Polyphyllin VII ameliorates neuroinflammation and brain injury via modulating Treg/Th17 balance in a mouse model of cerebral ischemia-reperfusion injury.

Dysregulation of Th17 and Treg cells contributes to the pathophysiology of cerebral ischemia. Metabolic changes of peripheral CD4+ T cells lead to the imbalance of Treg/Th17 polarization, which represents a promising strategy for post-stroke therapy. Polyphyllin VII (PVII), a steroidal saponin extracted from traditional Chinese herb Rhizoma Paridis, has multiple bioactivities, but the potential function of PVII in cerebral ischemia-reperfusion injury is not elucidated yet. In our study, a mouse transient middle cerebral artery occlusion (MCAO) model was constructed. TTC staining, H&E staining, TUNEL staining, ELISA assay, flow cytometry, western blot, RT-qPCR, Open-field test, Morris water maze test, hanging wire test, rotarod test and foot-fault test were performed to evaluate the potential function of PVII in MCAO mice. We found that PVII showed protective effects on cerebral ischemia-reperfusion injury by reducing infarct volume, ameliorating brain injury and neuroinflammation, and improving long-term functional recovery of MCAO mice. PVII promoted Treg infiltration and suppressed infiltration of Th1/Th17 cells in ischemic brain in vivo. Moreover, PVII impaired peripheral CD4+ T cell activation and modulated Treg/Th17 differentiation in vitro. Mechanistically, PVII suppressed mTORC1 activation to influence glycolytic metabolism and ROS generation of T cells, thus leads to the imbalance of Treg/Th17 polarization towards Treg skewed. Furthermore, reactivation of mTORC1 by MHY1485 abolished the influence of PVII on brain injury and neuroinflammation in MCAO mice. Our data provided a novel role of PVII in cerebral ischemia-reperfusion injury via manipulating Treg/Th17 imbalance.

Pichia pastoris secreted peptides crossing the blood-brain barrier and DSIP fusion peptide efficacy in PCPA-induced insomnia mouse models.

Background: Pichia pastoris-secreted delta sleep inducing peptide and crossing the blood-brain barrier peptides (DSIP-CBBBP) fusion peptides holds significant promise for its potential sleep-enhancing and neurotransmitter balancing effects. This study investigates these properties using a p-chlorophenylalanine (PCPA) -induced insomnia model in mice, an approach akin to traditional methods evaluating sleep-promoting activities in fusion peptides. Aim of the study: The research aims to elucidate the sleep-promoting mechanism of DSIP-CBBBP, exploring its impact on neurotransmitter levels and sleep regulation, and to analyze its composition and structure. Materials and methods: Using a PCPA-induced insomnia mouse model, the study evaluates the sleep-promoting effects of DSIP-CBBBP. The peptide's influence on neurotransmitters such as 5-HT, glutamate, dopamine, and melatonin is assessed. The functions of DSIP-CBBBP are characterized using biochemical and animal insomnia-induced behavior tests and compared without CBBBP. Results: DSIP-CBBBP demonstrates a capacity to modulate neurotransmitter levels, indicated by changes in 5-HT, glutamate, DA, and melatonin. DSIP-CBBBP shows a better restorative effect than DSIP on neurotransmitter imbalance and the potential to enhance sleep. Conclusion: The study underscores DSIP-CBBBP potential in correcting neurotransmitter dysregulation and promoting sleep, hinting at its utility in sleep-related therapies.

Contrast-enhanced magnetic resonance neurography for diagnosing brachial plexopathy: improved visualization and additional imaging features.

Contrast-enhanced magnetic resonance neurography (CE-MRN) holds promise for diagnosing brachial plexopathy by enhancing nerve visualization and revealing additional imaging features in various lesions. This study aims to validate CE-MRN's efficacy in improving brachial plexus (BP) imaging across different patient cohorts. Seventy-one subjects, including 19 volunteers and 52 patients with BP compression/entrapment, injury, and neoplasms, underwent both CE-MRN and plain MRN. Two radiologists assessed nerve visibility, with inter-reader agreement evaluated. Quantitative parameters such as signal intensity (SI), contrast-to-noise ratio (CNR), and contrast ratio (CR) of the C7 nerve were measured. Both qualitative scoring and quantitative metrics were compared between CE-MRN and plain MRN within each patient group. Patient classification followed the Neuropathy Score Reporting and Data System (NS-RADS), summarizing additional imaging features for each brachial plexopathy type. Inter-reader agreement for qualitative assessment was strong. CE-MRN significantly enhanced BP visualization and nerve-tissue contrast across all cohorts, particularly in volunteers and patients with injuries. It also uncovered additional imaging features such as hypointense signals in ganglia, compressed nerve sites, and neoplastic enhancements. CE-MRN effectively mitigated muscle edema and vascular contamination, enabling precise classification of BP injuries. Overall, CE-MRN consistently enhances BP visualization and provides valuable imaging features for accurate diagnosis.

