Cross-sectional and longitudinal evaluation of white matter microstructure damage and cognitive correlations by automated fibre quantification in relapsing-remitting multiple sclerosis patients.

The purpose of this study was to characterize whole-brain white matter (WM) fibre tracts by automated fibre quantification (AFQ), capture subtle changes cross-sectionally and longitudinally in relapsing-remitting multiple sclerosis (RRMS) patients and explore correlations between these changes and cognitive performance A total of 114 RRMS patients and 71 healthy controls (HCs) were enrolled and follow-up investigations were conducted on 46 RRMS patients. Fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (AD), and radial diffusivity (RD) at each node along the 20 WM fibre tracts identified by AFQ were investigated cross-sectionally and longitudinally in entire and pointwise manners. Partial correlation analyses were performed between the abnormal metrics and cognitive performance. At baseline, compared with HCs, patients with RRMS showed a widespread decrease in FA and increases in MD, AD, and RD among tracts. In the pointwise comparisons, more detailed abnormalities were localized to specific positions. At follow-up, although there was no significant difference in the entire WM fibre tract, there was a reduction in FA in the posterior portion of the right superior longitudinal fasciculus (R_SLF) and elevations in MD and AD in the anterior and posterior portions of the right arcuate fasciculus (R_AF) in the pointwise analysis. Furthermore, the altered metrics were widely correlated with cognitive performance in RRMS patients. RRMS patients exhibited widespread WM microstructure alterations at baseline and alterations in certain regions at follow-up, and the altered metrics were widely correlated with cognitive performance in RRMS patients, which will enhance our understanding of WM microstructure damage and its cognitive correlation in RRMS patients.

Efgartigimod as rescue treatment in acute phase of neuromyelitis optica spectrum disorder: A Case Report.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system demyelinating disease. Current therapy methods, however, have limited effect on acute attacks except for intravenous methylprednisolone (IVMP). Efgartigimod is a first-in-class novel human immunoglobulin G1 (IgG1) Fc fragment approved for the treatment of generalized myasthenia gravis. Its capacity to rapidly decrease serum IgG levels, including pathogenic autoantibodies, positions it as a potentially effective option for managing the acute phase of NMOSD. Case presentation: We report the case of a 59-year-old female patient with acute NMOSD, presenting with vision loss and numbness in all four limbs. Despite an initial inadequate response to intravenous methylprednisolone (IVMP), the addition of Efgartigimod to her treatment regimen led to rapid improvement, notably including a significant reduction in serum aquaporin-4 antibody titers, total IgG levels, and inflammation cytokine levels. Furthermore, no adverse events were reported during a four-month follow-up period. Conclusion: As an adjunct to glucocorticoid therapy, Efgartigimod has proven effective and safe for this patient. However, to ascertain its potential as a novel therapeutic option for acute NMOSD, larger-scale prospective clinical trials are required.

Interpretable and Intuitive Machine Learning Approaches for Predicting Disability Progression in Relapsing-Remitting Multiple Sclerosis Based on Clinical and Gray Matter Atrophy Indicators.

RATIONALE AND OBJECTIVES: To investigate whether clinical and gray matter (GM) atrophy indicators can predict disability in relapsing-remitting multiple sclerosis (RRMS) and to enhance the interpretability and intuitiveness of a predictive machine learning model. MATERIALS AND METHODS: 145 and 50 RRMS patients with structural MRI and at least 1-year follow-up Expanded Disability Status Scale (EDSS) results were retrospectively enrolled and placed in the discovery and external test cohorts, respectively. Six clinical and radiomics feature-based machine learning classifiers were trained and tested to predict disability progression in the discovery cohort and validated in the external test set. Partial dependence plot (PDP) analysis and a Shiny web application were conducted to enhance the interpretability and intuitiveness. RESULTS: In the discovery cohort, 98 patients had disability stability, and 47 patients were classified as having disability progression. In the external test set, 35 patients were disability stable, and 15 patients had disability progression. Models trained with both clinical and radiomics features (area under the curve (AUC), 0.725-0.950) outperformed those trained with clinical (AUC, 0.600-0.740) or radiomics features only (AUC, 0.615-0.945). Among clinical+ radiomics feature models, the logistic regression (LR) classifier-based model performed best, with an AUC of 0.950. Only the radiomics feature-only models were applied in the external test set due to the data collection problem and showed fair performance, with AUCs ranging from 0.617 to 0.753. PDP analysis showed that female patients and those with lower volume, surface area, and symbol digit modalities test (SDMT) scores; greater mean curvature and age; and no disease modifying therapy (DMT) had increased probabilities of disease progression. Finally, a Shiny web application (https://lauralin1104.shinyapps.io/LRshiny/) was developed to calculate the risk of disability progression. CONCLUSION: Interpretable and intuitive machine learning approaches based on clinical and GM atrophy indicators can help physicians predict disability progression in RRMS patients for clinical decision-making and patient management.

