Left ventricular strain changes at high altitude in rats: a cardiac magnetic resonance tissue tracking imaging study.

BACKGROUND: Long-term exposure to a high altitude environment with low pressure and low oxygen could cause abnormalities in the structure and function of the heart. Myocardial strain is a sensitive indicator for assessing myocardial dysfunction, monitoring myocardial strain is of great significance for the early diagnosis and treatment of high altitude heart-related diseases. This study applies cardiac magnetic resonance tissue tracking technology (CMR-TT) to evaluate the changes in left ventricular myocardial function and structure in rats in high altitude environment. METHODS: 6-week-old male rats were randomized into plateau hypoxia rats (plateau group, n = 21) as the experimental group and plain rats (plain group, n = 10) as the control group. plateau group rats were transported from Chengdu (altitude: 360 m), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (altitude: 3850 m), Yushu, China, and then fed for 12 weeks there, while plain group rats were fed in Chengdu(altitude: 360 m), China. Using 7.0 T cardiac magnetic resonance (CMR) to evaluate the left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), as well as myocardial strain parameters including the peak global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). The rats were euthanized and a myocardial biopsy was obtained after the magnetic resonance imaging scan. RESULTS: The plateau rats showed more lower left ventricular GLS and GRS (P < 0.05) than the plain rats. However, there was no statistically significant difference in left ventricular EDV, ESV, SV, EF and GCS compared to the plain rats (P > 0.05). CONCLUSIONS: After 12 weeks of exposure to high altitude low-pressure hypoxia environment, the left ventricular global strain was partially decreased and myocardium is damaged, while the whole heart ejection fraction was still preserved, the myocardial strain was more sensitive than the ejection fraction in monitoring cardiac function.

Paeoniflorin attenuates cuproptosis and ameliorates left ventricular remodeling after AMI in hypobaric hypoxia environments.

This study investigates the cardioprotective effects of Paeoniflorin (PF) on left ventricular remodeling following acute myocardial infarction (AMI) under conditions of hypobaric hypoxia. Left ventricular remodeling post-AMI plays a pivotal role in exacerbating heart failure, especially at high altitudes. Using a rat model of AMI, the study aimed to evaluate the cardioprotective potential of PF under hypobaric hypoxia. Ninety male rats were divided into four groups: sham-operated controls under normoxia/hypobaria, an AMI model group, and a PF treatment group. PF was administered for 4 weeks after AMI induction. Left ventricular function was assessed using cardiac magnetic resonance imaging. Biochemical assays of cuproptosis, oxidative stress, apoptosis, inflammation, and fibrosis were performed. Results demonstrated PF significantly improved left ventricular function and remodeling after AMI under hypobaric hypoxia. Mechanistically, PF decreased FDX1/DLAT expression and serum copper while increasing pyruvate. It also attenuated apoptosis, inflammation, and fibrosis by modulating Bcl-2, Bax, NLRP3, and oxidative stress markers. Thus, PF exhibits therapeutic potential for left ventricular remodeling post-AMI at high altitude by inhibiting cuproptosis, inflammation, apoptosis and fibrosis. Further studies are warranted to optimize dosage and duration and elucidate PF's mechanisms of action.

Protective effects of epigallocatechin-3-gallate counteracting the chronic hypobaric hypoxia-induced myocardial injury in plain-grown rats at high altitude.

Exposure to hypobaric hypoxia (HH) environment causes stress to the body, especially the oxygen-consuming organs. Chronic HH conditions have adverse effects on the myocardium. Thus, we conducted this experiment and aim to evaluate such adverse effects and explore the therapeutic role of epigallocatechin-3-gallate (EGCG) in rats' heart under chronic HH conditions. For that purpose, we transported rats from plain to a real HH environment at high altitude for establishing the HH model. At high altitude, animals were treated with EGCG while the salidroside was used as the positive control. General physiological data were collected, and routine blood test results were analyzed. Cardiac magnetic resonance (CMR) was examined to assess the structural and functional changes of the heart. Serum levels of cardiac enzymes and pro-inflammatory cytokines were examined. Oxidative markers in the left ventricle (LV) were detected. Additionally, ultrastructural and histopathological changes and apoptosis of the LV were assessed. Furthermore, the antioxidant stress-relevant proteins nuclear factor E2-related factor 2 (Nrf2) and the heme oxygenase-1 (HO-1) were detected. The experiment revealed that EGCG treatment decreased HH-induced elevation of cardiac enzymes and relieved mitochondrial damage of the LV. Notably, EGCG treatment significantly alleviated oxidative stress in the LV and inflammatory response in the blood. Western blot confirmed that EGCG significantly upregulated Nrf2 and HO-1. Therefore, EGCG may be considered a promising natural compound for treating the HH-induced myocardial injuries.

