Marleen Verhoye professor

Research Marleen Verhoye

Research team

Expertise

Acquisition and processing of high resolution in vivo Magnetic Resonance Imaging of small animals: diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), functional MRI, resting state fMRI, perfusion MRI, Manganese Enhanced MRI. This research is performed on rat and mouse models for different neuropathologies and on songbirds as a model for neuronal plasticity, auditory processing and learning. Using these MRI techniques the focus of the research lies on early detection and understanding of the mechanisms underlying neurodegeneration, neuro-developmental and mood disorders including Parkinson's, Huntington's, Alzheimer's disease, schizophrenia and depression.

Alliance for multidimensional and multidisciplinary neuroscience (µNEURO). 01/01/2026 - 31/12/2031

Abstract

Owing to their high spatiotemporal resolution and non-invasive nature, (bio)medical imaging technologies have become key to understanding the complex structure and function of the nervous system in health and disease. Recognizing this unique potential, μNEURO has assembled the expertise of eight complementary research teams from three different faculties, capitalizing on advanced neuro-imaging tools across scales and model systems to accelerate high-impact fundamental and clinical neuro-research. Building on the multidisciplinary collaboration that has been successfully established since its inception (2020-2025), μNEURO (2026-2031) now intends to integrate and consolidate the synergy between its members to become an international focal point for true multidimensional neuroscience. Technologically, we envision enriching spatiotemporally resolved multimodal imaging datasets (advanced microscopy, MRI, PET, SPECT, CT) with functional read-outs (fMRI, EEG, MEG, electrophysiology, behaviour and clinical evaluation) and a molecular context (e.g., fluid biomarkers, genetic models, spatial omics) to achieve unprecedented insight into the nervous system and mechanisms of disease. Biologically, μNEURO spans a variety of neurological disorders including neurodegeneration, movement disorders, spinal cord and traumatic brain injury, glioblastoma and peripheral neuropathies, which are investigated in a variety of complementary model systems ranging from healthy control and patient-derived organoids and assembloids to fruit flies, rodents, and humans. With close collaboration between fundamental and preclinical research teams, method developers, and clinical departments at the University Hospital Antwerp (UZA), μNEURO effectively encompasses a fully translational platform for bench-to-bedside research. Now that we have intensified the interaction, in the next phase, μNEURO intends to formalize the integration by securing additional large-scale international research projects, by promoting the interaction between its members and core facilities and by fuelling high-risk-high-gain research within the hub and beyond. This way, μNEURO will foster breakthroughs for the neuroscience community. In addition, by focusing on technological and biological innovations that will streamline the translational pipeline for discovery and validation of novel biomarkers and therapeutic compounds, μNEURO aims to generate a long-term societal impact on the growing burden of rare and common diseases of the nervous system, connecting to key research priorities of the University of Antwerp, Belgium, and Europe.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Improving QMRI By Realizing trustworthy integration of AI in Neuro-imaging (IQ-BRAIN). 01/12/2024 - 30/11/2028

Abstract

MRI is a key methodology in modern neuroimaging, but conventional MRI relies on visual interpretation of intensity differences in the images, which is heavily dependent on scanner settings. Quantitative MRI (qMRI) is an attractive alternative MRI method that allows quantitative measurement of physical tissue parameters, enabling objective comparison between patients and across time. Moreover, qMRI facilitates early detection of pathological changes in the brain resulting from neurological disorders such as multiple sclerosis. Unfortunately, and despite the demonstrated potential in research settings, the implementation of qMRI in routine clinical practice remains limited due to long scan and post-processing times. While recent developments in artificial intelligence have the potential to accelerate and improve medical imaging pipelines, reduced transparency about the underlying processes, the lack of training data sets and limited information about the accuracy of the results has limited its use for clinical qMRI applications so far. In IQ-BRAIN, we propose a unique research and training programme that tackles this urgent need for improved and accelerated qMRI methodology for neuroimaging applications. By integrating both physics-based models and trustworthy artificial intelligence methods along the qMRI pipeline, our innovative approach combines the best of both worlds. IQ-BRAIN will prepare the next generation of qMRI specialists trained in the different aspects of the qMRI-neuroimaging pipeline, that can bridge the gap between qMRI method development and clinical need. Through a training programme of network-wide events, international secondments, and strong interaction between partners from academia, industry and hospitals, IQ-BRAIN offers early-stage researchers a rich combination of knowledge, expertise and essential transferable skills that prepares them for a thriving career as R&D professionals in the qMRI field.

Researcher(s)

Research team(s)

Project website

Project type(s)

  • Research Project

Temporal profiling of neuroplasticity in the brain following spinal cord injury towards improved functional recovery. 01/11/2024 - 31/10/2026

Abstract

Traumatic spinal cord injury (SCI) is characterized by sensory, motor and autonomic deficits. Following a SCI, neuroplasticity levels are increased in the entire central nervous system, which is associated with functional recovery in people with SCI. Several neuro-imaging techniques are used to visualize this neuroplasticity. However, in the studies conducted in humans to evaluate brain plasticity following SCI, the results are often contradictory. Therefore, our understanding of brain plasticity following SCI is still limited. Additionally, different types of therapy are being developed, including neuromodulation of specific spared pathways to improve functional recovery of patients. However, the location of brain stimulation is often hypothesis based. So, in this project I will develop in-vivo brain imaging methods to visualize functional and structural brain plasticity following SCI to identify potential targets for stimulation by using a rat model of SCI. Afterwards, I will also assess if stimulation of these potential targets improves functional recovery in that same rat model. This project will give us essential information about the association between neuroplasticity in the brain and functional recovery. Because our methods are highly translatable to human patients, the identification of unique patterns of neuroplasticity in individual patients by using neuro-imaging methods will pave the way to a more personalized medicine for SCI patients.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Establishing a multimodal preclinical imaging platform for the in vivo assessment of spinal cord injury outcome and therapeutic response. 01/11/2023 - 31/10/2025

