Affiliation:
1. C.J. Gorter MRI Center, Department of Radiology Leiden University Medical Center Leiden The Netherlands
2. Department of Human Genetics Leiden University Medical Center Leiden The Netherlands
3. Department of Neurology Leiden University Medical Center Leiden The Netherlands
4. Duchenne Center Netherlands Leiden The Netherlands
5. Radiology and Nuclear Medicine Amsterdam University Medical Center, University of Amsterdam, Amsterdam Movement Sciences Amsterdam The Netherlands
6. Department of Pathology Leiden University Medical Center Leiden The Netherlands
Abstract
AbstractBackgroundBecker muscular dystrophy (BMD) is an X‐linked disorder characterized by slow, progressive muscle damage and muscle weakness. Hallmarks include fibre‐size variation and replacement of skeletal muscle with fibrous and adipose tissues, after repeated cycles of regeneration. Muscle histology can detect these features, but the required biopsies are invasive, are difficult to repeat and capture only small muscle volumes. Diffusion‐tensor magnetic resonance imaging (DT‐MRI) is a potential non‐invasive alternative that can calculate muscle fibre diameters when applied with the novel random permeable barrier model (RPBM). In this study, we assessed muscle fibre diameters using DT‐MRI in BMD patients and healthy controls and compared these with histology.MethodsWe included 13 BMD patients and 9 age‐matched controls, who underwent water‐fat MRI and DT‐MRI at multiple diffusion times, allowing RPBM parameter estimation in the lower leg muscles. Tibialis anterior muscle biopsies were taken from the contralateral leg in 6 BMD patients who underwent DT‐MRI and from an additional 32 BMD patients and 15 healthy controls. Laminin and Sirius‐red stainings were performed to evaluate muscle fibre morphology and fibrosis. Twelve ambulant patients from the MRI cohort underwent the North Star ambulatory assessment, and 6‐min walk, rise‐from‐floor and 10‐m run/walk functional tests.ResultsRPBM fibre diameter was significantly larger in BMD patients (P = 0.015): mean (SD) = 68.0 (25.3) μm versus 59.4 (19.2) μm in controls. Inter‐muscle differences were also observed (P ≤ 0.002). Both inter‐ and intra‐individual RPBM fibre diameter variability were similar between groups. Laminin staining agreed with the RPBM, showing larger median fibre diameters in patients than in controls: 72.5 (7.9) versus 63.2 (6.9) μm, P = 0.006. However, despite showing similar inter‐individual variation, patients showed more intra‐individual fibre diameter variability than controls—mean variance (SD) = 34.2 (7.9) versus 21.4 (6.9) μm, P < 0.001—and larger fibrosis areas: median (interquartile range) = 21.7 (5.6)% versus 14.9 (3.4)%, P < 0.001. Despite good overall agreement of RPBM and laminin fibre diameters, they were not associated in patients who underwent DT‐MRI and muscle biopsy, perhaps due to lack of colocalization of DT‐MRI with biopsy samples.ConclusionsDT‐MRI RPBM metrics agree with histology and can quantify changes in muscle fibre size that are associated with regeneration without the need for biopsies. They therefore show promise as imaging biomarkers for muscular dystrophies.
Subject
Physiology (medical),Orthopedics and Sports Medicine
Cited by
8 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献