Identifying and reverting the adverse effects of white matter hyperintensities on cortical surface analyses

ありふれた脳の白質病変がMRI画像解析を悪化させていた --従来手法に機械学習を組み入れた改善手法の開発--. 京都大学プレスリリース. 2023-10-02.The Human Connectome Project (HCP)-style surface-based brain MRI analysis is a powerful technique that allows precise mapping of the cerebral cortex. However, the strength of its surface-based analysis has not yet been tested in the older population that often presents with white matter hyperintensities (WMHs) on T2-weighted (T2w) MRI (hypointensities on T1w MRI). We investigated T1-weighted (T1w) and T2w structural MRI in 43 healthy middle-aged to old participants. Juxtacortical WMHs were often misclassified by the default HCP pipeline as parts of the gray matter in T1w MRI, leading to incorrect estimation of the cortical surfaces and cortical metrics. To revert the adverse effects of juxtacortical WMHs, we incorporated the Brain Intensity AbNormality Classification Algorithm into the HCP pipeline (proposed pipeline). Blinded radiologists performed stereological quality control (QC) and found a decrease in the estimation errors in the proposed pipeline. The superior performance of the proposed pipeline was confirmed using an originally-developed automated surface QC based on a large database. Here we showed the detrimental effects of juxtacortical WMHs for estimating cortical surfaces and related metrics and proposed a possible solution for this problem. The present knowledge and methodology should help researchers identify adequate cortical surface biomarkers for aging and age-related neuropsychiatric disorders

Neuroimaging at 7 Tesla: a pictorial narrative review

Neuroimaging using the 7-Tesla (7T) human magnetic resonance (MR) system is rapidly gaining popularity after being approved for clinical use in the European Union and the USA. This trend is the same for functional MR imaging (MRI). The primary advantages of 7T over lower magnetic fields are its higher signal-to-noise and contrast-to-noise ratios, which provide high-resolution acquisitions and better contrast, making it easier to detect lesions and structural changes in brain disorders. Another advantage is the capability to measure a greater number of neurochemicals by virtue of the increased spectral resolution. Many structural and functional studies using 7T have been conducted to visualize details in the white matter and layers of the cortex and hippocampus, the subnucleus or regions of the putamen, the globus pallidus, thalamus and substantia nigra, and in small structures, such as the subthalamic nucleus, habenula, perforating arteries, and the perivascular space, that are difficult to observe at lower magnetic field strengths. The target disorders for 7T neuroimaging range from tumoral diseases to vascular, neurodegenerative, and psychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, major depressive disorder, and schizophrenia. MR spectroscopy has also been used for research because of its increased chemical shift that separates overlapping peaks and resolves neurochemicals more effectively at 7T than a lower magnetic field. This paper presents a narrative review of these topics and an illustrative presentation of images obtained at 7T. We expect 7T neuroimaging to provide a new imaging biomarker of various brain disorders

T1/T2-weighted ratio in multiple sclerosis: A longitudinal study with clinical associations

Clinically isolated syndrome; Magnetic resonance imaging; Multiple sclerosisSíndrome clínicamente aislado; Imágenes por resonancia magnética; Esclerosis múltipleSíndrome clínicament aïllat; Imatges per ressonància magnètica; Esclerosi múltipleBackground T1w/T2-w ratio has been proposed as a clinically feasible MRI biomarker to assess tissue integrity in multiple sclerosis. However, no data is available in the earliest stages of the disease and longitudinal studies analysing clinical associations are scarce. Objective To describe longitudinal changes in T1-w/T2-w in patients with clinically isolated syndrome (CIS) and multiple sclerosis, and to investigate their clinical associations. Methods T1-w/T2-w images were generated and the mean value obtained in the corresponding lesion, normal-appearing grey (NAGM) and white matter (NAWM) masks. By co-registering baseline to follow-up MRI, evolved lesions were assessed; and by placing the mask of new lesions to the baseline study, the pre-lesional tissue integrity was measured. Results We included 171 CIS patients and 22 established multiple sclerosis patients. In CIS, evolved lesions showed significant T1-w/T2-w increases compared to baseline (+7.6%, P < 0.001). T1-w/T2-w values in new lesions were lower than in pre-lesional tissue (-28.2%, P < 0.001), and pre-lesional tissue was already lower than baseline NAWM (-7.8%, P < 0.001). In CIS at baseline, higher NAGM T1-w/T2-w was associated with multiple sclerosis diagnosis, and longitudinal decreases in NAGM and NAWM T1-w/T2-w were associated with disease activity. In established multiple sclerosis, T1-w/T2-w was inversely correlated with clinical disability and disease duration. Conclusion A decrease in T1-w/T2-w ratio precedes lesion formation. In CIS, higher T1-w/T2-w was associated with multiple sclerosis diagnosis. In established multiple sclerosis, lower T1-w/T2-w values were associated with clinical disability. The possible differential impact of chronic inflammation, iron deposition and demyelination should be considered to interpret these findings.This project was developed as a part of Mateus Boaventura ECTRIMS Clinical Training Fellowship Programme 2018–2019. This study was partially supported by the Project PI18/00823, from the Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III