Radiomics derived from T2-FLAIR: the value of 2- and 3-classification tasks for different lesions in multiple sclerosis.

Background: White matter (WM) lesions can be classified into contrast enhancement lesions (CELs), iron rim lesions (IRLs), and non-iron rim lesions (NIRLs) based on different pathological mechanism in relapsing-remitting multiple sclerosis (RRMS). The application of radiomics established by T2-FLAIR to classify WM lesions in RRMS is limited, especially for 3-class classification among CELs, IRLs, and NIRLs. Methods: A total of 875 WM lesions (92 CELs, 367 IRLs, 416 NIRLs) were included in this study. The 2-class classification was only performed between IRLs and NIRLs. For the 2- and 3-class classification tasks, all the lesions were randomly divided into training and testing sets with a ratio of 8:2. We used least absolute shrinkage and selection operator (LASSO), reliefF algorithm, and mutual information (MI) for feature selection, then eXtreme gradient boosting (XGBoost), random forest (RF), and support vector machine (SVM) were used to establish discrimination models. Finally, the area under the curve (AUC), accuracy, sensitivity, specificity, and precision were used to evaluate the performance of the models. Results: For the 2-class classification model, LASSO classifier with RF model showed the best discrimination performance with the AUC of 0.893 (95% CI: 0.838-0.942), accuracy of 0.813, sensitivity of 0.833, specificity of 0.781, and precision of 0.851. However, the 3-class classification model of LASSO with XGBoost displayed the highest performance with the AUC of 0.920 (95% CI: 0.887-0.950), accuracy of 0.796, sensitivity of 0.839, specificity of 0.881, and precision of 0.846. Conclusions: Radiomics models based on T2-FLAIR images have the potential for discriminating among CELs, IRLs, and NIRLs in RRMS.

U-fiber diffusion kurtosis and susceptibility characteristics in relapsing-remitting multiple sclerosis may be related to cognitive deficits and neurodegeneration.

OBJECTIVES: To evaluate the diffusion kurtosis and susceptibility change in the U-fiber region of patients with relapsing-remitting multiple sclerosis (pwRRMS) and their correlations with cognitive status and degeneration. MATERIALS AND METHODS: Mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), kurtosis fractional anisotropy (KFA), and the mean relative quantitative susceptibility mapping (mrQSM) values in the U-fiber region were compared between 49 pwRRMS and 48 healthy controls (HCs). The U-fiber were divided into upper and deeper groups based on the location. The whole brain volume, gray and white matter volume, and cortical thickness were obtained. The correlations between the mrQSM values, DKI-derived metrics in the U-fiber region and clinical scale scores, brain morphologic parameters were further investigated. RESULTS: The decreased MK, AK, RK, KFA, and increased mrQSM values in U-fiber lesions (p < 0.001, FDR corrected), decreased RK, KFA, and increased mrQSM values in U-fiber non-lesions (p = 0.034, p < 0.001, p < 0.001, FDR corrected) were found in pwRRMS. There were differences in DKI-derived metrics and susceptibility values between the upper U-fiber region and the deeper one for U-fiber non-lesion areas of pwRRMS and HCs (p < 0.05), but not for U-fiber lesions in DKI-derived metrics. The DKI-derived metrics and susceptibility values were widely related with cognitive tests and brain atrophy. CONCLUSION: RRMS patients show abnormal diffusion kurtosis and susceptibility characteristics in the U-fiber region, and these underlying tissue abnormalities are correlated with cognitive deficits and degeneration. CLINICAL RELEVANCE STATEMENT: The macroscopic and microscopic tissue damages of U-fiber help to identify cognitive impairment and brain atrophy in multiple sclerosis and provide underlying pathophysiological mechanism. KEY POINTS: • Diffusion kurtosis and susceptibility changes are present in the U-fiber region of multiple sclerosis. • There are gradients in diffusion kurtosis and susceptibility characteristics in the U-fiber region. • Tissue damages in the U-fiber region are correlated with cognitive impairment and brain atrophy.

