Eytan Raz

Clinically isolated syndrome suggestive of multiple sclerosis: Voxelwise regional investigation of white and gray matter

PURPOSE To quantify white matter (WM) and gray matter (GM) damage in patients who presented with clinically isolated syndrome (CIS), which is suggestive of multiple sclerosis (MS), by combining volume-based morphometry (VBM) and tract-based spatial statistics (TBSS). MATERIALS AND METHODS This prospective HIPAA-compliant study was approved by the institutional review board. Written informed consent was obtained from all participants. In this study, 34 consecutive patients (21 women, 13 men; mean age, 31.7 years +/- 7.7 [standard deviation]) who presented with CIS were recruited. The magnetic resonance (MR) examination included dual-echo fast spin-echo, three-dimensional T1, and diffusion-tensor imaging. Sixteen matched healthy volunteers served as control subjects. T2 lesion volumes were assessed with a semiautomatic technique. VBM and TBSS were used for the GM and WM analyses, respectively, to compare regional GM volumes and fractional anisotropy (FA) values in the two groups. RESULTS TBSS analysis revealed a pattern of diffuse FA reductions in patients with CIS at the cluster level (P < .05). Regions of decreased FA involved most of the WM pathways, including the corticospinal tracts, corpus callosum, and superior and inferior longitudinal fasciculi. There were no significant differences between the two groups in terms of global GM, WM, or cerebrospinal fluid volume or in terms of regional GM volume. CONCLUSION Diffuse WM damage not accompanied by any change in GM or WM volume is observed in patients with CIS. This suggests that WM involvement plays a relevant role in the early phases of MS. Subsequently detected GM damage may be secondary to WM alterations.

Gray- and white-matter changes 1 year after first clinical episode of multiple sclerosis: MR imaging.

PURPOSE To assess, by means of magnetic resonance (MR) imaging, the longitudinal changes in white matter (WM) and gray matter (GM) in a cohort of patients with clinically isolated syndrome (CIS) who were followed up for 1 year. MATERIALS AND METHODS This prospective, HIPAA-compliant study was approved by the institutional review board. Written informed consent was obtained from all the participants. Changes in GM and WM integrity were respectively investigated by using three-dimensional T1-weighted and diffusion-tensor (DT) imaging sequences and by applying voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses. Thirty-four consecutive patients (21 women, 13 men; mean age, 32.8 years ± 7.7 [standard deviation]) who had CIS were recruited. All the patients underwent a neurologic and an MR examination at baseline and 12 months later; the MR examination consisted of three-dimensional T1-weighted dual-echo turbo spin-echo DT imaging. VBM and TBSS were used to analyze GM volume and WM fractional anisotropy, respectively. RESULTS After 1 year, multiple sclerosis (MS) was diagnosed in 33 (97%) of 34 patients with CIS. Longitudinal volumetric analysis revealed a significant (P < .001) reduction in global GM volume. The VBM analysis showed the development of regional GM atrophy involving several cortical and subcortical regions in both hemispheres (P < .05). No significant longitudinal change in global or regional WM fractional anisotropy was otherwise observed. CONCLUSION WM damage was detectable early and involved most fiber tracts in patients with MS, but it did not worsen significantly during the 1st year after clinical onset. In contrast, GM damage was not detectable at the time of clinical onset, but a significant decrease in cortical and deep GM volume was observed at 1 year.

Assessing the Correlation between Grey and White Matter Damage with Motor and Cognitive Impairment in Multiple Sclerosis Patients

Background Multiple sclerosis (MS) is characterized by demyelinating and degenerative processes within the central nervous system. Unlike conventional MRI,new advanced imaging techniques improve pathological specificity and better highlight the relationship between anatomical damage and clinical impairment. Objective To investigate the relationship between clinical disability and both grey (GM) and white matter (WM) regional damage in MS patients. Methods Thirty-six relapsing remitting-MS patients and 25 sex- and age-matched controls were enrolled. All patients were clinically evaluated by the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite (MSFC) scale, which includes the 9-hole peg test (9HPT), the timed 25-feet walking test (T25FW) and the paced auditory serial addition test (PASAT). All subjects were imaged by a 3.0 T scanner: dual-echo fast spin-echo, 3DT1-weighted and diffusion-tensor imaging (DTI) sequences were acquired. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses were run for regional GM and WM assessment, respectively. T2 lesion volumes were also calculated, by using a semi-automated technique. Results Brain volumetric assessment of GM and DTI measures revealed significant differences between patients and controls. In patients, different measures of WM damage correlated each-other (p<0.0001), whereas none of them correlated with GM volume. In patients, focal GM atrophy and widespread WM damage significantly correlated with clinical measures. In particular, VBM analysis revealed a significant correlation (p<0.05) between GM volume and 9HPT in cerebellum and between GM volume and PASAT in orbito-frontal cortex. TBSS showed significant correlations between DTI metrics with 9HPT and PASAT scores in many WM bundles (p<0.05), including corpus callosum, internal capsule, posterior thalamic radiations, cerebral peduncles. Conclusions Selective GM atrophy and widespread WM tracts damage are associated with functional impairment of upper-limb motion and cognition. The combined analysis of volumetric and DTI data may help to better understand structural alterations underlying physical and cognitive dysfunction in MS.