Abstract

Spinal cord injury (SCI) is a devastating condition characterized by long-term motor and sensory neurological deficits, severely affecting the life of patients and their families. Although emerging therapeutic strategies focused on functional recovery are being explored, their development and translation to clinical use are severely limited by the lack of functional, objective, and non-invasive imaging biomarkers. Without quantifiable prognostic biomarkers, the clinical heterogeneity between SCI patients limits healthcare workers' qualitative measure of the potential future functional recovery. Using clinically relevant rat models, we propose a multimodal neuroimaging approach focused on synaptic and white matter markers to determine the prognostic and predictive outcome of (non)traumatic SCI. Longitudinal imaging with positron emission tomography (PET, for synaptic marker) and magnetic resonance imaging (MRI, for inflammation and white matter integrity) will be used for the establishment of a multimodal imaging platform to define lesions affecting the spinal cord to ultimately provide meaningful information related to lesion severity, functional outcome, and predictive value in a therapeutic context. Our platform will facilitate the interpretation of therapeutic results in preclinical studies, supporting the identification of most responsive treatment approaches and thus lowering the risks and costs for pharmaceutical companies' interest in the clinical translation of SCI.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Molecular Imaging Center Antwerp - Bio-Imaging Lab (MICA-BIL). 01/01/2022 - 31/12/2026

Abstract

The envisaged core facility brings together key preclinical imaging expertise and facilities within UA located in the Uc building on CDE. This joint venture provides preclinical imaging instruments of the highest performance of all Belgian universities. Concretely, the preclinical imaging infrastructure consists of 4 high‐field MRI systems with dedicated RF coils, 2 microPET/CT systems, 1 microSPECT/PET/CT. Using this equipment, virtual sections can be made through a living laboratory animal (which may or may not be a model for a particular pathology) enabling to quantitatively monitor various anatomical, morphological, physiological and molecular processes over time in the same animal. These techniques play a crucial role in basic and applied biomedical and pharmaceutical research and because the same techniques are used in humans/patients (translationally) they are vital for clinical diagnostics and research into early biomarkers of diseases and therapy follow‐up. In addition to the in‐vivo multi‐modal imaging systems, access to Bioluminescence/Fluorescence camera, animal monitoring (pulse oxygenation, temperature, respiration, ECG and EEG), microsurgery, and a radioprotected laboratory animal animalarium (150 laboratory animals single housed) are available.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

IMARK. Network for image-based biomarker discovery and evaluation 01/01/2021 - 31/12/2026

Abstract

IMARK capitalizes on the deeply rooted expertise in biomedical imaging at the University of Antwerp to push the boundaries of precision medicine. By resolving molecular and structural patterns in space and time, IMARK aims at expediting biomarker discovery and development. To this end, it unites research groups with complementary knowledge and tools that cover all aspects of imaging-centred fundamental research, preclinical validation and clinical evaluation. IMARK harbours high-end infrastructure for electron and light microscopy, mass spectrometry imaging, magnetic resonance imaging, computed tomography, positron emission tomography and single-photon emission computed tomography. Moreover, IMARK members actively develop correlative approaches that involve multiple imaging modalities to enrich information content, and conceive dedicated image analysis pipelines to obtain robust, quantitative readouts. This unique blend of technologies places IMARK in an excellent position as preferential partner for public-private collaborations and offers strategic advantage for expanding the flourishing IP portfolio. The major application fields of the consortium are neuroscience and oncology. With partners from the Antwerp University Hospital and University Psychiatric Centre Duffel, there is direct access to patient data/samples and potential for translational studies.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Multidimensional analysis of the nervous system in health and disease (µNeuro). 01/01/2020 - 31/12/2025

Abstract

Neuropathological research is an interdisciplinary field, in which imaging and image-guided interventions have become indispensable. However, the rapid proliferation of ever-more inquisitive technologies and the different scales at which they operate have created a bottleneck at the level of integration, a) of the diverse image data sets, and b) of multimodal image information with omics-based and clinical repositories. To meet a growing demand for holistic interpretation of multi-scale (molecule, cell, organ(oid), organism) and multi-layered (imaging, omics, chemo-physical) information on (dys)function of the central and peripheral nervous system, we have conceived μNEURO, a consortium comprising eight established teams with complementary expertise in neurology, biomedical and microscopic imaging, electrophysiology, functional genomics and advanced data analysis. The goal of μNEURO is to expedite neuropathological research and identify pathogenic mechanisms in neurodevelopmental and -degenerative disorders (e.g., Alzheimer's Disease, epilepsy, Charcot-Marie-Tooth disease) on a cell-to-organism wide scale. Processing large spatiotemporally resolved image data sets and cross-correlating multimodal images with targeted perturbations takes center stage. Furthermore, inclusion of (pre)clinical teams will accelerate translation to a clinical setting and allow scrutinizing clinical cases with animal and cellular models. As knowledge-hub for neuro-oriented image-omics, μNEURO will foster advances for the University and community including i) novel insights in molecular pathways of nervous system disorders; ii) novel tools and models that facilitate comprehensive experimentation and integrative analysis; iii) improved translational pipeline for discovery and validation of novel biomarkers and therapeutic compounds; iv) improved visibility, collaboration and international weight fueling competitive advantage for large multi-partner research projects.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Translational molecular imaging studies 01/01/2017 - 31/12/2024

