Arend Heerschap

Radboud University Medical Centre (Radboudumc) · Radiology and Nuclear Medicine

In in vivo 1H-MRSI of the prostate, small matrix sizes can cause voxel bleeding extending to regions far from a voxel, dispersing a signal of interest outside that voxel and mixing extra-prostatic residual lipid signals into the prostate. To resolve this problem, we developed a three-dimensional overdiscretized reconstruction method. Without increa...

Purpose: To develop a robust processing procedure of raw signals from water-unsuppressed MRSI of the prostate for the mapping of absolute tissue concentrations of metabolites. Methods: Water-unsuppressed 3D MRSI data were acquired from a phantom, from healthy volunteers, and a patient with prostate cancer. Signal processing included sequential c...

Background Facioscapulohumeral dystrophy (FSHD) is a major muscular dystrophy characterized by asymmetric fatty replacement of muscles. We aimed to determine the initiation site and progression profile of the disease in lower extremity muscles of FSHD patients by assessing fat infiltration along their full proximo-distal axis using quantitative MRI...

Introduction In situ tumor ablation releases a unique repertoire of antigens from a heterogeneous population of tumor cells. High-intensity focused ultrasound (HIFU) is a completely noninvasive ablation therapy that can be used to ablate tumors either by heating (thermal (T)-HIFU) or by mechanical disruption (mechanical (M)-HIFU). How different HIF...

Bone tissue engineering (BTE) has made significant progress in developing and assessing different types of bio‐substitutes. However, scaffolds production through standardized methods, as required for good manufacturing process (GMP), and post‐transplant in vivo monitoring still limit their translation into the clinic. 3D printed 5% GelMA scaffolds...

Purpose To evaluate the value of convolutional neural network (CNN) in the diagnosis of human brain tumor or Alzheimer’s disease by MR spectroscopic imaging (MRSI) and to compare its Matthews correlation coefficient (MCC) score against that of other machine learning methods and previous evaluation of the same data. We address two challenges: 1) lim...

Significance The human prostate accumulates high luminal citrate levels to serve sperm viability. There is only indirect qualitative evidence about metabolic pathways and carbon sources maintaining these levels. Human citrate-secreting prostate cancer cells were supplied with ¹³ C-labeled substrates, and NMR spectra of extracellular fluid were reco...

In this paper, we review the developments of 1H-MR spectroscopic imaging (MRSI) methods designed to investigate prostate cancer, covering key aspects such as specific hardware, dedicated pulse sequences for data acquisition and data processing and quantification techniques. Emphasis is given to recent advancements in MRSI methodologies, as well as...

Introduction Impaired awareness of hypoglycemia, clinically reflected by the inability to timely detect hypoglycemia, affects approximately 25% of the people with type 1 diabetes. Both altered brain lactate handling and increased cerebral blood flow (CBF) during hypoglycemia appear to be involved in the pathogenesis of impaired awareness of hypogly...

With several therapeutic strategies for facioscapulohumeral muscular dystrophy (FSHD) entering clinical testing, outcome measures are becoming increasingly important. Considering the spatiotemporal nature of FSHD disease activity, clinical trials would benefit from non-invasive imaging-based biomarkers that can predict FSHD-associated transcriptome...

IntroductionMolecular interactions in prostatic fluid are of biological interest and may affect MRI and MRS of the prostate. We investigated the existence of interactions between the major components of this fluid: spermine, citrate and myoinositol, metal ions, including zinc, and proteins.Materials and methodsSolutions of 90 mM citrate, 18 mM sper...

Purpose Until now, ¹H MRSI of the prostate has been performed with suppression of the large water signal to avoid distortions of metabolite signals. However, this signal can be used for absolute quantification and spectral corrections. We investigated the feasibility of water-unsuppressed MRSI in patients with prostate cancer for water signal–media...

Increased glucose and choline uptake are hallmarks of cancer. We investigated whether the uptake and conversion of [2H9]choline alone and together with that of [6,6′-2H2]glucose can be assessed in tumors via deuterium metabolic imaging (DMI) after administering these compounds. Therefore, tumors with human renal carcinoma cells were grown subcutane...

