UCLA

Background

Cardiovascular disease is the leading cause of death in patients with Duchenne muscular dystrophy (DMD)-a fatal X-linked genetic disorder. Late gadolinium enhancement (LGE) imaging is the current gold standard for detecting myocardial tissue remodeling, but it is often a late finding. Current research aims to investigate cardiovascular magnetic resonance (CMR) biomarkers, including native (pre-contrast) T₁ and extracellular volume (ECV) to evaluate the early on-set of microstructural remodeling and to grade disease severity. To date, native T₁ measurements in DMD have been reported predominantly at 1.5T. This study uses 3T CMR: (1) to characterize global and regional myocardial pre-contrast T₁ differences between healthy controls and LGE + and LGE- boys with DMD; and (2) to report global and regional myocardial post-contrast T₁ values and myocardial ECV estimates in boys with DMD, and (3) to identify left ventricular (LV) T₁-mapping biomarkers capable of distinguishing between healthy controls and boys with DMD and detecting LGE status in DMD.

Methods

Boys with DMD (N = 28, 13.2 ± 3.1 years) and healthy age-matched boys (N = 20, 13.4 ± 3.1 years) were prospectively enrolled and underwent a 3T CMR exam including standard functional imaging and T₁ mapping using a modified Look-Locker inversion recovery (MOLLI) sequence. Pre-contrast T₁ mapping was performed on all boys, but contrast was administered only to boys with DMD for post-contrast T₁ and ECV mapping. Global and segmental myocardial regions of interest were contoured on mid LV T₁ and ECV maps. ROI measurements were compared for pre-contrast myocardial T₁ between boys with DMD and healthy controls, and for post-contrast myocardial T₁ and ECV between LGE + and LGE- boys with DMD using a Wilcoxon rank-sum test. Results are reported as median and interquartile range (IQR). p-Values < 0.05 were considered significant. Receiver Operating Characteristic analysis was used to evaluate a binomial logistic classifier incorporating T₁ mapping and LV function parameters in the tasks of distinguishing between healthy controls and boys with DMD, and detecting LGE status in DMD. The area under the curve is reported.

Results

Boys with DMD had significantly increased global native T₁ [1332 (60) ms vs. 1289 (56) ms; p = 0.004] and increased within-slice standard deviation (SD) [100 (57) ms vs. 74 (27) ms; p = 0.001] compared to healthy controls. LGE- boys with DMD also demonstrated significantly increased lateral wall native T₁ [1322 (68) ms vs. 1277 (58) ms; p = 0.001] compared to healthy controls. LGE + boys with DMD had decreased global myocardial post-contrast T₁ [565 (113) ms vs 635 (126) ms; p = 0.04] and increased global myocardial ECV [32 (8) % vs. 28 (4) %; p = 0.02] compared to LGE- boys. In all classification tasks, T₁-mapping biomarkers outperformed a conventional biomarker, LV ejection fraction. ECV was the best performing biomarker in the task of predicting LGE status (AUC = 0.95).

Conclusions

Boys with DMD exhibit elevated native T₁ compared to healthy, sex- and age-matched controls, even in the absence of LGE. Post-contrast T₁ and ECV estimates from 3T CMR are also reported here for pediatric patients with DMD for the first time and can distinguish between LGE + from LGE- boys. In all classification tasks, T₁-mapping biomarkers outperform a conventional biomarker, LVEF.