Right Adrenocortical Carcinoma Coexisting With Left Adrenal Sarcomatoid Carcinoma on FDG PET/CT.

ABSTRACT: Bilateral adrenal glands synchronously involved by different types of pathologies are uncommon. An 80-year-old man underwent FDG PET/CT to evaluate bilateral adrenal masses, which were initially discovered by ultrasonography and confirmed by MRI. The images demonstrated elevated FDG activity in both lesions, which were subsequently diagnosed as concurrent right adrenocortical carcinoma and left adrenal sarcomatoid carcinoma respectively by histopathological examination.

Golden-angle radial sparse parallel magnetic resonance imaging of rectal perfusion: utility in the diagnosis of poorly differentiated rectal cancer.

Background: The objective of this retrospective investigation is to evaluate the diagnostic efficacy of a dual-parameter strategy that integrates either time-resolved angiography with stochastic trajectories (TWIST) or golden-angle radial sparse parallel (GRASP)-derived dynamic contrast agent-enhanced magnetic resonance imaging (DCE-MRI) with diffusion-weighted imaging (DWI) for the identification of poorly differentiated rectal cancer (RC). The purpose of this investigation is to contrast the aforementioned methodology with conventional single-factor assessments that rely solely on DWI, and ascertain its comparative efficacy. Methods: This study was not registered on a clinical trial platform. Consecutive individuals diagnosed with non-mucinous rectal adenocarcinoma through endoscopy-guided biopsy between December 2020 and October 2022 were involved in our study. These patients had also undergone DCE-MRI and DWI. The perfusion metrics of influx forward volume transfer constant (Ktrans) and rate constant (Kep), along with the apparent diffusion coefficient (ADC), were quantified by a pair of investigators. The study compared the area under the curve (AUC) of the receiver operating characteristic (ROC) for both sequences to identify poorly differentiated RC. The investigation incorporated patients who fulfilled the specified criteria. The inclusion criteria for the investigation were as follows: (I) a diagnosis of RC proved through pathological examination, either via endoscopically-guided biopsy or surgical resection; (II) availability of complete MRI images; (III) absence of any prior history of neoadjuvant chemoradiotherapy during the MRI scan. Results: Our investigation comprised a total of 179 participants. Compared to diffusion parameter alone, an integrated assessment of diffusion parameter (ADC) and perfusion parameters (Ktrans or Kep) obtained with GRASP leads to a superior diagnostic accuracy (AUC, 0.97±0.02 vs. 0.89±0.03, 0.97±0.02 vs. 0.89±0.03, P=0.005 and 0.003, respectively); however, there was no additional benefit from ADC with perfusion parameters obtained from TWIST (Ktrans or Kep) (AUC, 0.93±0.04 vs. 0.89±0.03, 0.93±0.03 vs. 0.89±0.03; P= 0.955 and 0.981, respectively, for the integration of ADC with Ktrans and Kep). Conclusions: By integrating diffusion and perfusion features into a dual-parameter model, the GRASP method enhances the diagnostic efficacy of MRI in discriminating RCs with poor differentiation. Conversely, the TWIST approach did not yield the aforementioned outcome.

7.0T cardiac magnetic resonance imaging of right ventricular function in rats with high-altitude deacclimatization.

