Team, Visitors, External Collaborators
Overall Objectives
Research Program
Application Domains
Highlights of the Year
New Software and Platforms
New Results
Bilateral Contracts and Grants with Industry
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Section: New Results

Research axis 2: Applications in Neuroradiology and Neurological Disorders

Our objectives is also to provide new computational solutions for our target clinical applications (radiology, neurology, psychiatry and rehabilitation...), allowing a more appropriate representation of data for image analysis and the detection of biomarkers specific to a form or grade of pathology, or specific to a population of subjects. In this section, we present our contributions in different clinical applications.


Efficacy of EEG-fMRI Neurofeedback for stroke rehabilitation in relation to the DTI structural damage: a pilot study.

Participants : Giulia Lioi, Mathis Fleury, Christian Barillot, Isabelle Bonan.

Recent studies have shown the potential of neurofeedback (NF) for motor rehabilitation after stroke. The majority of these NF approaches have relied solely on one imaging technique: mostly on EEG recordings. Recent study have gone further, revealing the potential of integrating complementary techniques such as EEG and fMRI to achieve a more specific regulation. In this exploratory work, multisession bimodal EEG-fMRI NF for upper limb motor recovery was tested in four stroke patients.The feasibility of the NF training was investigated with respect to the integrity of the corticospinal tract (CST), a well-established predictor of the potential for clinical improvement. Results indicated that patients exhibiting a high degree of integrity of the ipsilesional CST showed significant increased activation of the ipsilesional M1 at the end of the training (p<<0.001, Wilcoxon test). These preliminary findings confirm the critical role of the CST integrity for stroke motor recovery and indicate that this is importantly related also to functional brain regulation of the ipsilesional motor cortex [43].

Multiple sclerosis

Tissue microstructure information from T2 relaxometry and diffusion MRI can identify multiple sclerosis (MS) lesions undergoing blood-brain barrier breakdown (BBB)

Participants : Olivier Commowick, Christian Barillot.

Gadolinium-based contrast agents (GBCA) play a critical role in identifying MS lesions undergoing BBB which is of high clinical importance. However, repeated use of GBCAs over a long period of time and the risks associated with administering it to patients with renal complications has mandated for greater caution in its usage. In this work we explored the plausibility of identifying MS lesions undergoing BBB from tissue microstructure information obtained from T2 relaxometry and dMRI data. We also proposed a framework to predict MS lesions undergoing BBB using the tissue microstructure information and demonstrated its potential on a test case [26].

Neural basis of irony in patients with Multiple Sclerosis: an exploratory fMRI study

Participants : Quentin Duché, Élise Bannier.

Irony is a form of non-literal language that is characterized by the opposition between the literal meaning of a statement and the message that the speaker wishes to convey. Knowledge about the neural bases of non-literal language has largely developed in recent years from injury studies or more recently through data from functional imaging studies. Multiple sclerosis (MS) is a neurodegenerative disease that, in addition to cognitive dysfunction, results in variable impairment of theory of mind and non-literal language skills. This work aims at exploring neural basis underpinning the comprehension of irony in MS patients compared to a group of healthy subjects. The results suggest that multiple sclerosis patients require higher left hemisphere resources than healthy controls to understand irony [32].

This work is done in collaboration with by Florian Chapelain (Pôle Saint Hélier), Philippe Gallien (Pôle Saint Hélier) and Virginie Dardier (Université Rennes 2).

Joint assessment of brain and spinal cord motor tract damage in patients with early relapsing remitting multiple sclerosis (RRMS): predominant impact of spinal cord lesions on motor function

Participants : Benoit Combès, Élise Bannier, Haykel Snoussi, Jean-Christophe Ferré, Christian Barillot.

The effect of structural multiple sclerosis damage to the corticospinal tract (CST) has been separately evaluated in the brain and spinal cord (SC), even though a cumulative impact is suspected. In this work, we evaluated CST damages on both the cortex and cervical SC, and examine their relative associations with motor function, measured both clinically and by electrophysiology. This study highlights the major contribution of SC lesions to CST damage and motor function abnormalities [8].

