Marleen Verhoye

• University of Antwerp

The value of preclinical diffusion MRI (dMRI) is substantial. While dMRI enables in vivo non‐invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages including higher SNR and spatial resolution compared to in vivo studies, and...

Preclinical diffusion MRI (dMRI) has proven value in methods development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. While dMRI enables in vivo non‐invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI...

Small‐animal diffusion MRI (dMRI) has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be...

Introduction Dietary interventions such as caloric restriction (CR) exert positive effects on brain health. Unfortunately, poor compliance hinders the success of this approach. A proposed alternative is resveratrol (Rsv), a CR-mimetic known to promote brain health. Direct comparison between the effects of Rsv and CR on brain health is lacking, with...

Background Missense mutations in the HSPB8 gene, encoding the small heat shock protein B8, cause distal hereditary motor neuropathy (dHMN) or an axonal form of Charcot–Marie–Tooth disease (CMT subtype 2L). Mice expressing mutant Hspb8 (Lys141Asn) mimic the human disease, whereas mice lacking Hspb8 show no overt phenotype. We aimed to design an RNA...

Brain organoids encompass a large collection of in vitro stem cell–derived 3D culture systems that aim to recapitulate multiple aspects of in vivo brain development and function. First, this review provides a brief introduction to the current state-of-the-art for neuro-ectoderm brain organoid development, emphasizing their biggest advantages in com...

Preclinical diffusion MRI (dMRI) has proven value in methods development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI...

Background Huntington's disease (HD) is marked by irreversible loss of neuronal function for which currently no availability for disease‐modifying treatment exists. Advances in the understanding of disease progression can aid biomarker development, which in turn can accelerate therapeutic discovery. Methods We characterised the progression of alte...

Background: Amyloid-related imaging abnormalities (ARIA) have been reported with some anti-amyloid-β (Aβ) immunotherapy trials. They are detected with magnetic resonance imaging (MRI) and thought to represent transient accumulation of fluid/edema (ARIA-E) or microhemorrhages (ARIA-H). Although the clinical significance and pathophysiology are unkno...

Introduction: Dietary interventions such as caloric restriction (CR) exert positive effects on brain health. Unfortunately, poor compliance hinders the success of this approach. A proposed alternative is resveratrol (Rsv), a CR–mimetic known to promote brain health. Direct comparison between the effects of Rsv and CR on brain health is lacking, wit...

Echolocating bats are among the most social and vocal of all mammals. These animals are ideal subjects for functional MRI (fMRI) studies of auditory social communication given their relatively hypertrophic limbic and auditory neural structures and their reduced ability to hear MRI gradient noise. Yet, no resting-state networks relevant to social co...

This study investigates brain network alterations in the default mode-like network (DMLN) at early stages of disease progression in a rat model of Alzheimer’s disease (AD) with application in the development of early diagnostic biomarkers of AD in translational studies. Thirteen male TgF344-AD (TG) rats, and eleven male wild-types (WT) littermates...

Background: Huntington’s disease (HD) is marked by a CAG-repeat expansion in the huntingtin gene that causes neuronal dysfunction and loss, affecting mainly the striatum and the cortex. Alterations in the neurovascular coupling system have been shown to lead to dysregulated energy supply to brain regions in several neurological diseases, including...

Objective To compare the diagnostic performance of postmortem ultrasound (PMUS), 9.4 T magnetic resonance imaging (MRI) and microfocus computed tomography (micro‐CT) for the examination of early gestation fetuses. Method Eight unselected fetuses (10–15 weeks gestational age) underwent at least 2 of the 3 listed imaging examinations. Six fetuses un...

Alzheimer’s disease (AD) is a progressive neurodegenerative disease resulting in memory loss and cognitive decline. Synaptic dysfunction is an early hallmark of the disease whose effects on whole-brain functional architecture can be identified using resting-state functional MRI (rsfMRI). Insights into mechanisms of early, whole-brain network altera...

Neurodevelopmental disorders (NDDs) are a group of complex neurologic and psychiatric disorders. Functional and molecular imaging techniques, such as resting-state functional magnetic resonance imaging (rs-fMRI) and positron emission tomography (PET), can be used to measure network activity noninvasively and longitudinally during maturation in both...

Distinct resting-state networks (RSNs) are differentially altered in the course of Huntington’s disease (HD). However, these RSN changes are depicted using traditional functional connectivity analyses which ignore the dynamic brain states that constitute these RSNs and their time-dependent relationship. Dynamic states are represented by recurring s...

