Dysfunction of the triple-network model is associated with cognitive impairment in patients with cerebral small vessel disease.

Purpose: This study aimed to demonstrate the correlations between the altered functional connectivity patterns in the triple-network model and cognitive impairment in patients with cerebral small vascular disease (CSVD). Methods: Resting-state functional magnetic resonance imaging data were obtained from 22 patients with CSVD and 20 healthy controls. The resting-state data were analyzed using independent component analysis and functional network connectivity (FNC) analysis to explore the functional alterations in the intrinsic triple-network model including the salience network (SN), default mode network (DMN), and central executive network (CEN), and their correlations with the cognitive deficits and clinical observations in the patients with CSVD. Results: Compared to the healthy controls, the patients with CSVD exhibited increased connectivity patterns in the CEN-DMN and decreased connectivity patterns in the DMN-SN, CEN-SN, intra-SN, and intra-DMN. Significant negative correlations were detected between the intra-DMN connectivity pattern and the Montreal Cognitive Assessment (MoCA) total scores (r = -0.460, p = 0.048) and MoCA abstraction scores (r = -0.565, p = 0.012), and a positive correlation was determined between the intra-SN connectivity pattern and the MoCA abstraction scores (r = 0.491, p = 0.033). Conclusions: Our study findings suggest that the functional alterations in the triple-network model are associated with the cognitive deficits in patients with CSVD and shed light on the importance of the triple-network model in the pathogenesis of CSVD.

Intranasal delivery of thin-film freeze-dried monoclonal antibodies using a powder nasal spray system.

Monoclonal antibodies (mAbs) administered intranasally as dry powders can be potentially applied for the treatment or pre-exposure prevention of viral infections in the upper respiratory tract. However, a method to transform the mAbs from liquid to dry powders suitable for intranasal administration and a device that can spray the dry powders to the desired region of the nasal cavity are needed to fully realize the potentials of the mAbs. Herein, we report that thin-film freeze-dried mAb powders can be sprayed into the posterior nasal cavity using Aptar Pharma's Unidose (UDS) Powder Nasal Spray System. AUG-3387, a human-derived mAb that neutralizes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was used in the present study. First, we prepared thin-film freeze-dried AUG-3387 powders (i.e., TFF AUG-3387 powders) from liquid formulations containing different levels of mAbs. The TFF AUG-3387 powder with the highest solid content (i.e., TFF AUG-3387C) was then chosen for further characterization, including the evaluation of the plume geometry, spray pattern, and particle size distribution after the powder was sprayed using the UDS Powder Nasal Spray. Finally, the deposition patterns of the TFF AUG-3387C powder sprayed using the UDS Powder delivery system were studied using 3D-printed nasal replica casts based on the CT scans of an adult and a child. It is concluded that it is feasible to intranasally deliver mAbs as dry powders by transforming the mAbs into dry powders using thin-film freeze-drying and then spraying the powder using a powder nasal spray system.

Abnormal causal connectivity of anterior cingulate cortex-visual cortex circuit related to nonsteroidal anti-inflammatory drug efficacy in migraine.

The anterior cingulate cortex (ACC) and visual cortex are integral components of the neurophysiological mechanisms underlying migraine, yet the impact of altered connectivity patterns between these regions on migraine treatment remains unknown. To elucidate this issue, we investigated the abnormal causal connectivity between the ACC and visual cortex in patients with migraine without aura (MwoA), based on the resting-state functional magnetic resonance imaging data, and its predictive ability for the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs). The results revealed increased causal connectivity from the bilateral ACC to the lingual gyrus (LG) and decreased connectivity in the opposite direction in nonresponders compared with the responders. Moreover, compared with the healthy controls, nonresponders exhibited heightened causal connectivity from the ACC to the LG, right inferior occipital gyrus (IOG) and left superior occipital gyrus, while connectivity patterns from the LG and right IOG to the ACC were diminished. Based on the observed abnormal connectivity patterns, the support vector machine (SVM) models showed that the area under the receiver operator characteristic curves for the ACC to LG, LG to ACC and bidirectional models were 0.857, 0.898, and 0.939, respectively. These findings indicate that neuroimaging markers of abnormal causal connectivity in the ACC-visual cortex circuit may facilitate clinical decision-making regarding NSAIDs administration for migraine management.

