R'equip grant for Visual Sonics Vevo 770 high resolution small animal ultrasound system.
Research Project
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01.12.2010
- 30.11.2011
Gene knockout and transgenic techniques in mice and rats have contributed to the outstanding importance of small animal models of disease in cardiovascular research. Noninvasive imaging of cardiovascular function provides a means for serially assessing the effects of a gene mutation or a therapy on cardiovascular phenotype. Some phenotypic aspects can be examined postmortem (e.g. left ventricular mass), but a majority of cardiovascular phenotypic markers (e.g. left ventricular systolic/diastolic function) can only be determined in vivo . The small size and fast rate of mouse and rat hearts demand imaging equipments with a high spatial and temporal resolution not met by clinical ultrasound systems. With the current grant application we therefore request financing for a VisualSonics Vevo 770 High Frequency Ultrasound System. The Vevo 770 is a dedicated small animal imaging system fulfilling the aforementioned requirements. It offers 2-dimensional real-time ultrasound imaging with high spatial and temporal resolution with frequencies up to 60MHz, pulsed wave doppler imaging for hemodynamic assessment and tissue doppler imaging for analysis of myocardial deformation. In addition, contrast ultrasound imaging with high spatial resolution will be possible. The availability of the Vevo 770 will significantly contribute to the innovative potential of the research proposals included in this application and will allow us to initiate new research directions. In brief, this system will make possible the following main research projects: 1. Sequential contrast enhanced and high resolution ultrasound molecular imaging of inflammatory cell adhesion molecules in atherosclerosis. The Vevo 770 will be used for high resolution in vivo assessment of plaque development in murine atherosclerosis. Also, high resolution contrast enhanced molecular imaging of inflammatory markers will become possible, which constitutes a new research direction. 2. Corticotropin-releasing factor (CRF)-related peptides in ischemic heart disease, left ventricular hypertrophy (LVH) and heart failure. The Vevo 770 will be used to (a) assess the effect of CRF on LVH and development of heart failure, and (b) the cardioprotective effects of CRF-related peptides in myocardial ischemia. For both aims, high quality serial assessment with noninvasive imaging is essential. 3. Role of the tyrosine kinase receptor fetal liver kinase (Flt3) and its ligand (FL) in the myocardium. The Vevo 770 will be used for characterizing cardiac function in Flt3-knockout and FL-knockout mice under physiological and pathological (ischemic) conditions. A detailed analysis of global and regional left ventricular function with high image quality is essential in this project. 4. Role of reactive oxygen species (ROS)-producing NOX-family NADPH oxidases in diabetic cardiomyopathy (CMP). The Vevo 770 will be used to investigate the role of NOX-derived ROS in the development of diabetic CMP. LVH and diastolic dysfunction are hallmarks of diabetic CMP, and thus repetitive exact measurement of these parameters will be essential for this project. 5. Cardiac metabolic pathways in health and disease. The Vevo 770 will be used to determine the role of mammalian target of rapamycin complex 1 and 2 (mTORC1 and mTORC2) in cardiac pathways of energy metabolism and protein turnover (protein synthesis versus protein degradation by the ubiquitin proteasome pathway) in healthy mice and in models of metabolic and cardiovascular disease.