An Exploratory Pilot Study on the Application of Radiofrequency Ablation for Atrial Fibrillation Guided by Computed Tomography-Based 3D Printing Technology.

Radiofrequency ablation (RFA) is the treatment of choice for atrial fibrillation (AF). Additionally, the utilization of 3D printing for cardiac models offers an in-depth insight into cardiac anatomy and cardiovascular diseases. The study aims to evaluate the clinical utility and outcomes of RFA following in vitro visualization of the left atrium (LA) and pulmonary vein (PV) structures via 3D printing (3DP). Between November 2017 and April 2021, patients who underwent RFA at the First Affiliated Hospital of Xinxiang Medical University were consecutively enrolled and randomly allocated into two groups: the 3DP group and the control group, in a 1:1 ratio. Computed tomography angiography (CTA) was employed to capture the morphology and diameter of the LA and PV, which facilitated the construction of a 3D entity model. Additionally, surgical procedures were simulated using the 3D model. Parameters such as the duration of the procedure, complications, and rates of RFA recurrence were meticulously documented. Statistical analysis was performed using the t-test or Mann-Whitney U test to evaluate the differences between the groups, with a P-value of less than 0.05 considered statistically significant. In this study, a total of 122 patients were included, with 53 allocated to the 3DP group and 69 to the control group. The analysis of the morphological measurements of the LA and PV taken from the workstation or direct entity measurement showed no significant difference between the two groups (P > 0.05). However, patients in the 3DP group experienced significantly shorter RFA times (97.03 ± 28.39 compared to 120.51 ± 44.76 min, t = 3.05, P = 0.003), reduced duration of radiation exposure (2.55 [interquartile range 2.01, 3.24] versus 3.20 [2.28, 3.91] min, Z = 3.23, P < 0.001), and shorter modeling times (7.68 ± 1.03 compared to 8.89 ± 1.45 min, t = 5.38, P < 0.001). 3DP technology has the potential to enhance standard RFA practices by reducing the time required for intraoperative interventions and exposure to radiation.

Plasmonic Titanium Nitride Facilitates Indium Oxide CO2 Photocatalysis.

Nanoscale titanium nitride TiN is a metallic material that can effectively harvest sunlight over a broad spectral range and produce high local temperatures via the photothermal effect. Nanoscale indium oxide-hydroxide, In2 O3- x (OH)y , is a semiconducting material capable of photocatalyzing the hydrogenation of gaseous CO2 ; however, its wide electronic bandgap limits its absorption of photons to the ultraviolet region of the solar spectrum. Herein, the benefits of both nanomaterials in a ternary heterostructure: TiN@TiO2 @In2 O3- x (OH)y are combined. This heterostructured material synergistically couples the metallic TiN and semiconducting In2 O3- x (OH)y phases via an interfacial semiconducting TiO2 layer, allowing it to drive the light-assisted reverse water gas shift reaction at a conversion rate greatly surpassing that of its individual components or any binary combinations thereof.

15-hydroxy-6α,12-epoxy-7ß,10αH,11ßH-spiroax-4-ene-12-one exerts anti-tumor effects against osteosarcoma through apoptosis induction.

Osteosarcoma is the most common type of malignant bone tumor, which has an overall survival rate of only 15-30%. The present study aimed to investigate the effects of 15-hydroxy-6α,12-epoxy-7ß,10αH,11ßH-spiroax-4-ene-12-one (HESEO), a compound extracted from the endophytic fungus Penicillium sp. FJ-1 isolated from Avicennia marina, on the proliferation of osteosarcoma cells and to explore its underlying mechanisms of action. Cell number was counted to measure the cell proliferation. JC-1 reagent was used to measure mitochondrial membrane potential. ELISA was used to measure the cytochrome c level and caspase activities. Apoptosis was detected by Annexin V-Propidium Iodide staining. Gene and protein expression were measured by reverse-transcription-PCR and western blot analysis, respectively. Additionally, the anti-tumor effects of HESEO were explored within a syngeneic osteosarcoma tumor model. The results suggested that HESEO significantly inhibited the proliferation of osteosarcoma cells and induced apoptosis of MG-63 cells, evidenced by their decreased mitochondrial membrane potential, and increased cytochrome c release, caspase activities and percentage of apoptotic cells. In addition, HESEO increased the expression of pro-apoptotic genes and proteins compared with control cells. The results indicated that HESEO may act through increasing p53 upregulated modulator of apoptosis expression. Furthermore, HESEO treatment significantly increased the survival time and decreased the tumor burden of osteosarcoma tumor-bearing mice compared with vehicle treatment. Furthermore, combined treatment with HESEO enhanced the effects of the chemotherapeutic agent methotrexate on a lung metastasis osteosarcoma model. These data suggested that HESEO could be developed as a potential anti-tumor agent against osteosarcoma.