Inhalable dry powders of microRNA-laden extracellular vesicles prepared by thin-film freeze-drying.

Extracellular vesicles (EVs) are endogenous vesicles that comprise a variety of submicron vesicular structures. Among these, exosomes have been widely investigated as delivery systems for small and large molecules. Herein, the thin-film freeze-drying technology was utilized to engineer aerosolizable dry powders of miR-335-laden induced EVs (iEV-335) generated in B cells for potential delivery into the lung to treat primary lung cancer and/or pulmonary metastases. The size distribution, structure, and morphology of iEV-335 were preserved after they were subjected to thin-film freeze-drying with the proper excipients. Importantly, iEV-335, in liquid or reconstituted from thin-film freeze-dried powders, were equally effective in downregulating SOX4 gene expression in LM2 human triple-negative mammary cancer cells. The iEV-335 dry powder compositions showed mass median aerodynamic diameters (MMAD) of around 1.2 µm with > 60 % of the emitted doses had an MMAD of ≤ 3 µm, indicating that the powders can potentially achieve efficient deposition within the alveolar region following oral inhalation, which is desirable for treatment of primary lung cancer and pulmonary metastases. Overall, it is concluded that it is feasible to apply thin-film freeze-drying to prepare aerosolizable dry powders of iEVs for pulmonary delivery.

Single-Cell Transcriptomics Reveals Cellular Heterogeneity and Complex Cell-Cell Communication Networks in the Mouse Cornea.

Purpose: To generate a single-cell RNA-sequencing (scRNA-seq) map and construct cell-cell communication networks of mouse corneas. Methods: C57BL/6 mouse corneas were dissociated to single cells and subjected to scRNA-seq. Cell populations were clustered and annotated for bioinformatic analysis using the R package "Seurat." Differential expression patterns were validated and spatially mapped with whole-mount immunofluorescence staining. Global intercellular signaling networks were constructed using CellChat. Results: Unbiased clustering of scRNA-seq transcriptomes of 14,732 cells from 40 corneas revealed 17 cell clusters of six major cell types: nine epithelial cell, three keratocyte, two corneal endothelial cell, and one each of immune cell, vascular endothelial cell, and fibroblast clusters. The nine epithelial cell subtypes included quiescent limbal stem cells, transit-amplifying cells, and differentiated cells from corneas and two minor conjunctival epithelial clusters. CellChat analysis provided an atlas of the complex intercellular signaling communications among all cell types. Conclusions: We constructed a complete single-cell transcriptomic map and the complex signaling cross-talk among all cell types of the cornea, which can be used as a foundation atlas for further research on the cornea. This study also deepens the understanding of the cellular heterogeneity and heterotypic cell-cell interaction within corneas.

Predicting the efficacy of non-steroidal anti-inflammatory drugs in migraine using deep learning and three-dimensional T1-weighted images.

Deep learning (DL) models based on individual images could contribute to tailored therapies and personalized treatment strategies. We aimed to construct a DL model using individual 3D structural images for predicting the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in migraine. A 3D convolutional neural network model was constructed, with ResNet18 as the classification backbone, to link structural images to predict the efficacy of NSAIDs. In total, 111 patients were included and allocated to the training and testing sets in a 4:1 ratio. The prediction accuracies of the ResNet34, ResNet50, ResNeXt50, DenseNet121, and 3D ResNet18 models were 0.65, 0.74, 0.65, 0.70, and 0.78, respectively. This model, based on individual 3D structural images, demonstrated better predictive performance in comparison to conventional models. Our study highlights the feasibility of the DL algorithm based on brain structural images and suggests that it can be applied to predict the efficacy of NSAIDs in migraine treatment.

Scaling-up of carbon dots hydrothermal synthesis from sugars in a continuous flow microreactor system for biomedical application as in vitro antimicrobial drug nanocarrier.

