[Ameliorative Effects of Cang-ai Volatile Oil on Left Ventricular Remodeling in Rats].

Objective: To evaluate with 7T cardiac magnetic resonance tissue tracking imaging (CMR-TT) the ameliorative effect of Cang-ai volatile oil (CAVO) on left ventricular remodeling (LVR) in rats induced by isoproterenol (ISO), and to make preliminary investigation into CAVO's effects on endothelial dysfunction in LVR. Methods: A total of 35 healthy male Sprague-Dawley (SD) rats were randomly assigned to two groups, the experimental group ( n=27) and the normal control group ( n=8). The rat model of LVR was established by subcutaneous injection of ISO solution at 10 mg·kg -1·d -1 at multiple sites for 10 consecutive days. After modeling was completed, the surviving rats ( n=24) in the experimental group were then randomly assigned to the blank experimental group, CAVO group, and Shexiang Baoxin pill (SXBXP) group ( n=8 in each group). Rats in each group were given via gavage the corresponding intervention medicine or an equivalent amount of normal saline solution for 28 consecutive days. At the end of modeling and intragastric intervention, 7T CMR cine sequence scanning was conducted to collect data. Then, post-processing software CVI42 was used to analyze the images and to compare and contrast the changes in the parameters of left ventricular cardiac function and myocardial strain in each group before and after the administration of the medication. The rats were sacrificed after MRI scanning, and their hearts were harvested for pathological examination. The levels of serum biochemical indicators were measured by enzyme-linked immunosorbent assay (ELISA). Results: CAVO significantly increased LV ejection fraction and overall myocardial strain parameters in LVR rats, while it decreased LV volume, mass, and serum levels of endothelial function indicators in LVR rats. In addition, pathological staining showed marked improvements in the hypertrophy, necrosis and interstitial fibrosis of cardiomyocytes. Conclusion: Through the regulation of myocardial vascular endothelial function, CAVO can significantly improve cardiac functions in LVR rats, delay the process of ventricular remodeling, and have a certain amount of protective effect on cardiac structure and function in rats.

Right and left ventricular interactions, strain, and remodeling in repaired pulmonary stenosis patients with preserved right ventricular ejection fraction: A cardiac magnetic resonance study.

BACKGROUND: Right ventricular dilation and dysfunction is a common long-term complication in patients with repaired pulmonary stenosis (rPS). Additionally, abnormal right and left ventricular interactions have been reported in right-sided heart defect after intervention, including in pulmonary stenosis. PURPOSE: To analyze ventricular strain, remodeling, and left and right ventricular interactions in rPS patients with preserved right ventricular ejection fraction (RVEF) compared with healthy children using cardiac magnetic resonance. STUDY TYPE: A cross-sectional study. POPULATION: In all, 34 rPS patients and 10 healthy children volunteers (controls). FIELD STRENGTH/SEQUENCE: 3.0T/2D balanced steady-state free precession (2D b-SSFP) cine, late gadolinium enhancement (LGE), and 2D phase contrast (2D-PC). ASSESSMENT: Pulmonary regurgitation (PR) fractions of the main pulmonary artery, biventricular volumes, masses, function, and cardiac strain. STATISTICAL TESTS: Mann-Whitney U-test, t-test, Pearson correlation coefficients, Spearman's correlation coefficients, and intraclass correlation coefficients analysis were performed. RESULTS: For group analysis, the right ventricular (RV) global circumferential strain and radial strain were significantly increased in patients when compared with controls (-13.57 ± 2.69 vs. -5.91 ± 3.16, P < 0.001; 25.31 ± 8.12 vs. 9.87 ± 5.32, P < 0.001, respectively). The fraction of PR displayed moderate correlation with right ventricular end-diastolic volume index (RVEDVi) (r = 0.452, P = 0.022). RVEDVi and mass index were larger in patients vs. control (104.92 ± 27.46 vs. 85.15 ± 11.98, P = 0.016; 18.28 ± 4.95g/m2 vs. 11.67 ± 2.14 g/m2 , P < 0.001, respectively). Patients presented with preserved left ventricular ejection function, but was lower than healthy controls (60.89% ± 4.89% vs. 65.95% ± 4.56%, P = 0.006). Regional circumferential strain of segment 3 of left ventricle (LV) were significantly decreased in patients (-7.79 ± 6.52 vs. -13.56 ± 3.22, P = 0.003). DATA CONCLUSION: Compensated increased RV strain, myocardial remodeling of RV, and adverse right and left ventricular interactions occur in rPS patients with preserved RVEF. The decreased interventricular septum strain may lead to impaired LV function due to RV dilation as a result of PR. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;52:129-138.

