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1.
AIDS ; 33(7): 1197-1205, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30870193

RESUMO

OBJECTIVE: The objective of this study is to investigate whether cerebral small vessel disease (CSVD) is more common in virologically suppressed HIV-positive participants compared with HIV-negative controls and examine the potential synergistic effects of HIV and CSVD on brain structure and cognition. DESIGN: Cross-sectional analysis of 119 treated, virologically suppressed HIV-positive and 55 HIV-negative participants. Forty-six HIV-positive and 30 HIV-negative participants had follow-up 2 years later. All participants underwent MRI and neuropsychological testing. METHODS: Volume of white matter hyperintensities (WMH) was used as a surrogate measure of CSVD severity. Tensor-based morphometry and cortical modeling estimated brain volumes and cortical thickness, respectively. Rasch measurement theory was applied to neuropsychological test scores to estimate overall cognition. Linear models compared WMH loads, brain volumes, and cognition between groups; evaluated the association of WMH loads with brain volumes and cognition; and tested the interaction between HIV and WMH loads on brain volumes and cognition. Mixed-effects models compared the change in WMH loads between groups. RESULTS: WMH loads and change in WMH loads were similar between the groups. HIV-positive participants had poorer cognition, thinner cortex and reduced subcortical volumes compared with HIV-negative controls. Higher WMH loads were associated with reduced cortical thickness and subcortical volumes and worse cognition, regardless of HIV serostatus. No significant interactions were observed between HIV and WMH loads with regards to brain volumes or cognition. CONCLUSION: These findings suggest that the contributions of HIV and CSVD on brain atrophy and cognitive impairment are independent but additive processes. This argues that optimizing vascular health may mitigate brain injury and cognitive decline, especially in treated, virologically suppressed HIV-positive individuals.

2.
Brain ; 142(3): 633-646, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30715195

RESUMO

Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success, however, suggesting that lesion location may be a contributor. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsing-remitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. Cervical spine lesions were manually delineated on T2- and T2*-weighted axial and sagittal MRI scans acquired at 3 or 7 T. With an automatic publicly-available analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterized by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalized lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (P < 0.001), which was further confirmed by absolute and normalized lesion volumes (P < 0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (P < 0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (P < 0.001); however when normalizing by each region, normalized lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (P < 0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than long disease duration. Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the distribution of spinal cord lesions in various patient groups.

3.
Neurobiol Aging ; 76: 71-79, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30703628

RESUMO

White matter hyperintensities (WMHs) are common in individuals with mild cognitive impairment (MCI) and Alzheimer's disease. Patients with MCI with high WMH volumes are known to have an increased chance of conversion to Alzheimer's disease compared with those without WMHs. In this article, we assess the differences between patients with MCI that remain stable (N = 413) and those that progress to dementia (N = 178) in terms of WMH volume (as a surrogate of amount of tissue damage) and T1-weighted (T1w) image hypointensity (as a surrogate of severity of tissue damage) in periventricular, deep, and juxtacortical brain regions. Together, lesion volume and T1w hypointensity are used as a surrogate of vascular disease burden. Our results show a significantly greater increase of all regional WMH volumes in the MCI population that converts to dementia (p < 0.001). T1w hypointensity for the juxtacortical WMHs was significantly lower in the converter group (p < 0.0001) and was not affected by age. Conversely, T1w hypointensity in other regions showed a significant decrease with age (p < 0.0001). Within the converters, Time2Conversion was associated with both WMH volume and T1w hypointensity (p < 0.0001), and conversion to dementia was significantly associated with decreased intensity (and not volume) of periventricular and juxtacortical WMHs (p < 0.001). These changes differ according to the WM region, suggesting that different mechanisms affect the juxtacortical area in comparison to deep and periventricular regions in the process of conversion to dementia.