Carbon dots (CDs) are a new class of nanomaterials exhibiting high biocompatibility, water solubility, functionality, and tunable fluorescence (FL) property. Due to the limitations of batch hydrothermal synthesis in terms of low CDs yield and long synthesis duration, this work aimed to increase its production capacity through a continuous flow reactor system. The influence of temperature and time was first studied in a batch reactor for glucose, xylose, sucrose and table sugar precursors. CDs synthesized from sucrose precursor exhibited the highest quantum yield (QY) (175.48%) and the average diameter less than 10 nm (~6.8 ± 1.1 nm) when synthesized at 220°C for 9 h. For a flow reactor system, the best condition for CDs production from sucrose was 1 mL min-1 flow rate at 280°C, and 0.2 MPa pressure yielding 53.03% QY and ~ 6.5 ± 0.6 nm average diameter (6.6 mg min-1 of CDs productivity). CDs were successfully used as ciprofloxacin (CP) nanocarrier for antimicrobial activity study. The cytotoxicity study showed that no effect of CDs on viability of L-929 fibroblast cells was detected until 1000 µg mL-1 CDs concentration. This finding demonstrates that CDs synthesized via a flow reactor system have a high zeta potential and suitable surface properties for nano-theranostic applications.

Nanostructured N/S doped carbon dots/mesoporous silica nanoparticles and PVA composite hydrogel fabrication for anti-microbial and anti-biofilm application.

Regarding the convergence of the worldwide epidemic, the appearance of bacterial infection has occasioned in a melodramatic upsurge in bacterial pathogens with confrontation against one or numerous antibiotics. The implementation of engineered nanostructured particles as a delivery vehicle for antimicrobial agent is one promising approach that could theoretically battle the setbacks mentioned. Among all nanoparticles, silica nanoparticles have been found to provide functional features that are advantageous for combatting bacterial contagion. Apart from that, carbon dots, a zero-dimension nanomaterial, have recently exhibited their photo-responsive property to generate reactive oxygen species facilitating to enhance microorganism suppression and inactivation ability. In this study, potentials of core/shell mesoporous silica nanostructures (MSN) in conjugation with carbon dots (CDs) toward antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli have been investigated. Nitrogen and sulfur doped CDs (NS/CDs) conjugated with MSN which were cost effective nanoparticles exhibited much superior antimicrobial activity for 4 times as much as silver nanoparticles against all bacteria tested. Among all nanoparticles tested, 0.40 M NS/CDs@MSN showed the greatest minimal biofilm inhibitory at very low concentration (< 0.125 mg mL-1), followed by 0.20 M NS/CDs@MSN (0.5 mg mL-1), CD@MSN (25 mg mL-1), and MSN (50 mg mL-1), respectively. Immobilization of NS/CDs@MSN in polyvinyl alcohol (PVA) hydrogel was performed and its effect on antimicrobial activity, biofilm controlling efficiency, and cytotoxicity toward fibroblast (NIH/3 T3 and L-929) cells was additionally studied for further biomedical applications. The results demonstrated that 0.40 M NS/CDs-MSN@PVA hydrogel exhibited the highest inhibitory effect on S. aureus > P. aeruginosa > E. coli. In addition, MTT assay revealed some degree of toxicity of 0.40 M NS/CDs-MSN@PVA hydrogel against L-929 cells by a slight reduction of cell viability from 100% to 81.6% when incubated in the extract from 0.40 M NS/CDs-MSN@PVA hydrogel, while no toxicity of the same hydrogel extract was detected toward NIH/3 T3 cells.

Viability of Lactobacillus acidophilus in Thin-Film Freeze-Dried Powders Filled in Delayed-Release Vegetarian Capsules in a Simulated Gastric Fluid.

