Dynamic Evolution of Infarct Volumes at MRI in Ischemic Stroke Due to Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: The typical infarct volume trajectories in stroke patients, categorized as slow or fast progressors, remain largely unknown. This study aimed to reveal the characteristic spatiotemporal evolutions of infarct volumes caused by large vessel occlusion (LVO) and show that such growth charts help anticipate clinical outcomes. METHODS: We conducted a secondary analysis from prospectively collected databases (FRAME, 2017-2019; ETIS, 2015-2022). We selected acute MRI data from anterior LVO stroke patients with witnessed onset, which were divided into training and independent validation datasets. In the training dataset, using Gaussian mixture analysis, we classified the patients into 3 growth groups based on their rate of infarct growth (diffusion volume/time-to-imaging). Subsequently, we extrapolated pseudo-longitudinal models of infarct growth for each group and generated sequential frequency maps to highlight the spatial distribution of infarct growth. We used these charts to attribute a growth group to the independent patients from the validation dataset. We compared their 3-month modified Rankin scale (mRS) with the predicted values based on a multivariable regression model from the training dataset that used growth group as an independent variable. RESULTS: We included 804 patients (median age 73.0 years [interquartile range 61.2-82.0 years]; 409 men). The training dataset revealed nonsupervised clustering into 11% (74/703) slow, 62% (437/703) intermediate, and 27% (192/703) fast progressors. Infarct volume evolutions were best fitted with a linear (r = 0.809; p < 0.001), cubic (r = 0.471; p < 0.001), and power (r = 0.63; p < 0.001) function for the slow, intermediate, and fast progressors, respectively. Notably, the deep nuclei and insular cortex were rapidly affected in the intermediate and fast groups with further cortical involvement in the fast group. The variable growth group significantly predicted the 3-month mRS (multivariate odds ratio 0.51; 95% CI 0.37-0.72, p < 0.0001) in the training dataset, yielding a mean area under the receiver operating characteristic curve of 0.78 (95% CI 0.66-0.88) in the independent validation dataset. DISCUSSION: We revealed spatiotemporal archetype dynamic evolutions following LVO stroke according to 3 growth phenotypes called slow, intermediate, and fast progressors, providing insight into anticipating clinical outcome. We expect this could help in designing neuroprotective trials aiming at modulating infarct growth before EVT.

Microstructural Gray Matter Integrity Deteriorates After an Ischemic Stroke and Is Associated with Processing Speed.

Microstructural changes after an ischemic stroke (IS) have mainly been described in white matter. Data evaluating microstructural changes in gray matter (GM) remain scarce. The aim of the present study was to evaluate the integrity of GM on longitudinal data using mean diffusivity (MD), and its influence on post-IS cognitive performances. A prospective study was conducted, including supra-tentorial IS patients without pre-stroke disability. A cognitive assessment was performed at baseline and 1 year, including a Montreal Cognitive Assessment, an Isaacs set test, and a Zazzo cancelation task (ZCT): completion time and number of errors. A 3-T brain MRI was performed at the same two time-points, including diffusion tensor imaging for the assessment of GM MD. GM volume was also computed, and changes in GM volume and GM MD were evaluated, followed by the assessment of the relationship between these structural changes and changes in cognitive performances. One hundred and four patients were included (age 68.5 ± 21.5, 38.5% female). While no GM volume loss was observed, GM MD increased between baseline and 1 year. The increase of GM MD in left fronto-temporal regions (dorsolateral prefrontal cortex, superior and medial temporal gyrus, p < 0.05, Threshold-Free Cluster Enhancement, 5000 permutations) was associated with an increase time to complete ZCT, regardless of demographic confounders, IS volume and location, GM, and white matter hyperintensity volume. GM integrity deterioration was thus associated with processing speed slowdown, and appears to be a biomarker of cognitive frailty. This broadens the knowledge of post-IS cognitive impairment mechanisms.

Fast-spin-echo versus rapid gradient-echo for 3D magnetization-prepared acquisitions: Application to inhomogeneous magnetization transfer.