Dual-modality imaging of endothelial progenitor cells transplanted after ischaemic photothrombotic stroke.

AIMS: Stroke is a refractory cerebral blood circulation disorder. Endothelial progenitor cells (EPCs) participate in the repair and regeneration of vascular injury through the combination of cell replacement and bystander effects. Here, we evaluated the biological function of EPCs in treating a mouse model of cerebral ischaemic stroke, using dual-mode bioluminescence and magnetic resonance imaging to trace EPCs in vivo. MAIN METHODS: We constructed a viral vector with a luciferase-enhanced green fluorescent protein (Luc-eGFP) reporter gene for bioluminescence imaging (BLI) detection, and simultaneously synthesized the magnetic resonance imaging (MRI) contrast agent, nano-sized superparamagnetic iron oxide (USPIO), to co-label human umbilical cord blood-derived EPCs (hEPCs). The labelled hEPCs were transplanted into mice with stroke, and the biological behaviours of the cells in-vivo were studied using BLI and MRI, and methods of molecular biology and histology. KEY FINDINGS: Comparing the two cell transplantation routes by BLI confirmed that many cells transplanted via the left ventricular route homed to ischaemic brain tissue. The dual-modality-imaging showed the prognosis of in-vivo tracking cells after transplantation in ischaemic tissues at different time points. Histological staining and neurological function scores confirmed that EPC transplantation can improve the symptoms of nerve deficit in the mouse stroke model. Histological staining revealed that cell transplantation can lead to recovery of neurological function after stroke, via various processes. These include reduced blood brain barrier permeability, recovery of white matter and of myelin, and the enhancement of neuroneogenesis. SIGNIFICANCE: Dual-modality imaging revealed EPCs as potential candidates for the treatment of ischaemic stroke.

Atorvastatin Blocks Advanced Glycation End Products Induced Reduction in Macrophage Cholesterol Efflux Mediated With ATP-Binding Cassette Transporters G 1.

BACKGROUND: There is accumulating evidence that the AGEs-RAGE interaction plays an important role in accelerated atherosclerosis in diabetes. Our previous study showed that the AGEs-RAGE axis can reduce the cholesterol efflux of THP-1 macrophages through suppression of the expression of ABCG1 and that statins can inhibit the expression of RAGE. However, the role of statins in recovering the cholesterol efflux of macrophages reduced by AGEs has not been assessed.Methods and Results:ApoE-/-mice and THP-1 macrophages were both treated by AGEs or AGEs combined with anti-RAGE antibody (only in THP-1 cells), ALT711 and atorvastatin separately. Cholesterol efflux of THP-1 macrophages and murine peritoneal macrophages was tested by fluorescence microplate technique. RT-PCR and western blot analysis were used to measure the expression of RAGE and molecules included in cholesterol efflux. After co-incubating with atorvastatin and AGEs, reduction in lipid accumulation in THP-1 macrophages and improvement of lesions complexity occurred compared with treating by AGEs only. Atorvastatin increased cholesterol efflux and ABCG1 expression of macrophages, which were reduced by AGEs, and decreased the expression of RAGE at the same time. CONCLUSIONS: This study demonstrated that atorvastatin can recover the deleterious ABCG1-mediated cholesterol efflux induced by AGEs in THP-1 macrophages and murine peritoneal macrophages by downregulating RAGE expression. It may contribute to the protective action of atorvastatin in diabetic subjects with atherosclerosis.