Previously, we have shown that thin-film freeze-drying can be applied to prepare dry powders of bacteria such as Lactobacillus acidophilus. Herein, we tested the viability of L. acidophilus in thin-film freeze-dried powders (TFF powders) filled in delayed-release vegetarian capsules in a simulated gastric fluid (SGF) consisting of 0.1N hydrochloric acid and sodium chloride. Initially, we determined the water removal rate from frozen thin films on relatively larger scales (i.e., 10-750 g). We then prepared and characterized two TFF powders of L. acidophilus with either sucrose and maltodextrin or sucrose and hydroxypropyl methylcellulose acetate succinate (HPMC-AS), a pH-sensitive polymer, as excipients and evaluated the viability of the bacteria after the TFF powders were filled in delayed-release vegetarian capsules and the capsules were incubated in the SGF for 30 min. On 10-750 g scales and at the settings specified, water removal from frozen thin films was faster than from slow shelf-frozen bulk solids. When the L. acidophilus in sucrose and HPMC-AS TFF powder was filled into a delayed-release capsule that was placed into another delayed-release capsule, the bacterial viability reduction after incubation in the SGF can be minimized to within 1 log in colony forming unit (CFU). However, for the L. acidophilus in sucrose and maltodextrin TFF powder, even in the capsule-in-capsule dosage form, bacterial CFU reduction was > 2 logs. TFF powders of live microorganisms containing an acid-resistant material in capsule-in-capsule delayed-release vegetarian capsules have the potential for oral delivery of those microorganisms.

Feasibility of intranasal delivery of thin-film freeze-dried, mucoadhesive vaccine powders.

Intranasal vaccination by directly applying a vaccine dry powder is appealing. However, a method that can be used to transform a vaccine from a liquid to a dry powder and a device that can be used to administer the powder to the desired region(s) of the nasal cavity are critical for successful intranasal vaccination. In the present study, using a model vaccine that contains liposomal monophosphoryl lipid A and QS-21 adjuvant (AdjLMQ) and ovalbumin (OVA) as a model antigen, it was shown that thin-film freeze-drying can be applied to convert the liquid vaccine containing sucrose at a sucrose to lipid ratio of 15:1 (w/w) into dry powders, in the presence or absence of carboxymethyl cellulose sodium salt (CMC) as a mucoadhesive agent. Ultimately, the thin-film freeze-dried AdjLMQ/OVA vaccine powder containing 1.9% (w/w) of CMC (i.e., TFF AdjLMQ/OVA/CMC1.9% powder) was selected for additional evaluation because the TFF AdjLMQ/OVA/CMC1.9% powder was mucoadhesive and maintained the integrity of the antigen and the physical properties of the vaccine. Compared to the TFF AdjLMQ/OVA powder that did not contain CMC, the TFF AdjLMQ/OVA/CMC1.9% powder had a lower moisture content and a higher glass transition temperature. In addition, the TFF AdjLMQ/OVA/CMC1.9% thin films were relatively thicker than the TFF AdjLMQ/OVA thin films without CMC. When sprayed with Aptar Pharma's Unidose Powder Nasal Spray System (UDSP), the TFF AdjLMQ/OVA powder and the TFF AdjLMQ/OVA/CMC1.9% powder generated similar particle size distribution curves, spray patterns, and plume geometries. Importantly, after the TFF AdjLMQ/OVA/CMC1.9% powder was sprayed with the UDSP nasal device, the integrity of the OVA antigen and the AdjLMQ liposomes did not change. Finally, a Taguchi L4 orthogonal array was applied to identify the optimal parameters for using the UDSP device to deliver the TFF AdjLMQ/OVA/CMC1.9% powder to the middle and lower turbinate and the nasopharynx regions in both adult and child nasal replica casts. Results from this study showed that it is feasible to apply the thin-film freeze-drying technology to transform a nasal vaccine candidate from liquid to a dry powder and then use the UDSP nasal device to deliver the vaccine powder to the desired regions in the nasal cavity for intranasal vaccination.

Potential predictors for the efficacy of non-steroidal anti-inflammatory drugs in patients with migraine.

