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1.
Neurobiol Aging ; 81: 30-37, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31207467

RESUMO

We provide here normative values of yearly percentage brain volume change (PBVC/y) as obtained with Structural Imaging Evaluation, using Normalization, of Atrophy, a widely used open-source software, developing a PBVC/y calculator for assessing the deviation from the expected PBVC/y in patients with neurological disorders. We assessed multicenter (34 centers, 11 acquisition protocols) magnetic resonance imaging data of 720 healthy participants covering the whole adult lifespan (16-90 years). Data of 421 participants with a follow-up > 6 months were used to obtain the normative values for PBVC/y and data of 392 participants with a follow-up <1 month were selected to assess the intrasubject variability of the brain volume measurement. A mixed model evaluated PBVC/y dependence on age, sex, and magnetic resonance imaging parameters (scan vendor and magnetic field strength). PBVC/y was associated with age (p < 0.001), with 60- to 70-year-old participants showing twice more volume decrease than participants aged 30-40 years. PBVC/y was also associated with magnetic field strength, with higher decreases when measured by 1.5T than 3T scanners (p < 0.001). The variability of PBVC/y normative percentiles was narrower as the interscan interval was longer (e.g., 80th normative percentile was 50% smaller for participants with 2-year than with 1-year follow-up). The use of these normative data, eased by the freely available calculator, might help in better discriminating pathological from physiological conditions in the clinical setting.

2.
Magn Reson Med ; 82(3): 1025-1040, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31081239

RESUMO

PURPOSE: To enable clinical applications of quantitative magnetization transfer (qMT) imaging by developing a fast method to map one of its fundamental model parameters, the bound pool fraction (BPF), in the human brain. THEORY AND METHODS: The theory of steady-state MT in the fast-exchange approximation is used to provide measurements of BPF, and bound pool transverse relaxation time ( T 2 B ). A sequence that allows sampling of the signal during steady-state MT saturation is used to perform BPF mapping with a 10-min-long fully echo planar imaging-based MRI protocol, including inversion recovery T1 mapping and B1 error mapping. The approach is applied in 6 healthy subjects and 1 multiple sclerosis patient, and validated against a single-slice full qMT reference acquisition. RESULTS: BPF measurements are in agreement with literature values using off-resonance MT, with average BPF of 0.114(0.100-0.128) in white matter and 0.068(0.054-0.085) in gray matter. Median voxel-wise percentage error compared with standard single slice qMT is 4.6%. Slope and intercept of linear regression between new and reference BPF are 0.83(0.81-0.85) and 0.013(0.11-0.16). Bland-Altman plot mean bias is 0.005. In the multiple sclerosis case, the BPF is sensitive to pathological changes in lesions. CONCLUSION: The method developed provides accurate BPF estimates and enables shorter scan time compared with currently available approaches, demonstrating the potential of bringing myelin sensitive measurement closer to the clinic.

3.
J Neurol Neurosurg Psychiatry ; 90(7): 755-760, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30948625

RESUMO

OBJECTIVE: Sodium (23Na)-MRI is an emerging imaging technique to investigate in vivo changes in tissue viability, reflecting neuroaxonal integrity and metabolism. Using an optimised 23Na-MRI protocol with smaller voxel sizes and improved tissue contrast, we wanted to investigate whether brain total sodium concentration (TSC) is a biomarker for long-term disease outcomes in a cohort of patients with relapse-onset multiple sclerosis (MS), followed from disease onset. METHODS: We performed a cross-sectional study in 96 patients followed up ~ 15 years after a clinically isolated syndrome (CIS) and 34 healthy controls. Disease course was classified as CIS, relapsing-remitting MS or secondary progressive MS (SPMS). We acquired 1H-MRI and 23Na-MRI and calculated the TSC in cortical grey matter (CGM), deep grey matter, normal-appearing white matter (WM) and WM lesions. Multivariable linear regression was used to identify independent associations of tissue-specific TSC with physical disability and cognition, with adjustment for tissue volumes. RESULTS: TSC in all tissues was higher in patients with MS compared with healthy controls and patients who remained CIS, with differences driven by patients with SPMS. Higher CGM TSC was independently associated with Expanded Disability Status Scale (R2=0.26), timed 25-foot walk test (R2=0.23), 9-hole peg test (R2=0.23), Paced Auditory Serial Addition Test (R2=0.29), Symbol Digit Modalities Test (R2=0.31) and executive function (R2=0.36) test scores, independent of grey matter atrophy. CONCLUSIONS: Sodium accumulation in CGM reflects underlying neuroaxonal metabolic abnormalities relevant to disease course heterogeneity and disability in relapse-onset MS. TSC and should be considered as an outcome measure in future neuroprotection trials.