PURPOSE: To evaluate the benefits of fast spin echo (FSE) imaging over rapid gradient-echo (RAGE) for magnetization-prepared inhomogeneous magnetization transfer (ihMT) imaging. METHODS: A 3D FSE sequence was modified to include an ihMT preparation (ihMT-FSE) with an optional CSF suppression based on an inversion-recovery (ihMT-FLAIR). After numeric simulations assessing SNR benefits of FSE and the potential impact of an additional inversion-recovery, ihMT-RAGE, ihMT-FSE, and ihMT-FLAIR sequences were compared in a group of six healthy volunteers, evaluating image quality, thermal, and physiological noise as well as quantification using an ihMT saturation (ihMTsat) approach. A preliminary exploration in the cervical spinal cord was also conducted in a group of three healthy volunteers. RESULTS: Several fold improvements in thermal SNR were observed with ihMT-FSE in agreement with numerical simulations. However, we observed significantly higher physiological noise in ihMT-FSE compared to ihMT-RAGE that was mitigated in ihMT-FLAIR, which provided the best total SNR (+74% and +49% compared to ihMT-RAGE in the white and gray matter, P ≤ 0.004). IhMTsat quantification was successful in all cases with strong correlation between all sequences (r2 > 0.75). Early experiments showed potential for spinal cord imaging. CONCLUSIONS: FSE generally offers higher SNR compared to gradient-echo based acquisitions for magnetization-prepared contrasts as illustrated here in the case of ihMT. However, physiological noise has a significant effect, but an inversion-recovery-based CSF suppression was shown to be efficient in mitigating effects of CSF motion.

The Boston ASL Template and Simulator: Initial development and implementation.

BACKGROUND AND PURPOSE: Templates are a hallmark of image analysis in neuroimaging. However, while numerous structural templates exist and have facilitated single-subject and large group studies, templates based on functional contrasts, such as arterial spin labeling (ASL) perfusion, are scarce, have an inherently low spatial resolution, and are not as widely distributed. Having such tools at one's disposal is desirable, for example, in the case of studies not acquiring structural scans. We here propose an initial development of an ASL adult template based on high-resolution fast spin echo acquisitions. METHODS: High-resolution single-delay ASL, low-resolution multi-delay ASL, T1 -weighted magnetization prepared rapid acquisition 2 gradient echoes, and T2 fluid attenuated inversion recovery data were acquired in a cohort of 10 healthy volunteers (6 males and 4 females, 30± 7 years old). After offline reconstruction of high-resolution perfusion arterial transit time (ATT) and T1 maps, we built a multi-contrast template relying on the Advanced Normalization Toolbox multivariate template nonlinear construction framework. We offer examples for the registration of ASL data acquired with different sequences. Finally, we propose an ASL simulator based on our templates and a standard kinetic model that allows generating synthetic ASL contrasts based on user-specified parameters. RESULTS: Boston ASL Template and Simulator (BATS) offers high-quality, high-resolution perfusion-weighted and quantitative perfusion templates accompanied by ATT and different anatomical contrasts readily available in the Montreal Neurological Institute space. In addition, examples of use for data registration and as a synthetic contrast generator show various applications in which BATS could be used. CONCLUSIONS: We propose a new ASL template collection, named BATS, that also includes a simulator allowing the generation of synthetic ASL contrasts. BATS is available at http://github.com/manueltaso/batsasltemplate.

Normal-Appearing White Matter Deteriorates over the Year After an Ischemic Stroke and Is Associated with Global Cognition.

Normal-appearing white matter (NAWM) is a hub of plasticity, but data relating to its influence on post-ischemic stroke (IS) outcome remain scarce. The aim of this study was to evaluate the relationship between NAWM integrity and cognitive outcome after an IS. A longitudinal study was conducted including supra-tentorial IS patients. A 3-Tesla brain MRI was performed at baseline and 1 year, allowing the analyses of mean fractional anisotropy (FA) and mean diffusivity (MD) in NAWM masks, along with the volume of white matter hyperintensities (WMH) and IS. A Montreal Cognitive Assessment (MoCA), an Isaacs set test, and a Zazzo's cancellation task were performed at baseline, 3 months and 1 year. Mixed models were built, followed by Tract-based Spatial Statistics (TBSS) analyses. Ninety-five patients were included in the analyses (38% women, median age 69 ± 20). FA significantly decreased, and MD significantly increased between baseline and 1 year, while cognitive scores improved. Patients who decreased their NAWM FA more over the year had a slower cognitive improvement on MoCA (ß = - 0.11, p = 0.05). The TBSS analyses showed that patients who presented the highest decrease of FA in various tracts of white matter less improved their MoCA performances, regardless of WMH and IS volumes, demographic confounders, and clinical severity. NAWM integrity deteriorates over the year after an IS, and is associated with a cognitive recovery slowdown. The diffusion changes recorded here in patients starting with an early preserved white matter structure could have long term impact on cognition.

Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is associated with alterations in cortical perfusion that correlate with cognitive impairment. Recently, neural activity in the gamma band has been identified as a driver of arteriolar vasomotion while, on the other hand, gamma activity induction on preclinical models of AD has been shown to promote protein clearance and cognitive protection. METHODS: In two open-label studies, we assessed the possibility to modulate cerebral perfusion in 15 mild to moderate AD participants via 40Hz (gamma) transcranial alternating current stimulation (tACS) administered 1 h daily for 2 or 4 weeks, primarily targeting the temporal lobe. Perfusion-sensitive MRI scans were acquired at baseline and right after the intervention, along with electrophysiological recording and cognitive assessments. RESULTS: No serious adverse effects were reported by any of the participants. Arterial spin labeling MRI revealed a significant increase in blood perfusion in the bilateral temporal lobes after the tACS treatment. Moreover, perfusion changes displayed a positive correlation with changes in episodic memory and spectral power changes in the gamma band. CONCLUSIONS: Results suggest 40Hz tACS should be further investigated in larger placebo-controlled trials as a safe, non-invasive countermeasure to increase fast brain oscillatory activity and increase perfusion in critical brain areas in AD patients. TRIAL REGISTRATION: Studies were registered separately on ClinicalTrials.gov ( NCT03290326 , registered on September 21, 2017; NCT03412604 , registered on January 26, 2018).

Effects of tDCS dose and electrode montage on regional cerebral blood flow and motor behavior.

We used three dose levels (Sham, 2 mA, and 4 mA) and two different electrode montages (unihemispheric and bihemispheric) to examine DOSE and MONTAGE effects on regional cerebral blood flow (rCBF) as a surrogate marker of neural activity, and on a finger sequence task, as a surrogate behavioral measure drawing on brain regions targeted by transcranial direct current stimulation (tDCS). We placed the anodal electrode over the right motor region (C4) while the cathodal or return electrode was placed either over a left supraorbital region (unihemispheric montage) or over the left motor region (C3 in the bihemispheric montage). Performance changes in the finger sequence task for both hands (left hand: p = 0.0026, and right hand: p = 0.0002) showed a linear tDCS dose response but no montage effect. rCBF in the right hemispheric perirolandic area increased with dose under the anodal electrode (p = 0.027). In contrast, in the perirolandic ROI in the left hemisphere, rCBF showed a trend to increase with dose (p = 0.053) and a significant effect of montage (p = 0.00004). The bihemispheric montage showed additional rCBF increases in frontomesial regions in the 4mA condition but not in the 2 mA condition. Furthermore, we found strong correlations between simulated current density in the left and right perirolandic region and improvements in the finger sequence task performance (FSP) for the contralateral hand. Our data support not only a strong direct tDCS dose effect for rCBF and FSP as surrogate measures of targeted brain regions but also indirect effects on rCBF in functionally connected regions (e.g., frontomesial regions), particularly in the higher dose condition and on FSP of the ipsilateral hand (to the anodal electrode). At a higher dose and irrespective of polarity, a wider network of sensorimotor regions is positively affected by tDCS.

Severity of Small Vessel Disease Biomarkers Reduces the Magnitude of Cognitive Recovery after Ischemic Stroke.