Radiomics models based on cortical damages for identification of multiple sclerosis with cognitive impairment.

BACKGROUND: Cognitive impairment (CI) is a common symptom in multiple sclerosis (MS) patients. Cortical damages can be closely associated with cognitive network dysfunction and clinically significant CI in MS. So, in this study, We aimed to develop a radiomics model to efficiently identify the MS patients with CI based on clinical data and cortical damages. METHODS: One hundred and eighteen patients with MS were divided into CI and normal cognitive (NC) cohorts (62/56) as defined by the Montreal Cognitive Assessment (MoCA). All participants were randomly divided into train and test sets with a ratio of 7:3. The radiomic features were selected by using the least absolute shrinkage and selection operator (LASSO) method. The discrimination models were built with the support vector machines (SVM) by the clinical data, radiomic features, and merge data, respectively. And the patients were further divided according to each cognitive domain including memory, visuospatial, language, attention and executive, and each domain model was applied by the most suitable classifier. RESULTS: A total of 2298 features were extracted, of which 36 were finally selected. The merge model showed the greatest performance with the area under the curve (AUC) of 0.86 (95 % confidence interval: 0.81-0.91), accuracy (ACC) of 0.78, sensitivity of 0.79 and specificity of 0.77 in test cohort. However, although the visuospatial domain model showed the highest AUC of 0.71 (95 % confidence interval: 0.61-0.81) among five domain models, other domain models did not meet satisfactory results with a relatively low AUC, ACC, sensitivity and specificity. CONCLUSIONS: The radiomics model based on clinical data and cortical damages had a great potential to identify the MS patients with CI for clinical cognitive assessment.

Increased cortical lesion load contributed to pathological changes beyond focal lesion in cortical gray matter of multiple sclerosis: a diffusion kurtosis imaging analysis.

Biomarkers specific to cortical gray matter (cGM) pathological changes of multiple sclerosis (MS) are desperately needed to better understand the disease progression. The cGM damage occurs in cortical lesion (CL) and normal-appearing cGM (NAcGM) areas. While the association between CL load and cGM damage has been reported, little is known about how different CL types, i.e. intracortical lesion (ICL) and leukocortical lesion (LCL) would be associated with cGM damage. In our study, relapsing-remitting MS patients and healthy controls were divided into 4 groups according to CL load level. NAcGM diffusion kurtosis imaging (DKI)/diffusion tensor imaging (DTI) values and cGM volume (cGMV) were used to characterize the pathological changes in cGM. Univariate general linear model was used for group comparisons and stepwise regression analysis was used to assess the effects of ICL volume and LCL volume on NAcGM damage. We found peak values in DKI/DTI values, cGMV and neuropsychological scores in high CL load group. Kurtosis fractional anisotropy (KFA) was the most sensitive in characterizing NAcGM damage, and LCL volume related more to NAcGM damage. Our findings suggested KFA could become a surrogate biomarker to cGM damage, and LCL might be the main factor in whole brain NAcGM damage.

Enlarged choroid plexus related to iron rim lesions and deep gray matter atrophy in relapsing-remitting multiple sclerosis.

BACKGROUND: Choroid plexus (CP) is considered to be linked to inflammation of multiple sclerosis (MS), but its connection with markers of inflammation in vivo in MS is unclear, the markers such as lesions load and brain atrophy, particularly the white matter lesions (WMLs) edge surrounded by an iron rim, termed as iron rim lesions (IRLs). PURPOSE: To investigate the association between CP volume and brain lesions load, especially IRLs load and atrophy in MS, and its relationship with clinical characteristics. METHODS: 3.0 T brain MRI images were acquired from 99 relapsing-remitting MS (RRMS) and 60 healthy controls (HCs) to obtain the volumes of CP, whole brain and lesions. Volumes were expressed as a ratio of intracranial volume. Expanded Disability Status Scale (EDSS), Montreal Cognitive Assessment (MoCA) and Symbol Digit Modalities Test (SDMT) were used to assess the severity of disability and cognitive function. Student's t-test and Multivariable regression analyses were performed to evaluate the difference of CP volumes between RRMS and HC and the association between CP volume and lesions load, brain volumes and clinical scale scores in RRMS. RESULTS: CP volume was 30% larger in patients with RRMS than HCs (p < 0.001) and was 20% larger in patients with IRLs than those without IRLs (p = 0.007). Moreover, the larger CP volume was related to greater WMLs volume in the whole RRMS (r = 0.46, p < 0.001). Further analysis in patients with IRLs showed a positive correlation between CP volume and WMLs volume (r = 0.45, p = 0.003), and IRLs volume (r = 0.51, p < 0.001). Meanwhile, enlarged CP was related to lower volumes in the whole brain (r = -0.30, p = 0.006), deep gray matter (r = -0.51, p < 0.001) and most regional deep gray matter nuclei (except amygdala), but no correlation with cortical lesions or cortex volume (both p > 0.05). In addition, CP volume was significantly higher in patients with cognitive impairment than those with cognitive preservation by MoCA scores (p = 0.011); the larger CP volume was associated with higher EDSS scores (r = 0.25, p = 0.014) and lower SDMT Z scores in RRMS (r = -0.26, p = 0.014). CONCLUSION: The enlargement of CP in RRMS had close correlations with inflammatory lesions, especially IRLs and deep gray matter atrophy, but not the cortex. Meanwhile, the larger CP volume was associated with higher disability and lower cognitive scores. CP volume may be a surrogate imaging marker for MS disease activity.

