A Better Characterization of Spinal Cord Damage in Multiple Sclerosis: A Diffusional Kurtosis Imaging Study

BACKGROUND AND PURPOSE: The spinal cord is a site of predilection for MS lesions. While diffusion tensor imaging is useful for the study of anisotropic systems such as WM tracts, it is of more limited utility in tissues with more isotropic microstructures (on the length scales studied with diffusion MR imaging) such as gray matter. In contrast, diffusional kurtosis imaging, which measures both Gaussian and non-Gaussian properties of water diffusion, provides more biomarkers of both anisotropic and isotropic structural changes. The aim of this study was to investigate the cervical spinal cord of patients with MS and to characterize lesional and normal-appearing gray matter and WM damage by using diffusional kurtosis imaging. MATERIALS AND METHODS: Nineteen patients (13 women, mean age = 41.1 ± 10.7 years) and 16 controls (7 women, mean age = 35.6 ± 11.2-years) underwent MR imaging of the cervical spinal cord on a 3T scanner (T2 TSE, T1 magnetization-prepared rapid acquisition of gradient echo, diffusional kurtosis imaging, T2 fast low-angle shot). Fractional anisotropy, mean diffusivity, and mean kurtosis were measured on the whole cord and in normal-appearing gray matter and WM. RESULTS: Spinal cord T2-hyperintense lesions were identified in 18 patients. Whole spinal cord fractional anisotropy and mean kurtosis ( P = .0009, P = .003), WM fractional anisotropy ( P = .01), and gray matter mean kurtosis ( P = .006) were significantly decreased, and whole spinal cord mean diffusivity ( P = .009) was increased in patients compared with controls. Mean spinal cord area was significantly lower in patients ( P = .04). CONCLUSIONS: Diffusional kurtosis imaging of the spinal cord can provide a more comprehensive characterization of lesions and normal-appearing WM and gray matter damage in patients with MS. Diffusional kurtosis imaging can provide additional and complementary information to DTI on spinal cord pathology

A combination of functional magnetic resonance imaging and diffusion tensor image to explore structure-function relationship in healthy and myelopathic spinal cord

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Correlation of Diffusion Tensor Imaging Indices with Histological Parameters in Rat Cervical Spinal Cord Gray Matter Following Distal Contusion Spinal Cord Injury

The purpose of this study was to delineate the diffusion tensor imaging (DTI) parameters across the cervical spinal cord gray matter (GM) in a distal (T8) rat contusion spinal cord injury (SCI) model. DTI data were obtained from ex vivo rat spinal cords and registered to corresponding histological slices in samples from the acute through chronic stages of SCI including uninjured control, 2 weeks post injury, 15 weeks post injury and 25 weeks post injury groups (n = 5 in all groups). After imaging, samples were dehydrated, blocked in paraffin, sliced axially and stained with eriochrome cyanine R stain and H&E counter-stain. A corresponding sample was post fixed with osmium tetroxide and stained with toluidine blue. Histology images of the eriochrome cyanine R stained and H&E counter-stained slices were captured at 4x and then segmented into white matter (WM) and GM and dorsal and ventral GM using a custom cluster analysis. Using whole cord templates, DTI images for each animal were then registered to the corresponding histology images. The WM and the GM regions of interest (ROI) histological templates were then used to map DTI indices, including fractional anisotropy (FA), longitudinal apparent diffusion coefficient (lADC) and transverse apparent diffusion coefficient (tADC) across the GM. The average values for each index were also calculated in predefined gray matter ROIs. Histology images of the above mentioned ROIs were captured at 40x resolution using the toluidine blue stained slices for the control and post injury groups (n=4). Motoneuron size in the ventral GM was calculated for each of the control and post injury groups. It was observed that the FA and lADC values in the dorsal GM ROI were significantly higher than that in the ventral GM ROI in controls, fifteen weeks post injury and twenty five weeks post injury groups (P \u3c 0.05). The overall GM FA value at twenty five weeks was significantly higher than the FA value at two weeks post injury (P \u3c 0.05) and the FA value in controls (P \u3c 0.05). Group analysis of the size of the motor neurons showed a 9% increase in the motoneuron size at two weeks (P \u3c 0.01) and 42% increase at twenty five weeks (P \u3c 0.01) post injury as compared to controls. The motor neurons also showed a significant increase in size at twenty five weeks post injury (P \u3c 0.01) as compared to the motor neuron size at two weeks post injury. These results indicate changes in gray matter structure rostral to a contusion injury that can be detected and monitored using DTI