Background: High-altitude deacclimatization syndrome (HADAS) is a severe public health issue. The study of the changes in right ventricular function caused by high-altitude deacclimatization (HADA) is of great significance for the prevention and treatment of HADAS. Methods: Six-week-old, male Sprague Dawley (SD) rats were randomly divided into the plain, plateau and the HADA group. Rats in the plateau and plain group were exposed to altitudes of 3,850 and 360 m, respectively, for 12 weeks. Rats in HADA group were exposed to the plateau altitude of 3,850 m for 12 weeks and subsequently transported to the plain altitude of 360 m for 4 weeks. Right ventricular ejection fraction (RVEF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and myocardial strain parameters, including the global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS), were evaluated by 7.0T cardiac magnetic resonance (CMR). The levels of red blood cell (RBC), hemoglobin (HGB), and hematocrit (HCT) in the blood were measured, and hematoxylin-eosin (HE) staining was used to observe the pathological changes in the myocardium. Results: In rats in the plateau group, the right ventricular fibrous space was slightly widened, and partial focal steatosis were observed. However, in the HADA group, only a few focal steatoses were found. Rats in the plateau group had elevated levels of RBC, HGB and HCT, increased right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV) and right ventricular stroke volume (RVSV), and decreased right ventricular global longitudinal strain (RVGLS), right ventricular global circumferential strain (RVGCS), and right ventricular global radial strain (RVGRS) compared to rats in the plain group (P<0.001). The RVEDV, RVGCS, and RVGRS in the HADA group basically returned to the plain state. Interestingly, the RVESV in the HADA group was higher, while the RVSV, RVEF, and RVGLS were lower than those in the other two groups. Conclusions: After 12 weeks of exposure to high-altitude environment, there were some pathological changes and the whole contractile strain of the right ventricle was observed. Some pathological changes in the myocardial tissue and stroma recovered after returning to the plain for 4 weeks. However, the right ventricular systolic function and strain did not recover completely.

[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.

Nicorandil Ameliorates Doxorubicin-Induced Cardiotoxicity in Rats, as Evaluated by 7 T Cardiovascular Magnetic Resonance Imaging.

PURPOSE: Doxorubicin-induced cardiotoxicity (DIC) is a common side effect of doxorubicin chemotherapy, and a major mechanism of DIC is inflammation. However, no effective method exists to prevent DIC. In the present study, we investigated the cardioprotective effects of nicorandil against DIC using multiparametric cardiac magnetic resonance (CMR) imaging and elucidated the anti-inflammatory properties of nicorandil in rat models. METHODS: Male Sprague-Dawley rats received four weekly intraperitoneal doxorubicin doses (4 mg/kg/injection) to establish the DIC model. After treatment with or without nicorandil (3 mg/kg/day) or diazoxide (10 mg/kg/day) orally, all the groups underwent weekly CMR examinations, including cardiac function and strain assessment and T2 mapping, for 6 weeks. Additionally, blood samples and hearts were collected to examine inflammation and histopathology. RESULTS: According to our results, the earliest DIC CMR parameter in the doxorubicin group was T2 mapping time prolongation compared with the DIC rats treated with nicorandil (doxorubicin+nicorandil group) at week 2. Subsequently, the left ventricular ejection fraction (LVEF) and global peak systolic myocardial strain in the doxorubicin group were significantly reduced, and nicorandil effectively inhibited these effects at week 6. Our results were confirmed by histopathological evaluations. Furthermore, nicorandil treatment had a protective effect against the doxorubicin-induced inflammatory response. Interestingly, similar protective results were obtained using the KATP channel opener diazoxide. CONCLUSION: Collectively, our findings indicate that nicorandil application ameliorates DIC in rats with significantly higher cardiac function and myocardial strain and less fibrosis, apoptosis and inflammatory cytokine production. Nicorandil prevents T2 abnormalities in the early stages of DIC, showing a high clinical value for early nicorandil treatment in chemotherapy patients.

The value of intravoxel incoherent motion model-based diffusion-weighted imaging for predicting long-term outcomes in nasopharyngeal carcinoma.

