White Matter Lesion Volume Research Articles

Peak width of skeletonized mean diffusivity (PSMD) and cognitive functions in relapsing-remitting multiple sclerosis.

Peak width of skeletonized mean diffusivity (PSMD) is a new MRI marker, which has shown clinical relevance in some neurological conditions and, in preliminary data, in multiple sclerosis (MS). We aimed here to investigate, in a group of relapsing-remitting MS (RRMS) patients, the relationship between PSMD and cognitive performances, in comparison with other MRI measures. RRMS patients (n= 60) and normal controls (n= 15) underwent a 3T MRI examination. MRI-based white matter (WM) lesion volume, microstructural integrity (assessed with Tract-Based Spatial Statistics of diffusion tensor imaging [DTI] images) and brain volumes (i.e., total brain, grey matter [GM] and WM) were computed. In addition, PSMD was calculated through "skeletonization" of WM tracts and diffusion histograms. Cognition was evaluated with Rao's Brief Repeatable Battery (BRB), which incorporated tests of verbal and visual memory, attention, concentration, information processing speed and verbal fluency. PSMD closely correlated with symbol digit modalities test (SDMT) (r = -0.70, p< 0.001)and, to a lesser extent, with verbal and visual memory tests. Multiple regression analysis showed that PSMD explained SDMT variance (R2= 0.54, p< 0.001) more than other MRI measures. Results point out the relevance of microstructural damage, as assessed by PSMD, as a reliable marker of cognition in MS, especially in explaining dysfunction in information processing speed.

Identification of White Matter Lesions in Patients With Acute Ischemic Lesions Using U-net.

Background: White matter lesions (WML) have been proved to be significantly associated with many brain diseases. Precise evaluation of burden of WML at early stage could provide insights in the prognosis and assist in intervention. However, acute ischemic lesions (AIL) exhibit hyperintensities on FLAIR images either, and are detected by diffusion weighted imaging (DWI). It is challenging to identify and segment WML in the patients with WML and AIL. Convolutional neural network (CNN) based architecture has been validated as an efficient tool for automatic segmentation. This study aimed to evaluate the performance of U-net in evaluation of WML in the patients with WML and AIL.Methods: A total of 208 cases from Chinese Atherosclerosis Risk Evaluation (CARE II) study were recruited in the present study. All subjects underwent imaging of FLAIR and DWI on 3.0 Tesla scanners. The contours of WML delineated by the observer and its scores rated by the observer were considered as gold standard. Among all 208 cases, 108 were randomly selected as train set, and the remaining 100 cases were used as test set. The performance of lesion segmentation toolbox (LST) and three U-net models were evaluated on three levels: pixel, lesion, and subject levels. The performance of all methods in WML identification and segmentation was also evaluated among the cases with different lesion volumes and between the cases with and without AIL.Results: All U-net models outperformed LST on pixel, lesion, and subject levels, while no differences were found among three U-net models. All segmentation methods performed best in the cases with WML volume (WMLV) > 20 ml but worst in those with WMLV < 5 ml. In addition, all methods showed similar performance between the cases with and without AIL. The scores determined by U-net exhibited a strong correlation with the gold standard (all Spearman correlation coefficients >0.89, ICCs >0.88, p-values <0.001).Conclusion: U-net performs well on identification and segmentation of WML in the patients with WML and AIL. The performance of U-net is validated by a dataset of multicenter study. Our results indicate that U-net has an advantage in assessing the burden of WML in the patients suffered from both WML and AIL.

Evolution of Cortical and White Matter Lesion Load in Early-Stage Multiple Sclerosis: Correlation With Neuroaxonal Damage and Clinical Changes.