Abstract

Huntington's disease (HD) is a dominantly inherited disorder characterized by a progressive neurodegeneration of the striatum that also involves other regions, primarily the cerebral cortex. Patients display progressive motor, cognitive, and psychiatric impairment. Symptoms usually start at midlife. The mutation responsible for this fatal disease is an abnormally expanded and unstable CAG repeat within the coding region of the gene encoding huntingtin. The pathogenic mechanisms by which mutant huntingtin cause neuronal dysfunction and cell death remain uncertain (Menalled, 2005). The mechanism underlying HD-related suppression of inhibition has been shown to include tonic activity of metabotropic glutamate receptor subtype 5 (mGluR5) as a pathophysiological hallmark (Dvorzhak, Semtner, Faber, & Grantyn, 2013) and inhibition of glutamate neurotransmission via specific interaction with mGluRs might be interesting for both inhibition of disease progression as well as early symptomatic treatment (Scheifer et al., 2004). With the objective to elucidate the role of glutamatergic pathways using small animal PET imaging, this study aims to use several PET imaging agents as tracers in a knock-in model of Huntington's disease.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Support maintenance scientific equipment (Bio-Imaging). 01/01/2005 - 31/12/2024

Abstract

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Long‐term functional re‐myelination and neuroprotection via a multi‐modal biomaterial system studied in vivo in a mouse model of Multiple Sclerosis (MS). 01/06/2023 - 31/05/2024

Abstract

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease affecting the central nervous system (CNS). The damage caused to the neurons disrupts the ability of parts of the nervous system to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and, sometimes, psychiatric problems. There is increasing evidence that a combination therapy will be necessary to achieve a significant slowing of MS progression. In this study, we will test - in vivo in a specific mouse model of MS - the efficacy of the small-molecular weight compound proliferation-inducing ligand (APRIL) in modulating the known myelination-inhibitory effects within MS, combined with a new device for their transcranial delivery. At first, we aim to assess the efficacy of the immune-modulating protein APRIL against de-myelination and inflammation, in vivo and longitudinally with Magnetic Resonance Imaging (MRI) within the Cuprizone mouse model of MS. In parallel to this, we aim to test the biocompatibility and transcranial delivery efficacy of a new delivery system (a modified Ommaya reservoir device - OM pod) developed within the Marie Skłodowska-Curie-PMSMatTrain consortium. Finally, we will evaluate longitudinally the efficacy of the combined APRIL OM pod-delivery to reduce inflammation and demyelination in vivo in the Cuprizone mouse model of MS. Such critically delivery of the therapeutics released from the hydrogel would represent a step change in the approach for treating MS.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Understanding therapeutic efficacy of calorie restriction in Alzheimer's disease: dynamic rsfMRI and vascular reactivity as biomarkers in an AD rat model 01/09/2021 - 31/08/2024

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function associated with Aβ -peptide plaques and neurofibrillary tangles. Because aging is the major risk factor for AD, and dietary energy restriction can retard aging processes in the brain, researchers have been testing the hypothesis that caloric restriction (CR) regimens can protect against cognitive decline. The exact mechanisms through which CR promotes health and lifespan are still not fully understood. Nevertheless, numerous studies were designed to unravel the responses to CR. There is increasing evidence that synaptic defects affect synaptic transmission mechanisms. These synaptic transmission deficits may influence the functional connectivity (FC) in the brain, by impairing communication between brain regions. FC can be measured using resting state functional MRI (rsfMRI), and is defined as the temporal correlation between low frequency fluctuations in the BOLD fMRI signal in distinct brain areas. RsfMRI has identified default mode and task positive network disruptions as promising biomarkers for AD. Recently, the rsfMRI field has seen a shift from 'static' BOLD signal analysis to more time-resolved dynamic analysis. Dynamic rsfMRI is a state-of-the-art approach, which has revealed new insights into the macro-scale organization of functional networks. While CR is already known to influence memory performance, tauopathy and Aβ plaque formation, AD patients also have cerebral amyloid angiopathy (CAA), which influences vascular reactivity and therefore neurovascular coupling. It is of interest to identify these early markers of pathology progression using non-invasive imaging, as well as monitor the effect of CR on CAA, cerebral blood flow (CBF) and vascular reactivity using arterial spin labeling. In contrast to the BOLD signal which depends on the local cerebral metabolic rate of oxygen, CBF and cerebral blood volume, pCASL provides an absolute measure that only reflects CBF and hence enables to further disentangle the BOLD response and associated FC analysis. An alternative to dietary CR are nutrients that mimic these beneficial effects on brain aging (CR mimetics). These compounds mimic the biochemical and functional effects of CR without the need to reduce energy intake. In this project, we will combine dynamic rsfMRI, pCASL and behavioral tests in a TgF344-AD rat model, which recapitulates the major hallmarks of AD. We postulate the hypotheses that early decreases in (dynamic) FC and CBF may be potential prognostic biomarkers of the long-term outcome (memory and neuropsychiatric deficits) in this AD rat model; that FC and CBF at the time point when behavioural deficits occur, may be predictive biomarkers of the therapy (i.e. CR); that CR alleviates both memory and neurovascular deficits in this AD rat model; and that CR mimetics provide a therapeutic alternative with the same effects on memory and vascular reactivity.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Upgrade of 9.4T Bruker BioSpec MRI imaging system to Avance NEO hardware architecture. 01/05/2020 - 30/04/2024

Abstract

Upgrade of the hardware of existing equipment (9.4T MRI system from Bruker) to perform state of the art MRI investigations in the brain of small animals such as mice, rats and birds. This hardware upgrade will enable implementation of all new Bruker software packages.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Improved classification of Alzheimer's disease assessed from the slowly propagating waves of BOLD intensity, the Quasi-Periodic patterns, observed in dynamic resting-state fMRI in a AD rat model at rest and upon sensory stimulation. 01/01/2020 - 31/12/2023

