Publications of Christophe Phillips
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See detailQuantitative MRI, EM head modelling and more: practical considerations and applications
Phillips, Christophe ULiege

Scientific conference (2021, November 03)

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See detailqMRI-BIDS: an extension to the brain imaging data structure for quantitative magnetic resonance imaging data
Karakuzu, Agah; Appelhoff, Stefan; Auer, Tibor et al

E-print/Working paper (2021)

The Brain Imaging Data Structure (BIDS) established community consensus on the organization of data and metadata for several neuroimaging modalities. Traditionally, BIDS had a strong focus on functional ... [more ▼]

The Brain Imaging Data Structure (BIDS) established community consensus on the organization of data and metadata for several neuroimaging modalities. Traditionally, BIDS had a strong focus on functional magnetic resonance imaging (MRI) datasets and lacked guidance on how to store multimodal structural MRI datasets. Here, we present and describe the BIDS Extension Proposal 001 (BEP001), which adds a range of quantitative MRI (qMRI) applications to the BIDS. In general, the aim of qMRI is to characterize brain microstructure by quantifying the physical MR parameters of the tissue via computational, biophysical models. By proposing this new standard, we envision standardization of qMRI which makes multicenter dissemination of interoperable data possible. As a result, BIDS can act as a catalyst of convergence between qMRI methods development and application-driven neuroimaging studies that can help develop quantitative biomarkers for neural tissue characterization. Finally, our BIDS extension offers a common ground for developers to exchange novel imaging data and tools, reducing the practical barriers to standardization that is currently lacking in the field of neuroimaging. [less ▲]

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See detailParkinson’s disease multimodal imaging: F-DOPA PET, neuromelanin-sensitive and quantitative iron-sensitive MRI
DEPIERREUX, Frédérique ULiege; PARMENTIER, Eric ULiege; MACKELS, Laurane ULiege et al

in NPJ Parkinson's Disease (2021)

Parkinson’s disease is a neurodegenerative synucleinopathy characterized by the degeneration of neuromelanin-containing dopaminergic neurons and deposition of iron in the substantia nigra (SN). How ... [more ▼]

Parkinson’s disease is a neurodegenerative synucleinopathy characterized by the degeneration of neuromelanin-containing dopaminergic neurons and deposition of iron in the substantia nigra (SN). How regional neuromelanin (NM) loss and iron accumulation within specific areas of SN relates to nigro-striatal dysfunction needs to be clarified. We measured dopaminergic function in pre- and post-commissural putamen by [18F]DOPA PET in twenty-three Parkinson’s disease (PD) patients and 23 healthy control (HC) participants in whom NM content and iron load was assessed in medial and lateral SN, respectively by neuromelanin-sensitive and quantitative R2* MRI. Data analysis consisted of voxelwise regressions testing the group effect and its interaction with NM or iron signals. In PD patients, R2* was selectively increased in left lateral SN as compared to healthy participants, suggesting a local accumulation of iron in Parkinson’s disease. By contrast, NM signal differed between PD and HC, without specific regional specificity within SN. Dopaminergic function in posterior putamen decreased as R2* increased in lateral SN, indicating that dopaminergic function impairment progresses with iron accumulation in the SN. Dopaminergic function was also positively correlated with NM signal in lateral SN, indicating that dopaminergic function impairment progresses with depigmentation in the SN. A complex relationship was detected between R2* in the lateral SN and NM signal in the medial substantia nigra. In conclusion, multimodal imaging reveals regionally-specific relationships between iron accumulation and depigmentation within the SN of Parkinson’s disease and provides in vivo insights in its neuropathology. [less ▲]

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See detailExploratory radiomic analysis of conventional versus quantitative brain MRI: Towards automatic diagnosis of early multiple sclerosis
Lavrova, Elizaveta ULiege; LOMMERS, Emilie ULiege; WOODRUFF, Henry et al

in Frontiers in Neuroscience (2021)

Conventional magnetic resonance imaging (cMRI) is poorly sensitive to pathological changes related to multiple sclerosis (MS) in normal-appearing white matter (NAWM) and grey matter (GM), with the added ... [more ▼]

