Klaas Nicolay

Eindhoven University of Technology | TUE · Department of Biomedical Engineering

This article was corrected/updated to include the complete graphic legend of Fig. 3.

Purpose Recent studies have shown rapid accumulation of nanobodies (NBs) in tumors and fast clearance of the unbound fraction, making NBs exceptional tracers for cancer imaging. In this study, we investigate the combination of in vitro imaging of tumor spheroids, in vivo dual-isotope single-photon emission computed tomography (SPECT), and ex vivo a...

The current state‐of‐the‐art diagnosis method for deep tissue injury in muscle, a subcategory of pressure ulcers, is palpation. It is recognized that deep tissue injury is frequently preceded by altered biomechanical properties. A quantitative understanding of the changes in biomechanical properties preceding and during deep tissue injury developme...

Aims: Mitochondrial fatty acid oxidation (FAO) is an important energy provider for cardiac work and changes in cardiac substrate preference are associated with different heart diseases. Carnitine palmitoyltransferase 1B (CPT1B) is thought to perform the rate limiting enzyme step in FAO and is inhibited by malonyl-CoA. The role of CPT1B in cardiac...

Early diagnosis of deep tissue injury remains problematic due to the complicated and multi-factorial nature of damage induction, and the many processes involved in damage development and recovery. In this paper we present a comprehensive assessment of deep tissue injury development and remodeling in a rat model by multi-parametric magnetic resonanc...

Dynamic contrast-enhanced MRI (DCE-MRI) is a promising technique for assessing the response of tumor vasculature to anti-vascular therapies. Multi-agent DCE-MRI employs a combination of low and high molecular weight contrast agents, which potentially improves the accuracy of estimation of tumor hemodynamic and vascular permeability parameters. In t...

Objective: The endothelium has a crucial role in wound healing, acting as a barrier to control transit of leukocytes. Endothelial barrier function is impaired in atherosclerosis preceding myocardial infarction (MI). Besides lowering lipids, statins modulate endothelial function. Here, we noninvasively tested whether statins affect permeability at...

Early evaluation of response to therapy is crucial for selecting the optimal therapeutic follow-up strategy for cancer patients. PDT is a photochemistry-based treatment modality that induces tumor tissue damage by cytotoxic oxygen radicals, generated by a pre-injected photosensitive drug upon light irradiation of tumor tissue. Vascular shutdown is...

Objectives: Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a method to heat lesions noninvasively to a stable, elevated temperature and a well-suited method to induce local hyperthermia (41°C-43°C) in deep-seated tissues. Magnetic Resonance (MR) imaging provides therapy planning on anatomical images and offers temperature...

Aim: Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development...

The use of contrast agents is an important component of diagnostic biomedical imaging, both in preclinical and clinical applications. Injected contrast agents both increase the sensitivity and the specificity of disease detection. This chapter provides an overview of the most important design considerations of contrast materials and how this affect...

We aimed to elucidate the effects of caloric and non-caloric sweeteners on liver lipid metabolism in rats using in vivo magnetic resonance spectroscopy (MRS) and to determine their roles in the development of liver steatosis. Wistar rats received normal chow and either normal drinking water, or solutions containing 13% (w/v) glucose, 13% fructose,...

A noninvasive method is introduced for quantification and visualization of fluence rate in light-irradiated biological tissues. The method is based on magnetic resonance thermometry (MRT) measurements of tissue temperature changes resulting from absorption of light. From the spatial-temporal temperature data, the generated heat is calculated. Final...

Fibrin deposition is observed in several diseases such as atherosclerosis, deep vein thrombosis and also tumors, where it contributes to the formation of mature tumor stroma. The aim of this study was to develop a gallium-labeled peptide tracer based on the fibrin targeting peptide Epep for PET imaging of fibrin deposition. For this purpose, the pe...

Muscle weakness and exercise intolerance negatively affect the quality of life of mitochondrial myopathy patients. Short-term dietary nitrate supplementation has been shown to improve exercise performance and reduce oxygen cost of exercise in healthy humans and trained athletes. We investigated if 1 week of dietary inorganic nitrate supplementation...

Deformation of skeletal muscle in the proximity of bony structures may lead to deep tissue injury category of pressure ulcers. Changes in mechanical properties have been proposed as a risk factor in the development of deep tissue injury and may be useful as a diagnostic tool for early detection. MRE allows for the estimation of mechanical propertie...