Objective: The aim of this study was to evaluate the prognostic value for survival of parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in patients with nasopharyngeal carcinoma (NPC). Materials: Baseline IVIM-DWI was performed on 97 newly diagnosed NPC patients in this prospective study. The relationships between the pretreatment IVIM-DWI parametric values (apparent diffusion coefficient (ADC), D, D*, and f) of the primary tumors and the patients' 3-year survival were analyzed in 97 NPC patients who received chemoradiotherapy. The cutoff values of IVIM parameters for local relapse-free survival (LRFS) were identified by a non-parametric log-rank test. The local-regional relapse-free survival (LRRFS), LRFS, regional relapse-free survival (RRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were calculated by using the Kaplan-Meier method. A Cox proportional hazards model was used to explore the independent predictors for prognosis. Results: There were 97 participants (mean age, 48.4 ± 10.5 years; 65 men) analyzed. Non-parametric log-rank test results showed that the optimal cutoff values of ADC, D, D*, and f were 0.897 × 10-3 mm2/s, 0.699 × 10-3 mm2/s, 8.71 × 10-3 mm2/s, and 0.198%, respectively. According to the univariable analysis, the higher ADC group demonstrated significantly higher OS rates than the low ADC group (p = 0.036), the higher D group showed significantly higher LRFS and OS rates than the low D group (p = 0.028 and p = 0.017, respectively), and the higher D* group exhibited significantly higher LRFS and OS rates than the lower D* group (p = 0.001 and p = 0.002, respectively). Multivariable analyses indicated that ADC and D were the independent prognostic factors for LRFS (p = 0.041 and p = 0.037, respectively), D was an independent prognostic factor for LRRFS (p = 0.045), D* and f were the independent prognostic factors for OS (p = 0.019 and 0.029, respectively), and f acted was an independent prognostic factor for DMFS (p = 0.020). Conclusions: Baseline IVIM-DWI perfusion parameters ADC and D, together with diffusion parameter D*, could act as useful factors for predicting long-term outcomes and selecting high-risk patients with NPC.

Left ventricular strain patterns and their relationships with cardiac biomarkers in hypertrophic cardiomyopathy patients with preserved left ventricular ejection fraction.

Aims: This study aims to assess left ventricular (LV) function in hypertrophic cardiomyopathy (HCM) patients with preserved left ventricular ejection fraction (LVEF) by LV strain patterns based on cardiac magnetic resonance feature tracking (CMR-FT) and to explore the relationships between LV strain patterns and cardiac biomarkers in these patients, such as cardiac troponin (cTnT) and N-terminal prohormone of the brain natriuretic peptide (NT-proBNP). Methods: A total of 64 HCM patients with preserved LVEF and 33 healthy people were included in this study. All subjects underwent contrast-enhanced CMR, and all patients took blood tests for cTnT and NT-proBNP during hospitalization. Results: Despite the absence of a significant difference in LVEF between HCM patients and healthy controls, almost all global and segmental strains in radial, circumferential, and longitudinal directions in the HCM group deteriorated significantly as compared to controls (p < 0.05). Moreover, some global and segmental strains correlated significantly with NT-proBNP and cTnT in HCM patients, and the best correlations were global radial strain (GRS) (r = -0.553, p < 0.001) and mid-ventricular radial strain (MRS) (r = -0.582, p < 0.001), respectively, with a moderate correlation. The receiver operating characteristic (ROC) results showed that among the LV deformation parameters, GRS [area under the curve (AUC), 0.76; sensitivity, 0.49; specificity, 1.00], MRS (AUC, 0.81; sensitivity, 0.77; specificity, 0.79) demonstrated greater diagnostic accuracy to predict elevated NT-proBNP, and abnormal cTnT, respectively. Their cut-off values were 21.17 and 20.94%, respectively. Finally, all global strains demonstrated moderate, good, and excellent intra- and inter-observer reproducibility. Conclusion: LV strain patterns can be used to assess the subclinical cardiac function of HCM patients on the merit of being more sensitive than LVEF. In addition, LV strain patterns can detect serious HCM patients and may be helpful to non-invasively predict elevated NT-proBNP and cTnT.

Myocardial infarction size as an independent predictor of intramyocardial haemorrhage in acute reperfused myocardial ischaemic rats.

