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Histopathological correlations and fat replacement imaging patterns in recessive limb‐girdle muscular dystrophy type 12

BACKGROUND: Despite the widespread use of proton density fat fraction (PDFF) measurements with magnetic resonance imaging (MRI) to track disease progression in muscle disorders, it is still unclear how these findings relate to histopathological changes in muscle biopsies of patients with limb‐girdle...

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Autores principales: De Wel, Bram, Huysmans, Lotte, Depuydt, Christophe E., Goosens, Veerle, Peeters, Ronald, Santos, Filipa P., Thal, Dietmar R., Dupont, Patrick, Maes, Frederik, Claeys, Kristl G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235862/
https://www.ncbi.nlm.nih.gov/pubmed/37078404
http://dx.doi.org/10.1002/jcsm.13234
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author De Wel, Bram
Huysmans, Lotte
Depuydt, Christophe E.
Goosens, Veerle
Peeters, Ronald
Santos, Filipa P.
Thal, Dietmar R.
Dupont, Patrick
Maes, Frederik
Claeys, Kristl G.
author_facet De Wel, Bram
Huysmans, Lotte
Depuydt, Christophe E.
Goosens, Veerle
Peeters, Ronald
Santos, Filipa P.
Thal, Dietmar R.
Dupont, Patrick
Maes, Frederik
Claeys, Kristl G.
author_sort De Wel, Bram
collection PubMed
description BACKGROUND: Despite the widespread use of proton density fat fraction (PDFF) measurements with magnetic resonance imaging (MRI) to track disease progression in muscle disorders, it is still unclear how these findings relate to histopathological changes in muscle biopsies of patients with limb‐girdle muscular dystrophy autosomal recessive type 12 (LGMDR12). Furthermore, although it is known that LGMDR12 leads to a selective muscle involvement distinct from other muscular dystrophies, the spatial distribution of fat replacement within these muscles is unknown. METHODS: We included 27 adult patients with LGMDR12 and 27 age‐matched and sex‐matched healthy controls and acquired 6‐point Dixon images of the thighs and T1 and short tau inversion recovery (STIR) MR images of the whole body. In 16 patients and 15 controls, we performed three muscle biopsies, one in the semimembranosus, vastus lateralis, and rectus femoris muscles, which are severely, intermediately, and mildly affected in LGMDR12, respectively. We correlated the PDFF to the fat percentage measured on biopsies of the corresponding muscles, as well as to the Rochester histopathology grading scale. RESULTS: In patients, we demonstrated a strong correlation of PDFF on MRI and muscle biopsy fat percentage for the semimembranosus (r = 0.85, P < 0.001) and vastus lateralis (r = 0.68, P = 0.005). We found similar results for the correlation between PDFF and the Rochester histopathology grading scale. Out of the five patients with inflammatory changes on muscle biopsy, three showed STIR hyperintensities in the corresponding muscle on MRI. By modelling the PDFF on MRI for 18 thigh muscles from origin to insertion, we observed a significantly inhomogeneous proximo‐distal distribution of fat replacement in all thigh muscles of patients with LGMDR12 (P < 0.001), and different patterns of fat replacement within each of the muscles. CONCLUSIONS: We showed a strong correlation of fat fraction on MRI and fat percentage on muscle biopsy for diseased muscles and validated the use of Dixon fat fraction imaging as an outcome measure in LGMDR12. The inhomogeneous fat replacement within thigh muscles on imaging underlines the risk of analysing only samples of muscles instead of the entire muscles, which has important implications for clinical trials.
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spelling pubmed-102358622023-06-03 Histopathological correlations and fat replacement imaging patterns in recessive limb‐girdle muscular dystrophy type 12 De Wel, Bram Huysmans, Lotte Depuydt, Christophe E. Goosens, Veerle Peeters, Ronald Santos, Filipa P. Thal, Dietmar R. Dupont, Patrick Maes, Frederik Claeys, Kristl G. J Cachexia Sarcopenia Muscle Original Articles BACKGROUND: Despite the widespread use of proton density fat fraction (PDFF) measurements with magnetic resonance imaging (MRI) to track disease progression in muscle disorders, it is still unclear how these findings relate to histopathological changes in muscle biopsies of patients with limb‐girdle muscular dystrophy autosomal recessive type 12 (LGMDR12). Furthermore, although it is known that LGMDR12 leads to a selective muscle involvement distinct from other muscular dystrophies, the spatial distribution of fat replacement within these muscles is unknown. METHODS: We included 27 adult patients with LGMDR12 and 27 age‐matched and sex‐matched healthy controls and acquired 6‐point Dixon images of the thighs and T1 and short tau inversion recovery (STIR) MR images of the whole body. In 16 patients and 15 controls, we performed three muscle biopsies, one in the semimembranosus, vastus lateralis, and rectus femoris muscles, which are severely, intermediately, and mildly affected in LGMDR12, respectively. We correlated the PDFF to the fat percentage measured on biopsies of the corresponding muscles, as well as to the Rochester histopathology grading scale. RESULTS: In patients, we demonstrated a strong correlation of PDFF on MRI and muscle biopsy fat percentage for the semimembranosus (r = 0.85, P < 0.001) and vastus lateralis (r = 0.68, P = 0.005). We found similar results for the correlation between PDFF and the Rochester histopathology grading scale. Out of the five patients with inflammatory changes on muscle biopsy, three showed STIR hyperintensities in the corresponding muscle on MRI. By modelling the PDFF on MRI for 18 thigh muscles from origin to insertion, we observed a significantly inhomogeneous proximo‐distal distribution of fat replacement in all thigh muscles of patients with LGMDR12 (P < 0.001), and different patterns of fat replacement within each of the muscles. CONCLUSIONS: We showed a strong correlation of fat fraction on MRI and fat percentage on muscle biopsy for diseased muscles and validated the use of Dixon fat fraction imaging as an outcome measure in LGMDR12. The inhomogeneous fat replacement within thigh muscles on imaging underlines the risk of analysing only samples of muscles instead of the entire muscles, which has important implications for clinical trials. John Wiley and Sons Inc. 2023-04-20 /pmc/articles/PMC10235862/ /pubmed/37078404 http://dx.doi.org/10.1002/jcsm.13234 Text en © 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
De Wel, Bram
Huysmans, Lotte
Depuydt, Christophe E.
Goosens, Veerle
Peeters, Ronald
Santos, Filipa P.
Thal, Dietmar R.
Dupont, Patrick
Maes, Frederik
Claeys, Kristl G.
Histopathological correlations and fat replacement imaging patterns in recessive limb‐girdle muscular dystrophy type 12
title Histopathological correlations and fat replacement imaging patterns in recessive limb‐girdle muscular dystrophy type 12
title_full Histopathological correlations and fat replacement imaging patterns in recessive limb‐girdle muscular dystrophy type 12
title_fullStr Histopathological correlations and fat replacement imaging patterns in recessive limb‐girdle muscular dystrophy type 12
title_full_unstemmed Histopathological correlations and fat replacement imaging patterns in recessive limb‐girdle muscular dystrophy type 12
title_short Histopathological correlations and fat replacement imaging patterns in recessive limb‐girdle muscular dystrophy type 12
title_sort histopathological correlations and fat replacement imaging patterns in recessive limb‐girdle muscular dystrophy type 12
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10235862/
https://www.ncbi.nlm.nih.gov/pubmed/37078404
http://dx.doi.org/10.1002/jcsm.13234
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