Photograph of a rat positioned in the setup. Rat, Indentation and MRE component are indicated with arrows. In A, the indentor, put through the surface RF coil, positioned on top of TA muscle in rats hindleg, and the MRE piston attached at distal side of TA muscle are shown. Indentation component is removed in B, revealing the MRE component and surf...

Detail of indentation and MRE actuator part of setup. Following parts are labeled: u-shaped profile (a), cutout for the rat’s groin (b), indentor (c), movable indentor holder (d), rotatable half arch (e), dovetail profile (f), spacer plates (g), MRE piston (h), drive rod (i), cantilever (j). (TIF)

MRE pre and post indentation movie. Movie of a 16 offsets 900 Hz SE-EPI-MRE (A) before and (B) after indentation. (AVI)

Figure S1. Bland–Altman of fascicle length measured in two different sessions for all muscles of the calf. Figure S2. Mean muscle fascicle length in dorsiflexed, neutral, and plantarflexed foot position for all muscles of the calf. Table S1. Mean fascicle length and standard deviation (SD), coefficient of variation (CV) and minimal detectable dif...

Musculoskeletal (dys-)function relies for a large part on muscle architecture which can be obtained using Diffusion-Tensor MRI (DT-MRI) and fiber trac-tography. However, reconstructed tracts often continue along the tendon or aponeurosis when using conventional methods, thus overestimating fascicle lengths. In this study, we propose a new method fo...

Objective The aim of this study was to characterize response to photodynamic therapy (PDT) in a mouse cancer model using a multi-parametric quantitative MRI protocol and to identify MR parameters as potential biomarkers for early assessment of treatment outcome. Methods CT26.WT colon carcinoma tumors were grown subcutaneously in the hind limb of B...

Ktrans and AUC maps of all slices of the entire tumor of three animals. The first example is a mouse with complete tumor response at 2 weeks after PDT, while the other two had recurring growth, both in the distal part of the tumor. Ktrans right after PDT and AUC at 72 h after PDT are shown. For Ktrans, only the contrast-enhanced pixels in the tumor...

Overview of experiment groups and their timelines. Numbers of animals are indicated per group. Grey blocks represent different measurement days. The following abbreviations are used: CT26: subcutaneous inoculation of CT26.WT tumor cells. MRI: Multi-parametric MRI scan session (approximate duration: 2.5 h). PS: photosensitizer injection, 6 h before...

The cover image, by Katrien Vandoorne et al., is based on the Research Article Noninvasive mapping of endothelial dysfunction in myocardial ischemia by magnetic resonance imaging using an albumin-based contrast agent, DOI: 10.1002/nbm.3599.

In this study we investigated the changes in fiber length and diffusion parameters as a consequence of passive lengthening and stretching of the calf muscles. We hypothesized that changes in radial diffusivity (RD) are caused by changes in the muscle fiber cross sectional area (CSA) as a consequence of lengthening and shortening of the muscle. Diff...

Noninvasive preclinical methods for the characterization of myocardial vascular function are crucial to an understanding of the dynamics of ischemic cardiac disease. Ischemic heart disease is associated with myocardial endothelial dysfunction, resulting in leakage of plasma albumin into the extravascular space. These features can be harnessed in a...

Purpose: To introduce a method for obtaining fat-suppressed images in real-time MRI of moving joints at 3 Tesla (T) using a bSSFP sequence with phase detection to enhance visualization of soft tissue structures during motion. Methods: The wrist and knee of nine volunteers were imaged with a real-time bSSFP sequence while performing dynamic tasks...

Type 2 diabetes (T2D) has reached epidemic proportions and is a major threat to global public health. In vivo magnetic resonance spectroscopy (MRS) allows the noninvasive study of tissue metabolism and has made major contributions to our understanding of the etiology of insulin resistance and T2D. Moreover, MRS has proved extremely useful in the ev...

Objectives: Drug-loaded temperature-sensitive liposomes (TSLs) allow heat-triggered local drug delivery to tumors. When magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is applied to heat up the tumor, corelease of a drug together with an MR contrast agent (CA) from TSLs allows for indirect imaging of the drug release with MR...

Synopsis Distinction between benign and malignant breast lesions remains diတcult with conventional (dynamic) contrast-enhanced MRI. MR Elastography (MRE) can distinguish benign and malignant tissues based on their viscoelastic properties but breast MRE has not found widespread use in daily clinical practice, because of the complex equipment require...