[Basic Research on Neuroprotective Effect of Volatile Oil of Cang Ai after Cerebral Ischemia-Reperfusion Injury Based on Diffusion Tensor Imaging].

OBJECTIVE: To study the neuroprotective effect of inhalation of volatile oil of Cang Ai (VOCA) on cerebral ischemia-reperfusion injury model by MRI diffusion tensor imaging. METHODS: Twenty-four healthy adult male SD rats were randomly divided into sham operation group, model (middle cerebral artery occlusion (MCAO) ) group and VOCA group. Evaluated the degree of neurological impairment of rats in each group immediately after successful establishment of model or 7 d later according to Zea Longa scoring. Coronal diffusion tensor imaging (DTI) scan was performed at 3 h, 3 d, and 7 d after the model successfully established by using 7.0 T magnetic resonance imaging. Measured the apparent diffusion coefficient (ADC) and anisotropy score (FA) of the DTI in the striatal region and the motion flat zone of the maximum infarct level and then calculate the relative apparent diffusion coefficient (rADC) and relative anisotropy score (rFA). TTC staining was used to evaluate the cerebral infarction volume of rats in each group at 7 d post model establishment, and the correlation analysis of rFA, rADC and neural score was performed. RESULTS: No neurological defect was detected in mice in the sham operation group. The MCAO group and the VOCA group showed neurological defect to different degrees. The neurological function score of the VOCA group was obviously lower than that of MCAO group at 7 th day (P<0.05). The DTI scan results showed that the rADC value of striatum of rats in VOCA group was higher than that in MCAO group at 3 h and 3 d after modeling (P<0.05), while there was no significant difference between the three groups at 7 th day. The rADC value of the motor cortex in the VOCA group was higher than that in the MCAO group at 3 h after modeling (P<0.01), and there was no significant difference at 3 rdday and 7 thday. The rFA value of striatum in VOCA group was higher than that in MCAO group at 3 rd day and 7 th day after modeling (P<0.05). There were no significant differences in rFA value between the MCAO and the VOCA group at three time points. TTC staining results showed that there was no infarcted area in the sham operation group, and the infarct volume in the VOCA group was smaller than that of the MCAO group (P<0.05). Correlation analysis showed that the striatum rFA value was highly correlated with neurological scores (r=－0.847, P<0.01). CONCLUSION: For the first time, we found that VOCA can effectively protect the neurological function of MCAO rats by reducing the toxic edema of cells in the ischemic area and accelerating the recovery of nerve fiber bundles after cerebral ischemia and reperfusion. rFA and rADC values can be used as effective indicators to evaluate the recovery of nerve function after cerebral ischemia and reperfusion.

[Cardiac Magnetic Resonance in Cardiovascular Disease Research and Its Clinical Application: an Update].

Cardiac magnetic resonance (CMR) is a non-invasive imaging technology, which has been used widely in clinical and basic researches on cardiovascular disease in recent years. With the innovation and optimization of CMR technologies, significant progress has been developed in the evaluation of myocardial viability, the function of regions and global myocardium, and the myocardial texture characteristics. Therefore, with the discussion on the progress of CMR to draw more and more attention in clinics, we hope to improve the application of CMR not only in the basic research but also in the diagnosis and precise evaluation aspects of cardiovascular disease.

[Cardiac Magnetic Resonance Imaging Study of Ventricular Myocardial Deformation in Spontaneous T2DM Rhesus Monkey].