Abstract

The rsfMRI field has seen a shift from 'static' blood-oxygen level dependent (BOLD) signal analysis to time-resolved dynamic analysis. Dynamic rsfMRI (drsfMRI) is a state-of-the-art approach, which has revealed many new insights into the macro-scale organization of functional networks and could already identify short-lasting large scale spatiotemporal patterns of BOLD activity, the 'Quasi-Periodic Patterns' (QPPs) in humans and rats. The QPPs describe recurring spatiotemporal neural events that display anti-correlation between two major brain networks (DMN and TPN), and therefore represent likely contributors to their functional organisation. Therefore, we reason that QPPs could provide new insights into AD network dysfunction and improve disease diagnosis. We postulate the hypothesis that QPPs would help understand the aberrant DMN and TPN Functional Connectivity (FC) observed in Alzheimer's disease, and might serve as a more sensitive biomarker than conventional rsfMRI measures, improving AD classification both in an early pre-plaque stage as late post-plaque stage. In this project, we will use state-of-the-art MRI to investigate: a) how QPPs in a rat model for AD (TgF344), differs from control animals, b) the vascular contribution to QPPs, c) how these QPPs might interact with sensory stimulation processing, d) how the QPPs acquired at rest or sensory stimulation contribute to the DMN and DMN-TPN FC, and how they improve AD classification.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Neurobiological predictors and social enhancers of vocal learning. 01/10/2019 - 30/09/2023

Abstract

Cultural transmission of vocal behaviours such as human speech or bird song, are greatly influenced by how adults interact with each other and with their young. Even though these behavioural observations are well established, surprisingly, the neurobiological mechanisms via which social enhancement potentiates learning are still poorly understood. Recently, we discovered that future song learning accuracy can be predicted very early in the song learning process based on the structural properties of the auditory areas of the zebra finch brain. Building further on this recent discovery, we aim to (1) identify the neurobiological basis of this prediction; (2) uncover the functional neural circuit that selectively responds to social factors inherent to song learning; and (3) unravel the functional and structural connectivity between the prediction site and remote brain areas. To reach these aims, we will use advanced magnetic resonance imaging (MRI) tools that enable to repeatedly quantify the structural architecture and connectivity of the zebra finch brain along the process of vocal learning. We will validate these insights by advanced histology. Moreover, this will be the first study to employ awake functional MRI in juvenile zebra finches to repeatedly probe brain activation patterns in response to specific stimuli presented by a video. To establish brain-behaviour relationship, we will evaluate the MRI outcome relative to several behavioural measures in the same bird.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Novel Biomaterial-based Device for the Treatment of Progressive MS - An Integrated Pan- European Approach (PMSMatTrain). 01/05/2019 - 31/01/2024

Abstract

PMSMatTrain is focusing on gaining a comprehensive understanding of the progressive (late degenerative phase) of multiple sclerosis (PMS) from basics to translation, fully supported by 8 beneficiaries (6 research institutions, 2 SMEs). Recruited ESRs will receive compulsory discipline-specific, generic and complementary transferable skills training. PMSMatTrain's Joint Research Education and Training programme (JRTP) will provide early stage researchers with high quality research and transferable skills training in intellectual property, leadership skills, innovation, regulatory affairs, entrepreneurship, gender policy, and medical device evaluation, which will ensure that they are immediately employable in industry. The consortium will develop a multi-modal hyaluronan-based medical device designed to release small molecular weight anti-inflammatory molecules (APRIL and sPIF) followed by remyelination and neuroprotective drugs (ibudilast and miconazole). PMSMatTrain will for the first time utilise these functionalised multi-modal biomimetic hyaluronan scaffolds as a tool to investigate cross-talk between signals arising due to chronic neuroinflammation and those leading to demyelination and axonal loss, while identifying molecular mechanisms that facilitate remyelination and neuroprotection in PMS. This approach could yield the first cortex-proximal and directed biomaterials-based disease-modifying therapy for PMS. These scaffolds will be tested in state of the art MS patient induced stem cell-derived oligodendrocyte cultures and organotypic cultures to investigate MS pathophysiology. In vivo responses will be characterised using field-leading MRI and mass spectrophotometry protocols. PMSMatTrain will also generate a clinically-relevant in silico model of drug elusion and dispersal within the CNS. Our industry partners will develop the end-device by providing standardised manufacturing protocols for scaled-up production and commercialisation of the cGMP product.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Improved classification of Alzheimer's disease: differentiation of slow propagating waves of BOLD intensity of dynamic rsfMRI in AD mice models in pre-plaque and post-plaque stages. 01/01/2019 - 31/12/2020

Abstract

There is increasing evidence that in neurodegenerative diseases (ND) synaptic defects affect synaptic transmission mechanisms. These synaptic transmission deficits may influence the functional connectivity (FC) in the brain, by impairing communication between brain regions. FC can be measured using resting state functional MRI (rsfMRI), and is defined as the temporal correlation between low frequency fluctuations in the blood-oxygen-level-dependent (BOLD) fMRI signal in distinct brain areas. Thus rsfMRI enables a nuanced appreciation of the system-scale network structure of the brain. It was reported that various topological properties of resting state functional networks correlate with higher cognitive functions and are susceptible to various pathological disruptions. Patients with Alzheimer's disease (AD) display aberrant brain function. RsfMRI has identified default mode (DMN) and task positive (TPN) network disruptions as promising biomarkers for AD. Recently, the rsfMRI field has seen a shift from 'static' BOLD signal analysis to more time-resolved dynamic analysis. Dynamic rsfMRI (drsfMRI) is a state-of-the-art approach, which has revealed many new insights into the macro-scale organization of functional networks and could already identify short-lasting large scale patterns of spatiotemporal BOLD activity, the 'Quasi- Periodic Patterns' (QPPs) in human and rats. Just recently, we observed the existence of QPPs of a set of large-scale Quasi-Periodic patterns in healthy anesthetized mice, similar as to what has been observed in other species, and which highly resemble known mouse resting state networks. The latter hints at a neuronal origin and a contribution to brain functional connectivity. We further illustrated how global signal regression affects the spatiotemporal dynamics, suggesting a potential role for its effect in conventional rsfMRI studies. Patterns could be observed reliably at the single subject level, marking promise in the advance towards more reliable rsfMRI research. Finally, the QPPs of neural activity, describe recurring spatiotemporal events that display DMN with TPN anti-correlation. QPPs therefore represent likely contributors to the DMN's and TPN's functional organisation. Therefore, we reason that QPPs could provide new insights into AD network dysfunction and improve disease diagnosis. We postulate the hypothesis that QPPs would help understand the aberrant DMN and TPN FC observed in Alzheimer's disease, and might serve as a more sensitive biomarker than conventional rsfMRI measures, improving AD classification both in an early pre-plaque stage as late post-plaque stage. In this project, we will use state-of-the-art MRI to investigate: a) how QPPs in a mouse models for AD (Tg2576), differs from control animals, b) how these QPPs might interact with sensory stimulation processing, c) how the QPP acquired at rest or sensory stimulation contribute to the DMN and DMN-TPN FC, and how they improve AD classification.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