Microstructural alterations in different types of lesions and their perilesional white matter in relapsing-remitting multiple sclerosis based on diffusion kurtosis imaging.

BACKGROUND AND OBJECTIVES: In multiple sclerosis (MS), contrast enhancement lesions and chronic active lesions have been demonstrated to have different degrees of inflammation. Accordingly, they exist different degrees of tissue damage, one is short and acute, and another is slow and longstanding. This study aimed to explore whether diffusion parameters can differentiate different types of lesions, and investigate the microstructural damage between different types of MS lesions by using diffusion magnetic resonance imaging (dMRI) and its correlation with clinical biomarkers of disability and cognitive states. METHODS: We retrospectively identified 77 contrast enhancement lesions (CELs), 384 iron rim lesions (IRLs), 393 non-iron rim lesions (NIRLs), their corresponding perilesional white matter (PLWM), and 68 normal-appearing white matter (NAWM) from 68 relapsing-remitting MS (RRMS). Additionally, 44 white matter in healthy controls (WM in HCs) were also enrolled in this study. The DTI and DKI parameters were measured in the above white matter, including kurtosis fractional anisotropy (KFA), fractional anisotropy (FA), mean kurtosis (MK), and mean diffusivity (MD). All the patients were assessed with the Digital Span Test (DST), the Symbol Digit Modalities Test (SDMT), the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Expanded Disability Status Scale (EDSS). RESULTS: The lowest KFA, FA, MK values and the highest MD values were found in CELs, followed by IRLs, NIRLs, NAWM, and WM in HCs. In KFA and FA values, there were significant differences between each type of lesion, as well as each type of PLWM (P < 0.05). The MK values of CELs and IRLs were significantly lower than NIRLs, but inversely for MD (P < 0.05). There were no differences between CELs and IRLs for MK (P = 1) and MD (P = 0.261). The results of MK and MD values in CELs-PLWM and IRLs-PLWM were similar to the CELs and IRLs. There were no significant differences between NAWM and WM in HCs in all the enrolled diffusion parameters (P >0.05) and the FA values between NIRLs-PLWM and NAWM or between NIRLs-PLWM and WM in HCs were no significant differences (P >0.05). The KFA and MD values in IRLs-PLWM (r =0.443, P =0.021; r =-0.518, P =0.006) were correlated with the DST scores and the KFA of CELs-PLWM (r =0.396, P =0.041) was correlated with SDMT scores. CONCLUSION: Our findings demonstrate that the KFA values have the potential to distinguish different types of MS white matter tissues. Furthermore, the diffusion parameters can reflect the microstructure abnormalities in different MS lesions and might help us better understand the pathological mechanism and lesion evolution.

Effect of fermentation with Lactobacillus fermentum FL-0616 on probiotic-rich bean powders.

Plant-based diets have received considerable attention for balancing human health and environmental sustainability. This study investigated the effects of fermentation with Lactobacillus fermentum FL-0616 on probiotic-rich mung bean, chickpea and tiger skin kidney bean powders. A particle size distribution experiment showed that the particle size of probiotic-rich bean powder was significantly reduced and the specific surface area was increased. This was critical for improving the dissolution rate, wettability and dispersibility. Simultaneously, the angles of repose and slide of the fermented bean powder were significantly reduced. Scanning electron microscopy confirmed that particle size of the bean powder decreased and became more uniform after fermentation. The results of dynamic and static rheology jointly demonstrated that fermentation improved the flowability of probiotic-rich bean powder, which was related to its decreased particle size. This study provides a technical foundation for the deep processing of bean resources. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05668-5.