OBJECTIVE: The objective of this study was to evaluate the impact of radiological biomarkers suggestive of cerebral small vessel disease (SVD) on the evolution of cognitive performances after an ischemic stroke (IS). METHODS: We studied patients with a supratentorial IS recruited consecutively to a prospective monocentric longitudinal study. A cognitive assessment was performed at baseline, 3 months, and 1 year and was based on a Montreal Cognitive Assessment, an Isaacs set test of verbal fluency (IST), and a Zazzo's cancellation task (ZCT) for the evaluation of attentional functions and processing speed. The following cerebral SVD biomarkers were detected on a 3-T brain MRI performed at baseline: white matter hyperintensities (WMHs), deep and lobar microbleeds, enlarged perivascular spaces in basal ganglia and centrum semiovale, previous small deep infarcts, and cortical superficial siderosis (cSS). Generalized linear mixed models were used to evaluate the relationship between these biomarkers and changes in cognitive performances. RESULTS: A total of 199 patients (65 ± 13 years, 68% male) were analyzed. Overall, the cognitive performances improved, more significantly in the first 3 months. Severe WMH was identified in 34% of the patients, and focal cSS in 3.5%. Patients with severe WMH and focal cSS had overall worse cognitive performances. Those with severe WMH had less improvement over time for IST (ß = -0.16, p = 0.02) and the number of errors to ZCT (ß = 0.19, p = 0.02), while those with focal cSS had less improvement over time for ZCT completion time (ß = 0.14, p = 0.01) and number of errors (ß = 0.17, p = 0.008), regardless of IS volume and location, gray matter volume, demographic confounders, and clinical and cardiovascular risk factors. CONCLUSION: The severity of SVD biomarkers, encompassing WMH and cSS, seems to reduce the magnitude of cognitive recovery after an IS. The detection of such SVD biomarkers early after stroke might help to identify patients with a cognitive vulnerability and a higher risk of poststroke cognitive impairment.

Regional and depth-dependence of cortical blood-flow assessed with high-resolution Arterial Spin Labeling (ASL).

Methods for imaging of cerebral blood flow do not typically resolve the cortex and thus underestimate flow. However, recent work with high-resolution MRI has emphasized the regional and depth-dependent structural, functional and relaxation times variations within the cortex. Using high-resolution Arterial Spin Labeling (ASL) and T1 mapping acquisitions, we sought to probe the effects of spatial resolution and tissue heterogeneity on cortical cerebral blood flow (CBF) measurements with ASL. We acquired high-resolution (1.6mm)3 whole brain ASL data in a cohort of 10 volunteers at 3T, along with T1 and transit-time (ATT) mapping, followed by group cortical surface-based analysis using FreeSurfer of the different measured parameters. Fully resolved regional analysis showed higher than average mid-thickness CBF in primary motor areas (+15%,p<0.002), frontal regions (+17%,p<0.01) and auditory cortex, while occipital regions had lower average CBF (-20%,p<10-5). ASL signal was higher towards the pial surface but correction for the shorter T1 near the white matter surface reverses this gradient, at least when using the low-resolution ATT map. Similar to structural measures, fully-resolved ASL CBF measures show significant differences across cortical regions. Depth-dependent variation of T1 in the cortex complicates interpretation of depth-dependent ASL signal and may have implications for the accurate CBF quantification at lower resolutions.

Characterization of the cortical myeloarchitecture with inhomogeneous magnetization transfer imaging (ihMT).

BACKGROUND: Myelin specific imaging techniques to characterize white matter in demyelinating diseases such as multiple sclerosis (MS) have become an area of increasing focus. Gray matter myelination is an important marker of cortical microstructure, and its impairment is relevant in progressive MS. However, its assessment is challenging due to its thin layers. While myelin water imaging and ultra-short TE imaging have not yet been implemented to assess cortical myeloarchitecture, magnetization transfer (MT) shows promise. A recent development of the MT technique, ihMT, has demonstrated greater myelin sensitivity/specificity. Here we implemented a 3D ihMT acquisition and analysis to characterize cortical gray matter myeloarchitecture. METHODS: 20 young healthy volunteers were imaged with a 3D ihMTRAGE sequence and quantitative metrics of ihMT (ihMTsat), and dual frequency-offset MT (dual MTsat) were calculated. Cortical surface-based analysis of ihMTsat and dual MTsat were performed and compared. We also compared the cortical ihMTsat map to a cortical surface-based map of T1-weighted images (T1w), defined as a proxy of myelin content. RESULTS: Cortical ihMTsat and dual MTsat maps were in qualitative agreement with previous work and the cortical T1w map, showing higher values in primary cortices and lower values in the insula. IhMTsat and dual MTsat were significantly correlated but with important regional differences. The ratio ihMTsat/dual MTsat highlighted higher ihMTsat values in the primary cortices and sulci. CONCLUSION: ihMTsat, a quantitative metric of ihMT, can be reliably measured in cortical gray matter and shows unique contrast between cortical regions.