Introduction: Changes in cortical and white matter lesion (CL, WML) load are pivotal metrics to diagnose and monitor multiple sclerosis patients. Yet, the relationship between (i) changes in CL/WML load and disease progression and between (ii) changes in CL/WML load and neurodegeneration at early MS stages is not yet established. In this work, we have assessed the hypothesis that the combined CL and WML load as well as their 2-years evolution are surrogate markers of neurodegeneration and clinical progression at early MS stages. To achieve this goal, we have studied a group of RRMS patients and have investigated the impact of both CL and WML load on neuroaxonal damage as measured by serum neurofilament light chain (sNfL). Next, we have explored whether changes in CL/WML load over 2 years in the same cohort of early-MS are related to motor and cognitive changes.Methods: Thirty-two RRMS patients (<5 years disease duration) underwent: (i) 3T MRI for CL/WML detection and clinical assessment at baseline and 2-years follow-up; and (ii) baseline blood test for sNfL. The correlation between the number and volume of CL/WML and sNfL was assessed by using the Spearman's rank correlation coefficient and a generalized linear model (GLM). A GLM was also used to assess the relationship between (i) the number/volume of new, enlarged, resolved, shrunken, stable lesions and (ii) the difference in clinical scores between two time-points.Results: At baseline, sNfL levels correlated with both total CL count/volume (ρ = 0.6/0.7, Corr-P <0.017/Corr-P < 0.001) and with total WML count/volume (ρ = 0.6/0.6, Corr-P < 0.01 for both). Baseline sNfL levels also correlated with new WML count/volume (ρ = 0.6/0.5, Corr-P < 0.01/Corr-P < 0.05) but not with new CL. Longitudinal changes in CL and WML count and volume were significantly associated with (i) sustained attention, auditory information, processing speed and flexibility (p < 0.01), (ii) verbal memory (p < 0.01); (iii) verbal fluency (p < 0.05); and (iv) hand-motor function (p < 0.05).Discussion: Changes in cortical and white matter focal damage in early MS patients correlate with global neuroaxonal damage and is associated to cognitive performances.

Association of Renal Clearance with Cerebral White Matter Vascular Disease in Hospitalized Veterans With and Without Delirium.

To assess the relation between renal function and delirium and to assess and compare the relation between cerebral white matter lesion (WML) and renal function as estimated by three formulas for the estimated glomerular filtration rate (eGFR) in older adult hospitalized veterans with and without delirium. Commonly used formulas to assess renal function-the four-variable Modification of Diet in Renal Disease (MDRD), the six-variable MDRD, and the Cockcroft-Gault eGFR equations-were used to assess renal function in 100 older adult hospitalized veterans with delirium (delirium group) and 100 hospitalized veterans without delirium (nondelirium group) that were age, sex, and race matched. WML location and volumes were assessed using brain computed tomography imaging for each of the 200 veterans in the study. One radiologist, blinded to the diagnoses of the veterans, examined head computed tomography scans for WML in the cortex, subcortex (frontal, temporal, parietal, occipital lobes), basal ganglia (globus pallidus, caudate, putamen), and internal capsule. WML were graded as not present, <1 cm, 1 to 2 cm, or >2 cm. Exploratory χ2 analyses were used to determine the association between the stage of chronic kidney disease and WML. Simple logistic regression analyses were then used to estimate the strength of association between the stages of kidney disease and WML for particular regions of the brain. The mean age of delirium group and nondelirium group veterans was 66 years. χ2 tests revealed no reliable relation between stages of renal disease and delirium. χ2 exploratory analyses of WML in brain regions by renal disease stages demonstrated significant differences in associations among the MDRD-4, MDRD-6, and Cockcroft-Gault formulas for measuring eGFR. The MDRD-4 formula was least associated with the presence or absence of WML. The Cockcroft-Gault estimation of eGFR was most associated with the presence or absence of WML. Simple logistic regressions showed notable increases in the association between stages of renal failure and WMLs in specific areas of the brain, with the MDRD-4 being the least associative with the fewest specific areas and the Cockcroft-Gault formula being the most associative with the most specific areas. The association between stages 2 through 5 of chronic kidney disease and WLM support the role of kidney function as a potential risk factor for WML in older adult military veterans. The Cockcroft-Gault formula is an important renal index of suspected WML and renal stages 2 through 5, superior to the MDRD-6 and MDRD-4, respectively, in association with WML in older adult military veterans.

