Time-restricted feeding is an intervention against excessive dark-phase sleepiness induced by obesogenic diet.

High-fat diet (HFD)-induced obesity is a growing epidemic and major health concern. While excessive daytime sleepiness (EDS) is a common symptom of HFD-induced obesity, preliminary findings suggest that reduced wakefulness could be improved with time-restricted feeding (TRF). At present, however, the underlying neural mechanisms remain largely unknown. The paraventricular thalamic nucleus (PVT) plays a role in maintaining wakefulness. We found that chronic HFD impaired the activity of PVT neurons. Notably, inactivation of the PVT was sufficient to reduce and fragment wakefulness during the active phase in lean mice, similar to the sleep-wake alterations observed in obese mice with HFD-induced obesity. On the other hand, enhancing PVT neuronal activity consolidated wakefulness in mice with HFD-induced obesity. We observed that the fragmented wakefulness could be eliminated and reversed by TRF. Furthermore, TRF prevented the HFD-induced disruptions on synaptic transmission in the PVT, in a feeding duration-dependent manner. Collectively, our findings demonstrate that ad libitum access to a HFD results in inactivation of the PVT, which is critical to impaired nocturnal wakefulness and increased sleep, while TRF can prevent and reverse diet-induced PVT dysfunction and excessive sleepiness. We establish a link between TRF and neural activity, through which TRF can potentially serve as a lifestyle intervention against diet/obesity-related EDS.

A circuit from the ventral subiculum to anterior hypothalamic nucleus GABAergic neurons essential for anxiety-like behavioral avoidance.

Behavioral observations suggest a connection between anxiety and predator defense, but the underlying neural mechanisms remain unclear. Here we examine the role of the anterior hypothalamic nucleus (AHN), a node in the predator defense network, in anxiety-like behaviors. By in vivo recordings in male mice, we find that activity of AHN GABAergic (AHNVgat+) neurons shows individually stable increases when animals approach unfamiliar objects in an open field (OF) or when they explore the open-arm of an elevated plus-maze (EPM). Moreover, object-evoked AHN activity overlap with predator cue responses and correlate with the object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHNVgat+ neurons reduces object and open-arm avoidance. Furthermore, retrograde viral tracing identifies the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHNVgat+ neurons in driving avoidance behaviors in anxiogenic situations. Thus, convergent activation of AHNVgat+ neurons serves as a shared mechanism between anxiety and predator defense to promote behavioral avoidance.

Tissue Characteristics of Endometrial Carcinoma Analyzed by Quantitative Synthetic MRI and Diffusion-Weighted Imaging.

BACKGROUND: This study investigates the association of T1, T2, proton density (PD) and the apparent diffusion coefficient (ADC) with histopathologic features of endometrial carcinoma (EC). METHODS: One hundred and nine EC patients were prospectively enrolled from August 2019 to December 2020. Synthetic magnetic resonance imaging (MRI) was acquired through one acquisition, in addition to diffusion-weighted imaging (DWI) and other conventional sequences using 1.5T MRI. T1, T2, PD derived from synthetic MRI and ADC derived from DWI were compared among different histopathologic features, namely the depth of myometrial invasion (MI), tumor grade, cervical stromal invasion (CSI) and lymphovascular invasion (LVSI) of EC by the Mann-Whitney U test. Classification models based on the significant MRI metrics were constructed with their respective receiver operating characteristic (ROC) curves, and their micro-averaged ROC was used to evaluate the overall performance of these significant MRI metrics in determining aggressive histopathologic features of EC. RESULTS: EC with MI had significantly lower T2, PD and ADC than those without MI (p = 0.007, 0.006 and 0.043, respectively). Grade 2-3 EC and EC with LVSI had significantly lower ADC than grade 1 EC and EC without LVSI, respectively (p = 0.005, p = 0.020). There were no differences in the MRI metrics in EC with or without CSI. Micro-averaged ROC of the three models had an area under the curve of 0.83. CONCLUSIONS: Synthetic MRI provided quantitative metrics to characterize EC with one single acquisition. Low T2, PD and ADC were associated with aggressive histopathologic features of EC, offering excellent performance in determining aggressive histopathologic features of EC.

Histogram Analysis Comparison of Monoexponential, Advanced Diffusion-Weighted Imaging, and Dynamic Contrast-Enhanced MRI for Differentiating Borderline From Malignant Epithelial Ovarian Tumors.