4.
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.

5.
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
6.
J Neuroimaging ; 29(3): 410-417, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30582252

RESUMO

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI)-derived spinal cord (SC) gray and white matter (GM/WM) volume are useful indirect measures of atrophy and neurodegeneration over time, typically obtained in the upper SC. Neuropathological evidence suggests that in certain neurological conditions, early degeneration may occur as low as the sacral SC. In this study, the feasibility of GM/WM segmentation of the conus medullaris (CM) was assessed in vivo. METHODS: Twenty-three healthy volunteers (11 female, mean age 47 years) underwent high-resolution 3T MRI of the CM using a 3-dimensional fast field echo sequence. Reproducibility of the volume measurements was assessed in 5 subjects (2 female, 25-37 years) by one rater who repeated the analysis 3 times and also with 2 additional raters working independently in order to calculate the intra- and interrater coefficient of variation (COV), respectively. Furthermore, the influence of age, gender, spine and SC metrics on tissue-specific measures of the CM was investigated. RESULTS: Volumetric CM analyses (N = 23) for the SC, GM, and WM revealed a mean (SD) total volume of CM-TV = 1746.9 (296.7) mm3 , CM-GM-TV = 731.2 (106.0) mm3 , and CM-WM-TV = 1014.6 (211.3) mm3 , respectively. The intra-rater COV for measuring the CM-TV and CM-GM-TV was 3.38% and 7.42%, respectively; the interrater COV was 3.43% and 10.80%, respectively. Using age, gender, spine and SC metrics in regression models substantially reduced group variability for CM-TV, CM-WM-TV, and CM-GM-TV by up to 39.2%, 42.7%, and 21.2%, respectively. CONCLUSIONS: The results from this study demonstrate the feasibility of obtaining tissue-specific volume measurements in the CM by means of MRI with good reproducibility and provide normative data for future applications in neurological diseases affecting the lower SC.

7.
Neurology ; 90(14): e1183-e1190, 2018 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-29514948

RESUMO

OBJECTIVE: To assess the value of the central vein sign (CVS) on a clinical 3T scanner to distinguish between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). METHODS: Eighteen aquaporin-4-antibody-positive patients with NMOSD, 18 patients with relapsing-remitting MS, and 25 healthy controls underwent 3T MRI. The presence of a central vein in white matter lesions on susceptibility-weighted imaging, defined as a thin hypointense line or a small dot, was recorded. RESULTS: The proportion of lesions with the CVS was higher in MS than NMOSD (80% vs 32%, p < 0.001). A greater proportion of lesions with the CVS predicted the diagnosis of MS, rather than NMOSD (odds ratio 1.10, 95% confidence interval [CI] 1.04 to 1.16, p = 0.001), suggesting that each percent unit increase in the proportion of lesions with the CVS in an individual patient was associated with a 10% increase in the risk of the same patient having MS. If more than 54% of the lesions on any given scan show the CVS, then the patient can be given a diagnosis of MS with an accuracy of 94% (95% CIs 81.34, 99.32, p < 0.001, sensitivity/specificity 90%/100%). CONCLUSION: The clinical value of the CVS in the context of the differential diagnosis between MS and NMOSD, previously suggested using 7T scanners, is now extended to clinical 3T scanners, thereby making a step towards the use of CVS in clinical practice. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the CVS on 3T MRI accurately distinguishes patients with MS from those with seropositive NMOSD.