Microstructural Alterations Analogous to Accelerated Aging of the Cerebral Cortex in Carotid Occlusive Disease

PurposeTo investigate cortical thickness and cortical quantitative T2 values as imaging markers of microstructural tissue damage in patients with unilateral high-grade internal carotid artery occlusive disease (ICAOD).MethodsA total of 22 patients with ≥70% stenosis (mean age 64.8 years) and 20 older healthy control subjects (mean age 70.8 years) underwent structural magnetic resonance imaging (MRI) and high-resolution quantitative (q)T2 mapping. Generalized linear mixed models (GLMM) controlling for age and white matter lesion volume were employed to investigate the effect of ICAOD on imaging parameters of cortical microstructural integrity in multivariate analyses.ResultsThere was a significant main effect (p < 0.05) of the group (patients/controls) on both cortical thickness and cortical qT2 values with cortical thinning and increased cortical qT2 in patients compared to controls, irrespective of the hemisphere. The presence of upstream carotid stenosis had a significant main effect on cortical qT2 values (p = 0.01) leading to increased qT2 in the poststenotic hemisphere, which was not found for cortical thickness. The GLMM showed that in general cortical thickness was decreased and cortical qT2 values were increased with increasing age (p < 0.05).ConclusionUnilateral high-grade carotid occlusive disease is associated with widespread cortical thinning and prolongation of cortical qT2, presumably reflecting hypoperfusion-related microstructural cortical damage similar to accelerated aging of the cerebral cortex. Cortical thinning and increase of cortical qT2 seem to reflect different aspects and different pathophysiological states of cortical degeneration. Quantitative T2 mapping might be a sensitive imaging biomarker for early cortical microstructural damage.

Serum neurofilament light in atrial fibrillation: clinical, neuroimaging and cognitive correlates.

Emerging evidence suggests that atrial fibrillation is associated with cognitive dysfunction independently of stroke, but the underlying mechanisms remain unclear. In this cross-sectional analysis from the Swiss-atrial fibrillation Study (NCT02105844), we investigated the association of serum neurofilament light protein, a neuronal injury biomarker, with (i) the CHA2DS2-VASc score (congestive heart failure, hypertension, age 65–74 or >75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, sex), clinical and neuroimaging parameters and (ii) cognitive measures in atrial fibrillation patients. We measured neurofilament light in serum using an ultrasensitive single-molecule array assay in a sample of 1379 atrial fibrillation patients (mean age, 72 years; female, 27%). Ischaemic infarcts, small vessel disease markers and normalized brain volume were assessed on brain MRI. Cognitive testing included the Montreal cognitive assessment, trail-making test, semantic verbal fluency and digit symbol substitution test, which were summarized using principal component analysis. Results were analysed using univariable and multivariable linear regression. Neurofilament light was associated with the CHA2DS2-VASc score, with an average 19.2% [95% confidence interval (17.2%, 21.3%)] higher neurofilament per unit CHA2DS2-VASc increase. This association persisted after adjustment for age and MRI characteristics. In multivariable analyses, clinical parameters associated with neurofilament light were higher age [32.5% (27.2%, 38%) neurofilament increase per 10 years], diabetes mellitus, heart failure and peripheral artery disease [26.8% (16.8%, 37.6%), 15.7% (8.1%, 23.9%) and 19.5% (6.8%, 33.7%) higher neurofilament, respectively]. Mean arterial pressure showed a curvilinear association with neurofilament, with evidence for both an inverse linear and a U-shaped association. MRI characteristics associated with neurofilament were white matter lesion volume and volume of large non-cortical or cortical infarcts [4.3% (1.8%, 6.8%) and 5.5% (2.5%, 8.7%) neurofilament increase per unit increase in log-volume of the respective lesion], as well as normalized brain volume [4.9% (1.7%, 8.1%) higher neurofilament per 100 cm3 smaller brain volume]. Neurofilament light was inversely associated with all cognitive measures in univariable analyses. The effect sizes diminished after adjusting for clinical and MRI variables, but the association with the first principal component was still evident. Our results suggest that in atrial fibrillation patients, neuronal loss measured by serum neurofilament light is associated with age, diabetes mellitus, heart failure, blood pressure and vascular brain lesions, and inversely correlates with normalized brain volume and cognitive function.