Background Alzheimer’s disease (AD) is a severe neurodegenerative disorder that is hallmarked by the progressive accumulation of amyloid beta (Aβ) and tau proteins in the brain, leading to dementia. Sleep alterations occur at early stages of AD, before cognitive symptoms become apparent, which could play an important role in the pathophysiology and...

Avian innate nestling begging calls are similar to human infant cries in the behavioral response they elicit. However, it remains unknown whether the auditory processing of innate begging calls changes in seasonal songbirds from non-breeding to breeding season when hormonal neuromodulation of the auditory forebrain occurs. An fMRI experiment was se...

Background Actual Flip angle Imaging (AFI) is a sequence used for B1 mapping, also embedded in the Variable flip angle with AFI for simultaneous estimation of T1, B1 and equilibrium magnetization. Purpose To investigate the design of a preparation module for AFI to allow a fast approach to steady state (SS) without requiring the use of dummy acqui...

The hippocampus plays a vital role in navigation, learning, and memory, and is affected in Alzheimer’s disease (AD). This study investigated the classification of AD-transgenic rats versus wild-type littermates using electrophysiological activity recorded from the hippocampus at an early, presymptomatic stage of the disease (6 months old) in the Tg...

Huntington’s disease (HD) is a neurodegenerative disorder caused by expanded (≥ 40) glutamine-encoding CAG repeats in the huntingtin gene, which leads to dysfunction and death of predominantly striatal and cortical neurons. While the genetic profile and clinical signs and symptoms of the disease are better known, changes in the functional architect...

Alzheimer’s disease (AD) is a severe neurodegenerative disorder caused by the accumulation of toxic proteins, amyloid-beta (Aβ) and tau, which eventually leads to dementia. Disease-modifying therapies are still lacking, due to incomplete insights into the neuropathological mechanisms of AD. Synaptic dysfunction is known to occur before cognitive sy...

Huntington's disease is an autosomal, dominantly inherited neurodegenerative disease caused by an expansion of the CAG repeats in exon 1 of the huntingtin gene. Neuronal degeneration and dysfunction that precedes regional atrophy result in the impairment of striatal and cortical circuits that affect the brain's large-scale network functionality. Ho...

Longitudinal MRI is an important diagnostic imaging tool for evaluating the effects of treatment and monitoring disease progression. However, MRI, and particularly longitudinal MRI, is known to be time consuming. To accelerate imaging, compressed sensing (CS) theory has been applied to exploit sparsity, both on single image as on image sequence lev...

Huntington’s disease (HD) is a neurodegenerative disorder caused by expanded (≥ 40) glutamine-encoding CAG repeats in the huntingtin gene, which leads to dysfunction and death of predominantly striatal and cortical neurons. While the genetic profile and clinical signs and symptoms of the disease are better known, changes in the functional architect...

Background: Huntington's diseaseis an autosomal, dominantly inherited neurodegenerative disease caused by an expansion of the CAG repeats in exon 1 of the huntingtin gene. Neuronal degeneration and dysfunction that precedes regional atrophy result in the impairment of striatal and cortical circuits that affect the brain’s large-scale network functi...

Huntington’s disease is an autosomal, dominantly inherited neurodegenerative disease caused by an expansion of the CAG repeats in exon 1 of the huntingtin gene. Neuronal degeneration and dysfunction that precedes regional atrophy result in the impairment of striatal and cortical circuits that affect the brain’s large-scale network functionality. Ho...

Background Imbalanced synaptic transmission appears to be an early driver in Alzheimer’s disease (AD) leading to brain network alterations. Early detection of altered synaptic transmission and insight into mechanisms causing early synaptic alterations would be valuable treatment strategies. This study aimed to investigate how whole-brain networks a...

Purpose To introduce a novel imaging and parameter estimation framework for accurate multi‐shot diffusion MRI. Theory and Methods We propose a new framework called ADEPT (Accurate Diffusion Echo‐Planar imaging with multi‐contrast shoTs) that enables fast diffusion MRI by allowing diffusion contrast settings to change between shots in a multi‐shot...

The septohippocampal pathway plays an important role in learning and memory. It projects from the medial septum-vertical limb of the diagonal band of Broca (MSDB) to the hippocampus and provides the latter with its main cholinergic innervation. To assess the importance of cholinergic selectivity and timing of MSDB stimulation in modulating learning...

The hippocampus is thought to guide navigation and has an essential contribution to learning and memory. Hippocampus is one of the brain regions impaired in Alzheimer's disease (AD), a neurodegenerative disease with progressive memory impairments and cognitive decline. Although successful treatments for AD are still not available, developing new st...

