A comparison of MR imaging with fast-FLAIR, HASTE-FLAIR, and EPI-FLAIR sequences in the assessment of patients with multiple sclerosis

BACKGROUND AND PURPOSE: Fast fluid-attenuated inversion-recovery (FLAIR) sequences are sensitive for detecting lesions in patients with multiple sclerosis (MS). More rapid fast-FLAIR imaging of the brain can be achieved by the concomitant use of half-Fourier acquisition single-shot turbo spin-echo (HASTE-FLAIR) and echo-planar imaging (EPI-FLAIR). The present study was performed in a large cohort of subjects to assess and compare the number and volume of brain lesions detected by the fast-FLAIR, HASTE-FLAIR, and EPI-FLAIR sequences in patients with MS. METHODS: Fast-FLAIR, HASTE-FLAIR, and EPI-FLAIR sequences were obtained from 46 consecutive MS patients. Lesions seen on each type of sequence were counted and classified by consensus by two observers. Lesion volumes were measured using a semiautomated segmentation technique based on local thresholding. RESULTS: The quality of the fast-FLAIR images was significantly better than that of HASTE-FLAIR and EPI-FLAIR images. Fast-FLAIR revealed significantly more lesions and higher lesion volumes than did HASTE-FLAIR and EPI-FLAIR. A similar number of large lesions was detected by the three sequences, but HASTE-FLAIR and EPI-FLAIR showed significantly fewer small and intermediate lesions than did fast-FLAIR. The number of lesions seen on HASTE-FLAIR and EPI-FLAIR images was similar. CONCLUSION: HASTE-FLAIR and EPI-FLAIR sequences revealed as many large MS lesions as fast-FLAIR. Because their acquisition times are only a fraction of that needed for fast-FLAIR sequences, they may be useful for making a rapid diagnosis of MS in uncooperative patients. Their reduced ability to detect smaller lesions indicates that they should not be used as a routine approach to imaging patients with MS.     

Different effect of statins on platelet oxidized-LDL receptor (CD36 and LOX-1) expression in hypercholesterolemic subjects.

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular mortality by decreasing cholesterol as well as by non-lipid-related actions. Oxidized low-density lipoproteins (ox-LDL) are pro-atherogenic molecules and potent platelet agonists. CD36 and lectin-like ox-LDL receptor-1 (LOX-1) are specific ox-LDL receptors also expressed in platelets. This study was planned to address whether treatment with atorvastatin 10 mg/day, pravastatin 40 mg/day or simvastatin 20 mg/day could affect platelet CD36 and LOX-1 expression. Twenty-four patients for each treatment were evaluated after 3, 6, and 9 days and at 6 weeks for complete lipid profile (chromogenic), ox-LDL (ELISA), platelet P-selectin (P-sel), CD36, LOX-1 (FACS), and intracellular citrullin recovery (iCit) (HPLC). Data show hyperactivated platelets (P-sel absolute values, percent variation in activated cells, all p < 0.001), and CD36 and LOX-1 overexpression (all p < 0.001) in patients at baseline. P-sel, CD36, and LOX-1 were significantly decreased by atorvastatin and simvastatin (all p < 0.01) and related with iCit increase (r = 0.58, p < 0.001) and platelet-associated ox-LDL (r = 0.51, p < 0.01) at 9 days. Pravastatin reduced LOX-1 and P-sel (p < 0.05) at 6 weeks in relation with decreased LDL and ox-LDL (r = 0.39, p < 0.01 and r = 0.37, p < 0.01, respectively). These data suggest that atorvastatin and simvastatin reduce platelet activity by exposure of CD36 and LOX-1 before significant LDL reduction, whereas pravastatin action is detected later and in relation with LDL and ox-LDL lowering. Rapid and consistent reduction of CD36 and LOX-1 could be considered a direct anti-atherothrombotic mechanism related to the role of ox-LDL in platelet activation, platelet-endothelium interactions, and NO synthase activity.     

Effect of Parasympathetic Stimulation on Brain Activity During Appraisal of Fearful Expressions

Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets.     

