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01/06/2020 | neuroradiology   IF 2.2
Higher b-values improve the correlation between diffusion MRI and the cortical microarchitecture.
Mournet S, Okubo G, Koubiyr I, Zhang B, Kusahara H, Prevost VH, Ichinose N, Triaire B, Hiba B, Dousset V, Tourdias T

PURPOSE: In diffusion MRI (dMRI), it remains unclear to know how much increase of b-value is conveying additional biological meaning. We tested the correlations between cortical microarchitecture and diffusion metrics computed from standard (1000 s/mm(2)), high (3000 s/mm(2)), to very high (5000 s/mm(2)) b-value dMRI. METHODS: Healthy volunteers were scanned with a dMRI pulse sequence that was first optimized together with a T1-WI and T2-WI. Averaged cortical surface map of estimated myelin (T1-WI/T2-WI) was compared with surface maps of mean diffusivity (MD) computed from each b-value (MD1000, MD3000, and MD5000) and to surface map of mean kurtosis (MK computed from the 0-, 1000-, to 3000-s/mm(2) shells) in 360 cortical parcels using Spearman correlations, multiple linear regressions, and Akaike information criteria (AIC). RESULTS: Surface map from MD1000 showed variations not related to myelin but the MD3000 and MD5000 maps inversely mirrored estimated myelin map; lower MD values being observed in more myelinated cortical areas. MK mirrored myelinated cortical areas. Quantitatively, Spearman correlations between myelin and MD became more and more negative as long as b-values increased while the correlation was positive between myelin and MK. Multiple regression models confirmed negative associations between myelin and MD that were significantly better from MD1000 to MD3000 and MD5000 (R(2) = 0.33, p < 0.001; R(2) = 0.43, p < 0.001; and R(2) = 0.50, p < 0.001) and positive association between myelin and MK (R(2) = 0.53, p < 0.001). Comparisons of the 3 statistical models showed the best performances with MK and MD5000 (AICMK < AICMD5000 < AICMD3000 < AICMD1000). CONCLUSION: Higher b-values are more closely related to subtle cellular variations of the cortical microarchitecture.

06/2020 | j Neuroradiol   IF 3.4
New OFSEP recommendations for MRI assessment of multiple sclerosis patients: Special consideration for gadolinium deposition and frequent acquisitions.
Brisset JC, Kremer S, Hannoun S, Bonneville F, Durand-Dubief F, Tourdias T, Barillot C, Guttmann C, Vukusic S, Dousset V, Cotton F

PURPOSE: New multiple sclerosis (MS) disease-modifying therapies (DMTs), which exert beneficial effects through prevention of relapse, limitation of disability progression, and improvement of patients' quality of life, have recently emerged. Nonetheless, these DMTs are not without associated complications (severe adverse events like. progressive multifocal leukoencephalopathy). Patient follow-up requires regular clinical evaluations and close monitoring with magnetic resonance imaging (MRI). Detection of new T2 lesions and potential brain atrophy measurements contribute to the evaluation of treatment effectiveness. Current MRI protocols for MS recommend the acquisition of an annual gadolinium (Gd) enhanced MRI, resulting in administration of high volume of contrast agents over time and Gd accumulation in the brain. METHODS: A consensus report was established by neuroradiologists and neurologists from the French Observatory of MS, which aimed at reducing the number of Gd injections required during MS patient follow-up. RECOMMENDATIONS: The French Observatory of MS recommends the use of macrocyclic Gd enhancement at time of diagnosis, when a new DMT is introduced, at 6-month re- baseline, and when previous scans are unavailable for comparison. Gd administration can be performed as an option in case of relapse or suspicion of intercurrent disease such as progressive multifocal leukoencephalopathy. Other follow-up MRIs do not require contrast enhancement, provided current and previous MRI acquisitions follow the same standardized protocol including 3D FLAIR sequences.

