Previous studies have shown that the intrinsic brain functional activity significantly reduced in a variety of regions of Alzheimer's disease (AD) patients. However, the associated underlying metabolic mechanism remains not clear. Brain activity is primarily driven by the dynamic activity of neurons and their interconnections, which are regulated by synapses and are closely related to glucose uptakes. Simultaneous FDG-PET/fMRI imaging provides a unique opportunity to measure the concurrent brain functional activity and cerebral glucose metabolism information. In this study, using simultaneous resting-state PET/fMRI imaging, we investigated the concurrent global intrinsic activity and metabolic signal changes in AD patients. Twenty-two controls and nineteen AD patients were included. We compared the whole-brain amplitude of low frequency fluctuations (ALFF) measured using fMRI imaging and glucose uptake maps acquired from PET imaging between the two groups. Both maps showed significant reductions in the precuneus and left inferior parietal lobule (IPL) in AD compared to the control groups. Moreover, the ALFF within the precuneus and left IPL were significantly correlated with the colocalized glucose metabolism. The ALFF in the left IPL was significantly correlated with patient cognitive performance evaluated using MMSE or MoCA. Our findings provide useful insights into the understanding of brain intrinsic functional-metabolic activity and its role in AD pathology.
Deep learning models have shown great potential in reducing low-dose (LD) positron emission tomography (PET) image noise by estimating full-dose (FD) images from the corresponding LD images. Those models, however, when trained on paired LD-FD PET images from a source scanner, fail to generalize well when applied to LD PET images from a target scanner, due to a phenomenon called "domain drift." In this study, we present a method for cross-scanner LD PET image noise reduction. This is done via a self-ensembling framework using a limited number of paired LD-FD PET images and a large number of LD PET images from the target scanner. The self-ensembling framework leverages the paired 2-D slices from both scanners to learn a regression model. It additionally incorporates a consistency loss on the LD PET images from the target scanner to enhance the model's generalization capability. We conduct experiments on three datasets, respectively, acquired from three different scanners, including a GE Discovery MI (DMI) scanner, a Siemens Biograph Vision 450 (Vision) scanner, and a UI uMI 780 (uMI) scanner. Results from our comprehensive experiments demonstrate the generalization capability of our method.
The aim of the present study was to explore the feasibility of lentiviral‑mediated sodium iodide symporter (NIS) gene delivery for monitoring bone marrow‑derived mesenchymal stem cell (BMSC) transplantation into the infarcted myocardium. For this purpose, we constructed a lentiviral vector (Lv‑EF1α‑NIS‑IRES‑EGFP) expressing NIS and enhanced green fluorescent protein (EGFP), and introduced it into BMSCs at different multiplicities of infection (MOI). The expression of EGFP was observed under a fluorescence microscope. Iodine uptake and the inhibition of iodine uptake by sodium perchlorate (NaClO4) in the Lv‑EF1α‑NIS‑IRES‑EGFP‑treated BMSCs were dynamically monitored in vitro. The Lv‑EF1α‑NIS‑IRES‑EGFP‑treated BMSCs were transplanted into the infarcted myocardium of Sprague‑Dawley rats, and 99mTc99g (Tc, technetium; 99m indicates that technetium is at its excited stage; 99g indicates the atomic weight of technetium) micro‑single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging was performed in vivo 1 week following transplantation. The isolated BMSCs successfully differentiated into adipocytes and osteoblasts. The BMSCs were positive for the cell surface markers, CD105, CD29 and CD90, and negative for CD14, CD34 and CD45. Lv‑EF1α‑NIS‑IRES‑EGFP was efficiently transfected into the BMSCs. RT‑qPCR and western blot analysis confirmed that the BMSCs expressed high protein and mRNA levels of NIS by day 7 following infection, and NIS expression remained at a consistent level from day 14 to 21. In the Lv‑EF1α‑NIS‑IRES‑EGFP‑treated BMSCs, the accumulation of iodine-125 (125I) was observed in vitro and was successfully monitored by 99mTc99g micro‑SPECT/CT imaging at 1 week following transplantation. These results suggest that lentiviral vectors are powerful vehicles for studying gene delivery in BMSCs. It is feasible to use lentiviral vectors to deliver an NIS gene for the non‑invasive monitoring of BMSC transplantation and survival in the infarcted myocardium in vivo.
Background Our study aimed to demonstrate the feasibility of using the sodium/iodide symporter (NIS) to monitor vascular endothelial growth factor (VEGF165) expression in vivo. Methods We constructed a recombinant lentivirus plasmid with the MLC-2v promoter driving the sodium/iodide symporter (NIS) reporter gene linked to the VEGF165 gene. Expression of NIS and VEGF gene were identified by Western blot. On days 2 and 54, 99mTc-MIBI imaging was used to evaluate changes in myocardial ischemia. Noninvasive 125I micro-SPECT/CT imaging was used to assess the expression of NIS reporter gene dynamically over the next 2 months. Results Western blot analysis showed that both NIS and VEGF165 were highly expressed in rat cardiomyoblast H9C2 cells transduced with Lenti-MLC-2v-NIS--VEGF165. 125I micro-SPECT/CT reporter imaging showed higher uptake in mouse myocardium transduced with Lenti-MLC-2v-VEGF165-IRES-NIS. NIS expression peaked on day 1 after transduction followed by a progressive decline to negligible levels by day 21. On day 1, mean 125I activity value in group 1 was higher than that in group 2 (P<0.05). The mean 125I activity value in group 3 was statically lower than that in group 1 and 2 (P<0.01). On day 60, 125I uptakes in test and positive control groups became very low, and no significant differences in the mean 125I activity values were detected between group 1 and group 2 (P = 0.531 > 0.05). In group 1 (test group), 99mTc-MIBI SPECT/CT revealed improvements in perfusion and wall thickening in the apical anterior wall. Mean IOD values of NIS and CD34 were significantly higher in group 1 than group 3 (P<0.05). Our study proved mean I-125 uptake was significantly correlated with mean IOD value of NIS and CD34 (P<0.05). Conclusion This study demonstrates the feasibility of using the NIS gene to monitor VEGF165 expression in a mouse myocardial ischemia model.
