Alard Roebroeck

• Maastricht University

Purpose Magnetic resonance imaging (MRI) is the preferred diagnostic tool for the detection of structural cerebral lesions in patients with epilepsy. Ultra-high field (UHF) MRI with field strengths ≥7 Tesla has been reported to improve the visualization and delineation of epileptogenic lesions. The use of ex vivo UHF MRI may expand our knowledge on...

Purpose Resective epilepsy surgery is a well-established, evidence-based treatment option in patients with drug-resistant focal epilepsy. A major predictive factor of good surgical outcome is visualization and delineation of a potential epileptogenic lesion by MRI. However, frequently, these lesions are subtle and may escape detection by convention...

Previous studies aimed to unravel a digit-specific somatotopy in the primary sensorimotor (SM1) cortex. However, it remains unknown whether digit somatotopy is associated with motor preparation and/or motor execution during different types of tasks. We adopted multivariate representational similarity analysis to explore digit activation patterns in...

Previous studies aimed to unravel a digit-specific somatotopic organization in the primary sensorimotor (SM1) cortex. It is, however, yet to be determined whether such digit somatotopy is associated with motor performance (i.e., effector selection) and digit enslaving (unintentional co-contraction of fingers) during different types of motor tasks....

There is an increasing interest in quantitative imaging of T1, T2 and diffusion contrast in the brain due to greater robustness against bias fields and artifacts, as well as better biophysical interpretability in terms of microstructure. However, acquisition time constraints are a challenge, particularly when multiple quantitative contrasts are des...

Vocal flexibility is a hallmark of the human species, most particularly the capacity to speak and sing. This ability is supported in part by the evolution of a direct neural pathway linking the motor cortex to the brainstem nucleus that controls the larynx - the primary sound source for communication. Early brain imaging studies demonstrated that l...

Background The emerging field of ultra-high field MRI (UHF-MRI, 7 Tesla and higher) provides the opportunity to image human brains at a higher resolution and with higher signal-to-noise ratios compared to the more widely available 1.5 and 3T scanners. Scanning postmortem tissue additionally allows for greatly increased scan times and fewer movement...

Rationale Resective epilepsy surgery is an evidence-based curative treatment option for patients with drug-resistant focal epilepsy. The major preoperative predictor of a good surgical outcome is detection of an epileptogenic lesion by magnetic resonance imaging (MRI). Application of ultra-high field (UHF) MRI, i.e. field strengths ≥7 Tesla (T), ma...

Here, we describe a new immersion-based clearing method suitable for optical clearing of thick adult human brain samples while preserving its lipids and lipophilic labels such as 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI). This clearing procedure is simple, easy to implement, and allowed for clearing of 5 mm thick huma...

Surprisingly, estimated voxel displacement maps (VDMs), based on image registration, seem to work just as well to correct geometrical distortion in functional MRI data (EPI) as VDMs based on actual information about the magnetic field. In this article, we compare our new image registration-based distortion correction method ‘COPE’ to an implementat...

There is an increasing interest in quantitative imaging of T 1 , T 2 and diffusion contrast in the brain due to greater robustness against bias fields and artifacts, as well as better biophysical interpretability in terms of microstructure. However, acquisition time constraints are a challenge, particularly when multiple quantitative contrasts are...

Objective: To determine the ability 7T-MRI for characterizing brain tissue integrity in early relapsing-remitting MS patients compared to conventional 3T-MRI and to investigate whether 7T-MRI improves the performance for detecting cortical grey matter neurodegeneration and its associated network reorganization dynamics. Methods: Seven early relaps...

Surprisingly, estimated voxel displacement maps (VDMs), based on image registration, seem to work just as well to correct geometrical distortion in functional MRI data (EPI) as VDMs based on actual information about the magnetic field. In this article, we compare our new image registration-based distortion correction method ‘COPE’ to an implementat...

Research investigating neural responses to visual food stimuli has produced inconsistent results. Crucially, high-caloric palatable foods have a double-sided nature - they are often craved but are also considered unhealthy - which may have contributed to the inconsistency in the literature. Taking this double-sided nature into account in the curren...

