Quantitative Dixon MRI sequences to relate muscle atrophy and fatty degeneration with range of motion and muscle force in brachial plexus injury

Duijnisveld, B.J.; Henseler, Jan Ferdinand; Reijnierse, M.; Fiocco, Marta; Kan, Hermien E.; Nelissen, Rob G H H

doi:10.1016/j.mri.2016.10.020

Cited by 16 publications

(17 citation statements)

References 32 publications

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“…DMD is a lethal disease caused by the absence of dystrophin, leading to chronic muscle damage followed up by fibro-fatty substitution of muscle mass. 28,29 Downstream effects of lack of dystrophin have been characterized by histological, gene expression, and proteomic analyses of muscles biopsies obtained from affected patients (and animal models) enabling the identification of morphological alterations and pathological pathways behind the clinical presentation. [30][31][32][33] The examination of muscle biopsies is still often performed during interventional clinical trials to study the effect of the drug (e.g.…”

Section: Discussionmentioning

confidence: 99%

Tracking disease progression non‐invasively in Duchenne and Becker muscular dystrophies

Spitali

Hettne

Tsonaka

et al. 2018

J cachexia sarcopenia muscle

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BackgroundAnalysis of muscle biopsies allowed to characterize the pathophysiological changes of Duchenne and Becker muscular dystrophies (D/BMD) leading to the clinical phenotype. Muscle tissue is often investigated during interventional dose finding studies to show in situ proof of concept and pharmacodynamics effect of the tested drug. Less invasive readouts are needed to objectively monitor patients' health status, muscle quality, and response to treatment. The identification of serum biomarkers correlating with clinical function and able to anticipate functional scales is particularly needed for personalized patient management and to support drug development programs.MethodsA large‐scale proteomic approach was used to identify serum biomarkers describing pathophysiological changes (e.g. loss of muscle mass), association with clinical function, prediction of disease milestones, association with in vivo 31P magnetic resonance spectroscopy data and dystrophin levels in muscles. Cross‐sectional comparisons were performed to compare DMD patients, BMD patients, and healthy controls. A group of DMD patients was followed up for a median of 4.4 years to allow monitoring of individual disease trajectories based on yearly visits.ResultsCross‐sectional comparison enabled to identify 10 proteins discriminating between healthy controls, DMD and BMD patients. Several proteins (285) were able to separate DMD from healthy, while 121 proteins differentiated between BMD and DMD; only 13 proteins separated BMD and healthy individuals. The concentration of specific proteins in serum was significantly associated with patients' performance (e.g. BMP6 serum levels and elbow flexion) or dystrophin levels (e.g. TIMP2) in BMD patients. Analysis of longitudinal trajectories allowed to identify 427 proteins affected over time indicating loss of muscle mass, replacement of muscle by adipose tissue, and cardiac involvement. Over‐representation analysis of longitudinal data allowed to highlight proteins that could be used as pharmacodynamic biomarkers for drugs currently in clinical development.ConclusionsSerum proteomic analysis allowed to not only discriminate among DMD, BMD, and healthy subjects, but it enabled to detect significant associations with clinical function, dystrophin levels, and disease progression.

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Section: Discussionmentioning

confidence: 99%

Tracking disease progression non‐invasively in Duchenne and Becker muscular dystrophies

Spitali

Hettne

Tsonaka

et al. 2018

J cachexia sarcopenia muscle

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“…DMD is a lethal disease caused by the absence of dystrophin resulting in substitution of muscle mass by adipose tissue . Downstream effects of lack of dystrophin have largely been studied in muscles samples from patients and animal models enabling the identification of morphological alterations and pathological pathways behind the clinical presentation .…”

Section: Discussionmentioning

confidence: 99%

“…ing in substitution of muscle mass by adipose tissue. 26,27 Downstream effects of lack of dystrophin have largely been studied in muscles samples from patients and animal models enabling the identification of morphological alterations and pathological pathways behind the clinical presentation. [28][29][30][31] Clear metabolic alterations have been described in DMD muscle tissue affecting the energy metabolism (eg glycolysis) and mitochondrial alterations (eg the tricarboxylic acid cycle and electron transport chain).…”

Section: Data Availabilitymentioning

confidence: 99%

Cross‐sectional serum metabolomic study of multiple forms of muscular dystrophy

Spitali

Hettne

Tsonaka

et al. 2018

J Cellular Molecular Medi

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Muscular dystrophies are characterized by a progressive loss of muscle tissue and/or muscle function. While metabolic alterations have been described in patients'-derived muscle biopsies, non-invasive readouts able to describe these alterations are needed in order to objectively monitor muscle condition and response to treatment targeting metabolic abnormalities. We used a metabolomic approach to study metabolites concentration in serum of patients affected by multiple forms of muscular dystrophy such as Duchenne and Becker muscular dystrophies, limb-girdle muscular dystrophies type 2A and 2B, myotonic dystrophy type 1 and facioscapulohumeral muscular dystrophy.We show that 15 metabolites involved in energy production, amino acid metabolism, testosterone metabolism and response to treatment with glucocorticoids were differentially expressed between healthy controls and Duchenne patients. Five metabolites were also able to discriminate other forms of muscular dystrophy. In particular, creatinine and the creatine/creatinine ratio were significantly associated with Duchenne patients performance as assessed by the 6-minute walk test and north star ambulatory assessment. The obtained results provide evidence that metabolomics analysis of serum samples can provide useful information regarding muscle condition and response to treatment, such as to glucocorticoids treatment.

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“…21 Other investigators have used approaches based on chemical shift such as Dixon MRI to quantitate the long-term sequelae of denervation, such as muscular atrophy, fatty infiltration, and interstitial fibrosis, all of which may occur in traumatic brachial plexus injury. 22 This technique attempts to improve on the prior qualitative strategies of estimating muscle degeneration, such as the Goutallier score on T1weighted turbo spin-echo images 23 that is moderately reliable at best even in experienced hands. 24 Another semiquantitative method called Mercuri scoring evaluates fibrofatty replacement of muscle by scoring on T1-weighted images.…”

Section: Quantitative Mrimentioning

confidence: 99%

Advanced MRI Techniques for Muscle Imaging

Kalia

Leung

Sneag

et al. 2017

Semin Musculoskelet Radiol

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Advanced magnetic resonance imaging (MRI) techniques can evaluate a wide array of muscle pathologies including acute or chronic muscle injury, musculotendinous response to injury, intramuscular collections and soft tissue masses, and others. In recent years, MRI has played a more important role in muscle disease diagnosis and monitoring. MRI provides excellent spatial and contrast resolution and helps direct optimal sites for muscle biopsy. Whole-body MRI now helps identify signature patterns of muscular involvement in large anatomical regions with relative ease. Quantitative MRI has advanced the evaluation and disease tracking of muscle atrophy and fatty infiltration in entities such as muscular dystrophies. Multivoxel magnetic resonance spectroscopy (MRS) now allows a more thorough, complete evaluation of a muscle of interest without the inherent sampling bias of single-voxel MRS or biopsy. Diffusion MRI allows quantification of muscle inflammation and capillary perfusion as well as muscle fiber tracking.

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Quantitative Dixon MRI sequences to relate muscle atrophy and fatty degeneration with range of motion and muscle force in brachial plexus injury

Cited by 16 publications

References 32 publications

Tracking disease progression non‐invasively in Duchenne and Becker muscular dystrophies

Tracking disease progression non‐invasively in Duchenne and Becker muscular dystrophies

Cross‐sectional serum metabolomic study of multiple forms of muscular dystrophy

Advanced MRI Techniques for Muscle Imaging

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