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ULTRASONIC TELEMETRIC IMPLANTABLE PULSED DOPPLER BLOOD FLOW VELOCITIMETER FOR SMALL ANIMALS

$225,000R43FY2018HLNIH

Indus Instruments, Houston TX

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Abstract

TITLE: Ultrasonic Telemetric Implantable Pulsed Doppler Blood Flow Velocimeter for Small Animals ABSTRACT Ultrasonic Pulsed Doppler devices for measuring flow velocities in blood vessels of small animals such as mice are routinely used by cardiovascular researchers for preclinical research. Undisturbed and non-tethered acquisition of physiologic data in awake (unanesthetized) animals using wireless telemetry is the most realistic way to study physiological function. However, due to the lack of suitable devices, these studies at present are done under anesthesia which can be problematic in physiological and pharmacological studies because all anesthetic agents alter basal cardiovascular parameters and control in some way. To allow researchers to monitor blood flow velocities in undisturbed, untethered, awake mice serially over the course of several months to facilitate longitudinal cardiovascular and aging studies we propose to develop a 20MHz Ultrasonic Implantable Pulsed Doppler (IPD) telemetric device. The 2cc volume IPD will be implanted in the peritoneal cavity and connected to a 20MHz ultrasonic single crystal transducer cuff probe that is placed around the blood vessel of interest (aorta, abdominal/renal/carotid arteries). We will use the commercially available Doppler Flow Velocity System, and the Small Animal Implantable Telemetry System, both of which are manufactured by us, as a starting point to accomplish our objective with the following specific aims in phase I: AIM 1: Develop 13.56MHz wireless power transfer charging system for rodent cages AIM 2: Develop a compact, 2cc volume, ultrasonic Doppler blood flow velocimeter AIM 3: Record mouse aortic blood flow measurements in a 3 month study During phase II we will refine, miniaturize, and reduce power consumption of the Pulsed Doppler electronics using custom CMOS silicon integrated circuit design, conduct 12 month long term studies in 60 mice, and update the backend data acquisition system in preparation for commercial manufacture and sale of the IPDs to researchers worldwide. Our specific innovations are: 1) Under the cage wireless power transfer for continuous for long term use, 2) Ultra low power Doppler electronics suitable for long term operation, and 3) Compact Doppler electronics to enable 2cc telemetric device. The proposed device will advance the state of the art in preclinical cardiovascular and aging research by allowing: 1) Undisturbed, untethered, physiologically realistic blood flow velocity measurements in awake mice, 2) Monitoring of cardiovascular changes in longitudinal pharmacological studies for 6+ months. The proposed device may also be applicable for cardiovascular function assessment in aging studies lasting up to 24 months.

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