Conventional magnetic resonance imaging (cMRI) is poorly sensitive to pathological changes related to multiple sclerosis (MS) in normal-appearing white matter (NAWM) and grey matter (GM), with the added difficulty of not being very reproducible. Quantitative MRI (qMRI) on the other hand attempts to represent physical properties of tissues, making it an ideal candidate for quantitative medical image analysis, or radiomics. We therefore hypothesized that qMRI-based radiomic features have added diagnostic value in MS compared to cMRI. This study investigated the ability of cMRI (T1w) and qMRI features extracted from WM, NAWM, and GM to distinguish between MS patients (MSP) and healthy control subjects (HCS). We developed exploratory radiomic classification models on a dataset comprising 36 MSP and 36 HCS recruited in CHU Liege, Belgium, acquired with cMRI and qMRI. For each image type and region of interest, qMRI radiomic models for MS diagnosis were developed on a training subset and validated on a testing subset. Radiomic models based on cMRI were developed on the entire training dataset and externally validated on open-source datasets with 167 HCS and 10 MSP. Ranked by region of interest, the best diagnostic performance was achieved in the whole WM. Here the model based on magnetization transfer imaging (a type of qMRI) features yielded a median area under the receiver operating characteristic curve (AUC) of 1.00 in the testing sub-cohort. Ranked by image type, the best performance was achieved by the magnetization transfer models, with median AUCs of 0.79 (0.69-0.90 90% CI) in NAWM and 0.81 (0.71-0.90) in GM. External validation of the T1w models yielded an AUC of 0.78 (0.47-1.00) in whole WM, demonstrating a large 95% CI and low sensitivity of 0.30 (0.10-0.70). This exploratory study indicates that qMRI Radiomics could provide efficient diagnostic information using NAWM and GM analysis in MSP. T1w radiomics could be useful for a fast and automated check of conventional MRI for WM abnormalities once acquisition and reconstruction heterogeneities have been overcome. Further prospective validation is needed involving more data for better interpretation and generalization of the results. [less ▲]

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See detailShamo v1.0 - Stochastic electromagnetic head modelling made easy
Grignard, Martin ULiege; Geuzaine, Christophe ULiege; Phillips, Christophe ULiege

Poster (2021, June)

We introduce a Python 3 package: “shamo”. It can perform mesh generation, electromagnetic simulations and sensitivity analysis.

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See detailTime course of cortical response complexity during extended wakefulness and its differential association with vigilance in young and older individuals
Gaggioni, Giulia ULiege; Shumbayawonda, Elizabeth; Montanaro, Umberto et al

in Biochemical Pharmacology (2021), epub ahead of print

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See detailVoxel-Based quantitative MRI reveals spatial patterns of grey matter alteration in multiple sclerosis
LOMMERS, Emilie ULiege; Guillemin, Camille ULiege; REUTER, Gilles ULiege et al

in Human Brain Mapping (2021), 42(4), 1003-1012

Despite robust postmortem evidence and potential clinical importance of gray matter (GM) pathology in multiple sclerosis (MS), assessing GM damage by conventional magnetic resonance imaging (MRI) remains ... [more ▼]

Despite robust postmortem evidence and potential clinical importance of gray matter (GM) pathology in multiple sclerosis (MS), assessing GM damage by conventional magnetic resonance imaging (MRI) remains challenging. This prospective cross-sectional study aimed at characterizing the topography of GM microstructural and volumetric alteration in MS using, in addition to brain atrophy measures, three quantitative MRI (qMRI) parameters—magnetization transfer (MT) saturation, longitudinal (R1), and effective transverse (R2*) relaxation rates, derived from data acquired during a single scanning session. Our study involved 35 MS patients (14 relapsing–remitting MS; 21 primary or secondary progressive MS) and 36 age-matched healthy controls (HC). The qMRI maps were computed and segmented in different tissue classes. Voxel-based quantification (VBQ) and voxelbased morphometry (VBM) statistical analyses were carried out using multiple linear regression models. In MS patients compared with HC, three configurations of GM microstructural/volumetric alterations were identified. (a) Co-localization of GM atrophy with significant reduction of MT, R1, and/or R2*, usually observed in primary cortices. (b) Microstructural modifications without significant GM loss: hippocampus and paralimbic cortices, showing reduced MT and/or R1 values without significant atrophy. (c) Atrophy without significant change in microstructure, identified in deep GM nuclei. In conclusion, this quantitative multiparametric voxel-based approach reveals three different spatially-segregated combinations of GM microstructural/volumetric alterations in MS that might be associated with different neuropathology. [less ▲]

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See detailshamo: A tool for electromagnetic modelling, simulation and sensitivity analysis of the head
Grignard, Martin ULiege; Geuzaine, Christophe ULiege; Phillips, Christophe ULiege

E-print/Working paper (2021)

Accurate electromagnetic modelling of the head of a subject is of main interest in the fields of source reconstruction and brain stimulation. Those processes rely heavily on the quality of the model and ... [more ▼]

