Non-invasive time sampled venous pressure detection for research and clinical applications

The venous system of the lower limbs has unique anatomy that provides a skeletal muscle pump for the transport of blood against the hydrostatic gradient of erect postures. This muscle pump enables the regulation of venous pressures in the legs and is essential to maintain healthy tissue in the lower extremities. Chronic venous insufficiency and chronic venous ulcers are severe, related disease states associated with elevated venous pressures of the lower limb. The development and evaluation of new therapies for these diseases requires quantitative information about the haemodynamics of the venous system in normal, pathologic, pre-therapeutic, and post-therapeutic states. The diagnostic methods and instruments for venous system evaluation and clinical diagnosis are reviewed with respect to their historical and contemporary capabilities and limitations. Their progression has moved toward non-invasive modes, culminating in the widespread use of duplex ultrasonography. The practice of duplex ultrasonography for the assessment of venous diseases leverages the structure, flow, and velocity data rendered by this technology. However, the observation of dynamic venous pressures with ultrasonography is not currently available, and there is an unmet need for non-invasive venous pressure capability congruent with duplex ultrasonography. A novel method of assessing venous pressures using a time-sampled pressure probe (TSVPP) with ultrasonically imaged vessels is proposed. A set of requirements to define this instrument is developed from the vascular physiology and anatomy, and from the characteristics of contemporary ultrasound imagers. A proof-of-concept prototype is designed, fabricated and tested using artificial structures. The device and methods are optimized and then tested in animal models. A healthy human study is conducted using 12 volunteers. The evaluation of the TSVPP in animal models demonstrated the feasibility of the instrument. R2 fit values of 0.94 to 0.98 were achieved in Slow and Very Slow sampling modes. The results of the healthy volunteer study included 64 successful static pressure estimations from 72 observations. Over the 64 valid results, the mid and high pressure average error was within +/- 10%. Ambulatory venous pressure measurements were attempted using the slow sampling mode, and 5 of 9 attempts demonstrated a pressure recovery characteristic consistent with the classical ambulatory venous pressure response. This thesis has explored a novel concept in venous pressure measurement and has extended the knowledge of its potential and limitations with qualitative and quantitative evidence. The results support an assertion that the TSVPP has promise for improving our insights into clinical diseases of the venous system. Further, the TSVPP can be developed as a useful tool for evaluating the effects of venous therapies designed to reduce venous stasis and hypertension. A foundation of conceptual work, bench evaluation, pre-clinical tests, and clinical study has been established. Future development of the concepts and implementations discussed appear justified from the potential intellectual, clinical, and societal benefits that can be associated with the product of this work2019-09-1