Global and local feature extraction based on convolutional neural network residual learning for MR image denoising.

Objective.Given the different noise distribution information of global and local magnetic resonance (MR) images, this study aims to extend the current work on convolutional neural networks that preserve global structure and local details in MR image denoising tasks.Approach.This study proposed a parallel and serial network for denoising 3D MR images, called 3D-PSNet. We use the residual depthwise separable convolution block to learn the local information of the feature map, reduce the network parameters, and thus improve the training speed and parameter efficiency. In addition, we consider the feature extraction of the global image and utilize residual dilated convolution to process the feature map to expand the receptive field of the network and avoid the loss of global information. Finally, we combine both of them to form a parallel network. What's more, we integrate reinforced residual convolution blocks with dense connections to form serial network branches, which can remove redundant information and refine features to further obtain accurate noise information.Main results.The peak signal-to-noise ratio, structural similarity index measure, and root mean square error metrics of 3D-PSNet are as high as 47.79%, 99.81%, and 0.40%, respectively, achieving competitive denoising effect on three public datasets. The ablation experiments demonstrated the effectiveness of all the designed modules regarding all the evaluated metrics in both datasets.Significance.The proposed 3D-PSNet takes advantage of multi-scale receptive fields, local feature extraction and residual dense connections to more effectively restore the global structure and local fine features in MR images, and is expected to help doctors quickly and accurately diagnose patients' conditions.

Machine learning based prediction models for analyzing risk factors in patients with acute abdominal pain: a retrospective study.

Background: Acute abdominal pain (AAP) is a common symptom presented in the emergency department (ED), and it is crucial to have objective and accurate triage. This study aims to develop a machine learning-based prediction model for AAP triage. The goal is to identify triage indicators for critically ill patients and ensure the prompt availability of diagnostic and treatment resources. Methods: In this study, we conducted a retrospective analysis of the medical records of patients admitted to the ED of Wuhan Puren Hospital with acute abdominal pain in 2019. To identify high-risk factors, univariate and multivariate logistic regression analyses were used with thirty-one predictor variables. Evaluation of eight machine learning triage prediction models was conducted using both test and validation cohorts to optimize the AAP triage prediction model. Results: Eleven clinical indicators with statistical significance (p < 0.05) were identified, and they were found to be associated with the severity of acute abdominal pain. Among the eight machine learning models constructed from the training and test cohorts, the model based on the artificial neural network (ANN) demonstrated the best performance, achieving an accuracy of 0.9792 and an area under the curve (AUC) of 0.9972. Further optimization results indicate that the AUC value of the ANN model could reach 0.9832 by incorporating only seven variables: history of diabetes, history of stroke, pulse, blood pressure, pale appearance, bowel sounds, and location of the pain. Conclusion: The ANN model is the most effective in predicting the triage of AAP. Furthermore, when only seven variables are considered, including history of diabetes, etc., the model still shows good predictive performance. This is helpful for the rapid clinical triage of AAP patients and the allocation of medical resources.

The finite element analysis study of the impact of single and double lag screw fixation on ankle fractures of different sizes.

In clinical practice, the choice of single vs. double screw fixation for posterior malleolus fractures (PMF) is theoretically unclear, particularly concerning the size-stability relationship. This study, employing Finite Element Analysis (FEA), assesses biomechanical stability in PMF of varying sizes under both fixation methods. Utilizing a 3D model based on CT scans, we simulated fractures with 10-50% fragment sizes and applied a 600 N force to mimic the single-leg stance. Our evaluation focused on screw Von Mises stress (VMS) and fracture relative displacement (RD). Results show that stability increases with fragment size for both fixation types. Single screw fixation is comparable to double screw in fragments up to 25%, but in larger fragments, double screw significantly enhances stability. This suggests that for fragments over 25%, double screw fixation is preferable, marking a critical threshold for PMF stability.

Polyphyllin I alleviates neuroinflammation after cerebral ischemia-reperfusion injury via facilitating autophagy-mediated M2 microglial polarization.