8.
Magn Reson Med ; 79(4): 2142-2148, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28736946

RESUMO

PURPOSE: To develop a fast and robust method for measuring T1 in the whole cervical spinal cord in vivo, and to assess its reproducibility. METHODS: A spatially nonselective adiabatic inversion pulse is combined with zonally oblique-magnified multislice echo-planar imaging to produce a reduced field-of-view inversion-recovery echo-planar imaging protocol. Multi- inversion time data are obtained by cycling slice order throughout sequence repetitions. Measurement of T1 is performed using 12 inversion times for a total protocol duration of 7 min. Reproducibility of regional T1 estimates is assessed in a scan-rescan experiment on five heathy subjects. RESULTS: Regional mean (standard deviation) T1 was: 1108.5 (±77.2) ms for left lateral column, 1110.1 (±83.2) ms for right lateral column, 1150.4 (±102.6) ms for dorsal column, and 1136.4 (±90.8) ms for gray matter. Regional T1 estimates showed good correlation between sessions (Pearson correlation coefficient = 0.89 (P value < 0.01); mean difference = 2 ms, 95% confidence interval ± 20 ms); and high reproducibility (intersession coefficient of variation approximately 1% in all the regions considered, intraclass correlation coefficient = 0.88 (P value < 0.01, confidence interval 0.71-0.95)). CONCLUSIONS: T1 estimates in the cervical spinal cord are reproducible using inversion-recovery zonally oblique-magnified multislice echo-planar imaging. The short acquisition time and large coverage of this method paves the way for accurate T1 mapping for various spinal cord pathologies. Magn Reson Med 79:2142-2148, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

9.
Ann Clin Transl Neurol ; 4(9): 663-679, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28904988

RESUMO

OBJECTIVE: Conventional magnetic resonance imaging (MRI) of the multiple sclerosis spinal cord is limited by low specificity regarding the underlying pathological processes, and new MRI metrics assessing microscopic damage are required. We aim to show for the first time that neurite orientation dispersion (i.e., variability in axon/dendrite orientations) is a new biomarker that uncovers previously undetected layers of complexity of multiple sclerosis spinal cord pathology. Also, we validate against histology a clinically viable MRI technique for dispersion measurement (neurite orientation dispersion and density imaging, NODDI), to demonstrate the strong potential of the new marker. METHODS: We related quantitative metrics from histology and MRI in four post mortem spinal cord specimens (two controls; two progressive multiple sclerosis cases). The samples were scanned at high field, obtaining maps of neurite density and orientation dispersion from NODDI and routine diffusion tensor imaging (DTI) indices. Histological procedures provided markers of astrocyte, microglia, myelin and neurofilament density, as well as neurite dispersion. RESULTS: We report from both NODDI and histology a trend toward lower neurite dispersion in demyelinated lesions, indicative of reduced neurite architecture complexity. Also, we provide unequivocal evidence that NODDI-derived dispersion matches its histological counterpart (P < 0.001), while DTI metrics are less specific and influenced by several biophysical substrates. INTERPRETATION: Neurite orientation dispersion detects a previously undescribed and potentially relevant layer of microstructural complexity of multiple sclerosis spinal cord pathology. Clinically feasible techniques such as NODDI may play a key role in clinical trial and practice settings, as they provide histologically meaningful dispersion indices.

10.
Neuroimage ; 163: 106-114, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28899746

RESUMO

BACKGROUND AND PURPOSE: In vivoidentification of white matter lesions plays a key-role in evaluation of patients with multiple sclerosis (MS). Automated lesion segmentation methods have been developed to substitute manual outlining, but evidence of their performance in multi-center investigations is lacking. In this work, five research-domain automated segmentation methods were evaluated using a multi-center MS dataset. METHODS: 70 MS patients (median EDSS of 2.0 [range 0.0-6.5]) were included from a six-center dataset of the MAGNIMS Study Group (www.magnims.eu) which included 2D FLAIR and 3D T1 images with manual lesion segmentation as a reference. Automated lesion segmentations were produced using five algorithms: Cascade; Lesion Segmentation Toolbox (LST) with both the Lesion growth algorithm (LGA) and the Lesion prediction algorithm (LPA); Lesion-Topology preserving Anatomical Segmentation (Lesion-TOADS); and k-Nearest Neighbor with Tissue Type Priors (kNN-TTP). Main software parameters were optimized using a training set (N = 18), and formal testing was performed on the remaining patients (N = 52). To evaluate volumetric agreement with the reference segmentations, intraclass correlation coefficient (ICC) as well as mean difference in lesion volumes between the automated and reference segmentations were calculated. The Similarity Index (SI), False Positive (FP) volumes and False Negative (FN) volumes were used to examine spatial agreement. All analyses were repeated using a leave-one-center-out design to exclude the center of interest from the training phase to evaluate the performance of the method on 'unseen' center. RESULTS: Compared to the reference mean lesion volume (4.85 ± 7.29 mL), the methods displayed a mean difference of 1.60 ± 4.83 (Cascade), 2.31 ± 7.66 (LGA), 0.44 ± 4.68 (LPA), 1.76 ± 4.17 (Lesion-TOADS) and -1.39 ± 4.10 mL (kNN-TTP). The ICCs were 0.755, 0.713, 0.851, 0.806 and 0.723, respectively. Spatial agreement with reference segmentations was higher for LPA (SI = 0.37 ± 0.23), Lesion-TOADS (SI = 0.35 ± 0.18) and kNN-TTP (SI = 0.44 ± 0.14) than for Cascade (SI = 0.26 ± 0.17) or LGA (SI = 0.31 ± 0.23). All methods showed highly similar results when used on data from a center not used in software parameter optimization. CONCLUSION: The performance of the methods in this multi-center MS dataset was moderate, but appeared to be robust even with new datasets from centers not included in training the automated methods.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Esclerose Múltipla/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Esclerose Múltipla/patologia , Substância Branca/patologia
11.
Neuroimage ; 152: 312-329, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28286318