Objectives: To explore potential predictors of the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with migraine. Methods: Consecutive migraine patients were recruited and divided into responders and non-responders to NSAIDs according to follow-up for at least three months. Demographic data, migraine-related disabilities and characteristics, and psychiatric comorbidities were evaluated and used to build multivariable logistic regression models. Subsequently, we generated receiver operating characteristic (ROC) curves to explore the performance of these traits in predicting NSAIDs efficacy. Results: A total of 567 patients with migraine who completed at least three months of follow-up were enrolled. In the multivariate regression analysis, five factors were identified as potential predictors for NSAIDs efficacy in treating migraine. Namely, attack duration (odds ratio (OR) = 0.959; p < 0.001), headache impact (OR = 0.966; p = 0.015), depression (OR = 0.889; p < 0.001), anxiety (OR = 0.748; p < 0.001), and education level (OR = 1.362; p < 0.001) were associated with response to NSAIDs treatment. The area under the curve, sensitivity, and specificity combining these five factors for predicting the efficacy of NSAIDs were 0.834, 0.909 and 0.676. Conclusions: These findings suggest that migraine-related and psychiatric factors are associated with the response to NSAIDs in migraine management. Identifying such key factors may help to optimize individualized migraine management strategy.

Disrupted resting-state functional connectivity of the thalamus in patients with coronary heart disease.

Background: Although homeostasis of the cardiovascular system is regulated by the cerebral cortex via the autonomic nervous system, the role of abnormal brain functional connectivity (FC) networks in patients with cardiac dysfunction remains unclear. Here, we report thalamus-based FC alterations and their relationship with clinical characteristics in patients with coronary heart disease (CHD). Methods: We employed resting-state functional magnetic resonance imaging (rs-fMRI) to acquire imaging data in twenty-six patients with CHD alongside sixteen healthy controls (HCs). Next, we performed a thalamus-based FC analysis to profile abnormal FC patterns in the whole brain. Subsequently, the mean time series of the brain regions that survived in the FC analysis were used to determine correlations with clinical parameters in patients with CHD. Results: We found no statistically significant differences in demographic and clinical data between patients with CHD and HCs. Patients with CHD showed decreased FC patterns between bilateral thalami and left hemisphere, encompassing supplementary motor area, superior frontal gyrus, superior parietal gyrus, inferior parietal gyrus, middle cingulate cortex, lingual gyrus and calcarine sulcus. Conclusions: These findings not only have implications in clarifying the relationship between cerebral functional imbalance and cardiovascular system, but also provide valuable insights to guide future evaluation and management of cardiac autonomic regulation via the brain-heart axis.

Altered static functional network connectivity predicts the efficacy of non-steroidal anti-inflammatory drugs in migraineurs without aura.

Brain networks have significant implications for the understanding of migraine pathophysiology and prognosis. This study aimed to investigate whether large-scale network dysfunction in patients with migraine without aura (MwoA) could predict the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs). Seventy patients with episodic MwoA and 33 healthy controls (HCs) were recruited. Patients were divided into MwoA with effective NSAIDs (M-eNSAIDs) and with ineffective NSAIDs (M-ieNSAIDs). Group-level independent component analysis and functional network connectivity (FNC) analysis were used to extract intrinsic networks and detect dysfunction among these networks. The clinical characteristics and FNC abnormalities were considered as features, and a support vector machine (SVM) model with fivefold cross-validation was applied to distinguish the subjects at an individual level. Dysfunctional connections within seven networks were observed, including default mode network (DMN), executive control network (ECN), salience network (SN), sensorimotor network (SMN), dorsal attention network (DAN), visual network (VN), and auditory network (AN). Compared with M-ieNSAIDs and HCs, patients with M-eNSAIDs displayed reduced DMN-VN and SMN-VN, and enhanced VN-AN connections. Moreover, patients with M-eNSAIDs showed increased FNC patterns within ECN, DAN, and SN, relative to HCs. Higher ECN-SN connections than HCs were revealed in patients with M-ieNSAIDs. The SVM model demonstrated that the area under the curve, sensitivity, and specificity were 0.93, 0.88, and 0.89, respectively. The widespread FNC impairment existing in the modulation of medical treatment suggested FNC disruption as a biomarker for advancing the understanding of neurophysiological mechanisms and improving the decision-making of therapeutic strategy.