Accurate electromagnetic modelling of the head of a subject is of main interest in the fields of source reconstruction and brain stimulation. Those processes rely heavily on the quality of the model and, even though the geometry of the tissues can be extracted from magnetic resonance images (MRI) or computed tomography (CT), their physical properties such as the electrical conductivity are hard to measure with non intrusive techniques. In this paper, we propose a tool to assess the uncertainty in the model parameters as well as compute a parametric electroencephalography (EEG) forward solution and current distribution for transcranial direct current stimulation (tDCS). [less ▲]

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See detailRestoring statistical validity in group analyses of motion-corrupted MRI data
Lutti, Antoine; Corbin, Nadège; Ashburner, John et al

E-print/Working paper (2021)

Motion during the acquisition of magnetic resonance imaging (MRI) data degrades image quality, hindering our capacity to characterize disease in patient populations. Quality control procedures allow the ... [more ▼]

Motion during the acquisition of magnetic resonance imaging (MRI) data degrades image quality, hindering our capacity to characterize disease in patient populations. Quality control procedures allow the exclusion of the most affected images from analysis. However, the criterion for exclusion is difficult to determine objectively and exclusion can lead to a suboptimal compromise between image quality and sample size. We provide an alternative, data-driven solution that assigns weights to each image, computed from an index of image quality using restricted maximum likelihood. We illustrate this method through the analysis of brain MRI data. The proposed method restores the validity of statistical tests, and performs near optimally in all brain regions, despite local effects of head motion. This method is amenable to the analysis of a broad type of MRI data and can accommodate any measure of image quality. [less ▲]

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See detailPositive Effect of Cognitive Reserve on Episodic Memory, Executive and Attentional Functions Taking Into Account Amyloid-Beta, Tau, and Apolipoprotein E Status
Narbutas, Justinas ULiege; Chylinski, Daphné ULiege; Van Egroo, Maxime et al

in Frontiers in Aging Neuroscience (2021), 13

Studies exploring the simultaneous influence of several physiological and environmental factors on domain-specific cognition in late middle-age remain scarce. Therefore, our objective was to determine the ... [more ▼]

Studies exploring the simultaneous influence of several physiological and environmental factors on domain-specific cognition in late middle-age remain scarce. Therefore, our objective was to determine the respective contribution of modifiable risk/protective factors (cognitive reserve and allostatic load) on specific cognitive domains (episodic memory, executive functions, and attention), taking into account non-modifiable factors [sex, age, and genetic risk for Alzheimer’s disease (AD)] and AD-related biomarker amount (amyloid-beta and tau/neuroinflammation) in a healthy late-middle-aged population. One hundred and one healthy participants (59.4 ± 5 years; 68 women) were evaluated for episodic memory, executive and attentional functioning via neuropsychological test battery. Cognitive reserve was determined by the National Adult Reading Test. The allostatic load consisted of measures of lipid metabolism and sympathetic nervous system functioning. The amyloid-beta level was assessed using positron emission tomography in all participants, whereas tau/neuroinflammation positron emission tomography scans and apolipoprotein E genotype were available for 58 participants. Higher cognitive reserve was the main correlate of better cognitive performance across all domains. Moreover, age was negatively associated with attentional functioning, whereas sex was a significant predictor for episodic memory, with women having better performance than men. Finally, our results did not show clear significant associations between performance over any cognitive domain and apolipoprotein E genotype and AD biomarkers. This suggests that domain-specific cognition in late healthy midlife is mainly determined by a combination of modifiable (cognitive reserve) and non-modifiable factors (sex and age) rather than by AD biomarkers and genetic risk for AD. [less ▲]

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See detailAssociations between cognitive complaints, memory performance, mood and amyloid-β accumulation in healthy amyloid negative late-midlife individuals
Narbutas, Justinas ULiege; Van Egroo, Maxime; Chylinski, Daphné ULiege et al

in Journal of Alzheimer's Disease (2021), 83

Background. Cognitive complaints are gaining more attention as they may represent an early marker of increased risk for AD in individuals without objective decline at standard neuropsychological ... [more ▼]