Nomogram and Artificial Neural Network for Prognostic Performance on the Albumin-Bilirubin Grade for Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

PURPOSE: To construct the albumin-bilirubin (ALBI) grade and the Child-Turcotte-Pugh (CTP) score based on nomograms, as well as to develop an artificial neural network (ANN) to compare the prognostic performance of the 2 scores for hepatocellular carcinoma (HCC) that has undergone transarterial chemoembolization. MATERIALS AND METHODS: This multicentric retrospective study included patients with HCC who underwent transarterial chemoembolization monotherapy as an initial treatment at 4 institutions between January 2008 and December 2016. In the training cohort, significant risk factors associated with overall survival (OS) were identified by univariate and multivariate analyses. The prognostic nomograms and ANN were established and then validated in 2 validation cohorts. RESULTS: A total of 838 patients (548, 115, and 175 in the training cohort and validation cohorts 1 and 2, respectively) were included. The median OS was 10.4, 15.7, and 9.2 months in the training cohort and validation cohorts 1 and 2, respectively. In the training cohort, both ALBI grade and CTP score were identified as significant risk factors. The ALBI grade and CTP score based on nomograms were established separately and showed similar prognostic performance when assessed externally in validation cohorts (C-index in validation cohort 1: 0.823 vs 0.802, P = .417; in validation cohort 2: 0.716 vs 0.729, P = .793). ANN showed that ALBI grade had higher importance on survival prediction than CTP score. CONCLUSIONS: ALBI grade performs at least no worse than CTP score regarding survival prediction for HCC receiving transarterial chemoembolization. Considering the easy application, ALBI grade has the potential to be regarded as an alternative to CTP score.

HIF-prolyl hydroxylase 2 silencing using siRNA delivered by MRI-visible nanoparticles improves therapy efficacy of transplanted EPCs for ischemic stroke.

Endothelial progenitor cell (EPC)-based therapy has brought potential benefits to stroke patients as an important restorative therapeutics. However, its efficacy is limited by poor migration and survival ability. Here, we found out that hif-prolyl hydroxylase 2 (PHD2) silencing could enhance the migration and survival ability of EPCs which could improve the therapy efficacy for ischemic stroke. We successfully developed a siRNA delivery system, which could achieve siRNA delivery and EPCs tracking with magnetic resonance imaging (MRI) simultaneously. Besides, combining MRI and bioluminescence imaging (BLI), we successfully observed full temporal profile of EPCs dynamics in vivo. Furthermore, we found out that PHD2 silencing in EPCs elevated the expression of C-X-C chemokine receptor type 4 (CXCR4) and hypoxia-inducible factor 1α (HIF-1α), which enhanced the migration and survival ability of EPCs respectively. Significantly decreased infarct volume, functional deficits and increased fractional anisotrophy (FA) value, fiber counts were observed in the siPHD2-EPCs (EPCs transfected with siRNA targeting PHD2) group. What's more, higher level of BNDF, CD31, DCX, NeuN and MBP were also observed in the siPHD2-EPCs group. Altogether, our study provides an effective method to improve EPC-based therapy efficacy for ischemic stroke.

Multicentric Assessment of the Hong Kong Liver Cancer Staging System in Chinese Patients Following Transarterial Chemoembolization.

PURPOSE: We aimed to validate the performance of the hepatitis B-based Hong Kong Liver Cancer (HKLC) staging system compared with the Barcelona Clinic Liver Cancer (BCLC) staging system in Chinese hepatocellular carcinoma (HCC) patients treated with conventional transarterial chemoembolization (TACE) as the initial treatment. MATERIALS AND METHODS: The study was approved by the Institutional Review Boards at all participating centers. This retrospective study included 715 patients with HCC who underwent TACE as the initial treatment between January 2008 and December 2016 at three Chinese institutions. All of the patients calculated HCC stage using 5-substage HKLC (HKLC-5), 9-substage HKLC (HKLC-9), and the BCLC system. Based on overall survival (OS), these three staging systems' performance on treatment outcome prediction were compared using C statistic, Akaike information criterion (AIC), area under the receiver operating characteristic curve (AUC), linear trend Chi-square, likelihood ratio Chi-square, and calibration plots, respectively. RESULTS: The median OS was 10.1 months. Compared with the BCLC system, the HKLC system, especially HKLC-9, showed better performance on survival prediction (HKLC-9: C = 0.689, AIC = 6646.162; HKLC-5: C = 0.683, AIC = 6662.663; BCLC: C = 0.680, AIC = 6654.146), homogeneity (likelihood ratio Chi-square: HKLC-9 = 232.38, HKLC-5 = 215.87, and BCLC = 224.39, P < 0.001), and calibration (R2: HKLC-9 = 0.923, HKLC-5 = 0.916, and BCLC = 0.914). HKLC-9 outperformed on AUC at 6-, 12-, and 24-month survival prediction than HKLC-5 and BCLC. BCLC showed better performance on monotonicity (linear trend Chi-square: HKLC-9 = 121.641, HKLC-5 = 117.389, and BCLC = 125.752; P < 0.001). CONCLUSIONS: Combining survival prediction, discrimination, and calibration, the HKLC, especially HKLC-9 system, performed better for Chinese patients treated with TACE than the BCLC system.