A novel approach with “skeletonised MTR” measures tract‐specific microstructural changes in early primary‐progressive MS

We combined tract‐based spatial statistics (TBSS) and magnetization transfer (MT) imaging to assess white matter (WM) tract‐specific short‐term changes in early primary‐progressive multiple sclerosis (PPMS) and their relationships with clinical progression. Twenty‐one PPMS patients within 5 years from onset underwent MT and diffusion tensor imaging (DTI) at baseline and after 12 months. Patients' disability was assessed. DTI data were processed to compute fractional anisotropy (FA) and to generate a common WM “skeleton,” which represents the tracts that are “common” to all subjects using TBSS. The MT ratio (MTR) was computed from MT data and co‐registered with the DTI. The skeletonization procedure derived for FA was applied to each subject's MTR image to obtain a “skeletonised” MTR map for every subject. Permutation tests were used to assess (i) changes in FA, principal diffusivities, and MTR over the follow‐up, and (ii) associations between changes in imaging parameters and changes in disability. Patients showed significant decreases in MTR over one year in the corpus callosum (CC), bilateral corticospinal tract (CST), thalamic radiations, and superior and inferior longitudinal fasciculi. These changes were located both within lesions and the normal‐appearing WM. No significant longitudinal change in skeletonised FA was found, but radial diffusivity (RD) significantly increased in several regions, including the CST bilaterally and the right inferior longitudinal fasciculus. MTR decreases, RD increases, and axial diffusivity decreases in the CC and CST correlated with a deterioration in the upper limb function. We detected tract‐specific multimodal imaging changes that reflect the accrual of microstructural damage and possibly contribute to clinical impairment in PPMS. We propose a novel methodology that can be extended to other diseases to map cross‐subject and tract‐specific changes in MTR. Hum Brain Mapp 35:723–733, 2014. © 2013 Wiley Periodicals, Inc.     

Changes in functional connectivity in people with HIV switching antiretroviral therapy

Journal of NeuroVirology - We assessed changes in functional connectivity by fMRI (functional magnetic resonance imaging) and cognitive measures in otherwise neurologically asymptomatic people with...     

Estimation of the macromolecular proton fraction and bound pool T2 in multiple sclerosis

This study used a model for magnetization transfer (MT) to estimate two underlying parameters: the macromolecular proton fraction (f) and the bound pool T2 (T2b) in patients with multiple sclerosis (MS). Sixty patients with clinically definite MS and 27 healthy controls were imaged using: (1) a dual echo fast spin echo sequence, (2) a MT sequence (with ten MT power and offset frequency combinations) and (3) proton density and T1 weighted sequences (for T1 relaxation time estimation). Fourteen normal-appearing white matter (NAWM) regions of interest (ROI) and six normal-appearing gray matter (NAGM) ROIs were outlined in all subjects. Lesions were also contoured in subjects affected by MS. The model was fitted to the data leading to estimates of T2b and f. Results showed that T2b was increased in lesions whereas f was reduced. In NAWM, f was decreased while T2b was only increased in secondary progressive MS. NAWM f correlated modestly with disability. Further studies are needed to investigate the pathological basis of the abnormalities observed.     

Inter-sequence and inter-imaging unit variability of diffusion tensor MR imaging histogram-derived metrics of the brain in healthy volunteers

