Objective To investigate the application of cardiovascular magnetic resonance feature tracking(CMR-FT)in assessing myocardial strain in dilated cardiomyopathy(DCM)patients residing at high altitudes.Methods We retrospectively enrolled 29 DCM patients living at high altitudes(DCM-H),27 DCM patients living in a low-altitude plain environment(DCM-P),23 healthy volunteers living at a high altitude(HV-H),and 24 healthy volunteers living in a low-altitude plain environment(HV-P).All subjects underwent cine MRI scanning using a 3.0T rapid steady-state free precession sequence.The CMR images thus acquired were analyzed using cvi42,a post-processing software,to obtain left ventricular function and myocardial strain parameters.Results Compared with the HV-H group,the DCM-H group showed higher left ventricle end-diastolic volume(LVEDV)and left ventricle end-systolic volume(LVESV),and lower left ventricular ejection fraction(LVEF)and stroke volume(LVSV)(all P＜0.01).No significant difference was observed in cardiac function between the DCM-H and DCM-P groups(all P＞0.05).The absolute values of global radial strain(GRS),global circumferential strain(GCS),and global longitudinal strain(GLS)in the DCM-H group were lower than those in the HV-P group([14.5±6.5]％vs.[34.2±10.7]％,[-11.1±4.4]％vs.[-19.9±2.8]％,and[-7.7±3.2]％vs.[-13.6±4.1]％,respectively),with the differences being statistically significant(all P＜0.001).The DCM-H group had higher absolute GRS,GCS,and GCS values than the DCM-P group did([14.5±6.5]％vs.[7.0±2.7]％,[-11.1±4.4]％vs.[—5.4±2.2]％,and[—7.7±3.2]％vs.[—4.3±1.7]％,respectivley,all P＜0.01).Conclusion Myocardial strain in DCM patients living at a high altitude is lower than that in healthy volunteers living at a high altitude,but higher than that in DCM patients living in a low-altitude plain environment.CMR-FT can be used to quantitatively assess myocardial contractility in DCM patients living at a high altitude,showing promise for clinical application.

Purpose To investigate the application value of cardiac magnetic resonance tissue tracking imaging in assessing early heart failure(HF)in plateau environment.Materials and Methods Thirty male SD rats were randomly divided into 10 in the control group and 20 in the experimental group.The rats in the experimental group were transported to the Qinghai Plateau laboratory(average altitude 4 250 metre)for eight weeks of exposure,and then divided into the plateau hypoxia group and the plateau HF group,and the HF group was treated with 5 mg/ml Isoprenaline 10 mg/(kg·d)subcutaneously for 14 consecutive days to establish a HF rat model.The rats were then transported back to the plains(average elevation 500 metre)for 7T cardiac magnetic resonance movie sequence scanning.Cardiac function parameters and myocardial strain parameters were obtained using CVI 42 software.Myocardial pathological changes were detected using HE staining and Masson trichrome staining.Serum levels of malondialdehyde and glutathione peroxidase were detected by enzyme-linked immunosorbent assay.Western blot and PCR were used to detect the expression of nuclear factor-E2-related factor 2(NRF2)and heme oxygenase 1(HO-1)in myocardial tissues.Results Left ventricular ejection fraction was reduced in the HF group compared with the control group[(67.06±4.66)%vs.(61.91±2.11)%;F=4.149,P=0.037],and overall left ventricular circumferential strain was significantly reduced in the HF group compared with the control group[(-24.60±0.81)%vs.(-20.16±1.86)%;F=12.241,P=0.001],and pathologic staining showed necrosis as well as interstitial fibrosis in cardiomyocytes.Enzyme-linked immunosorbent assay results showed decreased glutathione peroxidase levels in the HF group[(1 079.94±70.58)U vs.(311.99±39.47)U;F=209.294,P=0.001]and increased malondialdehyde in the HF group compared with those in the control group[(7.24±2.48)μmol/L vs.(53.28±4.51)μmol/L;F=156.39,P=0.010).Western blot results showed significantly lower NRF2 and HO-1 expression in myocardial tissues of the HF group compared with those in the control group(1.00±0.00 vs.0.52±0.13;F=26.607,P=0.001).PCR results showed significantly lower NRF2 and HO-1 mRNA expression in myocardial tissues of the HF group compared with those in the control group(1.19±0.16 vs.0.31±0.07;F=84.784,P=0.010).Conclusion Magnetic resonance tissue tracking imaging can be used for early assessment of HF caused by plateau environment.