02/2020 | Stroke   IF 7.2
Normal-Appearing White Matter Integrity Is a Predictor of Outcome After Ischemic Stroke.
Sagnier S, Catheline G, Dilharreguy B, Linck PA, Coupe P, Munsch F, Bigourdan A, Debruxelles S, Poli M, Olindo S, Renou P, Rouanet F, Dousset V, Berthoz S, Tourdias T, Sibon I

Background and Purpose- The aim of the present study was to evaluate the relationship between normal-appearing white matter (NAWM) integrity and postischemic stroke recovery in 4 main domains including cognition, mood, gait, and dependency. Methods- A prospective study was conducted, including patients diagnosed for an ischemic supratentorial stroke on a 3T brain MRI performed 24 to 72 hours after symptom onset. Clinical assessment 1 year after stroke included a Montreal Cognitive Assessment, an Isaacs set test, a Zazzo cancelation task, a Hospital Anxiety and Depression scale, a 10-meter walking test, and a modified Rankin Scale (mRS). Diffusion tensor imaging parameters in the NAWM were computed using FMRIB (Functional Magnetic Resonance Imaging of the Brain) Diffusion Toolbox. The relationships between mean NAWM diffusion tensor imaging parameters and the clinical scores were assessed using linear and ordinal regression analyses, including the volumes of white matter hyperintensities, gray matter, and ischemic stroke as radiological covariates. Results- Two hundred seven subjects were included (66+/-13 years old; 67% men; median National Institutes of Health Stroke Scale score, 3; interquartile range, 2-6). In the models including only radiological variables, NAWM fractional anisotropy was associated with the mRS and the cognitive scores. After adjusting for demographic confounders, NAWM fractional anisotropy remained a significant predictor of mRS (beta=-0.24; P=0.04). Additional path analysis showed that NAWM fractional anisotropy had a direct effect on mRS (beta=-0.241; P=0.001) and a less important indirect effect mediating white matter hyperintensity burden. Similar results were found with mean diffusivity, axial diffusivity, and radial diffusivity. In further subgroup analyses, a relationship between NAWM integrity in widespread white matter tracts, mRS, and Isaacs set test was found in right hemispheric strokes. Conclusions- NAWM diffusion tensor imaging parameters measured early after an ischemic stroke are independent predictors of functional outcome and may be additional markers to include in studies evaluating poststroke recovery.

10/2019 | j med imaging (bellingham)
Active learning strategy and hybrid training for infarct segmentation on diffusion MRI with a U-shaped network.
Olivier A, Moal O, Moal B, Munsch F, Okubo G, Sibon I, Dousset V, Tourdias T

Automatic and reliable stroke lesion segmentation from diffusion magnetic resonance imaging (MRI) is critical for patient care. Methods using neural networks have been developed, but the rate of false positives limits their use in clinical practice. A training strategy applied to three-dimensional deconvolutional neural networks for stroke lesion segmentation on diffusion MRI was proposed. Infarcts were segmented by experts on diffusion MRI for 929 patients. We divided each database as follows: 60% for a training set, 20% for validation, and 20% for testing. Our hypothesis was a two-phase hybrid learning scheme, in which the network was first trained with whole MRI (regular phase) and then, in a second phase (hybrid phase), alternately with whole MRI and patches. Patches were actively selected from the discrepancy between expert and model segmentation at the beginning of each batch. On the test population, the performances after the regular and hybrid phases were compared. A statistically significant Dice improvement with hybrid training compared with regular training was demonstrated ( p < 0.01 ). The mean Dice reached 0.711 +/- 0.199 . False positives were reduced by almost 30% with hybrid training ( p < 0.01 ). Our hybrid training strategy empowered deep neural networks for more accurate infarct segmentations on diffusion MRI.

