Utilization of Multi-Parametric Quantitative Magnetic Resonance Imaging in the Early Diagnosis of Duchenne Muscular Dystrophy.

BACKGROUND: It is challenging to diagnose suspected Duchenne muscular dystrophy (DMD) patients in the very early stage of the disease. More evidence is needed to demonstrate the potential of quantitative MRI (qMRI) in precisely identifying patients before substantial physical decline occurs. PURPOSE: To assess the early diagnostic performance of multi-parametric qMRI for DMD patients, and the ability to identify DMD patients with mild functional decline. STUDY TYPE: Prospective. SUBJECTS: One hundred and forty DMD subjects (9.0 ± 2.2 years old), 24 male healthy controls (HCs) (9.2 ± 2.5 years old). FIELD STRENGTH/SEQUENCE: 3.0 T/3-point Dixon, T1-mapping, and T2-mapping. ASSESSMENT: qMRI measurements (fat fraction [FF], T1, and T2) of 11 thigh muscles (rectus femoris [RF], vastus lateralis [VL], vastus intermedius, vastus medialis, gracilis, sartorius, adductor longus, adductor magnus [AM], semitendinosus, semimembranosus, biceps femoris long head [BFLH]) on the right side were conducted. NorthStar ambulatory assessment (NSAA) score used to evaluate the function of DMD patients and divided them into three subgroups: mild (76-100 score), moderate (51-75 score), and severe (0-50 score) functional decline. STATISTICAL TESTS: Independent t-test, ANOVA analysis, and receiver operating characteristic (ROC) curves. A P-value <0.05 was considered statistically significant. RESULTS: Compared with HCs, FF and T2 were significantly higher in the group of all DMD patients, while T1 was significantly lower. The combination of T1 and T2 in RF, VL, AM, and BFLH achieved excellent area under curve (AUCs) (0.967-0.992) in differentiating five DMD patients without abnormal fat infiltration from HCs. Overall, T2 reached higher AUCs than FF and T1 in distinguishing DMD with mild functional decline from HCs, whereas FF achieved higher AUCs than T1 and T2 in distinguishing three DMD subgroups with functional decline. DATA CONCLUSION: Multi-parametric qMRI demonstrate effective diagnostic capabilities for DMD patients in the early stage of the disease, and can identify patients with mild physical decline. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Quantifying Variability in Motor Function in Duchenne Muscular Dystrophy: UK Centiles for the NorthStar Ambulatory Assessment, 10 m Walk Run Velocity and Rise from Floor Velocity in GC Treated Boys.

Background Boys with Duchenne Muscular Dystrophy (DMD) display heterogeneous motor function trajectory in clinics, which represents a significant obstacle to monitoring. OBJECTIVE: In this paper, we present the UK centiles for the North Star Ambulatory Assessment (NSAA), the 10 m walk/run time (10MWR) and velocity (10MWRV), and the rise from floor time (RFF) and velocity (RFFV) created from a cohort of glucocorticoid treated DMD boys between the age of 5 and 16 years. METHODS: Participants were included from the UK NorthStar registry if they had initiated steroids (primarily deflazacorts/prednisolone, intermittent/daily) and were not enrolled in an interventional trial. Assessments were included if the participant had a complete NSAA, the timed tests had been completed or the corresponding items were 0, or the participant was recorded as non-ambulant, in which case the NSAA was assumed 0. RESULTS: We analysed 3987 assessments of the NSAA collected from 826 participants. Of these, 1080, 1849 and 1199 were imputed as 0 for the NSAA, RFFV and 10MWRV respectively. The 10th, 25th, 50th, 75th and 90th centiles were presented. The NSAA centiles showed a peak score of 14, 20, 26, 30 and 32 respectively, with loss of ambulation at 10.7, 12.2 and 14.3 years for the 25th, 50th and 75th centiles, respectively. The centiles showed loss of rise from floor at 8.6, 10.1 and 11.9 years and a loss of 10MWR of 0 at 8.9, 10.3 and 13.8 years for the 25th, 50th and 75th centiles, respectively. The centiles were pairwise less correlated than the raw scores, suggesting an increased ability to detect variability in the DMD cohort. CONCLUSIONS: The NSAA, 10MWR and RFF centiles may provide insights for clinical monitoring of DMD boys, particularly in late ambulatory participants who are uniformly declining. Future work will validate the centiles in national and international natural history cohorts.

Longitudinal study of multi-parameter quantitative magnetic resonance imaging in Duchenne muscular dystrophy: hyperresponsiveness of gluteus maximus and detection of subclinical disease progression in functionally stable patients.

OBJECTIVE: To describe the disease progression of Duchenne muscular dystrophy (DMD) in the pelvic and thigh muscles over 1-year using multiple-parameter quantitative magnetic resonance imaging (qMRI), and to determine the most responsive muscle and predict subclinical disease progression in functionally stable patients. METHODS: Fifty-four DMD patients (mean age 8.9 ± 2.5, range 5-15 years) completed baseline and 1-year follow-up qMRI examinations/biomarkers [3-point Dixon/fat fraction (FF); T1 mapping/T1; T2 mapping/T2]. Meanwhile, clinical assessments [NorthStar ambulatory assessment (NSAA) score] and timed function tests were performed in DMD patients. Twenty-four healthy male controls (range 5-15 years) accomplished baseline qMRI examinations. Group differences were compared using the Wilcoxon test. The standardized response mean (SRM) was taken as the responsiveness to the disease progression index. RESULTS: FF, T1, and T2 in all DMD age subgroups changed significantly over 1-year (P < 0.05). Even in functionally stable patients (NSAA score increased, unchanged, or decreased by 1-point) over 1-year, significant increases in FF and T2 and decreases in T1 were observed in gluteus maximus (GMa), gluteus medius, vastus lateralis, and adductor magnus (P < 0.05). Overall, the SRM of FF, T1, and T2 was all the highest in GMa, which were 1.25, - 0.92, and 0.93, respectively. CONCLUSIONS: qMRI biomarkers are responsive to disease progression and can also detect subclinical disease progression in functionally stable DMD patients over 1-year. GMa is the most responsive to disease progression of all the muscles analyzed. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ) ChiCTR1800018340, 09/12/2018, prospectively registered.