Purpose To quantitatively evaluate myocardial three-dimensional strains using cardiac magnetic resonance feature tracking,investigate whether ferroptosis contributes to myocardial injury in experimental autoimmune myocarditis(EAM),and explore the relationship between strains and ferroptosis biomarkers.Materials and Methods EAM was induced in Lewis rats via subcutaneous injections with porcine cardiac myosin emulsified in same amount of complete Freund's adjuvant.Both EAM(n=15)and control(n=15)rats underwent 7T cardiac magnetic resonance and were euthanatized at day 21.Cardiac magnetic resonance assessments included left ventricular function and strains.The cardiac damage and ferroptosis-related markers were measured with histopathology,serology,Western blot and polymerase chain reaction.Results The left ventricular ejection fraction declined in the rats post-immunization with porcine cardiac myosin at day 21(t=7.86,P<0.001).Global,basal,middle and apical strains encompassing radial strain,circumferential strain and longitudinal strain were significantly lower in the EAM group compared to the control group(t=2.61-10.45,P<0.05).Cardiac and inflammatory biomarkers,including lactate dehydrogenase,cardiac troponin I and interferon γ indicated myocardial injury in EAM group compared to the control group(t=16.54,21.20,16.06,all P<0.001).Prussian blue staining revealed iron overload in EAM group.Compared to the control group,malondialdehyde and reactive oxygen significantly increased in EAM group(t=15.75,3.47,both P<0.01),and superoxide dismutase were significantly decreased(t=14.21,P<0.001).Western blot and histopathology showed that the protein expression of ferritin heavy chain was significantly higher in the EAM group compared to the control group(t=5.15,P<0.01).The solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 axis was down regulated at serum,mRNA and protein expression levels in EAM group(t=7.73-30.14,all P<0.001).Global circumferential and longitudinal strains were significantly associated with ferroptosis biomarkers(r=-0.854-0.829,all P<0.05).Conclusion Cardiac magnetic resonance feature tracking has the potential to quantitatively evaluate myocardial damage of EAM which involves ferroptosis.The strains are related with ferroptosis biomarkers.

Purpose To explore the application value of magnetic resonance feature tracking to assess early heart failure in different rat models.Materials and Methods Fifty male SD rats were randomly divided into four groups:the control group(8 rats),the isoproterenol high dose(ISO-H)group(14 rats),the isoproterenol low dose(ISO-L)group(14 rats)and the coronary artery ligation surgery(myocardial infarction,MI)group(14 rats).The ISO-H group received intraperitoneal injections of ISO at 100 mg/kg once a week for two consecutive weeks.The ISO-L group received continuous intraperitoneal injections of ISO at 5 mg/(kg·d)for 14 days.The MI group underwent coronary ligation to establish a heart failure rat model.Scans using a 7T cardiac MRI cine sequence were performed after two weeks and four weeks.Heart function parameters and myocardial strain parameters were obtained using CVI 42 software.Serum markers of myocardial injury,including creatine kinase,creatine kinase-MB,lactate dehydrogenase and α-hydroxybutyric dehydrogenase levels,were measured.HE staining and Masson staining were used to detect myocardial pathological changes.Results Compared with the control group,the ISO-H group,ISO-L group and MI group showed significant changes in left ventricular ejection fraction(t=-2.387,P=0.04;t=5.622,P<0.001;t=17.715,P<0.001)and overall radial strain(t=-4.570,P=0.001;t=6.587,P<0.001;t=10.649,P<0.001)after two weeks.Compared with the control group,the ISO-H group,ISO-L group and MI group showed varying degrees of reduction in left ventricular ejection fraction(t=4.834,P=0.001;t=10.325,P<0.001;t=26.286,P<0.001)and overall radial strain(t=3.890,P=0.003;t=9.547,P<0.001;t=13.751,P<0.001)after four weeks.The serum markers of myocardial injury,including creatine kinase,creatine kinase-MB,lactate dehydrogenase and α-hydroxybutyric dehydrogenase levels,were significantly elevated(t=-93.373--11.019,P<0.001),and pathological staining revealed that all model groups exhibited varying degrees of myocardial cell hypertrophy,necrosis and interstitial fibrosis compared with the control group.Conclusion Magnetic resonance feature tracking has guiding significance for the dynamic monitoring,early diagnosis and prognosis assessment of heart failure in different rat models.