Effectiveness of regional diffusion MRI measures in distinguishing multiple sclerosis abnormalities within the cervical spinal cord

ABSTRACT: Introduction Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system. Although conventional magnetic resonance imaging (MRI) is widely used for MS diagnosis and clinical follow-up, quantitative MRI has the potential to provide valuable intrinsic values of tissue properties that can enhance accuracy. In this study, we investigate the efficacy of diffusion MRI in distinguishing MS lesions within the cervical spinal cord, using a combination of metrics extracted from diffusion tensor imaging and Ball-and-Stick models. Methods We analyzed spinal cord data acquired from multiple hospitals and extracted average diffusion MRI metrics per vertebral level using a collection of image processing methods and an atlas-based approach. We then performed a statistical analysis to evaluate the feasibility of these metrics for detecting lesions, exploring the usefulness of combining different metrics to improve accuracy. Results Our study demonstrates the sensitivity of each metric to underlying microstructure changes in MS patients. We show that selecting a specific subset of metrics, which provide complementary information, significantly improves the prediction score of lesion presence in the cervical spinal cord. Furthermore, the Ball-and-Stick model has the potential to provide novel information about the microstructure of damaged tissue. Conclusion Our results suggest that diffusion measures, particularly combined measures, are sensitive in discriminating abnormal from healthy cervical vertebral levels in patients. This information could aid in improving MS diagnosis and clinical follow-up. Our study highlights the potential of the Ball-and-Stick model in providing additional insights into the microstructure of the damaged tissue

Spinal and encephalic structural damage in spinocerebellar ataxia type 1 : characterization and clinical correlates