This work was done in collaboration with Anne Kerbrat (Neuropoly Montréal) and Raphael Chouteau (CHU Rennes).

Spatial distribution of multiple sclerosis lesions in the cervical spinal cord

Participants : Élise Bannier, Gilles Edan.

Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsing-remitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. With an automatic publicly-available analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterized by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalized lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (P < 0.001), which was further confirmed by absolute and normalized lesion volumes (P < 0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (P < 0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (P < 0.001); however when normalizing by each region, normalized lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (P < 0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than long disease duration. Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the distribution of spinal cord lesions in various patient groups [14].

This work was done in collaboration with Julien Cohen-Adad (Neuropoly, Montreal) and Anne Kerbrat (Neuropoly Montréal).

Automatic segmentation of the spinal cord and intramedullary multiple sclerosis lesions with convolutional neural networks

Participants : Élise Bannier, Gilles Edan.

The goal of this study was to develop a fully-automatic framework - robust to variability in both image parameters and clinical condition - for segmentation of the spinal cord and intramedullary MS lesions from conventional MRI data of MS and non-MS cases. Scans of 1042 subjects (459 healthy controls, 471 MS patients, and 112 with other spinal pathologies) were included in this multi-site study (n = 30). Data spanned three contrasts (T1-, T2-, and T2∗-weighted) for a total of 1943 vol and featured large heterogeneity in terms of resolution, orientation, coverage, and clinical conditions. The proposed cord and lesion automatic segmentation approach is based on a sequence of two Convolutional Neural Networks (CNNs). CNNs were trained independently with the Dice loss. When compared against manual segmentation, our CNN-based approach showed a median Dice of 95% vs. 88% for PropSeg (p ≤ 0.05), a state-of-the-art spinal cord segmentation method. Regarding lesion segmentation on MS data, our framework provided a Dice of 60%, a relative volume difference of -15%, and a lesion-wise detection sensitivity and precision of 83% and 77%, respectively. In this study, we introduce a robust method to segment the spinal cord and intramedullary MS lesions on a variety of MRI contrasts. The proposed framework is open-source and readily available in the Spinal Cord Toolbox.

This work was done in collaboration with Julien Cohen-Adad (Neuropoly, Montreal) and Anne Kerbrat (Neuropoly Montréal).

Arterial Spin Labeling in pediatric populations

Changes in brain perfusion in successive arterial spin labeling MRI scans in neonates with hypoxic-ischemic encephalopathy

Participants : Maia Proisy, Isabelle Corouge, Antoine Legouhy, Christian Barillot, Jean-Christophe Ferré.

The primary objective of this study was to evaluate changes in cerebral blood flow (CBF) using arterial spin labeling MRI between day 4 of life (DOL4) and day 11 of life (DOL11) in neonates with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia. The secondary objectives were to compare CBF values between the different regions of interest (ROIs) and between infants with ischemic lesions on MRI and infants with normal MRI findings. We prospectively included all consecutive neonates with HIE admitted to the neonatal intensive care unit of our institution who were eligible for therapeutic hypothermia. Each neonate systematically underwent two MRI examinations as close as possible to day 4 (early MRI) and day 11 (late MRI) of life. We proposed an innovative processing pipeline for morphological and ASL data suited to neonates that enable automated segmentation to obtain CBF values over ROIs. We evaluated CBF on two successive scanswithin thefirst 15 days of life in the same subjects. ASL imaging in asphyxiated neonates seems more relevant when used relatively early, in the first days of life. The correlation of intra-subject changes in cerebral perfusion between early and late MRI with neurodevelopmental outcome warrants investigation in a larger cohort, to determine whether the CBF pattern change can provide prognostic information beyond that provided by visible structural abnormalities on conventional MRI [18], [47].