Test-retest Reliability Of Cognitive And Neuroimaging Measures In Older Adults

PURPOSE: Exercise is a promising strategy to help maintain brain function during aging. Determining the efficacy of exercise interventions requires reliable clinical outcome measures. In addition to measurement error and biological variability, long-term test-retest values can also be influenced by biasing factors - namely aging and practice effects. The purpose of this study was to determine the 12-week test-retest reliability of cognitive and neuroimaging measures in older adults. METHODS: Twenty healthy older adults (14 females, 60-80 years of age) participated in two sessions of cognitive testing and multimodal 3T MRI scanning (Siemens MAGNETOM Prisma). All tests were performed by a single rater separated by a 12-week control period. The NIH Toolbox Cognition Battery (NIHTB-CB) was used to assess fluid and crystallized cognitive function. T-2 FLAIR images were processed for white matter lesion volume (WMLV, ml) using the Lesion Segmentation Toolbox. T-1 MPRAGE images were processed for gray matter volume (GMV, mm3) in 3 subcortical regions using FreeSurfer cortical segmentation. Statistical analyses were performed in SPSS (v.25) including mean percent difference, effect size, paired t-test, and two-way mixed intraclass correlation coefficient (ICC) with absolute agreement. RESULTS: Results are presented in Table 1. There were no significant t-test values indicating good agreement between the two sessions. As expected, reliability was excellent in crystallized cognition and moderate to good in fluid cognition. Last, all brain segmentations showed good to excellent reliability. CONCLUSIONS: The long-term (12-weeks) test-retest reliability of standard cognitive and neuroimaging measures were within an acceptable tolerance for use in future intervention studies. Although fluid cognition has the greatest implications for and neurobiological link to cognitive aging, investigators should consider the greater variability in these measures.

Characterization of thalamic lesions and their correlates in multiple sclerosis by ultra-high-field MRI

Background: Thalamic pathology is a marker for neurodegeneration and multiple sclerosis (MS) disease progression. Objective: To characterize (1) the morphology of thalamic lesions, (2) their relation to cortical and white matter (WM) lesions, and (3) clinical measures, and to assess (4) the imaging correlates of thalamic atrophy. Methods: A total of 90 MS patients and 44 healthy controls underwent acquisition of 7 Tesla images for lesion segmentation and 3 Tesla scans for atrophy evaluation. Thalamic lesions were classified according to the shape and the presence of a central venule. Regression analysis identified the predictors of (1) thalamic atrophy, (2) neurological disability, and (3) information processing speed. Results: Thalamic lesions were mostly ovoid than periventricular, and for the great majority (78%) displayed a central venule. Lesion volume in the thalamus, cortex, and WM did not correlate with each other. Thalamic atrophy was only associated with WM lesion volume (p = 0.002); subpial and WM lesion volumes were associated with neurological disability (p = 0.016; p < 0.001); and WM and thalamic lesion volumes were related with cognitive impairment (p < 0.001; p = 0.03). Conclusion: Thalamic lesions are unrelated to those in the cortex and WM, suggesting that they may not share common pathogenic mechanisms and do not contribute to thalamic atrophy. Combined WM, subpial, and thalamic lesion volumes at 7 Tesla contribute to the disease severity.

7T MPFLAIR versus MP2RAGE for Quantifying Lesion Volume in Multiple Sclerosis.

Use of fluid-attenuated inversion recovery (FLAIR) scans to quantify multiple sclerosis (MS) lesion volume on 7 Tesla (7T) magnetic resonance imaging (MRI) has many downsides, including poor image homogeneity. There are little data about the relative benefit of alternative modalities. The purpose of this paper is to investigate if magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) is a viable alternative to FLAIR for robust lesion volume measurement and disability correlations. Forty-seven participants with MS underwent annual brain 7T MRIs. Magnetization-prepared FLAIR (MPFLAIR) and MP2RAGE (both at .7 mm3 isotropic resolution) sequences from a total of 80 MRI scans from 47 subjects were reviewed. White matter lesion (WML) masks were manually constructed from MPFLAIR and T1 maps (from MP2RAGE). Lesion volumes (normalized to intracranial volume) were compared to clinical characteristics and disability scales scores by Pearson or Spearman correlation, as appropriate. Relative correlation strength was compared by Fisher r- to z-transformation. Normalized lesion volume was greater in MPFLAIR masks (median .005 [range, .001-.030]) than from T1 maps (median .003 [range, .000-.015]). However, lesion volumes between MPFLAIR and T1 maps were highly correlated (rho = .87, P < .001). WML masks from both modalities correlated with most disability measures with no significant difference in the strength of correlation. 7T MPFLAIR and MP2RAGE T1 map-based WML volumes are highly intercorrelated and both correlate with disability. Thus, MP2RAGE may be a viable alternative to FLAIR-based methods for WML measurement on 7T MRI in MS research.