Disrupted intra- and inter-network connectivity in unilateral acute tinnitus with hearing loss.

Purpose: Currently, the underlying neurophysiological mechanism of acute tinnitus is still poorly understood. This study aimed to explore differences in brain functional connectivity (FC) within and between resting-state networks (RSNs) in acute tinnitus patients with hearing loss (ATHL). Furthermore, it also evaluated the correlations between FC alterations and clinical characteristics. Methods: Two matched groups of 40 patients and 40 healthy controls (HCs) were included. Independent component analysis (ICA) was employed to obtain RSNs and FC differences were calculated within RSNs. In addition, the relationships between networks were conducted using functional network connectivity (FNC) analysis. Finally, an analysis of correlation was used to evaluate the relationship between FNC abnormalities and clinical data. Results: Results of this study found that seven major RSNs including the auditory network (AN), cerebellum network (CN), default mode network (DMN), executive control network (ECN), sensorimotor network (SMN), ventral attention network (VAN), and visual network (VN) were extracted using the group ICA in both groups. Furthermore, it was noted that the ATHL group showed aberrant FC within the CN, ECN, and VN as compared with HCs. Moreover, different patterns of network interactions were observed between groups, including the SMN-ECN, SMN-CN, ECN-AN, DMN-VAN, and DMN-CN connections. The correlations between functional disconnection and clinical characteristics in ATHL were also found in this study. Conclusion: In conclusion, this study indicated widespread alterations of intra- and inter-network connectivity in ATHL, suggesting that multiple large-scale network dysfunctions and interactions are involved in the early stage. Furthermore, our findings may provide new perspectives to understand the neuropathophysiological mechanism of acute tinnitus.

Disrupted Functional Connectivity of the Amygdala Predicts the Efficacy of Non-steroidal Anti-inflammatory Drugs in Migraineurs Without Aura.

Machine learning (ML) has been largely applied for predicting migraine classification. However, the prediction of efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in migraine is still in the early stages. This study aims to evaluate whether the combination of machine learning and amygdala-related functional features could help predict the efficacy of NSAIDs in patients with migraine without aura (MwoA). A total of 70 MwoA patients were enrolled for the study, including patients with an effective response to NSAIDs (M-eNSAIDs, n = 35) and MwoA patients with ineffective response to NSAIDs (M-ieNSAIDs, n = 35). Furthermore, 33 healthy controls (HCs) were matched for age, sex, and education level. The study participants were subjected to resting-state functional magnetic resonance imaging (fMRI) scanning. Disrupted functional connectivity (FC) patterns from amygdala-based FC analysis and clinical characteristics were considered features that could promote classification through multivariable logistic regression (MLR) and support vector machine (SVM) for predicting the efficacy of NSAIDs. Further, receiver operating characteristic (ROC) curves were drawn to evaluate the predictive ability of the models. The M-eNSAIDs group exhibited enhanced FC with ipsilateral calcarine sulcus (CAL), superior parietal gyrus (SPG), paracentral lobule (PCL), and contralateral superior frontal gyrus (SFG) in the left amygdala. However, the M-eNSAIDs group showed decreased FC with ipsilateral caudate nucleus (CAU), compared to the M-ieNSAIDs group. Moreover, the M-eNSAIDs group showed higher FC with left pre-central gyrus (PreCG) and post-central gyrus (PoCG) compared to HCs. In contrast, the M-ieNSAIDs group showed lower FC with the left anterior cingulate cortex (ACC) and right SFG. Furthermore, the MwoA patients showed increased FC with the left middle frontal gyrus (MFG) in the right amygdala compared to HCs. The disrupted left amygdala-related FC patterns exhibited significant correlations with migraine characteristics in the M-ieNSAIDs group. The MLR and SVM models discriminated clinical efficacy of NSAIDs with an area under the curve (AUC) of 0.891 and 0.896, sensitivity of 0.971 and 0.833, and specificity of 0.629 and 0.875, respectively. These findings suggest that the efficacy of NSAIDs in migraine could be predicted using ML algorithm. Furthermore, this study highlights the role of amygdala-related neural function in revealing underlying migraine-related neuroimaging mechanisms.