How the interplay between basal forebrain neuronal populations determines brain state and how this is changed in Alzheimer's disease. 01/10/2018 - 31/12/2019

Abstract

During the last decades, the achievement of a better and improved quality of life has resulted in increased life expectancy. This is mainly due to progress in translational research and development of new therapeutic approaches. The downside is that age is one of the major risk factors for dementias and neurodegenerative disorders such as Alzheimer's disease (AD), characterized by a marked decline of cognitive functions (e.g. short- and long-term memory loss) and dysregulation of higher cortical functions (e.g. impaired judgement and thinking). The pathological condition of these diseases is disabling enough to compromise the activity of everyday life. Lengthening the life span has little value if the quality of life cannot be ensured. Unfortunately, the pathogenesis of AD is still far from being understood and this could be the reason why none of the currently available pharmacological therapies for this disease are satisfactory. Current treatments are purely symptomatic and do not act on the onset and progression of the pathology. It is well known that Basal Forebrain (BF) cholinergic neurons are prone to degeneration during aging as well as in dementias like AD. Furthermore, "the cholinergic hypothesis of geriatric cognitive dysfunction" is also supported by the significant correlation between the level of cholinergic depletion and the degree of cognitive deficits. Acetylcholine is a neuromodulator broadly investigated for its role in learning and memory, but it is not the only player in AD. In fact, in the BF, intermingled with cholinergic neurons, there are also two non-cholinergic neuronal types: GABAergic and glutamatergic neurons. It has been discovered that dysfunctions at the level of glutamatergic and GABAergic systems are involved as well in AD. Until recently, neuroscientists have limited the research of AD to the study of a single neuronal type (mainly BF cholinergic neurons), overlooking the possible role of non-cholinergic neuronal populations (GABAergic and glutamatergic). However, it is of the utmost importance to uncover the interaction between BF cholinergic and non-cholinergic neurons to develop novel strategies for the treatment of AD. The proposed research project aims to investigate the interaction between the three distinct BF populations and to elucidate how the BF cholinergic neuronal activity influences the other two BF neuronal types both in healthy and in pathological conditions. To date, it is still far from being understood how the neural state of the cholinergic neurons influences the GABAergic and glutamatergic neurons in the BF and how these, in turn, adjust cholinergic neuromodulation. We suggest to study the activity of BF neuronal populations and their interactions during spontaneous activity and determine the relationship of the activity of these three neuronal populations with whole brain functional connectivity. Then we will target and stimulate the BF cholinergic neurons using optogenetics to understand how it influences network interactions and to identify the optimal conditions of stimulation in an AD animal model that can induce network states as observed during spontaneous activity in healthy animals. To achieve these goals, we propose a methodological approach that is both innovative and multimodal because it combines cutting edge techniques such as fMRI tools, optogenetics and fiber-optic calcium recording. The results of this study will provide an increased and better understanding of BF neural circuitry, thus opening new future perspectives for the treatment of cognitive disorders.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Breakthroughs in Quantitative Magnetic resonance ImagiNg for improved Detection of brain Diseases (B-Q MINDED). 01/01/2018 - 31/03/2022

Abstract

Magnetic resonance imaging (MRI) is one of the most useful and rapidly growing neuroimaging tools. Unfortunately, signal intensities in conventional MRI images are expressed in relative units that depend on scanner hardware and acquisition protocols. While this does not hinder visual inspection of anatomy, it hampers quantitative comparison of tissue properties within a scan, between successive scans, and between subjects. In contrast, advanced quantitative MRI (Q-MRI) methods like MR relaxometry or diffusion MRI do enable absolute quantification of biophysical tissue characteristics. Evidence is growing that Q-MRI techniques detect subtle microscopic damage, enabling more accurate and early diagnosis of neurodegenerative diseases. However, due to the long scan time required for Q-MRI, causing discomfort for patients and limiting the throughput, Q-MRI methods have not entered clinical practice yet. B-Q MINDED aims to overcome the current barriers by developing widely-applicable post-processing breakthroughs for accelerating Q-MRI. The originality of B-Q MINDED lies in its ambition to replace the conventional rigid multi-step processing pipeline with an integrated single-step parameter estimation framework. This approach will unlock a wealth of options for optimization of Q-MRI. To accomplish this goal, B-Q MINDED proposes a collaborative cross-disciplinary approach (from basic MR physics to clinical applications) with strong involvement of industry.