BACKGROUND AND PURPOSE: Diffusion tensor MR imaging has the potential to improve our ability to monitor several neurologic conditions. As a preliminary step to the assessment of the role of diffusion tensor MR imaging in the context of longitudinal and multicenter studies, we evaluated the effect of sequence-, imaging unit-, and imaging-reimaging-induced variations on diffusion tensor MR imaging quantities derived from histogram analysis of a large portion of the central brain of healthy volunteers. METHODS: Each of eight healthy volunteers underwent imaging on two MR imaging units using three different pulsed gradient spin-echo single shot echo-planar pulse sequences (each of them having a different diffusion gradient scheme). Four additional healthy participants underwent imaging twice on the same imaging unit to assess imaging-reimaging variability. RESULTS: For mean diffusivity histograms, the differences between inter-sequence and inter-imaging unit coefficients of variation were significant for all the considered quantities with P values ranging from.003 to <.001. Also, the inter-imaging unit coefficient of variation for average fractional anisotropy was significantly higher than the corresponding inter-sequence coefficient of variation (P =.002). In general, inter-sequence mean diffusivity histogram-derived metrics (coefficients of variation ranging from 1.72% to 5.56%) were more reproducible than were fractional anisotropy histogram-derived metrics (coefficients of variation ranging from 5.45% to 7.34%). Imaging-reimaging variability was found to fall in the range of inter-sequence coefficients of variation for all the considered quantities. CONCLUSION: This study shows that inter-sequence, imaging-reimaging, and inter-imaging unit variabilities of diffusion tensor MR imaging-derived measurements are relatively low, suggesting that diffusion tensor MR imaging might provide additional measures of outcome with which to assess the evolution of brain structural damage in large scale studies of various neurologic conditions.     

Investigation of quantitative magnetisation transfer parameters of lesions and normal appearing white matter in multiple sclerosis

The aim of this study was to use quantitative magnetisation transfer (MT) imaging to assess the different pathological substrates of tissue damage in multiple sclerosis (MS) and examine whether the MT parameters may be used to explain the disability in relapsing remitting (RR) MS. Thirteen patients with RRMS and 14 healthy controls were prescribed conventional MRI and quantitative MT imaging at 3.0 T. A two‐pool model of MT (where A refers to the free pool and B to the macromolecular pool) was fitted to the data yielding a longitudinal relaxation rate R_A, a relative size F of macromolecular pool, transverse relaxation times T and T for the two pools and a forward exchange rate RM. The MT ratio (MTR) was also computed. The mean MT parameters of the normal appearing white matter (NAWM) and of lesions in patients, and of white matter in controls were estimated. MT parameters were significantly different between lesions and NAWM in patients, and between the NAWM and the white matter of controls (with the exception of T and the MTR). Two models were investigated using ordered logistic regression, with the expanded disability status scale (EDSS) as the dependent variable. In the first one, mean NAWM MT parameters and lesion load were entered as explanatory variables; in the second one, mean MT variables within lesions and lesion load were entered as explanatory variables. Unexpectedly, T was the parameter most significantly associated with EDSS in NAWM. This parameter might represent a weighted average of the relaxation times of spins with different molecular environments, and therefore its variation could indicate a change in the balance between subpopulations of macromolecular spins. Conversely, in lesions, RM, T, F, R_A, and lesion load significantly predicted disability only when combined together. This might reflect the complex interaction between demyelination, remyelination, gliosis, inflammation and axonal loss taking place within lesions. Copyright © 2009 John Wiley & Sons, Ltd.     

Theta Burst Stimulation of the Precuneus Modulates Resting State Connectivity in the Left Temporal Pole

It has been shown that continuous theta burst stimulation (cTBS) over the precuneus acts on specific memory retrieval abilities. In order to study the neural mechanisms beyond these findings, we combined cTBS and resting-state functional magnetic resonance imaging. Our experimental protocol involved stimulation and sham conditions on a group of healthy subjects, and each condition included a baseline and two follow-up acquisitions (5 and 15 min after baseline) after cTBS. We analysed brain functional connectivity by means of graph theoretical measures, with a specific focus on the network modular structure. Our results showed that cTBS of the precuneus selectively affects the left temporal pole, decreasing its functional connectivity in the first follow-up. Moreover, we observed a significant increase in the size of the module of the precuneus in the second follow-up. Such effects were absent in the sham condition. We observed here a modulation of functional connectivity as a result of inhibitory stimulation over the precuneus. Such a modulation first acts indirectly on the temporal area and then extends the connectivity of the precuneus itself by a feed-back mechanism. Our current findings extend our previous behavioural observations and increase our understanding of the mechanisms underlying the stimulation of the precuneus.