Abstract Background Current multiparametric MRI (mp-MRI) in routine clinical practice has poor-to-moderate diagnostic performance for transition zone prostate cancer. The aim of this study was to evaluate the potential diagnostic performance of novel 1H magnetic resonance spectroscopic imaging (MRSI) using a semi-localized adiabatic selective refoc...

: Increased glucose and choline uptake are hallmarks of cancer. We investigated if the uptake and conversion of [2H9]choline alone and together with that of [6,6’ 2H2]glucose can be assessed in subcutaneous tumors by deuterium metabolic imaging (DMI) after bolus administration of these compounds. Therefore tumors with human renal carcinoma cells we...

Introduction: Specific force, i.e. the amount of force generated per unit of muscle tissue, is reduced in patients with facioscapulohumeral muscular dystrophy (FSHD). The causes of reduced specific force and its relation with FSHD disease severity are unknown. Methods: Quantitative muscle MRI, measurement of voluntary maximum force generation an...

Background Patients with myotonic dystrophy type 1 (DM1) increased their physical activity and exercise capacity following a behavioral intervention. However, it is unknown what is altered in muscles of patients with DM1 as a result of this intervention. The increased exercise capacity suggests that decelerated fat infiltration or increased muscle...

Background: Muscle MRI is increasingly used as a diagnostic and research tool in muscle disorders. However, the correlation between MRI abnormalities and histopathological severity is largely unknown. Objective: To investigate correlations between muscle MRI abnormalities and histopathological severity in healthy controls and patients with muscl...

With a 40‐year history of use for in vivo studies, the terminology used to describe the methodology and results of magnetic resonance spectroscopy (MRS) has grown substantially and is not consistent in many aspects. Given the platform offered by this special issue on advanced MRS methodology, the authors decided to describe many of the implicated t...

Reprogramming of energy metabolism in the development of prostate cancer can be exploited for a better diagnosis and treatment of the disease. The goal of this study was to determine whether differences in glucose and pyruvate metabolism of human prostate cancer cells with dissimilar aggressivenesses can be detected using hyperpolarized [1‐¹³C]pyru...

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...

Objective: To investigate single muscle fiber contractile performance in muscle biopsies from patients with facioscapulohumeral muscular dystrophy (FSHD), one of the most common hereditary muscle disorders. Methods: We collected 50 muscle biopsies (26 vastus lateralis, 24 tibialis anterior) from 14 patients with genetically confirmed FSHD and 12...

The use of polymeric nanoparticles (NPs) as therapeutics has been steadily increasing over past decades. In vivo imaging of NPs is necessary to advance the therapeutic performance. 19F Magnetic Resonance Imaging (19F MRI) offers multiple advantages for in vivo imaging. However, design of a probe for both biodistribution and degradation has not been...

Purpose: To propose a novel segmentation framework that is dedicated to the follow-up of fat infiltration in individual muscles of patients with neuromuscular disorders. Methods: We designed a semi-automatic segmentation pipeline of individual leg muscles in MR images based on automatic propagation through nonlinear registrations of initial deli...

31 P MR spectroscopic imaging (MRSI) is a versatile technique to study phospholipid precursors and energy metabolism in the healthy and diseased human brain. However, mainly due to its low sensitivity, 31 P MRSI is currently limited to research purposes. To obtain 3D 31 P MRSI spectra with improved signal-to-noise ratio on clinical 3 T MR systems,...

Obsessive–compulsive disorder (OCD) is a neuropsychiatric disorder with childhood onset, and is characterized by intrusive thoughts and fears (obsessions) that lead to repetitive behaviors (compulsions). Previously, we identified insulin signaling being associated with OCD and here, we aim to further investigate this link in vivo. We studied TALLYH...

Healthy human prostate epithelial cells have the unique ability to produce and secrete large amounts of citrate into the lumen of the prostate. Citrate is a Krebs cycle metabolite produced in the condensation reaction between acetyl-CoA and oxaloacetate in the mitochondria of the cell. Using $^{13}$C-enriched substrates, the contributions of differ...

Aims/hypothesis Chronic hyperglycaemia in type 1 diabetes affects the structure and functioning of the brain, but the impact of recurrent hypoglycaemia is unclear. Changes in the neurochemical profile have been linked to loss of neuronal function. We therefore aimed to investigate the impact of type 1 diabetes and burden of hypoglycaemia on brain m...

