Hemostasis biomarkers in multiple sclerosis.

BACKGROUND AND PURPOSE: The aim was to investigate the plasma levels of hemostasis components in multiple sclerosis (MS) and their association with clinical and magnetic resonance imaging (MRI) outcomes. METHODS: In all, 138 MS patients [85 with relapsing-remitting MS (RR-MS) and 53 with progressive MS (P-MS) with a mean age of 54 years; 72.5% female; median Expanded Disability Status Scale 3.5; mean disease duration 21 years] and 42 age- and sex-matched healthy individuals (HI) were studied. All subjects were examined with 3 T MRI and clinical examinations. Plasma levels of hemostasis factors [procoagulant, factor XII (FXII)] and inhibitors [tissue factor pathway inhibitor (TFPI), thrombomodulin, heparin cofactor II, a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) and plasminogen activator inhibitor 1 (PAI-1)] were evaluated by magnetic Luminex assays and enzyme-linked immunosorbent assay. Associations between hemostasis plasma levels and clinical and MRI outcomes were assessed. RESULTS: Lower ADAMTS13 levels were found in MS patients compared to HI (P = 0.008) and in MS patients presenting with cerebral microbleeds compared to those without (P = 0.034). Higher PAI-1 levels were found in MS patients compared to HI (P = 0.02). TFPI levels were higher in the P-MS subgroup compared to RR-MS patients (P = 0.011) and compared to HI (P = 0.002). No significant associations between hemostasis plasma levels and clinical or MRI outcomes were found. CONCLUSIONS: Decreased ADAMTS13, particularly in MS patients with cerebral microbleeds, which deserves further investigation, and increased PAI-1 and TFPI levels were observed in MS patients, which deserves further investigation. No relationship between hemostasis plasma levels and measures of disease severity was detected.

Evaluation of Leptomeningeal Contrast Enhancement Using Pre-and Postcontrast Subtraction 3D-FLAIR Imaging in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Leptomeningeal contrast enhancement is found in patients with multiple sclerosis, though reported rates have varied. The use of 3D-fluid-attenuated inversion recovery pre- and postcontrast subtraction imaging may more accurately determine the frequency of leptomeningeal contrast enhancement. The purpose of this study was to investigate the frequency of leptomeningeal contrast enhancement using the pre- and postcontrast subtraction approach and to evaluate 3 different methods of assessing the presence of leptomeningeal contrast enhancement. MATERIALS AND METHODS: We enrolled 258 consecutive patients with MS (212 with relapsing-remitting MS, 32 with secondary-progressive MS, and 14 with clinically isolated syndrome) who underwent both pre- and 10-minute postcontrast 3D-FLAIR sequences after a single dose of gadolinium injection on 3T MR imaging. The analysis included leptomeningeal contrast-enhancement evaluation on 3D-FLAIR postcontrast images in native space (method A), on pre- and postcontrast 3D-FLAIR images in native space (method B), and on pre-/postcontrast 3D-FLAIR coregistered and subtracted images (method C, used as the criterion standard). RESULTS: In total, 51 (19.7%) patients with MS showed the presence of leptomeningeal contrast enhancement using method A; 39 (15.1%), using method B; and 39 (15.1%), using method C (P = .002). Compared with method C as the criterion standard, method A showed 89.8% sensitivity and 92.7% specificity, while method B showed 84.6% sensitivity and 97.3% specificity (P < .001) at the patient level. Reproducibility was the highest using method C (κ agreement, r = 088, P < .001). The mean time to analyze the 3D-FLAIR images was significantly lower with method C compared with methods A and B (P < .001). CONCLUSIONS: 3D-FLAIR postcontrast imaging offers a sensitive method for detecting leptomeningeal contrast enhancement in patients with MS. However, the use of subtraction imaging helped avoid false-positive cases, decreased reading time, and increased the accuracy of leptomeningeal contrast-enhancement foci detection in a clinical routine.

Quantitative Susceptibility Mapping: Concepts and Applications.

PURPOSE: To review the fundamental principles of susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM), and to discuss recent clinical developments. METHODS: SWI is a magnetic resonance imaging method that takes advantage of magnitude signal loss and phase information to reveal anatomic and physiologic information about tissue and venous vasculature. The method enhances image contrast qualitatively, relying on phase shifts due to differences in magnetic susceptibility between tissues. QSM, extending SWI in an elegant way, is a new sophisticated postprocessing technique that numerically solves the inverse source-effect problem to derive local tissue magnetic susceptibility (source) from the measured magnetic field distribution (effect) as it is reflected in the phase images of gradient-echo sequences. RESULTS: SWI has meanwhile been established in numerous clinical as well as basic biomedical applications due to its ability to highlight tissue structures and compounds that are difficult to detect by conventional magnetic resonance imaging (MRI), including iron, calcifications, small veins, blood, and bones. The field of QSM has also progressed rapidly, both in terms of optimizing the post-processing strategies and algorithms as well as in gaining ground for new clinical applications that take advantage of its quantitative nature and improved specificity to identify the magnetic signature of lesions. CONCLUSIONS: Though magnetic susceptibility may be a major nuisance producing image artifacts in MRI, recent work has transformed it into a useful source of image contrast. Both SWI and QSM are gaining increasing acceptance in clinical practice. In particular, QSM provides new insights into tissue composition and organization due to its more direct relation to the actual physical tissue magnetic properties.

Effect of age on MRI phase behavior in the subcortical deep gray matter of healthy individuals.

BACKGROUND AND PURPOSE: It has been demonstrated that increased levels of iron in the brain occur with aging. In this study we investigated the nature of the association between age and SWI-filtered phase values, indicative of iron content, in the subcortical deep gray matter of healthy individuals. MATERIALS AND METHODS: A total of 210 healthy individuals (men: n = 89, women: n = 121), mean age, 39.8 years (standard deviation = 15.5; range = 6-76 years), were imaged on a 3T scanner. Mean MRI phase, mean phase of low-phase voxels, and normalized volumes were determined for total subcortical deep gray matter, caudate, putamen, globus pallidus, thalamus, pulvinar nucleus, hippocampus, amygdala, nucleus accumbens, red nucleus, and substantia nigra. Linear and nonlinear regression models were used to explore the relationship between phase and volume measures, and aging. RESULTS: Mean phase values of subcortical deep gray matter structures showed a quadratic relationship, with individuals in late middle age (40-59 years) having the lowest mean phase values, followed by a reversal of this trend in the elderly. In contrast, mean phase of low-phase voxel measurements showed strong negative linear relationships with aging. Significantly lower phase values were detected in women compared with men (P < .001), whereas no sex differences were observed for mean phase of low-phase voxels. Normalized volume measurements were also linearly related to aging, and women showed smaller normalized volumes of subcortical deep gray matter structures than men (P < .001). Lower mean phase of low-phase voxels was related to decreased volume measures. CONCLUSIONS: A strong association between phase (quadratic effect; phase decreases are followed by increases), mean phase of low-phase voxels (linear effect), volume (linear effect), and age was observed. Low phase was related to brain atrophy.