4.
Neuroimage ; 184: 901-915, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30300751

RESUMO

The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI data provides measures of damage, which are key criteria for the diagnosis, prognosis, and longitudinal monitoring in MS. Automating this operation eliminates inter-rater variability and increases the efficiency of large-throughput analysis pipelines. Robust and reliable segmentation across multi-site spinal cord data is challenging because of the large variability related to acquisition parameters and image artifacts. In particular, a precise delineation of lesions is hindered by a broad heterogeneity of lesion contrast, size, location, and shape. The goal of this study was to develop a fully-automatic framework - robust to variability in both image parameters and clinical condition - for segmentation of the spinal cord and intramedullary MS lesions from conventional MRI data of MS and non-MS cases. Scans of 1042 subjects (459 healthy controls, 471 MS patients, and 112 with other spinal pathologies) were included in this multi-site study (n = 30). Data spanned three contrasts (T1-, T2-, and T2∗-weighted) for a total of 1943 vol and featured large heterogeneity in terms of resolution, orientation, coverage, and clinical conditions. The proposed cord and lesion automatic segmentation approach is based on a sequence of two Convolutional Neural Networks (CNNs). To deal with the very small proportion of spinal cord and/or lesion voxels compared to the rest of the volume, a first CNN with 2D dilated convolutions detects the spinal cord centerline, followed by a second CNN with 3D convolutions that segments the spinal cord and/or lesions. CNNs were trained independently with the Dice loss. When compared against manual segmentation, our CNN-based approach showed a median Dice of 95% vs. 88% for PropSeg (p ≤ 0.05), a state-of-the-art spinal cord segmentation method. Regarding lesion segmentation on MS data, our framework provided a Dice of 60%, a relative volume difference of -15%, and a lesion-wise detection sensitivity and precision of 83% and 77%, respectively. In this study, we introduce a robust method to segment the spinal cord and intramedullary MS lesions on a variety of MRI contrasts. The proposed framework is open-source and readily available in the Spinal Cord Toolbox.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Redes Neurais (Computação) , Medula Espinal/patologia , Humanos , Imagem por Ressonância Magnética/métodos , Variações Dependentes do Observador , Reconhecimento Automatizado de Padrão , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
Neuroimage Clin ; 20: 892-900, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30292088

RESUMO

White Matter Hyperintensities (WMHs) are associated with cognitive decline in aging and Alzheimer's disease. However, the pathogenesis of cognitive decline in Parkinson's disease (PD) is not as clearly related to vascular causes, and therefore the role of WMHs as a marker of small-vessel disease (SVD) in PD is less clear. Currently, SVD in PD is assessed and treated independently of the disease. However, if WMH as the major MRI sign of SVD has a higher impact on cognitive decline in PD patients than in healthy controls, vascular pathology needs to be assessed and treated with a higher priority in this population. Here we investigate whether the presence of WMHs leads to increased cognitive decline in de novo PD, and if these effects relate to cortical atrophy. WMHs and cortical thickness were measured in de novo PD patients and age-matched controls (NPD = 365, NControl = 174) from Parkinson's Progression Markers Initiative (PPMI) to study the relationship between baseline WMHs, future cognitive decline (follow-up: 4.09 ±â€¯1.14 years) and cortical atrophy (follow-up: 1.05 ±â€¯0.10 years). PD subjects with high baseline WMH loads had significantly greater cognitive decline than i) PD subjects with low WMH load, and ii) control subjects with high WMH load. Furthermore, in PD subjects, high WMH load resulted in more cortical thinning in the right frontal lobe. Theses results show that the presence of WMHs in de novo PD patients predicts greater future cognitive decline and cortical atrophy than in normal aging.