Purpose To investigate the application value of cardiac magnetic resonance tissue tracking imaging in assessing early heart failure(HF)in plateau environment.Materials and Methods Thirty male SD rats were randomly divided into 10 in the control group and 20 in the experimental group.The rats in the experimental group were transported to the Qinghai Plateau laboratory(average altitude 4 250 metre)for eight weeks of exposure,and then divided into the plateau hypoxia group and the plateau HF group,and the HF group was treated with 5 mg/ml Isoprenaline 10 mg/(kg·d)subcutaneously for 14 consecutive days to establish a HF rat model.The rats were then transported back to the plains(average elevation 500 metre)for 7T cardiac magnetic resonance movie sequence scanning.Cardiac function parameters and myocardial strain parameters were obtained using CVI 42 software.Myocardial pathological changes were detected using HE staining and Masson trichrome staining.Serum levels of malondialdehyde and glutathione peroxidase were detected by enzyme-linked immunosorbent assay.Western blot and PCR were used to detect the expression of nuclear factor-E2-related factor 2(NRF2)and heme oxygenase 1(HO-1)in myocardial tissues.Results Left ventricular ejection fraction was reduced in the HF group compared with the control group[(67.06±4.66)%vs.(61.91±2.11)%;F=4.149,P=0.037],and overall left ventricular circumferential strain was significantly reduced in the HF group compared with the control group[(-24.60±0.81)%vs.(-20.16±1.86)%;F=12.241,P=0.001],and pathologic staining showed necrosis as well as interstitial fibrosis in cardiomyocytes.Enzyme-linked immunosorbent assay results showed decreased glutathione peroxidase levels in the HF group[(1 079.94±70.58)U vs.(311.99±39.47)U;F=209.294,P=0.001]and increased malondialdehyde in the HF group compared with those in the control group[(7.24±2.48)μmol/L vs.(53.28±4.51)μmol/L;F=156.39,P=0.010).Western blot results showed significantly lower NRF2 and HO-1 expression in myocardial tissues of the HF group compared with those in the control group(1.00±0.00 vs.0.52±0.13;F=26.607,P=0.001).PCR results showed significantly lower NRF2 and HO-1 mRNA expression in myocardial tissues of the HF group compared with those in the control group(1.19±0.16 vs.0.31±0.07;F=84.784,P=0.010).Conclusion Magnetic resonance tissue tracking imaging can be used for early assessment of HF caused by plateau environment.