Cerebrovascular reactivity in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S) is a small vessel disease caused by TREX1 mutations. RVCL-S is characterized by retinal vasculopathy and brain white matter lesions with and without contrast enhancement. We aimed to investigate cerebrovascular reactivity (CVR) in RVCL-S. In this cross-sectional observational study, 21 RVCL-S patients, 23 mutation-negative family members, and 31 healthy unrelated controls were included. CVR to a hypercapnic challenge was measured using dual-echo arterial spin labeling magnetic resonance imaging. Stratified analyses based on age were performed. We found that CVR was decreased in gray and white matter of RVCL-S patients compared with family members and healthy controls (ANCOVA; P < 0.05 for all comparisons). This was most noticeable in RVCL-S patients aged ≥40 years (ANCOVA, P < 0.05 for all comparisons). In RVCL-S patients aged < 40 years, only CVR in white matter was lower when compared to healthy controls (P < 0.05). Gray matter CVR was associated with white matter lesion volume in RVCL-S patients (r = –0.527, P = 0.01). In conclusion, impaired cerebrovascular reactivity may play an important role in the pathophysiology of RVCL-S and may be an useful early biomarker of cerebrovascular disease severity.

Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease

Neurofilament light chain (NfL) is a protein that is selectively expressed in neurons. Increased levels of NfL measured in either cerebrospinal fluid or blood is thought to be a biomarker of neuronal damage in neurodegenerative diseases. However, there have been limited investigations relating NfL to the concurrent measures of white matter (WM) decline that it should reflect. White matter damage is a common feature of Alzheimer's disease. We hypothesized that serum levels of NfL would associate with WM lesion volume and diffusion tensor imaging (DTI) metrics cross-sectionally in 117 autosomal dominant mutation carriers (MC) compared to 84 non-carrier (NC) familial controls as well as in a subset (N = 41) of MC with longitudinal NfL and MRI data.In MC, elevated cross-sectional NfL was positively associated with WM hyperintensity lesion volume, mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy. Greater change in NfL levels in MC was associated with larger changes in fractional anisotropy, mean diffusivity, and radial diffusivity, all indicative of reduced WM integrity. There were no relationships with NfL in NC. Our results demonstrate that blood-based NfL levels reflect WM integrity and supports the view that blood levels of NfL are predictive of WM damage in the brain. This is a critical result in improving the interpretability of NfL as a marker of brain integrity, and for validating this emerging biomarker for future use in clinical and research settings across multiple neurodegenerative diseases.

4329 Investigating the role of Klotho in neurocognitive outcomes, brain volumes, and white matter changes in pediatric brain tumor survivors

OBJECTIVES/GOALS: Klotho is a protein linked to improved cognition in aging adults. A specific KLOTHO gene variant, KL-VS, increases circulating levels of Klotho. The current study aims to identify if the KL-VS haplotype and Klotho levels are associated with improved neurocognition in pediatric brain tumor survivors. METHODS/STUDY POPULATION: We are actively accruing pediatric brain tumor patients at UCSF alongside an existing multi-institutional cohort study investigating radiation-induced vasculopathies and cognitive outcomes in this population. Normal controls are being enrolled in parallel. Each patient undergoes: 1) single nucleotide polymorphism genotyping to identify KL-VS haplotype status, 2) enzyme-linked immunosorbent assays to measure circulating Klotho, 3) neurocognitive assessments with a computer-based, validated Cogstate battery, and 4) brain volume and white matter lesion segmentation analyses using MRI sequences obtained as part of routine care. RESULTS/ANTICIPATED RESULTS: Genotyping has been performed on 99 enrolled patients. KL-VS heterozygosity was seen in 22.7% of patients. To date, KL-VS status is not associated with neurocognitive outcomes at baseline or Year 1 testing. Association between KL-VS status, circulating Klotho levels, neurocognitive outcomes, brain volume and white matter lesion segmentation analyses is ongoing. We hypothesize that elevated Klotho levels will be associated with improved neurocognition, increased brain volumes in regions of interest and decreased white matter lesion volumes. DISCUSSION/SIGNIFICANCE OF IMPACT: If circulating Klotho leads to improved neurocognition in pediatric brain tumor survivors, Klotho levels might serve as a prognostic biomarker. Furthermore, as Klotho is being investigated for therapeutic indications, it may represent an intervention to prevent cognitive deficits in these patients.

The Impact of Intracortical Lesions on Volumes of Subcortical Structures in Multiple Sclerosis.