Thyroid hormones clearly play a role in the seasonal regulation of reproduction, but any role they might play in song behavior and the associated seasonal neuroplasticity in songbirds remains to be elucidated. To pursue this question, we first established seasonal patterns in the expression of thyroid hormone regulating genes in male European starl...

Background: Imbalanced synaptic transmission appears to be an early driver in Alzheimer’s Disease (AD) leading to brain network alterations. Early detection of altered synaptic transmission and insight into mechanisms causing early synaptic alterations would be valuable treatment strategies. This study aimed to investigate how whole-brain networks...

Quantitative Magnetic Resonance (MR) imaging provides reproducible measurements of biophysical parameters, and has become an essential tool in clinical MR studies. Unfortunately, 3D isotropic high resolution (HR) parameter mapping is hardly feasible in clinical practice due to prohibitively long acquisition times. Moreover, accurate and precise est...

This document includes supplementary material that complements the main body of the paper. In Section 1, we provide analytical derivations of the Jacobian and Hessian of the alternating minimization scheme which was used to obtain the joint Maximum a Posteriori estimates of the tissue and motion parameters. Next, Section 2 elaborates on the impleme...

Cerebral vascular abnormalities can have a large impact on brain function and have been frequently detected as a comorbidity in various neuropathologies. The mouse is the most common pre-clinical animal model used to investigate neuropathologies and thus cerebral vascular atlases of this species are indispensable. In particular, an atlas derived fr...

Traditionally, research unraveling seasonal neuroplasticity in songbirds has focused on the male song control system and testosterone. We longitudinally monitored the song behavior and neuroplasticity in male and female starlings during multiple photoperiods using Diffusion Tensor and Fixel-Based techniques. These exploratory data-driven whole-brai...

Premenopausal bilateral ovariectomy is considered to be one of the risk factors of Alzheimer's disease (AD). However, the underlying mechanisms remain unclear. Here, we aimed to investigate long-term neurological consequences of ovariectomy in a rodent AD model, TG2576 (TG), and wild-type mice (WT) that underwent an ovariectomy or sham-operation, u...

Alzheimer’s disease (AD), a neurodegenerative disorder marked by accumulation of extracellular amyloid-β (Aβ) plaques leads to progressive loss of memory and cognitive function. Resting-state fMRI (RS-fMRI) studies have provided links between these two observations in terms of disruption of default mode and task-positive resting-state networks (RSN...

Traditionally, research unraveling seasonal neuroplasticity in songbirds has focused on the male song control system and testosterone. We longitudinally monitored the song and neuroplasticity in male and female starlings during multiple photoperiods using Diffusion Tensor and Fixel-Based techniques. These exploratory data-driven whole-brain methods...

Background The abrupt loss of ovarian hormones before menopause, induced by oophorectomy, has been associated with accelerated aging, multimorbidity, and Alzheimer’s disease (AD). We investigated the impact of prolonged loss of ovarian hormones on AD progression in a transgenic mouse model of amyloid pathology using in vivo diffusion tensor MRI, re...

How do intrinsic brain dynamics interact with processing of external sensory stimuli? We sought new insights using functional magnetic resonance imaging to track spatiotemporal activity patterns at the whole brain level in lightly anesthetized mice, during both resting conditions and visual stimulation trials. Our results provide evidence that quas...

Alzheimer’s disease (AD), a neurodegenerative disorder marked by accumulation of extracellular amyloid-beta (Aβ) plaques leads to progressive loss of memory and cognitive function. Resting state fMRI (RS-fMRI) studies have provided links between these two observations in terms of disruption of default mode and task positive resting state networks (...

Purpose Echo planar imaging (EPI) is commonly used to acquire the many volumes needed for high angular resolution diffusion Imaging (HARDI), posing a higher risk for artifacts, such as distortion and deformation. An alternative to EPI is fast spin echo (FSE) imaging, which has fewer artifacts but is inherently slower. The aim is to accelerate FSE s...

Progressive accumulation of hyperphosphorylated tau is a hallmark of various neurodegenerative disorders including Alzheimer's disease. However, to date, the functional effects of tau pathology on brain network connectivity have been investigated to a limited extent. To directly interrogate the impact of tau pathology on functional brain connectivi...

The anterior cingulate area (ACC) is an integral part of the prefrontal cortex in mice and supports cognitive functions, including attentional processes, motion planning and execution as well as remote memory, fear and pain. Previous anatomical and functional imaging studies demonstrated that the ACC is interconnected with numerous brain regions, s...