BACKGROUND: In previous studies, haemorrhage occurred only with large infarct sizes, and studies found a moderate correlation between the extent of necrosis and haemorrhage, but the extent of infarction size in these studies was limited. This study aimed to find the correlations between intramyocardial haemorrhage (IMH), myocardial infarction (MI), and myocardial oedema (ME) from small to large sizes of MI in a 7.0-T MR scanner. METHODS: Different sizes of myocardial infarction were induced by occluding different sections of the proximal left anterior descending coronary artery (1-3 mm under the left auricle). T2*-mapping, T2-mapping and late gadolinium enhancement (LGE) sequences were performed on a 7.0 T MR system at Days 2 and 7. T2*- and T2-maps were calculated using custom-made software. All areas were expressed as a percentage of the entire myocardial tissue of the left ventricle. The rats were divided into two groups based on the T2* results and pathological findings; MI with IMH was referred to as the + IMH group, while MI without IMH was referred to as the -IMH group. RESULTS: The final experimental sample consisted of 25 rats in the + IMH group and 10 rats in the -IMH group. For the + IMH group on Day 2, there was a significant positive correlation between IMH size and MI size (r = 0.677, P < 0.01) and a positive correlation between IMH size and ME size (r = 0.552, P < 0.01). On Day 7, there was a significant positive correlation between IMH size and MI size (r = 0.711, P < 0.01), while no correlation was found between IMH size and ME size (r = 0.429, P = 0.097). The MI sizes of the + IMH group were larger than those of the -IMH group (P < 0.01). CONCLUSIONS: Infarction size prior to reperfusion is a critical factor in determining IMH size in rats.

The role of sex and ovarian hormones in hippocampal damage and cognitive deficits induced by chronic exposure to hypobaric hypoxia.

Purpose: This study aims to investigate the role of sex and ovarian hormones in hippocampal damage and cognitive deficits and behavioral dysfunction in rats induced by chronic exposure to hypobaric hypoxia. Methods: Six-week-old male and female SD rats were housed for 3 months either in a real altitude (4,250 m) environment as the model of chronic hypobaric-hypoxia (CHH) or in a plain as controls. The animal behavioral and hippocampal neurons at subcellular, molecular, and ultrastructural levels were characterized after CHH exposure. Results: After 3 months of CHH exposure, (1) male CHH rats' serum testosterone level was lower than male controls' whereas female CHH rats' serum estradiol level was higher than female controls'; (2) Morris water maze test finds that male rats showed more learning and spatial memory deficits than female rats; (3) male rats showed more severe hippocampal damage, hippocampal inflammation, oxidative stress and decreased hippocampal integrity (neurogenesis and dendritic spine density) than female rats; (4) Western blot analysis shows that, compared with the male control group, in male CHH group's hippocampus, expression of nNOS, HO-1, and Bax protein increased whereas that of Bcl-2 protein decreased; (5) Expression of PON2 protein in male rats (CHH and controls) was lower than female rats (CHH and controls). In addition, CHH exposure decreased the expression of PON2 protein in both male and female rats; (6) qPCR analysis reveals that CHH exposure reduced the gene expression of N-methyl-D-aspartate receptor NR2A and NR2B subunits in male rats' hippocampus. In addition, compared with the sham CHH group, the expression level of PON2 protein decreased in the OVX-CHH group's hippocampus whereas oxidative stress, neuroinflammation, and degeneration of hippocampal neurons increased in the OVX-CHH group's hippocampus. Conclusion: After CHH exposure, male rats were significantly more likely than female rats to develop hippocampal damage, hippocampal neuroinflammation, and cognitive decline and deficits, suggesting that sex and ovarian hormones were significantly involved in regulating the rats' susceptibility to CHH exposure-induced hippocampal damage.

Compact MR-compatible ergometer and its application in cardiac MR under exercise stress: A preliminary study.

PURPOSE: To develop a compact MR-compatible ergometer for exercise stress and to initially evaluate the reproducibility of myocardial native T1 and myocardial blood flow (MBF) measurements during exercise stress performed on this ergometer. METHODS: The compact ergometer consists of exercise, workload, and data processing components. The exercise stress can be achieved by pedaling on a pair of cylinders at a predefined frequency with adjustable resistances. Ten healthy subjects were recruited to perform cardiac MRI scans twice in a 3.0T MR scanner, at different days to assess reproducibility. Myocardial native T1 and MBF were acquired at rest and during a moderate exercise. The reproducibility of the two tests was determined by the intra-group correlation coefficient (ICC) and coefficient of variation (CoV). RESULTS: The mean exercise intensity in this pilot study was 45 Watts (W), with an exercise duration of 5 min. Stress induced a significant increase in systolic blood pressure (from 113 ± 11 mmHg to 141 ± 12, P < 0.05) and maximal increase in heart rate by 74 ± 19%. The rate pressure product increased two-fold (P < 0.001). Excellent reproducibility was demonstrated in native T1 during the exercise (CoV = 3.0%), whereas the reproducibility of MBF and myocardial perfusion reserve during the exercise was also good (CoV = 10.7% and 8.8%, respectively). CONCLUSION: This pilot study demonstrated that it is possible to acquire reproducible measurements of myocardial native T1 and MBF during the exercise stress in healthy volunteers using our new compact ergometer.