Targeting Early Apoptosis in Acute Ischemic Stroke with a Small-Molecule Probe.

Inhibiting apoptotic cells helps ameliorate ischemic injury. Actually, only the apoptotic cells in early stage could be rescued. Molecular imaging of the early apoptosis would make sense in ischemic stroke; however, few of apoptosis molecular probes could specifically target early apoptosis. This study developed a small-molecule early apoptosis targeting probe CYS-F, which was synthesized by cystine with fluorescein isothiocyanate dyes. And the final molecular weight of CYS-F was only 1013 Da, which was much smaller than the traditional apoptosis marker annexin V. CYS-F showed excellent early apoptosis targeting ability both in vitro and in vivo. And CYS-F was cleared rapidly from the circulation with a blood half-life of 1.325 h. A favorable match was obtained between the images in fluorescence imaging and magnetic resonance imaging in stroke models. The target-to-background ratio of the lesions on 0 h was negative, which reflected the decreased blood flow. Multimodal molecular imaging showed the therapeutic effect of cystamine was dose dependence and CYS-F could also predict the outcome of ischemic stroke at an early stage. The versatility of CYS-F provides a comprehensive and convenient route for clinical decision-making in acute ischemic stroke.

Advanced glycation end products increase lipids accumulation in macrophages through upregulation of receptor of advanced glycation end products: increasing uptake, esterification and decreasing efflux of cholesterol.

BACKGROUND: Previous reports have suggested that advanced glycation end products (AGEs) participate in the pathogenesis of diabetic macroangiopathy. Our previous study have found that AGEs can increase the lipid droplets accumulation in aortas of diabetic rats, but the current understanding of the mechanisms remains incomplete by which AGEs affect lipids accumulation in macrophages and accelerate atherosclerosis. In this study, we investigated the role of AGEs on lipids accumulation in macrophages and the possible molecular mechanisms including cholesterol influx, esterification and efflux of macrophages. METHODS: THP-1 cells were incubated with PMA to differentiate to be macrophages which were treated with AGEs in the concentration of 300 µg/ml and 600 µg/ml with or without anti-RAGE (receptor for AGEs) antibody and then stimulated by oxidized-LDL (oxLDL) or Dil-oxLDL. Lipids accumulation was examined by oil red staining. The cholesterol uptake, esterification and efflux were detected respectively by fluorescence microscope, enzymatic assay kit and fluorescence microplate. Quantitative RT-PCR and Western blot were used to measure expression of the moleculars involved in cholesterol uptake, synthesis/esterification and efflux. RESULTS: AGEs increased lipids accumulation in macrophages in a concentration-dependent manner. 600 µg/ml AGEs obviously upregulated oxLDL uptake, increased levels of cholesterol ester in macrophages, and decreased the HDL-mediated cholesterol efflux by regulating the main molecular expression including CD36, Scavenger receptors (SR) A2, HMG-CoA reductase (HMGCR), ACAT1 and ATP-binding cassette transporter G1 (ABCG1). The changes above were inversed when the cells were pretreated with anti-RAGE antibody. CONCLUSIONS: The current study suggest that AGEs can increase lipids accumulation in macrophages by regulating cholesterol uptake, esterification and efflux mainly through binding with RAGE, which provide a deep understanding of mechanisms how AGEs accelerating diabetic atherogenesis.

Bioluminescence imaging of transplanted human endothelial colony-forming cells in an ischemic mouse model.