Human speech and bird song are acoustically complex communication signals that are learned by imitation during a sensitive period early in life. Although the brain areas indispensable for speech and song learning are known, the neural circuits important for enhanced or reduced vocal performance remain unclear. By combining in vivo structural Magnet...

Development of the songbird brain provides an excellent experimental model for understanding the regulation of sex differences in ontogeny. Considering the regulatory role of the hypothalamus in endocrine, in particular reproductive, physiology, we measured the structural (volume) and molecular correlates of hypothalamic development during ontogeny...

Magnetic resonance imaging (MRI) based T1 mapping allows spatially resolved quantification of the tissue-dependent spin-lattice relaxation time constant T1, which is a potential biomarker of various neurodegenerative diseases, including Multiple Sclerosis, Alzheimer disease, and Parkinson’s disease. In conventional T1 MR relaxometry, a quantitative...

Learning has been proposed to coincide with changes in connections between brain regions. In the present study, we used resting-state fMRI (rsfMRI) to map brain-wide functional connectivity (FC) in mice that were trained in the hidden-platform version of the Morris water maze. C57BL6 mice were investigated in a small animal MRI scanner following 2,...

Adult neuroplasticity in the song control system of seasonal songbirds is largely driven by photoperiod-induced increases in testosterone. Prior studies of the relationships between testosterone, song performance and neuroplasticity used invasive techniques, which prevent analyzing the dynamic changes over time and often focus on pre-defined region...

Alzheimer's disease (AD) is the most common form of dementia in the elderly. According to the amyloid hypothesis, the accumulation and deposition of amyloid-beta (Aβ) peptides play a key role in AD. Soluble Aβ (sAβ) oligomers were shown to be involved in pathological hypersynchronisation of brain resting-state networks in different transgenic devel...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

To date, 3D high resolution (HR) quantitative T1 mapping is not feasible in clinical practice due to prohibitively long acquisition times. Recent work has shown that super-resolution reconstruction (SRR), in which a 3D HR T1 map is directly estimated from a set of low through-plane resolution (LR) multi-slice (ms) T1-weighted (T1w) images with diff...

Quantitative T1 mapping allows spatially resolved quantification of the tissue-dependent spin-lattice relaxation time constant T1. Prohibitively long acquisition times impede the introduction of 3D high resolution (HR) quantitative T1 mapping in clinical practice. Model-based super-resolution reconstruction (SRR), in which a 3D HR T1 map is directl...

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories worldwide. Here we descri...

Background: Although effective in reducing relapse rate and delaying progression, current therapies for multiple sclerosis (MS) do not completely halt disease progression. T cell autoimmunity to myelin antigens is considered one of the main mechanisms driving MS. It is characterized by autoreactivity to disease-initiating myelin antigen epitope(s)...

Background Alzheimer’s disease (AD) is the most common form of dementia in the elderly population. Currently, no effective cure is available for AD. According to the amyloid hypothesis, the accumulation and deposition of the amyloid-beta (Aβ) peptides plays a key role in AD pathology. Soluble Aβ (sAβ) oligomers were shown to be synaptotoxic and inv...

The anterior cingulate area (ACA) is an integral part of the prefrontal cortex in mice and has been implicated in several cognitive functions. Previous anatomical and functional imaging studies demonstrated that the ACA is highly interconnected with numerous brain regions acting as a hub region in functional networks. However, the importance of the...

How do intrinsic brain dynamics interact with processing of external sensory stimuli? We sought new insights using functional (f)MRI to track spatiotemporal activity patterns at the whole brain level in lightly anesthetized mice, during both resting conditions and visual stimulation trials. Our results provide evidence that quasiperiodic patterns (...

The default mode network is a large-scale brain network that is active during rest and internally focused states and deactivates as well as desynchronizes during externally oriented (top-down) attention demanding cognitive tasks. However, it is not sufficiently understood if salient stimuli, able to trigger bottom-up attentional processes, could al...

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories world-wide. Here we descr...

Different types of brain injury, such as status epilepticus (SE), trauma, or stroke may initiate the process of epileptogenesis and lead to the development of temporal lobe epilepsy. Epileptogenesis is characterized by an initial latent period during which impaired network communication and synaptic circuit alterations are occurring. Ultimately, th...

Background: Immune activation during pregnancy is an important risk factor for schizophrenia. Brain dysconnectivity and NMDA receptor (NMDAR) hypofunction have been postulated to be central to schizophrenia pathophysiology. The aim of this study was to investigate resting-state functional connectivity (resting-state functional MRI-rsfMRI), microst...