Synopsis We have investigated the feasibility of using Magnetic Resonance Elastography (MRE) to quantify muscle-tissue mechanical properties and changes therein related to the development of deep tissue injury type of pressure ulcers. MRE measurements were performed before and after damage-inducing indentation of the tibialis-anterior muscle of Spr...

Structural brain networks constructed based on diffusion-weighted MRI (dMRI) have provided a systems perspective to explore the organization of the human brain. Some redundant and nonexistent fibers, however, are inevitably generated in whole brain tractography. We propose to add one critical step while constructing the networks to remove these fib...

Background: Excess consumption of energy-dense, high-fat Western diets contributes to the development of obesity and obesity-related disorders, such as fatty liver disease. However, not only the quantity but also the composition of dietary fat may play a role in the development of liver steatosis. The aim of this study was to determine the effects...

Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent fo...

Pioglitazone is a PPAR- agonist that redirects lipids from ectopic sites into subcutaneous adipose tissue and is hypothesized to improve mitochondrial function in skeletal muscle. This study assessed whether the insulin-sensitizing effect of pioglitazone is accompanied by improved skeletal muscle mitochondrial function and intramyocellular lipid (I...

Increased supply of fatty acids (FA) to the diabetic heart has been shown to increase the reliance of the heart on FA oxidation to provide the energy for its function.

Hepatic steatosis is the abnormal and excessive accumulation of triglycerides in the liver and a histological hallmark of non-alcoholic fatty liver disease (NAFLD).

Insulin resistance and type 2 diabetes have been associated with ectopic lipid accumulation. Physical activity improves insulin sensitivity, but the impact of exercise on lipid handling in insulin-resistant skeletal muscle and, in particular, liver remains to be elucidated.

Angiogenesis is a prerequisite for solid tumors to grow and metastasize, providing oxygen and nutrients to the tumor site. The protein galectin-1 has been identified to be overexpressed on tumor vasculature and represents an interesting target for anti-angiogenic therapy, as well as in molecular imaging. Therefore, the galectin-1-binding peptide An...

Insulin resistance is associated with ectopic lipid accumulation. Physical activity improves insulin sensitivity, but the impact of exercise on lipid handling in insulin-resistant tissues remains to be elucidated. The present study characterizes the effects of acute exercise on lipid content and dietary lipid partitioning in liver and skeletal musc...

Evaluation of high intensity focused ultrasound (HIFU) treatment with MRI is generally based on assessment of the non-perfused volume from contrast-enhanced T1-weighted images. However, the vascular status of tissue surrounding the non-perfused volume has not been extensively investigated with MRI. In this study, cluster analysis of the transfer co...

The use of MR imaging and spectroscopy for studying cardiovascular disease processes in small animals has increased tremendously over the past decade. This is the result of the remarkable advances in MR technologies and the increased availability of genetically modified mice. MR techniques provide a window on the entire timeline of cardiovascular d...

Muscle lipid overload and the associated accumulation of lipid intermediates plays an important role in the development of insulin resistance. Carnitine insufficiency is a common feature of insulin-resistant states and might lead to incomplete fatty acid oxidation and impaired export of lipid intermediates out of the mitochondria. The aim of the pr...

(31) P MRS provides a unique non-invasive window into myocardial energy homeostasis. Mouse models of cardiac disease are widely used in preclinical studies, but the application of (31) P MRS in the in vivo mouse heart has been limited. The small-sized, fast-beating mouse heart imposes challenges regarding localized signal acquisition devoid of cont...

The clinical utility of supine in-magnet bicycling in combination with phosphorus magnetic resonance spectroscopy ((31)P MRS) to evaluate quadriceps muscle metabolism was examined in four children with juvenile dermatomyositis (JDM) in remission and healthy age- and gender-matched controls. Two identical maximal supine bicycling tests were performe...

In this study, a new (89) Zr- and Fe(3+) -labeled micelle nanoplatform ((89) Zr/Fe-DFO-micelles) for dual modality position emission tomography/magnetic resonance (PET/MR) imaging is investigated. The nanoplatform consists of self-assembling amphiphilic diblock copolymers that are functionalized with (89) Zr-deferoxamine ((89) Zr-DFO) and Fe(3+) -d...

The development of efficient contrast agents for cell labelling coupled with powerful medical imaging techniques is of great interest for monitoring cell trafficking with potential clinical applications such as organ repair and regenerative medicine. In this paper, functionalised multi-walled carbon nanotubes (MWNTs) were engineered for cell labell...