Development of an image processing pipeline for the study of corticol lesions in multiple sclerosis patients using ultra-high field MRI

Tese de mestrado integrado, Engenharia Biomédica e Biofísica (Biofísica Médica e Fisiologia de Sistemas), Universidade de Lisboa, Faculdade de Ciências, 2019A esclerose múltipla é uma doença crónica e inflamatória do sistema nervoso central de alta prevalência nos dias de hoje. Durante anos, o foco da doença foi a patologia visível na matéria branca. Apesar dos primeiros estudos de patologia cortical em esclerose múltipla apontarem para a década de 60, foi apenas no início do novo século que o córtex passou a ser estudado como parte integral da doença. Desde então, estudos têm vindo a demonstrar que o comprometimento do córtex parece estar relacionado com danos cognitivos e físicos, frequentemente associados à doença. A necessidade de melhor compreender o impacto das lesões corticais no desenvolvimento da doença e na vida diária destes pacientes tem motivado o seu estudo, sendo a Ressonância Magnética (RM), em particular scanners de campo ultra-alto, a melhor ferramenta para as detetar e estudar. A melhoria da razão sinal-ruído e da resolução espacial dos scanners de RM de campo ultra-alto tem permitido o aumento da deteção de lesões corticais. Ainda assim, a sua sensibilidade continua a não ser ideal e a estar fortemente dependente do tipo de lesão cortical, do contraste de RM usado na sua deteção e da existência de ferramentas robustas que permitam a sua deteção de modo automático, mais eficiente e com menor espaço para erro. A falta de marcadores de imagem para a remielinização ou desmielinização parcial, tal como a ausência de diretrizes para a deteção destas lesões com campos de 7 (T)esla parece explicar a dificuldade em distinguir e identificar falsos positivos e as diferenças encontradas nas deteções realizadas por diferentes avaliadores. Uma desvantagem dos scanners de campo ultra-alto é o maior efeito de bias que, caso não seja removido aquando da aquisição de imagens, terá de ser removido na fase de processamento por softwares e algoritmos que não estão originalmente construídos para trabalhar com imagens de maior resolução e cuja prestação não está ainda bem explorada nestas condições. Estes desafios comprometem o potencial dos scanners de RM de campo ultra-alto para o estudo das lesões corticais na esclerose múltipla. Este projeto procura desenvolver uma pipeline semiautomática para o pré-processamento e processamento de imagens de RM de cariz estrutural de doentes com esclerose múltipla obtidas num scanner de campo ultra-alto. A pipeline é criada de modo gradual, recorrendo a análises visuais, ou de outro tipo, para confirmar a qualidade de cada passo antes de avançar para o seguinte, no pressuposto de que a qualidade dos softwares de imagem comercialmente disponíveis será menor ao utilizar imagens de maior resolução. A ocorrência de lesões corticais no córtex sensório-motor (SM1) é igualmente determinada e usada para validar a qualidade da pipeline. Doze doentes com esclerose múltipla na sua forma recidivante-remitente ou secundariamente progressiva e seis controlos foram incluídos neste projeto. Todas as permissões necessárias do comité local de ética, proteção de dados e da Danish Medicines Agency foram previamente obtidas. Os doentes foram estudados num scanner de RM de corpo inteiro da Philips, Achieva 7,0 T, dedicado a investigação. Os participantes foram observados usando quatro tipos distintos de contraste: magnetization prepared rapid acquisition by gradient echo (MPRAGE) a três dimensões (3D) com 0,65-mm de resolução isotrópica, 3D fluid attenuated inversion recovery (FLAIR) com 0,7-mm de resolução isotrópica, 3D T1-weighted (T1w) de resolução 0,85x0,85x1,0 mm3 e 3D T2-weighted Turbo Spin Echo (T2w-TSE) de 0,4-mm de resolução isotrópica. A vertente de pré-processamento da pipeline incluiu uma correção de bias e o co-registo de imagens. Para a correção de bias, o software SPM foi testado utilizando os parâmetros habituais e uma alteração dos parâmetros relativos à smoothness e regularização, como sugerido na literatura. O processo de co-registo seguiu o procedimento utilizado no processamento de imagens de doentes com