Light-sheet microscopy is an ideal technique for imaging large cleared samples; however, the community is still lacking instruments capable of producing volumetric images of centimeter-sized cleared samples with near-isotropic resolution within minutes. Here, we introduce the mesoscale selective plane-illumination microscopy initiative, an open-har...

Diffusion MRI (dMRI) in ex vivo human brain specimens is an important research tool for neuroanatomical investigations and the validation of dMRI techniques. Many ex vivo dMRI applications have benefited from very high dMRI resolutions achievable on small-bore preclinical or animal MRI scanners for small tissue samples. However, the investigation o...

Optical clearing techniques and light sheet microscopy have transformed fluorescent imaging of rodent brains, and have provided a crucial alternative to traditional confocal or bright field techniques for thin sections. However, clearing and labeling human brain tissue through all cortical layers and significant portions of a cortical area, has so...

Diffusion MRI (dMRI) allows for non-invasive investigation of brain tissue microstructure. By fitting a model to the dMRI signal, various quantitative measures can be derived from the data, such as fractional anisotropy, neurite density and axonal radii maps. The uncertainty in these dMRI measures is often ignored, while previous work in functional...

Purpose Neurodegenerative diseases such as Alzheimer’s disease cause changes and disruption to cortical microstructure and architecture. Diffusion MRI (dMRI) could potentially be sensitive to such changes. There is a growing interest in modeling of human cortical areas using a combination of quantitative MRI and 3D microscopy. The purpose of this s...

Background: Recent work showed a vast structural grey matter networks reorganization in patients with multiple sclerosis (MS) and depicted quantifiable longitudinal patterns of increased local clustering, increased modularity and long-range disconnection. These are detectable even beyond clinical markers of disease progression as measured with esta...

Over the course of the past decade, tissue clearing methods have reached a high level of sophistication with a wide variety of approaches now available. To image large cleared samples, light-sheet microscopes have proven to be ideal due to their excellent optical sectioning capability in transparent tissue. Such instruments have recently seen exten...

In diffusion MRI analysis, advances in biophysical multi-compartment modeling have gained popularity over the conventional Diffusion Tensor Imaging (DTI), because they can obtain a greater specificity in relating the dMRI signal to underlying cellular microstructure. Biophysical multi-compartment models require a parameter estimation, typically per...

Mapping non-invasively the complex microstructural architecture of the living human brain, diffusion magnetic resonance imaging (dMRI) is one of the core imaging modalities in current population studies. For the application in longitudinal population imaging, the dMRI protocol should deliver reliable data with maximum potential for future analysis....

This review discusses ex vivo diffusion magnetic resonance imaging (dMRI) as an important research tool for neuroanatomical investigations and the validation of in vivo dMRI techniques, with a focus on the human brain. We review the challenges posed by the properties of post‐mortem tissue, and discuss state‐of‐the‐art tissue preparation methods and...

In diffusion MRI analysis, advances in biophysical multi-compartment modeling have gained popularity over the conventional Diffusion Tensor Imaging (DTI), because they possess greater specificity in relating the dMRI signal to underlying cellular microstructure. Biophysical multi-compartment models require parameter estimation, typically performed...

Here we explore the high resolution acquisition of multi-shell and undersampled diffusion data with 9.4T kT-dSTEAM and analysis of such data for crossing fiber tractography. This permits effective usage of both high SNR and diffusion-weighting inherent to data with multiple b-values and shows superior definition of white matter tracks at ultra-high...

The recent introduction of advanced magnetic resonance (MR) imaging techniques to characterize focal and global degeneration in multiple sclerosis (MS), like the Composite Hindered and Restricted Model of Diffusion, or CHARMED, diffusional kurtosis imaging (DKI) and Neurite Orientation Dispersion and Density Imaging (NODDI) made available new tools...

We describe MASH (Multiscale Architectonic Staining of Human cortex): a simple, fast and low-cost cytoarchitectonic labeling and optical clearing approach for human cortex samples, which can be applied to large formalin fixed adult brain samples. A suite of small-molecule fluorescent nuclear and cytoplasmic dyes in combination with new refractive i...

