Intervention Ultrasound Indentation System And Its Application For Detecting Myocardium Stiffness

Tissue stiffness usually changed with different pathologic situations. Detection of tissue stiffness in vivo could be contributed to clinical diagnosis and assessment of pathologic state. Up to now, ultrasound indentation technique has been widely used for assessing for the stiffness of tissue including residual limbs, diabetic feet, fibrotic neck induced by radiotherapy, spinae , and articular cartilage, which indicated that the technique can provide a quantitative measurement of tissue stiffness. Compared with palpation method , ultrasound indentation technique could determine the material property of pathologic tissue in vivo or in situ and then more precise quantitative data about pathologic state can be acquired. Actually, stiffness change in most of pathologic tissue occured at deep coelom. However, tissue stiffness instruments invented were not suitable for detecting stiffness of coelom-tissue, especially the cardiovascular system. The change of myocardium stiffness could influenced systolic and/or diastolic function, especially increased ventricular passive stiffness would result into diastolic dysfunction and then deteriorate to diastolic heart failure. Consequently it was vital to assess for local myocardium stiffness. So far, there was no direct and reliable way of detecting myocardium stiffness. So the study was engaged to design an apparatus for detecting myocardium stiffness in vivo and explore its feasibility further more.PART I DEVELOPMENT OF INTERVENTIONAL ULTRASOUND INDENTATION SYSTEMObjective: To develop an intervention ultrasound indentation system for quantitative measurement of myocardium stiffness.Idea: The system was composed of an intervention ultrasound stiffness detection catheter(ultrasound catheter) ,ECG preamplifier and mainframe. Ultrasound catheter (Diameter :7F) with balloon and ultrasound mini-transducer fixed on its head and pressure transducer linked to its tail passed through peripheral artery into chambers heart and indented ventricle wall. Balloon offered direct pressure, ultrasound mini-transducer detected ventricle wall thickness during indentation , and pressure transducer measured balloon pressure . ECG preamplifier provided electrocardiogram and at same time offered time reference point for indentation and data analysis. Mainframe can show, saved, analyze and measure the images of stress , strain, and electrocardiogram .According to strain-stress relation ,stiffness value reflecting mechanical properties of myocardium tissue was gained.Results: The ultrasound catheter had been successfully used for the measurement of thickness and pressure of phantom. ECG amplifier was able to provide surface electrocardiogram, with myocardium thickness displayed by M-type ultrasound, pressure wave showed by curves, and electrocardio-signals demonstrated by surface electrocardiogram.Conclusion: Interventional ultrasound indentation system was able to provide strain-stress data and electrocardio-signals ,meanwhile it was also able to display,save,and analyze strain,deformation and electrocardiogram,which satisfied expecting design requirement .This system made it possible to assess the myocardium tissue stiffness in vivo .PARTⅡAN EXPERIMENTAL STUDY ON ASSESSMENT OF ELASTICITY PHANTOMS STIFFNESS BY INTERVENTION ULTRASOUND INDENTION SYSTEMObjective : To explore the feasibility and accurate of interventional ultrasound indention system detecting phantoms stiffness.Methods: The different stiffness phantoms were made and Young's modulus measured by a uniaxial compression trial was regarded as a standard. Calibration was conducted between actual indentation pressure of three kinds of balloons (Diameter: 4.72mm,5.3mm,7.0mm) and tested indentation pressure. These balloons were applied for detecting the same stiffness phantom respectively and then the different stiffness phantoms were tested by a balloon (Diameter: 4.72mm) and at last the different stiffness phantoms inserted cardiac model were also assessed by a balloon (Diameter: 4.72mm)Results: These phantoms Young's module measured by uniaxial compression trial were (21.8±5.1) kPa, (44.8±7.1) kPa, (85.2±7.7) kPa respectively and calibrating regression coefficient were 0.62, 0.78, 0.98, respectively. Stiffness value of the same stiffness phantom measured by different diameter balloons were (86.1±15.0) kPa, (87.2±18.0)kPa and (82.9±14.9)kPa respectively, there were no strikingly difference (P>0.05).Stiffness value of the phantom with different stiffness assessed by balloon with same diameter were (45.5±5.7 )kPa, (86.1±15.0)kPa and (117.9±10.9) kPa respectively, there was significant difference (P<0.05)and correlation coefficient between these value and Young's modulus was 0.94( r=0.94,P<0.05) and at the same time these value were also consistent with Bland-Altman curve。Stiffness values of phantom fixed heart model indented were (47.7±7.9) kPa, (89.3±17.3)kPa and (121.7±13.9) kPa respectively, and compared with those of phantom directly indented, there was no apparent difference (P>0.05).Conclusion: These results demonstrated that the intervention ultrasound indention system may be applied for detecting stiffness of different phantoms and there was apparent relationship of tested values with Young's modulus. The result of Bland-Altman plot demonstrated that the results were acceptable for clinical applications.PARTⅢINTERVENTION ULTRASOUND INDENTION ASSESSMENT OF MYOCARDIAL STIFFNESS: IN VIVO EXPERIMENTAL STUDYObjective: To explore the feasibility of interventional ultrasound indention for detecting myocardial stiffness in vivo and to offer a direct measurement method of myocardial stiffness in vivo.Methods : Adult dogs were assigned randomly to myocardial infarct group(n=9)and sham operation group (n=9). Myocardial infarct model was established by coronary artery ligation. Six weeks post operation, using self-made interventional ultrasound stiffness detection meter and under X-ray guidance,Ultrasound catheter passed through peripheral artery into left ventricle and indented left ventricle wall. Myocardium deformation value was acquired by ultrasound and indentation pressure was also obtained. According to Strain-stress relation, myocardium stiffness parameter of left ventricle was gained through calculation and curve fitting. After assessment of myocardium stiffness, HE staining and Sirius red staining of myocardium were conducted and endocardium indented by balloon was observed by scan electron microscope in sham group.Results: Stiffness values of left ventricular anterior and apex wall myocardium during diastasis in heart infarction group were (140.7±30.7) kPa and (49.1±6.2) kPa; those of sham operation group were (34.2±6.5) kPa and (19.3±4.6) kPa. Myocardium strain-stress relation in infarct region was linearity and its correlation coefficient was 0.90 (r= 0.90, P<0.05) and that of sham operation was also linearity and its correlation coefficient was 0.84 (r= 0.84, P<0.05). By HE staining, it showed a large quantity of fibrotic hyperplasia within infarct zone. By Sirius red staining, it showed an amount of collagen hyperplasia. To the anterior wall and the apex of infarction group, the values of CVF, IOD and CVFⅠ/CVFⅢwere 33.0±11.9,10.23±0.79, 17.01±4.2 and 6.6±1.3, 7.22±0.7, 9.0±3.1 separately, while to the sham group, the values of CVF, IOD and CVFⅠ/CVFⅢwere 3.0±0.9, 0.69±0.1, 7.7±1.9 and 3.4±1.1, 0.79±0.09, 7.0±2.01 separately. Content of collagen and the value of CVFⅠ/CVFⅢwere higher in the anterior wall and the apex of infarction group than in the sham group(P<0.05). There wasn't any damage of endothelial cells detected under electron microscope in the endocardium of the sham group.Conclusions: The interventional ultrasound indention meter for stiffness detection was able to detect and measure the stiffness of regional myocardium directly in vivo through a safe and reliable method and steps. With the help of detection meter, local diastolic dysfunction of myocardium would be assessed conveniently, while deep tissue stiffness would be assessed easily.