A5014703706- Advanced MRI Techniques and Applications
- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Advanced NMR Techniques and Applications
- Mitochondrial Function and Pathology
- Liver Disease Diagnosis and Treatment
- Protein Structure and Dynamics
- Cardiovascular Function and Risk Factors
- Medical Imaging Techniques and Applications
- Metabolism and Genetic Disorders
- Cardiac Imaging and Diagnostics
- MRI in cancer diagnosis
- Muscle metabolism and nutrition
- Enzyme Structure and Function
- Lanthanide and Transition Metal Complexes
- Atomic and Subatomic Physics Research
- Diet, Metabolism, and Disease
- Metabolomics and Mass Spectrometry Studies
- Electron Spin Resonance Studies
- Microplastics and Plastic Pollution
- Ultrasound and Hyperthermia Applications
- Cardiovascular and exercise physiology
- Enzyme Catalysis and Immobilization
- Metabolism, Diabetes, and Cancer
- Photodynamic Therapy Research Studies
University Medical Center Utrecht
2017-2025
Maastricht University Medical Centre
2025
Maastricht University
2024
Erasmus MC Cancer Institute
2024
Eindhoven University of Technology
2009-2018
Amsterdam UMC Location University of Amsterdam
2011-2017
NXP (Netherlands)
2017
Philips (Netherlands)
2017
St. Antonius Ziekenhuis
2017
University of Amsterdam
2011
The effects of internal motions on residual dipolar NMR couplings proteins partially aligned in a liquid-crystalline environment are analyzed using 10 ns molecular dynamics (MD) computer simulation ubiquitin. For set alignment tensors with different orientations and rhombicities, MD-averaged determined subsequently interpreted for scenarios terms effective tensors, average vectors, intramolecular reorientational vector distributions. Analytical relationships derived that reflect similarities...
A general framework is presented for the interpretation of NMR relaxation data proteins. The method, termed isotropic reorientational eigenmode dynamics (iRED), relies on a principal component analysis isotropically averaged covariance matrix lattice functions spin interactions responsible relaxation. matrix, which evaluated using molecular (MD) simulation, diagonalized yielding eigenmodes and amplitudes that reveal detailed information about correlated protein dynamics. eigenvalue...
Skeletal muscle phosphorus‐31 31 P MRS is the oldest methodology to be applied in vivo metabolic research. The technical requirements of skeletal depend on research question, and assess those questions requires understanding both relevant physiology, how methods can probe it. Here we consider basic signal‐acquisition parameters related radio frequency excitation, TR, TE , spectral resolution, shim localisation. We make specific recommendations for studies resting exercising muscle, including...
Metformin is a widely prescribed drug for the treatment of type 2 diabetes. Previous studies have demonstrated in vitro that metformin specifically inhibits Complex I mitochondrial respiratory chain. This seems contraindicative since muscle dysfunction has been linked to pathogenesis However, its significance vivo skeletal function yet be elucidated. The aim this study was assess effects on and ex rat model Healthy (fa/+) diabetic (fa/fa) Zucker fatty rats were treated by oral gavage with...
Camelids produce functional "heavy chain" antibodies which are devoid of light chains and CH1 domains [Hamers-Casterman, C., et al. (1993) Nature 363, 446-448]. It has been shown that the variable these heavy chain (the V(HH) fragments) at or after exposure to high temperatures, in contrast conventional [Linden van der, R. H. J., (1999) Biochim. Biophys. Acta 1431, 37-44]. For a detailed understanding higher thermostability fragments, knowledge their structure conformational dynamics is...
Several lines of evidence support a potential role skeletal muscle mitochondrial dysfunction in the pathogenesis insulin resistance and/or type 2 diabetes. However, it remains to be established whether represents either cause or consequence disease. We examined vivo function early and advanced stages diabetes, with aim gain insight proposed aetiology diabetes.Ten long-standing, insulin-treated diabetes patients, 11 subjects impaired fasting glucose, glucose tolerance recently diagnosed 12...
Conflicting data exist on mitochondrial function and physical activity in type 2 diabetes mellitus (T2DM) development.The aim was to assess at different stages during T2DM development combination with exercise longstanding patients.We performed cross-sectional analysis of skeletal muscle from 12 prediabetic 11 male subjects controls matched by age body mass index.One-year intrasubject controlled supervised training intervention done patients.Extensive ex vivo analyses quality, quantity, were...
Introduction Both sarcopenia and spinal cord injury (SCI) are characterized by the loss of skeletal muscle mass function. Despite obvious similarities in atrophy between both models, differences fiber size satellite cell content may exist on a type–specific level. Methods In present study, we compared characteristics wheelchair-dependent young males with SCI (n = 8, 32 ± 4 yr), healthy elderly 75 2 controls 31 3 yr). Muscle biopsies were collected to determine type composition, size,...