Structure and properties of Pickering emulsions stabilized solely with novel buckwheat protein colloidal particles.

In this paper, buckwheat protein colloidal particles (BPCPs) were prepared by heat treatment to stabilize oil-water interface. The results of particle size, surface hydrophobicity and wettability indicated that the prepared BPCPs could be used as novel Pickering emulsifier. The effects of BPCPs concentration, ionic strength and heat treatment on the structure and properties of Pickering emulsions were explored. The microstructure results showed that BPCPs could tightly coated on the surface of oil droplets to form a tight interfacial film, confirming that BPCPs could be used as an effective Pickering-like stabilizer. With the increase of BPCPs concentration, the droplet size of the Pickering emulsion gradually decreased, and the viscoelasticity and storage stability of the emulsion were effectively improved. Different from the effect of ionic strength, heat treatment was beneficial to increasing the viscoelasticity of BPCPs-stabilized Pickering emulsion. The Pickering emulsions exhibited certain flocculation at different temperatures and ionic strengths, while still maintained good solid-like behavior. These results suggest that the structure and properties of BPCPs-stabilized Pickering emulsion could be regulated by changing the ionic strength and temperature.

Enlarged choroid plexus related to cortical atrophy in multiple sclerosis.

OBJECTIVES: To investigate the correlation between choroid plexus volume and whole brain morphology in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). METHODS: Fifty-one patients with MS, 42 patients with NMOSD, and 56 healthy controls (HC) were recruited. The morphological changes in choroid plexus and whole brain tissue were compared between three groups and the correlations between choroid plexus volume and brain atrophy were further investigated. The longitudinal alterations of brain morphology in 25 MS and 20 NMOSD patients were compared. RESULTS: Compared to the HC group, the choroid plexus volumes were increased in the MS group (p < 0.001) but not in the NMOSD group (p > 0.05). Compared to the HC group, the MS group showed reduced cortex thickness, deep gray matter volume, and increased ventricle system volume, and the NMOSD group showed increased third ventricle volume (all p < 0.05, false discovery rate corrected). In the MS group, there were widespread correlations between enlarged choroid plexus volume and reduced cerebral cortex thickness (p < 0.05, r = -0.292~-0.538, false discovery rate corrected). The interval time was not significantly different between the MS (median: 1.37 years) and NMOSD group (median: 1.25 years) (p > 0.05). In MS, compared with the baseline, the right hippocampus and nucleus accumbens volumes were decreased in long follow-up, and bilateral lateral ventricle volumes were increased both in short and long follow-up (all p < 0.05, false discovery rate corrected). CONCLUSIONS: The enlarged choroid plexus related to reduced cortical thickness and progressive local brain atrophy are shown in MS patients, but not obvious in NMOSD patients. KEY POINTS: • MS and NMOSD have different altered patterns in choroid plexus volume and brain atrophy. • The enlarged choroid plexus related to brain atrophy is shown in MS patients, but not obvious in NMOSD patients. • Progressive local brain atrophy is shown in MS patients, but not obvious in NMOSD patients.

The different damage patterns of short-, middle- and long-range connections between patients with relapse-remitting multiple sclerosis and neuromyelitis optica spectrum disorder.

Objective: To investigate the differences in short-, middle- and long-range connections between patients with relapse-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD), and their correlation with brain tissue volume, structural and functional network parameters. Methods: A total of 51 RRMS, 42 NMOSD and 56 health controls (HC) were recruited. Of these 25 RRMS (median: 1.37 years) and 20 NMOSD (median: 1.25 years) patients were also studied at follow-up. The whole-brain fiber connection was divided into three groups according to the trisected lengths of the tract in HC group, including short-, middle- and long-range connections. The brain tissue features (including total brain tissue and deep grey matter volumes) and parameters of DTI and functional networks (including the shortest path, clustering coefficient, local efficiency and global efficiency) were calculated. The differences in fiber number (FN) and average fractional anisotropy (FA) were compared between RRMS and NMOSD by the One-way ANOVA and post hoc tests. The correlation between the FN or FA and the brain tissue volume, DTI and functional network parameters were further analyzed by Pearson analysis. Results: Compared to HC and NMOSD, the total number of fibers in RRMS was decreased, including the reduced FN of middle- and long-range connections, but increased FN of short-range connections. Compared to HC, the FA of three fibers in RRMS and NMOSD were reduced significantly, and the decrease of FA in RRMS was greater than in NMOSD. There were correlations between the FN of short-, and long-range connections and the atrophy of whole brain tissue in two diseases and structural network topological parameters in RRMS. Additionally, there was no significant difference of FN and FA in short-, middle- and long-range connections between the baseline and follow-up in two diseases. Conclusions: RRMS and NMOSD patients have different patterns of fiber connection damage. The FN of different lengths in RRMS and NMOSD patients may be associated with brain atrophy. The FN and FA of different lengths may explain the decreased efficiency of the structural network in RRMS patients. In the short-term follow-up, neither has worsened damage of different fibers in two diseases.

