Quantifying myofiber integrity using diffusion MRI and random permeable barrier modeling in skeletal muscle growth and Duchenne muscular dystrophy model in mice.

TitleQuantifying myofiber integrity using diffusion MRI and random permeable barrier modeling in skeletal muscle growth and Duchenne muscular dystrophy model in mice.
Publication TypeJournal Article
Year of Publication2018
AuthorsWinters KV, Reynaud O, Novikov DS, Fieremans E, Kim SGene
JournalMagn Reson Med
Volume80
Issue5
Pagination2094-2108
Date Published2018 11
ISSN1522-2594
KeywordsAnimals, Diffusion Magnetic Resonance Imaging, Disease Models, Animal, Hindlimb, Image Interpretation, Computer-Assisted, Male, Mice, Mice, Inbred C57BL, Mice, Inbred mdx, Muscle, Skeletal, Muscular Dystrophy, Duchenne, Myofibrils
Abstract

PURPOSE: To measure the microstructural changes during skeletal muscle growth and progressive pathologies using the random permeable model with diffusion MRI, and compare findings to conventional imaging modalities such as three-point Dixon and T imaging.

METHODS: In vivo and ex vivo DTI experiments with multiple diffusion times (20-700 ms) were completed on wild-type (n = 22) and muscle-dystrophic mdx mice (n = 8) at various developmental time points. The DTI data were analyzed with the random permeable model framework that provides estimates of the unrestricted diffusion coefficient (D ), membrane surface-to-volume ratio (S/V), and membrane permeability (κ). In addition, the MRI experiments included conventional measures, such as tissue fat fractions and T relaxation.

RESULTS: During normal muscle growth between week 4 and week 13, the in vivo S/V, fractional anisotropy, and fat fraction correlated positively with age (ρ = 0.638, 0.664, and 0.686, respectively), whereas T correlated negatively (ρ = -0.847). In mdx mice, all DTI random permeable model parameters and fat fraction had significant positive correlation with age, whereas fractional anisotropy and T did not have significant correlation with age. Histological measurements of the perimeter-to-area ratio served as a proxy for the model-derived S/V in the cylindrical myofiber geometry, and had a significant correlation with the ex vivo S/V (r = 0.71) as well as the in vivo S/V (r = 0.56).

CONCLUSION: The present study demonstrates that DTI at multiple diffusion times with the random permeable model analysis allows for noninvasively quantifying muscle fiber microstructural changes during both normal muscle growth and disease progression. Future studies can apply our technique to evaluate current and potential treatments to muscle myopathies.

DOI10.1002/mrm.27188
Alternate JournalMagn Reson Med
PubMed ID29577406
PubMed Central IDPMC6107391
Grant ListR21 NS081230 / NS / NINDS NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
R21 CA188217 / CA / NCI NIH HHS / United States
R01 CA160620 / CA / NCI NIH HHS / United States
P41 EB017183 / EB / NIBIB NIH HHS / United States
Related Institute: 
MRI Research Institute (MRIRI)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065