Background. Cognitive complaints are gaining more attention as they may represent an early marker of increased risk for AD in individuals without objective decline at standard neuropsychological examination. Objective. Our aim was to assess whether cognitive complaints in late middle-aged individuals not seeking medical help are related to objective cognitive outcomes known as early markers for AD risk, concomitant affective state, and amyloid-β (Aβ) burden. Methods. Eighty-seven community-based cognitively normal individuals aged 50-69 years underwent neuropsychological assessment for global cognition, using Preclinical Alzheimer’s Cognitive Composite 5 (PACC5) score, and a more specific episodic memory measure. Affective state was based on self-assessment questionnaires for depression and anxiety. Aβ PET burden was assessed via [18F]Flutemetamol (N=84) and [18F]Florbetapir (N=3) uptake. Cognitive complaints were evaluated using Cognitive Difficulties Scale. Results. Higher cognitive complaints were significantly associated with lower episodic memory performance and worse affective state. Moreover, higher level of cognitive complaints was related to higher (but still sub-clinical) global Aβ accumulation (at uncorrected significance level). Importantly, all three aspects remained significant when taken together in the same statistical model, indicating that they explained distinct parts of variance. Conclusion. In healthy Aβ negative late middle-aged individuals, a higher degree of cognitive complaints is associated with lower episodic memory efficiency, more anxiety and depression, as well as, potentially, with higher Aβ burden, suggesting that complaints might signal subtle decline. Future studies should untangle how cognitive complaints in healthy aging populations are related to longitudinal changes in objective cognition and AD biomarker correlates. [less ▲]

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See detailEarly brainstem [18F]THK5351 uptake is linked to cortical hyper-excitability in healthy aging
Van Egroo, Maxime ULiege; Chylinski, Daphné ULiege; Narbutas, Justinas ULiege et al

in JCI Insight (2020), Online ahead of print

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See detailAssociation between sleep regulation and neuroimaging-derived myelin markers
Deantoni, Michele ULiege; Muto, Vincenzo ULiege; Hammad, Grégory ULiege et al

Conference (2020, September 22)

Introduction Sleep plays a crucial role in brain plasticity, and has been suggested to be involved in myelin organization. Here we assessed the association between sleep homeostatic responses and ... [more ▼]

Introduction Sleep plays a crucial role in brain plasticity, and has been suggested to be involved in myelin organization. Here we assessed the association between sleep homeostatic responses and quantitative MRI-derived myelin content in a sample of healthy young men. Methods: 238 male participants (age: 22.12.7) underwent an in-lab protocol to assess homeostatic responses in slow wave and REM sleep through a modulation of prior wakefulness and sleep duration. The protocol encompassed four conditions: a baseline night (BAS, duration adjusted on participant’s sleep-wake schedule), a 12h sleep extension night (EXT) followed by a 4-h nap and an 8-h sleep opportunity night (sleep saturation; SAT) and a 12h recovery night (REC) following 40-hours sleep deprivation. For each night, four sleep parameters were extracted: sleep slow wave activity at the beginning of the night (SWA0), its overnight exponential dissipation rate (tau), and overnight mean theta and beta power per REM epoch. Participants underwent a multiparameter brain MRI protocol at 3T to extract quantitative maps sensitive to different myelin biomarkers. F-contrasts were calculated to assess whether the modularity of sleep parameters across sleep conditions explains variance in myelin biomarkers. Reported statistics are family-wise-error corrected over the entire brain volume (pFWE <.05). Results: Slow wave sleep duration and SWA0 were modulated across all sleep conditions (REC>BAS>EXT>SAT; all p < 0.001), while REM sleep percentage significantly differed only between SAT and the other sleep contexts (F(3,1257)= 13.676743, p<.001). The modulation of NREM SWA0 was associated with myelin content in the medio-temporal lobe, encompassing the bilateral hippocampus and entorhinal cortex (grey and white matter), while the modulation of REM beta power was associated to myelin content in diffuse thalamocortical tracts and overhead cortices. Discussion: Spectral power in sleep-specific frequency bands across sleep homeostasis contexts is associated with myelin content in the hippocampus and surrounding cortices as well as thalamocortical fibers. The hippocampus has been proposed as a key player for temporal coupling of brain oscillations, while thalamocortical fibers myelination may facilitate the cortical response to sleep-dependent diencephalic activity. As myelin stands for conduction velocity, it could facilitate the modulation of brain electrical oscillations, and putatively also the homeostatic response of sleep. [less ▲]

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See detailPrecision of neural codes involved in storing phonological information in working memory
Bouffier, Marion ULiege; Kowialiewski, Benjamin ULiege; Attout, Lucie ULiege et al

Poster (2020, September 03)

Working memory (WM) precision is defined as the quality with which representations are stored in WM, and has to be distinguished from WM capacity, which is the quantity of information that can be ... [more ▼]