OBJECTIVE: To assess biventricular, especially right ventricular, function and deformationin rhesus monkeys with spontaneous type 2 diabetes mellitus (T2DM) using cardiac magnetic resonance (CMR). METHODS: Twelve male spontaneous T2DM rhesus monkeys and age, sex, body mass matched 9 healthy rhesus monkeys without hypertension and myocardial infarction were included in this study. Fasting blood glucose (FPG), glycated hemoglobin (HbA1c) and blood liquid levels were measured. Biventricular function and myocardial deformations were evaluated by CMR cine and tissue-tracking. RESULTS: Compared with control, the FPG and HbA1c levers were significantly increased in T2DM group, but there was no significant difference in body mass and age between the two groups. CMR result showed that there was no significant decrease in right ventricle and left ventricle ejection fraction in T2DM (P < 0.05). However, the absolute value of radial and circumferential global peak systolic strain, systolic strain rate and three directions global peak diastolic strain rate of the right ventricle free wall were lower in the T2DM group (P < 0.05). Also, only radial and circumferential peak systolic strain and radial diastolic strain rate of left ventricle were higher (P < 0.05). CONCLUSIONS: Right ventricle showed systolic and diastolic dysfunction which were consistent with left ventricle in T2DM by CMR-tissue tracking.

[Magnetic Resonance Imaging Tissue Feature Tracking for Cardiac Amyloidosis].

OBJECTIVE: To detect cardiac amyloidosis (CA) using cardiac magnetic resonance feature tracking(CMR-FT). METHODS: Forty-three CA patients and 24 healthy volunteers underwent steady-state free precession cine sequence on 3.0T MRI after injection of Magnevist. Software cvi 42 was used for analyzing the left ventricular function including left ventricular mass (diastole) (LVMD), left ventricular mass (systole) (LVMS), left ventricle end-diastolic volume (LVEDV), left ventricle end-systolic volume (LVESV), left ventricle stroke volume (LVSV), and left ventricular ejection fraction (LVEF), as well as myocardial strains including 3D global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS), and 2D endocardial and epicardial longitudinal strain, circumferential strain, and radial strain (ENDO-LS, EPI-LS, ENDO-CS, EPI-CS, ENDO-RS, and EPI-RS). The global and layer-specific strains were compared between the CA patients with LVEF >50%, the CA patients with LVEF ≤50%, and the healthy controls. RESULTS: For the left ventricular function, the CA patients had greater myocardial mass than the healthy controls (P < 0.05); the CA patients with LVEF ≤50% had greater LVESV and lower LVSV than those with LVEF >50% (P < 0.05). For the global strains, significant differences also appeared in GLS and GCS among the three groups (all P < 0.05). The CA patients had lower GRS than the healthy controls (P < 0.05), while no significant difference was found in GRS between the CA patients with LVEF >50% and those with LVEF ≤50% (P>0.05). For the layer-specific strains, significant differences in ENDO-LS, EPI-LS, ENDO-CS, EPI-CS, ENDO-RS, and EPI-RS were found among the three groups (all P < 0.05). There were significant correlations between GLS and LVEF (r=-0.404, P=0.016), and between GCS and LVEF (r=-0.602, P < 0.001) in the CA patients. CONCLUSION: CMR-FT can assess not only global strains but also layer-specific strains for the myocardial function of CA patients.

[Diagnostic Values and Reliability of Cardiac Magnetic Resonance Tissue Tracking 2D and 3D Strain Assessments for Experimental Autoimmune Myocarditis in Rats].