RESUMO

An important image processing step in spinal cord magnetic resonance imaging is the ability to reliably and accurately segment grey and white matter for tissue specific analysis. There are several semi- or fully-automated segmentation methods for cervical cord cross-sectional area measurement with an excellent performance close or equal to the manual segmentation. However, grey matter segmentation is still challenging due to small cross-sectional size and shape, and active research is being conducted by several groups around the world in this field. Therefore a grey matter spinal cord segmentation challenge was organised to test different capabilities of various methods using the same multi-centre and multi-vendor dataset acquired with distinct 3D gradient-echo sequences. This challenge aimed to characterize the state-of-the-art in the field as well as identifying new opportunities for future improvements. Six different spinal cord grey matter segmentation methods developed independently by various research groups across the world and their performance were compared to manual segmentation outcomes, the present gold-standard. All algorithms provided good overall results for detecting the grey matter butterfly, albeit with variable performance in certain quality-of-segmentation metrics. The data have been made publicly available and the challenge web site remains open to new submissions. No modifications were introduced to any of the presented methods as a result of this challenge for the purposes of this publication.


Assuntos
Mapeamento Encefálico/métodos , Medula Cervical/anatomia & histologia , Substância Cinzenta/anatomia & histologia , Processamento de Imagem Assistida por Computador/métodos , Adulto , Algoritmos , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Substância Branca/anatomia & histologia
12.
PLoS One ; 11(10): e0164890, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27741303

RESUMO

Diffusion tensor imaging (DTI) has recently started to be adopted into clinical investigations of spinal cord (SC) diseases. However, DTI applications to the lower SC are limited due to a number of technical challenges, related mainly to the even smaller size of the SC structure at this level, its position relative to the receiver coil elements and the effects of motion during data acquisition. Developing methods to overcome these problems would offer new means to gain further insights into microstructural changes of neurological conditions involving the lower SC, and in turn could help explain symptoms such as bladder and sexual dysfunction. In this work, the feasibility of obtaining grey and white matter (GM/WM) DTI indices such as axial/radial/mean diffusivity (AD/RD/MD) and fractional anisotropy (FA) within the lumbosacral enlargement (LSE) was investigated using a reduced field-of-view (rFOV) single-shot echo-planar imaging (ss-EPI) acquisition in 14 healthy participants using a clinical 3T MR system. The scan-rescan reproducibility of the measurements was assessed by calculating the percentage coefficient of variation (%COV). Mean FA was higher in WM compared to GM (0.58 and 0.4 in WM and GM respectively), AD and MD were higher in WM compared to GM (1.66 µm2ms-1 and 0.94 µm2ms-1 in WM and 1.2 µm2ms-1 and 0.82 µm2ms-1 in GM for AD and MD respectively) and RD was lower in WM compared to GM (0.58 µm2ms-1 and 0.63 µm2ms-1 respectively). The scan-rescan %COV was lower than 10% in all cases with the highest values observed for FA and the lowest for MD. This pilot study demonstrates that it is possible to obtain reliable tissue-specific estimation of DTI indices within the LSE using a rFOV ss-EPI acquisition. The DTI acquisition and analysis protocol presented here is clinically feasible and may be used in future investigations of neurological conditions implicating the lower SC.