Using 7.0 T cardiac magnetic resonance to investigate the effect of estradiol on biventricular structure and function of ovariectomized rats exposed to chronic hypobaric hypoxia at high altitude.

BACKGROUND: Despite that estradiol can reduce the risk of cardiovascular diseases in ovariectomized animals in the plains, its effect on animals at high altitude has seldom been reported. We hypothesize that estradiol can ameliorate cardiac damage to ovariectomized rats induced by chronic exposure to hypobaric hypoxia at high altitude. PURPOSE: This study was intended to investigate whether cardiovascular magnetic resonance (CMR) imaging could reveal cardioprotective effect of estradiol on ovariectomized rats under chronic exposure to hypobaric hypoxia at high altitude. METHODS: Thirty-two rats were randomized into the Control group (Plain), HH + Sham group (Hypobaric Hypoxia + Sham), HH + OVX group (Hypobaric Hypoxia + Bilateral Ovariectomy) and HH-OVX + E2 group (Hypobaric Hypoxia + Bilateral Ovariectomy + Estradiol, 50 µg/kg, 3 times a week, for 6 weeks) (n = 8 per group). Except the Control group (altitude: 500 m), rats in other groups were subcutaneously injected with 17ß -estradiol or vehicle and exposed to chronic hypobaric hypoxia in Qinghai-Tibet Plateau (altitude: 4250 m), China, for 6 weeks. Biventricular cardiac function and global strain of the rats were measured by CMR and analyzed using the cine tissue tracking techniques. Biochemical tests, histopathology and electronic microscopy were used to evaluate the protective effect of estradiol on the heart tissue of ovariectomized rats exposed to a high-altitude environment. RESULTS: The biventricular ejection fraction and global strains decreased in the HH + OVX group compared with that in the Control group (all p < 0.05). All the aforementioned changes in the HH + OVX group ameliorated in the HH-OVX + E2 group (all p < 0.05). Estradiol also alleviated the right ventricular dilatation and hypertrophy in the HH + OVX group (all p < 0.05). In addition, histological and biochemical analyses also supported these in vivo results. CONCLUSIONS: Estradiol ameliorated the biventricular structural and functional damage in ovariectomized rats exposed to chronic hypobaric hypoxia at high altitude.

Epigallocatechin-3-Gallate Ameliorated Iron Accumulation and Apoptosis and Promoted Neuronal Regeneration and Memory/Cognitive Functions in the Hippocampus Induced by Exposure to a Chronic High-Altitude Hypoxia Environment.

We aimed to explore the protective effects and potential treatment mechanism of Epigallocatechin-3-gallate (EGCG) in an animal model of chronic exposure in a natural high-altitude hypoxia (HAH) environment. Behavioral alterations were assessed with the Morris water maze test. Iron accumulation in the hippocampus was detected by using DAB enhanced Perls' staining, MRI, qPCR and colorimetry, respectively. Oxidative stress (malondialdehyde, MDA), apoptosis (Caspase-3), and neural regeneration (brain-derived neurotrophic factor, BDNF) were detected by using ELISA and western blotting. Neural ultrastructural changes were evaluated by transmission electron microscopy (TEM). The results showed that learning and memory performance of rats decreased when exposure to HAH environment. It was followed by iron accumulation, dysfunctional iron metabolism, reduced BDNF and the upregulation of MDA and Caspase-3. TEM confirmed the ultrastructural changes in neurons and mitochondria. EGCG reduced HAH-induced cognitive impairment, iron deposition, oxidative stress, and apoptosis and promoted neuronal regeneration against chronic HAH-mediated neural injury.