Cerebral blood flow in sickle cell populations

White matter has impaired resting oxygen delivery in sickle cell patients

Participant : Julie Coloigner.

Although modern medical management has lowered overt stroke occurrence in patients with sickle cell disease (SCD), progressive white matter (WM) damage remains common. It is known that cerebral blood flow (CBF) increases to compensate for anemia, but sufficiency of cerebral oxygen delivery, especially in the WM, has not been systematically investigated. Cerebral perfusion was measured by arterial spin labeling in 32 SCD patients (age range: 10-42 years old, 14 males, 7 with hemoglobin SC, 25 hemoglobin SS) and 25 age and race-matched healthy controls (age range: 15-45 years old, 10 males, 12 with hemoglobin AS, 13 hemoglobin AA); 8/24 SCD patients were receiving regular blood transfusions and 14/24 non-transfused SCD patients were taking hydroxyurea. Imaging data from control subjects were used to calculate maps for CBF and oxygen delivery in SCD patients and their T-score maps. Whole brain CBF was increased in SCD patients with a mean T-score of 0.5 and correlated with lactate dehydrogenase (r2  = 0.58, P < 0.0001). When corrected for oxygen content and arterial saturation, whole brain and gray matter (GM) oxygen delivery were normal in SCD, but WM oxygen delivery was 35% lower than in controls. Age and hematocrit were the strongest predictors for WM CBF and oxygen delivery in patients with SCD. There was spatial co-localization between regions of low oxygen delivery and WM hyperintensities on T2 FLAIR imaging. To conclude, oxygen delivery is preserved in the GM of SCD patients, but is decreased throughout the WM, particularly in areas prone to WM silent strokes [7].

This work was done in collaboration with Natasha Leporé and her team, Children's hospital Los Angeles, University of Southern California, USA.

Alzheimer disease

Abnormal fMRI response in sub-hippocampal structures: how prior knowledge impairs memory in AD

Participants : Quentin Duché, Pierre-Yves Jonin.

Early Alzheimer's disease typically impairs associative learning abilities, up to 18 years before dementia. Importantly, patients' concerns refer to their daily routine, meaning that they lack associative memory for highly familiar stimuli. However, most of the tests involve much less familiar stimuli (e.g. isolated words). It follows that we ignore whether prior knowledge about memoranda alters memory formation and its neural correlates in Alzheimer’s Disease. Here, we aimed at manipulating prior knowledge available at encoding and repetition to investigate whether prior knowledge could alter the neural underpinnings of associative encoding, in a way sensitive to early AD. The results suggest that distinct forms of prior knowledge may drive partly non-overlapping brain networks at encoding, and in turn these regions differentially contribute to successful memory formation. Thus, our finding that sub-hippocampal, not hippocampal, activation underlie the inability of the patients to benefit remote prior knowledge in new learning opens perspectives for further diagnostic and prognostic markers development [37].

Learning what you know: how prior knowledge impairs new associative learning in early AD.

Participants : Pierre-Yves Jonin, Quentin Duché, Élise Bannier, Isabelle Corouge, Jean-Christophe Ferré, Christian Barillot.

While associative memory impairment is a core feature of prodromal Alzheimer’s Disease (AD), whether prior knowledge affects associative learning is largely overlooked. Stimuli repetition yields suppression or enhancement of the BOLD signal, allowing the functional mapping of brain networks. We addressed the role of prior knowledge in associative encoding by manipulating repetition and familiarity of the memoranda in a subsequent memory fMRI study design. 17 patients with prodromal AD (AD-MCI) and 19 Controls learned face-scene associations presented twice in the scanner. Pre-experimental knowledge trials (PEK) involved famous faces while in Experimental Knowledge trials (EK), unknown faces familiarized before scanning were used. Study events were sorted as associative hits, associative misses or misses after a recognition test outside the scanner. We computed the Repetition X Prior knowledge interaction contrast to test whether the encoding networks differed along with prior knowledge, then looked for subsequent associative memory effects in the resulting clusters. PEK and EK yielded similar associative memory performance in AD-MCI, while PEK increased associative memory by 28% in Controls. Repetition effects were modulated by Prior knowledge in Controls, but AD-MCI showed aberrant repetition effects. Subsequent memory effects were observed only in Controls for PEK in the right subhippocampal structures. By contrast, in both groups, EK triggered a subsequent memory effect in the right hippocampus. Provided that tau pathology starts within anterior subhippocampal regions in early AD, our findings that subhippocampal, not hippocampal, involvement underlies the inability of the patients to benefit from PEK open innovative clinical and research perspectives [38].