Ischemic strokes are devastating events responsible for high mortality and morbidity worldwide each year. Endothelial colony-forming cell (ECFC) therapy holds promise for stroke treatment; however, grafted ECFCs need to be monitored better understand their biological behavior in vivo, so as to evaluate their safety and successful delivery. The objectives of this study are to visualize the fate of infused human cord blood derived ECFCs via bioluminescence imaging (BLI) in an ischemic stroke mouse model and to determine the therapeutic effects of ECFC transplantation. ECFCs derived from human umbilical cord blood were infected with lentivirus carrying enhanced green fluorescent protein (eGFP) and firefly luciferase (Luc2) double fusion reporter gene. Labeled ECFCs were grafted into a photothrombotic ischemic stroke mouse model via intra-arterial injection though the left cardiac ventricle. The homing of infused cells and functional recovery of stroke mice were evaluated using BLI, neurological scoring, and immunohistochemistry. Significantly, BLI signals were highest in the brain on day 1 and decreased steadily until day 14. GFP-positive cells were also found surrounding infarct border zones in brain sections using immunohistochemical staining, suggesting that ECFCs properly homed to the ischemic brain tissue. Using a modified neurological severity score assay and histological analysis of brain slices with CD31 immunostaining in brain tissue, double cortin analysis, and the TdT-mediated dUTP nick end labeling (TUNEL) assay, we demonstrated functional restoration, improved angiogenesis, neurogenesis, and decreased apoptosis in ischemic mice after ECFC infusion. Collectively, our data support that ECFCs may be a promising therapeutic agent for stroke.

Precise Characterization of the Penumbra Revealed by MRI: A Modified Photothrombotic Stroke Model Study.

AIMS: To precisely characterize the penumbra by MRI based on a modified photothrombotic stroke mouse model. METHODS: The proximal middle cerebral artery was occluded by a convenient laser system in conjunction with an intravenous injection of Rose Bengal in mice. And the suture MCAO model was performed in seven mice as a comparison of the reproducibility. One hour after occlusion, the penumbra was defined in six random photothrombotic stroke mice by mismatch between perfusion-weighted imaging and the apparent diffusion coefficient map on a home-made workstation. After imaging, three random mice of them were chosen to perform the reperfusion surgery. And the other three mice were sacrificed to stain for several potential penumbra markers, such as c-fos and heart shock protein 90. In the remaining mice, the evolution of the lesions was detected on the apparent diffusion coefficient map, diffusion-weighted imaging and T2-weighted imaging at 1, 3, 6, 12 and 24 hours. After evaluating the neurological deficit scores, the brains were sectioned and stained by triphenyltetrazolium chloride and Nissl. RESULTS: The mice subjected to photothrombosis showed significant behavioral deficits. One hour after occlusion, the low perfusion areas on the perfusion-weighted imaging interlaced with the hypointense areas on the apparent diffusion coefficient map, demonstrating that the penumbra was located both surrounding and inside the lesions. This phenomenon was subsequently confirmed by the c-fos and heart shock protein 90 staining. The final T2-weighted images of the mice subjected to the reperfusion surgery were also consistent with the penumbra images at one hour. At early stages, the lesions were clearly identified on the apparent diffusion coefficient map; the volumes of the lesions on the diffusion-weighted imaging and T2-weighted imaging did not reach a maximum until 12 hours. The coefficient of variation (CV) of the final lesions in the photothrombotic stroke mice was 21.7% (0.08 of 0.37) on T2-weighted imaging and 27.8% (0.10 of 0.35) on triphenyltetrazolium chloride, representing a high reproducibility (n = 7). While the CV of the lesions in the MCAO stroke mice was only 70% (0.24 of 0.34, n = 4). CONCLUSIONS: This study has provided a precise imaging definition of the penumbra based on a reproducible photothrombotic stroke mouse model.

Dual-reporter Imaging and its Potential Application in Tracking Studies.

By tracking reporter molecules such as green fluorescent protein and luciferase, researchers can determine physiological status and follow processes both in vitro and in vivo.Here, we describe a dual-reporter imaging method, in which a fusion of eGFP and Luc2 is introduced into hosts using lentiviral particles based on HIV-1. The fusion molecule is both fluorescent and bioluminescent, and is therefore ideal as an optical marker in clinical and research applications.We characterized multiple technical indices of the molecule,including sensibility, biocompatibility, lifetime, and others.Lentiviral particles carrying the reporter were strongly infective in endothelial progenitor (EPC) and GL261 glioma cells,as well as in live mice. By transforming Luc2-eGFP into hosts, morphological and quantitative data can be collected not only from tissue specimens but also from live animal models.