Variable Porosity of the Pipeline Embolization Device in Straight and Curved Vessels: A Guide for Optimal Deployment Strategy

BACKGROUND AND PURPOSE: Low-porosity endoluminal devices for the treatment of intracranial aneurysms, also known as flow diverters, have been in experimental and clinical use for close to 10 years. Despite rigorous evidence of their safety and efficacy in well-controlled trials, a number of key factors concerning their use remain poorly defined. Among these, none has received more attention to date than the debate on how many devices are optimally required to achieve a safe, effective, and economical outcome. Additional, related questions concern device sizing relative to the parent artery and optimal method of deployment of the devices. While some or all of these issues may be ultimately answered on an empiric basis via subgroup analysis of growing treatment cohorts, we believe that careful in vitro examination of relevant device properties can also help guide its in vivo use. MATERIALS AND METHODS: We conducted a number of benchtop experiments to investigate the varied porosity of Pipeline Embolization Devices deployed in a simulated range of parent vessel diameters and applied these results toward conceptualizing optimal treatment strategies of fusiform and wide-neck aneurysms. RESULTS: The results of our studies confirm a predictable parabolic variability in device porosity based on the respective comparative sizes of the device and recipient artery, as well as device curvature. Even modest oversizing leads to a significant increase in porosity. CONCLUSIONS: The experiments demonstrate various deleterious effects of device oversizing relative to the parent artery and provide strategies for addressing size mismatches when they are unavoidable.

Brain Iron Quantification in Mild Traumatic Brain Injury: A Magnetic Field Correlation Study

BACKGROUND AND PURPOSE: Experimental studies have suggested a role for iron accumulation in the pathology of TBI. Magnetic field correlation MR imaging is sensitive to the presence of non-heme iron. The aims of this study are to 1) assess the presence, if any, and the extent of iron deposition in the deep gray matter and regional white matter of patients with mTBI by using MFC MR imaging; and 2) investigate the association of regional brain iron deposition with cognitive and behavioral performance of patients with mTBI. MATERIALS AND METHODS: We prospectively enrolled 28 patients with mTBI. Eighteen healthy subjects served as controls. The subjects were administered the Stroop color word test, the Verbal Fluency Task, and the Post-Concussion Symptoms Scale. The MR imaging protocol (on a 3T imager) consisted of conventional brain imaging and MFC sequences. After the calculation of parametric maps, MFC was measured by using a region of interest approach. MFC values across groups were compared by using analysis of covariance, and the relationship of MFC values and neuropsychological tests were evaluated by using Spearman correlations. RESULTS: Compared with controls, patients with mTBI demonstrated significant higher MFC values in the globus pallidus (P = .002) and in the thalamus (P = .036). In patients with mTBI, Stroop test scores were associated with the MFC value in frontal white matter (r = −0.38, P = .043). CONCLUSIONS: MFC values were significantly elevated in the thalamus and globus pallidus of patients with mTBI, suggesting increased accumulation of iron. This supports the hypothesis that deep gray matter is a site of injury in mTBI and suggests a possible role for iron accumulation in the pathophysiological events after mTBI.

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.