Microglial activation and polarization play a central role in poststroke inflammation and neuronal damage. Modulating microglial polarization from pro-inflammatory to anti-inflammatory phenotype is a promising therapeutic strategy for the treatment of cerebral ischemia. Polyphyllin I (PPI), a steroidal saponin, shows multiple bioactivities in various diseases, but the potential function of PPI in cerebral ischemia is not elucidated yet. In our study, the influence of PPI on cerebral ischemia-reperfusion injury was evaluated. Mouse middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation and reoxygenation (OGD/R) model were constructed to mimic cerebral ischemia-reperfusion injury in vivo and in vitro. TTC staining, TUNEL staining, RT-qPCR, ELISA, flow cytometry, western blot, immunofluorescence, hanging wire test, rotarod test and foot-fault test, open-field test and Morris water maze test were performed in our study. We found that PPI alleviated cerebral ischemia-reperfusion injury and neuroinflammation, and improved functional recovery of mice after MCAO. PPI modulated microglial polarization towards anti-inflammatory M2 phenotype in MCAO mice in vivo and post OGD/R in vitro. Besides, PPI promoted autophagy via suppressing Akt/mTOR signaling in microglia, while inhibition of autophagy abrogated the effect of PPI on M2 microglial polarization after OGD/R. Furthermore, PPI facilitated autophagy-mediated ROS clearance to inhibit NLRP3 inflammasome activation in microglia, and NLRP3 inflammasome reactivation by nigericin abolished the effect of PPI on M2 microglia polarization. In conclusion, PPI alleviated post-stroke neuroinflammation and tissue damage via increasing autophagy-mediated M2 microglial polarization. Our data suggested that PPI had potential for ischemic stroke treatment.

ITPR2 Mediated Calcium Homeostasis in Oligodendrocytes is Essential for Myelination and Involved in Depressive-Like Behavior in Adolescent Mice.

Ca2+ signaling is essential for oligodendrocyte (OL) development and myelin formation. Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) is an endoplasmic reticulum calcium channel and shows stage-dependent high levels in postmitotic oligodendrocyte precursor cells (OPCs). The role and potential mechanism of ITPR2 in OLs remain unclear. In this study, it is revealed that loss of Itpr2 in OLs disturbs Ca2+ homeostasis and inhibits myelination in adolescent mice. Animals with OL-specific deletion of Itpr2 exhibit anxiety/depressive-like behaviors and manifest with interrupted OPC proliferation, leading to fewer mature OLs in the brain. Detailed transcriptome profiling and signal pathway analysis suggest that MAPK/ERK-CDK6/cyclin D1 axis underlies the interfered cell cycle progression in Itpr2 ablated OPCs. Besides, blocking MAPK/ERK pathway significantly improves the delayed OPC differentiation and myelination in Itpr2 mutant. Notably, the resting [Ca2+]i is increased in Itpr2 ablated OPCs, with the elevation of several plasma calcium channels. Antagonists against these plasma calcium channels can normalize the resting [Ca2+]i level and enhance lineage progression in Itpr2-ablated OPCs. Together, the findings reveal novel insights for calcium homeostasis in manipulating developmental transition from OPCs to pre-OLs; additionally, the involvement of OLs-originated ITPR2 in depressive behaviors provides new therapeutic strategies to alleviate myelin-associated psychiatric disorders.

KIF2A Upregulates PI3K/AKT Signaling through Polo-like Kinase 1 (PLK1) to Affect the Proliferation and Apoptosis Levels of Eriocheir sinensis Spermatogenic Cells.

E. sinensis is an animal model for studying the reproduction and development of crustaceans. In this study, we knocked down the Es-Kif2a gene by injecting dsRNA into E. sinensis and inhibited Es-Plk1 gene expression by injecting PLK1 inhibitor BI6727 into E. sinensis. Then, the cell proliferation level, apoptosis level, and PI3K/AKT signaling expression level were detected. Our results showed that the proliferation level of spermatogenic cells decreased, while the apoptosis level increased after Es-Kif2a knockdown or Es-Plk1 inhibition. In order to verify whether these changes are caused by regulating the PI3K/AKT pathway, we detected the expression of PI3K and AKT proteins after Es-Kif2a knockdown or Es-Plk1 inhibition. Western Blot showed that in both the Es-Kif2a knockdown group and the Es-Plk1 inhibition group, the expression of PI3K and AKT proteins decreased. In addition, immunofluorescence showed that Es-KIF2A and Es-PLK1 proteins were co-localized during E. sinensis spermatogenesis. To further explore the upstream and downstream relationship between Es-KIF2A and Es-PLK1, we detected the expression level of Es-PLK1 after Es-Kif2a knockdown as well as the expression level of Es-KIF2A after Es-Plk1 inhibition. Western Blot showed that the expression of Es-PLK1 decreased after Es-Kif2a knockdown, while there was no significant change of Es-KIF2A after Es-Plk1 inhibition, indicating that Es-PLK1 may be a downstream factor of Es-KIF2A. Taken together, these results suggest that Es-KIF2A upregulates the PI3K/AKT signaling pathway through Es-PLK1 during the spermatogenesis of E. sinensis, thereby affecting the proliferation and apoptosis levels of spermatogenic cells.