White matter abnormalities in depression: a categorical and phenotypic diffusion MRI study.

Participants : Julie Coloigner, Olivier Commowick, Isabelle Corouge, Christian Barillot.

Mood depressive disorder is one of the most disabling chronic diseases with a high rate of everyday life disability that affects 350 million people around the world. Recent advances in neuroimaging have reported widespread structural abnormalities, suggesting a dysfunctional frontal-limbic circuit involved in the pathophysiological mechanisms of depression. However, a variety of different white matter regions has been highlighted and these results lack reproducibility of such categorical-based biomarkers. These inconsistent results might be attributed to various factors: actual categorical definition of depression as well as clinical phenotype variability. In this study, we 1/ examined WM changes in a large cohort (114 patients) compared to a healthy control group and 2/ sought to identify specific WM alterations in relation to specific depressive phenotypes such as anhedonia (i.e. lack of pleasure), anxiety and psychomotor retardation –three core symptoms involved in depression. Consistent with previous studies, reduced white matter was observed in the genu of the corpus callosum extending to the inferior fasciculus and posterior thalamic radiation, confirming a frontal-limbic circuit abnormality. Our analysis also reported other patterns of increased fractional anisotropy and axial diffusivity as well as decreased apparent diffusion coefficient and radial diffusivity in the splenium of the corpus callosum and posterior limb of the internal capsule. Moreover, a positive correlation between FA and anhedonia was found in the superior longitudinal fasciculus as well as a negative correlation in the cingulum. Then, the analysis of the anxiety and diffusion metric revealed that increased anxiety was associated with greater FA values in genu and splenium of corpus callosum, anterior corona radiata and posterior thalamic radiation. Finally, the motor retardation analysis showed a correlation between increased Widlöcher depressive retardation scale scores and reduced FA in the body and genu of the corpus callosum, fornix, and superior striatum. Through this twofold approach (categorical and phenotypic), this study has underlined the need to move forward to a symptom-based research area of biomarkers, which help to understand the pathophysiology of mood depressive disorders and to stratify precise phenotypes of depression with targeted therapeutic strategies [9]. This work was done with Centre Hospitalier Guillaume Régnier, Academic Psychiatry Department, 35703 Rennes, France.

Structural connectivity analysis in treatment-resistant depression

Participants : Julie Coloigner, Isabelle Corouge, Christian Barillot.

Depressive disorder is characterized by a profound dysregulation of affect and mood as well as additional abnormalities including cognitive dysfunction, insomnia, fatigue and emotional disturbance. Converging evidence shows that a dysfunction in prefrontal-subcortical circuits is associated with depressive state. However, the process of treatment resistance was poorly studied. One study of functional magnetic resonance imaging has reported more disrupted connectivity in prefrontal areas and in thalamus for resistant (R) group (Lui et al., 2011). These observations suggest a modification of functional connectivity in the prefrontal-subcortical circuits in the R patients. Using graph theory-based analysis, we examined white matter changes in the organization of networks in R patients compared with non-resistant (NR) group. We revealed 15 areas with significant density differences in R patients compared to NR subjects. The NR depression seems associated with decreased connectivity among distributed limbic areas, particularly in the ACC and in basal ganglia. However, the R patients exhibit a reduced connectivity in anterior limb of internal capsule and genu of corpus callosum compared with NR patients. Combined with previous studies, which described a widespread disruption in prefrontal-subcortical networks, this result suggests a more important connectivity decrease in the frontal cortex, as well as a smaller reduction in the limbic circuit for the patients with pejorative outcome. These results were consistent with connectivity studies, which suggested that the degree of disruption could influence the resistance severity and that two distinct networks could be implicated in NR end R depression.  [27].