esclerose múltipla de 3 T no Danish Research Centre for Magnetic Resonance (DRCMR), com alterações posteriormente adicionadas para melhorar a qualidade do alinhamento das imagens de cada indivíduo a 7 T. Após o pré-processamento, uma deteção de lesões corticais, seguida da sua segmentação, foi realizada manualmente utilizando as ferramentas do software FSL. A vertente de processamento da pipeline incluiu uma segmentação do cérebro, um registo das imagens dos doentes e a criação de superfícies corticais. A segmentação foi testada utilizando três diferentes ferramentas: o software SPM, uma toolbox do SPM, CAT, e a ferramenta de segmentação do FSL, FAST. A toolbox do SPM, DARTEL, foi usada no registo de imagens e o software FreeSurfer permitiu a criação de superfícies individuais e de grupo no último passo da pipeline. As máscaras com as lesões criadas após a segmentação manual de lesões seguiram um caminho semelhante de processamento de modo a permitir a sua correta sobreposição no respetivo volume, e, posteriormente, superfície, e a possibilidade de fazer análises individuais ou de grupo. Os resultados obtidos mostraram que os softwares para processamento de imagens de RM disponíveis apresentam, em geral, uma boa prestação e fornecem resultados de confiança. Ainda assim, a sua prestação pode ser otimizada incluindo procedimentos adicionais em cada passo ou por alteração das configurações originais dos softwares. A diminuição do parâmetro de largura à meia altura com um aumento do parâmetro de regularização na correção de bias com o SPM permitiu a criação de campos de bias mais fieis às imagens originais, consequentemente melhorando a sua correção e a diferenciação da matéria branca e matéria cinzenta nas imagens resultantes. A criação adicional de máscaras contendo apenas o cérebro e a utilização exclusiva de transformações de corpo rígido no co-registo de imagens permitiu a utilização de vários contrastes na tarefa de deteção de lesões, sem interferir com a sua localização ou morfologia. Na segmentação, a toolbox do SPM, CAT, mostrou melhorias na capacidade de separar as diferentes classes de tecidos com maior confiança e qualidade, particularmente nas regiões de contacto entre a matéria branca e cinzenta. Consequentemente, a qualidade do alinhamento das imagens dos diferentes doentes e a posterior criação de uma imagem média a partir de imagens individuais foi melhorada. O sucesso da pipeline permitiu a sobreposição das lesões corticais manualmente segmentadas nas superfícies individuais e/ou comuns criadas, onde foi descoberto que a maioria das lesões ocorreu no hemisfério direito, com sobreposições de lesões respetivas a diferentes doentes a ocorrer maioritariamente nos sulcos corticais, comparativamente aos giros. Porém, a segmentação de lesões demonstrou ser dispendiosa, dependente do avaliador e altamente influenciada por fatores inerentes ao avaliador, tal como o cansaço, nível de concentração ou de aborrecimento, e fatores externos, no qual se destacam a luminosidade do computador ou a luminosidade da sala onde a deteção foi feita. A feature do FreeSurfer para imagens de maior resolução não se mostrou fiável no tratamento dos dados de resolução isotrópica de 0,5-mm deste projeto, uma possível razão pela qual ainda se encontra em desenvolvimento. Apesar dos bons resultados obtidos, investigação adicional será necessária para melhor compreender a prestação destes e de outros softwares para imagem médica no processamento de imagens de RM de maior resolução, tal como a melhor maneira de tirar partido dos mesmos em estudos clínicos a 7 T. A extensão da pipeline a outros doentes com esclerose múltipla irá aumentar a amostra em estudo e permitir um estudo mais extensivo da patologia cortical e a compreensão do impacto de uma ou mais lesões localizadas na região SM1 na conectividade e integridade funcional da região cortical afetada.The importance of grey matter pathology to the understanding of multiple sclerosis has been acknowledged. However, the sensitivity to cortical lesions is limited when using conventional magnetic resonance imaging (MRI) systems. Ultra-high field (UHF) MRI systems have improved detection sensitivity but impose the additional challenge of a higher