Improved visualization of median, ulnar nerves, and small branches in the wrist and palm using contrast-enhanced magnetic resonance neurography.

Background: Magnetic resonance imaging of peripheral nerves in the wrist and palm is challenging due to the small size, tortuous course, complex surrounding tissues, and accompanying blood vessels. The occurrence of carpal palmar lesions leads to edema, swelling, and mass effect, which may further interfere with the display and identification of nerves. Objective: To evaluate whether contrast-enhanced magnetic resonance neurography (ceMRN) improves the visualization of the morphology and pathology of the median, ulnar nerves, and their small branches in the wrist and palm. Design: An observational study. Methods: In total 57 subjects, including 36 volunteers and 21 patients with carpal palmar lesions, were enrolled and underwent ceMRN and non-contrast MRN (ncMRN) examination at 3.0 Tesla. The degree of vascular suppression, nerve visualization, diagnostic confidence, and lesion conspicuity was qualitatively assessed by two radiologists. Kappa statistics were obtained for inter-reader agreement. The signal-to-noise ratio, contrast ratio (CR), and contrast-to-noise ratio (CNR) of the median nerve were measured. The subjective ratings and quantitative measurements were compared between ncMRN and ceMRN. Results: The inter-reader agreement was excellent (k > 0.8) for all qualitative assessments and visualization assessment of each nerve segment. Compared with ncMRN, ceMRN significantly improved vascular suppression in volunteers and patients (both p < 0.001). The ceMRN significantly enhanced nerve visualization of each segment (all p < 0.05) and diagnostic confidence in volunteers and patients (both p < 0.05). The ceMRN improved lesion conspicuity (p = 0.003) in patients. Quantitatively, ceMRN had significantly higher CRs of nerve versus subcutaneous fat, bone marrow, and vessels and CNR of nerve versus vessel than ncMRN (all p < 0.05). Conclusion: The ceMRN significantly improves the visualization of peripheral nerves and pathology in the wrist and palm by robustly suppressing the signals of fat, bone marrow, and especially vessels in volunteers and patients.

Study on the improvement of magnetic resonance imaging and lesion display of small nerves in the wrist and palm using contrast agents Why was the study done? Because the nerves and branches in the wrist and palm are numerous, small, tortuous, and surrounded by muscles, fat, bones, blood vessels and other tissues, it is difficult to show their complete shape with conventional magnetic resonance imaging. Hand lesions often lead to swelling, edema and masses, which interfere with the display of nerves. Therefore, it is difficult to directly diagnose the relationship between the lesions and nerves in clinical practice. What did the researchers do? The research team used contrast agent plus three-dimensional high-resolution magnetic resonance sequence to display the nerves of volunteers and patients with hand lesions, and used subjective and objective evaluation methods to compare the display effect of the sequence on the nerves before and after the use of contrast agent. What did the researchers find? The imaging method of contrast agent plus three-dimensional high-resolution magnetic resonance sequence can reduce the interference of fat, blood vessels, etc. on nerve display, improve the display effect of each nerve segment of the wrist and palm, increase readers' confidence in identifying nerves, and improve the detection of lesions. What do the findings mean? This study verified the feasibility and advantages of using contrast agents for magnetic resonance imaging of nerves in the wrist and palm. It provides a new method for clinical and imaging diagnosis of hand lesions, which can simultaneously display the morphological characteristics of nerves and lesions, reducing the difficulty of clinical diagnosis and improving the efficiency of imaging diagnosis.

Subtractionless compressed-sensing-accelerated whole-body MR angiography using two-point Dixon fat suppression with single-pass half-reduced contrast dose: feasibility study and initial experience.