Assuntos
Imagem por Ressonância Magnética , Medula Espinal/diagnóstico por imagem , Adulto , Feminino , Substância Cinzenta/diagnóstico por imagem , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reprodutibilidade dos Testes , Razão Sinal-Ruído , Substância Branca/diagnóstico por imagem , Adulto Jovem
13.
Sci Rep ; 6: 36151, 2016 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-27786306

RESUMO

Axonal loss in the spinal cord is one of the main contributing factors to irreversible clinical disability in multiple sclerosis (MS). In vivo axonal loss can be assessed indirectly by estimating a reduction in the cervical cross-sectional area (CSA) of the spinal cord over time, which is indicative of spinal cord atrophy, and such a measure may be obtained by means of image segmentation using magnetic resonance imaging (MRI). In this work, we propose a new fully automated spinal cord segmentation technique that incorporates two different multi-atlas segmentation propagation and fusion techniques: The Optimized PatchMatch Label fusion (OPAL) algorithm for localising and approximately segmenting the spinal cord, and the Similarity and Truth Estimation for Propagated Segmentations (STEPS) algorithm for segmenting white and grey matter simultaneously. In a retrospective analysis of MRI data, the proposed method facilitated CSA measurements with accuracy equivalent to the inter-rater variability, with a Dice score (DSC) of 0.967 at C2/C3 level. The segmentation performance for grey matter at C2/C3 level was close to inter-rater variability, reaching an accuracy (DSC) of 0.826 for healthy subjects and 0.835 people with clinically isolated syndrome MS.


Assuntos
Imagem por Ressonância Magnética , Medula Espinal/diagnóstico por imagem , Adulto , Algoritmos , Automação , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Substância Branca/diagnóstico por imagem
14.
Neuroimage Clin ; 10: 71-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26793433

RESUMO

Spinal cord (SC) atrophy, i.e. a reduction in the SC cross-sectional area (CSA) over time, can be measured by means of image segmentation using magnetic resonance imaging (MRI). However, segmentation methods have been limited by factors relating to reproducibility or sensitivity to change. The purpose of this study was to evaluate a fully automated SC segmentation method (PropSeg), and compare this to a semi-automated active surface (AS) method, in healthy controls (HC) and people with multiple sclerosis (MS). MRI data from 120 people were retrospectively analysed; 26 HC, 21 with clinically isolated syndrome, 26 relapsing remitting MS, 26 primary and 21 secondary progressive MS. MRI data from 40 people returning after one year were also analysed. CSA measurements were obtained within the cervical SC. Reproducibility of the measurements was assessed using the intraclass correlation coefficient (ICC). A comparison between mean CSA changes obtained with the two methods over time was performed using multivariate structural equation regression models. Associations between CSA measures and clinical scores were investigated using linear regression models. Compared to the AS method, the reproducibility of CSA measurements obtained with PropSeg was high, both in patients and in HC, with ICC > 0.98 in all cases. There was no significant difference between PropSeg and AS in terms of detecting change over time. Furthermore, PropSeg provided measures that correlated with physical disability, similar to the AS method. PropSeg is a time-efficient and reliable segmentation method, which requires no manual intervention, and may facilitate large multi-centre neuroprotective trials in progressive MS.


Assuntos
Medula Cervical/patologia , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Esclerose Múltipla/patologia , Adulto , Atrofia , Processamento Eletrônico de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos
15.
Lancet Neurol ; 15(3): 259-69, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26822749