effect of bias to account for. Currently, image processing tools are not designed for higher resolution data and the performance of common software packages under these conditions has not been properly explored. These challenges have impaired the potential of UHF-MRI to study cortical lesions in multiple sclerosis. This project aims at developing a semi-automated pipeline for the pre-processing and processing of structural UHF-MRI data of multiple sclerosis patients. The pipeline is built in a step-by-step fashion, making use of visual assessments and other analyses to confirm the quality of each step before advancing to the next, under the assumption that the performance of common imaging software packages will be poorer when using higher resolution data. The occurrence of cortical lesions within the primary sensory-motor cortex (SM1) is also determined and used to validate the quality of the pipeline. Twelve patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis and six healthy age-matched controls were included in this project. All relevant permissions from the local ethics committee and data protection had been obtained beforehand. All participants were studied with whole-brain ultra-high field MRI at 7 Tesla (T), using a research-only 7 T Achieva MR system. The participants were scanned using four different MRI modalities, namely 3-dimensional (3D) magnetization prepared rapid acquisition by gradient echo (MPRAGE) at 0.65-mm isotropic resolution, 3D fluid attenuated inversion recovery (FLAIR) at 0.7-mm isotropic resolution, 3D T1-weighted (T1w) of 0.85x0.85x1.0 mm3 reconstructed resolution and 3D T2-weighted Turbo Spin Echo (T2w-TSE) at 0.4-mm isotropic reconstructed resolution. The pre-processing pipeline included a bias correction and a coregistration step. For the bias correction, SPM was tested using its default parameters and an alternative configuration that altered the smoothness and regularization parameters. The coregistration followed an approach used in the processing of multiple sclerosis data at 3 T, with changes added to improve the quality of the within-subject alignment at 7 T. After the data pre-processing, manual detection and segmentation of cortical lesions was performed using FSLeyes. The processing pipeline included brain segmentation, subject registration and cortical surface creation. Brain segmentation was tested with SPM, with SPM’s toolbox, CAT, and with FSL’s segmentation tool, FAST. SPM’s DARTEL tool was used for subject registration and FreeSurfer allowed the creation of individual and an average cortical surface. The lesion masks created after the manual segmentation task followed a similar processing route to allow their overlay on the respective brain volumes and, posteriorly, surfaces, and the possibility of individual and group analyses. Results showed that the currently available MRI image processing tools present overall good performance and reliability in the processing of higher resolution data of multiple sclerosis patients. Still, the quality of the outcomes can be optimized by including additional steps or changes to the original software configurations. Modifying SPM’s smoothness and regularization parameters for the estimation of bias minimized its effect in the data, allowing a better differentiation between grey matter and white matter. Removing the skull whilst keeping the coregistration to rigid body transformations allowed the use of several contrasts in the lesion detection task without interfering with the lesions’ morphology and topography. Brain segmentation using CAT showed more stability across the dataset, improving the quality of the subsequent subject registration and consequently of the average brain created. The success of the pipeline led to the possibility of overlaying the manually segmented lesions on the individual and group surfaces where it was found that the majority of lesions occurred on the right hemisphere and that lesion overlaps were more common in cortical sulci. Despite the results obtained, further research is needed to understand the performance of other software packages in the processing of higher resolution MRI data and how to fully exploit these tools in the study of clinical data at 7 T