BACKGROUND: The accurate preoperative differentiation between borderline and malignant epithelial ovarian tumors (BEOTs vs. MEOTs) is crucial for determining the proper surgical strategy and improving the patient's postoperative quality of life. Several diffusion and perfusion MRI technologies are valuable for the differentiation; however, which is the best remains unclear. PURPOSE: To compare the whole solid-tumor volume histogram analysis of diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM), and dynamic contrast-enhanced MRI (DCE-MRI) in the differentiation of BEOTs vs. MEOTs and to identify the correlations between the perfusion parameters from IVIM and DCE-MRI. STUDY TYPE: Retrospective. POPULATION: Twenty patients with BEOTs and 42 patients with MEOTs. FIELD STRENGTH/SEQUENCE: 1.5T/DWI, DKI, and IVIM models fitting from 13 different b factors and 40 phases DCE-MRI. ASSESSMENT: Histogram metrics were derived from the apparent diffusion coefficient (ADC), diffusion kurtosis (K), diffusion coefficient (Dk), pure diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), volume transfer constant (Ktrans ), rate constant (kep ), and extravascular extracellular volume fraction (ve ). STATISTICAL TESTS: The Mann-Whitney U-test and receiver operating characteristic curve were used to determine the best histogram metrics and parameters. Multivariate logistic regression analysis was used to determine the best combined model for each two from the four technologies. Spearman's rank correlation was used to analyze the correlations between the IVIM and DCE-MRI parameters. RESULTS: ADC, D, Dk, and D* were significantly higher in BEOTs than in MEOTs (P < 0.05). K, Ktrans , kep , and ve were significantly lower in BEOTs than in MEOTs (P < 0.05). The 10th percentile of Dk was the most reliable single metric, with an area under the curve (AUC) of 0.921. Dk combined with Ktrans yielded the highest AUC of 0.950. A weak inverse correlation was found between D and Ktrans (r = -0.320, P = 0.025) and between D and kep (r = -0.267, P = 0.037). DATA CONCLUSION: The 10th percentile of Dk was the most valuable metric and Dk combined with Ktrans had the best performance for differentiating BEOTs from MEOTs. There was no evident link between perfusion-related parameters derived from IVIM and DCE-MRI. LEVEL OF EVIDENCE: 4 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;52:257-268.

Differentiation between sinonasal natural killer/T-cell lymphomas and diffuse large B-cell lymphomas by RESOLVE DWI combined with conventional MRI.

OBJECTIVE: To explore the feasibility of using RESOLVE DWI combined with conventional magnetic resonance imaging (MRI) to discriminate between sinonasal NKTLs and DLBCLs and to investigate the correlation between ADC value and Ki-67 expression in the two subtypes of NHLs. MATERIALS AND METHODS: Sixty patients with NKTLs and twenty-six patients with DLBCLs in the sinonasal region who were confirmed by histopathology underwent high-resolution DWI and conventional MRI. The apparent diffusion coefficients (ADCs) and conventional MRI features associated with NKTLs and DLBCLs were compared using multivariate logistic regression. Receiver operating characteristic (ROC) curve analysis was performed, and the area under the curve (AUC) values for conventional MRI and MRI in combination with DWI were compared to determine the diagnostic performances of the approaches in the differentiation of NKTLs and DLBCLs. Spearman's rank correlations were used to analyze the correlation between ADC value with the higher AUC and Ki-67 expression. RESULTS: For conventional MRI, localization in the nasal cavity and poor or moderate enhancement indicated an NKTL, whereas localization in the paranasal sinus and intense enhancement indicated a DLBCL, with sensitivity, specificity and area under the curve(AUC)value of 88.5%, 85.0% and 0.883, respectively. A combination with a cut-off ADC value of 0.646 × 10-3 mm2/s yielded sensitivity, specificity and AUC values of 100.0%, 80.0% and 0.951, respectively. A significant difference between the AUCs for conventional MRI and MRI in combination with DWI (p = 0.02) was identified. Ki-67 expression of NKTLs was significantly lower than that of DLBCLs (p < 0.001). Besides, there was an inversely poor correlation between them in the overall sample (r = -0.395, p < 0.001). However, the ADC value was not significantly correlated with Ki-67 LI in neither NKTLs nor DLBCLs (both p > 0.05). CONCLUSIONS: Location and enhancement degree were the most valuable conventional MRI features for differentiating between NKTLs and DLBCLs. A combination of DWI and MRI could significantly improve the differential performance. ADC values may be used to noninvasively evaluate the proliferation level of sinonasal NHLs.