6.
Mult Scler ; : 1352458518781999, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29909771

RESUMO

BACKGROUND: Studies including patients with well-established multiple sclerosis (MS) have shown a significant and disability-related reduction in the cervical spinal cord (SC) magnetisation transfer ratio (MTR). OBJECTIVES: The objectives are to (1) assess whether MTR reduction is already measurable in the SC of patients with early relapsing-remitting multiple sclerosis (RRMS) and (2) describe its spatial distribution. METHODS: We included 60 patients with RRMS <12 months and 34 age-matched controls at five centres. Axial T2*w, sagittal T2w, sagittal phase-sensitive inversion recovery (PSIR), 3DT1w, and axial magnetisation transfer (MT) images were acquired from C1 to C7. Lesions were manually labelled and mean MTR values computed both for the whole SC and for normal-appearing SC in different regions of interest. RESULTS: Mean whole SC MTR was significantly lower in patients than controls (33.7 vs 34.9 pu, p = 0.00005), even after excluding lesions (33.9 pu, p = 0.0003). We observed a greater mean reduction in MTR for vertebral levels displaying the highest lesion loads (C2-C4). In the axial plane, we observed a greater mean MTR reduction at the SC periphery and barycentre. CONCLUSION: Cervical SC tissue damage measured using MTR is not restricted to macroscopic lesions in patients with early RRMS and is not homogeneously distributed.

7.
Mult Scler ; : 1352458518779952, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29852831

RESUMO

OBJECTIVE: To determine the frequency of cortical lesions (CLs) in patients with pediatric-onset multiple sclerosis (POMS) using multi-contrast magnetic resonance imaging (MRI), and the relationship between frontal CL load and upper limb dexterity assessed with the Nine-Hole Peg Test (9-HPT). METHODS: Participants completed the 9-HPT and were imaged on a 3T MRI scanner to collect T1-weighted three-dimensional (3D) magnetization prepared rapid gradient echo (MPRAGE), proton density-weighted, T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. CLs were manually segmented using all MRI contrasts. RESULTS: We enrolled 24 participants with POMS (mean (standard deviation) age at first symptom: 13.3 (±2.7) years; mean age at scan: 18.8 (±3) years; mean disease duration of 5 (±3.2) years). A total of 391 CLs (mean, 16.3 ± 27.2; median, 7) were identified in 19 of 24 POMS patients (79%). The total number of CLs was positively associated with white matter lesion volume ( p = 0.04) but not with thalamic volume, age at the time of the scan, or disease duration. The number of frontal CLs was associated with slower performance on the 9-HPT ( p = 0.05). CONCLUSION: Multi-contrast 3T MRI led to a high rate of CL detection, demonstrating that cortical pathology occurs even in pediatric-onset disease. Frontal lobe CL count was associated with reduced manual dexterity, indicating that these CLs are clinically relevant.

8.
Hum Brain Mapp ; 39(3): 1093-1107, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29181872

RESUMO

INTRODUCTION: Fluid-attenuated Inversion Recovery (FLAIR) and dual T2w and proton density (PD) magnetic resonance images (MRIs) are considered to be the optimum sequences for detecting white matter hyperintensities (WMHs) in aging and Alzheimer's disease populations. However, many existing large multisite studies forgo their acquisition in favor of other MRI sequences due to economic and time constraints. METHODS: In this article, we have investigated whether FLAIR and T2w/PD sequences are necessary to detect WMHs in Alzheimer's and aging studies, compared to using only T1w images. Using a previously validated automated tool based on a Random Forests classifier, WMHs were segmented for the baseline visits of subjects from ADC, ADNI1, and ADNI2/GO studies with and without T2w/PD and FLAIR information. The obtained WMH loads (WMHLs) in different lobes were then correlated with manually segmented WMHLs, each other, age, cognitive, and clinical measures to assess the strength of the correlations with and without using T2w/PD and FLAIR information. RESULTS: The WMHLs obtained from T1w-Only segmentations correlated with the manual WMHLs (ADNI1: r = .743, p < .001, ADNI2/GO: r = .904, p < .001), segmentations obtained from T1w + T2w + PD for ADNI1 (r = .888, p < .001) and T1w + FLAIR for ADNI2/GO (r = .969, p < .001), age (ADNI1: r = .391, p < .001, ADNI2/GO: r = .466, p < .001), and ADAS13 (ADNI1: r = .227, p < .001, ADNI2/GO: r = .190, p < 0.001), and NPI (ADNI1: r = .290, p < .001, ADNI2/GO: r = 0.144, p < .001), controlling for age. CONCLUSION: Our results suggest that while T2w/PD and FLAIR provide more accurate estimates of the true WMHLs, T1w-Only segmentations can still provide estimates that hold strong correlations with the actual WMHLs, age, and performance on various cognitive/clinical scales, giving added value to datasets where T2w/PD or FLAIR are not available.