RESUMO

BACKGROUND: Acute demyelinating optic neuritis, a common feature of multiple sclerosis, can damage vision through neurodegeneration in the optic nerve and in its fibres in the retina. Inhibition of voltage-gated sodium channels is neuroprotective in preclinical models. In this study we aimed to establish whether sodium-channel inhibition with phenytoin is neuroprotective in patient with acute optic neuritis. METHODS: We did a randomised, placebo-controlled, double-blind phase 2 trial at two UK academic hospitals in London and Sheffield. Patients with acute optic neuritis aged 18-60 years, presenting within 2 weeks of onset, with visual acuity of 6/9 or worse, were randomly assigned (1:1) by minimisation via a web-based service to oral phenytoin (maintenance dose 4 mg/kg per day if randomised before or on July 16, 2013, and 6 mg/kg per day if randomised on or after July 17, 2013) or placebo for 3 months, stratified by time from onset, centre, previous multiple sclerosis diagnosis, use of disease-modifying treatment, and use of corticosteroids for acute optic neuritis. Participants and treating and assessing physicians were masked to group assignment. The primary outcome was retinal nerve fibre layer (RNFL) thickness in the affected eye at 6 months, adjusted for fellow-eye RNFL thickness at baseline, analysed in a modified intention-to-treat population of all randomised participants who were followed up at 6 months. Safety was analysed in the entire population, including those who were lost to follow-up. The trial is registered with ClinicalTrials.gov, number NCT 01451593. FINDINGS: We recruited 86 participants between Feb 3, 2012, and May 22, 2014 (42 assigned to phenytoin and 44 to placebo). 29 were assigned to phenytoin 4 mg/kg and 13 to phenytoin 6 mg/kg. Five participants were lost to follow-up, so the primary analysis included 81 participants (39 assigned to phenytoin and 42 to placebo). Mean 6-month RNFL thickness in the affected eye at 6 months was 81.46 µm (SD 16.27) in the phenytoin group (a mean decrease of 16.69 µm [SD 13.73] from baseline) versus 74.29 µm (15.14) in the placebo group (a mean decrease of 23.79 µm [13.97] since baseline; adjusted 6-month difference of 7.15 µm [95% CI 1.08-13.22]; p=0.021), corresponding to a 30% reduction in the extent of RNFL loss with phenytoin compared with placebo. Treatment was well tolerated, with five (12%) of 42 patients having a serious adverse event in the phenytoin group (only one, severe rash, was attributable to phenytoin) compared with two (5%) of 44 in the placebo group. INTERPRETATION: These findings support the concept of neuroprotection with phenytoin in patients with acute optic neuritis at concentrations at which it blocks voltage-gated sodium channels selectively. Further investigation in larger clinical trials in optic neuritis and in relapsing multiple sclerosis is warranted. FUNDING: US National Multiple Sclerosis Society, Multiple Sclerosis Society of Great Britain and Northern Ireland, Novartis, UK National Institute for Health Research (NIHR), and NIHR UCLH/UCL Biomedical Research Centre.


Assuntos
Fármacos Neuroprotetores/farmacologia , Neurite Óptica/tratamento farmacológico , Avaliação de Resultados (Cuidados de Saúde) , Fenitoína/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/administração & dosagem , Fenitoína/administração & dosagem , Fenitoína/efeitos adversos , Bloqueadores do Canal de Sódio Disparado por Voltagem/administração & dosagem , Bloqueadores do Canal de Sódio Disparado por Voltagem/efeitos adversos
16.
Mult Scler ; 22(7): 910-20, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26432854

RESUMO

BACKGROUND: The in vivo relationship of spinal cord lesion features with clinical course and function in multiple sclerosis (MS) is poorly defined. OBJECTIVE: The objective of this paper is to investigate the associations of spinal cord lesion features on MRI with MS subgroup and disability. METHODS: We recruited 120 people: 25 clinically isolated syndrome, 35 relapsing-remitting (RR), 30 secondary progressive (SP), and 30 primary progressive (PP) MS. Disability was measured using the Expanded Disability Status Scale. We performed 3T axial cervical cord MRI, using 3D-fast-field-echo and phase-sensitive-inversion-recovery sequences. Both focal lesions and diffuse abnormalities were recorded. Focal lesions were classified according to the number of white matter (WM) columns involved and whether they extended to grey matter (GM). RESULTS: The proportion of patients with focal lesions involving at least two WM columns and extending to GM was higher in SPMS than in RRMS (p = 0.03) and PPMS (p = 0.015). Diffuse abnormalities were more common in both PPMS and SPMS, compared with RRMS (OR 6.1 (p = 0.002) and 5.7 (p = 0.003), respectively). The number of lesions per patient involving both the lateral column and extending to GM was independently associated with disability (p < 0.001). CONCLUSIONS: More extensive focal cord lesions, extension of lesions to GM, and diffuse abnormalities are associated with progressive MS and disability.


Assuntos
Doenças Desmielinizantes/diagnóstico por imagem , Imagem por Ressonância Magnética , Esclerose Múltipla Crônica Progressiva/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Vértebras Cervicais , Estudos Transversais , Doenças Desmielinizantes/fisiopatologia , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Medula Espinal/fisiopatologia , Substância Branca/fisiopatologia , Adulto Jovem
17.
PLoS One ; 10(7): e0134495, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26230729

