Development and evaluation of a manual segmentation protocol for deep grey matter in multiple sclerosis: Towards accelerated semi-automated references.

BACKGROUND: Deep grey matter (dGM) structures, particularly the thalamus, are clinically relevant in multiple sclerosis (MS). However, segmentation of dGM in MS is challenging; labeled MS-specific reference sets are needed for objective evaluation and training of new methods. OBJECTIVES: This study aimed to (i) create a standardized protocol for manual delineations of dGM; (ii) evaluate the reliability of the protocol with multiple raters; and (iii) evaluate the accuracy of a fast-semi-automated segmentation approach (FASTSURF). METHODS: A standardized manual segmentation protocol for caudate nucleus, putamen, and thalamus was created, and applied by three raters on multi-center 3D T1-weighted MRI scans of 23 MS patients and 12 controls. Intra- and inter-rater agreement was assessed through intra-class correlation coefficient (ICC); spatial overlap through Jaccard Index (JI) and generalized conformity index (CIgen). From sparse delineations, FASTSURF reconstructed full segmentations; accuracy was assessed both volumetrically and spatially. RESULTS: All structures showed excellent agreement on expert manual outlines: intra-rater JI > 0.83; inter-rater ICC ≥ 0.76 and CIgen ≥ 0.74. FASTSURF reproduced manual references excellently, with ICC ≥ 0.97 and JI ≥ 0.92. CONCLUSIONS: The manual dGM segmentation protocol showed excellent reproducibility within and between raters. Moreover, combined with FASTSURF a reliable reference set of dGM segmentations can be produced with lower workload.

Multimodal Quantitative MR Imaging of the Thalamus in Multiple Sclerosis and Neuromyelitis Optica.

PURPOSE: To systematically investigate structural and functional alterations of the thalamus and its subregions through a multimodal magnetic resonance (MR) imaging technique and examine its clinical relevance in multiple sclerosis (MS) and neuromyelitis optica (NMO). MATERIALS AND METHODS: The institutional review board approved this study, and written informed consent was obtained from each participant. Thirty-seven patients with MS, 39 patients with NMO, and 40 healthy control subjects were recruited. Six MR imaging measurements were obtained for each participant and compared between groups in the thalamus and its seven subregions, including gray matter (GM) volume, fractional anisotropy, mean diffusivity, amplitude of low-frequency fluctuation, cross-correlation coefficient of spontaneous low frequency, and weighted functional connectivity strength. Partial correlation was used to estimate the MR imaging-clinical relationships. RESULTS: Both MS and NMO exhibited widespread GM atrophy (GM volume in MS, 0.244; NMO, 0.297; and control subjects, 0.329; P < .001) and diffusion abnormalities (fractional anisotropy in MS, 0.293; NMO, 0.323; and control subjects, 0.355; P < .001) in the whole thalamus and several subregions, while MS showed more severe changes than NMO. Decreased cross-correlation coefficient of spontaneous low-frequency and weighted functional connectivity strength was observed in several thalamus subregions in MS (P < .05), but no significant functional abnormalities were identified in NMO. GM volume, fractional anisotropy, and mean diffusivity, not functional changes of the thalamus and thalamic subregions, correlated with the patients' clinical variables and exhibited high discriminative power in distinguishing the three groups. CONCLUSION: Similar patterns of thalamic structural alteration were identified in MS and NMO, but MS showed more severe pathologic changes. The thalamus is a key node for functional disconnection in MS but not in NMO.

Altered thalamic functional connectivity in multiple sclerosis.

OBJECTIVE: To compare thalamic functional connectivity (FC) in patients with multiple sclerosis (MS) and healthy controls (HC), and correlate these connectivity measures with other MRI and clinical variables. METHODS: We employed resting-state functional MRI (fMRI) to examine changes in thalamic connectivity by comparing thirty-five patients with MS and 35 age- and sex-matched HC. Thalamic FC was investigated by correlating low frequency fMRI signal fluctuations in thalamic voxels with voxels in all other brain regions. Additionally thalamic volume fraction (TF), T2 lesion volume (T2LV), EDSS and disease duration were recorded and correlated with the FC changes. RESULTS: MS patients were found to have a significantly lower TF than HC in bilateral thalami. Compared to HC, the MS group showed significantly decreased FC between thalamus and several brain regions including right middle frontal and parahippocampal gyri, and the left inferior parietal lobule. Increased intra- and inter-thalamic FC was observed in the MS group compared to HC. These FC alterations were not correlated with T2LV, thalamic volume or lesions. In the MS group, however, there was a negative correlation between disease duration and inter-thalamic connectivity (r=-0.59, p<0.001). CONCLUSION: We demonstrated decreased FC between thalamus and several cortical regions, while increased intra- and inter-thalamic connectivity in MS patients. These complex functional changes reflect impairments and/or adaptations that are independent of T2LV, thalamic volume or presence of thalamic lesions. The negative correlation between disease duration and inter-thalamic connectivity could indicate an adaptive role of thalamus that is gradually lost with increasing disease duration.

Bioavailability and pharmacokinetics of sorafenib suspension, nanoparticles and nanomatrix for oral administration to rat.

Sorafenib is slightly absorbed in the gastrointestinal tract due to its poor solubility in water. To improve its absorption, a novel nanoparticulate formulation-nanomatrix was used in the study. The nanomatrix was a system prepared from a porous material Sylysia(®) 350 and a pH sensitive polymer Eudragit(®). The formulations were optimized by orthogonal design (L(9)(3(4))) and their bioavailability were evaluated in rat, comparing to pH-sensitive Eudragit nanoparticles and suspension of sorafenib. In the formulations, the ratio of sorafenib to Eudragit(®) S100 was found to be more important determinant of the sorafenib bioavailability than the ratio of sorafenib to Sylysia(®) 350. As for the bioavailability, the AUC(0-36 h) of sorafenib nanomatrix was 13-33 times to that of sorafenib suspension, but only 16.8% to 40.8% that of Eudragit(®) S100 nanoparticles. This may be resulted from the different drug dispersion degree, release character and bioadhension activity. However, because all the materials used in the nanomatrix formulation are commonly adjuvant, safe, easy to get and cheap, above all, the nanomatrix formulation can solve the stability and scaling up problems in the nanoparticles, it had potential to develop into a product in the future.

[Effect of ligustrazine, synthetic borneol on lasting time of ciliary movement].

OBJECTIVE: To study the using of the method in vitro and in vivo of lasting time of ciliary movement in ligustrazine, synthetic borneol. METHODS: (1) Method in vitro-The lasting time of ciliary movement was observed with forty-fold optical microscope after dropping liquid medicine on exteacorporeal frog palate mucosa. Then mucosa was cleared. It was observed whether the ciliary movement was recovered and the lasting time was recorded from recovering to stopping once again. (2) Method in vivo-Liquid medicine or normal saline was dropped on frog palate mucosa by contacting thirty minutes. Then mucosa was cleared. The lasting time of ciliary movement was observed with forty-fold optical microscope by separating palate mucosa. RESULTS: Relatively percentage of lasting time of ciliary movement of ligustrazine in vitro and in vivo was 9.8%, 87.3%; The relatively percentage of synthetic borneol in vitro and in vivo was 9.3%, 89.5%. CONCLUSION: The method in vitro and in vivo of lasting time of ciliary movement can be the one of the selecting ways of Chinese drug's toxicity of nasal mucosa, and it have virtues and defects respectively. Ligustrazine, synthetic borneol have significantly toxical effect on exteacorporeal lasting time of ciliary movement.