OBJECTIVE: To determinethe diagnostic valuesand reliabilityof cardiac magnetic resonance tissue tracking (CMR-TT) derived two-dimensional(2D) and three-dimensional(3D) strains in assessing experimental autoimmunity myocarditis (EAM) in rats. METHODS: 20 Lewis rats were randomly divided into model and control groups. The animal model of autoimmune myocarditis was induced by injecting porcine cardiac myosin into the footpads of the rats.On day 35, all of the rats were examined using the 7.0T CMR cine scan. The cardiac function and global strain of the left ventricular of the rats were analyzed with specific cardiac post-processing. The rats were then sacrificed and myocardial samples were taken and stained with HE and Masson. The diagnostic values of the strain parameters were assessed by receiver operating characteristic (ROC) curves with the pathological results as diagnostic criteria.The reliability of the strain parameters were tested using interclass correlation coefficient (ICC), coefficients of variation (CV) and Bland-Altman. RESULTS: No abnormal pathological changes in myocardial cells were found in the control group. Myocarditis was successfully induced in all of the rats in the model group, showing myocardial fiber arrangement disorder, degeneration, necrosis, inflammatory cell infiltration and interstitial fibrosis. The ROC showed that 2D global strain parameters possessed higher diagnostic values than 3D strain parameters. The 2D had an area under the curve (AUC) of 0.96 in global circumferential strain (GCS), 0.95 in global radial strain (GRS), and 0.90 in global longitudinal strain (GLS), compared with 0.87 GCS, 0.85 GRS, and 0.77 GLS in the 3D, respectively.The reliability of the 2D strain parameters was high, except for inter-observer 2D GRS(ICC=0.893). The 3D strain parameters had lower reliability (ICCs:0.421-0.79) than the 2D strain parameters (ICCs:0.893-0.986). CONCLUSION: The diagnostic values of 2D strain parameters are higher than 3D strain parameters in diagnosing myocarditis.

[Evaluating Cardiac Function of Tree Shrew (Tupaiabelangeri) using CMR at 7T with 2D Tissue Tracking].

OBJECTIVE: To determine the potential value of the two-dimensional (2D) cardiac magnetic resonance imaging (CMR) tissue tracking (CMR-TT) method in assessing the cardiac function of tree shrew at 7T. METHODS: Healthy adult tree shrews (male, n=8) and spraguedawley rats(male, n=8) were selected for this study. CMR was performed to acquire the short-axis images of left ventricle at 7T using the same appropriative coil and cine sequence for all experimental animals. The CMR images were processed using the professional cardiac analysis software, calculating ejection fraction (EF), radial peak sysolic strain (Err), circumferential peak sysolic strain (Ecc), radial peak sysolic displacement (DR), and LVM/BM 〔the ratio of left ventricular mass (LVM) to body mass (BM)〕. RESULTS: Cine imaging for the tree shrews was 100% successful following the CMR protocol for the rats, with clearly visible main segments of cardiac. Significant differences in EF, Err, Ecc and DR were found between the two groups of animals (P < 0.01). The tree shrews has lower EF, Err and Ecc than the rats. Err and Ecc appeared in the fifteenth phase in left ventriclar systole in the tree shrews, compared with the tenth phase in the rats.The tree shrews also had higher LVM/BM than the rats. CONCLUSION: The cardiac function of tree shrew can be assessed using the 2D CMR-TT method despite significant differences across species.

[Tracking Early Reperfused Myocardial Infarction using Cardiac MR].

OBJECTIVE: To determine segmental myocardial changes in cardiovascular magnetic resonance feature-tracking (CMR-FT) in the early phase of reperfused myocardial infarction in patients and rats. METHODS: Ten patients receiving percutaneous coronary interventions (2-10 d) and 10 rats with 60 min induced myocardial ischemia followed by reperfusions (48 h and 7 d) were investigated by MRI. The steady state free precession cine and late gadolinium enhancement (LGE) sequences were measured to evaluate the standard short axis of the whole heart after an injection of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA, Magnevist, Bayer Health Care Pharmaceuticals) at a dose of 0.1 mmol/kg. The infarction sizes (all areas were expressed as a percentage of the whole myocardial tissues of left ventricle (LV), end-diastolic volume (EDV) and ejection fractions (EF) were calculated. The MRI cine images were analyzed using the myocardial feature tracking software CVI, estimating the peak value of radial strains (RS) and circumferential strains (CS) of the 16 AHA segments excluding apex cordis. The complete myocardial infarction (CMI) segments, partial myocardial infarction (PMI) segments and non-myocardial infarction (NMI) segments were identified and compared. RESULTS: Patients: The radial strain and circumferential strain of the CMI and PMI segments were smaller than the NMI segment (both P < 0.01). However, there was no significant difference between the CMI and the PMI segment (P>0.05). Rats: No significance differences were found in EF and EDV between the two time period 48 h and 7 d (both P>0.05). The radial strain and circumferential strain of the CMI and PMI segments were smaller than the NMI segment (all P < 0.01). But there was no significance difference between the CMI segment and the PMI segment (P>0.05). No significant changes in the global radial strain and the circumferential strain were found over time (both P>0.05). But the segmental radial strain and circumferential strain became larger over time (all P < 0.05). CONCLUSIONS: The systolic ability of myocardium decreases as a result of reperfusion injury in the early phase of reperfused myocardial infarction. But it can gradually recover over time with reperfusion.

