Baseline fat fraction is a strong predictor of disease progression in Becker muscular dystrophy

Veeger, Thom T J; Velde, Nienke M van de; Keene, Kevin R.; Niks, Erik H.; Hooijmans, Melissa T.; Webb, Andrew; Groot, Jurriaan H. de; Kan, Hermien E.

doi:10.1002/nbm.4691

Cited by 11 publications

(18 citation statements)

References 55 publications

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“…Quantitative MRI is used as opposed to MRS due to the obvious advantage of spatial coverage, especially in neuromuscular disorders that are known for being characterized by heterogeneous muscle involvement. 1,[3][4][5][6][7][8]10,11,33 The strong correlation between MRS and MRI for FF seems to be in agreement with an earlier study conducted in dystrophic muscles. 3 In contrast, a strong correlation between MRS and MRI for T 2,H2O was found only when excluding patients with FF MRS > 30%.…”

Section: Discussionsupporting

confidence: 91%

“…In contrast to the MRS study of Schlaeger et al, 23 we also compared FF MRS and T 2,H2O,MRS with FF MRI and T 2,H2O,MRI . Quantitative MRI is used as opposed to MRS due to the obvious advantage of spatial coverage, especially in neuromuscular disorders that are known for being characterized by heterogeneous muscle involvement 1,3–8,10,11,33 . The strong correlation between MRS and MRI for FF seems to be in agreement with an earlier study conducted in dystrophic muscles 3 .…”

Section: Discussionsupporting

confidence: 65%

“…the degree of disease progression and almost always has a cumulative nature. 10,11 Another quantitative MRI biomarker is the water T 2 (T 2,H2O ) relaxation time, which is sensitive to changes in tissue water compartmentation, free-to-bound water ratio, and pH alterations. 1,12 An increase in T 2,H2O can be due to a range of different causes such as interstitial or cellular edema, inflammation, or necrosis, which can reflect disease activity mechanisms that precede fat replacement of skeletal muscle in neuromuscular diseases such as Duchenne muscular dystrophy (DMD).…”

mentioning

confidence: 99%

“…The most extensively used quantitative MRI biomarker is based on the separation of water and lipid signals to determine the amount of muscle replacement by fat, generally known as fat fraction (FF) mapping 2–9 . The extent of fat replacement of muscle tissue can provide information about the degree of disease progression and almost always has a cumulative nature 10,11 . Another quantitative MRI biomarker is the water T 2 ( T 2,H2O ) relaxation time, which is sensitive to changes in tissue water compartmentation, free‐to‐bound water ratio, and pH alterations 1,12 .…”

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confidence: 99%

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New Insights into the Spread of MRS‐Based Water T2 Values Observed in Highly Fatty Replaced Muscles

Reyngoudt

Baudin

Carlier

et al. 2023

Magnetic Resonance Imaging

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BackgroundThe reference standard for assessing water T2 (T2,H2O) at high fat fraction (FF) is 1H MRS. T2,H2O (T2,H2O,MRS) dependence on FF (FFMRS) has recently been demonstrated in muscle at high FF (i.e. ≥60%).PurposeTo investigate the relationship between T2,H2O,MRS and FFMRS in the thigh/leg muscles of patients with neuromuscular diseases and to compare with quantitative MRI.Study TypeRetrospective case–control study.PopulationA total of 151 patients with neuromuscular disorders (mean age ± standard deviation = 52.5 ± 22.6 years, 54% male), 44 healthy volunteers (26.5 ± 13.0 years, 57% male).Field Strength/SequenceA 3‐T; single‐voxel stimulated echo acquisition mode (STEAM) MRS, multispin echo (MSE) imaging (for T2 mapping, T2,H2O,MRI), three‐point Dixon imaging (for FFMRI and mapping).AssessmentMono‐exponential and bi‐exponential models were fitted to water T2 decay curves to extract T2,H2O,MRS and FFMRS. Water resonance full‐width‐at‐half‐maximum (FWHM) and B0 spread (∆B0) values were calculated. T2,H2O,MRI (mean), FFMRI (mean, kurtosis, and skewness), and (mean) values were estimated in the MRS voxel.Statistical TestsMann–Whitney U tests, Kruskal–Wallis tests. A P‐value <0.05 was considered statistically significant.ResultsNormal T2,H2O,MRS threshold was defined as the 90th percentile in healthy controls: 30.3 msec. T2,H2O,MRS was significantly higher in all patients with FFMRS < 60% compared to healthy controls. We discovered two subgroups in patients with FFMRS ≥ 60%: one with T2,H2O,MRS ≥ 30.3 msec and one with T2,H2O,MRS < 30.3 msec including abnormally low T2,H2O,MRS. The latter subgroup had significantly higher water resonance FWHM, ∆B0, FFMRI kurtosis, and skewness values but nonsignificantly different (P = 1.00) and long T2,H2O,MRS component and its fraction (P > 0.11) based on the bi‐exponential analysis.Data ConclusionThe findings suggest that the cause for (abnormally) T2,H2O,MRS at high FFMRS is biophysical, due to differences in susceptibility between muscle and fat (increased FWHM and ∆B0), rather than pathophysiological such as compartmentation changes, which would be reflected by the bi‐exponential analysis.Evidence Level3Technical EfficacyStage 3

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 65%

mentioning

confidence: 99%

mentioning

confidence: 99%

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New Insights into the Spread of MRS‐Based Water T2 Values Observed in Highly Fatty Replaced Muscles

