Characteristics of magnetic resonance imaging biomarkers in a natural history study of golden retriever muscular dystrophy

Zheng Fan; Jiahui Wang; Mihye Ahn; Yael Shiloh-Malawsky; Nizar Chahin; Sandra Elmore; C. Robert Bagnell; Kathy Wilber; Hongyu An; Weili Lin; Hongtu Zhu; Martin Styner; Joe N. Kornegay

doi:10.1016/j.nmd.2013.10.005

Characteristics of magnetic resonance imaging biomarkers in a natural history study of golden retriever muscular dystrophy

Zheng Fan, Jiahui Wang, Mihye Ahn, Yael Shiloh-Malawsky, Nizar Chahin, Sandra Elmore, C. Robert Bagnell, Kathy Wilber, Hongyu An, Weili Lin, Hongtu Zhu, Martin Styner, Joe N. Kornegay

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

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.

Original language	English (US)
Pages (from-to)	178-191
Number of pages	14
Journal	Neuromuscular Disorders
Volume	24
Issue number	2
DOIs	https://doi.org/10.1016/j.nmd.2013.10.005
State	Published - Feb 2014
Externally published	Yes

Keywords

Biomarker
GRMD
MRI
Muscular dystrophy
T2 mapping
Texture analysis

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Neurology
Clinical Neurology
Genetics(clinical)

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10.1016/j.nmd.2013.10.005

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Fan, Z., Wang, J., Ahn, M., Shiloh-Malawsky, Y., Chahin, N., Elmore, S., Bagnell, C. R., Wilber, K., An, H., Lin, W., Zhu, H., Styner, M., & Kornegay, J. N. (2014). Characteristics of magnetic resonance imaging biomarkers in a natural history study of golden retriever muscular dystrophy. Neuromuscular Disorders, 24(2), 178-191. https://doi.org/10.1016/j.nmd.2013.10.005

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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.",

keywords = "Biomarker, GRMD, MRI, Muscular dystrophy, T2 mapping, Texture analysis",

author = "Zheng Fan and Jiahui Wang and Mihye Ahn and Yael Shiloh-Malawsky and Nizar Chahin and Sandra Elmore and Bagnell, {C. Robert} and Kathy Wilber and Hongyu An and Weili Lin and Hongtu Zhu and Martin Styner and Kornegay, {Joe N.}",

note = "Funding Information: This work was supported by K (50KR71104)] (Fan) and UNC Intellectual and Developmental Disabilities Research Center [P30 HD03110]. The authors thank Janet and Dan Bogan and Jennifer Dow for technical assistance in managing the dogs. National Institutes of Health Grant Nos. R42 NS059095-03 (NINDS) (Styner), P30-HD003110-41 (NICHD) (Styner) and 1U24NS059696-01A1 (NINDS) (Kornegay), the Muscular Dystrophy Association (Kornegay), Wellstone Center for Muscular Dystrophy Research [USPHS (NIAMS) 1U54AR056953-01], The North Carolina Translational and Clinical Sciences (NC TraCS) Institute [Tracs50 ",

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doi = "10.1016/j.nmd.2013.10.005",

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AU - Fan, Zheng

AU - Wang, Jiahui

AU - Ahn, Mihye

AU - Shiloh-Malawsky, Yael

AU - Chahin, Nizar

AU - Elmore, Sandra

AU - Bagnell, C. Robert

AU - Wilber, Kathy

AU - An, Hongyu

AU - Lin, Weili

AU - Zhu, Hongtu

AU - Styner, Martin

AU - Kornegay, Joe N.

N1 - Funding Information: This work was supported by K (50KR71104)] (Fan) and UNC Intellectual and Developmental Disabilities Research Center [P30 HD03110]. The authors thank Janet and Dan Bogan and Jennifer Dow for technical assistance in managing the dogs. National Institutes of Health Grant Nos. R42 NS059095-03 (NINDS) (Styner), P30-HD003110-41 (NICHD) (Styner) and 1U24NS059696-01A1 (NINDS) (Kornegay), the Muscular Dystrophy Association (Kornegay), Wellstone Center for Muscular Dystrophy Research [USPHS (NIAMS) 1U54AR056953-01], The North Carolina Translational and Clinical Sciences (NC TraCS) Institute [Tracs50

PY - 2014/2

Y1 - 2014/2

N2 - 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.

AB - 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.

KW - Biomarker

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KW - MRI

KW - Muscular dystrophy

KW - T2 mapping

KW - Texture analysis

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ER -

Characteristics of magnetic resonance imaging biomarkers in a natural history study of golden retriever muscular dystrophy

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Keywords

ASJC Scopus subject areas

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