Working memory (WM) precision is defined as the quality with which representations are stored in WM, and has to be distinguished from WM capacity, which is the quantity of information that can be maintained in WM. This study is the first to assess the neural precision of WM traces for auditory-verbal information, using a functional magnetic resonance imaging (fMRI) approach. In this experiment, we asked 27 young adults to actively maintain 4-syllable nonwords during a 7-second interval. The nonwords were highly similar or dissimilar at the phonological level. Using multivariate voxel pattern analysis (MVPA), we explored the neural patterns associated with each nonword. We hypothesized that if auditory-verbal WM precision is limited, as indicated by the well-established phonological similarity effect in the WM literature, then dissimilar but not similar nonwords should be associated with distinctive neural patterns during WM, especially during the maintenance stage. Using Bayesian one sample t-tests on whole-brain classification accuracies, we observed that neural decoding of similar nonwords was at chance level, while neural decoding of dissimilar nonwords was clearly above chance during the maintenance stage. Searchlight analyses showed that the informative neural patterns were located in the dorsal language pathway known to support phonological processing. These results provide evidence for the neural basis of the phonological similarity effect in WM and the limited precision of phonological coding in WM. [less ▲]

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See detailMultiparameter quantitative histological MRI values in high-grade gliomas: a potential biomarker of tumor progression
REUTER, Gilles ULiege; Lommers, Emilie ULiege; Balteau, Evelyne ULiege et al

in Neuro-Oncology Practice (2020)

Background. Conventional MRI poorly distinguishes brain parenchyma microscopically invaded by high-grade gliomas (HGGs) from the normal brain. By contrast, quantitative histological MRI (hMRI) measures ... [more ▼]

Background. Conventional MRI poorly distinguishes brain parenchyma microscopically invaded by high-grade gliomas (HGGs) from the normal brain. By contrast, quantitative histological MRI (hMRI) measures brain microstructure in terms of physical MR parameters influenced by histochemical tissue composition. We aimed to determine the relationship between hMRI parameters in the area surrounding the surgical cavity and the presence of HGG recurrence. Methods. Patients were scanned after surgery with an hMRI multiparameter protocol that allowed for estimations of longitudinal relaxation rate (R1) = 1/T1, effective transverse relaxation rate (R2)*=1/T2*, magnetization transfer saturation (MTsat), and proton density. The initial perioperative zone (IPZ) was segmented on the postoperative MRI. Once recurrence appeared on conventional MRI, the area of relapsing disease was delineated (extension zone, EZ). Conventional MRI showing recurrence and hMRI were coregistered, allowing for the extraction of parameters R1, R2*, MTsat, and PD in 3 areas: the overlap area between the IPZ and EZ (OZ), the peritumoral brain zone, PBZ (PBZ = IPZ – OZ), and the area of recurrence (RZ = EZ – OZ). Results. Thirty-one patients with HGG who underwent gross-total resection were enrolled. MTsat and R1 were the most strongly associated with tumor progression. MTsat was significantly lower in the OZ and RZ, compared to PBZ. R1 was significantly lower in RZ compared to PBZ. PD was significantly higher in OZ compared to PBZ, and R2* was higher in OZ compared to PBZ or RZ. These changes were detected 4 to 120 weeks before recurrence recognition on conventional MRI. Conclusions. HGG recurrence was associated with hMRI parameters’ variation after initial surgery, weeks to months before overt recurrence. [less ▲]

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See detailGlobal sensitivity analysis of the EEG forward problem
Grignard, Martin ULiege; Geuzaine, Christophe ULiege; Phillips, Christophe ULiege

Poster (2020, June 24)

When carrying out an EEG experiment for source reconstruction, one has to provide both accurate geometry and electrical properties of the head tissues. Authors usually set the electrical conductivities ... [more ▼]

When carrying out an EEG experiment for source reconstruction, one has to provide both accurate geometry and electrical properties of the head tissues. Authors usually set the electrical conductivities based on values reported in the literature which have been shown to vary widely. Here we propose a method to assess the sensitivity of the EEG forward problem to those parameters using a realistic finite element (FEM) head model including white matter anisotropic tensor. The chosen sensitivity descriptor are the first and total order Sobol indices. [less ▲]

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See detailNeuroimaging data from multiple sources in PRoNTo v3.0: spatiotemporal patterns of face processing
David, Isabel A.; Schrouff, Jessica ULiege; Wu, Tong et al

Poster (2020, June)

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See detailA standard for the organization of quantitative MRI data: BIDS extension proposal 001
de Hollander, Gilles; Karakuzu, Agah; Appelhof, Stefan et al

Poster (2020, June)

Detailed reference viewed: 32 (4 ULiège)