Cerebral Small Vessel Disease MRI Features Do Not Improve the Prediction of Stroke Outcome.

OBJECTIVE: To determine whether the total small vessel disease (SVD) score adds information to the prediction of stroke outcome compared to validated predictors, we tested different predictive models of outcome in patients with stroke. METHODS: White matter hyperintensity, lacunes, perivascular spaces, microbleeds, and atrophy were quantified in 2 prospective datasets of 428 and 197 patients with first-ever stroke, using MRI collected 24 to 72 hours after stroke onset. Functional, cognitive, and psychological status were assessed at the 3- to 6-month follow-up. The predictive accuracy (in terms of calibration and discrimination) of age, baseline NIH Stroke Scale score (NIHSS), and infarct volume was quantified (model 1) on dataset 1, the total SVD score was added (model 2), and the improvement in predictive accuracy was evaluated. These 2 models were also developed in dataset 2 for replication. Finally, in model 3, the MRI features of cerebral SVD were included rather than the total SVD score. RESULTS: Model 1 showed excellent performance for discriminating poor vs good functional outcomes (area under the curve [AUC] 0.915), and fair performance for identifying cognitively impaired and depressed patients (AUCs 0.750 and 0.688, respectively). A higher SVD score was associated with a poorer outcome (odds ratio 1.30 [1.07-1.58], p = 0.0090 at best for functional outcome). However, adding the total SVD score (model 2) or individual MRI features (model 3) did not improve the prediction over model 1. Results for dataset 2 were similar. CONCLUSIONS: Cerebral SVD was independently associated with functional, cognitive, and psychological outcomes, but had no clinically relevant added value to predict the individual outcomes of patients when compared to the usual predictors, such as age and baseline NIHSS.

Rotated spiral RARE for high spatial and temporal resolution volumetric arterial spin labeling acquisition.

BACKGROUND: Arterial Spin Labeling (ASL) MRI can provide quantitative images that are sensitive to both time averaged blood flow and its temporal fluctuations. 3D image acquisitions for ASL are desirable because they are more readily compatible with background suppression to reduce noise, can reduce signal loss and distortion, and provide uniform flow sensitivity across the brain. However, single-shot 3D acquisition for maximal temporal resolution typically involves degradation of image quality through blurring or noise amplification by parallel imaging. Here, we report a new approach to accelerate a common stack of spirals 3D image acquisition by pseudo golden-angle rotation and compressed sensing reconstruction without any degradation of time averaged blood flow images. METHODS: 28 healthy volunteers were imaged at 3T with background-suppressed unbalanced pseudo-continuous ASL combined with a pseudo golden-angle Stack-of-Spirals 3D RARE readout. A fully-sampled perfusion-weighted volume was reconstructed by 3D non-uniform Fast Fourier Transform (nuFFT) followed by sum-of-squares combination of the 32 individual channels. Coil sensitivities were estimated followed by reconstruction of the 39 single-shot volumes using an L1-wavelet Compressed-Sensing reconstruction. Finally, brain connectivity analyses were performed in regions where BOLD signal suffers from low signal-to-noise ratio and susceptibility artifacts. RESULTS: Image quality, assessed with a non-reference 3D blurring metric, of full time averaged blood flow was comparable to a conventional interleaved acquisition. The temporal resolution provided by the acceleration enabled identification and quantification of resting-state networks even in inferior regions such as the amygdala and inferior frontal lobes, where susceptibility artifacts can degrade conventional resting-state fMRI acquisitions. CONCLUSION: This approach can provide measures of blood flow modulations and resting-state networks for free within any research or clinical protocol employing ASL for resting blood flow.

Three-dimensional inhomogeneous magnetization transfer with rapid gradient-echo (3D ihMTRAGE) imaging.