[Myocardial Magnetic Resonance Texture Characteristics of Healthy Volunteers].

OBJECTIVE: To determine the myocardial texture features of cardiac magnetic resonance (CMR) in healthy adult Han populations. METHODS: 59 healthy Han volunteers were recruited for this study from May 2016 to November 2017. CMR examinations were performed on the participants with a 3.0T scanner (Tim Trio, Siemens Medical Solution) to estimate the functional parameters, Native T1 value and ECV. Texture analysis (TA) was performed on the region of interest (ROI) in the left ventricle myocardium on T1 mapping images, with 40 myocardial texture features being extracted. Differences in the myocardial texture features across gender and age groups were analyzed through Student's t-tests or Wilcoxon signed-rank tests. Spearman correlations were analyzed between the myocardial texture features and age, native T1 value and extracellular volume (ECV). RESULTS: Of the 59 participants, 28 were women and 29 were in the younger age group (< 45 years old). The male participants had higher left ventricular mass index (Lvmassi) and lower native T1 than their female counterparts (P < 0.01). No gender differences in blood pressure, heart rate, left ventricular ejection fraction (LVEF) and ECV values were found. Ten of the forty myocardial texture features showed gender differences, including two first order features and eight Grey-level co-occurrence matrix (GLCM) features. Gender differences appeared in five first order features and eight GLCM features in the younger group (< 45 years old), but not in the older group (≥45 years old). Eight myocardial texture features were correlated with age, including five first order features and three GLCM features (all P < 0.01). Six first-order texture features were correlated with Native T1 values of the left ventricle middle myocardium. Three first-order texture features were correlated with ECV. CONCLUSION: Myocardial texture features in T1 mapping images vary by gender and age in healthy Han populations.

Injection of Aß1-40 into hippocampus induced cognitive lesion associated with neuronal apoptosis and multiple gene expressions in the tree shrew.

Alzheimer's disease (AD) can incur significant health care costs to the patient, their families, and society; furthermore, effective treatments are limited, as the mechanisms of AD are not fully understood. This study utilized twelve adult male tree shrews (TS), which were randomly divided into PBS and amyloidbetapeptide1-40 (Aß1-40) groups. AD model was established via an intracerebroventricular (icv) injection of Aß1-40 after being incubated for 4 days at 37 °C. Behavioral, pathophysiological and molecular changes were evaluated by hippocampal-dependent tasks, magnetic resonance imaging (MRI), silver staining, hematoxylin-eosin (HE) staining, TUNEL assay and gene sequencing, respectively. At 4 weeks post-injection, as compared with the PBS group, in Aß1-40 injected animals: cognitive impairments happened, and the hippocampus had atrophied indicated by MRI findings; meanwhile, HE staining showed the cells of the CA3 and DG were significantly thinner and smaller. The average number of cells in the DG, but not the CA3, was also significantly reduced; furthermore, silver staining revealed neurotic plaques and neurofibrillary tangles (NFTs) in the hippocampi; TUNEL assay showed many cells exhibited apoptosis, which was associated with downregulated BCL-2/BCL-XL-associated death promoter (Bad), inhibitor of apoptosis protein (IAP), Cytochrome c (CytC) and upregulated tumor necrosis factor receptor 1 (TNF-R1); lastly, gene sequencing reported a total of 924 mobilized genes, among which 13 of the downregulated and 19 of the upregulated genes were common to the AD pathway. The present study not only established AD models in TS, but also reported on the underlying mechanism involved in neuronal apoptosis associated with multiple gene expression.

[Bone mesenchymal stem cell transplantation for acute myocardial infarction: in vivo tracing with multi-modality molecular imaging].