Hemodynamic responses, in general, and the blood oxygenation level-dependent (BOLD) fMRI signal, in particular, provide an indirect measure of neuronal activity. There is strong evidence that the BOLD response correlates well with post-synaptic changes, induced by changes in the excitatory and inhibitory (E-I) balance between active neuronal popula...

Purpose: The aim of this project was to implement an ultra-high field (UHF) optimized double inversion recovery (DIR) sequence for gray matter (GM) imaging, enabling whole brain coverage in short acquisition times ( ≈5 min, image resolution 1 mm(3) ). Methods: A 3D variable flip angle DIR turbo spin echo (TSE) sequence was optimized for UHF appl...

Supplementary material

The investigation of entire human brains post mortem with diffusion MRI is an important research tool. However, the achievable resolutions and contrast are limited by gradient performance, RF-field inhomogeneity and strongly reduced T and diffusivity. Here, a diffusion-weighted STEAM sequence was modified to enable the use of k-points B + homogeniz...

Advances in biophysical multi-compartment modeling for diffusion MRI (dMRI) have gained popularity because of greater specificity than DTI in relating the dMRI signal to underlying cellular microstructure. A large range of these diffusion microstructure models have been developed and each of the popular models comes with its own, often different, o...

Effective connectivity is commonly assessed using blood oxygenation level-dependent (BOLD) signals. In (Havlicek et al., 2015), we presented a novel, physiologically informed dynamic causal model (P-DCM) that extends current generative models. We demonstrated the improvements afforded by P-DCM in terms of the ability to model commonly observed neur...

Several magnetic resonance imaging (MRI) contrasts are sensitive to myelin content in gray matter in vivo which has ignited ambitions of MRI-based in vivo cortical histology. Ultra-high field (UHF) MRI, at fields of 7 T and beyond, is crucial to provide the resolution and contrast needed to sample contrasts over the depth of the cortex and get clos...

Traditionally, our view of the connectivity in the human brain mostly relies on analogies to findings in other species, gross morphological observations, and functional studies. Direct visualization of connections in the human brain has been limited to very few tracing techniques which could be applied postmortem. Recent advances in diffusion MR op...

Neurite orientation dispersion and density imaging (NODDI) enables more specific characterization of tissue microstructure by estimating neurite density (NDI) and orientation dispersion (ODI), two key contributors to fractional anisotropy (FA). The present work compared NODDI- with diffusion tensor imaging (DTI)-derived indices for investigating wh...

Analysis pipeline for the TBSS analysis of DTI and NODDI data. (DOCX)

Background The role of cortical lesions (CLs) in disease progression and clinical deficits is increasingly recognized in multiple sclerosis (MS); however the origin of CLs in MS still remains unclear. Objective Here, we report a para-sulcal CL detected two years after diagnosis in a relapsing-remitting MS (RRMS) patient without manifestation of cl...

Purpose To design, construct and validate radiofrequency (RF) transmit and receive phased array coils for high-resolution visual cortex imaging at 7 Tesla. Methods A 4 channel transmit and 16 channel receive array was constructed on a conformal polycarbonate former. Transmit field efficiency and homogeneity were simulated and validated, along with...

Recently, several magnetic resonance imaging contrast mechanisms have been shown to distinguish cortical substructure corresponding to selected cortical layers. Here, we investigate cortical layer and area differentiation by automatized unsupervised clustering of high-resolution diffusion MRI data. Several groups of adjacent layers could be disting...

Introduction The subthalamic nucleus (STN), a well known target for deep brain stimulation (DBS) in Parkinson’s disease (PD), is involved in motor, limbic, and cognitive processes ( Temel et al., 2005) . To achieve a successful outcome of DBS surgery the electrode should be placed in its motor part. In current clinical practice, targeting is perfor...

Deep brain stimulation of the subthalamic nucleus (STN) is a widely performed surgical treatment for patients with Parkinson's disease. The goal of the surgery is to place an electrode centered in the motor region of the STN while lowering the effects of electrical stimulation on the non-motor regions. However, distinguishing the motor region from...