Micron-sized paramagnetic iron oxide particles (MPIO) are commonly used as contrast agents in magnetic resonance imaging (MRI) that produce negative contrast enhancement, i.e. darkening, on T2*-weighted images. However, estimation and quantification of MPIO in vivo is still challenging. This limitation mainly arises from smearing and displacement o...

The default mode network is a large-scale brain network that is active during rest and internally focused states and deactivates as well as desynchronizes during externally oriented (top-down) attention demanding cognitive tasks. However, it is not sufficiently understood if unpredicted salient stimuli, able to trigger bottom-up attentional process...

Human speech and bird song are acoustically complex communication signals that are learned by imitation during a sensitive period early in life. Although the neural networks indispensable for song learning are well established, it remains unclear which neural circuits differentiate good from bad song copiers. By combining in vivo structural Magneti...

The development and characterization of new improved animal models is pivotal in Alzheimer's Disease (AD) research, since valid models enable the identification of early pathological processes, which are often not accessible in patients, as well as subsequent target discovery and evaluation. The TgF344-AD rat model of AD, bearing mutant human amylo...

A large proportion of the population suffers from endocrine disruption, e.g., menopausal women, which might result in accelerated aging and a higher risk for developing cognitive disorders. Therefore, it is crucial to fully understand the impact of such disruptions on the brain to identify potential therapeutic strategies. Here, we show using resti...

The first months of life are characterized by massive neuroplastic processes that parallel the acquisition of skills and abilities vital for proper functioning in later life. Likewise, juvenile songbirds learn the song sung by their tutor during the first months after hatching. To date, most studies targeting brain development in songbirds exclusiv...

There is currently a lack of prognostic biomarkers to predict the different sequelae following traumatic brain injury (TBI). The present study investigated the hypothesis that subacute neuroinflammation and microstructural changes correlate with chronic TBI deficits. Rats were subjected to Controlled Cortical Impact (CCI) injury, sham surgery or sk...

Resting state (rs)fMRI allows measurement of brain functional connectivity and has identified default mode (DMN) and task positive (TPN) network disruptions as promising biomarkers for Alzheimer's disease (AD). Quasi-periodic patterns (QPPs) of neural activity describe recurring spatiotemporal patterns that display DMN with TPN anti-correlation. We...

Similar to human speech, bird song is controlled by several pathways including a cortico-basal ganglia-thalamo-cortical (C-BG-T-C) loop. Neurotoxic disengagement of the basal ganglia component, i.e. Area X, induces long-term changes in song performance, while most of the lesioned area regenerates within the first months. Importantly however, the ti...

Impairment of the metabotropic glutamate receptor 5 (mGluR5) has been implicated with various neurologic disorders. Although mGluR5 density can be quantified with the PET radiotracer [¹¹C]ABP688, the methods for reproducible quantification of [¹¹C]ABP688 PET imaging in mice have not been thoroughly investigated yet. Thus, this study aimed to assess...

Comparison of [11C]ABP688 striatal quantification in WT and HET Q175 mice (n = 6 per genotype) using volume of distribution (VT) based on Logan plot with AV shunt (inv) (A) and IDIF (B) as well as binding potential (BPND) using SRTM (C). WT, wild type; HET, heterozygous; AV, arteriovenous; IDIF, image-derived input function; SRTM, simplified refere...

Representative power analysis to detect striatal difference in [11C]ABP688 quantification between WT and HET Q175 mice at 6 months of age.

Average SUV TACs for the test and retest scans of WT and HET Q175 mice (n = 5 per genotype). STR, striatum; CB, cerebellum; WT, wild type; HET, heterozygous. Data are represented as mean ± standard error mean.

Relationship between VT and DVR-1 [11C]ABP688 quantification based on invasive (AV shunt) and noninvasive input function (IDIF). AV, arteriovenous; IDIF, image-derived input function; DVR, distribution volume ratio; r, Pearson's correlation; r2, coefficient of determination.

Correlations between DVR-1 and BPND for [11C]ABP688. AV, arteriovenous; IDIF, image-derived input function; DVR, distribution volume ratio; BPND, binding potential; SRTM, simplified reference tissue model; r, Pearson's correlation; r2, coefficient of determination.

Scan parameters for each of the performed studies. AV, arteriovenous; IDIF, image-derived input function; WT, wild type; HET, heterozygous.

"Dynamic resting state fMRI in mice: detection of Quasi-Periodic Patterns." This was the first abstract we have presented on the discovery of quasi-periodic patterns in mice. A research articles covering these findings is currently under production at Neuroimage, soon to appear!