RESUMO

Magnetisation transfer (MT) imaging of the central nervous system has provided further insight into the pathophysiology of neurological disease. However, the use of this method to study the lower spinal cord has been technically challenging, despite the important role of this region, not only for motor control of the lower limbs, but also for the neural control of lower urinary tract, sexual and bowel functions. In this study, the feasibility of obtaining reliable grey matter (GM) and white matter (WM) magnetisation transfer ratio (MTR) measurements within the lumbosacral enlargement (LSE) was investigated in ten healthy volunteers using a clinical 3T MRI system. The mean cross-sectional area of the LSE (LSE-CSA) and the mean GM area (LSE-GM-CSA) were first obtained by means of image segmentation and tissue-specific (i.e. WM and GM) MTR measurements within the LSE were subsequently obtained. The reproducibility of the segmentation method and MTR measurements was assessed from repeated measurements and their % coefficient of variation (%COV). Mean (± SD) LSE-CSA across 10 healthy subjects was 59.3 (± 8.4) mm2 and LSE-GM-CSA was 17.0 (± 3.1) mm2. The mean intra- and inter-rater % COV for measuring the LSE-CSA were 0.8% and 2.3%, respectively and for the LSE-GM-CSA were 3.8% and 5.4%, respectively. Mean (± SD) WM-MTR was 43.2 (± 4.4) and GM-MTR was 40.9 (± 4.3). The mean scan-rescan % COV for measuring WM-MTR was 4.6% and for GM-MTR was 3.8%. Using a paired t-test, a statistically significant difference was identified between WM-MTR and GM-MTR in the LSE (p<0.0001). This pilot study has shown that it is possible to obtain reliable tissue-specific MTR measurements within the LSE using a clinical MR system at 3T. The MTR acquisition and analysis protocol presented in this study can be used in future investigations of intrinsic spinal cord diseases that affect the LSE.


Assuntos
Substância Cinzenta/anatomia & histologia , Vértebras Lombares/anatomia & histologia , Magnetismo , Sacro/anatomia & histologia , Substância Branca/anatomia & histologia , Adulto , Feminino , Voluntários Saudáveis , Humanos , Imagem por Ressonância Magnética , Masculino , Projetos Piloto
18.
Brain ; 138(Pt 6): 1568-82, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25863355

RESUMO

Spinal neurodegeneration is an important determinant of disability progression in patients with primary progressive multiple sclerosis. Advanced imaging techniques, such as single-voxel (1)H-magnetic resonance spectroscopy and q-space imaging, have increased pathological specificity for neurodegeneration, but are challenging to implement in the spinal cord and have yet to be applied in early primary progressive multiple sclerosis. By combining these imaging techniques with new clinical measures, which reflect spinal cord pathology more closely than conventional clinical tests, we explored the potential for spinal magnetic resonance spectroscopy and q-space imaging to detect early spinal neurodegeneration that may be responsible for clinical disability. Data from 21 patients with primary progressive multiple sclerosis within 6 years of disease onset, and 24 control subjects were analysed. Patients were clinically assessed on grip strength, vibration perception thresholds and postural stability, in addition to the Expanded Disability Status Scale, Nine Hole Peg Test, Timed 25-Foot Walk Test, Multiple Sclerosis Walking Scale-12, and Modified Ashworth Scale. All subjects underwent magnetic resonance spectroscopy and q-space imaging of the cervical cord and conventional brain and spinal magnetic resonance imaging at 3 T. Multivariate analyses and multiple regression models were used to assess the differences in imaging measures between groups and the relationship between magnetic resonance imaging measures and clinical scores, correcting for age, gender, spinal cord cross-sectional area, brain T2 lesion volume, and brain white matter and grey matter volume fractions. Although patients did not show significant cord atrophy when compared with healthy controls, they had significantly lower total N-acetyl-aspartate (mean 4.01 versus 5.31 mmol/l, P = 0.020) and glutamate-glutamine (mean 4.65 versus 5.93 mmol/l, P = 0.043) than controls. Patients showed an increase in q-space imaging-derived indices of perpendicular diffusivity in both the whole cord and major columns compared with controls (P < 0.05 for all indices). Lower total N-acetyl-aspartate was associated with higher disability, as assessed by the Expanded Disability Status Scale (coefficient = -0.41, 0.01 < P < 0.05), Modified Ashworth Scale (coefficient = -3.78, 0.01 < P < 0.05), vibration perception thresholds (coefficient = -4.37, P = 0.021) and postural sway (P < 0.001). Lower glutamate-glutamine predicted increased postural sway (P = 0.017). Increased perpendicular diffusivity in the whole cord and columns was associated with increased scores on the Modified Ashworth Scale, vibration perception thresholds and postural sway (P < 0.05 in all cases). These imaging findings indicate reduced structural integrity of neurons, demyelination, and abnormalities in the glutamatergic pathways in the cervical cord of early primary progressive multiple sclerosis, in the absence of extensive spinal cord atrophy. The observed relationship between imaging measures and disability suggests that early spinal neurodegeneration may underlie clinical impairment, and should be targeted in future clinical trials with neuroprotective agents to prevent the development of progressive disability.