Prenatal exposure

Prenatal exposure to glycol ethers and motor inhibition function evaluated by functional MRI at the age of 10 to 12 years in the PELAGIE mother-child cohort

Participants : Élise Bannier, Christian Barillot.

Pregnant women are ubiquitously exposed to organic solvents, such as glycol ethers. Several studies suggest potential developmental neurotoxicity following exposure to glycol ethers with a lack of clarity of possible brain mechanisms. We investigated the association between urinary levels of glycol ethers of women during early pregnancy and motor inhibition function of their 10- to 12-year-old children by behavioral assessment and brain MR imaging. Prenatal urinary levels of two glycol ether metabolites were associated with poorer Go/No-Go task performance. Differential activations were observed in the brain motor inhibition network in relation with successful inhibition, but not with cognitive demand. Nevertheless, there is no consistence between performance indicators and cerebral activity results. Other studies are highly necessary given the ubiquity of glycol ether exposure [5].

This work is done in collaboration with Fabienne Pelé and Cécile Chevrier (IRSET). Anne Claire Binter defended her PhD in December 2019 supervised by Fabienne Pelé, Cécile Chevrier and Élise Bannier. t

Effect of prenatal organic solvent exposure on structural connectivity at childhood

Participants : Julie Coloigner, Élise Bannier, Jean-Christophe Ferré, Christian Barillot.

Glycol ethers are part of organic solvents. They are used in industry and at home during manufacturing or usage of products such as paints, cleaning agents and cosmetics. The specific detection of subtle, low-dose effects of early-life exposure to these solvents on neuropsychological performance in children is a trendy subject of investigation. Neuroimaging allows looking into brain function and identifying different cerebral connections that may be affected by these neurotoxicants. In this paper, we investigated the specific effects of prenatal low-level exposure to different glycol ethers, on brain development of children between 10 and 12 years old. Based on previous studies suggesting cognitive disabilities in the attention, inhibition and working memory, we proposed a structural connectivity analysis using graph theory restricted to the regions involved in these functions. Our results suggest a possible relationship between the attention, working memory and inhibition and prenatal exposure to specific glycol ethers, such as ethoxyacetic acid, ethoxyethoxyacetic acid and 2-butoxyacetic acid [28].

Cognitive food-choice task

Implemenation of a new food picture database in the context of fMRI and visual cognitive food-choice task in healthy volunteers

Participant : Élise Bannier.

This pilot study aimed at implementing a new food picture database in the context of functional magnetic resonance imaging (fMRI) cognitive food-choice task, with an internal conflict or not, in healthy normal- weight adults. The fMRI analyses showed that the different liking foods (i.e. foods with different hedonic appraisals) condition elicited the activation of dorsal anterior cingulate cortex, involved in internal conflict monitoring, whereas similar liking (ie, foods with similar hedonic appraisals) condition did not, and that low- energy (LE) food choice involved high-level cognitive processes with higher activation of the hippocampus (HPC) and fusiform gyrus compared to high-energy (HE) food choice. Overall, this pilot study validated the use of the food picture database and fMRI-based procedure assessing decision-making processing during a food choice cognitive task with and without internal conflict[15].

This work was done in collaboration with Yentl Gautier, Paul Meurice, Yann Serrand, Nicolas Coquery Romain Moirand and David Val-Laillet from the NuMeCan Institute (Nutrition Metabolisms Cancer, UMR 1241, Inserm - Université de Rennes 1) and INRA.