The heterogeneity of tissue destruction between iron rim lesions and non-iron rim lesions in multiple sclerosis: A diffusion MRI study.

OBJECTIVES: This study aimed to explore the microstructural heterogeneity of different white matter (WM) tissues in relapsing-remitting multiple sclerosis (RRMS) patients by diffusion magnetic resonance imaging (dMRI) and its correlation with disability and cognitive status. MATERIALS AND METHODS: A total of 337 iron rim lesions (IRLs), 337 perilesional white matters of IRLs (IRLs-PLWMs), 330 non-iron rim lesions (non-IRLs), 330 non-IRLs-PLWMs, 42 normal-appearing white matters (NAWMs) in 42 RRMS patients, and 30 white matters in healthy controls (WMs in HCs) were enrolled in the lesion-wise analysis. Diffusion kurtosis imaging (DKI) parameters including kurtosis fractional anisotropy (KFA) and mean kurtosis (MK), and diffusion tensor imaging (DTI) parameters including fractional anisotropy (FA) and mean diffusivity (MD) were measured in the six types of tissues. Subgroup analysis was performed between non-IRLs with QSM hyperintense (non-IRLs-H) and non-IRLs with QSM isointense or hypointense (non-IRLs-I), as well as between non-IRLs-H-PLWMs and non-IRLs-I-PLWMs. Thirty-four out of forty-two patients were enrolled in patient-wise analysis. The relationships between these diffusion metrics of patients and their Kurtzke Expanded Disability Status Scale (EDSS) score and Symbol Digit Modalities Test (SDMT) score were analyzed separately by partial correlation analysis with age and disease duration (DD) as covariates. RESULTS: The KFA, FA, MK, and MD values were significantly different among the six types of tissues. The lowest KFA, FA, and MK values and the highest MD values were revealed in IRLs. There were significant differences in all the enrolled diffusion metrics between IRLs and non-IRLs, as well as between IRLs-PLWMs and non-IRLs-PLWMs (p < 0.05). There were no significant differences between NAWMs and WMs in HCs (p = 1.000 for all enrolled diffusion metrics). For all the enrolled diffusion metrics, no significant differences were found in the subgroup analysis. The FA, MK, and MD values of total lesions (including IRLs and non-IRLs) (r = -0.420, p = 0.017; r = -0.472, p = 0.006; r = -0.475, p = 0.006) and the MK values of IRLs (r = -0.438, p = 0.012) were correlated with the EDSS scores. There was no significant correlation between the diffusion parameter values and the SDMT scores. CONCLUSION: Our findings demonstrate that IRLs are more destructive than non-IRLs. Similarly, IRLs-PLWMs are more destructive than non-IRLs-PLWMs. Additionally, diffusion parameter values of MS lesions can reflect the disability degree. These findings contribute to a better understanding of the different evolution of MS lesions and the relationship between the disability level of patients and focal lesion damage degree.

Alterations in White Matter Fiber Tracts Characterized by Automated Fiber-Tract Quantification and Their Correlations With Cognitive Impairment in Neuromyelitis Optica Spectrum Disorder Patients.

