{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:59:21Z","timestamp":1790513961380,"version":"4.1.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T00:00:00Z","timestamp":1623888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>As putative treatments are developed for Duchenne muscular dystrophy (DMD), sensitive, non-invasive measures are increasingly important to quantify disease progression. Fibrosis is one of the histological hallmarks of muscular dystrophy and has been directly linked to prognosis. EP3533 is a novel contrast agent with an affinity to collagen 1 that has demonstrated a significant and high correlation to <jats:italic>ex vivo<\/jats:italic> fibrosis quantification. Halofuginone is an established anti-fibrotic compound shown to reduce collagen skeletal muscle fibrosis in murine models of DMD. This experiment explored whether EP3533 could be used to detect signal change in skeletal muscle of <jats:italic>mdx<\/jats:italic> mice before and after a 12 week course of halofuginone compared to controls. Four age-matched groups of treated and untreated mice were evaluated: 2 groups of <jats:italic>mdx<\/jats:italic> (<jats:italic>n<\/jats:italic> = 8 and <jats:italic>n<\/jats:italic> = 13, respectively), and 2 groups of BL10 mice (<jats:italic>n<\/jats:italic> = 5 and <jats:italic>n<\/jats:italic> = 3, respectively). Treated mice received an intraperitoneal injection with halofuginone three times per week for 12 weeks, with the remaining mice being given vehicle. Both <jats:italic>mdx<\/jats:italic> groups and the untreated BL10 were scanned at baseline, then all groups were scanned on week 13. All subjects were scanned using a 7T Varian scanner before and after administration of EP3533 using a T1 mapping technique. Mice underwent grip testing in week 13 prior to dissection. Skeletal muscle was used for Masson's trichrome quantification, hydroxyproline assay, and immunofluorescent antibody staining. Untreated <jats:italic>mdx<\/jats:italic> mice demonstrated a significant increase in R1 signal from pre- to post-treatment scan in three out of four muscles (gastrocnemius <jats:italic>p<\/jats:italic> = 0.04, hamstrings <jats:italic>p<\/jats:italic> = 0.009, and tibialis anterior <jats:italic>p<\/jats:italic> = 0.01), which was not seen in either the treated <jats:italic>mdx<\/jats:italic> or the BL10 groups. Histological quantification of fibrosis also demonstrated significantly higher levels in the untreated <jats:italic>mdx<\/jats:italic> mice with significant correlation seen between histology and EP3533 signal change. Forelimb weight adjusted-grip strength was significantly lower in the untreated <jats:italic>mdx<\/jats:italic> group, compared to the treated group. EP3533 can be used over time as an outcome measure to quantify treatment effect of an established anti-fibrotic drug. Further studies are needed to evaluate the use of this contrast agent in humans.<\/jats:p>","DOI":"10.3389\/fneur.2021.636719","type":"journal-article","created":{"date-parts":[[2021,6,17]],"date-time":"2021-06-17T15:50:53Z","timestamp":1623945053000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Use of EP3533-Enhanced Magnetic Resonance Imaging as a Measure of Disease Progression in Skeletal Muscle of mdx Mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Alexander 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