Recent studies showed thalamic atrophy in the early stages of MS. We investigated the impact of intracortical lesions on the volumes of subcortical structures (especially the thalamus) compared with other lesions in MS. Seventy-one patients with MS were included. The volumes of intracortical lesions and white matter lesions were identified on double inversion recovery and FLAIR, respectively, by using 3D Slicer. Volumes of white matter T1 hypointensities and subcortical gray matter, thalamus, caudate, putamen, and pallidum volumes were calculated using FreeSurfer. Age, MS duration, and the Expanded Disability Status Scale score were assessed. Patients with intracortical lesions were older (P = .003), had longer disease duration (P < .001), and higher Expanded Disability Status Scale scores (P = .02). The presence of intracortical lesions was associated with a significant decrease of subcortical gray matter volume (P = .02). In our multiple regression model, intracortical lesion volume was the only predictor of thalamic volume (R 2 = 0.4, b* = -0.28, P = .03) independent of white matter lesion volume and T1 hypointensity volume. White matter lesion volume showed an impact on subcortical gray matter volume in patients with relapsing-remitting MS (P = .04) and those with disease duration of <5 years (P = .04) and on thalamic volume in patients with Expanded Disability Status Scale scores of <4.0 (P = .01). By contrast, intracortical lesion volume showed an impact on subcortical gray matter and thalamic volumes in the secondary-progressive MS subgroup (P = .02 and P < .001) in patients with a long-standing disease course (P < .001 and P = .001) and more profound disability (P < .001 and P < .001). Thalamic atrophy was explained better by intracortical lesions than by white matter lesion and T1 hypointensity volumes, especially in patients with more profound disability.

Does vascular stiffness predict white matter hyperintensity burden in ischemic heart disease with preserved ejection fraction?

The survival rate of patients with ischemic heart disease (IHD) is increasing. However, survivors experience increased risk for neurological complications. The mechanisms for this increased risk are unknown. We tested the hypothesis that patients with IHD have greater carotid and cerebrovascular stiffness, and these indexes predict white matter small vessel disease. Fifty participants (age, 40-78 yr), 30 with IHD with preserved ejection fraction and 20 healthy age-matched controls, were studied using ultrasound imaging of the common carotid artery (CCA) and middle cerebral artery (MCA), as well as magnetic resonance imaging (T1, T2-FLAIR), to measure white matter lesion volume (WMLv). Carotid β-stiffness provided the primary measure of peripheral vascular stiffness. Carotid-cerebral pulse wave transit time (ccPWTT) provided a marker of cerebrovascular stiffness. Pulsatility index (PI) and resistive index (RI) of the MCA were calculated as measures of downstream cerebrovascular resistance. When compared with controls, patients with IHD exhibited greater β-stiffness [8.5 ± 3.3 vs. 6.8 ± 2.2 arbitrary units (AU); P = 0.04], MCA PI (1.1 ± 0.20 vs. 0.98 ± 0.18 AU; P = 0.02), and MCA RI (0.66 ± 0.06 vs. 0.62 ± 0.07 AU; P = 0.04). There was no difference in WMLv between IHD and control groups (0.95 ± 1.2 vs. 0.86 ± 1.4 mL; P = 0.81). In pooled patient data, WMLv correlated with both β-stiffness (R = 0.34, P = 0.02) and cerebrovascular ccPWTT (R = -0.43, P = 0.02); however, β-stiffness and ccPWTT were not associated (P = 0.13). In multivariate analysis, WMLv remained independently associated with ccPWTT (P = 0.02) and carotid β-stiffness (P = 0.04). Patients with IHD expressed greater β-stiffness and cerebral microvascular resistance. However, IHD did not increase risk of WMLv or cerebrovascular stiffness. Nonetheless, pooled data indicate that both carotid and cerebrovascular stiffness are independently associated with WMLv.NEW & NOTEWORTHY This study found that patients with ischemic heart disease (IHD) with preserved ejection fraction and normal blood pressures exhibit greater carotid β-stiffness, as well as middle cerebral artery pulsatility and resistive indexes, than controls. White matter lesion volume (WMLv) was not different between vascular pathology groups. Cerebrovascular pulse wave transit time (ccPWTT) and carotid β-stiffness independently associate with WMLv in pooled participant data, suggesting that regardless of heart disease history, ccPWTT and β-stiffness are associated with structural white matter damage.