Assuntos
Medula Cervical/patologia , Esclerose Múltipla Crônica Progressiva/patologia , Degeneração Neural/patologia , Adolescente , Adulto , Idoso , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Atrofia/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Estudos de Casos e Controles , Medula Cervical/metabolismo , Avaliação da Deficiência , Diagnóstico Precoce , Feminino , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Substância Cinzenta/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/metabolismo , Degeneração Neural/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Medula Espinal/metabolismo , Medula Espinal/patologia , Substância Branca/patologia , Adulto Jovem
19.
Neurology ; 84(4): 367-73, 2015 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-25540312

RESUMO

OBJECTIVE: To investigate whether spinal cord (SC) lesion load, when quantified on axial images with high in-plane resolution, is associated with disability in multiple sclerosis (MS). METHODS: Twenty-eight healthy controls and 92 people with MS had cervical SC 3T MRI with axial phase sensitive inversion recovery, T2, and magnetization transfer (MT) sequences. We outlined all visible focal lesions from C2 to C4 to obtain lesion load and also measured upper cervical cord area. We measured MT ratio in normal-appearing cord tissue and in lesions. Disability was recorded using the Expanded Disability Status Scale (EDSS) and MS Functional Composite. We used linear regression models to determine associations with disability. RESULTS: SC lesion load was significantly higher in both secondary progressive MS (SPMS) (p = 0.008) and primary progressive MS (PPMS) (p = 0.02) compared to relapsing-remitting MS (RRMS); in each comparison, adjustment was made for age, sex, and brain volume. These differences were not evident when EDSS was added as a covariate. SC area was significantly lower in both SPMS (p < 0.001) and PPMS (p = 0.009) compared to RRMS. In a multiple regression model, cord lesion load (p < 0.001), cord area (p = 0.003), age (p < 0.001), and sex (p = 0.001) were independently associated with EDSS (R(2) = 0.58). Cord lesion load (p = 0.003), cord area (p = 0.034), and brain parenchymal fraction (p = 0.007) were independently associated with the 9-hole peg test (R(2) = 0.42). CONCLUSIONS: When quantified on axial MRI with high in-plane resolution, upper cervical cord lesion load is significantly and independently correlated with physical disability and is higher in progressive forms of MS than RRMS.


Assuntos
Medula Cervical/patologia , Imagem por Ressonância Magnética/métodos , Esclerose Múltipla Crônica Progressiva/patologia , Esclerose Múltipla Recidivante-Remitente/patologia , Doenças da Medula Espinal/patologia , Adulto , Atrofia/patologia , Avaliação da Deficiência , Feminino , Humanos , Imagem por Ressonância Magnética/instrumentação , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Crônica Progressiva/fisiopatologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia
20.
PLoS One ; 9(10): e105774, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25310093

RESUMO

Magnetic resonance spectroscopy (MRS) studies have previously described metabolite changes associated with aging of the healthy brain and provided insights into normal brain aging that can assist us in differentiating age-related changes from those associated with neurological disease. The present study investigates whether age-related changes in metabolite concentrations occur in the healthy cervical spinal cord. 25 healthy volunteers, aged 23-65 years, underwent conventional imaging and single-voxel MRS of the upper cervical cord using an optimised point resolved spectroscopy sequence on a 3T Achieva system. Metabolite concentrations normalised to unsuppressed water were quantified using LCModel and associations between age and spinal cord metabolite concentrations were examined using multiple regressions. A linear decline in total N-Acetyl-aspartate concentration (0.049 mmol/L lower per additional year of age, p = 0.010) and Glutamate-Glutamine concentration (0.054 mmol/L lower per additional year of age, p = 0.002) was seen within our sample age range, starting in the early twenties. The findings suggest that neuroaxonal loss and/or metabolic neuronal dysfunction, and decline in glutamate-glutamine neurotransmitter pool progress with aging.


Assuntos
Envelhecimento/metabolismo , Ácido Aspártico/metabolismo , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Medula Espinal/metabolismo , Adulto , Fatores Etários , Idoso , Colina/metabolismo , Creatina/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
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