PURPOSE: To investigate the feasibility and clinical utility of a compressed-sensing-accelerated subtractionless whole-body MRA (CS-WBMRA) protocol with only contrast injection for suspected arterial diseases, by comparison to conventional dual-pass subtraction-based whole-body MRA (conventional-WBMRA) and available computed tomography angiography (CTA). MATERIALS AND METHODS: This prospective study assessed 86 patients (mean age, 56 years ± 16.4 [standard deviation]; 25 women) with suspected arterial diseases from May 2021 to December 2022, who underwent CS-WBMRA (n = 48, mean age, 55.9 years ± 16.4 [standard deviation]; 25 women) and conventional-WBMRA (n = 38, mean age, 48 years ± 17.4 [standard deviation]; 20 women) on a 3.0 T MRI after random group assignment based on the chronological order of enrolment. Of all enrolled patients administered the CS-WBMRA protocol, 35% (17/48) underwent CTA as required by clinical demands. Two experienced radiologists independently scored the qualitative image quality and venous enhancement contamination. Quantitative image assessment was carried out by determining and comparing the apparent signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of four representative arterial segments. The total examination time and contrast-dose were also recorded. The independent samples t-test or the Wilcoxon rank sum test was used for statistical analysis. RESULTS: The overall scores of CS-WBMRA outperformed those of conventional-WMBRA (3.40 ± 0.60 vs 3.22 ± 0.55, P < 0.001). In total, 1776 and 1406 arterial segments in the CS-WBMRA and conventional-WBMRA group were evaluated. Qualitative image scores for 7 (of 15) vessel segments in the CS-WMBRA group had statistically significantly increased values compared to those of the conventional-WBMRA groups (P < 0.05). Scores from the other 8 segments showed similar image quality (P > 0.05) between the two protocols. In the quantitative analysis, overall apparent SNRs were significantly higher in the conventional-WBMRA group than in the CS-WBMRA group (214.98 ± 136.05 vs 164.90 ± 118.05; P < 0.001), while overall apparent CNRs were not significantly different in these two groups (CS vs conventional: 107.13 ± 72.323 vs 161.24 ± 118.64; P > 0.05). In the CS-WBMRA group, 7 of 1776 (0.4%) vessel segments were contaminated severely by venous enhancement, while in the convention-WBMRA group, 317 of 1406 (23%) were rated as severe contamination. In the CS-WBMRA group, total examination and reconstruction times were only 7 min and 10 min, respectively, vs 20 min and < 30 s for the conventional WBMRA group, respectively. The contrast agent dose used in the CS-WBMRA protocol was reduced by half compared to conventional-WBMRA protocol (18.7 ± 3.5 ml vs 37.2 ± 5.4 ml, P = 0.008). CONCLUSION: The CS-WBMRA protocol provides excellent image quality and sufficient diagnostic accuracy for whole-body arterial disease, with relatively faster workflow and half-dose reduction of contrast agent, which has greater potential in clinical practice compared with conventional-WBMRA.

TiO2 nanoparticles affect spermatogenesis and adhesion junctions via the ROS-mediated mTOR signalling pathway in Eriocheir sinensis testes.

Recent findings found that TiO2 nanoparticles (TiO2-NPs) have male reproductive toxicity. However, few reports have studied the toxicity of TiO2-NPs in crustaceans. In this study, we first chose the freshwater crustacean Eriocheir sinensis (E. sinensis) to explore the male toxicity of TiO2-NP exposure and the underlying mechanisms. Three nm and 25 nm TiO2-NPs at a dose of 30 mg/kg bw induced apoptosis and damaged the integrity of the haemolymph-testis-barrier (HTB, a structure similar to the blood-testis-barrier) and the structure of the seminiferous tubule. The 3-nm TiO2-NPs caused more severe spermatogenesis dysfunction than the 25-nm TiO2-NPs. We initially confirmed that TiO2-NP exposure affected the expression patterns of adherens junctions (α-catenin and ß-catenin) and induced tubulin disorganization in the testis of E. sinensis. TiO2-NP exposure caused reactive oxygen species (ROS) generation and an imbalance of mTORC1-mTORC2 (mTORC1/rps6/Akt levels were increased, while mTORC2 activity was not changed). After using the ROS scavenger NAC to inhibit ROS generation, both the mTORC1-mTORC2 imbalance and alterations in AJs were rescued. More importantly, the mTORC1 inhibitor rapamycin abolished mTORC1/rps6/Akt hyperactivation and partially restored the alterations in AJs and tubulin. Collectively, the mTORC1-mTORC2 imbalance induced by TiO2-NPs was involved in the mechanism of AJ and HTB disruption, resulting in spermatogenesis in E. sinensis.

Es-ß-CATENIN affects the hemolymph-testes barrier in Eriocheir sinensis by disrupting cell junctions and cytoskeleton.

ß-CATENIN is an evolutionarily conserved multifunctional molecule that maintains cell adhesion as a cell junction protein to safeguard the integrity of the mammalian blood-testes barrier, and also regulates cell proliferation and apoptosis as a key signaling molecule in the WNT/ß-CATENIN signaling pathway. In the crustacean Eriocheir sinensis, Es-ß-CATENIN has been shown to be involved in spermatogenesis, but the testes of E. sinensis have large and well-defined structural differences from those of mammals, and the impact of Es-ß-CATENIN in them is still unknown. In the present study, we found that Es-ß-CATENIN, Es-α-CATENIN and Es-ZO-1 interact differently in the testes of the crab compared to mammals. In addition, defective Es-ß-CATENIN resulted in increased Es-α-CATENIN protein expression levels, distorted and deformed F-ACTIN, and disturbed localization of Es-α-CATENIN and Es-ZO-1, leading to loss of hemolymph-testes barrier integrity and impaired sperm release. In addition to this, we also performed the first molecular cloning and bioinformatics analysis of Es-AXIN in the WNT/ß-CATENIN pathway to exclude the effect of the WNT/ß-CATENIN pathway on the cytoskeleton. In conclusion, Es-ß-CATENIN participates in maintaining the hemolymph-testes barrier in the spermatogenesis of E. sinensis.