Purpose To quantitatively evaluate myocardial three-dimensional strains using cardiac magnetic resonance feature tracking,investigate whether ferroptosis contributes to myocardial injury in experimental autoimmune myocarditis(EAM),and explore the relationship between strains and ferroptosis biomarkers.Materials and Methods EAM was induced in Lewis rats via subcutaneous injections with porcine cardiac myosin emulsified in same amount of complete Freund's adjuvant.Both EAM(n=15)and control(n=15)rats underwent 7T cardiac magnetic resonance and were euthanatized at day 21.Cardiac magnetic resonance assessments included left ventricular function and strains.The cardiac damage and ferroptosis-related markers were measured with histopathology,serology,Western blot and polymerase chain reaction.Results The left ventricular ejection fraction declined in the rats post-immunization with porcine cardiac myosin at day 21(t=7.86,P<0.001).Global,basal,middle and apical strains encompassing radial strain,circumferential strain and longitudinal strain were significantly lower in the EAM group compared to the control group(t=2.61-10.45,P<0.05).Cardiac and inflammatory biomarkers,including lactate dehydrogenase,cardiac troponin I and interferon γ indicated myocardial injury in EAM group compared to the control group(t=16.54,21.20,16.06,all P<0.001).Prussian blue staining revealed iron overload in EAM group.Compared to the control group,malondialdehyde and reactive oxygen significantly increased in EAM group(t=15.75,3.47,both P<0.01),and superoxide dismutase were significantly decreased(t=14.21,P<0.001).Western blot and histopathology showed that the protein expression of ferritin heavy chain was significantly higher in the EAM group compared to the control group(t=5.15,P<0.01).The solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 axis was down regulated at serum,mRNA and protein expression levels in EAM group(t=7.73-30.14,all P<0.001).Global circumferential and longitudinal strains were significantly associated with ferroptosis biomarkers(r=-0.854-0.829,all P<0.05).Conclusion Cardiac magnetic resonance feature tracking has the potential to quantitatively evaluate myocardial damage of EAM which involves ferroptosis.The strains are related with ferroptosis biomarkers.

Purpose To explore the application value of magnetic resonance feature tracking to assess early heart failure in different rat models.Materials and Methods Fifty male SD rats were randomly divided into four groups:the control group(8 rats),the isoproterenol high dose(ISO-H)group(14 rats),the isoproterenol low dose(ISO-L)group(14 rats)and the coronary artery ligation surgery(myocardial infarction,MI)group(14 rats).The ISO-H group received intraperitoneal injections of ISO at 100 mg/kg once a week for two consecutive weeks.The ISO-L group received continuous intraperitoneal injections of ISO at 5 mg/(kg·d)for 14 days.The MI group underwent coronary ligation to establish a heart failure rat model.Scans using a 7T cardiac MRI cine sequence were performed after two weeks and four weeks.Heart function parameters and myocardial strain parameters were obtained using CVI 42 software.Serum markers of myocardial injury,including creatine kinase,creatine kinase-MB,lactate dehydrogenase and α-hydroxybutyric dehydrogenase levels,were measured.HE staining and Masson staining were used to detect myocardial pathological changes.Results Compared with the control group,the ISO-H group,ISO-L group and MI group showed significant changes in left ventricular ejection fraction(t=-2.387,P=0.04;t=5.622,P<0.001;t=17.715,P<0.001)and overall radial strain(t=-4.570,P=0.001;t=6.587,P<0.001;t=10.649,P<0.001)after two weeks.Compared with the control group,the ISO-H group,ISO-L group and MI group showed varying degrees of reduction in left ventricular ejection fraction(t=4.834,P=0.001;t=10.325,P<0.001;t=26.286,P<0.001)and overall radial strain(t=3.890,P=0.003;t=9.547,P<0.001;t=13.751,P<0.001)after four weeks.The serum markers of myocardial injury,including creatine kinase,creatine kinase-MB,lactate dehydrogenase and α-hydroxybutyric dehydrogenase levels,were significantly elevated(t=-93.373--11.019,P<0.001),and pathological staining revealed that all model groups exhibited varying degrees of myocardial cell hypertrophy,necrosis and interstitial fibrosis compared with the control group.Conclusion Magnetic resonance feature tracking has guiding significance for the dynamic monitoring,early diagnosis and prognosis assessment of heart failure in different rat models.