Bone Marrow Endothelial Progenitor Cell Transplantation After Ischemic Stroke: An Investigation Into Its Possible Mechanism.

AIMS: We tested the hypothesis that endothelial progenitor cell (EPC)-mediated functional recovery after stroke may be associated with the endothelial nitric oxide synthase (eNOS)/brain-derived neurotrophic factor (BDNF) signaling pathway. METHODS: Mice were infused with either EPCs or saline after being subjected to middle cerebral artery occlusion. The EPC-treated mice also received intravenous injections of either Nω-nitro-l-arginine methyl ester (L-NAME, the NOS inhibitor) or saline. RESULTS: The activation of eNOS and the expression of BDNF were significantly increased in ischemic brain of the EPC-treated mice, along with increased angiogenesis and neurogenesis. On diffusion tensor imaging (DTI), significant increases in fractional anisotropy and fiber count were observed in white matter, indicating axonal growth stimulated by EPCs. However, the EPC-treated mice that were received an L-NAME injection failed to exhibit the observed increases in angiogenesis, neurogenesis, and axonal growth. In addition, the neurons cocultured with EPCs in vitro exhibited the increased expression of BDNF and decreased apoptosis after oxygen-glucose deprivation compared with the control group. This EPC-induced protective effect was virtually absent in the L-NAME treatment group. CONCLUSION: The eNOS/BDNF pathway may be involved in the EPC-mediated functional recovery of stroke mice. DTI is feasible for dynamically tracking the orientation of axonal projections after EPC treatment.

Cystamine improves functional recovery via axon remodeling and neuroprotection after stroke in mice.

AIMS: Stroke is a leading cause of disability. However, there is no pharmacological therapy available for promoting recovery. Although treatment of stroke with cystamine has gained increasing interest, the detailed mechanisms underlying this process remain elusive. Thus, our aim is to examine the effect of cystamine on the function recovery after stroke and investigate further cystamine mechanisms. METHODS: Adult male C57BL/6J mice were subjected to photothrombotic model of focal stroke or sham operation. Cystamine or saline was administered intraperitoneally at 24 h after stroke. Functional recovery was analyzed using behavioral tests; axon remodeling was analyzed using magnetic resonance diffusion tensor imaging (DTI) and histological assessment. ANA-12, an antagonist of tropomyosin-related kinase B (TrkB), was administrated to examine the mechanisms underlying the neuroprotection mediated by cystamine. RESULTS: Treatment with cystamine resulted in amelioration of impaired function with concomitant enhancement of axonal remodeling. Cystamine treatment significantly increased brain-derived neurotrophic factor (BDNF) levels and phosphorylation of TrkB in brain after stroke. Cystamine significantly enhanced neuronal progenitor cell proliferation, neuronal survival, and plasticity through BDNF/TrkB pathway. CONCLUSIONS: These data provide evidence to investigate the promising utility of cystamine for therapy of stroke in a variety of ways, acting principally through BDNF/TrkB pathway.

Classification of cirrhotic patients with or without minimal hepatic encephalopathy and healthy subjects using resting-state attention-related network analysis.

BACKGROUND: Attention deficit is an early and key characteristic of minimal hepatic encephalopathy (MHE) and has been used as indicator for MHE detection. The aim of this study is to classify the cirrhotic patients with or without MHE (NMHE) and healthy controls (HC) using the resting-state attention-related brain network analysis. METHODS AND FINDINGS: Resting-state fMRI was administrated to 20 MHE patients, 21 NMHE patients, and 17 HCs. Three attention-related networks, including dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN), were obtained by independent component analysis. One-way analysis of covariance was performed to determine the regions of interest (ROIs) showing significant functional connectivity (FC) change. With FC strength of ROIs as indicators, Linear Discriminant Analysis (LDA) was conducted to differentiate MHE from HC or NMHE. Across three groups, significant FC differences were found within DAN (left superior/inferior parietal lobule and right inferior parietal lobule), VAN (right superior parietal lobule), and DMN (bilateral posterior cingulate gyrus and precuneus, and left inferior parietal lobule). With FC strength of ROIs from three networks as indicators, LDA yielded 94.6% classification accuracy between MHE and HC (100% sensitivity and 88.2% specificity) and 85.4% classification accuracy between MHE and NMHE (90.0% sensitivity and 81.0% specificity). CONCLUSIONS: Our results suggest that the resting-state attention-related brain network analysis can be useful in classification of subjects with MHE, NMHE, and HC and may provide a new insight into MHE detection.

