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Introduction
Publications
Publications (198)
Repeated muscle micro-trauma may cause severe muscle damage. Diffusion tensor imaging (DTI) exhibits sensitivity to microstructural changes in skeletal muscle. We hypothesize that longer diffusion times enhance sensitivity to micro-trauma and that membrane permeability increases with micro-trauma. We obtained DTI scans of the thighs in ten male run...
Classic infantile Pompe disease is caused by abnormal lysosomal glycogen accumulation in multiple tissues, including the brain due to a deficit in acid α-glucosidase (GAA). Although treatment with recombinant human GAA (rhGAA) has dramatically improved survival, rhGAA does not reach the brain, and surviving classic infantile Pompe patients develop...
Serum biomarkers are promising minimally invasive outcome measures in clinical studies in Duchenne muscular dystrophy (DMD). However, biomarkers strongly associated with clinical progression and predicting performance decline are lacking. In this study we aimed to identify serum biomarkers associated with clinical performance and able to predict cl...
Duchenne muscular dystrophy (DMD) is a progressive X‐linked neuromuscular disorder caused by the absence of functional dystrophin protein. In addition to muscle, dystrophin is expressed in the brain in both neurons and glial cells. Previous studies have shown altered white matter microstructure in patients with DMD using diffusion tensor imaging (D...
Static quantitative magnetic resonance imaging (MRI) provides readouts of structural changes in diseased muscle, but current approaches lack the ability to fully explain the loss of contractile function. Muscle contractile function can be assessed using various techniques including phase‐contrast MRI (PC‐MRI), where strain rates are quantified. How...
Objective
Duchenne muscular dystrophy (DMD) is a neuromuscular disorder in which many patients also have neurobehavioral problems. Corticosteroids, the primary pharmacological treatment for DMD, have been shown to affect brain morphology in other conditions, but data in DMD are lacking. This study aimed to investigate the impact of two corticostero...
Purpose
Activated brown adipose tissue (BAT) enhances lipid catabolism and improves cardiometabolic health. Quantitative MRI of the fat fraction (FF) of supraclavicular BAT (scBAT) is a promising noninvasive measure to assess BAT activity but suffers from high scan variability. We aimed to test the effects of coregistration and mutual thresholding...
Introduction:
MRI of extra-ocular muscles (EOM) in patients with myasthenia gravis (MG) could aid in diagnosis and provide insights in therapy-resistant ophthalmoplegia. We used quantitative MRI to study the EOM in MG, healthy and disease controls, including Graves' ophthalmopathy (GO), oculopharyngeal muscular dystrophy (OPMD) and chronic progres...
Background:
Becker muscular dystrophy (BMD) is an X-linked disorder characterized by slow, progressive muscle damage and muscle weakness. Hallmarks include fibre-size variation and replacement of skeletal muscle with fibrous and adipose tissues, after repeated cycles of regeneration. Muscle histology can detect these features, but the required bio...
Semantic segmentation is a crucial step to extract quantitative information from medical (and, specifically, radiological) images to aid the diagnostic process, clinical follow-up. and to generate biomarkers for clinical research. In recent years, machine learning algorithms have become the primary tool for this task. However, its real-world perfor...
Skeletal muscles support the stability and mobility of the skeleton but differ in biomechanical properties and physiological functions. The intrinsic factors that regulate muscle-specific characteristics are poorly understood. To study these, we constructed a large atlas of RNA-seq profiles from six leg muscles and two locations from one muscle, us...
Objective
No 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.
Methods
Males 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....
Skeletal muscles are composed of different myofiber types characterized by the expression of myosin heavy chain isoforms, which can be affected by physical activity, aging, and pathological conditions. Here, we present a step-by-step high-throughput semi-automated approach for performing myofiber type quantification of entire human or mouse muscle...
Infrared thermography (IRT) is widely used to assess skin temperature in response to physiological changes. Yet, it remains challenging to standardize skin temperature measurements over repeated datasets. We developed an open-access semi-automated segmentation tool (the IRT-toolbox) for measuring skin temperatures in the thoracic area to estimate s...
Introduction
Diagnosing ocular myasthenia gravis (MG) can be challenging because serum antibodies are often not detected. We aimed to explore whether determining extraocular muscle (EOM) weakness using orthoptic measures, including an adapted Hess chart examination, can aid in diagnosing MG.
Methods
We conducted a prospective study among patients...
Recent studies show lower gray matter volumes and altered white matter networks in boys with Duchenne Muscular Dystrophy (DMD) compared with healthy controls, suggesting a lack of dystrophin impacts brain structures. However, the majority of boys with DMD are chronically treated with corticosteroids (CS), which are known to cross the blood-brain ba...
The slow and highly variable disease progression observed in BMD stresses the need to develop outcome measures for clinical trials. We evaluated the responsiveness of different assessments in a cohort of adult BMD patients followed for 3 years. We included 36 genetically confirmed BMD patients (median age at baseline 42.3 years, range 18.6-67.3) of...