Regional grey matter microstructural changes and volume loss according to disease duration in multiple sclerosis patients

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER, "Otra manera de hacer Europa", "Investing in your future"); Red Española de Esclerosis Múltiple (REEM - RD16/0015/0002, RD16/0015/0003, RD12/0032/0002, RD12/0060/01-02); TEVA Spain; Fundación Merck Salud (Ayudas Merck de Investigación 2017); Proyecto Societat Catalana Neurologia 2017; CIBERNED program (Program 1, Alzheimer Disease and SIGNAL study); National Institutes of Health (NIA grants 1R01AG056850-01A1, R21AG056974, R01AG061566;, Fundació La Marató de TV3 (20142030, 20141210); Fundació Catalana Síndrome de Down; Fundació Víctor Grífols i Lucas; Generalitat de Catalunya (SLT006/17/00119); Universitat de Barcelona (APIF Pre-doctoral grant); Hospital Clinic Emili Letang).The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease duration. Additionally, we investigated the relationship between GM changes with disease severity. We studied 54 healthy controls and 247 MS patients classified regarding disease duration: MS1 (less than 5 years, n = 67); MS2 (5-15 years, n = 107); and MS3 (more than15 years, n = 73). We compared GM mean diffusivity (MD), fractional anisotropy (FA) and volume between groups, and estimated their clinical associations. Regional modifications in diffusion measures (MD and FA) and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in deep GM and left precuneus. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes in MD and volume extended to more than 80% of regions in MS3 group. Conversely, increments in FA, with very low effect size, were observed in the parietal cortex and thalamus in MS1 and MS2 groups, and extended to the frontal lobe in the later group. MD and GM changes were associated with white matter lesion load and with physical and cognitive disability. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage

Assessment Of The Interplay Between Regional β-Amyloid Burden And White Matter Hyperintensities On Cognition And Default Mode Network In Clinically Normal Older Participants

Objective: Alzheimer’s disease (AD) and subcortical vascular dementia are considered the most common pathologic contributors to dementia in the aging population. Both frequently coexist in over 80% of community dwelling adults with dementia. The neuropathological development of AD arguably begins with β-amyloid (Aβ) deposition in the brain. This series of studies aims to test the hypothesis that early focal regional amyloid deposition in the brain is associated with cognitive performance in specific cognitive domain scores in preclinical AD (pAD) (study1). Since mixed dementia is widely recognized as the norm rather than the exception, the second study aimed to explore the relation between regional and global Aβ and WMH with core cognitive function (executive function (EF) and memory) scores in cognitively normal (CN) older adults (study2). Finally, the relationship between WMH and Aβ is strongly determined by the spatial distribution of the two pathologies, so the third study aimed to quantify Aβ in Default mode network (DMN) regions to examine whether cerebral small vessels disease (SVD) disruption of connectivity affects Aβ deposition in disconnected DMN regions (study3). Method: Global and regional Standard Uptake Value ratios (SUVr) from Aβ-PET, WMH volumes from MRI FLAIR images, and cognitive test scores were analyzed across a sample of CN participants. Linear regression models adjusted for age, sex and education used to assess the relationships between regional SUVr and cognitive test scores across 99 CN from Sanders Brown Center on Aging (study1). Moderation, and mediation modeling were used to define the interplay between global, regional Aβ and WMHs measures in relation to EF and memory composite scores outcomes at baseline and after approximately 2 years across a sample of 714 CN from the Alzheimer’s Disease Neuroimaging Initiative ADNI (study2). The association of WMH volume in anatomically defined white matter tracts of atlas-based fiber tract with Aβ SUVr specifically in connected cortical regions within DMN was tested across sample of 74 CN from ADNI3. Results: EF performance was associated with increased regional SUVr in the precuneus and posterior cingulate regions only (p \u3c 0.05). The moderation regression analysis showed additive effects of Aβ and WMH over baseline memory and EF scores (p =0.401 and 0.061 respectively) and synergistic effects over follow-up EF (p \u3c 0.05). Through mediation analysis, the data from study 2 showed that WMH affects, mediated by global and regional amyloid burden, are responsible for baseline cognitive performance deficits in memory and EF. Finally, the regression analysis from study 3 demonstrated that increased WMH volumes in superior longitudinal fasciculus (SLF) was associated with increased regional SUVr in inferior parietal lobule (IPL) (p \u3c 0.05). Conclusion: While the prevailing view in the field suggests that memory performance is the earliest clinical hallmark of AD, the present data demonstrate that changes in EF, mediated by Aβ deposition in the precuneus and posterior cingulate may precede memory decline in pAD. After adding the second key driver of cognitive decline in CN, the finding suggested that WMH dependent changes in baseline cognitive performance are related to direct effect of WMH and an indirect effect through both global and regional Aβ burden. Further studies are needed to show the longitudinal influences of WMH on Aβ distributions in participants with mixed dementia