Reyngoudt

Baudin

Carlier

et al. 2023

Magnetic Resonance Imaging

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“…This is consistent with the change that we observed in the placebo group in our study. For a patient with BMD, the fat fraction increase over time can be described by a sigmoidal curve, similar to that which has been shown in DMD ( 32 – 34 ), and the baseline value can therefore predict future fat fractions ( 23 , 35 ). Given these various findings, it may be useful not only to stratify patients into future studies by their functional status (the 6MWT may not be the best instrument for this), but, if MRI is to be used as an endpoint, according to their MRI fat fraction ( 22 ).…”

Section: Discussionmentioning

confidence: 65%

Givinostat for Becker muscular dystrophy: A randomized, placebo-controlled, double-blind study

et al. 2023

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ObjectiveNo treatments are approved for Becker muscular dystrophy (BMD). This study investigated the efficacy and safety of givinostat, a histone deacetylase pan-inhibitor, in adults with BMD.MethodsMales aged 18–65 years with a diagnosis of BMD confirmed by genetic testing were randomized 2:1 to 12 months treatment with givinostat or placebo. The primary objective was to demonstrate statistical superiority of givinostat over placebo for mean change from baseline in total fibrosis after 12 months. Secondary efficacy endpoints included other histological parameters, magnetic resonance imaging and spectroscopy (MRI and MRS) measures, and functional evaluations.ResultsOf 51 patients enrolled, 44 completed treatment. At baseline, there was greater disease involvement in the placebo group than givinostat, based on total fibrosis (mean 30.8 vs. 22.8%) and functional endpoints. Mean total fibrosis did not change from baseline in either group, and the two groups did not differ at Month 12 (least squares mean [LSM] difference 1.04%; p = 0.8282). Secondary histology parameters, MRS, and functional evaluations were consistent with the primary. MRI fat fraction in whole thigh and quadriceps did not change from baseline in the givinostat group, but values increased with placebo, with LSM givinostat–placebo differences at Month 12 of −1.35% (p = 0.0149) and −1.96% (p = 0.0022), respectively. Adverse events, most mild or moderate, were reported by 88.2% and 52.9% patients receiving givinostat and placebo.ConclusionThe study failed to achieve the primary endpoint. However, there was a potential signal from the MRI assessments suggesting givinostat could prevent (or slow down) BMD disease progression.

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MR Neurography and Quantitative Muscle MRI of Parsonage Turner Syndrome Involving the Long Thoracic Nerve

Morena,

Tan,

Campbell

et al. 2023

Magnetic Resonance Imaging

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BackgroundParsonage‐Turner syndrome (PTS) is characterized by severe, acute upper extremity pain and subsequent paresis and most commonly involves the long thoracic nerve (LTN). While MR neurography (MRN) can detect LTN hourglass‐like constrictions (HGCs), quantitative muscle MRI (qMRI) can quantify serratus anterior muscle (SAM) neurogenic changes.Purpose/Hypothesis1) To characterize qMRI findings in LTN‐involved PTS. 2) To investigate associations between qMRI and clinical assessments of HGCs/electromyography (EMG).Study TypeProspective.Population30 PTS subjects (25 M/5 F, mean/range age = 39/15–67 years) with LTN involvement who underwent bilateral chest wall qMRI and unilateral brachial plexus MRN.Field Strength/Sequences3.0 Tesla/multiecho spin‐echo T2‐mapping, diffusion‐weighted echo‐planar‐imaging, multiecho gradient echo.AssessmentqMRI was performed to obtain T2, muscle diameter fat fraction (FF), and cross‐sectional area of the SAM. Clinical reports of MRN and EMG were obtained; from MRN, the number of HGCs; from EMG, SAM measurements of motor unit recruitment levels, fibrillations, and positive sharp waves. qMRI/MRN were performed within 90 days of EMG. EMG was performed on average 185 days from symptom onset (all ≥2 weeks from symptom onset) and 5 days preceding MRI.Statistical TestsPaired t‐tests were used to compare qMRI measures in the affected SAM versus the contralateral, unaffected side (P < 0.05 deemed statistically significant). Kendall's tau was used to determine associations between qMRI against HGCs and EMG.ResultsRelative to the unaffected SAM, the affected SAM had increased T2 (50.42 ± 6.62 vs. 39.09 ± 4.23 msec) and FF (8.45 ± 9.69 vs. 4.03% ± 1.97%), and decreased muscle diameter (74.26 ± 21.54 vs. 88.73 ± 17.61 μm) and cross‐sectional area (9.21 ± 3.75 vs. 16.77 ± 6.40 mm2). There were weak to negligible associations (tau = −0.229 to <0.001, P = 0.054–1.00) between individual qMRI biomarkers and clinical assessments of HGCs and EMG.Data ConclusionqMRI changes in the SAM were observed in subjects with PTS involving the LTN.Level of Evidence2Technical EfficacyStage 1

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Baseline fat fraction is a strong predictor of disease progression in Becker muscular dystrophy

Cited by 11 publications

References 55 publications

New Insights into the Spread of MRS‐Based Water T2 Values Observed in Highly Fatty Replaced Muscles

New Insights into the Spread of MRS‐Based Water T2 Values Observed in Highly Fatty Replaced Muscles

Givinostat for Becker muscular dystrophy: A randomized, placebo-controlled, double-blind study

MR Neurography and Quantitative Muscle MRI of Parsonage Turner Syndrome Involving the Long Thoracic Nerve

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