Orientador: Marcondes Cavalcante França JuniorTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: A ataxia espinocerebelar do tipo 1 (SCA1) é uma doença neurodegenerativa cuja expressão clínica predominante é a ataxia cerebelar progressiva associada à hiperreflexia profunda e às alterações sacádicas. Causada por expansão instável de uma sequência CAG no gene ATXN1 no cromossomo 6, foi a primeira ataxia espinocerebelar que teve seu substrato genético elucidado. Apesar disso, existem poucos estudos acerca de seus aspectos clínicos e morfológicos, principalmente no que diz respeito às manifestações não motoras e suas correlações estruturais. Desta forma, o objetivo deste trabalho é caracterizar, clínica e morfologicamente, os pacientes com SCA1, utilizando escalas clínicas bem estabelecidas e técnicas multimodais de ressonância magnética. Para tanto, foram recrutados 33 pacientes adultos com teste molecular positivo para SCA1 acompanhados nos serviços de neurologia da UNICAMP e UNIFESP. Os pacientes foram submetidos a exame neurológico pormenorizado, enfatizando aspectos motores e não-motores. Para a graduação da ataxia utilizou-se a Scale for the Assessment and Rating of Ataxia (SARA). Para avaliação de sintomas não-motores utilizou-se a Modified Fatigue Impact Scale (MFIS) para fadiga, Epworth Sleepiness Scale (ESS) para sonolência excessiva diurna, Beck Depression Inventory (BDI) para depressão e Addenbrooke¿s Cognitive Examination ¿ Revised (ACE-R) para cognição. O dano estrutural encefálico e medular foi avaliado por imagens de ressonância magnética ponderadas em T1 e DTI. Para análise, foram utilizadas as ferramentas FreeSurfer, T1 MultiAtlas, DTI MultiAtlas, CERES e SpineSeg. Com o objetivo de avaliar evolutivamente a SCA1, os pacientes foram divididos em três grupos de acordo com o tempo de doença. Variáveis clínicas e imaginológicas foram comparadas nesses grupos a fim de determinar, temporalmente, o padrão evolutivo das alterações no SNC. Os sintomas motores correlacionaram-se diretamente com o dano dos núcleos rubros, medular e cerebelar. Os níveis de fadiga foram significativamente maiores nos pacientes comparado aos controles e apresentaram relação direta com depressão e duração da doença. A depressão foi mais frequente nos pacientes e correlacionou-se com aspectos motores, entretanto, não houve correlação com áreas encefálicas. As alterações cognitivas foram importantes, principalmente nos domínios de memória e fluência, os quais correlacionaram-se diretamente com atrofia na amígdala e lóbulo VIII cerebelar, respectivamente. Evidenciou-se redução da área e aumento da excentricidade significativos na medula cervical dos pacientes quando comparados aos controles. A redução da área medular correlacionou-se diretamente com aspectos motores, apresentando duração e CAGn como possíveis determinantes. Avaliações transversais do encéfalo revelaram danos significativos em áreas primárias e associativas em córtex cerebral, substância cinzenta profunda, córtex cerebelar e subtância branca encefálica, principalmente em regiões infratentoriais. Do ponto de vista evolutivo, verificou-se padrão lesional em sentido caudo-cranial. Por fim, fomos capazes de caracterizar fenoticamente a SCA1 e correlacionar seus aspectos clínicos e estruturaisAbstract: Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease expressed clinically by progressive cerebellar ataxia associated with deep hyperreflexia and saccadic alterations. Caused by unstable expansions of a CAG sequence in the ATXN1 gene on chromosome 6, it was the first spinocerebellar ataxia that had its genetic substrate elucidated. Despite this, there are few studies about its clinical and morphological aspects, mainly regarding non-motor manifestations and their structural correlations. In this way, the objective of this study is to characterize, clinically and morphologically, patients with SCA1, using well-established clinical scales and multimodal magnetic resonance techniques. We have thus evaluated 33 consecutive adult patients regularly followed at UNICAMP and UNIFESP and 33 healthy age-and-sex matched controls. All patients had molecular confirmation of SCA1. The patients underwent detailed neurological examination, emphasizing motor and non-motor aspects. For ataxia quantification, the Scale for the Assessment and Rating of Ataxia (SARA) was used. For the evaluation of non-motor symptoms, we used the Modified Fatigue Impact Scale (MFIS) for fatigue, Epworth Sleepiness Scale (ESS) for excessive daytime sleepiness, Beck Depression Inventory (BDI) for depression and Addenbrooke's Cognitive Examination ¿ Revised (ACE-R) for cognition aspects. The encephalic and spinal structural damage were evaluated by DTI and T1-weighted magnetic resonance imaging. For MRI analyses, the tools FreeSurfer, T1 MultiAtlas, DTI MultiAtlas, CERES and SpineSeg were used. Attempting to analyse the evolution pattern, the patients were divided into three groups according to the disease duration. Clinical and imaging variables were compared in these groups to determine the evolutionary pattern of CNS changes. Motor symptoms correlated to damage of red nuclei, spinal cord and cerebellar cortex. Fatigue levels were significantly higher in patients compared to controls and were directly related to depression and disease duration. Depression was more frequent in patients and correlated to motor aspects, however, there was no association with brain areas. Cognitive alterations were important, especially in memory and fluency domains, which correlated directly to atrophy in the amygdala and cerebellar lobe VIII, respectively. Significant area reduction and eccentricity increase were observed in patients' cervical spinal cord when compared to controls. The reduction of the cord area correlated directly to motor aspects; and duration and CAGn were possible determinants. Cross-sectional brain evaluations revealed significant damage in primary and associative areas in cerebral cortex, deep gray matter, cerebellar cortex and encephalic white matter, especially in infratentorial regions. Analysis of disease course disclosed a caudal-cranial pattern of damage in the CNS. Finally, we were able to phenotypically characterize SCA1 and to correlate its clinical and structural aspectsDoutoradoFisiopatologia MédicaDoutor em Ciência