Cognitive impairment in early MS: contribution of white matter lesions, deep grey matter atrophy, and cortical atrophy

BackgroundCognitive impairment (CI) is a frequent and debilitating symptom in MS. To better understand the neural bases of CI in MS, this magnetic resonance imaging (MRI) study aimed to identify and quantify related structural brain changes and to investigate their relation to each other.MethodsWe studied 51 patients with CI and 391 patients with cognitive preservation (CP). We analyzed three-dimensional T1-weighted and FLAIR scans at 3 Tesla. We determined mean cortical thickness as well as volumes of cortical grey matter (GM), deep GM including thalamus, cerebellar cortex, white matter, corpus callosum, and white matter lesions (WML). We also analyzed GM across the whole brain by voxel-wise and surface-based techniques.ResultsMean disease duration was 5 years. Comparing MS patients with CI and CP, we found higher volumes of WML, lower volumes of deep and cortical GM structures, and lower volumes of the corpus callosum (all corrected p values < 0.05). Effect sizes were largest for WML and thalamic volume (standardized ß values 0.25 and − 0.25). By logistic regression analysis including both WML and thalamic volume, we found a significant effect only for WML volume. Inclusion of the interaction term of WML and thalamic volume increased the model fit and revealed a highly significant interaction of WML and thalamic volume. Moreover, voxel-wise and surface-based comparisons of MS patients with CI and CP showed regional atrophy of both deep and cortical GM independent of WML volume and overall disability, but effect sizes were lower.ConclusionAlthough several mechanisms contribute to CI already in the early stage of MS, WML seem to be the main driver with thalamic atrophy primarily intensifying this effect.

Evaluating severity of white matter lesions from computed tomography images with convolutional neural network

PurposeSeverity of white matter lesion (WML) is typically evaluated on magnetic resonance images (MRI), yet the more accessible, faster, and less expensive method is computed tomography (CT). Our objective was to study whether WML can be automatically segmented from CT images using a convolutional neural network (CNN). The second aim was to compare CT segmentation with MRI segmentation.MethodsThe brain images from the Helsinki University Hospital clinical image archive were systematically screened to make CT-MRI image pairs. Selection criteria for the study were that both CT and MRI images were acquired within 6 weeks. In total, 147 image pairs were included. We used CNN to segment WML from CT images. Training and testing of CNN for CT was performed using 10-fold cross-validation, and the segmentation results were compared with the corresponding segmentations from MRI.ResultsA Pearson correlation of 0.94 was obtained between the automatic WML volumes of MRI and CT segmentations. The average Dice similarity index validating the overlap between CT and FLAIR segmentations was 0.68 for the Fazekas 3 group.ConclusionCNN-based segmentation of CT images may provide a means to evaluate the severity of WML and establish a link between CT WML patterns and the current standard MRI-based visual rating scale.

Alcohol Consumption, Brain Amyloid-β Deposition, and Brain Structural Integrity Among Older Adults Free of Dementia.

Light to moderate alcohol consumption has been variably associated with lower or higher risk of dementia, but effects on Alzheimer's disease pathology are less clear. We determined whether late-life alcohol consumption was associated with Alzheimer's disease pathology among older adults. We assessed the associations of alcohol consumption self-reported in 2000-2002 with brain amyloid-β deposition on PET scans, and white matter lesion and hippocampal volume on MRIs measured 7-9 years later in 189 participants of the Ginkgo Evaluation of Memory Study (age 75-87 years at baseline) who were free of clinical dementia, using multivariable-adjusted and inverse probability-weighted robust linear regression models. Alcohol consumption was not statistically significantly associated with amyloid-β deposition (standardized uptake value ratio difference per drink: -0.013 [95% CI: -0.027, 0.002]). Both non-drinkers and participants consuming ≥1 drink(s)/week had higher white matter lesion volume (% intracranial volume) than did the reference group of those consuming <1 drink/week (differences: 0.25 % [95% CI: 0.01, 0.50]; 0.26 % [95% CI: 0.02, 0.50]). The association of alcohol consumption and hippocampal volume was modified by age (p = 0.02). Among participants younger than 77 years, participants consuming 1-7 drinks/week had larger hippocampal volume compared with participants consuming <1 drink/week. Alcohol consumption was not statistically significantly associated with amyloid-β deposition 7-9 years later. Non-drinking and greater alcohol consumption were associated with higher white matter lesion volume compared with drinking <1 drink/week. Moderate drinking was associated with higher hippocampal volume in younger individuals. Given the selective nature of this population and adverse health effects of excessive alcohol consumption, these findings warrant further investigation, but cannot be translated into clinical recommendations.

