Whether some gray matter (GM) regions are differentially vulnerable at the early stages of MS is still unknown. The objective of this study is to investigate whether deep and cortical GM are ...differentially vulnerable after a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS).
Fifty-six patients with CIS (PwCIS) and 38 healthy controls (HC) had conventional and diffusion tensor imaging (DTI) at baseline and 46 PwCIS and 20 HC were rescanned after 1 year. Deep GM (DGM) volumes, cortical thickness (CTh), and DTI metrics (FA: fractional anisotropy; MD: mean diffusivity) within these structures were calculated for each participant at each time-point and compared between PwCIS and HC. Linear regression models were used to investigate whether baseline DTI parameters could predict GM volume loss over time.
At baseline, GM volumes did not differ between PwCIS and HC, but hippocampal MD was higher in PwCIS than HC (
< 0.01). Over 1 year, GM alterations became more widespread with putamen and hippocampus volumes decreasing in PwCIS (
< 0.01), and cortical thinning in different parts of the cortex along with a significant increase of MD. Hippocampus MD at baseline could predict its volume loss (
= 0.159;
< 0.05) and cortical thinning was associated to microstructural damage (Spearman's rho ranging from -0.424 to -0.603 with
< 0.003).
Along with MS being a diffuse inflammatory disease, GM showed a differential vulnerability at the early stage spreading from hippocampus to the cortex. Hippocampus volume loss could be predicted by its MD at baseline.
Cognition and gait have often been studied separately after stroke whereas it has been suggested that these two domains could interact through a cognitive-motor interference.
To evaluate the ...influence of gait changes on cognitive outcome after an ischemic stroke (IS).
We conducted a prospective and monocentric study including patients admitted for an acute supratentorial IS with a National Institute of Health Stroke Score ≤ 15. Cognition, gait and motor disability were evaluated at baseline, 3 months and 1 year post-stroke, using the Montreal Cognitive Assessment (MoCA), the 10-m walking test (10-MWT) and the Fugl-Meyer motor assessment (FMMA). The effect of changes in 10-MWT over the year of follow-up on MoCA changes was estimated using a generalized linear mixed model with FMMA, age and gender as covariates.
Two hundred and Twelve patients were included (71% male, age 64 ± 13 years old). 10-MWT improved from baseline to 1 year (
< 0.001), as did MoCA (
< 0.001) and FMMA (
< 0.001) scores. Ninety-nine patients (47%) had a MoCA <26 at 1 year. Changes in 10-MWT were independently associated with changes in MoCA (β = -0.2, 95% CI -0.24 to -0.07, Bonferroni-corrected
-value = 0.002). Analyses of MoCA sub-scores suggested that changes in gait performance was associated with changes in executive functions and recall.
Gait performance is associated with cognitive outcome after a mild to moderate IS, suggesting that they should be managed together to improve post-stroke independence.
Summary Multiple sclerosis (MS) is most generally considered as a severe disease with high physical and mental risks of disability. Since the end of the 1990s, several high cost long-term ...disease-modifying treatments provided some clinical efficiency. However, patient's follow-up was needed for the detection and the assessment of their side-effects. The “Observatoire français de la sclérose en plaques” (OFSEP) project aims to improve the clinical, biological and imaging systematic longitudinal follow-up of patients. It should increase the quality, efficiency and safety of patients’ care, with a unique opportunity of large scale, about 41,000 patients followed in 62 French centers using the European Database for Multiple Sclerosis (EDMUS) software. OFSEP is divided into three working groups (clinical, biological and imaging). The imaging working group defines standards for routine MRI follow-up in the whole cohort and contains three subgroups: acquisition, workflow, and data processing. A common and feasible brain and spinal cord acquisition protocol has been defined by the acquisition group, and accepted by the OFSEP steering and scientific committees. This protocol can be implemented in all French MRI centers. The major MRI manufacturers have agreed to provide the dedicated collection of sequences as an “OFSEP box” with every software upgrade or new MRI machine. The new OFSEP protocol will provide a unique opportunity to study a population-based collection of data from people with MS.
