Robert Zivadinov

To determine the sensitivity and specificity of decreased venous vasculature visibility (VVV) on susceptibility-weighted imaging (SWI) venography in multiple sclerosis (MS) patients versus controls, and to compare this with assessment of whole brain atrophy.

The purpose of this research was to examine the extent of global brain atrophy and white matter hyperintensities (WMH) in early Parkinson's disease (PD) compared to normal controls (NC), to explore the relationship between the MRI variables and cognition in PD. In this multicenter study we included 155 PD patients (age 65.6 ± 9.1 years, disease duration 26.7 ± 19.9 months) and 101 age‐matched NC. On 3D‐T1‐WI, we calculated normalized brain volumes using SIENAX software. WMH volumes were assessed semiautomatically. In PD patients, correlation and regression analyses investigated the association between atrophy and WMH outcomes and global, attention‐executive, visuospatial, and memory cognitive functions. Regression analysis was controlled for age, education, depression score, motor severity, cerebrovascular risk, and sex. No significant MRI variable volume group differences were found. The models did not retain any of the imaging variables as significant predictors of cognitive impairment. There was no evidence of brain atrophy or higher WMH volume in PD compared to NC, and MRI volumetric measurements were not significant predictors of cognitive functions in PD patients. We conclude that global structural brain changes are not a major feature in patients with incident PD. © 2009 Movement Disorder Society

MRI findings of primary anti-phospholipid antibody syndrome (PAPLS) are difficult to distinguish from those of multiple sclerosis (MS). Only a few previous studies have compared conventional and non-conventional MRI findings in MS and PAPLS patients. In addition, MRI differences between anti-phospholipid antibody (APLA) positive (+) and APLA negative (−) MS patients have not been reported. Therefore, the aim of this study was to investigate the differences in MRI measures among patients with PAPLS, MS and normal control (NC) subjects. We also explored non-conventional MRI measures in APLA+ and APLA− MS patients. Forty-nine (49) consecutive MS patients among whom 39 had relapsing-remitting (RR) and 10 secondary-progressive (SP) disease course, 30 patients with PAPLS and 49 NC were enrolled. Twenty-eight (28) MS patients were APLA+. MRI measures of T1- and T2-lesion volumes (LV) and brain atrophy, including fractions of whole brain (BPF), gray matter (GMF) and white matter (WMF), were evaluated. The magnetization transfer ratio (MTR) of T2- and T1-LVs and different normal-appearing brain tissue (NABT) compartments as well as diffusion-weighted imaging of whole brain mean parenchyma diffusivity (MPD) were obtained. MS patients differed significantly from NC in all MRI measures. PAPLS patients differed from NC in their T2-LV, in MTR measures and in MPD. When MS patients were compared to PAPLS patients, they showed significantly higher T2- and T1-LVs and T2-LV MTR, lower BPF and GMF and higher MPD. APLA+ RR and SPMS (all APLA+) patients showed significantly higher T2-LV, lower GMF, lower normal-appearing gray matter MTR and higher MPD when compared to APLA− patients. The results indicate that brain abnormalities can be detected in PAPLS patients with non-conventional MRI. MRI reveals more profound injury in patients with MS versus PAPLS. APLA mediates heterogeneous cerebral pathology that remains to be further investigated.

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Disease-modifying agents (DMAs), including interferon beta (IFNbeta) and glatiramer acetate (GA), are the mainstays of long-term treatment of multiple sclerosis (MS). Other potent anti-inflammatory agents like natalizumab and different types of chemotherapeutics are increasingly being used for treatment of MS, particularly in patients with breakthrough disease activity. Brain volume (BV) loss occurs early in the disease process, accelerates over time, and may be only partially affected by DMA therapy. Low-dose, low frequency IFNbeta administered once weekly and GA appear to partially reduce BV decline over the second and third years of treatment. High dose, high frequency IFNbeta demonstrated no clear effect on BV loss during this time period. Current evidence suggests that changes in BV after immunoablation may not be due entirely to the resolution of edema but may be related to potential chemotoxicity of high dose cyclophosphamide. Natalizumab reduces the development of BV decline in the second and third years of treatment. IV immunoglobulin showed a positive effect on decelerating BV reduction in relapsing and advanced stages of MS. These differences between DMAs may be explained by the extent of their therapeutic effects on inflammation and on the balance between inhibition or promotion of remyelination and neuronal repair in the CNS. We described the mechanisms of action by which DMAs induce accelerated, non-tissue-related BV loss (pseudoatrophy) in the short term but, in the long run, may still potentially lead to permanent BV decline. The effects of corticosteroid therapy on changes in BV in patients with MS help clarify the mechanisms through which potent anti-inflammatory treatments may prevent, stabilize, or induce BV loss.

Magnetic resonance imaging (MRI) is the most important paraclinical measure for assessing and monitoring the pathologic changes implicated in the onset and progression of multiple sclerosis (MS). Conventional MRI sequences, such as T1-weighted gadolinium (Gd) enhanced and spin-echo T2-weighted imaging, only provide an incomplete picture of the degree of inflammation and underlying neurodegenerative changes in this disease. Two- and three-dimensional fluid-attenuated inversion recovery and double inversion recovery sequences allow better identification of cortical, periventricular and infratentorial lesions. Ultra-high field strength MRI has the potential to detect subpial cortical and deep gray matter lesions. Unenhanced T1-weighted imaging can reveal hypointense black holes, a measure of chronic neurodegeneration. Magnetization transfer imaging (MTI) is increasingly used to characterize the evolution of MS lesions and normal-appearing brain tissue. Evidence suggests that the dynamics of magnetization transfer changes correlate with the extent of demyelination and remyelination. Magnetic resonance spectroscopy, which provides details on tissue biochemistry, metabolism, and function, also has the capacity to reveal neuroprotective mechanisms. By measuring the motion of water, diffusion imaging can provide information about the orientation, size, and geometry of tissue damage in white and gray matter. These advanced non-conventional MRI techniques relate better to clinical impairment, disease progression, accumulation of disability, and have the potential to detect neuroprotective effects of treatment. Although detecting the status of neuronal integrity using MRI techniques continues to improve, a “gold standard” model remains to be established.

BACKGROUND The goal of this study was to develop and validate a method for generation of regional magnetization transfer ratio (MTR). We also studied the topography of MTR changes in multiple sclerosis (MS) and in normal controls (NC), and preliminarily examined the clinical usefulness of this method. METHODS We examined 45 patients with MS (relapsing remitting [RR]= 28 and secondary progressive [SP]= 17] and 19 NC. Mean disease duration was 14.3 years and median Expanded Disability Status Scale was 3.0. Regions of the brain were determined using semiautomated brain region extraction (SABRE). Twenty‐six regional masks were automatically applied to MTR maps that were further split into gray matter (GM) and white matter (WM) compartments. RESULTS Mean MTR from 12 SABRE regions differed significantly between MS patients and NC. For WM, all regional mean MTRs differed significantly between RR, SP, and NC participants (P < .001). In regression analysis, only 3 regions remained significantly different when corrected for total T2‐LV. The regression model predicting disability selected GM mean MTR of the right medial inferior frontal region (P= .031). CONCLUSIONS The study results showed that this regional MTR approach is reproducible, reliable and clinically relevant. MTI changes occur selectively in specific sub‐regions.