OBJECTIVE: To investigate the feasibility of tracking bone mesenchymal stem cell (BMSCs) dual- labeled with polyethylenimine 2k-superparamagnetic iron oxide (PEI2k-SPIO) and Luciferase transplantation for acute myocardial infarction in vivo by using magnetic resonance imaging (MRI) and fluorescence imaging. METHODS: BMSCs/Luciferase was incubated with culture medium containing PEI2k-SPIO for 24 h. Prussian-blue staining and MTT were used to assess the efficacy and safety of labeling with PEI2k-SPIO. Guided with echocardiography, the dual-labeled BMSCs were injected into the margin of infarction myocardium. MRI and fluorescence imaging were performed to monitor the cells in vivo at different times (1,2,3,7 d). RESULTS: As demonstrated by MTT, there was no significant difference in survival rate between the labeled and unlabeled cells (P>0. 05). Within a week after transplantation, all PEI2k-SPIO-labeled BMSCs showed a significant decreased signal on MRI. Dual-labeled BMSCs were detected bioluminescence with fluorescence imaging, but disappeared after one week. CONCLUSION: Multi- modality imaging can not only trace the location of labeled BMSCs but also demonstrate the survival of labeled BMSCs in vivo.

Construction and identification of the adenoviral vector with dual reporter gene for multimodality molecular imaging.

In this study, the recombinant adenovirus (Ad) vector containing dual reporter gene [i.e. human transferrin receptor gene (TFRC) and firefly luciferase reporter gene] was constructed to provide a novel experimental tool for magnetic resonance (MR) and bioluminescence dual-modality molecular imaging. The cDNA of TFRC was amplified by polymerase chain reaction (PCR) and cloned into the multiple cloning site of pShuttle-CMV-CMV-Luciferase vector. After identification by Sfi I digestion and sequencing, pShuttle-TFRC-Luciferase vector and the adenoviral backbone vector (pAdeno) were subjected to homologous recombination. The correct recombinant plasmid was then transfected into 293 packaging cells to produce adenoviral particles and confirmed by PCR. After infection of human colorectal cancer LOVO cells with Ad-TFRC-Luciferase, the expressions of transferrin receptor (TfR) and luciferase protein were detected respectively by Western blotting and bioluminescence imaging in vitro. The results showed that TFRC gene was successfully inserted into the adenoviral shuttle vector carrying luciferase gene. DNA sequence analysis indicated that the TFRC gene sequence in the shuttle plasmid was exactly the same as that reported in GenBank. The recombinant plasmid was identified correct by restriction digestion. Ad-TFRC-Luciferase recombinant adenovirus was constructed successfully, and the virus titer was 1.6×10(10) pfu/mL. Forty-eight h after dual reporter gene transfection, the expressions of TfR and luciferase protein were increased significantly (P<0.01). It was concluded that the recombinant adenovirus vector with dual reporter gene was successfully established, which may be used for in vivo tracing target cells in multimodality imaging.

[MR imaging of polyethylenimine-superparamagnetic iron oxide nanoparticle labeled bone marrow mesenchymal stem cells in vitro].

OBJECTIVE: To explore the optimal concentration of polyethylenimine-superparamagnetic iron oxide (PEI2k-SPIO) particles for labeling bone marrow mesenchymal stem cells (BMSCs) in vitro, then to demonstrate the imaging characteristics of the cells by 7.0-T MR scanner. The lowest cell quantity and the optimal cell quantity detected on MR was observed. METHODS: Cells at 2nd passage were inoculated into the 6-hole plate with cover glass. The different concentrations of PEI2k-SPIO (5 microg/mL, 7 microg/mL, 10 microg/mL, 15 microg/mL, 20 microg/mL) were added into different holes, respectively. After labeled with different concentrations of PEI2k-SPIO, the Prussian blue stain was used for determining the labeling efficiency. MTT growth curves were used to identify the activity of BMSCs and to determine the optimal threshold of SPIO nanocomposite particles labeled the stem cells at different PEI2k-SPIO concentrations (7, 10, 15, 20 microg Fe/mL medium). To definite the lowest cells quantity and the optimal observable cells quantity on MR imaging, 1 x 10(6), 1 x 10(5), 1 x 10(4) and 1 x 10(3) cells labeled with optimal threshold of PEI2k-SPIO and 1 x 10(6) cells unlabeled suspended in 0.2 mL agarose (10 g/L), respectively undergone MR scan. RESULTS: MTT growth curves showed the optimal threshold of PEI2k-SPIO labeled BMSCs was 7 microg/mL, which indicates has no adverse effects on the growth of stem cells. At the opimal concentration (7 microg Fe/mL), the lowest observable cell quantity of PEI2k-SPIO-labeled cells for MRI was 1 x 10(4), and the optimal observable cell quantity was 1 x 10(6). CONCLUSION: At the opimal concentration, adverse effect to stem cell activities had not be detected when were labeled with PEI2k-SPIO and the clearly image of MRI of labeled BMSCs could be obtained.