A Rare Case of Neuralgic Amyotrophy Associated with Brucella Infection.

Multiple micro-organisms associated with Neuralgic Amyotrophy (NA) have been reported and Brucella species should be an important and overlooked infectious cause or trigger.We report a rare case of neuralgic amyotrophy associated with Brucella infection and is believed to be the first such case report in China. A 42-year-old male with brucellosis was confirmed serologically, who presented recurrent fever and fatigue and suddenly developed severe pain in the right shoulder within one week, followed by the inability to lift and abduct the proximal end of the right upper limb. Based on typical clinical manifestions, MRI neuroimaging of the brachial plexus and neuro-electrophysiological studies to confirm a diagnosis of NA and presented spontaneous recovery during this period, immunomodulatory treatment with corticosteroid or intravenous immunoglobulin had not been attempted, leaving a serious movement disorder in the right upper limb. Even rare, NA and other neurobrucellosis forms should be considered as complications of Brucella infection.

Simultaneous T1, T2, and T2* Mapping of Carotid Plaque: The SIMPLE* Technique.

Background Quantitative T1, T2, and T2* measurements of carotid atherosclerotic plaque are important in evaluating plaque vulnerability and monitoring its progression. Purpose To develop a sequence to simultaneously quantify T1, T2, and T2* of carotid plaque. Materials and Methods The simultaneous T1, T2, and T2* mapping of carotid plaque (SIMPLE*) sequence is composed of three modules with different T2 preparation pulses, inversion-recovery pulses, and acquisition schemas. Single-echo data were used for T1 and T2 quantification, while the multiecho (ME) data were used for T2* quantification. The quantitative accuracy of SIMPLE* was tested in a phantom study by comparing its measurements with those of reference standard sequences. In vivo feasibility of the technique was prospectively evaluated between November 2020 and February 2022 in healthy volunteers and participants with carotid atherosclerotic plaque. The Pearson or Spearman correlation test, Student t test, and Wilcoxon rank-sum test were used. Results T1, T2, and T2* estimated with SIMPLE* strongly correlated with inversion-recovery spin-echo (SE) (correlation coefficient [r] = 0.99), ME-SE (r = 0.99), and ME gradient-echo (r = 0.99) sequences in the phantom study. In five healthy volunteers (mean age, 25 years ± 3 [SD]; three women), measurements were similar between SIMPLE* and modified Look-Locker inversion recovery, or MOLLI (1151 msec ± 71 vs 1098 msec ± 64; P = .14), ME turbo SE (31 msec ± 1 vs 31 msec ± 1; P = .32), and ME turbo field echo (24 msec ± 2 vs 25 msec ± 2; P = .19). In 18 participants with carotid plaque (mean age, 65 years ± 9; 16 men), quantitative T1, T2, and T2* of plaque components were consistent with their signal characteristics on multicontrast images. Conclusion A quantitative technique for simultaneous T1, T2, and T2* mapping of carotid plaque with 100-mm3 coverage and 0.8-mm3 resolution was developed using the proposed SIMPLE* sequence and demonstrated high accuracy and in vivo feasibility. © RSNA, 2023 Supplemental material is available for this article.

Turbo Gradient and Spin-Echo BLADE-DWI for Extraocular Muscles in Thyroid-Associated Ophthalmopathy.