A comprehensive tract-based characterisation of white matter should include the ability to quantify myelin and axonal attributes irrespective of the complexity of fibre organisation within the voxel. Recently, a new experimental framework that combines inversion recovery and diffusion MRI, called inversion recovery diffusion tensor imaging (IR-DTI)...

Introduction: The subthalamic nucleus, substantia nigra, and globus pallidus, three nuclei of the human basal ganglia, play an important role in motor, associative, and limbic processing. The network of the basal ganglia is generally characterized by a direct, indirect, and hyperdirect pathway. This study aims to investigate the mesoscopic nature o...

Direct connections between the STN (green), SNc (red), SNr (orange), GPe (dark blue), and GPi (light blue) in a 3D rotation visualization. The tracks are colored as follows: STN-GPe, red; STN-GPi, blue; SNc-GPe, purple; SNc-GPi, green; SNr-GPi, brown; and SNr-GPe, orange.

Background: Although widespread reduced white matter (WM) integrity is a consistent finding in cross-sectional diffusion tensor imaging (DTI) studies of schizophrenia, little is known about the course of these alterations. This study examined to what degree microstructural WM alterations display differential trajectories over time as a function of...

Small-bore animal scanners or spectroscopy systems have often been used for the investigation of small post-mortem human brain samples. These studies use the high field strengths and strong gradients, but are inherently limited to very small sample sizes. In this abstract, we discuss the acquisition of very high resolution anatomical images (100μm...

Example of signal fit in one selected voxel for Monte Carlo simulated data (left) and real data (right). Data are colored according to the orientation of the applied gradient (red along z and blue along x).

Axonal density and diameter are two fundamental properties of brain white matter. Recently, advanced diffusion MRI techniques have made these two parameters accessible in vivo. However, the techniques available to estimate such parameters are still under development. For example, current methods to map axonal diameters capture relative trends over...

Granger causality or G-causality is a measurable concept of causality or directed influence for time series data, defined using predictability and temporal precedence. A variable y G-causes another variable x if the prediction of x’s values improves when we use past values of y, given that all other relevant information z is taken into account. In...

Diffusion tensor imaging (DTI) is amongst the simplest mathematical models available for diffusion magnetic resonance imaging, yet still by far the most used one. Despite the success of DTI as an imaging tool for white matter fibers, its anatomical underpinnings on a microstructural basis remain unclear. In this study, we used 65 myelin-stained sec...

The functional MRI (fMRI) signal is an indirect measure of neuronal activity. In order to deconvolve the neuronal activity from the experimental fMRI data, biophysical generative models have been proposed describing the link between neuronal activity and the cerebral blood flow (the neurovascular coupling), and further the hemodynamic response and...

Pre-clinical MRI systems (animal scanners or spectroscopy systems) can be used to examine small human brain tissue samples post mortem and investigate fundamental neuroanatomy questions at the mesoscale [1-4]. These studies benefit from the advantages of high field strength and gradient performance, but are limited to relatively small tissue sample...

The structural architecture and the anatomical connectivity of the human brain show different organizational principles at distinct spatial scales. Histological staining and light microscopy techniques have been widely used in classical neuroanatomical studies to unravel brain organization. Using such techniques is a laborious task performed on 2-d...

New generative model allows modeling of neuronal transients (via exitatory-inhibitory balance) together with vascular transients (via CBF-CBV uncoupling). It can explain dynamic relationship between diierent physiological variables underlying BOLD response. It is consistent across variety of measured data and experimental manipulations. Data descri...

INTRODUCTION The investigation of small human tissue samples post mortem in pre-clinical MRI systems (animal scanners or spectroscopy systems) has brought important information on fundamental neuroanatomy at the mesoscale. Recently, this has been extended to diffusion imaging, with applications in both high-detail imaging of white matter tracts and...

Images of the human brain at ultra-high fields of 7T and above are often acquired using a cylindrical quadrature volume transmit (Tx) coil and whole head phased array receive coil. Though this allows for a high B1 + value at the center of the head, the Tx efficiency is much lower along the periphery and inferior extents of the brain, particularly a...