AbstractBackground: The World Health Organization declared the outbreak a public health emergency of international concern (Corona Virus Disease 2019) on January 30th, this study aimed to investigate the epidemiological and clinical characteristics of Corona Virus Disease 2019 in Xiaoshan, Hangzhou, and evaluate scientific basis for disease control and prevention. Methods: A total of 30 patients had been admitted to hospital from Jan 22 to Feb 22, 2020, all of them were laboratory confirmed SARS-Cov-2. Demographic, epidemiological, clinical, laboratory data were collected from Hospital information system and Epidemiological investigation reports. All data was performed by descriptive analysis, Chi-square test or non-parametric Mann-Whitney U test, as appropriate. Two sided p value less than 0.05 was considered statistically significant.Results: 30 patients were enrolled, the median age was 44.5 years (IQR 33.8-52.3) and 17 (56.7%) patients were female, 14 (46.7%) patients were native and had no exposure to Hubei Province. At the time of study submission, only one patient had not been discharged and no patients died during the study. The median hospital stay was 16.0 days (IQR 12.5-20.5) and the median course of disease was 20.5 days (IQR 17.0-23.3). The most common symptoms were fever (66.7%), dry cough (26.7%), and pharyngalgia (23.3%) on first admission. Most patients were generally illness or more mild, but 10 (33.3%) patients received oxygen therapy and 14 (46.7%) patients received hormone therapy during their hospitalization. Almost half of patients showed mild lymphocytopenia and 40% patients had elevated concentrations of CRP in the early stages of COVID-19.Conclusions: Among the 30 patients were confirmed with SARA-Cov-2 infection in Xiaoshan, Hangzhou, most of them had clinical presentation of respiratory tract infection, but the median course of disease was more than 2 weeks. Further systematic prospective studies about COVID-19 should be urgently needed.
Abstract The uvula flapping is one of the most distinctive features of snoring and is critical in affecting airway aerodynamics and vibrations. This study aimed to elucidate the mechanism of pharyngeal vibration and pressure fluctuation due to uvula flapping employing fluid–structure interaction simulations. The followings are the methodology part: we constructed an anatomically accurate pediatric pharynx model and put attention on the oropharynx region where the greatest level of upper airway compliance was reported to occur. The uvula was assumed to be a rigid body with specific flapping frequencies to guarantee proper boundary conditions with as little complexity as possible. The airway tissue was considered to have a uniform thickness. It was found that the flapping frequency had a more significant effect on the airway vibration than the flapping amplitude, as the flapping uvula influenced the pharyngeal aerodynamics by altering the jet flow from the mouth. Breathing only through the mouth could amplify the effect of flapping uvula on aerodynamic changes and result in more significant oropharynx vibration.
ABSTRACT Background Sudden sensorineural hearing loss (SSNHL) is associated with abnormal changes in the brain's central nervous system. Previous studies on the brain networks of SSNHL have primarily focused on functional connectivity within the brain. However, in addition to functional connectivity, structural connectivity also plays a crucial role in brain networks. Moreover, traditional functional connectivity analyses often overlook the spatial and temporal characteristics of connectivity changes and fail to provide directional information and causal relationships. Aims This study utilized Structural Covariance Network (SCN), multilayer network analysis, and Dynamic Causal Modeling (DCM) to investigate the cross‐scale changes in neural network structure and function in SSNHL patients with accompanying cognitive and emotional disorders. Materials & Methods We collected 3D‐T1 structural magnetic resonance image data and functional magnetic resonance image data from 70 SSNHL patients and 81 healthy controls (HCs). SCN analysis was performed based on gray matter volume, and multilayer network analysis was used to calculate node switching rates. Based on the results of multilayer network analysis, six nodes exhibiting significant inter‐group differences in node switching rates were selected as regions of interest (ROIs). DCM was then conducted to explore the causal relationships of functional connectivity between these nodes. Results Based on SCN, there were no significant inter‐group differences in global network properties between SSNHL and HCs. At the node level, the left precentral gyrus in SSNHL showed a significant decrease in node efficiency. In the multilayer network analysis, SSNHL showed a significantly increased node switching rate at the level of the Left Superior Frontal Gyrus (L.SFG), Left Supplementary Motor Area (L.SMA), Left Superior Parietal Gyrus (L.SPG), Right Superior Parietal Gyrus (R.SPG), Right Inferior Parietal Lobe(R.IPL), and Left Thalamus (L.THA). Furthermore, the node switching rate of L.SFG showed a significant negative correlation with the Self‐Rating Anxiety Scale (SAS) scores. DCM analysis of these six nodes revealed differences in the functional effective connectivity between the left superior parietal gyrus (L.SPG) and the left supplementary motor area (L.SMA), which were positively correlated with the AVLT‐delay scores. Discussion These findings suggest that SSNHL patients experience structural and functional remodeling of the cerebral cortex, with hearing loss leading to the reallocation of cognitive resources. Conclusion This provides new insights into understanding the potential mechanisms between cross‐scale networks and cognitive‐emotional disorders in SSNHL.