Researcher(s)

Research team(s)

Project website

Project type(s)

  • Research Project

Breakthroughs towards high-resolution MR relaxometry within a clinically acceptable acquisition time for improved detection of brain diseases. 01/01/2017 - 31/03/2021

Abstract

Magnetic resonance imaging (MRI) is one of the most used neuroimaging techniques. Unfortunately, signal intensities in conventional MRI images are expressed in relative units that are dependent on hardware and software. This does not hinder visual inspection of anatomy, but severely complicates quantitative comparisons of the signal intensity within a scan, between successive scans, and between subjects. In contrast, MR relaxometry is an MRI technique that generates quantitative maps of absolute biophysical tissue characteristics (Deoni et al., 2010). Evidence is growing that MR relaxometry detects subtle microscopic tissue damage, which could lead to earlier diagnosis of various brain diseases including multiple sclerosis (Vrenken et al., 2006; Roosendaal et al., 2009 and Papadopoulos et al., 2010). Conventional MR relaxometry techniques, however, inherently require long scan times that impede the introduction in clinical practice. From a diagnostic perspective, long scan times increase the likelihood of motion artefacts, whereas from an economical perspective they reduce the throughput. In addition, long scan times cause discomfort for patients. For these reasons, MR relaxometry hasn't convinced the radiology community yet. The current project proposal aims to overcome these barriers by developing a radically new widely-applicable technological framework for accelerating MR relaxometry. At the end of this IOF SBO project, the feasibility and validity of our new approach for accelerated MR relaxometry will have been demonstrated. For final translation of the technology towards the market (and patients) we will team-up will industrial partners. Moreover, three companies (two MRI vendors and one specialized SME) already agreed to join the Industry Advisory Board and will support the project by providing early feedback. Finally, from a strategic perspective, this project bridges fundamental MR physics with applied bio-medical neuroimaging-MRI research. As such the project promotes cross-fertilization between the three Antwerp MRI-research groups (and faculties) involved. Hence, this research will enforce the mission and ambition of the University of Antwerp and its IOF consortium (Expert Group Antwerp Molecular imaging, EGAMI-image) to develop an IP portfolio and a strong translational and integrated MRI research program.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Ultrafast Functional Ultrasound (fUS) Imaging for highly resolved targetted mapping of functional connectivity in the awake mouse brain (FUSIMICE). 01/12/2015 - 30/11/2018

Abstract

In this project, a new imaging methodology (functional Ultra Sound) is developed, tested and compared with resting state functional Magnetic Resonance Imaging to study the functional connectivity between different brain circuits.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

The role of the extracellular matrix proteases MMP-9 and uPA in the development of posttraumatic epilepsy following traumatic brain injury. 01/10/2015 - 30/09/2017

Abstract

We propose a novel hypothesis for the development of PTE with a central role for ECM modulating components MMP-9 and uPA. TBI results in blood-brain barrier disruption, hyperexcitability and primary damage triggering repair mechanisms such as modulation of the ECM by proteases MMP-9 and uPA. These alterations in ECM proteases MMP-9 and uPA, followed by brain inflammation, induce abnormal synaptic remodeling and epileptogenesis, ultimately leading to PTE.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

WildCog: Evolution and local adaptation of cognitive abilities and brain structure in the wild. 01/09/2015 - 31/08/2018

Abstract

Cognition plays a critical role in how organisms interact with their social and ecological environment, and while the mechanisms underlying cognitive processes are becoming clearer, we still know little about the evolution of cognitive traits in natural populations. Cognitive abilities of organisms implicitly lie at the core of many fields since they determine in part how organisms compete with each other and acquire mates, how they find food and avoid being eaten, how they flexibly adjust to new contexts, and how they navigate landscapes. Many different cognitive capacities have been characterized and show within and across species variation, yet the extent to which this variation results from ecological imperatives faced by each species or population remains to be determined. Furthermore, despite progress in the neurophysiology of cognition in model organisms, we still have little understanding of the neural structure underlying cognitive traits important in wild organisms as well as how natural selection influences neural structure. Our goal is to examine the evolution of cognitive traits in a wild bird species by measuring multiple cognitive abilities, neural structure via MRI, and fitness to provide new insights into variation and the evolution of cognition. We will study 8 populations of great tits that lie along two ecological gradients (altitude, urbanization) that should favor different cognitive traits. Success in this ambitious project requires us to design new cognitive tests and a new touchscreen test system, new analytic methods (automated video analysis), explore brain structure in a non-model organism using MRI, and measure ecology and fitness of wild birds. To do this, we have assembled an interdisciplinary research group including specialties in brain imaging, animal cognition, computer sciences/ analytics, and evolutionary biology. This combination of expertise gives us the tools to succeed since each researcher has the appropriate skills to execute their portion of the study while contributing new methods and knowledge. In each case, there is considerable potential for novel contributions within each field as well as important advances for the interdisciplinary efforts linking evolution, cognition, and neurosciences. Combining data on fitness, cognition, and brain physiology on the same individuals in wild populations of birds will give us an unprecedented understanding of how selection operates on and shapes variation in cognition.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

The impact of reproductive axis hormones on changes in brain functional networks during healthy, accelerated and pathological aging (i.e. Alzheimer's disease). 01/11/2014 - 31/10/2018

Abstract

Aging has profound effects on many cellular processes that predispose to neurodegeneration, impairment in cognitive function, as well as changes in brain functional networks (e.g. default mode network (DMN) and its anticorrelated networks) and synaptic alterations. However, the key mechanisms orchestrating brain aging remain largely unknown. The hypothalamus, a key region of the hypothalamic–pituitary–gonadal axis (HPG-axis), is crucial for the neuroendocrine interaction between the central nervous system and various peripheral functions, but seems also involved in age-related neurodegeneration. This knowledge drives a new paradigm shift suggesting that the aging process is driven by the integration of immune and hormonal responses, with the hypothalamus having a leading role. A broad literature also suggests the involvement of menopause and age-related testosterone decline-induced alterations in HPG axis hormone levels in the etiology of Alzheimer's disease (AD), which is the most common form of dementia in elderly population. The overall goal of this preclinical project is to investigate patterns of functional alterations in the DMN and its anticorrelated networks using rsfMRI across from normal aging to accelerated and pathological aging (i.e, AD), and to explore whether differences in functional connectivity are associated with differences in HPG axis hormones and hypothalamic inflammation. The first aim of the study is to observe the short and long term effect of luteinizing hormone (LH) and estrogen hormone treatment, on the DMN and its anticorrelated networks. We hypothesize that loss of estrogenic support after ovariectomy will have significant effect on these networks, and these effect can be reversed after hormone therapy. The second aim of the project is to gain more insight into how the alterations of the GnRH-HPG axis receptor signalling alter functional networks of the brain during pathological aging (i.e. AD). The third aim is to examine the capacity of a GnRH agonist, leuprolide acetate, which decreases the release of LH, and amyloid load to modulate DMN and its anticorrelated networks, in the brain of Tg2576 carrying Swedish APP mutation.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Studying the interaction between synaptic loss, neuroinflammation and amyloid pathology in mouse models of Alzheimer's disease 01/01/2014 - 31/12/2017