Objectives: To investigate whether patients with neuromyelitis optica spectrum disorder (NMOSD) have tract-specific alterations in the white matter (WM) and the correlations between the alterations and cognitive impairment. Materials and Methods: In total, 40 patients with NMOSD and 20 healthy controls (HCs) who underwent diffusion tensor imaging (DTI) scan and neuropsychological scale assessments were enrolled. Automated fiber-tract quantification (AFQ) was applied to identify and quantify 100 equally spaced nodes of 18 specific WM fiber tracts for each participant. Then the group comparisons in DTI metrics and correlations between different DTI metrics and neuropsychological scales were performed. Results: Regardless of the entire or pointwise level in WM fiber tracts, patients with NMOSD exhibited a decreased fractional anisotropy (FA) in the left inferior fronto-occipital fasciculus (L_IFOF) and widespread increased mean diffusion (MD), axial diffusivity (AD), and radial diffusivity (RD), especially for the thalamic radiation (TR), corticospinal tract (CST), IFOF, inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF) [p < 0.05, false discovery rate (FDR) correction], and the pointwise analyses performed more sensitive. Furthermore, the negative correlations among MD, AD, RD, and symbol digit modalities test (SDMT) scores in the left TR (L_TR) were found in NMOSD. Conclusion: Patients with NMOSD exhibited the specific nodes of WM fiber tract damage, which can enhance our understanding of WM microstructural abnormalities in NMOSD. In addition, the altered DTI metrics were correlated with cognitive impairment, which can be used as imaging markers for the early identification of NMOSD cognitive impairment.

The Application of Diffusion Kurtosis Imaging on the Heterogeneous White Matter in Relapsing-Remitting Multiple Sclerosis.

Objectives: To evaluate the microstructural damage in the heterogeneity of different white matter areas in relapsing-remitting multiple sclerosis (RRMS) patients by using diffusion kurtosis imaging (DKI) and its correlation with clinical and cognitive status. Materials and Methods: Kurtosis fractional anisotropy (KFA), fractional anisotropy (FA), mean kurtosis (MK), and mean diffusivity (MD) in T1-hypointense lesions (T1Ls), pure T2-hyperintense lesions (pure-T2Ls), normal-appearing white matter (NAWM), and white matter in healthy controls (WM in HCs) were measured in 48 RRMS patients and 26 sex- and age-matched HCs. All the participants were assessed with the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Symbol Digit Modalities Test (SDMT) scores as the cognitive status. The Kurtzke Expanded Disability Status Scale (EDSS) scores were used to evaluate the clinical status in RRMS patients. Results: The lowest KFA, FA, and MK values and the highest MD values were found in T1Ls, followed by pure-T2Ls, NAWM, and WM in HCs. The T1Ls and pure-T2Ls were significantly different in FA (p = 0.002) and MK (p = 0.013), while the NAWM and WM in HCs were significantly different in KFA, FA, and MK (p < 0.001; p < 0.001; p = 0.001). The KFA, FA, MK, and MD values in NAWM (r = 0.360, p = 0.014; r = 0.415, p = 0.004; r = 0.369, p = 0.012; r = -0.531, p < 0.001) were correlated with the MMSE scores and the FA, MK, and MD values in NAWM (r = 0.423, p = 0.003; r = 0.427, p = 0.003; r = -0.359, p = 0.014) were correlated with the SDMT scores. Conclusion: Applying DKI to the imaging-based white matter classification has the potential to reflect the white matter damage and is correlated with cognitive impairment.

Demyelination and remyelination detected in an alternative cuprizone mouse model of multiple sclerosis with 7.0 T multiparameter magnetic resonance imaging.

The aim of this study was to investigate the mechanisms underlying demyelination and remyelination with 7.0 T multiparameter magnetic resonance imaging (MRI) in an alternative cuprizone (CPZ) mouse model of multiple sclerosis (MS). Sixty mice were divided into six groups (n = 10, each), and these groups were imaged with 7.0 T multiparameter MRI and treated with an alternative CPZ administration schedule. T2-weighted imaging (T2WI), susceptibility-weighted imaging (SWI), and diffusion tensor imaging (DTI) were used to compare the splenium of the corpus callosum (sCC) among the groups. Prussian blue and Luxol fast blue staining were performed to assess pathology. The correlations of the mean grayscale value (mGSV) of the pathology results and the MRI metrics were analyzed to evaluate the multiparameter MRI results. One-way ANOVA and post hoc comparison showed that the normalized T2WI (T2-nor), fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) values were significantly different among the six groups, while the mean phase (Φ) value of SWI was not significantly different among the groups. Correlation analysis showed that the correlation between the T2-nor and mGSV was higher than that among the other values. The correlations among the FA, RD, MD, and mGSV remained instructive. In conclusion, ultrahigh-field multiparameter MRI can reflect the pathological changes associated with and the underlying mechanisms of demyelination and remyelination in MS after the successful establishment of an acute CPZ-induced model.