The thalamus and its nuclei are largely indistinguishable on standard T1 or T2 weighted MRI. While diffusion tensor imaging based methods have been proposed to segment the thalamic nuclei based on ...the angular orientation of the principal diffusion tensor, these are based on echo planar imaging which is inherently limited in spatial resolution and suffers from distortion. We present a multi-atlas segmentation technique based on white-matter-nulled MP-RAGE imaging that segments the thalamus into 12 nuclei with computation times on the order of 10 min on a desktop PC; we call this method THOMAS (THalamus Optimized Multi Atlas Segmentation). THOMAS was rigorously evaluated on 7T MRI data acquired from healthy volunteers and patients with multiple sclerosis by comparing against manual segmentations delineated by a neuroradiologist, guided by the Morel atlas. Segmentation accuracy was very high, with uniformly high Dice indices: at least 0.85 for large nuclei like the pulvinar and mediodorsal nuclei and at least 0.7 even for small structures such as the habenular, centromedian, and lateral and medial geniculate nuclei. Volume similarity indices ranged from 0.82 for the smaller nuclei to 0.97 for the larger nuclei. Volumetry revealed that the volumes of the right anteroventral, right ventral posterior lateral, and both right and left pulvinar nuclei were significantly lower in MS patients compared to controls, after adjusting for age, sex and intracranial volume. Lastly, we evaluated the potential of this method for targeting the Vim nucleus for deep brain surgery and focused ultrasound thalamotomy by overlaying the Vim nucleus segmented from pre-operative data on post-operative data. The locations of the ablated region and active DBS contact corresponded well with the segmented Vim nucleus. Our fast, direct structural MRI based segmentation method opens the door for MRI guided intra-operative procedures like thalamotomy and asleep DBS electrode placement as well as for accurate quantification of thalamic nuclear volumes to follow progression of neurological disorders.
•White-matter nulled MP-RAGE sequence provides improved intra-thalamic contrast.•THOMAS exploits this improved contrast to segment 12 thalamic nuclei with excellent accuracy as measured by Dice against manual segmentation.•Volumetry results using THOMAS revealed atrophy of select nuclei in multiple sclerosis patients.•THOMAS can also be used to accurately predict the ventralis intermedius nucleus for deep brain stimulation targeting.
Magnetic resonance imaging is an established tool in the management of multiple sclerosis (MS). Loss of blood brain barrier integrity assessed by gadolinium (Gd) enhancement is the current standard ...marker of MS activity. To explore the complex cascade of the inflammatory events, other magnetic resonance imaging, but also positron emission tomographic markers reviewed in this article are being developed to address active neuroinflammation with increased sensitivity and specificity. Alternative magnetic resonance contrast agents, positron emission tomographic tracers and imaging techniques could be more sensitive than Gd to early blood brain barrier alteration, and they could assess the inflammatory cell recruitment and/or the associated edema accumulation. These markers of active neuroinflammation, although some of them are limited to experimental studies, could find great relevance to complete Gd information and thereby increase our understanding of acute lesion pathophysiology and its noninvasive follow-up, especially to monitor treatment efficacy. Furthermore, such accurate markers of inflammation combined with those of neurodegeneration hold promise to provide a more complete picture of MS, which will be of great benefit for future therapeutic strategies.
Assessment of ischemic lesions on computed tomography or MRI diffusion-weighted imaging (DWI) using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used to guide acute ...stroke treatment. However, it has never been defined how many voxels need to be affected to label a DWI-ASPECTS region ischemic. We aimed to assess the effect of various lesion load thresholds on DWI-ASPECTS and compare this automated analysis with visual rating.
We analyzed overlap of individual DWI lesions of 315 patients from the previously published predictive value of fluid-attenuated inversion recovery study with a probabilistic ASPECTS template derived from 221 CT images. We applied multiple lesion load thresholds per DWI-ASPECTS region (>0, >1, >10, and >20% in each DWI-ASPECTS region) to compute DWI-ASPECTS for each patient and compared the results to visual reading by an experienced stroke neurologist.
By visual rating, median ASPECTS was 9, 84 patients had a DWI-ASPECTS score ≤7. Mean DWI lesion volume was 22.1 (±35) ml. In contrast, by use of >0, >1-, >10-, and >20%-thresholds, median DWI-ASPECTS was 1, 5, 8, and 10; 97.1% (306), 72.7% (229), 41% (129), and 25.7% (81) had DWI-ASPECTS ≤7, respectively. Overall agreement between automated assessment and visual rating was low for every threshold used (>0%: κ
= 0.020 1%: κ
= 0.151; 10%: κ
= 0.386; 20% κ
= 0.381). Agreement for dichotomized DWI-ASPECTS ranged from fair to substantial (≤7: >10% κ = 0.48; >20% κ = 0.45; ≤5: >10% κ = 0.528; and >20% κ = 0.695).
Overall agreement between automated and the standard used visual scoring is low regardless of the lesion load threshold used. However, dichotomized scoring achieved more comparable results. Varying lesion load thresholds had a critical impact on patient selection by ASPECTS. Of note, the relatively low lesion volume and lack of patients with large artery occlusion in our cohort may limit generalizability of these findings.