Abstract

Alzheimer's disease (AD) is the most common form of dementia, with a high prevalence in the elderly population. Amyloid pathology and inflammatory cascades, which show toxic effects at the synapses, have been implied as possible driving forces behind AD. Gaining a deeper insight in these early events is crucial for a better understanding of the mechanisms that drive AD progression. In this project we focus on the interaction between synaptic deficits, amyloidosis and inflammation using resting-state functional Magnetic Resonance Imaging in a mouse model of amyloidosis..

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Functional imaging and analysis of tumors (FIAT). 01/01/2014 - 31/12/2015

Abstract

The FIAT consortium will make concrete improvements to quantitative functional imaging of tumours, which will be incorporated in clinical and preclinical application packages, clinical software modules, image analyses and ultimately routine clinical procedures.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Unravelling the complex interplay of Aβ, inflammation and synaptic defects in mouse models of Alzheimer's disease. 01/10/2013 - 31/12/2013

Abstract

Alzheimer's disease (AD) is the most common form of dementia, characterized by memory loss and cognitive and behavior changes. AD pathology consists of an increased formation of amyloid plaques, tau-fibrils, inflammation and neurodegeneration in the brain. Amyloidosis and inflammation, both early events, have gained interest as potential causes of AD, which puts the focus of many studies on these events. Soluble amyloid beta oligomers (sAβ) and inflammation lead to synaptic defects at an early stage, affecting synaptic transmission mechanisms (e.g. long term potentiation) necessary for learning and memory. This eventually results in cognitive defects arising in late stage AD. However, treatment studies targeting amyloidosis and inflammation have led to inconsistent results. A plausible explanation is that many studies have been focusing on amyloid plaques, while sAβ, occurring even earlier, is more likely to be the culprit behind the AD symptoms. Furthermore, amyloidosis and inflammation seem to be closely related, since tackling inflammation pre-and post-plaque stage show different effects on pathology i.e. amelioration and aggravation respectively. The synaptic defects caused by sAβ and inflammation may result in altered brain functional connectivity (FC), which can be measured in vivo using resting state functional MRI (rsfMRI) and which is defined as the temporal correlation of the low frequency fluctuations (LFF) in the Blood-Oxygenation-Level-Dependent (BOLD) signal of spatially distinct areas. Our hypothesis is that amyloidosis, inflammation and synaptic defects are closely related and influence each other starting from early stages in AD. They represent interesting targets for drug development but much is unknown about these events. We believe that unravelling this complex interplay in mouse models will be useful for studies in animals and AD patients. Furthermore, we believe that the synaptic defects in AD could be reflected as alterations in FC. This could mean that rsfMRI may represent an in vivo method to follow up synaptic integrity in different stages of disease and to monitor the effect of manipulations.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Research and applications in biological image and signal processing. 01/04/2013 - 30/03/2017

Abstract

The objective of the project is to develop a magnetic immunodiagnostic method for MRI - based assessment of brain tumors. Scientific problem: The role of different mechanisms in the progression of carcinogenesis process in brain tumors has not been fully identified. Hypothetic framework: We propose to explore three specifics mechanism of carcinogenesis: self-renewal process, cellular growth and proliferation and angiogenesis of the tumor; all of them, through the expression of molecular biomarkers (CD133, EGF-R and VEGF-R), its interactions and the role of these mechanisms in the carcinogenesis process. All of these mechanisms separately can be explored with single target, and has been explored since few decades ago, that is why we propose a multivariate approach, using multitarget contrast enhanced MRI techniques. We propose to use magnetic resonance approach to the molecular characterization of the disease, using both classic relaxation and magnetic transfer technique.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Longitudinal developmental changes in brain metabolism of the neonatal transgenic 'Huntington's Disease' rats, s tudied with MRspectroscopy, at rest and with a challenge. 01/01/2013 - 31/12/2015

Abstract

The aim of the project is to study the bioenergetics defects in HD pathogenesis using proton and phosphor magnetic resonance spectroscopy (1H MRS/31P MRS). More specifically, we want to study the longitudinal developmental changes in brain metabolism of the neonatal HD rat at different conditions: rest, during stimulation, and recovery. The work will shed new light on fundamental mechanisms of bioenergetics defects in HD pathogenesis, which may help provide useful biomarkers for disease onset that can be used to assess the effects of potential therapeutic agents for the disorder.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Diffusion Kurtosis Magnetic Resonance Imaging in Neurodevelopment and Neurodegeneration. 01/10/2012 - 31/03/2016

Abstract

This project represents a formal research agreement between UA and on the other hand Janssen Pharmaceutica. UA provides Janssen Pharmaceutica research results mentioned in the title of the project under the conditions as stipulated in this contract.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Optimized workflow for in vivo small animal diffusion weighted MRI studies of white matter diseases: from acquisition to quantification. 01/07/2012 - 30/06/2016