Interventions for muscular dystrophies (MDs) seek to preserve functioning muscle tissue, prior to its replacement with fat and fibrosis—which reflect disease progression. To test such interventions, imaging biomarkers should focus on muscle inflammation, degeneration and regeneration—hallmarks of MDs that represent disease activity. One consequence...
Ophthalmoparesis and ptosis can be caused by a wide range of rare or more prevalent diseases, several of which can be successfully treated. In this review, we provide clues to aid in the diagnosis of these diseases, based on the clinical symptoms, the involvement pattern and imaging features of extra-ocular muscles (EOM). Dysfunction of EOM includi...
Microvascular function is an important component in the physiology of muscle. One of the major parameters, blood perfusion, can be measured non‐invasively and quantitatively by arterial spin labeling (ASL) MRI. Most studies using ASL in muscle have only reported data from a single slice, thereby assuming that muscle perfusion is homogeneous within...
In a standard spin echo, the time evolution due to homonuclear couplings is not reversed, leading to echo‐time (TE) dependent modulation of the signal amplitude and signal loss in the case of overlapping multiplet resonances. This has an adverse effect on quantification of several important metabolites such as glutamate and glutamine. Here, we prop...
Background:
Background:Outcome measures for non-ambulant Duchenne muscular dystrophy (DMD) patients are limited, with only the Performance of the Upper Limb (PUL) approved as endpoint for clinical trials.
Objective:
Objective: We assessed four outcome measures based on devices developed for the gaming industry, aiming to overcome disadvantages o...
Skeletal muscles support the stability and mobility of the skeleton but differ in biomechanical properties and physiological functions. The intrinsic factors that regulate muscle-specific characteristics are poorly understood. To study these, we constructed a large atlas of RNA-seq profiles from six leg muscles and two locations from one muscle, us...
Purpose
Brown adipose tissue (BAT) increases metabolic heat production in response to cold exposure. Body size and composition are involved in the human cold response, yet the influence of BAT herein have not fully been explored. Here, we aimed to study the association of the cold-induced shivering threshold time with body composition, BAT, the per...
Introduction:
Muscle diffusion tensor imaging (mDTI)-based tractography is a promising tool to detect subclinical changes in muscle injuries and to evaluate pathophysiology in neuromuscular diseases. Classic regions of interest (ROI)-based tractography is very time-consuming and requires extensive experience from the examiner. (Semi-)automatic app...
The article of Lopez et al describes the use of a multi‐parametric MR approach to study muscle T2 relaxation times and 31P‐MRS indices of energetics and sarcolemma integrity in a mouse model of DMD, the mdx mouse. Muscular dystrophies have a multi‐factorial disease cascade, and there are several MR methods used to assess these. Aspects that reflect...
In Becker muscular dystrophy (BMD), muscle weakness progresses relatively slowly, with a highly variable rate between patients. This complicates clinical trials, as clinically relevant changes are difficult to capture within the typical duration of a trial. Therefore, predictors for disease progression are needed. We assessed if temporal increase o...
Introduction/Aims
Becker muscular dystrophy (BMD) is characterized by variable disease severity and progression, prompting the identification of biomarkers for clinical trials. We used data from an ongoing Phase II study to provide a comprehensive characterization of a cohort of patients with BMD, and to assess correlations between histological and...
Enhanced activity of the glutamatergic system has been linked to migraine pathophysiology. The present study aimed to assess the involvement of the glutamatergic system in the onset of attacks. We provoked attacks by infusion of glyceryl trinitrate (GTN; 0.5 µg/kg/min over 20 min) in 24 female episodic migraineurs without aura and 13 female age-mat...
Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder caused by absence of dystrophin protein. Dystrophin is expressed in muscle, but also in the brain. Difficulties with attention/inhibition, working memory and information processing are well described in DMD patients but their origin is poorly understood. The default m...
Objective
To study the potential of quantitative MRI (qMRI) fat fraction (FF) as biomarker in non-ambulant Duchenne muscular dystrophy (DMD) patients, we assessed the additive predictive value of elbow flexor FF to age on loss of hand-to-mouth movement.
Methods
Non-ambulant DMD patients (≥8 years) were included. 4-point Dixon MRI scans of the righ...
Introduction/Aim
Duchenne and Becker muscular dystrophies (DMD, BMD) are characterized by fat replacement of different skeletal muscles in a specific temporal order. Given the structural role of dystrophin in skeletal muscle mechanics, muscle architecture could be important in the progressive pathophysiology of muscle degeneration. Therefore, the a...
Objective
To identify the best quantitative fat-water MRI biomarker for disease progression of leg muscles in Becker muscular dystrophy (BMD) by applying a stepwise approach based on standardized response mean (SRM) over 24 months, correlations with baseline ambulatory tests and reproducibility.
