DESCRIPTION (provided by applicant): Minimally invasive interventions are rapidly emerging. In cell therapy of infarction by transendocardial injections, highly spatially accurate anatomical guidance towards an intramyocardial target, measurements of left ventricular (LV) wall motion, and identification of viable myocardium are required. While some imaging methods provide excellent anatomical depictions or electromechanical maps, echocardiography (echo) is the only one that could combine all the above requirements into a portable, nonionizing, and cost-effective guidance system. Such a comprehensive solution is highly desired, but currently does not exist. In response, we propose an innovative ultrasound navigation solution based on our acoustically active catheter (AAC) prototype, which has its tip fitted with a piezoelectric crystal The crystal vibrates at a specific frequency, and as a result, the AAC tip then acts as an acoustic "beacon," which is unambiguously identified and spatially localized by a pulsed-wave (PW) Doppler sample window. Thus, PW Doppler is used in a new application: It tracks the AAC tip within conventional (grayscale) scans and enables guidance of the tip to a desired anatomical target. There is no need to modify the conventional ultrasound imager. Our preliminary work has proven the proposed navigation principle and demonstrated its spatial targeting accuracy. In the current application, the existing functional AAC prototype will serve as
a platform for further investigations of acoustic navigation of minimally invasive procedures, advancement of depth control of catheter-based intramyocardial injections, and determination of the efficacy of intramyocardial agent administrations. We will also capitalize on our theoretical work in acoustics, in vitro and in vivo (open-chest and closed-chest) pig experiments, sonometric instrumentation for reference measurements, and state of the art ultrasound technologies. The application is organized to the following aims. In aim 1, we will advance the navigation function by implementing a color Doppler marker of the AAC tip, allowing real-time biplane visualization and 3D tracking of the catheter tip. In aim 2, we will address intramyocardial injection accuracy and safety by developing and testing a sonometric approach for needle insertion depth measurement. In aim 3, we will use our previous model of local biochemical (nondestructive) inhibition of LV function and test efficacy of intramyocardial agent delivery by an injection AAC guided from within the heart. Our team and complementary expertise of the two principal investigators in cardiac interventions, echo, cardiovascular models, and vibroacoustics are conducive to accomplishing these aims. The research is significant because the combination of the specific localized acoustic source with Doppler tracking alleviates artifacts complicating image-guided intervention with conventional ultrasonography.