PURPOSE: To demonstrate the feasibility of integrating the magnetization transfer (MT) preparations required for inhomogeneous MT (ihMT) within an MPRAGE-style acquisition. Such a sequence allows for reduced power deposition and easy inclusion of other modules. METHODS: An ihMT MPRAGE-style sequence (ihMTRAGE) was initially simulated to investigate acquisition of the 3D ihMT data sequentially, or in an interleaved manner. The ihMTRAGE sequence was implemented on a 3T clinical scanner to acquire ihMT data from the brain and spine. RESULTS: Both simulations and in vivo data provided an ihMT signal that was significantly greater using a sequential ihMTRAGE acquisition, compared with an interleaved implementation. Comparison with a steady-state ihMT acquisition (defined as having one MT RF pulse between successive acquisition modules) demonstrated how ihMTRAGE allows for a reduction in average power deposition, or greater ihMT signal at equal average power deposition. Inclusion of a prospective motion-correction module did not significantly affect the ihMT signal obtained from regions of interest in the brain. The ihMTRAGE acquisition allowed combination with a spatial saturation module to reduce phase wrap artifacts in a cervical spinal cord acquisition. CONCLUSIONS: Use of preparations necessary for ihMT experiments within an MPRAGE-style sequence provides a useful alternative for acquiring 3D ihMT data. Compared with our steady-state implementation, ihMTRAGE provided reduced power deposition, while allowing use of the maximum intensity from off-resonance RF pulses. The 3D ihMTRAGE acquisition allowed combination of other modules with the preparation necessary for ihMT experiments, specifically motion compensation and spatial saturation modules.

Normal-Appearing White Matter Integrity Is a Predictor of Outcome After Ischemic Stroke.

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 (ß=-0.24; P=0.04). Additional path analysis showed that NAWM fractional anisotropy had a direct effect on mRS (ß=-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.

Active learning strategy and hybrid training for infarct segmentation on diffusion MRI with a U-shaped network.

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.

Chronic Cortical Cerebral Microinfarcts Slow Down Cognitive Recovery After Acute Ischemic Stroke.

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.

Neurodegeneration of the Substantia Nigra after Ipsilateral Infarct: MRI R2* Mapping and Relationship to Clinical Outcome.

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 (ß = 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, ß = -.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. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Vernooij in this issue.

The Influence of Stroke Location on Cognitive and Mood Impairment. A Voxel-Based Lesion-Symptom Mapping Study.

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.

Anatomical predictors of cognitive decline after subthalamic stimulation in Parkinson's disease.

We investigated whether pre-operative MRI measures of focal brain atrophy could predict cognitive decline occurring after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). For that purpose, we prospectively collected data of 42 consecutive patients with PD who underwent bilateral STN-DBS. Normalized brain structure volumes and cortical thicknesses were measured on pre-operative T1-weighted MRI. Patients were tested for their cognitive performances before surgery and 1 year after. After controlling for age, gender, pre-operative disease severity, change in dopaminomimetic dose after surgery and contact location, we found correlations: (1) between the variation of the total Mattis dementia rating scale (MDRS) score and left lateral ventricle volume (p = 0.032), (2) between the variation of the initiation/perseveration subscore of the MDRS and the left nucleus accumbens volume (p = 0.042) and the left lateral ventricle volume (p = 0.017) and (3) between the variation of the backward digit-span task and the right and left superior frontal gyrus thickness (p = 0.004 and p = 0.007, respectively). Left nucleus accumbens atrophy was associated with decline in the initiation/perseveration subscore with the largest effect size (d = - 1.64). Pre-operative left nucleus accumbens volume strongly predicted postoperative decline in the initiation/attention subscore (AUC = 0.92, p < 0.001, 96.3% sensitivity, 80.0% specificity, 92.9% PPV and 92.9% NPV). We conclude that the morphometric measures of brain atrophy usually associated with cognitive impairment in PD can also explain or predict a part of cognitive decline after bilateral STN-DBS. In particular, the left accumbens nucleus volume could be considered as a promising marker for guiding surgical decisions.

Preliminary evidence of the cerebellar role on cognitive performances in clinically isolated syndrome.

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.