Establishment of a novel rat model of blast-related diffuse axonal injury.

Although studies concerning blast-related traumatic brain injury (bTBI) have demonstrated the significance of diffuse axonal injury (DAI), no standard models for this type of injury have been widely accepted. The present study investigated a mechanism of inducing DAI through real blast injury, which was achieved by performing instantaneous high-speed swinging of the rat head, thus establishing a stable animal model of blast DAI. Adult Sprague-Dawley rats weighing 150±10 g were randomly divided into experimental (n=16), control (n=10) and sham control (n=6) groups. The frontal, parietal and occipital cortex of the rats in the experimental group were exposed, whereas those of the control group were unexposed; the sham control group rats were anesthetized and attached to the craniocerebral blast device without experiencing a blast. The rats were subjected to craniocerebral blast injury through a blast equivalent to 400 mg of trinitrotoluene using an electric detonator. Biomechanical parameters, and physical and behavioural changes of the sagittal head swing were measured using a high-speed camera. Magnetic resonance imaging (MRI) scans were conducted at 2, 12, 24 and 48 h after craniocerebral injury, only the experimental group indicated brain stem injury. The rats were sacrificed immediately following the MRI at 48 h for pathological examination of the brain stem using haematoxylin and eosin staining. The results indicated that 14 rats (87.5%) in the experimental group exhibited blast DAI, while no DAI was observed in the control and sham control groups, and the difference between the groups was significant (P<0.05). The present results indicated that this experimental design may serve to provide a stable model of blast DAI in rats.

Brain structure alterations and cognitive impairment following repetitive mild head impact: An in vivo MRI and behavioral study in rat.

Mild traumatic brain injury (mTBI) or concussion is a common health issue. Several people repeatedly experience head impact milder than that causing concussion. The present study aimed to confirm the effects of such repeated impact on the brain structure and cognitive abilities. Rat models were established by closed skull weight-drop injury. The animals were anesthetized, subjected to single (s)-sham, s-mTBI, repetitive (r)-sham, and r-mTBI, and recovery times were recorded. MRI, including T2-weighted and diffusion tensor imaging (DTI), as well as, neurological severity scores (mNSS) were assessed for the dynamics of the brain structure and neurological function. Morris water maze (MWM) was used to evaluate the cognitive function. The histological examination of r-mTBI rats revealed the basis of structural changes in the brain. There was no significant difference in the recovery time, MRI, mNSS, and MWM between the s-sham and the s-mTBI groups. Compared with r-sham, r-mTBI induced significant differences in the following aspects. The recovery time was prolonged and beam balance test (BBT) in mNSS increased from day 5. MWM performances were worse even after the BBT was recovered. The volumes of the cortex (CT), hippocampus (HP), and lateral ventricle had changed from day 5, which reached a maximum at day 14. Abnormal DTI parameters were observed in CT, corpus callosum, and HP. Histological analyses showed that both in CT and HP, neuron counts reduced at the end of the experiment. Altogether, these findings indicate that non-symptomatic head injury may result in brain atrophy and cognitive impairment when occurred repeatedly.

Noninvasive Imaging of Ras Activity by Monomolecular Biosensor Based on Split-Luciferase Complementary Assay.