Abstract

While the number of applications of diffusion MRI has exploded in recent years, obtaining reliable and quantitative diffusion information remains a challenging task. In this project, we aim to develop diffusion weighted MRI (DWI) sequences and processing routines to obtain reliable diffusion measures within an acceptable acquisition time and at high spatial resolution to reduce partial volume effects. This would be of particular interest for in vivo pre-clinical research in small animals as mice in which the needed signal to noise ratio for reliable diffusion measures sets constraints on the spatial resolution and measure time. We will develop a diffusion –acquisition & reconstruction -workflow that reconstructs a high resolution isotropic DWI data from a set of multi-slice 2D diffusion weighted images -acquired with a 7 or 9.4 T Bruker MR scanner -with a high in-plane resolution and a lower through-plane resolution and in which the stacks of slices are differently orientated. The new reconstruction method needs to model both the different orientations of the MR images as the different orientations of the applied diffusion weighted gradients. For this super resolution at these high magnetic field, sampling the DWI with conventional fast echo planar imaging sequences will be (1) too sensitive to orientation dependent eddy current image distortions – which prevents the multi angle acquisitions and (2) suffers from local loss of signal due to B0-inhomogeneities. Therefore, we aim to develop the method based on DW-Fast Spin echo acquisition in which the images don't show B0-inhomogeneities problems and moreover can be acquired at different angles. First, we will optimize the DWI with Fast Spin Echo sampling and reconstruction. Based on this sequence, further developments will be performed to set the optimal acquisition scheme to get to super-resolution DWI: being the best combination of the set of orientations of the multi-slice stacks combined with the different directions of the DW gradients. Hereto, we can define different development steps which each will deal with specific MR acquisition and/or processing challenges : motion artifacts, multi-shot acquisition, minimization of eddy current effects, phase-wrapping, T2-modulation over k-space, denoising. The MR-sequences will be developed and implemented – in ParaVision software- on the Bruker MR scanners from the Bio-Imaging lab. The reconstruction algorithms will be developed in Matlab at the Vision lab. This new development can only be realized based on the experiences and close collaboration of both research labs.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Optimization and validation of a mouse model of atherosclerotic plaque rupture. 01/01/2011 - 31/12/2014

Abstract

The aims of the project are: 1) Further optimisation and characterisation of the model. We will investigate whether additional destabilising stimuli can augment and speed up the incidence of plaque rupture, which is important for the evaluation of plaque stabilising therapies. 2) Validation of this model with established plaque stabilising drugs such as statins. 3) Study of the effects of novel potential plaque stabilising therapies (phytosterols, NO-donor).

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Improvement of the image quality for fast Diffusion Tensor Imaging. 01/01/2008 - 31/12/2009

Abstract

Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) is a recently developed technique who permits to study the architecture of white brainmatter (WM) in vivo and in an non-invasive way. DT-MRI is based on the Brownian movement of H2O-molecules in biological tissue and makes it possible to determine the anisotropic diffusion of these molecules . This anisotropic diffusion can be related to aligned microstructures, like WM brain fibres, which has a great value in biomedical applications. Since a large amount of data is needed for this technique, it is desirable to use fast imaging sequences. However, these kind of sequences introduce specific artefacts in the images which degrade the quality of the DT-measurements. For this reason, several strategies will be used to upgrade this quality. The present acquisition standard for fast DTI, Echo Planar Imaging (EPI), is prone to severe susceptibility artefacts which introduce geometric distortions in the images. These artefacts are more explicit when working at higher field strengths (here: 7 Tesla and 9.4 Tesla). By using an adapted EPI-sequence, it is possible to measure the local susceptibility artefacts and to correct for distortions. Another strategy that will be used is to combine DTI with Fast Spin Echo (FSE). This technique should be less sensitive to susceptibility artefacts. A recent approach, in which multiple receivers are used (Parallel Imaging) will be used to reduce artefacts in DT-MRI.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Optimization of the image quality of fast Magnetic Resonance Diffusion Tenor Imaging through adapted acquisition and image processing. 01/01/2007 - 31/12/2008

Abstract

The framework of this project fits in the need to develop an optimized and fast DTI sequence suited to perform quantitative studies at high magnetic field strengths and enabling the follow up of the progression of diseases or possible therapies. To accomplish this, developments will be made both at the site of image acquisition and image post processing.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Corrections of EPI distorsions, necessarily for accurate high field functional Magnetic Resonance Imaging. 01/05/2003 - 30/04/2005

Abstract

): The use of Echo Planar Imaging (EPI) as a rapid Magnetic Resonance Imaging (MRI) technique, b1Jth in human as animal brain research, is susceptible to geometric distortions. In the frame of this project, new developments -both on the level of MR image acquisition and MR image processing will be made to correct for these EPI-distorsions. The developped correction technique will be implemented and validated in functional MRI (fMRI) studies perfonned in rats and songbirds.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Single grant for ranked but non-financed candidates for a FWO-aspirant mandate. 01/10/2001 - 30/09/2002

Abstract

Researcher(s)

Research team(s)

    Project type(s)

    • Research Project

    Functional MR Imaging (fMRI) of the cortex of the cerebellum of the rat. 01/05/1999 - 30/04/2001

    Abstract

    fMRI was up to now almost exclusively performed in human subjects and only few papers reveal the work done on small animals. This animal study exclusively deals with the brain cortex. However, the cerebellum has recently gained interest because it seems to have more functions than first expected. In the framework of this project we wish to study the tactile input projections to the cerebellum using fMRI.

    Researcher(s)

    Research team(s)

      Project type(s)

      • Research Project

      01/10/1997 - 30/09/1998

      Abstract

      Researcher(s)

      Research team(s)

        Project type(s)

        • Research Project

        Functional Magnetic Resonance Imaging (fMRI) of the cerebellar cortex of the rat 01/05/1997 - 30/04/1999

        Abstract

        fMRI was up to now almost exclusively performed on human subjects and very ew data exist on animals. Although the cerebellum is far more frequently activated that expected and therefore very interesting as a study object, fMRI was so far restricted to the cerebral cortex. We want to investigate the distribution of tactile inputs at the level of the upper lip of the rat in the cerebellar cortex of the rat. This will contribute to the unraveling of the underling mechanisms of cerebellar functioning.

        Researcher(s)

        Research team(s)

          Project type(s)

          • Research Project

          01/10/1992 - 30/09/1993

          Abstract

          Researcher(s)

          Research team(s)

            Project type(s)

            • Research Project