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Experimental Evaluation Of Radiation-induced Heart Disease And Prognosis Of Cancer Patients By Speckle Tracking Imaging Technique And LncRNA799

Posted on:2020-12-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:L M LiaoFull Text:PDF
GTID:1364330575999214Subject:Imaging and nuclear medicine
Abstract/Summary:PDF Full Text Request
Part Ⅰ:Experimental study on Quantitative Evaluation of Radiation-induced Heart Disease by Speckle Tracking Imaging Technique.Section Ⅰ:Quantitative Evaluation of Left Ventricular Systolic Function Changes after Local Irradiation in Beagle Dogs by Two-dimensional Speckle Tracking Imaging Technique.Objective:The early changes of left ventricular systolic function after local irradiation in beagle dogs were quantitatively evaluated by two-dimensional speckle tracking imaging(2D-STI)technique,and the potential value of 2D-STI in monitoring radioactive heart injury(RIHD)was discussed.Methods:1.36 healthy one-year-old beagle dogs were randomly divided into control group(18 dogs)and irradiation group(18 dogs).Single 20Gy precise irradiation was given to the anterior wall myocardium of the left ventricle of the beagle dogs in the irradiation group,and virtual irradiation was given to the myocardium of the same part of the beagle dogs in the control group.2.Routine echocardiography and 2D-STI examination were performed on beagle dogs in the two groups at four time points of 1 week before and 3,6 and 12 months after cardiac irradiation.At the same time,blood samples of small cryptic vein outside the hind limbs of dogs were collected to detect the concentration of cardiac troponin I(cTnI),a molecular marker of myocardial injury.3.At the end of each ultrasound examination,6 beagles were randomly selected from the control group and the irradiation group to be sacrificed.The myocardium in the irradiation group and the same segment of the myocardium in the control group were taken,and the morphological changes of myocardium before and after irradiation were observed by hematoxylin-eosin(HE)staining.Morphological changes of myocardial cells were observed by wheat embryo lectin(WGA)staining before and after irradiation.Myocardial fibrosis was observed by Masson staining.The changes of myocardial microvascular density were observed by CD34 immunohistochemical staining.4.The 2D-STI analysis software in EchoPAC workstation was used to quantitatively analyze the changes of left ventricular myocardial with overall longitudinal strain(GLS)and longitudinal strain(LS)of each segment.Compare the changes of left ventricular myocardial histopathology during the same period,so as to clarify the value of early detection of RIHD left ventricular systolic dysfunction by 2D-STI.Results:1.Before,3 months and 6 months after irradiation,there was no significant difference in body weight between the irradiation group and the control group.At 12 months after irradiation,the body weight of beagle dogs in the irradiation group was significantly lower than that of the control group,with poor diet,activity and mental state,and rough and dull hair.2.At 3 months after irradiation,there was no significant change in conventional ultrasonic measurement parameters(including LVEF of left ventricular systolic function)in the irradiation group.The 2D-STI results showed that in the irradiation group,LS was decreased in the left ventricular irradiation region and adjacent regions,and GLS in the left ventricle was also decreased,indicating decreased systolic function of the left ventricle.There was no significant difference in serum cTnI concentration between the irradiation group and the control group.The synchronous pathology showed that the myocardial cells in the irradiation group showed mild morphological abnormality,a small amount of interstitial fibrosis,mild fibrosis of small vascular wall,and slightly increased microvascular density in the interstitial myocardial cells.3.At 6 months after irradiation,part of conventional ultrasonic measurement parameters in the irradiation group changed,with an increase in LVESV,a change in LVEDV,and a decrease in LVEF.The 2D-STI results showed that the LS and GLS of multiple segmental myocardium in the left ventricular irradiation region and adjacent regions of the irradiation group were further decreased.There was no significant difference in serum cTnI concentration between the irradiation group and the control group.The synchronous pathology showed that the myocardial cells in the irradiated area had obvious degeneration,increased volume and disordered arrangement,moderate interstitial fibrous tissue hyperplasia,thickened small vascular wall and decreased microvascular density in the interstitial myocardium.4.At 12 months after irradiation,LVEDV and LVESV of conventional ultrasound measurement parameters in the irradiation group was increased,LVEF was decreased more significantly,and local ventricular wall activity was decreased in the left ventricular irradiation area and adjacent areas.The 2D-STI results showed that LS and GLS in the left ventricular myocardial strain were decreased further in the irradiation group.There was no significant difference in serum cTnI concentration between the irradiation group and the control group.The synchronous pathology showed that the myocardial cells in the irradiated area showed patchy necrosis,diffuse interstitial fibrosis,significantly thickened small blood vessel wall,Unsmooth inner wall and narrow lumen,and further reduced density of interstitial microvessels.Conclusion:1.Serum cTnI,a marker of myocardial injury,could not reflect the situation of delayed RIHD myocardial injury.2.2D-STI can detect the change of RIHD left ventricular systolic function at an early stage before conventional echocardiography detects the change of left ventricular morphology,ventricular wall movement and LVEF.3.The 