Comparative Study between ZOOMit and Conventional Intravoxel Incoherent Motion MRI for Assessing Parotid Gland Abnormalities in Patients with Early- or Mid-Stage Sjögren's Syndrome.

OBJECTIVE: To compare the reproducibility and performance of quantitative metrics between ZOOMit and conventional intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the diagnosis of early- and mid-stage Sjögren's syndrome (SS). MATERIALS AND METHODS: Twenty-two patients (mean age ± standard deviation, 52.0 ± 10.8 years; male:female, 2:20) with early- or mid-stage SS and 20 healthy controls (46.9 ± 14.6 years; male:female, 7:13) were prospectively enrolled in our study. ZOOMit IVIM and conventional IVIM MRI were performed simultaneously in all individuals using a 3T scanner. Quantitative IVIM parameters - including tissue diffusivity (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) - inter- and intra-observer reproducibility in measuring these parameters, and their ability to distinguish patients with SS from healthy individuals were assessed and compared between ZOOMit IVIM and conventional IVIM methods, appropriately. MR gland nodular grade (MRG) was also examined. RESULTS: Inter- and intra-observer reproducibility was better with ZOOMit imaging than with conventional IVIM imaging (ZOOMit vs. conventional, intraclass correlation coefficient of 0.897-0.941 vs. 0.667-0.782 for inter-observer reproducibility and 0.891-0.968 vs. 0.814-0.853 for intra-observer reproducibility). Significant differences in ZOOMit f, ZOOMit D*, conventional D*, and MRG between patients with SS and healthy individuals (all p < 0.05) were observed. ZOOMit D* outperformed conventional D* in diagnosing early- and mid-stage SS (area under receiver operating curve, 0.867 and 0.658, respectively; p = 0.002). The combination of ZOOMit D*, MRG, and ZOOMit f as a new diagnostic index for SS, increased diagnostic area under the curve to 0.961, which was higher than that of any single parameter (all p < 0.01). CONCLUSION: Considering its better reproducibility and performance, ZOOMit IVIM may be preferred over conventional IVIM MRI, and may subsequently improve the ability to diagnose early- and mid-stage SS.

Disrupted Dynamic Functional Connectivity of the Visual Network in Episodic Patients with Migraine without Aura.

Background: Visual symptoms are common in patients with migraine, even in interictal periods. The purpose was to assess the association between dynamic functional connectivity (dFC) of the visual cortex and clinical characteristics in migraine without aura (MwoA) patients. Methods: We enrolled fifty-five MwoA patients as well as fifty gender- and age-matched healthy controls. Regional visual cortex alterations were investigated using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF). Then, significant regions were selected as seeds for conducting dFC between the visual cortex and the whole brain. Results: Relative to healthy controls, MwoA patients exhibited decreased ReHo and ALFF values in the right lingual gyrus (LG) and increased ALFF values in the prefrontal cortex. The right LG showed abnormal dFC within the visual cortex and with other core brain networks. Additionally, ReHo values for the right LG were correlated with duration of disease and ALFF values of the right inferior frontal gyrus and middle frontal gyrus were correlated with headache frequency and anxiety scores, respectively. Moreover, the abnormal dFC of the right LG with bilateral cuneus was positively correlated with anxiety scores. Conclusions: The dFC abnormalities of the visual cortex may be involved in pain integration with multinetworks and associated with anxiety disorder in episodic MwoA patients.

Assessment of kidney function in chronic kidney disease by combining diffusion tensor imaging and total kidney volume.