9.
Neurology ; 89(7): 714-721, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28724581

RESUMO

OBJECTIVE: To identify gadolinium-enhancing lesions affecting the cortex of patients with early multiple sclerosis (MS) and to describe the frequency and evolution of these lesions. METHODS: We performed a retrospective, observational, longitudinal analysis of MRI scans collected as part of the Betaseron vs Copaxone in Multiple Sclerosis with Triple-Dose Gadolinium and 3T MRI Endpoints (BECOME) study. Seventy-five patients with early-stage MS were scanned monthly, over a period of 12-24 months, using 3T MRI after administration of triple-dose gadolinium. A total of 1,188 scans were included in the analysis. A total of 139 were selected using an image pipeline algorithm that integrated the image information from cortical gray matter masks and gadolinium-enhancing lesion masks. These scans were evaluated to identify gadolinium-enhancing lesions affecting the cortex. RESULTS: The total number of gadolinium-enhancing lesions was 2,044. The number of gadolinium-enhancing lesions affecting the cortex was 120 (6%), 95% of which were leukocortical. The number of patients who showed gadolinium-enhancing lesions affecting the cortex was 27 (36%). The number of gadolinium-enhancing lesions affecting the cortex at baseline was 25 (21%) and the number of new lesions that developed in follow-up scans was 49 (41%). The number of persistent lesions was 46 (38%). CONCLUSIONS: The presence of enhancing lesions affecting the cortex and adjacent white matter, although transient and not frequent, suggests that at least some cortical lesions are related to blood-brain barrier disruption. Our data support the concept that there may be an acute inflammatory phase in the development of leukocortical MS lesions. CLINICALTRIALSGOV IDENTIFIER: NCT00176592.


Assuntos
Barreira Hematoencefálica/patologia , Córtex Cerebral/patologia , Inflamação/patologia , Esclerose Múltipla/patologia , Substância Branca/patologia , Doença Aguda , Adolescente , Adulto , Córtex Cerebral/diagnóstico por imagem , Feminino , Gadolínio , Humanos , Aumento da Imagem , Inflamação/diagnóstico por imagem , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/patologia , Substância Branca/diagnóstico por imagem , Adulto Jovem
10.
Neuroimage ; 157: 233-249, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28602597

RESUMO

INTRODUCTION: White matter hyperintensities (WMHs) are areas of abnormal signal on magnetic resonance images (MRIs) that characterize various types of histopathological lesions. The load and location of WMHs are important clinical measures that may indicate the presence of small vessel disease in aging and Alzheimer's disease (AD) patients. Manually segmenting WMHs is time consuming and prone to inter-rater and intra-rater variabilities. Automated tools that can accurately and robustly detect these lesions can be used to measure the vascular burden in individuals with AD or the elderly population in general. Many WMH segmentation techniques use a classifier in combination with a set of intensity and location features to segment WMHs, however, the optimal choice of classifier is unknown. METHODS: We compare 10 different linear and nonlinear classification techniques to identify WMHs from MRI data. Each classifier is trained and optimized based on a set of features obtained from co-registered MR images containing spatial location and intensity information. We further assess the performance of the classifiers using different combinations of MRI contrast information. The performances of the different classifiers were compared on three heterogeneous multi-site datasets, including images acquired with different scanners and different scan-parameters. These included data from the ADC study from University of California Davis, the NACC database and the ADNI study. The classifiers (naïve Bayes, logistic regression, decision trees, random forests, support vector machines, k-nearest neighbors, bagging, and boosting) were evaluated using a variety of voxel-wise and volumetric similarity measures such as Dice Kappa similarity index (SI), Intra-Class Correlation (ICC), and sensitivity as well as computational burden and processing times. These investigations enable meaningful comparisons between the performances of different classifiers to determine the most suitable classifiers for segmentation of WMHs. In the spirit of open-source science, we also make available a fully automated tool for segmentation of WMHs with pre-trained classifiers for all these techniques. RESULTS: Random Forests yielded the best performance among all classifiers with mean Dice Kappa (SI) of 0.66±0.17 and ICC=0.99 for the ADC dataset (using T1w, T2w, PD, and FLAIR scans), SI=0.72±0.10, ICC=0.93 for the NACC dataset (using T1w and FLAIR scans), SI=0.66±0.23, ICC=0.94 for ADNI1 dataset (using T1w, T2w, and PD scans) and SI=0.72±0.19, ICC=0.96 for ADNI2/GO dataset (using T1w and FLAIR scans). Not using the T2w/PD information did not change the performance of the Random Forest classifier (SI=0.66±0.17, ICC=0.99). However, not using FLAIR information in the ADC dataset significantly decreased the Dice Kappa, but the volumetric correlation did not drastically change (SI=0.47±0.21, ICC=0.95). CONCLUSION: Our investigations showed that with appropriate features, most off-the-shelf classifiers are able to accurately detect WMHs in presence of FLAIR scan information, while Random Forests had the best performance across all datasets. However, we observed that the performances of most linear classifiers and some nonlinear classifiers drastically decline in absence of FLAIR information, with Random Forest still retaining the best performance.