2D-STI technique can early detect the reduced left ventricular myocardial longitudinal strain region consistent with the irradiation region,and can be used as a method for early diagnosis and monitoring of RIHD.Section Ⅱ:Quantitative Evaluation of Early Changes of Left Ventricular Systolic Function in Patients with Lung Cancer after Radiotherapy by Three-Dimensional Speckle Tracking ImagingObjective:The early changes of left ventricular systolic function in patients with lung cancer after radiotherapy were quantitatively evaluated by three-dimensional speckle tracking imaging(3D-STI)technique,and the clinical value of 3D-STI in monitoring RIHD was discussed.Methods:1.According to the inclusion and exclusion criteria,lung cancer patients who received the first radiotherapy in our hospital from December 2016 to December 2017 were recruited as the research objects.2.Routine echocardiography and 3D-STI examination were performed in all lung cancer patients before radiotherapy,at 2.5 to 3 weeks(radiation dose 25-33gy),at 5 to 6 weeks(radiation dose 50-66gy),and at 3,6 and 12 months after radiotherapy Routine ECG examination and serum cTnI concentration were performed simultaneously.3.The dynamic changes of left ventricular overall longitudinal strain(GLS),global radial strain(GRS),global peripheral strain(GCS)and global strain(GS)were quantitatively analyzed using the 3D-STI analysis software in Tom-tec workstation.Meanwhile,the changes of ECG and serum cTnI concentration were compared to explore the clinical application value of 3D-STI of RIHD early diagnosis.Results:1.A total of 55 patients with lung cancer radiotherapy were included in the study.All patients successfully completed the radiotherapy plan and completed routine ECG,routine echocardiography,3D-STI and serum cTnI data at each time point.Seven patients lost follow-up at3 months after radiotherapy,11 patients lost follow-up at 6 months after radiotherapy,and 15 patients lost follow-up 12 months after radiotherapy.2.The measured values of conventional echocardiography parameters(including left ventricular systolic function index LVEF)were not significantly changed before radiotherapy,3 months,6 months and 12 months after radiotherapy.However,at 5-6 weeks after radiotherapy,a small amount of pericardial effusion was found in 3 patients(3/55),presenting as acute RIHD.After clinical symptomatic treatment,all of them were absorbed at 3 months after radiotherapy.3.3D-STI results showed no significant changes in left ventricular myocardium GLS,GRS,GCS and GS at 2.5-3 weeks after radiotherapy compared with that before radiotherapy.GLS and GS of left ventricular myocardium were decreased at 5-6 weeks after radiotherapy,and the difference was statistically significant.The absolute values of GLS,GRS,GCS and GS of left ventricular myocardium were significantly lower than those before radiotherapy at 3,6 and 12 months after radiotherapy,suggesting decreased left ventricular systolic function in lung cancer patients after radiotherapy.4.Electrocardiogram results showed that 15 cases(15/55)of lung cancer patients presented ECG abnormalities during the course of radiotherapy and 1 case(1/55)3 months after the end of radiotherapy,and most cases(11/16)returned to normal within 3 months after the end of radiotherapy.The results of serum cTnI showed that the serum cTnI was increased in patients at 2.5 to 3 weeks and 5 to 6 weeks after radiotherapy,and the difference was statistically significant.Serum cTnI returned to normal at 3,6 and 12 months after radiotherapy.Conclusion:1.3D-STI technology can detect subclinical changes of RIHD left ventricular systolic function before routine echocardiography.2.Abnormal ECG,elevated serum cTnI and routine echocardiography had certain clinical value in the diagnosis of acute RIHD,but were not sensitive to delayed RIHD.3.STI is of more clinical value in the early diagnosis of tardy RIHD.Both 2D-STI and 3D-STIcan be used as new methods for non-invasive early detection of RIHD in clinical practice.Part Ⅱ:Experimental Evaluation on Prognosis of Cervical Cancer Patients by LncRNA799Objective:1.Clear LncRNA799 expression in cervical cancer.2.Clear the relationship between LncRNA799 expression and prognosis of patients with cervical cancer.Methods:1.Collect cervical cancer postoperative carcinoma tissue and corresponding beside tissue samples.2.Detection the expression of LncRNA799 in cervical cancer and adjacent tissue by Real-Time RT-PCR.3.Analysis the relationship between LncRNA799 expression,clincopathologic characteristics and prognosis of cervical cancer patients.Results:1.LncRNA799 expression was significantly upregulated in cancerous tissues compared with the corresponding normal tissues(P<0.001).LncRNA799 expression was significantly higher in patients with lymph node metastasis(P<0.0001).2.Survival analysis showed that patients with higher IncRNA799 expression had poorer overall survival(P=0.004)and disease-free survival(P=0.016)compared with patients with lower lncRNA799 expression.3.High lncRNA799 expression was found to be significantly correlated with International Federation of Gynecology and Obstetrics(FIGO)stage(P=0.014),SCC-Ag level(P=0.015),and lymphatic metastasis(P<0.0001),but it was not correlated with age,degree of differentiation of the tumor,size of the tumor,depth of tumor invasion,or invasion of the uterine corpus(P>0.05).Conclusion:1.LncRNA799 expression was significantly upregulated in cervical cancer.2.LncRNA799 expression was significantly higher in patients with lymph node metastasis.3.LncRNA 799 high expression indicated that cervical cancer patients with poor prognosis.
Keywords/Search Tags:radiation-induced heart disease, two-dimensional speckle tracking imaging, left ventricular, three-dimensional speckle tracking imaging, LncRNA 799, cervical cancer, prognosis
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