Objective To establish a hypobaric hypoxia rat model in a real high-altitude environment,to investigate the effects of the real high-altitude environment on rat bone mass and bone microstructure using multiple methods such as Micro CT,blood biochemistry,and pathology,and to explore the potential mechanisms involved.Methods Sprague Dawley(SD)rats were transported to the Yushu Plateau Laboratory(at 4250 m above sea level)in Qinghai Province and kept there for 4,or 8,or 18 months.These groups were designated as H-4,H-8,and H-18,respectively.Upon completion of the high-altitude exposure,these animals were transported to the Molecular Imaging Laboratory,West China Hospital,Sichuan University(at 500 m above sea level)in Chengdu for relevant testing and comparison with the control animals raised in a low-altitude environment for the same durations(designated L-4,L-8,and L-18).The tests performed included blood biochemistry,Micro CT imaging,and pathological assessments such as ELISA,Western blot,and HE and TRAP staining.Results Compared with that of the control group,the body mass of rats in the H-4 and H-18 groups decreased significantly(H-4 group vs.L-4 group:[513.75±35.10]g vs.[649.18±60.03]g,P＜0.01;H-18 group vs.L-18 group:[535.58±66.65]g vs.[670.86±44.96]g,P＜0.01).The serum Ca2+concentration was higher in the H-8 group and H-18 group compared to that in the control group(H-8 group vs.L-8 group:[2.48±0.09]mmol/L vs.[2.38±0.07]mmol/L,P＜0.05;H-18 group vs.L-18 group:[2.55±0.11]mmol/L vs.[2.13±0.27]mmol/L,P＜0.05).No statistically significant difference was observed in the concentration of P3+.Bone metabolism indicator cross-linked carboxy-terminal telopeptide of type Ⅰ collagen(CTX-Ⅰ)was significantly increased in all high-altitude groups compared to the low-altitude groups(H-4 group vs.L-4 group:[1.44±0.08]ng/mL vs.[0.70±0.13]ng/mL,P＜0.01;H-8 group vs.L-8 group:[1.52±0.10]ng/mL vs.[0.75±0.10]ng/mL,P＜0.01;H-18 group vs.L-18 group:[2.70±0.13]ng/mL vs.[1.94±0.15]ng/mL,P＜0.01).In addition,CT results showed a decrease in bone volume fraction of trabecular bone in the three high-altitude groups(H-4 group vs.L-4 group:[7.48±2.35]％vs.[10.40±2.93]％,P＜0.05;H-8 group vs.L-8 group:[7.17±2.68]％vs.[10.09±2.95]％,P＜0.05;H-18 group vs.L-18 group:[2.90±2.91]％vs.[8.68±4.11]％,P＜0.01),and increased trabecular separation in the three high-altitude groups(H-4 group vs.L-4 group:[0.70±0.12]mm vs.[0.60±0.06]mm,P＜0.05;H-8 group vs.L-8 group:[0.68±0.07]mm vs.[0.59±0.05]mm,P＜0.01;H-18 group vs.L-18 group:[0.80±0.09]mm vs.[0.70±0.09]mm,P＜0.05).TRAP staining showed an increase in osteoclasts in the H-4 and H-18 groups.Western blot results indicated an increase in the expression of receptor activator of nuclear factor-κB ligand(RANKL)and hypoxia inducible factor-1α(HIF-1α)in high-altitude environment,while the expression of osteoprotegerin(OPG)was inhibited.Conclusion The impact of high-altitude environment on rat femurs is characterized primarily by a reduction in trabecular bone mass and damage to bone microstructure.