06/2019 | Stroke   IF 6
Chronic Cortical Cerebral Microinfarcts Slow Down Cognitive Recovery After Acute Ischemic Stroke.
Sagnier S, Okubo G, Catheline G, Munsch F, Bigourdan A, Debruxelles S, Poli M, Olindo S, Renou P, Rouanet F, Dousset V, Tourdias T, Sibon I

Background and Purpose- Cortical cerebral microinfarcts (CMIs) have been associated with vascular dementia and Alzheimer disease. The aim of the present study was to evaluate the role of cortical CMI detected on 3T magnetic resonance imaging, on the evolution of cognition during the year following an acute ischemic stroke. Methods- We conducted a prospective and monocentric study, including patients diagnosed for a supratentorial ischemic stroke with a National Institutes of Health Stroke Scale score >/=1, without prestroke dementia or neurological disability. Cortical CMIs were assessed on a brain 3T magnetic resonance imaging realized at baseline, as well as markers of small vessel disease, stroke characteristics, and hippocampal atrophy. Cognitive assessment was performed at 3 time points (baseline, 3 months, and 1 year) using the Montreal Cognitive Assessment, the Isaacs set test, and the Zazzo's cancellation task. Generalized linear mixed models were performed to evaluate the relationships between the number of cortical CMI and changes in cognitive scores over 1 year. Results- Among 199 patients (65+/-13 years old, 68% men), 88 (44%) had at least one cortical CMI. Hypertension was the main predictor of a higher cortical CMI load (B=0.58, P=0.005). The number of cortical CMI was associated with an increase time at the Zazzo's cancellation task over 1 year (B=3.84, P=0.01), regardless of the other magnetic resonance imaging markers, stroke severity, and demographic factors. Conclusions- Cortical CMIs are additional magnetic resonance imaging markers of poorer processing speed after ischemic stroke. These results indicate that a high load of cortical CMI in patients with stroke can be considered as a cerebral frailty condition which counteracts to the recovery process, suggesting a reduced brain plasticity among these patients.

05/2019 | j stroke cerebrovasc dis
The Influence of Stroke Location on Cognitive and Mood Impairment. A Voxel-Based Lesion-Symptom Mapping Study.
Sagnier S, Munsch F, Bigourdan A, Debruxelles S, Poli M, Renou P, Olindo S, Rouanet F, Dousset V, Tourdias T, Sibon I

BACKGROUND AND PURPOSE: The role of stroke location as a determinant of mood and cognitive symptoms is still a matter of debate. The aim of this study was to identify the predictive value of ischemic stroke location, on a voxel basis, for mood and cognitive outcome. MATERIALS AND METHODS: A prospective monocentric study including patients with a supratentorial ischemic stroke was conducted. A 3 Tesla brain MRI was performed at baseline. Mood and cognition were assessed using Hospital Anxiety and Depression scale (HAD), apathy inventory (AI), and Montreal Cognitive Assessment scale subscores, performed at 3 months poststroke. Statistical maps of ischemic stroke location associated with 3 months mood and cognitive scores were obtained using a voxel-based lesion-symptom mapping approach (Brunner and Munzel test). Significant voxels (false discovery rate [FDR] corrected-P < .01) were identified using the standard Montreal Neurological Institute-152 space template. RESULTS: Two hundred and sixty-five nonsevere stroke patients were included (64% men, mean age 66 +/- 14, median National Institute of Health Stroke Score 3, interquartile range 2-6). Ischemic stroke location was not associated with HAD or AI scores. Language, abstraction, and delayed recall performances were mainly associated with left-side hemispheric lesions. Lesions in both hemispheres were associated with lower performances in visuospatial and executive functions, naming, attention, and orientation. CONCLUSION: Ischemic stroke location does not predict mood outcome at 3 months but is a determinant of cognitive outcome in specific domains.