Sulfated fucan/fucosylated chondroitin sulfate-dominated polysaccharide fraction from low-edible-value sea cucumber ameliorates type 2 diabetes in rats: New prospects for sea cucumber polysaccharide based-hypoglycemic functional food.

Sulfated fucan chondroitin sulfate-dominated polysaccharide fraction from low-edible-value sea cucumber may be a good alternative to high-edible-value sea cucumber-derived polysaccharide for application in hypoglycemic functional foods. To evaluate the potential effect of low-edible-value sea cucumber-derived polysaccharide fraction on type 2 diabetes (T2DM), two sulfated fucan/fucosylated chondroitin sulfate-dominated polysaccharide fractions screening from 10 global commercial low-edible-value sea cucumber species were investigated to identify their anti-diabetics efficacies using a high-fat diet and streptozotocin-induced T2DM rat model. Sulfated fucan-dominated polysaccharide fraction from Thelenota ananas and fucosylated chondroitin sulfate-dominated polysaccharide fraction from Cucumaria frondosa ameliorated hyperglycemia, restored hypertriglyceridemia and hypercholesterolemia, decreased inflammatory status and oxidative stress, protected against liver injury, as well as improved insulin resistance and promoted accumulation of hepatic glycogen by activating IRS/PI3K/AKT signaling and regulating GSK-3ß gene expression in T2DM rats. The current findings provide an available strategy for the commercialization of sea cucumber polysaccharide based-hypoglycemic functional food.

Comparison of physicochemical properties and antidiabetic effects of polysaccharides extracted from three seaweed species.

Three algae polysaccharides (APs) extracted from Ascophyllum nodosum (ANP), Fucus vesiculosus (FVP) and Undaria Pinnatifida (USP) significantly differed in the zeta potential, water and oil holding capacity, monosaccharide composition, organic element composition, molecular weight distribution, microstructure and rheological properties. Antidiabetic effects of APs were compared by oral intervention at the dose of 400 mg/kg·body weight/day in high sugar and fat diets and streptozotocin injection induced type 2 diabetic rats. The analysis of body weight, water intake, fasting blood glucose, insulin, oral glucose tolerance, blood lipid indicators (including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA)), liver function indexes (involving alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and renal function profiles (comprising uric acid (UA) and urea nitrogen (BUN)) showed that APs possessed obvious antidiabetic activities, and FVP showed better effects in controlling the levels of FFA, AST, ALT, UA and BUN. Intervention of FVP reduced the total bile acid (TBA) level and elevated high density lipoprotein cholesterol (HDL-C) level of diabetic rats. Histomorphological observation further demonstrated that APs, especially FVP, could attenuate liver and kidney damage caused by diabetes. This study concluded that the antidiabetic effects of ANP, FVP and USP were distinctly different, which might be attributed to their different chemical structures. Therefore, the structure-activity relationship and antidiabetic mechanism of APs will be our future research direction.

Physicochemical properties of polysaccharide fractions from Sargassum fusiforme and their hypoglycemic and hypolipidemic activities in type 2 diabetic rats.

Two polysaccharide fractions (SFPs, designated as respectively SFP-1 and SFP-2) were acquired from Sargassum fusiforme by ultrasound-assisted enzymatic extraction, and their physicochemical properties and hypoglycemic and hypolipidemic effects were investigated. Structural analysis indicated that SFPs were obvious different in the zeta potential, molecular weight distribution, characteristic organic group, microstructure and the contents of total sugar, uronic acid, sulfate and moisture. SFPs consisted of fucose, mannose, rhamnose, glucose, galactose and glucuronic acid with different molar ratios. Congo red test explained that SFPs had no triple-helix structure. SFP-1 exhibited lower viscosity due to its lower molecular weight. Regarding to hypoglycemic and hypolipidemic effects, oral administration of SFPs prominently restrained loss of body weight and increase of water intake, and also significantly controlled the increase of levels of fasting blood glucose, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), uric acid (UA), urea nitrogen (BUN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of diabetic rats, and SFP-2 showed better effects in controlling fasting blood glucose, ALT, UA and BUN levels. Intervention of SFP-2 reduced the levels of insulin, FFA and TBA of diabetic rats. Histomorphological observation further demonstrated that SFPs could attenuate liver and kidney damage caused by hyperglycemia and hyperlipidemia. Data indicated that SFPs, especially SFP-2, significantly improved hyperglycemia, hyperlipidemia and liver and kidney function of diabetic rats.