The major goal of obtaining the Vevo 3100 imaging system is to provide investigators at the John D. Dingell VA Medical Center with a state-of-the-art imaging platform that will enable non-invasive, in vivo high resolution assessment of anatomical structures with simultaneous evaluation of dynamic physiological parameters and imaging with custom molecular markers. The Vevo 3100 high frequency ultrasound is an imaging platform complete with Imaging Station, multiple transducers designed for specific capabilities, mouse and rat handling stations. The system provides M-mode and pulse wave, color and power Doppler modalities with a contrast imaging functionality and a left ventricular (LV) trace tool. Sophisticated software permits quantification of real-time, longitudinal and/or repeated measurements of dynamic cardiac function, vascular parameters such as stiffness and permeability, and tissue oxygenation in the same animal. Photoacoustic capabilities permit measures of tumor progression and regression. This high resolution ultrasound imaging will provide our five major users with the following capabilities to enhance their funded studies: (1) The Rossi laboratory will obtain serial, dynamic measurements of cardiac output, stroke volume, diastolic function, vascular wall thickness, arterial stiffness, and shear stress and in the two-kidney, one-clip rat model of renovascular hypertension rather than static histologic data at the termination of experiments or ex vivo measures of arterial parameters. (2) The Mateika laboratory will obtain a wide range of cardiovascular parameters, including right heart function, myocardial perfusion, tissue hypoxia and angiogenesis in murine models of acute intermittent hypoxia in transgenic mice lacking tryptophan hydroxylase needed for serotonin signaling and in mice with spinal cord injury. (3) The Conti laboratory has identified cardiovascular parameters associated with post traumatic stress disorder (PTSD) including hypertension and myocardial dysfunction Her studies will benefit from the ability to detect vascular remodeling of blood vessels and cerebral blood flow, cardiac load and shear stress in PTSD-hypertension. (4) Dr. Ding will evaluate cerebral blood flow and oxygenation in his model of stroke. (5) Dr. Rishi who studies new therapeutic agents for treatment of malignancies will be able to quantify tumor size and volume as well as angiogenesis within the tumors as the tumors grow and/or regress. This cutting edge technology will also permit minor users (Kowluru and Majumdar) to study the microanatomy of vascular remodeling and integrity in genetic models of diabetes and tumor angiogenesis and growth/regression, respectively. Most importantly, ultrasonic imaging is a technology that is currently available in clinical practice. Taken together, these investigators study diseases that impart substantial morbidity and mortality on Veterans: hypertension, heart failure, atherosclerosis, sleep apnea, spinal cord injury, traumatic brain injury, PTSD, stroke, diabetes mellitus and malignancy. The Vevo 3100 will permit repeated serial measurements in longitudinal studies, thereby permitting more robust statistical assessment and limiting the number of animals needed for the studies. As more refined and high resolution clinical ultrasound instruments become available to evaluate humans non-invasively and without the higher cost and risks inherent in imaging methodologies that involve radiation or contrast agents, the preclinical studies facilitated by the Vevo 3100 will provide vital data that can be translated into the clinical evaluation and improve the health of our Veterans.
This proposal requests shared equipment for investigators at the John D. Dingell VAMC to obtain a Vevo 3100 high frequency ultrasound instrument that provides high resolution cardiac, vascular, and tumor measurements in preclinical models of disease, specifically in rats and mice. This instrument will allow repeated, longitudinal measurements of important parameters of cardiac function, vascular stiffness, tissue perfusion and oxygenation, growth and regression of tumor in models of human disease that significantly impact Veterans: hypertension, atherosclerosis, sleep apnea, traumatic brain injury, post-traumatic stress disorder, spinal cord injury, stroke, diabetes and malignancies. Ultrasound technology is available in for use in patients, is noninvasive and does not require radiation. The Vevo 3100 system for our preclinical studies will increase the translational value of studies of diseases that impact the health of our Veterans.