For the clinical application of high intensity focused ultrasound (HIFU) for thermal ablation of malignant tumors, accurate treatment evaluation is of key importance. In this study, we have employed a multiparametric MRI protocol, consisting of quantitative T1, T2, ADC, amide proton transfer (APT), T1ρ and DCE-MRI measurements, to evaluate MR-guide...

Membrane type-1 matrix metalloproteinase (MT1-MMP or MMP-14) plays an important role in adverse cardiac remodelling. Here, we aimed to develop radiolabeled activatable cell penetrating peptides (ACPP) sensitive to MT1-MMP for the detection of elevated MT1-MMP levels in adverse cardiac remodelling. Three ACPP analogs were synthesized and the most po...

Background Myocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI). Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using contrast-enhanced T1 mapping. Detection of short...

Thermal ablation with high intensity focused ultrasound (HIFU) is an emerging noninvasive technique for the treatment of solid tumors. HIFU treatment of malignant tumors requires accurate treatment planning, monitoring and evaluation, which can be facilitated by performing the procedure in an MR-guided HIFU system. The MR-based evaluation of HIFU t...

Target audience (Pre) clinical scientists interested in vascular system, skeletal muscle damage, pressure ulcer research and musculoskeletal MRI. Purpose To investigate the relationship between the status of the arterial blood supply during prolonged skeletal muscle loading and the development of muscle injury, a study was performed in a rat model...

Target audience (Pre) clinical scientists interested in pressure ulcer research, skeletal muscle damage, musculoskeletal MRI, and MR Elastography. Purpose We built an MR Elastography (MRE) actuator to study the role of tissue mechanical properties and changes therein during the development of pressure ulcer related deep tissue injury. The setup is...

Fibrin deposition plays an important role in the formation of mature tumor stroma and provides a facilitating scaffold for tumor angiogenesis. This study investigates the potential of the 111In-labeled fibrin-binding peptide EPep for SPECT imaging of intratumoral fibrin deposition.111In-EPep and negative control 111In-NCEPep were synthesized and ch...

Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment l...

PurposeTo develop a novel tracer-kinetic modeling approach for multi-agent dynamic contrast-enhanced MRI (DCE-MRI) that facilitates separate estimation of parameters characterizing blood flow and microvascular permeability within one individual.Methods Monte Carlo simulations were performed to investigate the performance of the constrained multi-ag...

The shift in substrate preference away from fatty acid oxidation (FAO) towards increased glucose utilization in heart failure has long been interpreted as an oxygen-sparing mechanism. Inhibition of FAO has therefore evolved as an accepted approach to treat heart failure. However, recent data indicate that increased reliance on glucose might be detr...

Magnetic particle imaging (MPI) is an emerging medical imaging modality that directly visualizes magnetic particles in a hot-spot like fashion. We recently developed an iron oxide nanoparticle-micelle (ION-Micelle) platform that allows highly sensitive MPI. The goal of this study was to assess the potential of the ION-Micelles for MPI-based detecti...

Matrix metalloproteinases (MMPs) play a pivotal role in cancer progression and present therefore an interesting biomarker for early diagnosis, staging and therapy evaluation. Consequently, MMP-specific molecular imaging probes have been proposed for noninvasive visualization and quantification of MMP activity. An interesting approach is MMP-2/9 act...

This study aims at acquiring and reconstructing compressed sensing accelerated phosphorus MR spectroscopic imaging (31P-MRSI) of human brain in vivo. Accelerated 31P-MRSI volunteer data were acquired using pulse and acquire with compressed sensing at 3T. k-space data was randomly undersampled for a five fold scan time reduction while preserving the...

In recent years, extensive research in atherosclerosis disease has elucidated many of the biological and molecular mechanisms and pathways involved in plaque development and progression. This has identified dozens of novel targets for diagnosis, therapy, and treatment evaluation. In vivo molecular imaging techniques, and in particular molecular mag...

The objective of this study was to investigate the feasibility and the accuracy of spectral computed tomography (spectral CT) to determine the tissue concentrations and localization of high-attenuation, iodine-based contrast agents in mice. Iodine tissue concentrations determined with spectral CT are compared with concentrations measured with singl...

To evaluate spin-lock MR for detecting superparamagnetic iron oxides and compare the detection sensitivity of quantitative T1ρ with T2 imaging. In vitro experiments were performed to investigate the influence of iron oxide particle size and composition on T1ρ . These comprise T1ρ and T2 measurements (B0 = 1.41T) of agar (2%) with concentration rang...