05/2019 | Radiology   IF 7.6
Neurodegeneration of the Substantia Nigra after Ipsilateral Infarct: MRI R2* Mapping and Relationship to Clinical Outcome.
Linck PA, Kuchcinski G, Munsch F, Griffier R, Lopes R, Okubo G, Sagnier S, Renou P, Asselineau J, Perez P, Dousset V, Sibon I, Tourdias T

Background The substantia nigra (SN) is suspected to be affected after remote infarction, in view of its large array of connections with the supratentorial brain. Whether secondary involvement of SN worsens overall clinical outcome after a supratentorial stroke has not previously been studied. Purpose To assess longitudinal changes in SN R2* by using MRI in the setting of ipsilesional supratentorial infarct and the relationship of SN signal change to clinical outcome. Materials and Methods Participants prospectively included from 2012 to 2015 were evaluated at 24-72 hours (baseline visit) and at 1 year with MRI to quantify R2*. The SN was segmented bilaterally to calculate an R2* asymmetry index (SN-AI); greater SN-AI indicated greater relative R2* in the ipsilateral compared with contralateral SN. The 95th percentile of R2* (hereafter, SN-AI95) was compared according to infarct location with mixed linear regression models. We also conducted voxel-based comparisons of R2* and identified individual infarcted voxels associated with high SN-AI95 through voxel-based lesion-symptom mapping. Multivariable regression models tested the association between SN-AI95 and clinical scores. Results A total of 181 participants were evaluated (127 men, 54 women; mean age +/- standard deviation, 64.2 years +/- 13.1; 75 striatum infarcts, 106 other locations). Visual inspection, SN-AI95, and average maps consistently showed higher SN R2* at 1 year if ipsilateral striatum was infarcted than if it was not (SN-AI95, 4.25 vs -0.88; P < .001), but this was not observed at baseline. The striatal location of the infarct was associated with higher SN-AI95 at 1 year independently from infarct volume, SN-AI95 at baseline, microbleeds, age, and sex (beta = 4.99; P < .001). Voxel-based lesion-symptom mapping confirmed that striatum but also insula, internal capsule, and external capsule were associated with higher SN-AI95 at 1 year. SN-AI95 was an independent contributor of poor motor outcome (Box and Block Test, beta = -.62 points; P = .01). Conclusion In patients with stroke, greater substantia nigra R2*, likely reflective of greater iron content, can be observed at 1 year ipsilateral from remote infarcts of specific location, which is associated with worse motor function. (c) RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Vernooij in this issue.

07/02/2019 | Mult Scler   IF 5.6
White-matter-nulled MPRAGE at 7T reveals thalamic lesions and atrophy of specific thalamic nuclei in multiple sclerosis.
Planche V, Su JH, Mournet S, Saranathan M, Dousset V, Han M, Rutt BK, Tourdias T

BACKGROUND:: Investigating the degeneration of specific thalamic nuclei in multiple sclerosis (MS) remains challenging. METHODS:: White-matter-nulled (WMn) MPRAGE, MP-FLAIR, and standard T1-weighted magnetic resonance imaging (MRI) were performed on MS patients ( n = 15) and matched controls ( n = 12). Thalamic lesions were counted in individual sequences and lesion contrast-to-noise ratio (CNR) was measured. Volumes of 12 thalamic nuclei were measured using an automatic segmentation pipeline specifically developed for WMn-MPRAGE. RESULTS:: WMn-MPRAGE showed more thalamic MS lesions ( n = 35 in 9 out of 15 patients) than MP-FLAIR ( n = 25) and standard T1 ( n = 23), which was associated with significant improvement of CNR ( p < 0.0001). MS patients had whole thalamus atrophy ( p = 0.003) with lower volumes found for the anteroventral ( p < 0.001), the pulvinar ( p < 0.0001), and the habenular ( p = 0.004) nuclei. CONCLUSION:: WMn-MPRAGE and automatic thalamic segmentation can highlight thalamic MS lesions and measure patterns of focal thalamic atrophy.