Objective To explore the therapeutic effect of Cang-ai volatile oil(CAVO)on rats with myocardial hypertrophy(MH)exposed to the hypobaric hypoxic environment of the Qinghai-Tibet Plateau using 7.0-tesla(7.0T)cardiac magnetic resonance imaging(CMR).Methods A total of 50 male specific pathogen-free(SPF)Sprague-Dawley(SD)rats were randomly assigned to a low-altitude control(CON)group,hypobaric hypoxia(HH)group,myocardial hypertrophy modeling(MH)group,MH modeling plus CAVO treatment(MH+CAVO)group,and MH modeling plus benadryl hydrochloride treatment(MH+RX)group,with 10 rats in each group.Except for the CON group,the rats in all the groups were kept and fed in the standard way for 8 weeks in a high-altitude environment(at 4250 m above sea level),and then given the corresponding treatment drugs by gastric gavage.Afterwards,7.0T high field strength CMR was used to measure left ventricular(LV)function and myocardial strain.Hematoxylin-eosin(HE)staining and Masson staining were performed to observe myocardial interstitial fibrosis.Wheat germ agglutinin(WGA)staining was performed to analyze the cross-sectional area of cardiomyocytes.Transmission electron microscopy was used to observe the ultrastructural changes of the myocardium.Serum levels of cardiac troponin T(cTnT),superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-PX)were measured by ELISA.Results Compared with those of the control group,the MH group had significantly lower left ventricular global circumferential strain(LVGCS)at(-18.85±1.67)％and left ventricular global longitudinal strain(LVGLS)at(-20.39±1.48)％(P＜0.05).However,the MH+CAVO group had significantly higher LVGCS at(-22.10±1.08)％and LVGLS at(-24.60±1.72)％compared with those of the MH group(both P＜0.05),indicating that CAVO treatment improved LV function.The MH group had a decreased level of serum glutathione peroxidase(GSH-Px)in comparison with the CON group([1173.49±27.10]U/mL vs.[300.83±47.25]U/mL,P＜0.01),a decreased SOD level in comparison with the CON group([302.27±3.65]U/mL vs.[105.96±4.03]U/mL,P＜0.01),and an increased level of serum malondialdehyde(MDA)in comparison with the CON group([57.91±1.13]μmol/L vs.[6.65±2.99]μmol/L,P＜0.01),suggesting that the antioxidant capacity of rats in the MH group was decreased.After CAVO intervention,rats in the MH+CAVO group exhibited an increase in the serum levels of SOD at(278.51±5.97)U/mL and GSH-Px at(961.82±17.56)U/mL,as well as a decrease in MDA at(17.79±1.33)μmol/L(all P＜0.05).Conclusion CAVO can effectively improve cardiac function in rats with cardiac hypertrophy exposed to high-altitude environment by modulating oxidative stress and ameliorating cardiac hypertrophy.

Purpose To explore the cardioprotective effect of cang-ai volatile oil(CAVO)on rats with cardiac function impairment model under low-pressure and low-oxygen environment in Tibet Plateau based on 7.0T cardiovascular magnetic resonance(CMR)imaging.Materials and Methods Forty SD rats were randomly divided into the normal group,the high altitude model group,the CAVO-treated group and the rhodiola rosea-treated group,with 10 rats in each group.Except for the normal group,the rats in other groups were transferred from the plain(500 m above sea level)to the Tibet Plateau(4 250 m above sea level)for two months,and then administered with the corresponding drugs by gavage for 14 d.The left ventricle function was measured by using a 7.0T high-field strength CMR and myocardial strain was analysed by using tissue tracing technique.HE staining was used to observe the morphology of cardiomyocytes,Masson staining to observe interstitial fibrosis,wheat germ agglutinin staining to observe cardiomyocyte hypertrophy,and transmission electron microscopy to observe the morphological changes of mitochondria in each group.Serum levels of creatine kinase,creatine kinase isoenzyme,lactate dehydrogenase,cardiac troponin T,superoxide dismutase,malondialdehyde and glutathione peroxidase were detected.Intracellular reactive oxygen species levels were detected using flow cytometry.Results The left ventricular ejection fraction of rats in the CAVO-treated group was higher than that of the high altitude model group[(66.61±1.38)％vs.(60.94±3.21)％;t=3.969,P=0.032];meanwhile,the global circumferential strain of the left ventricle in the CAVO-treated group was higher than that of the high altitude model group(-25.68±1.30 vs.-22.84±1.17;t=3.967,P=0.003).HE,Masson and wheat germ agglutinin staining showed hypertrophy and necrosis as well as interstitial fibrosis and ultrastructural disruption of cardiomyocytes in the high altitude model group,which improved after CAVO treatment.The level of cardiac troponin T in the serum of rats with CAVO treatment group was significantly decreased compared with that of the high altitude model group[(314.03±20.05)pg/ml vs.(518.30±18.13)pg/ml;1=13.090,P=0.001].Conclusion CAVO treatment can reduce cardiac injury caused by low-pressure hypoxia in high altitude,and its effect can be detected dynamically and non-invasively by 7.0T high-field strength CMR.