Identifying early stages of doxorubicin-induced cardiotoxicity in rat model by 7.0 tesla cardiovascular magnetic resonance combining hematological and pathological parameters.

PURPOSE: To identify early doxorubicin-induced cardiotoxicity by applying 7.0 T cardiac magnetic resonance (CMR) combined with creatine kinase isoenzymes (CKMB) from rat models, using pathological results as a reference standard. METHODS: The 48 male rats included in the study were divided into a doxorubicin (DOX) group (n = 32) and a control group (n = 16). Each group was further divided into four subgroups according to the interval weeks between the first administration and CMR examination. DOX group and the controls were injected with DOX (2.5 mg/kg) or physiological saline (2.5 mg/kg) through vena caudalis weekly. The rats in first subgroup received 4 weekly injections and were sacrificed after CMR examination at week 4. Rats in the second, third and fourth DOX or control subgroups underwent 6 weekly injections and were sacrificed after CMR examination at weeks 6, 8 and 10, respectively. The conventional cardiac function parameters, myocardial strain, standardized myocardial T2 value, late gadolinium enhancement, CKMB and pathological results of each rat were analyzed. RESULTS: The LV mass index was reduced and CKMB was increased in the first subgroup (week 4), global circumference strain was decreased and normalized myocardial T2 relaxation time was prolonged in the second subgroup (week 6). At these early point of time, LVEF remained unaffected. Myocardial fibrosis was observed in the third and fourth subgroups (in week 8 and 10, respectively) and the collagen volume fraction was significantly negatively correlated with the LVEF and myocardial strain. CONCLUSIONS: CMR can be used to identify doxorubicin-induced cardiotoxicity at early stage, with the LV mass index, global circumference strain, normalized myocardial T2 relaxation time as the early markers. CKMB can indicate the optimal timing for CMR examination of chemotherapy recipients to improve medical efficiency. Myocardial fibrosis persists in the advanced stage of doxorubicin-induced cardiotoxicity which comprises the main cause of LV dysfunction.

Protective effect of a chronic hypobaric hypoxic environment at high altitude on cardiotoxicity induced by doxorubicin in rats: a 7 T magnetic resonance study.

BACKGROUND: Doxorubicin (DOX)-induced cardiotoxicity (DIC), a major clinical problem, has no effective preventive therapies. We hypothesized that left ventricular (LV) systolic function would be improved in a chronic hypobaric hypoxia environment at high altitude. The purpose of this study was to investigate whether cardiovascular magnetic resonance could reveal the cardioprotective effect of chronic hypobaric hypoxia on DIC. METHODS: In total, 60 rats were randomly assigned to 1 of 6 groups (n=10 per group): the P group (plain), PD group (plain + DOX), HH group (high altitude), HHD4 group (high altitude + DOX for 4 weeks), HHD8 group (high altitude + DOX for 8 weeks), and HHD12 group (high altitude + DOX for 12 weeks). The rats were transported to either Yushu (altitude: 4,250 m) or Chengdu (altitude: 500 m) where they underwent intraperitoneal injection of DOX (5 mg/kg/week for 3 weeks) or saline. Preclinical 7 T cardiovascular magnetic resonance was performed at weeks 4, 8, and 12. Tissue tracking was used to measure LV cardiac function and to analyze global and segmental strains. Subsequently, histological and oxidative stress tests were performed to evaluate the protective effect of a high-altitude environment on DIC. RESULTS: The left ventricular ejection fraction (LVEF) and global and regional strains in the middle, apical, anterior, septal, inferior, and lateral segments (all P<0.05) were improved in the HHD4 group compared with the PD group. The global strain was significantly greater in absolute value in the HHD8 and HHD12 groups than in the HHD4 group (all P<0.05). Additionally, histological and enzyme-linked immunosorbent assay evaluations supported the in vivo results. CONCLUSIONS: A chronic hypobaric and hypoxic environment at high altitude partially prevented cardiac dysfunction and increased global and regional strain in DIC rat models, thereby minimizing myocardial injury and fibrosis. In addition, by increasing the total duration of chronic hypobaric hypoxia, the global strain was further increased, which was likely due to reduced oxidative stress.