Objective: To determine the value of quantitative MRI in providing imaging biomarkers for disease in 20 different upper and lower leg muscles of patients with myotonic dystrophy type 1 (DM1). Methods: We acquired images covering these muscles in 33 genetically and clinically well-characterized patients with DM1 and 10 unaffected controls. MRIs w...

Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in various types of cancer and induce metabolic alterations resulting from the neomorphic activity that causes production of D-2-hydroxyglutarate (D-2-HG) at the expense of α-ketoglutarate (α-KG) and NADPH. To overcome metabolic stress induced by these alterations, IDH-mutated (IDH m...

Ultrasound is the most commonly used clinical imaging modality. However, in applications requiring cell‐labeling, the large size and short active lifetime of ultrasound contrast agents limit their longitudinal use. Here, 100 nm radius, clinically applicable, polymeric nanoparticles containing a liquid perfluorocarbon, which enhance ultrasound contr...

Quantitative radiomics features, extracted from medical images, characterize tumour-phenotypes and have been shown to provide prognostic value in predicting clinical outcomes. Stability of radiomics features extracted from apparent diffusion coefficient (ADC)-maps is essential for reliable correlation with the underlying pathology and its clinical...

Imaging of hyperpolarized ¹³C-labeled substrates has emerged as an important MR technique to study metabolic pathways in real time in vivo. Even though this technique has found its way to clinical trials, in vivo dynamic nuclear polarization is still mostly applied in preclinical models. Its tremendous increase in SNR overcomes the intrinsically lo...

Atrophy and fatty infiltration are important causes of muscle weakness in inclusion body myositis (IBM). Muscle weakness can also be caused by reduced specific force; i.e. the amount of force generated per unit of residual muscle tissue. This study investigates in vivo specific force of the quadriceps and ex vivo specific force of single muscle fib...

Purpose To demonstrate a ¹H/³¹P whole human brain volume coil configuration for 3 Tesla with separate ³¹P transmit and receive components that maintains ¹H MRS performance and delivers optimal ³¹P MRSI with ¹H decoupling. Methods We developed an 8‐channel ³¹P receive array coil covering the head to be used as an insert for a commercial double‐tune...

Proton MRS (1H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption ha...

Neuromuscular diseases are characterized by progressive muscle degeneration and muscle weakness resulting in functional disabilities. While each of these diseases is individually rare, they are common as a group, and a large majority lacks effective treatment with fully market approved drugs. Magnetic resonance imaging and spectroscopy techniques (...

Purpose Quality control (QC) is a prerequisite for clinical MR spectroscopic imaging (MRSI) to avoid that bad spectra hamper data interpretation. The aim of this work was to present a simple automatic QC for prostate ¹H MRSI that can handle data obtained with different commonly used pulse sequences, echo times, field strengths, and MR platforms. M...

Purpose: To investigate the associations of metabolite levels derived from magnetic resonance spectroscopic imaging (MRSI) and ¹⁸F-fluciclovine positron emission tomography (PET) with prostate tissue characteristics. Methods: In a cohort of 19 high-risk prostate cancer patients that underwent simultaneous PET/MRI, we evaluated the diagnostic perfor...

Purpose A relatively high signal for choline‐containing compounds (total choline, tCho) is commonly found in ¹H MR spectra of malignant tumors, but it is unclear if this also occurs in tumors in the liver. We evaluated the potential of the tCho signal in single voxel ¹H MR spectra of the human liver to assess metastases of colorectal cancers. Expe...

Direct in vivo monitoring of bioconstructs using noninvasive imaging modalities such as magnetic resonance imaging (MRI) or computed tomography (CT) is not possible for many materials. Calcium phosphate–based composites (CPCs) that are applicable to bone regeneration are an example where the materials have poor MRI and CT contrast; hence, they are...

In vivo monitoring of tissue‐engineered constructs is important to assess their integrity, remodeling, and degradation. However, this is challenging when the contrast with neighboring tissues is low, necessitating labeling with contrast agents (CAs), but current CAs have limitations (i.e., toxicity, negative contrast, label instability, and/or inap...

Diffuse gliomas often carry point mutations in isocitrate dehydrogenase (IDH1mut), resulting in metabolic stress. Although IDHmut gliomas are difficult to culture in vitro, they thrive in the brain via diffuse infiltration, suggesting brain-specific tumor-stroma interactions that can compensate for IDH-1 deficits. To elucidate the metabolic adjustm...