Deregulated activity of Ras GTPases has been observed in many types of human cancers, and contributes to the diverse aspects of carcinogenesis. Although the significance in tumorigenesis has been widely accepted and many therapeutic drugs are under development, little attention has been dedicated to the development of sensors for the Ras activity in vivo. Therefore, based on the split firefly luciferase complementation strategy, we developed a monomolecular bioluminescent biosensor to image endogenous Ras activity in living subject. In this biosensor, two inactive luciferase fragments are sandwiched by Raf-1, whose conformation changes upon GTP-Ras binding. Thus, the Ras activity can be surrogated by the intensity of the complementary luciferase. The bioluminescence analyses demonstrated that this novel biosensor behaved the robust and sensitive reporting efficiency in response to the dynamical changes of Ras activity, both in living colorectal cancer cells and in vivo. Compared to the traditional method, such as the pull-down assay, the bioluminescent sensor is simply, noninvasive, faster and more sensitive for the analysis of the endogenous Ras activity. This innovative work opens up the way for monitoring the preclinical curative effect and high-throughput screening of therapeutic drugs targeting Ras pathways.

Magnetic resonance T2 relaxation time at 7 Tesla associated with amyloid ß pathology and age in a double-transgenic mouse model of Alzheimer's disease.

The aim of this study was to better understand the effect of amyloid-ß plaques on magnetic resonance T2 relaxation time. We investigated these changes associated with age in an APP/PS1 mouse model of AD at 7 Tesla, combined with histology. Ten double-transgenic AD and ten wild type (WT) female mice (aged 12-20 months) were used in a cross-sectional study. Mean T2 values and standard deviations were calculated for each Regions of interest (ROIs) on T2 map. Immunohistochemistry for amyloid plaques and fluorescence staining with thioflavine S were performed of brain sections after imaging. The results showed that mean T2 values of the hippocampus, cortex, corpus callosum, and thalamus of older mice were significantly lower than of the younger. Compared to WT mice, the T2 values of the hippocampus, corpus callosum, and thalamus in younger AD mice were significantly greater, while the T2 values of the hippocampus and cortex in older AD mice were significantly less. Aß-40 immunohistochemistry and thioflavine S stainging were positive in the matched region both for younger and older AD mice, while neither Aß-40 nor thioflavine S were observed in WT mice. These findings suggest that regional T2 values of AD mice may decrease with age, and changes in T2 values in AD mice may be influenced by many factors besides amyloid-ß plaque accumulation. Furthermore, they support that the standard deviation of the mean T2 value should be considered as well as the mean.

Dynamic Diffusion Tensor Imaging Reveals Structural Changes in the Bilateral Pyramidal Tracts after Brain Stem Hemorrhage in Rats.

BACKGROUND AND PURPOSE: Few studies have concentrated on pyramidal tract (PY) changes after brain stem hemorrhage (BSH). In this study, we used a diffusion tensor imaging (DTI) technique and histologic identification to investigate longitudinal PY changes on both the contralateral and ipsilateral sides after experimental BSH. METHODS: BSH was induced in 61 Sprague-Dawley rats by infusing 30 µl of autogenous tail blood into each rat's right pons. DTI and motor function examinations were performed repeatedly on days 1, 3, 7, 14, and 28 after surgery. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity, and radial diffusivity were measured in the bilateral PYs. The axon and myelin injury in the PY were evaluated by histologic study. RESULTS: As compared with normal controls, the bilateral PYs in rats with induced BSH showed an early decrease and a late increase in FA and an early increase and a late decrease in MD. A progressive decrease in axial diffusivity with dramatic axon loss from day 1 to day 28 after BSH was found bilaterally. The bilateral PYs showed an early increase and a late decrease in radial diffusivity. Early myelin injury and late repair were also detected pathologically in the bilateral PYs of rats with BSH. Thus, the early motor function deficits of rats with BSH began to improve on day 14 and had almost completely disappeared by day 28. CONCLUSIONS: DTI revealed dynamic changes in the bilateral PYs after BSH, which was confirmed by histologic findings and which correlated with motor function alteration. These findings support the idea that quantitative DTI can track structural changes in the bilateral PYs and that DTI may serve as a noninvasive tool to predict the prognoses of patients with BSH.