Multiple Sclerosis: Changes in Microarchitecture of White Matter Tracts after Training with a Video Game Balance Board

PURPOSE To determine if high-intensity, task-oriented, visual feedback training with a video game balance board (Nintendo Wii) induces significant changes in diffusion-tensor imaging ( DTI diffusion-tensor imaging ) parameters of cerebellar connections and other supratentorial associative bundles and if these changes are related to clinical improvement in patients with multiple sclerosis. MATERIALS AND METHODS The protocol was approved by local ethical committee; each participant provided written informed consent. In this 24-week, randomized, two-period crossover pilot study, 27 patients underwent static posturography and brain magnetic resonance (MR) imaging at study entry, after the first 12-week period, and at study termination. Thirteen patients started a 12-week training program followed by a 12-week period without any intervention, while 14 patients received the intervention in reverse order. Fifteen healthy subjects also underwent MR imaging once and underwent static posturography. Virtual dissection of white matter tracts was performed with streamline tractography; values of DTI diffusion-tensor imaging parameters were then obtained for each dissected tract. Repeated measures analyses of variance were performed to evaluate whether DTI diffusion-tensor imaging parameters significantly changed after intervention, with false discovery rate correction for multiple hypothesis testing. RESULTS There were relevant differences between patients and healthy control subjects in postural sway and DTI diffusion-tensor imaging parameters (P < .05). Significant main effects of time by group interaction for fractional anisotropy and radial diffusivity of the left and right superior cerebellar peduncles were found (F2,23 range, 5.555-3.450; P = .036-.088 after false discovery rate correction). These changes correlated with objective measures of balance improvement detected at static posturography (r = -0.381 to 0.401, P < .05). However, both clinical and DTI diffusion-tensor imaging changes did not persist beyond 12 weeks after training. CONCLUSION Despite the low statistical power (35%) due to the small sample size, the results showed that training with the balance board system modified the microstructure of superior cerebellar peduncles. The clinical improvement observed after training might be mediated by enhanced myelination-related processes, suggesting that high-intensity, task-oriented exercises could induce favorable microstructural changes in the brains of patients with multiple sclerosis.

Imaging of the Carotid Artery Vulnerable Plaque

AbstractAtherosclerosis involving the carotid arteries has a high prevalence in the population worldwide. This condition is significant because accidents of the carotid artery plaque are associated with the development of cerebrovascular events. For this reason, carotid atherosclerotic disease needs to be diagnosed and those determinants that are associated to an increased risk of stroke need to be identified. The degree of stenosis typically has been considered the parameter of choice to determine the therapeutical approach, but several recently published investigations have demonstrated that the degree of luminal stenosis is only an indirect indicator of the atherosclerotic process and that direct assessment of the plaque structure and composition may be key to predict the development of future cerebrovascular ischemic events. The concept of “vulnerable plaque” was born, referring to those plaque’s parameters that concur to the instability of the plaque making it more prone to the rupture and distal embolization. The purpose of this review is to describe the imaging characteristics of “vulnerable carotid plaques.”

A Transverse and Longitudinal MR Imaging Voxel-Based Morphometry Study in Patients with Primary Cervical Dystonia

BACKGROUND AND PURPOSE: Findings of standard MR imaging examinations are usually normal in primary CD. These findings are now increasingly challenged by studies using advanced neuroimaging techniques detecting abnormalities in brain areas that may be functionally involved in the pathophysiology of CD. Our purpose was to evaluate GM volumes in patients with CD at baseline and 5 years later. MATERIALS AND METHODS: We enrolled 19 patients (F/M = 15:4, mean age = 53.2 + 11.2 years), 12 of whom were studied at baseline and again approximately 5 years later. Twenty-eight healthy volunteers acted as controls (F/M = 17:11, mean age = 47.5 + 15.6 years). The subjects were imaged with a 1.5T scanner by using a 3D T1-weighted sequence on 150 contiguous axial 1-mm-thick sections to apply VBM. RESULTS: At entry, VBM analysis disclosed significantly lower GM volumes in the left caudate head and putamen and in the premotor and primary sensorimotor cortices bilaterally in patients than in controls. No correlation was found between decreased GM volumes and patient age, severity of dystonia, or disease duration. At the 5-year follow-up, GM volumes in the left primary sensorimotor cortex in patients had decreased significantly from baseline. CONCLUSIONS: The findings obtained at entry and after a 5-year follow-up consistently showed decreased caudate, putamen, and sensorimotor cortex GM volumes in patients with CD, and they probably play a pathophysiologic role in CD.

MRI Findings in Lymphomatosis Cerebri: Description of a Case and Revision of the Literature

Lymphomatosis cerebri (LC) is a rare form of primary central nervous system lymphoma; we report a case of LC mainly involving the brainstem and cerebellum. This diagnosis should be considered in patients presenting with diffuse white matter disease, and a subacute clinical history of cognitive deficits, ataxic gait, and personality changes. We present our findings along with a review of the neuroradiological literature.