Deuterium metabolic imaging (DMI) is a novel MR‐based method to spatially map metabolism of deuterated substrates such as [6,6'‐ 2 H ]‐glucose in vivo. Compared with traditional 13 C‐MR‐based studies, the MR sensitivity DMI high due larger magnetic moment and favorable T 1 relaxation times. Here, field dependence transmit efficiency studied on phantoms rat brain postmortem at 4, 9.4 11.7 T. The spectral resolution human vivo are investigated 4 7 before after an oral dose ]‐glucose. For small...
Abstract Chemical exchange saturation transfer (CEST) exploits the chemical of labile protons an endogenous or exogenous compound with water to image former indirectly through signal. Z-spectra brain have traditionally been analyzed for two most common phenomena: downfield amide proton (APT) and upfield nuclear Overhauser enhancement (NOE). However, a great body metabolites, many interest in neurology oncology, contributes Z-spectra. The extraction these “hidden” metabolites from requires...
(31)P magnetic resonance spectroscopy provides the possibility of obtaining bioenergetic data during skeletal muscle exercise and recovery. The time constant phosphocreatine (PCr) recovery (tau(PCr)) has been used as a measure mitochondrial function. However, cytosolic pH strong influence on kinetics PCr recovery, it suggested that tau(PCr) should be normalized for end-exercise pH. A general correction can only applied if there are no intersubject differences in dependence tau(PCr). We...
Currently inherited or acquired skeletal muscle mitochondrial dysfunction is linked to dysregulated fatty acid metabolism, resulting in increased levels of intramyocellular lipids (IMCLs) and lipid intermediates, inducing insulin resistance. The present study aimed clarify the order changes IMCL function during development type 2 diabetes Zucker diabetic (ZDF) rats. oxidative capacity were determined vivo, using localized (1)H magnetic resonance spectroscopy (MRS) dynamic (31)P MRS,...
Lipotoxicity may be a key contributor to the pathogenesis of cardiac abnormalities in mitochondrial long-chain fatty acid β-oxidation (FAO) disorders. Few data are available on myocardial lipid levels and performance FAO deficiencies. The purpose this animal study is assess fasting-induced changes morphology, function, triglyceride (TG) storage as consequence deficiency noninvasive fashion.MRI proton magnetic resonance spectroscopy ((1)H-MRS) were applied vivo acyl-CoA dehydrogenase (LCAD)...
Targeted photodynamic therapy (PDT) has the potential to selectively damage tumor tissue and increase vessel permeability.Here we characterize biodistribution of two EGFR-targeted nanobody-photosensitizer conjugates (NB-PS), monovalent 7D12-PS biparatopic 7D12-9G8-PS.In addition, report on local acute phototoxic effects triggered by illumination these NB-PS which have previously shown lead extensive damage.Methods: Intravital microscopy skin-fold chamber model, containing OSC-19-luc2-cGFP...
Deuterium (2H) and phosphorus (31P) magnetic resonance spectroscopy (MRS) are complementary methods for evaluating tissue metabolism noninvasively in vivo. Combined 2H 31P MRS would therefore be of interest various applications, from cancer to diabetes. Loop coils commonly used X-nuclei studies the human body both transmit receive. However, loop suffer limited penetration depth inhomogeneous B1 + field. The purpose this work is develop a double tuned 2H/31P whole-body birdcage coil 7 T...
ABSTRACT Hepatic de novo lipogenesis (DNL) plays a key role in the pathogenesis of several metabolic diseases that affect liver. In humans, detection deuterium ( 2 H) triglycerides from very low density lipoprotein collected blood after administration deuterated water (D O) is commonly used as an indirect estimate hepatic DNL. Here, we tested rats (1) feasibility to detect H‐labeling directly liver lipids vivo by using noninvasive H MRS and (2) what extent these results correlated with gold...
ABSTRACT Glutamate (Glu) is the major excitatory neurotransmitter in central nervous system. The measurement of Glu/glutamine (Gln) neurotransmitters brain provides valuable insights into dynamic aspects neuroenergetics and cycles can be accomplished through detection 13 C‐labeling Glu Gln during administration C‐labeled glucose. Our goal to evaluate reproducibility selective proton‐observed, carbon‐edited (selPOCE) MRS at 7 T for human brain. Data three healthy participants, who were...
ABSTRACT This study evaluated whether dual‐energy X‐ray absorptiometry (DXA), computed tomography (CT), and magnetic resonance imaging (MRI) provide comparable outcomes in quantifying disuse‐induced skeletal muscle atrophy. Although the calculation of volume using MRI analysis may be considered gold standard, method remains labor intense and, as such, less practical more costly. In this context, we also efficacy a commercially available automated to measure changes leg after two weeks bed...
Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart development. We quantified to what extent changes in preference, lipid accumulation, energy status predict longitudinal development of hypertrophy non-diabetic diabetic heart.Transverse aortic constriction (TAC) was performed (db/+) (db/db) mice induce pressure overload. Magnetic resonance imaging, 31P...
AimsThe aim of this animal study is to assess fasting-induced changes in myocardial substrate metabolism and energy status as a consequence mitochondrial long-chain fatty acid β-oxidation deficiency, using magnetic resonance spectroscopy (MRS).