Methods
Dixon fat-water imaging was performed at bas...
Purpose
Multislice arterial spin labeling (ASL) MRI acquisitions are currently challenging in skeletal muscle because of long transit times, translating into low‐perfusion SNR in distal slices when large spatial coverage is required. However, fiber type and oxidative capacity vary along the length of healthy muscles, calling for multislice acquisit...
Background
Clinical trials in Duchenne muscular dystrophy (DMD) focus primarily on ambulant patients. Results cannot be extrapolated to later disease stages due to a decline in targeted muscle tissue. In non‐ambulant DMD patients, hand function is relatively preserved and crucial for daily‐life activities. We used quantitative MRI (qMRI) to establi...
Double diffusion encoding (DDE) of the water signal offers a unique ability to separate the effect of microscopic anisotropic diffusion in structural units of tissue from the overall macroscopic orientational distribution of cells. However, the specificity in detected microscopic anisotropy is limited as the signal is averaged over different cell t...
Aims
Huntington's disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. Toxic accumulation of misfolded mutant huntingtin protein induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. We evaluated the safety, pharmacokinetics and pharmacodynamics of SBT‐020, a...
Background:
Huntington's disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. A toxic accumulation of misfolded mutant huntingtin protein (Htt) induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. Improving mitochondrial function has been proposed as an oppo...
Double diffusion encoding (DDE) magnetic resonance measurements of the water signal offers a unique ability to separate the effect of microscopic anisotropic diffusion in structural units of tissue from the overall macroscopic orientational distribution of cells. However, the specificity in detected microscopic anisotropy is limited as the signal i...
Although quantitative MRI can be instrumental in the diagnosis and assessment of disease progression in orbital diseases involving the extra-ocular muscles (EOM), acquisition can be challenging as EOM are small and prone to eye-motion artefacts. We explored the feasibility of assessing fat fractions (FF), muscle volumes and water T2 (T2water ) of E...
Background:
Natural history data are essential for trial design in Duchenne (DMD) and Becker muscular dystrophy (BMD), but recruitment for observational studies can be challenging.
Objective:
We reviewed reasons why patients or caregivers declined participation, and compared characteristics of participants and non-participants to assess possible...
Quantitative MRI and MRS of muscle are increasingly being used to measure individual pathophysiological processes in Becker muscular dystrophy (BMD). In particular, muscle fat fraction was shown to be highly associated with functional tests in BMD. However, the muscle strength per unit of contractile cross‐sectional area is lower in patients with B...
The role of neuromuscular imaging in the diagnosis of inherited and acquired muscle diseases has gained clinical relevance. In particular, magnetic resonance imaging (MRI), especially whole-body applications, is increasingly being used for the diagnosis and monitoring of disease progression. In addition, they are considered as a powerful outcome me...
Aims:
To compare the effects of cold exposure and the β3-adrenergic receptor agonist mirabegron on plasma lipids, energy expenditure and brown adipose tissue (BAT) activity in South Asians versus Europids.
Material and methods:
Ten lean Dutch South Asian (age 18-30 years; BMI 18-25 kg/m2 ) and ten age- and BMI-matched Europid men participated in...
Identifying genes involved in functional differences between similar tissues from expression profiles is challenging, because the expected differences in expression levels are small. To exemplify this challenge, we studied the expression profiles of two skeletal muscles, deltoid and biceps, in healthy individuals. We provide a series of guides and...
Purpose
Multi‐echo spin‐echo (MSE) transverse relaxometry mapping using multi‐component models is used to study disease activity in neuromuscular disease by assessing the T2 of the myocytic component (T2water). Current extended phase graph algorithms are not optimized for fat fractions above 50% and the effects of inaccuracies in the T2fat calibrat...
Skeletal muscle phosphorus-31 31 P MRS is the oldest MRS methodology to be applied to in vivo metabolic research. The technical requirements of 31 P MRS in skeletal muscle depend on the research question, and to assess those questions requires understanding both the relevant muscle physiology, and how 31 P MRS methods can probe it. Here we consider...
Aims/hypothesis:
Brown adipose tissue (BAT) improves energy metabolism by combusting glucose and lipids into heat. Agonism of the glucagon-like peptide-1 receptor (GLP-1R) within the central nervous system activates BAT in mice. Moreover, in patients with type 2 diabetes, GLP-1R agonism lowers body weight and improves glucose and lipid levels, pos...
Objective:
We studied the potential of quantitative MRI (qMRI) as a surrogate endpoint in Duchenne muscular dystrophy by assessing the additive predictive value of vastus lateralis (VL) fat fraction (FF) to age on loss of ambulation (LoA).
Methods:
VL FFs were determined on longitudinal Dixon MRI scans from 2 natural history studies in Leiden Un...