Structural and functional connectivity abnormalities have been reported previously in multiple sclerosis. However, little is known about how each modality evolution relates to the other. Recent ...studies in other neurological disorders have suggested that structural-functional coupling may be more sensitive in detecting brain alterations than any single modality. Accordingly, this study aimed to investigate the longitudinal evolution of structural-functional coupling, both at the global and modular levels, in the first year following clinically isolated syndrome. We hypothesized that during the course of multiple sclerosis, patients exhibit a decoupling between functional and structural connectivity due to the disruptive nature of the disease. Forty-one consecutive patients with clinically isolated syndrome were prospectively enrolled in this study, along with 19 age-, sex- and educational level-matched healthy control subjects. These participants were followed for 1 year and underwent resting-state functional MRI and diffusion tensor imaging at each time point, along with an extensive neuropsychological assessment. Graph theory analysis revealed structural reorganization at baseline that appeared as an increase in the clustering coefficient in patients compared to controls (P < 0.05), as well as modular-specific alterations. After 1 year of follow-up, both structural and functional reorganization was depicted with abnormal modular-specific connectivity and an increase of the functional betweenness centrality in patients compared to controls (P < 0.01). More importantly, structural-functional decoupling was observed in the salience, visual and somatomotor networks. These alterations were present along with preserved cognitive performance at this stage. These results depict structural damage preceding functional reorganization at a global and modular level during the first year following clinically isolated syndrome along with normal cognitive performance, suggesting a compensation mechanism at this stage of the disease. Principally, structural-functional decoupling observed for the first time in multiple sclerosis suggests that functional reorganization occurs along indirect anatomical pathways.
Novel MR image acquisition strategies have been investigated to elicit contrast within the thalamus, but direct visualization of individual thalamic nuclei remains a challenge because of their small ...size and the low intrinsic contrast between adjacent nuclei. We present a step-by-step specific optimization of the 3D MPRAGE pulse sequence at 7T to visualize the intra-thalamic nuclei. We first measured T1 values within different sub-regions of the thalamus at 7T in 5 individuals. We used these to perform simulations and sequential experimental measurements (n=17) to tune the parameters of the MPRAGE sequence. The optimal set of parameters was used to collect high-quality data in 6 additional volunteers. Delineation of thalamic nuclei was performed twice by one rater and MR-defined nuclei were compared to the classic Morel histological atlas. T1 values within the thalamus ranged from 1400ms to 1800ms for adjacent nuclei. Using these values for theoretical evaluations combined with in vivo measurements, we showed that a short inversion time (TI) close to the white matter null regime (TI=670ms) enhanced the contrast between the thalamus and the surrounding tissues, and best revealed intra-thalamic contrast. At this particular nulling regime, lengthening the time between successive inversion pulses (TS=6000ms) increased the thalamic signal and contrast and lengthening the α pulse train time (N*TR) further increased the thalamic signal. Finally, a low flip angle during the gradient echo acquisition (α=4°) was observed to mitigate the blur induced by the evolution of the magnetization along the α pulse train. This optimized set of parameters enabled the 3D delineation of 15 substructures in all 6 individuals; these substructures corresponded well with the known anatomical structures of the thalamus based on the classic Morel atlas. The mean Euclidean distance between the centers of mass of MR- and Morel atlas-defined nuclei was 2.67mm (±1.02mm). The reproducibility of the MR-defined nuclei was excellent with intraclass correlation coefficient measured at 0.997 and a mean Euclidean distance between corresponding centers of mass found at first versus second readings of 0.69mm (±0.38mm). This 7T strategy paves the way to better identification of thalamic nuclei for neurosurgical planning and investigation of regional changes in neurological disorders.
•We optimized the MPRAGE sequence at 7T to enhance intra-thalamic T1 differences.•An inversion time that nearly nulls white matter enhances thalamus contrast.•In vivo 7T delineation of thalamic nuclei was reproducible and matched the atlas.•7T MPRAGE could improve surgical planning and studies of regional thalamic changes.
In this paper, we present an innovative MRI-based method for Alzheimer's Disease (AD) detection and mild cognitive impairment (MCI) prognostic, using lifespan trajectories of brain structures. After ...a full screening of the most discriminant structures between AD and normal aging based on MRI volumetric analysis of 3032 subjects, we propose a novel Hippocampal-Amygdalo-Ventricular Alzheimer score (HAVAs) based on normative lifespan models and AD lifespan models. During a validation on three external datasets on 1039 subjects, our approach showed very accurate detection (AUC ≥ 94%) of patients with AD compared to control subjects and accurate discrimination (AUC=78%) between progressive MCI and stable MCI (during a 3 years follow-up). Compared to normative modelling, classical machine learning methods and recent state-of-the-art deep learning methods, our method demonstrated better classification performance. Moreover, HAVAs simplicity makes it fully understandable and thus well-suited for clinical practice or future pharmaceutical trials.
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