Periventricular magnetisation transfer abnormalities in early multiple sclerosis

OBJECTIVE: Recent studies suggested that CSF-mediated factors contribute to periventricular (PV) T2-hyperintense lesion formation in multiple sclerosis (MS) and this in turn correlates with cortical damage. We thus investigated if such PV-changes are observable microstructurally in early-MS and if they correlate with cortical damage. METHODS: We assessed the magnetisation transfer ratio (MTR) in PV normal-appearing white matter (NAWM) and in MS lesions in 44 patients with a clinically isolated syndrome (CIS) suggestive of MS and 73 relapsing-remitting MS (RRMS) patients. Band-wise MTR values were related to cortical mean thickness (CMT) and compared with 49 healthy controls (HCs). For each band, MTR changes were assessed relative to the average MTR values of all HCs. RESULTS: Relative to HCs, PV-MTR was significantly reduced up to 2.63% in CIS and 5.37% in RRMS (p<0.0001). The MTR decreased towards the lateral ventricles with 0.18%/mm in CIS and 0.31%/mm in RRMS patients, relative to HCs. In RRMS, MTR-values adjacent to the ventricle and in PV-lesions correlated positively with CMT and negatively with EDSS. CONCLUSION: PV-MTR gradients are present from the earliest stage of MS, consistent with more pronounced microstructural WM-damage closer to the ventricles. The positive association between reduced CMT and lower MTR in PV-NAWM suggests a common pathophysiologic mechanism. Together, these findings indicate the potential use of multimodal MRI as refined marker for MS-related tissue changes

Cortical imaging as seen at ultrahigh field MRI

Multiple Sclerosis (MS) has long been considered as White matter (WM) disease. The last decade, the significance of cortical lesions (CL) and their contribution to MS pathology has been intensely investigated. They have been shown to play a major role in physical and cognitive impairment in MS patients. CL detection has proven to be challenging, mainly due to poor contrast between cortical lesion and surrounding normal grey matter (GM) tissue. Various magnetic resonance imaging (MRI) sequences have been used to improve cortical lesion detection in MS patients. In recent years, Double inversion recovery (DIR), Phase sensitive inversion recovery (PSIR) and 7 Tesla T2* have been found to improve CL detection. Magnetization Transfer Imaging (MTI) has the advantage over conventional imaging as it reflects tissue myelin content. In this thesis, I present our studies using MTI at 7 Tesla to study cortical pathology in MS. 1) For a pilot study aiming to validate the use of magnetization transfer ratio (MTR) to detect cortical lesions, We examined the sensitivity of MTR to detect cortical lesions in comparison with 3 T DIR, 7 T PSIR, and 7 T T2* in 18 MS patients and 9 healthy controls. 2) A further 42 patients (11 clinically isolated syndrome (CIS), 11 relapsing remitting MS (RRMS), 10 primary progressive MS (PPMS), and 10 secondary progressive MS (SPMS)) and 8 healthy controls were scanned at baseline, 23 of these patients had a follow up scan at 12 months. MTR at 7 Tesla has increased sensitivity to detect cortical lesions compared to 3T DIR, 7T PSIR and 7T T2*. CL myelin content as measured by the mean MTR lesional values were the lowest in SPMS patients in comparison with the rest of MS phenotypes. CL mean MTR values, more than volume was associated with the degree of physical and cognitive disability in MS patients. When MTR was studied in a longitudinal study, we have seen more changes in average MTR of cortical lesions in SPMS and CIS patients compared to RRMS and PPMS patients