Alterations in functional connectivity are associated with white matter lesions and information processing efficiency in multiple sclerosis.

Functional connectivity (FC) is typically altered in individuals with Multiple Sclerosis (MS). However, in relapsing-remitting multiple sclerosis (RRMS) patients, the relationship between brain FC, tissue integrity and cognitive impairment is still unclear as contradictory findings have been documented. In this exploratory study we compared both the whole brain connectome and resting state networks (RSNs) FC of twenty-one RRMS and seventeen healthy controls (HCs), using combined network based statistics and independent component analyses. The total white matter (WM) lesion volume and information processing efficiency were also correlated with FC in the RRMS group. Both whole brain connectome and individual RSNs FC were diminished in patients with RRMS compared to HC. Additionally, the reduction in FC was found to be a function of the total WM lesion volume, with greatest impact in those harboring the largest lesion volume. Finally, a positive correlation between FC and information processing efficiency was observed in RRMS. This complimentary whole brain and RSNs FC approach can contribute to clarify literature inconsistencies regarding FC alterations and provide new insights on the white matter structural damage in explaining functional abnormalities in RRMS.

Does the Babinski sign predict functional outcome in acute ischemic stroke?

ObjectiveThe aim of this prospective cohort study was to determine the incidence and neuroimaging risk factors associated with Babinski sign following acute ischemic stroke, as well as its relationship with the functional outcome of patients.MethodsA total of 351 patients were enrolled in the study within 7 days of acute ischemic stroke. The Babinski sign along with other upper motor neuron signs were examined upon admission and between days 1 and 3 and days 5 and 7 after admission. Neuroimaging parameters included site and volume of infarction and white matter lesions. All patients were followed up at 3 months. Functional outcome was assessed with the Lawton Activities of Daily Living scale and modified Rankin Scale.ResultsBabinski sign was observed in 115 of 351 (32.8%) patients in the acute ischemic stroke. These patients had higher National Institutes of Health Stroke Scale (NIHSS) scores at admission and higher rates of atrial fibrillation and cardioembolism; higher frequencies of frontal, temporal, and limbic lobes and basal ganglia infarcts; and larger infarct volume. Higher NIHSS score and basal ganglia infarct were significant predictors of the presence of Babinski sign. After adjusting for confounds, the presence of Babinski sign did not predict poor functional outcome.ConclusionThe incidence of Babinski sign was 32.8% in the acute ischemic stroke. Severe infarction and basal ganglia infarct were independent predictors of Babinski sign. Although Babinski sign is common in acute ischemic stroke patients, it does not predict poor functional outcome 3 months later.

Cerebrovascular reactivity and disease activity in relapsing-remitting multiple sclerosis

In multiple sclerosis (MS), insufficient blood supply might worsen energy deficiency of the brain tissue. Thus, cerebrovascular reactivity (CVR), which is the capacity of cerebral circulation to match blood supply to metabolic demand, might be important in MS pathology. The objective of this study was to investigate the relationship of CVR to disease activity and neuroimaging markers of disease progression in patients with MS. In 43 patients with relapsing remitting MS (RRMS) in clinical remission, 30 patients with a relapse of MS and 30 healthy controls, we measured CVR with transcranial Doppler as a relative change in flow velocity after breath-holding (breath-holding index) and voluntary hyperventilation (hyperventilation index). All patients in remission underwent brain magnetic resonance imaging at baseline and 33 underwent repeated imaging after 12 months, with various brain volume measurements taken. Cerebrovascular reactivity indices did not differ between patients in remission, patients with a relapse and controls. In patients in remission, CVR did not differ between those with or without contrast-enhancing lesions. In patients with a relapse, glucocorticoids significantly reduced both CVR indices. Cerebrovascular reactivity was not related to brain volume, white matter lesion volume, percent brain volume change, and the change in total white matter lesion volume. In RRMS, CVR appeared normal and unrelated to disease activity. There was no substantial association of CVR to brain atrophy and accumulation of white matter lesions.