Abnormal baseline brain activity in low-grade hepatic encephalopathy: a resting-state fMRI study.

Resting-state functional magnetic resonance imaging (fMRI) has been used to detect the alterations of spontaneous neuronal activity in various neuropsychiatric diseases, but rarely in low-grade hepatic encephalopathy (HE), a common neuropsychiatric complication of liver cirrhosis. We conducted a resting-state fMRI in 19 healthy controls, 18 cirrhotic patients without HE, and 22 cirrhotic patients with low-grade HE. The amplitude of low-frequency fluctuations (ALFF) of fMRI signal was computed to measure the spontaneous neuronal activity. Several regions showing significant ALFF differences among three groups were the precuneus, occipital lobe, left frontal lobe and anterior/middle cingulate cortex, and left cerebellum posterior lobe. Compared to controls or patients without HE, patients with low-grade HE showed decreased ALFF in the precuneus and adjacent cuneus, visual cortex, and left cerebellum posterior lobe. Compared to controls, patients with low-grade HE showed higher ALFF in both cortical and subcortical regions, including the right middle cingulate gyrus, and left anterior/middle cingulate gyrus, inferior frontal gyrus, insula lobe, parahippocampal gyrus, middle temporal gyrus and lentiform nucleus; compared to patients without HE, patients with low-grade HE showed higher ALFF in the left medial frontal gyrus and anterior cingulate gyrus, bilateral superior frontal gyrus, and right middle frontal gyrus. Moreover, correlations between ALFF changes and poor neurocognitive performances were found in patients with low-grade HE. These results suggested the existence of aberrant brain activity at the baseline state in low-grade HE, which may be implicated in the neurological pathophysiology underlying HE.

[Modeling of acute thromboembolic stroke in mice].

OBJECTIVE: To evaluate the controllability and reproducibility of a acute thromboembolic cerebral ischemia model for studying molecular imaging and thrombolysis in mice by 7.0 Tesla magnetic resonance imaging (MRI). METHODS: Twenty-four male C57BL/6J mice were randomly divided into embolic group (n = 14) and sham-operated group (n = 10). To prepare rich fibrin and optimal length of clots and measure diameters of clots under microscope, the clots were injected into internal carotid artery via a microcatheter inserted from external carotid artery to bifurcation of common carotid artery in embolic group. In sham-operated group, phosphate-buffered saline containing bovine serum albumin was injected similarly. At 1, 3 or 24 h after injection of clots or phosphate-buffered saline containing bovine serum albumin, mice underwent 7.0 Tesla magnetic resonance imaging including sequences of magnetic resonance angiography (MRA), diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI) by arterial spin labeling technology (ASL) and T(2) weighted imaging (T(2)WI) so as to evaluate the occlusive rate of middle cerebral artery (MCA) and the change of relative cerebral blood flow (rCBF) and lesion volumes. Triphenyl tetrazolium chloride (TTC) stain was performed at 24 h. RESULTS: The diameters of clots were 162 ± 14 µm. In embolic group at 1, 3 or 24 h after injection of clots, the occlusive rate of MCA was 78.6%, 71.4% and 57.1% respectively. And the values of rCBF decrease in mice showing occlusion of MCA in MRA images. The percents of rCBF value in embolic group were 26% ± 10% at 1 h and 26% ± 15% at 3 h respectively. They were significantly lower than the percents of rCBF value in sham-operated group at the same time points. The percents of infarct volumes at 24 h were 30% ± 4% from T(2)WI images and 30% ± 16% from TTC images. In sham-operated groups, both MRI and TTC images were negative. CONCLUSION: A murine model of acute thromboembolic cerebral ischemia has been successfully established. The improved method is both stable and feasible. It may be readily evaluated from multi-parameter imaging by 7.0 Tesla magnetic resonance imaging.