Purpose: To investigate feasibility and diagnostic performance of turbo gradient and spin-echo BLADE (proprietary name for Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction [PROPELLER] in Siemens MR systems)-diffusion weighted imaging (TGSE-BLADE-DWI) for depicting extraocular muscle (EOM) involvement and activity in thyroid-associated ophthalmopathy (TAO), and to compare TGSE-BLADE-DWI with readout-segmented echo-planar imaging (RESOLVE). Materials and methods: Thirty-five patients with identified TAO underwent the two DWI scans. Two radiologists visually scored the image quality of the two DWIs with respect to the susceptibility artifacts and geometric distortions on a three-point scale. The maximum size (Sizemax) of EOMs and corresponding ADCs (cADCs) of each patient were compared between the active and inactive phases. The clinical activity score (CAS) was used as a reference to assess the diagnostic performance of EOM ADCs for grading TAO activity. ROC analysis, Pearson correlation, and Wilcoxon signed-rank test were used for statistical analyses. Results: For scores of EOMs, the image quality of TGSE-BLADE-DWI was significantly higher than that of RESOLVE. There were no statistically significant differences between the AUCs of the two DWIs, Sizemax, or cADCs between the active and inactive phases. TGSE-BLADE-DWI ADCs were significantly higher than the RESOLVE ADCs in the right superior rectus, right lateral rectus, left superior rectus, and left inferior rectus. There were no statistically significant correlations between the cADC or Sizemax, and CAS. The highest AUC was 0.697 for RESOLVE and 0.657 for TGSE-BLADE-DWI. The best performing ADC threshold was 1.85 × 10-3 mm2/s with 85.7% sensitivity, 58.8% specificity and 66.67% accuracy for RESOLVE and 1.99 × 10-3 mm2/s with 79.0% sensitivity, and 55.6% specificity and 65.27% accuracy for TGSE-BLADE-DWI. Conclusion: Compared to RESOLVE, TGSE-BLADE-DWI provided improved image quality with fewer susceptibility artifacts and geometric distortions for EOM visualization and showed an equivalent performance in detecting active TAO.

Crosstalk Between ß-CATENIN-Mediated Cell Adhesion and the WNT Signaling Pathway.

Cell adhesion and stable signaling regulation are fundamental ways of maintaining homeostasis. Among them, the Wnt/ß-CATENIN signaling plays a key role in embryonic development and maintenance of body dynamic homeostasis. At the same time, the key signaling molecule ß-CATENIN in the Wnt signaling can also function as a cytoskeletal linker protein to regulate tissue barriers, cell migration, and morphogenesis. Dysregulation of the balance between Wnt signaling and adherens junctions can lead to disease. How ß-CATENIN maintains the independence of these two functions, or mediates the interaction and balance of these two functions, has been explored and debated for a long time. In this study, we will focus on five aspects of ß-CATENIN chaperone molecules, phosphorylation of ß-CATENIN and related proteins, epithelial mesenchymal transition, ß-CATENIN homolog protein γ-CATENIN and disease, thus deepening the understanding of the Wnt/ß-CATENIN signaling and the homeostasis between cell adhesion and further addressing related disease problems.

Integrated head and neck imaging of symptomatic patients with stroke using simultaneous non-contrast cardiovascular magnetic resonance angiography and intraplaque hemorrhage imaging as compared with digital subtraction angiography.

BACKGROUND: Both stenosis rate and intraplaque hemorrhage (IPH) are important predictors of stroke risk. Simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) cardiovascular magnetic resonance (CMR) imaging can detect both stenosis rate and IPH. We aimed to evaluate consistency between SNAP and digital subtraction angiography (DSA) to assess symptomatic patients with stroke and explore the performance of SNAP to identify IPH and the clinical factors associated with IPH. METHODS: Eighty-one symptomatic patients with stroke, admitted to Wuhan Union Hospital who underwent CMR high-resolution vessel wall imaging (HR-VWI) and SNAP, were retrospectively identified. For patients who received interventional therapy, the imaging functions of SNAP and HR-VWI were compared with DSA. The diameters of the intracranial and carotid vessels were measured, and stenotic vessels were identified. The consistency of SNAP and HR-VWI in identifying IPH was also examined, and the correlations between IPH and clinical factors were analyzed. RESULTS: SNAP was more consistent with DSA than HR-VWI in measuring vascular stenosis (intraclass correlation coefficient [ICC]SNAP-DSA = 0.917, ICC HR-VWI-DSA = 0.878). Regarding the diameter measurements of each intracranial and carotid vessel segment, SNAP was superior or similar to HR-VWI, and both were consistent with DSA in the measurement of major intracranial vascular segments. HR-VWI and SNAP exhibited acceptable agreement in identifying IPH (Kappa = 0.839, 95% confidence interval [CI]: 0.704-0.974). Patients who underwent interventional therapy had a higher plaque burden (P < 0.001). Patients with IPH had lower levels of high-density lipoprotein cholesterol (HDL) (P = 0.038) and higher levels of blood glucose (P = 0.007) and cystatin C (P = 0.040). CONCLUSIONS: CMR SNAP is consistent with DSA in measuring vessel diameters and identifying atherosclerosis stenosis in each intracranial and carotid vessel segment. SNAP is also a potential alternative to HR-VWI in identifying stenosis and IPH.

