water T2 has a closer relation with muscle, as it reflects inflammation and/or edema-like processes in this tissue. It has a low discriminative ability in DMD due to the use of corticosteroids—the difference in water T2 from a corticosteroid-treated boy with DMD and a healthy control is close to the detection limit of any difference.[7]
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