OBJECTIVE: This study aimed to investigate the value and feasibility of combining fractional anisotropy (FA) values from diffusion tensor imaging (DTI) and total kidney volume (TKV) for the assessment of kidney function in chronic kidney disease (CKD). MATERIALS AND METHODS: Fifty-one patients were included in this study. All MRI examinations were performed with a 3.0 T scanner. DTI was used to measure FA values, and TKV was obtained from DTI and T2-weighted imaging (T2WI). Patients were divided into three groups (mild, moderate, severe) according to eGFR, which was calculated with serum creatinine. Differences in the FA values of the cortex and medulla were analysed among the three groups, and the relationships of FA values, TKV, and the product of the FA values and TKV with eGFR were analysed. Receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficiency of the FA values, TKV, and the product of the FA values and TKV for kidney function in different CKD stages. RESULTS: Medullary FA values (m-FA), TKV, and the product of the m-FA values and TKV (m-FA-TKV) were significantly correlated with eGFR (r = 0.653, 0.685, and 0.797, respectively; all P < 0.001). ROC curve analysis showed that m-FA-TKV exhibited better diagnostic performance than m-FA values (P = 0.022). CONCLUSION: m-FA-TKV obtained by DTI significantly improves the accuracy of kidney function assessment in CKD patients.

Aberrant functional and effective connectivity of the frontostriatal network in unilateral acute tinnitus patients with hearing loss.

PURPOSE: The present study combined resting-state functional connectivity (FC) and Granger causality analysis (GCA) to explore frontostriatal network dysfunction in unilateral acute tinnitus (AT) patients with hearing loss. METHODS: The participants included 42 AT patients and 43 healthy control (HC) subjects who underwent resting-state functional magnetic resonance imaging (fMRI) scans. Based on the seed regions in the frontostriatal network, FC and GCA were conducted between the AT patients and HC subjects. Correlation analyses were used to examine correlations among altered FC values, GCA values, and clinical features in AT patients. RESULTS: Compared with HCs, AT patients showed a general reduction in FC between the seed regions in the frontostriatal network and nonauditory areas, including the frontal cortices, midcingulate cortex (MCC), supramarginal gyrus, and postcentral gyrus (PoCG). Using the GCA algorithm, we detected abnormal effective connectivity (EC) in the inferior occipital gyrus, MCC, Cerebelum_Crus1, and PoCG. Furthermore, correlations between disrupted FC/EC and clinical characteristics, especially tinnitus distress-related characteristics, were found in AT patients. CONCLUSIONS: Our work demonstrated abnormal FC and EC between the frontostriatal network and several nonauditory regions in AT patients with hearing loss, suggesting that multiple large-scale network dysfunctions and interactions are involved in the perception of tinnitus. These findings not only enhance the current understanding of the frontostriatal network in tinnitus but also serve as a reminder of the importance of focusing on tinnitus at an early stage.

Aberrant Brain Functional Connectivity Strength and Effective Connectivity in Patients with Type 2 Diabetes Mellitus.

Alterations of brain functional connectivity in patients with type 2 diabetes mellitus (T2DM) have been reported by resting-state functional magnetic resonance imaging studies, but the underlying precise neuropathological mechanism remains unclear. This study is aimed at investigating the implicit alterations of functional connections in T2DM by integrating functional connectivity strength (FCS) and Granger causality analysis (GCA) and further exploring their associations with clinical characteristics. Sixty T2DM patients and thirty-three sex-, age-, and education-matched healthy controls (HC) were recruited. Global FCS analysis of resting-state functional magnetic resonance imaging was performed to explore seed regions with significant differences between the two groups; then, GCA was applied to detect directional effective connectivity (EC) between the seeds and other brain regions. Correlations of EC with clinical variables were further explored in T2DM patients. Compared with HC, T2DM patients showed lower FCS in the bilateral fusiform gyrus, right superior frontal gyrus (SFG), and right postcentral gyrus, but higher FCS in the right supplementary motor area (SMA). Moreover, altered directional EC was found between the left fusiform gyrus and bilateral lingual gyrus and right medial frontal gyrus (MFG), as well as between the right SFG and bilateral frontal regions. In addition, triglyceride, insulin, and plasma glucose levels were correlated with the abnormal EC of the left fusiform, while disease duration and cognitive function were associated with the abnormal EC of the right SFG in T2DM patients. These results suggest that T2DM patients show aberrant brain function connectivity strength and effective connectivity which is associated with the diabetes-related metabolic characteristics, disease duration, and cognitive function, providing further insights into the complex neural basis of diabetes.