15/02/2018 | J Neurol Sci   IF 2.4
Preliminary evidence of the cerebellar role on cognitive performances in clinically isolated syndrome.
Moroso A, Ruet A, Lamargue-Hamel D, Munsch F, Deloire M, Ouallet JC, Cubizolle S, Charre-Morin J, Saubusse A, Tourdias T, Dousset V, Brochet B

BACKGROUND: Cerebellar and cognitive dysfunction can occur early in clinically isolated syndrome (CIS). Eye tracking is a reliable tool for the evaluation of both subtle cerebellar symptoms and cognitive impairment. OBJECTIVES: To investigate the early cognitive profile using neuropsychological and ocular motor (OM) testing in CIS with and without cerebellar dysfunction with OM testing compared to healthy subjects (HS). METHODS: Twenty-eight patients and 12 HC underwent OM and neuropsychological testing. Cerebellar impairment was defined by the registration of saccadic intrusions and/or at least 10% of dysmetria during ocular motor recording. Visually guided saccade (VGS), memory-guided saccade (MGS) and antisaccade (AS) paradigms were compared to neuropsychological assessments. RESULTS: The group of patients with cerebellar dysfunction (n=16) performed worse on MGS latencies and error rates, and had worse working memory, executive function and information processing speed (IPS) z scores than patients without cerebellar dysfunction. IPS was correlated with the AS error rate in all patients and with the VGS error rate and the MGS final eye position ratio in cerebellar patients. CONCLUSION: Eye tracking is a sensitive tool to assess cognitive and cerebellar dysfunctions in CIS. In CIS patients, cerebellar impairment is associated with working memory, executive functions and IPS slowness.

30/01/2018 | Neuroimage   IF 5.4
Deciphering the microstructure of hippocampal subfields with in vivo DTI and NODDI: Applications to experimental multiple sclerosis.
Crombe A, Planche V, Raffard G, Bourel J, Dubourdieu N, Panatier A, Fukutomi H, Dousset V, Oliet S, Hiba B, Tourdias T

The hippocampus contains distinct populations of neurons organized into separate anatomical subfields and layers with differential vulnerability to pathological mechanisms. The ability of in vivo neuroimaging to pinpoint regional vulnerability is especially important for better understanding of hippocampal pathology at the early stage of neurodegenerative disorders and for monitoring future therapeutic strategies. This is the case for instance in multiple sclerosis whose neurodegenerative component can affect the hippocampus from the early stage. We challenged the capacity of two models, i.e. the classical diffusion tensor imaging (DTI) model and the neurite orientation dispersion and density imaging (NODDI) model, to compute quantitative diffusion MRI that could capture microstructural alterations in the individual hippocampal layers of experimental-autoimmune encephalomyelitis (EAE) mice, the animal model of multiple sclerosis. To achieve this, the hippocampal anatomy of a healthy mouse brain was first explored ex vivo with high resolution DTI and NODDI. Then, 18 EAE mice and 18 control mice were explored 20 days after immunization with in vivo diffusion MRI prior to sacrifice for the histological quantification of neurites and glial markers in each hippocampal layer. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) maps were computed from the DTI model while the orientation dispersion index (ODI), the neurite density index (NDI) and the volume fraction of isotropic diffusivity (isoVF) maps were computed from the NODDI model. We first showed in control mice that color-coded FA and ODI maps can delineate three main hippocampal layers. The quantification of FA, AD, RD, MD, ODI, NDI and isoVF presented differences within these 3 layers, especially within the molecular layer of the dentate gyrus which displayed a specific signature based on a combination of AD (or MD), ODI and NDI. Then, the comparison between EAE and control mice showed a decrease of AD (p=0.036) and of MD (p=0.033) selectively within the molecular layer of EAE mice while NODDI indices did not present any difference between EAE and control mice in any layer. Histological analyses confirmed the differential vulnerability of the molecular layer of EAE mice that exhibited decreased dendritic length and decreased dendritic complexity together with activated microglia. Dendritic length and intersections within the molecular layer were independent contributors to the observed decrease of AD (R(2)=0.37 and R(2)=0.40, p<0.0001) and MD (R(2)=0.41 and R(2)=0.42, p<0.0001). We therefore identified that NODDI maps can help to highlight the internal microanatomy of the hippocampus but NODDI still presents limitations in grey matter as it failed to capture selective dendritic alterations occurring at early stages of a neurodegenerative disease such as multiple sclerosis, whereas DTI maps were significantly altered.