Comparison of contrast-enhanced T1-weighted imaging using DANTE-SPACE, PETRA, and MPRAGE: a clinical evaluation of brain tumors at 3 Tesla.

BACKGROUND: We aimed to compare the performance of three contrast-enhanced T1-weighted three-dimensional (3D) magnetic resonance (MR) sequences to detect brain tumors at 3 Tesla. The three sequences were: (I) delay alternating with nutation for tailored excitation sampling perfection with application-optimized contrasts using different flip angle evolution (DANTE-SPACE), (II) pointwise encoding time reduction with radial acquisition (PETRA), and (III) magnetization-prepared rapid acquisition with gradient echo (MPRAGE). METHODS: This study involved 77 consecutive patients, including 34 patients with known primary brain tumors and 43 patients suspected of intracranial metastases. All patients underwent each of the three sequences with comparable spatial resolution and acquisition time post-injection. Signal-to-noise ratios (SNRs) for gray matter (GM) and white matter (WM), contrast-to-noise ratios (CNRs) for lesion/GM, lesion/WM, and GM/WM were quantitatively compared. Two radiologists determined the total number of enhancing lesions by consensus. Intraclass correlation coefficients (ICCs) between the two radiologists for metastases presence, qualitative ratings for image quality, and acoustic noise level of each sequence were assessed. RESULTS: Among the three sequences, SNRs and CNRs between lesions and surrounding parenchyma were highest using DANTE-SPACE, but CNRWM/GM was the lowest with DANTE-SPACE. SNRs for PETRA images were significantly higher than those for MPRAGE (P<0.001). CNRs between lesions and surrounding parenchyma were similar for PETRA and MPRAGE (P>0.05). Significantly more brain metastases were detected with DANTE-SPACE (n=94) compared with MPRAGE (n=71) and PETRA (n=72). The ICCs were 0.964 for MPRAGE, 0.975 for PETRA, and 0.973 for DANTE-SPACE. Qualitative scores for lesion imaging using DANTE-SPACE were significantly higher than those obtained with PETRA and MPRAGE (P=0.002 and P=0.004, respectively). The acoustic noise level for PETRA (64.45 dB) was significantly lower than that for MPRAGE (78.27 dB, P<0.01) and DANTE-SPACE (80.18 dB, P<0.01). CONCLUSIONS: PETRA achieves comparable detection of brain tumors with MPRAGE and is preferred for depicting osseous metastases and meningeal enhancement. DANTE-SPACE with blood vessel suppression showed improved detection of cerebral metastases compared with MPRAGE and PETRA, which could be helpful for the differential diagnosis of tumors.

Quantitative Susceptibility Mapping of Brain Iron Relating to Cognitive Impairment in Hypertension.

BACKGROUND: Hypertension (HTN) might impair cognition. Brain iron deposition correlates with cognitive impairment. The relationship between brain iron and cognition in HTN patients is less clear. PURPOSE: To measure brain susceptibility in HTN patients using quantitative susceptibility mapping (QSM) and to explore the relationship between brain iron and cognition. STUDY TYPE: Retrospective cross-sectional study. SUBJECTS: Sixty HTN patients (35 with mild cognitive impairment [MCI] and 25 without MCI) and 24 age, gender, and education matched controls. FIELD STRENGTH/SEQUENCE: 3 T; strategically acquired gradient echo (STAGE) imaging protocol for QSM analysis. ASSESSMENT: All subjects underwent Montreal Cognitive Assessment (MoCA) scoring of visuospatial/executive, naming, attention, abstraction, language, delayed memory, and orientation functions. HTN patients were divided into two groups (with and without MCI) depending on the MoCA score. Regions of interest (ROIs) were manually demarcated on the STAGE images by three independent radiologists and susceptibility were determined for bilateral frontal white matter, parietal white matter, occipital white matter, caudate nucleus (CN), putamen (PU), globus pallidus (GP), thalamus (TH), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN). STATISTICAL TESTS: Analysis of variance with post-hoc least significant difference (LSD) tests and Pearson correlation coefficients (r). A P-value <0.05 was considered to be statistically significant. RESULTS: The susceptibility was significantly different in CN, PU, and DN among the three groups. The susceptibility of right CN and left PU were correlated with MoCA scores (r = -0.429 and r = -0.389, respectively). The susceptibility of left PU was also correlated with delayed memory scores (r = -0.664). The susceptibility of left and right GP were correlated with naming scores (r = -0.494 and r = -0.446, respectively) and the susceptibility of left DN were correlated with visuospatial/executive scores (r = 0.479). DATA CONCLUSION: QSM measured brain iron was significantly higher in CN, PU, and DN in HTN patients. Cognitive impairment was correlated with regional brain iron deposition. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.