The subthalamic nucleus (STN) is an important target for deep brain stimulation (DBS) in patients with Parkinson’s disease. Although fitting models of its complex interactions with other basal ganglia nuclei exist (1), its role in Parkinson’s disease and the effect of DBS are not completely understood. This study examines the high resolution anatom...

Deep brain stimulation is a treatment for Parkinson's disease and other related disorders, involving the surgical placement of electrodes in the deeply situated basal ganglia or thalamic structures. Good clinical outcome requires accurate targeting. However, due to limited visibility of the target structures on routine clinical MR images, direct ta...

White matter abnormalities have been observed in patients with classic galactosemia, an inborn error of galactose metabolism. However, magnetic resonance imaging (MRI) data collected in the past were generally qualitative in nature. Our objective was to investigate white matter microstructure pathology and examine correlations with outcome and beha...

Background / Purpose: We investigated the use of GPU accelerated programming to investigate diffusion microstructure modelling. Main conclusion: It is possible to achieve a dramatic speed-gain when using OpenCL which makes calculating computationally intensive microstructure models feasible.

Background / Purpose: Functional and diffusion-weighted MRI are usually performed using echo-planar imaging (EPI). A major problem with EPI are geometric distortions caused by magnetic field inhomogeneities, especially at high field strength. To determine the best way to deal with these, we compared three methods for EPI distortion correction. M...

We have introduced a new physiologically realistic DCM and applied it to ASL-fMRI data that models E-I neuronal balance, proper neurovascular coupling, and the actual balloon eeect. New P-DCM is clearly more accurate compared to S-DCM and 2S-DCM as indicated by various metrics, including precisely modeling of neuronal and vascu-lar origins of the h...

Multimodal neuroimaging has become a mainstay of basic and cognitive neuroscience in humans and animals, despite challenges to consider when acquiring and combining non-redundant imaging data. Multimodal data integration can yield important insights into brain processes and structures in addition to spatiotemporal resolution complementarity, includ...

Author Summary What are the commonalities and differences of human brains when compared to the brains of other primates? The brain can be conceived as a complex network. Its topological properties constrain its function. Ethical and technical reasons necessitate the use of animal brains, like the macaque monkey, as models for the human brain. Howe...

Behavioral evidence indicates that working memory (WM) in schizophrenia is already impaired at the encoding stage. However, the neurophysiological basis of this primary deficit remains poorly understood. Using event-related fMRI, we assessed differences in brain activation and functional connectivity during the encoding, maintenance and retrieval s...

Author Summary What are the commonalities and differences of human brains when compared to the brains of other primates? The brain can be conceived as a complex network. Its topological properties constrain its function. Ethical and technical reasons necessitate the use of animal brains, like the macaque monkey, as models for the human brain. Howev...

Decision-making involves a complex interplay of emotional responses and reasoning processes. In this study, we use TMS to explore the neurobiological substrates of moral decisions in humans. To examining the effects of TMS on the outcome of a moral-decision, we compare the decision outcome of moral-personal and moral-impersonal dilemmas to each oth...

In this study we were interested in the neural system supporting the audiovisual integration of emotional expression and emotional prosody. To this end normal participants were exposed to short videos of a computer-animated face voicing emotionally positive or negative words with the appropriate prosody. Facial expression of the face was either neu...

Background: There is evidence for microstructural white matter alterations in patients with psychotic disorder, suggesting altered interregional connectivity. Less is known about the presence and role of white matter alterations in well individuals at higher than average genetic risk for psychotic disorder. Methods: 85 patients with psychotic di...

Table 1: Results per b-value for different SNR, using Q-ball, Södermans model, with Ngrad=97, angle=60v and l=6. fix is the mean angular error,sis the standard deviation of the angular error and p is the fraction of samples for which we could retrieve two fiber populations. Table 2: Results per b-value for different SNR, using analytical DOT ODF, S...

Cue reactivity and craving can be influenced by cue exposure with response prevention (CERP). This study investigated the neural correlates of CERP using functional magnetic resonance imaging, while participants smelled chocolate (17 participants) or a control object (17 participants). CERP was interrupted by 7 scanning sequences measuring the brai...