title: Characteristics of magnetic resonance imaging biomarkers in a natural history study of golden retriever muscular dystrophy.
abstract: The goal of this study was to assess whether magnetic resonance imaging (MRI) biomarkers can quantify disease progression in golden retriever muscular dystrophy (GRMD) via a natural history study. The proximal pelvic limbs of ten GRMD and eight normal dogs were scanned at 3, 6, and 9-12 months of age. Several MRI imaging and texture analysis biomarkers were quantified in seven muscles. Almost all MRI biomarkers readily distinguished GRMD from control dogs; however, only selected biomarkers tracked with longitudinal disease progression. The biomarkers that performed best were full-length muscle volume and a texture analysis biomarker, termed heterogeneity index. The biceps femoris, semitendinosus and cranial sartorius muscles showed differential progression in GRMD versus control dogs. MRI features in GRMD dogs showed dynamic progression that was most pronounced over the 3- to 6-month period. Volumetric biomarkers and water map values correlated with histopathological features of necrosis/regeneration at 6-months. In conclusion, selected MRI biomarkers (volume and heterogeneity index) in particular muscles (biceps femoris, semitendinosus, and cranial sartorius) adjusted for age effect allow distinction of differential longitudinal progression in GRMD dogs. These biomarkers may be used as surrogate outcome measures in preclinical GRMD trials.
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, NC 27599, United States. Electronic address: zhengfan@med.unc.edu.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, NC 27599, United States.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, NC 27599, United States.
authors.forename: Mihye
authors.initials: M
authors.lastname: Ahn
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, NC 27599, United States.
authors.forename: Yael
authors.initials: Y
authors.lastname: Shiloh-Malawsky
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, NC 27599, United States.
authors.forename: Nizar
authors.initials: N
authors.lastname: Chahin
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC 27599, United States.
authors.forename: Sandra
authors.initials: S
authors.lastname: Elmore
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC 27599, United States.
authors.forename: C Robert
authors.initials: CR
authors.lastname: Bagnell
authors.affiliation: Department of Radiology, University of North Carolina at Chapel Hill, NC 27599, United States.
authors.forename: Kathy
authors.initials: K
authors.lastname: Wilber
authors.affiliation: Department of Radiology, University of North Carolina at Chapel Hill, NC 27599, United States.
authors.forename: Hongyu
authors.initials: H
authors.lastname: An
authors.affiliation: Department of Radiology, University of North Carolina at Chapel Hill, NC 27599, United States.
authors.forename: Weili
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, NC 27599, United States.
authors.forename: Hongtu
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, NC 27599, United States; Department of Computer Science, University of North Carolina at Chapel Hill, NC 27599, United States.
authors.forename: Martin
authors.initials: M
authors.lastname: Styner
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, NC 27599, United States; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC 27599, United States.
authors.forename: Joe N
authors.initials: JN
authors.lastname: Kornegay
mesh_terms: D000818:Animals; D001835:Body Weight; D003238:Connective Tissue / Q000473:pathology; D018450:Disease Progression; D004283:Dog Diseases / Q000473:pathology*; D004285:Dogs; D005269:Femur / Q000473:pathology; D006614:Hindlimb / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D018482:Muscle, Skeletal / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000473:pathology*; D009336:Necrosis / Q000473:pathology; D009929:Organ Size; D052097:Quadriceps Muscle / Q000473:pathology; D012372:ROC Curve
keywords: Biomarker; GRMD; MRI; Muscular dystrophy; T2 mapping; Texture analysis