Histopathological correlations and fat replacement imaging patterns in recessive limb‐girdle muscular dystrophy type 12
Abstract 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 lim...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-06-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jcsm.13234 |
| _version_ | 1797813629547970560 |
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| author | Bram De Wel Lotte Huysmans Christophe E. Depuydt Veerle Goosens Ronald Peeters Filipa P. Santos Dietmar R. Thal Patrick Dupont Frederik Maes Kristl G. Claeys |
| author_facet | Bram De Wel Lotte Huysmans Christophe E. Depuydt Veerle Goosens Ronald Peeters Filipa P. Santos Dietmar R. Thal Patrick Dupont Frederik Maes Kristl G. Claeys |
| author_sort | Bram De Wel |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-13T07:54:36Z |
| format | Article |
| id | doaj.art-f286867d6bd14e3eb8e4d4ab26587d3a |
| institution | Directory Open Access Journal |
| issn | 2190-5991 2190-6009 |
| language | English |
| last_indexed | 2024-03-13T07:54:36Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj.art-f286867d6bd14e3eb8e4d4ab26587d3a2023-06-02T06:44:01ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092023-06-011431468148110.1002/jcsm.13234Histopathological correlations and fat replacement imaging patterns in recessive limb‐girdle muscular dystrophy type 12Bram De Wel0Lotte Huysmans1Christophe E. Depuydt2Veerle Goosens3Ronald Peeters4Filipa P. Santos5Dietmar R. Thal6Patrick Dupont7Frederik Maes8Kristl G. Claeys9Department of Neurology University Hospitals Leuven Leuven BelgiumMedical Imaging Research Centre University Hospitals Leuven Leuven BelgiumDepartment of Neurosciences, Laboratory for Muscle Diseases and Neuropathies KU Leuven, Leuven Brain Institute (LBI) Leuven BelgiumDepartment of Radiology University Hospitals Leuven Leuven BelgiumDepartment of Radiology University Hospitals Leuven Leuven BelgiumDepartment of Neurosciences, Laboratory for Muscle Diseases and Neuropathies KU Leuven, Leuven Brain Institute (LBI) Leuven BelgiumDepartment of Imaging and Pathology, Laboratory for Neuropathology KU Leuven, Leuven Brain Institute (LBI) Leuven BelgiumDepartment of Neurosciences, Laboratory for Cognitive Neurology KU Leuven, Leuven Brain Institute (LBI) Leuven BelgiumMedical Imaging Research Centre University Hospitals Leuven Leuven BelgiumDepartment of Neurology University Hospitals Leuven Leuven BelgiumAbstract 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.https://doi.org/10.1002/jcsm.13234Limb‐girdle muscular dystrophy type R12Muscle biopsyMRIFat fractionFat replacement |
| spellingShingle | Bram De Wel Lotte Huysmans Christophe E. Depuydt Veerle Goosens Ronald Peeters Filipa P. Santos Dietmar R. Thal Patrick Dupont Frederik Maes Kristl G. Claeys Histopathological correlations and fat replacement imaging patterns in recessive limb‐girdle muscular dystrophy type 12 Journal of Cachexia, Sarcopenia and Muscle Limb‐girdle muscular dystrophy type R12 Muscle biopsy MRI Fat fraction Fat replacement |
| 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 | Limb‐girdle muscular dystrophy type R12 Muscle biopsy MRI Fat fraction Fat replacement |
| url | https://doi.org/10.1002/jcsm.13234 |
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