Assuntos
Envelhecimento/patologia , Doença de Alzheimer/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Substância Branca/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Conjuntos de Dados como Assunto , Feminino , Humanos , Processamento de Imagem Assistida por Computador/normas , Imagem por Ressonância Magnética/normas , Masculino
11.
Neuroimage Clin ; 12: 858-868, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27872808

RESUMO

The purpose of our study was to evaluate the utility of measurements of cortical surface magnetization transfer ratio (csMTR) on the inner, mid and outer cortical boundaries as clinically accessible biomarkers of cortical gray matter pathology in multiple sclerosis (MS). Twenty-five MS patients and 12 matched controls were recruited from the MS Clinic of the Montreal Neurological Institute. Anatomical and magnetization transfer ratio (MTR) images were acquired using 3 Tesla MRI at baseline and two-year time-points. MTR maps were smoothed along meshes representing the inner, mid and outer neocortical boundaries. To evaluate csMTR reductions suggestive of sub-pial demyelination in MS patients, a mixed model analysis was carried out at both the individual vertex level and in anatomically parcellated brain regions. Our results demonstrate that focal areas of csMTR reduction are most prevalent along the outer cortical surface in the superior temporal and posterior cingulate cortices, as well as in the cuneus and precentral gyrus. Additionally, age regression analysis identified that reductions of csMTR in MS patients increase with age but appear to hit a plateau in the outer caudal anterior cingulate, as well as in the precentral and postcentral cortex. After correction for the naturally occurring gradient in cortical MTR, the difference in csMTR between the inner and outer cortex in focal areas in the brains of MS patients correlated with clinical disability. Overall, our findings support multi-surface analysis of csMTR as a sensitive marker of cortical sub-pial abnormality indicative of demyelination in MS patients.


Assuntos
Córtex Cerebral/patologia , Imagem por Ressonância Magnética/métodos , Esclerose Múltipla/patologia , Adulto , Idoso , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Adulto Jovem
12.
Neuroimage ; 52(4): 1261-7, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20483380

RESUMO

Several methods exist and are frequently used to quantify grey matter (GM) atrophy in multiple sclerosis (MS). Fundamental to all available techniques is the accurate segmentation of GM in the brain, a difficult task confounded even further by the pathology present in the brains of MS patients. In this paper, we examine the segmentations of six different automated techniques and compare them to a manually defined reference standard. Results demonstrate that, although the algorithms perform similarly to manual segmentations of cortical GM, severe shortcomings are present in the segmentation of deep GM structures. This deficiency is particularly relevant given the current interest in the role of GM in MS and the numerous reports of atrophy in deep GM structures.


Assuntos
Algoritmos , Encéfalo/patologia , Interpretação de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Esclerose Múltipla/patologia , Neurônios/patologia , Reconhecimento Automatizado de Padrão/métodos , Atrofia/patologia , Humanos , Aumento da Imagem/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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