Evaluation of Upper Motor Neuron Pathology in Amyotrophic Lateral Sclerosis by Mri;Towards Identifying Noninvasive Biomarkers of the Disease

Amyotrophic lateral sclerosis (ALS) is the commonest adult motor neuron disease (MND) which causes progressive muscle paralysis and death usually within 5 years of symptom onset. As a result, only ̃30,000 individuals in the United States are afflicted at any one time even though 5,000 or more individuals are diagnosed yearly. The diagnosis of ALS requires evidence of degeneration in upper motor neurons (UMNs) in the brain and in lower motor neurons (LMNs) that exit the brainstem and spinal cord to innervate skeletal muscles. Diagnosis can be incorrect or delayed when disease is early or atypical because non-invasive objective tests of UMN involvement do not exist, unlike electromyography to assess the LMN. Although magnetic resonance imaging (MRI) of brain and spinal cord is used primarily to identify conditions which mimic ALS, novel MRI sequences and post-processing techniques can identify macroscopic and even sub-macroscopic changes in ALS brain related to neuronoaxonal degeneration (e.g., in corticospinal motor tracts). MRI-based techniques like diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H-MRS), as well as nuclear medicine modalities like positron emission tomography (PET) and single photon emission tomography (SPECT) are being used to study brains of patients with ALS. Many previous MRI studies of ALS brain are limited either in methodology or information obtained being primarily qualitative, i.e. changes visible to the naked eye (macroscopic). This study employed both routine and novel MRI sequences to objectively assess gray and white matter pathology of the brain in ALS patients, including T2 relaxometry, DTI, and voxel based morphometry (VBM) of 3D high resolution T1-weighted images. DTI metrics showed significant (p\u3c 0.05) changes in rostral extent of corticospinal tract (CST) in ALS patients with predominantly UMN symptoms and signs, and the ALS-dementia patients, whereas more caudal involvement was observed in ALS patients with classic findings of UMN and LMN

Characterization of DTI Indices in the Cervical, Thoracic, and Lumbar Spinal Cord in Healthy Humans

The aim of this study was to characterize in vivo measurements of diffusion along the length of the entire healthy spinal cord and to compare DTI indices, including fractional anisotropy (FA) and mean diffusivity (MD), between cord regions. The objective is to determine whether or not there are significant differences in DTI indices along the cord that must be considered for future applications of characterizing the effects of injury or disease. A cardiac gated, single-shot EPI sequence was used to acquire diffusion-weighted images of the cervical, thoracic, and lumbar regions of the spinal cord in nine neurologically intact subjects (19 to 22 years). For each cord section, FA versus MD values were plotted, and a k-means clustering method was applied to partition the data according to tissue properties. FA and MD values from both white matter (average FA = 0.69, average MD = 0.93 × 10 −3 mm 2 /s) and grey matter (average FA = 0.44, average MD = 1.8 × 10 −3 mm 2 /s) were relatively consistent along the length of the cord

Quantitative magnetic resonance imaging towards clinical application in multiple sclerosis

Quantitative MRI provides biophysical measures of the microstructural integrity of the CNS, which can be compared across CNS regions, patients, and centres. In patients with multiple sclerosis, quantitative MRI techniques such as relaxometry, myelin imaging, magnetization transfer, diffusion MRI, quantitative susceptibility mapping, and perfusion MRI, complement conventional MRI techniques by providing insight into disease mechanisms. These include: (i) presence and extent of diffuse damage in CNS tissue outside lesions (normal-appearing tissue); (ii) heterogeneity of damage and repair in focal lesions; and (iii) specific damage to CNS tissue components. This review summarizes recent technical advances in quantitative MRI, existing pathological validation of quantitative MRI techniques, and emerging applications of quantitative MRI to patients with multiple sclerosis in both research and clinical settings. The current level of clinical maturity of each quantitative MRI technique, especially regarding its integration into clinical routine, is discussed. We aim to provide a better understanding of how quantitative MRI may help clinical practice by improving stratification of patients with multiple sclerosis, and assessment of disease progression, and evaluation of treatment response