A Multimodal MR Imaging Study of the Effect of Hippocampal Damage on Affective and Cognitive Functions in a Rat Model of Chronic Exposure to a Plateau Environment.

Prolonged exposure to high altitudes above 2500 m above sea level (a.s.l.) can cause cognitive and behavioral dysfunctions. Herein, we sought to investigate the effects of chronic exposure to plateau hypoxia on the hippocampus in a rat model by using voxel-based morphometry, creatine chemical exchange saturation transfer (CrCEST) and dynamic contrast-enhanced MR imaging techniques. 58 healthy 4-week-old male rats were randomized into plateau hypoxia rats (H group) as the experimental group and plain rats (P group) as the control group. H group rats were transported from Chengdu (500 m a.s.l.), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (4250 m a.s.l.), Yushu, China, and then fed for 8 months there, while P group rats were fed in Chengdu (500 m a.s.l.), China. After 8 months of exposure to plateau hypoxia, open-field and elevated plus maze tests revealed that the anxiety-like behavior of the H group rats was more serious than that of the P group rats, and the Morris water maze test revealed impaired spatial memory function in the H group rats. Multimodal MR imaging analysis revealed a decreased volume of the regional gray matter, lower CrCEST contrast and higher transport coefficient Ktrans in the hippocampus compared with the P group rats. Further correlation analysis found associations of quantitative MRI parameters of the hippocampus with the behavioral performance of H group rats. In this study, we validated the viability of using noninvasive multimodal MR imaging techniques to evaluate the effects of chronic exposure to a plateau hypoxic environment on the hippocampus.

Machine learning to differentiate small round cell malignant tumors and non-small round cell malignant tumors of the nasal and paranasal sinuses using apparent diffusion coefficient values.

OBJECTIVE: We used radiomics feature-based machine learning classifiers of apparent diffusion coefficient (ADC) maps to differentiate small round cell malignant tumors (SRCMTs) and non-SRCMTs of the nasal and paranasal sinuses. MATERIALS: A total of 267 features were extracted from each region of interest (ROI). Datasets were randomized into two sets, a training set (∼70%) and a test set (∼30%). We performed dimensional reductions using the Pearson correlation coefficient and feature selection analyses (analysis of variance [ANOVA], relief, recursive feature elimination [RFE]) and classifications using 10 machine learning classifiers. Results were evaluated with a leave-one-out cross-validation analysis. RESULTS: We compared the AUC for all the pipelines in the validation dataset using FeAture Explorer (FAE) software. The pipeline using RFE feature selection and Gaussian process classifier yielded the highest AUCs with ten features. When the "one-standard error" rule was used, FAE produced a simpler model with eight features, including Perc.01%, Perc.10%, Perc.90%, Perc.99%, S(1,0) SumAverg, S(5,5) AngScMom, S(5,5) Correlat, and WavEnLH_s-2. The AUCs of the training, validation, and test datasets achieved 0.995, 0.902, and 0.710, respectively. For ANOVA, the pipeline with the auto-encoder classifier yielded the highest AUC using only one feature, Perc.10% (training/validation/test datasets: 0.886/0.895/0.809, respectively). For the relief, the AUCs of the training, validation, and test datasets that used the LRLasso classifier using five features (Perc.01%, Perc.10%, S(4,4) Correlat, S(5,0) SumAverg, S(5,0) Contrast) were 0.892, 0.886, and 0.787, respectively. Compared with the RFE and relief, the results of all algorithms of ANOVA feature selection were more stable with the AUC values higher than 0.800. CONCLUSIONS: We demonstrated the feasibility of combining artificial intelligence with the radiomics from ADC values in the differential diagnosis of SRCMTs and non-SRCMTs and the potential of this non-invasive approach for clinical applications. KEY POINTS: • The parameter with the best diagnostic performance in differentiating SRCMTs from non-SRCMTs was the Perc.10% ADC value. • Results of all the algorithms of ANOVA feature selection were more stable and the AUCs were higher than 0.800, as compared with RFE and relief. • The pipeline using RFE feature selection and Gaussian process classifier yielded the highest AUC.