Phosphorus magnetic resonance spectroscopy (³¹P MRS) has been employed before to assess phosphocreatine (PCr) and other high-energy phosphates in the visual cortex during visual stimulation with inconsistent results. We performed functional ³¹P MRS imaging in the visual cortex and control regions during a visual stimulation paradigm at an unprecede...

Background Sampling error is a common problem in muscle biopsies. MRI-guided biopsy allows verification of biopsy site during the procedure, which may reduce sampling error in patients with focal disease. Objectives To describe the technique for MRI-guided muscle biopsy and discuss potential applications. Methods Axial MRI images were acquired to...

Creatine serves as fast energy buffer in organs of high-energy demand such as brain and skeletal muscle. L-Arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase are responsible for endogenous creatine synthesis. Subsequent uptake into target organs like skeletal muscle, heart and brain is mediated by the creatine trans...

Monitoring hydrogel degradation in real time using noninvasive imaging techniques is of great interest for designing a scaffold in tissue engineering. We report the preparation of gadolinium (Gd)-labeled and injectable hyaluronic acid (HA) hydrogels that can be visualized using T1- and T2-weighted magnetic resonance imaging (MRI). An HA derivative...

Background: Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care a...

Administration of lactate during hypoglycemia suppresses symptoms and counterregulatory responses, as seen in patients with type 1 diabetes and impaired awareness of hypoglycemia (IAH), presumably because lactate can substitute for glucose as a brain fuel. Here, we examined whether lactate administration, in a dose sufficient to impair awareness of...

In Alzheimer's disease (AD), defects in essential metabolic processes for energy supply and phospholipid membrane function have been implicated in the pathological process. However, post-mortem investigations are generally limited to late stage disease and prone to tissue decay artifacts. In vivo assessments of high energy phosphates, tissue pH and...

Key points: During exercise skeletal muscles use the energy buffer phosphocreatine. The post-exercise recovery of phosphocreatine is a measure of the oxidative capacity of muscles and is traditionally assessed by31P magnetic resonance spectroscopy of a large tissue region, assuming homogeneous energy metabolism. To test this assumption, we collect...

The aim was to test whether strength per unit of muscle area (specific muscle strength) is affected in facioscapulohumeral dystrophy (FSHD) patients, as compared to healthy controls. Ten patients and ten healthy volunteers underwent an MRI examination and maximum voluntary isometric contraction measurements (MVICs) of the quadriceps muscles. Contra...

Reduced top-down control by cortical areas is assumed to underlie pathological forms of aggression. While the precise underlying molecular mechanisms are still elusive, it seems that balancing the excitatory and inhibitory tones of cortical brain areas has a role in aggression control. The molecular mechanisms underpinning aggression control were e...

H magnetic resonance imaging (MRI) by a zero echo time (ZTE) sequence is an excellent method to image teeth. Calcium phosphate cement (CPC) materials are applied in the restoration of tooth lesions, but it has not yet been investigated whether they can be detected by computed tomography (CT) or MRI. The aim of this study was to optimize high-field...

Apparent Diffusion Coefficient (ADC) is a potential quantitative imaging biomarker for tumour cell density and is widely used to detect early treatment changes in cancer therapy. We propose a strategy to improve confidence in the interpretation of measured changes in ADC using a data-driven model that describes sources of measurement error. Observe...

Since altered brain lactate handling has been implicated in the development of impaired awareness of hypoglycemia (IAH) in type 1 diabetes, the capacity to transport lactate into the brain during hypoglycemia may be relevant in its pathogenesis. High-intensity interval training (HIIT) increases plasma lactate levels. We compared the effect of HIIT-...

Although limb girdle weakness is not part of the major diagnostic criteria of oculopharyngeal muscular dystrophy (OPMD), it has frequently been observed in the Dutch and other OPMD cohorts. In the Dutch cohort, this might be related to the relatively old age or the severity of the genetic defect. This patient-control study (14 OPMD patients and 12...

Statement of significance: In this study, we combined diagnostic and therapeutic agents in order to developed a theranostic pulp capping agent with enhanced MRI and CT contrast and improved dentin regeneration ability. In our study we cover all the steps from material preparation, mechanical and in vitro characterization, to in vivo study in a goa...