Abstract-Validation is arguably the bottleneck in the diffusion MRI community. This paper evaluates and compares 20 algorithms for recovering the local intra-voxel fiber structure from diffusion MRI data and is based on the results of the "HARDI reconstruction challenge" organized in the context of the "ISBI 2012" conference. Evaluated methods encompass a mixture of classical techniques well-known in the literature such as Diffusion Tensor, Q-Ball and Diffusion Spectrum imaging, algorithms inspired by the recent theory of compressed sensing and also brand new approaches proposed for the first time at this contest. To quantitatively compare the methods under controlled conditions, two datasets with known ground-truth were synthetically generated and two main criteria were used to evaluate the quality of the reconstructions in every voxel: correct assessment of the number of fiber populations and angular accuracy in their orientation. This comparative study investigates the behavior of every algorithm with varying experimental conditions and highlights strengths and weaknesses of each approach.

IntroductionIn patients with multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) provides only limited insights into the nature of brain damage with modest clinic-radiological correlation. In this study, we applied recent advances in MRI techniques to study brain microstructural alterations in early relapsing-remitting MS (RRMS) patients with minor deficits. Further, we investigated the potential use of advanced MRI to predict functional performances in these patients.MethodsBrain relaxometry (T1, T2, T2*) and magnetization transfer MRI were performed at 3T in 36 RRMS patients and 18 healthy controls (HC). Multicontrast analysis was used to assess for microstructural alterations in normal-appearing (NA) tissue and lesions. A generalized linear model was computed to predict clinical performance in patients using multicontrast MRI data, conventional MRI measures as well as demographic and behavioral data as covariates.ResultsQuantitative T2 and T2* relaxometry were significantly increased in temporal normal-appearing white matter (NAWM) of patients compared to HC, indicating subtle microedema (P = 0.03 and 0.004). Furthermore, significant T1 and magnetization transfer ratio (MTR) variations in lesions (mean T1 z-score: 4.42 and mean MTR z-score: −4.09) suggested substantial tissue loss. Combinations of multicontrast and conventional MRI data significantly predicted cognitive fatigue (P = 0.01, Adj-R2 = 0.4), attention (P = 0.0005, Adj-R2 = 0.6), and disability (P = 0.03, Adj-R2 = 0.4).ConclusionAdvanced MRI techniques at 3T, unraveled the nature of brain tissue damage in early MS and substantially improved clinical–radiological correlations in patients with minor deficits, as compared to conventional measures of disease.

Background: Cerebellar pathology occurs in late multiple sclerosis (MS) but little is known about cerebellar changes during early disease stages. In this study, we propose a new multicontrast "connectometry" approach to assess the structural and functional integrity of cerebellar networks and connectivity in early MS. Methods: We used diffusion spectrum and resting-state functional MRI (rs-fMRI) to establish the structural and functional cerebellar connectomes in 28 early relapsing-remitting MS patients and 16 healthy controls (HC). We performed multicontrast "connectometry" by quantifying multiple MRI parameters along the structural tracts (generalized fractional anisotropy-GFA, T1/T2 relaxation times and magnetization transfer ratio) and functional connectivity measures. Subsequently, we assessed multivariate differences in local connections and network properties between MS and HC subjects; finally, we correlated detected alterations with lesion load, disease duration, and clinical scores. Results: In MS patients, a subset of structural connections showed quantitative MRI changes suggesting loss of axonal microstructure and integrity (increased T1 and decreased GFA, P < 0.05). These alterations highly correlated with motor, memory and attention in patients, but were independent of cerebellar lesion load and disease duration. Neither network organization nor rs-fMRI abnormalities were observed at this early stage. Conclusion: Multicontrast cerebellar connectometry revealed subtle cerebellar alterations in MS patients, which were independent of conventional disease markers and highly correlated with patient function. Future work should assess the prognostic value of the observed damage. Hum Brain Mapp 36:1609-1619, 2015. V C 2014 Wiley Periodicals, Inc.

Introduction. Local microstructural pathology in multiple sclerosis patients might influence their clinical performance. This study applied multicontrast MRI to quantify inflammation and neurodegeneration in MS lesions. We explored the impact of MRI-based lesion pathology in cognition and disability. Methods. 36 relapsing-remitting MS subjects and 18 healthy controls underwent neurological, cognitive, behavioural examinations and 3 T MRI including (i) fluid attenuated inversion recovery, double inversion recovery, and magnetization-prepared gradient echo for lesion count; (ii) T1, T2, and T2* relaxometry and magnetisation transfer imaging for lesion tissue characterization. Lesions were classified according to the extent of inflammation/neurodegeneration. A generalized linear model assessed the contribution of lesion groups to clinical performances. Results. Four lesion groups were identified and characterized by (1) absence of significant alterations, (2) prevalent inflammation, (3) concomitant inflammation and microdegeneration, and (4) prevalent tissue loss. Groups 1, 3, 4 correlated with general disability (Adj-R 2 = 0.6; P = 0.0005), executive function (Adj-R 2 = 0.5; P = 0.004), verbal memory (Adj-R 2 = 0.4; P = 0.02), and attention (Adj-R 2 = 0.5; P = 0.002). Conclusion. Multicontrast MRI provides a new approach to infer in vivo histopathology of plaques. Our results support evidence that neurodegeneration is the major determinant of patients' disability and cognitive dysfunction.

In total, forty six compounds, including the novel compound lobechine (1), were characterized from the methanol extracts of Lobelia chinensis. The chemical structures of known metabolites were identified by comparing their spectroscopic and physical data with compounds reported in the literature. The structure of lobechine (1) was comprehensively established with the aid of 1D and 2D NMR spectroscopic analyses. In addition, selected isolates were screened for their inhibition of HSV-1 replication, superoxide anion generation, and elastase release. Among the tested compounds, scoparone (10) exhibited significant inhibition of superoxide anion generation with IC(50) of 6.14 ± 1.97 μM and lobechine (1) exhibited moderate inhibition of elastase release with IC(50) of 25.01 ± 6.95 μM, respectively.