"If I have seen further, it is by standing on the shoulders of giants."
—Isaac Newton
This thesis documents the scientific journey of a medical device from a bench top prototype to a multi-site clinical study. Throughout this process we have had a flavor of all intricacies that are involved with ideation, design, development, manu- facturing, and testing of a non-invasive diagnostic medical device. This experience taught how to take ideas from a whiteboard and create functional prototypes that can be safely tested, how to translate laboratory prototypes into manufacturable devices, and how to analyze human data to develop algorithmic models that reflect the underlying physiology. In particular this work focused on the development of a brachial cufftechnology for high-resolution pulse waveform acquisition. The tests and studies performed have shown its accuracy and reliability in capturing high fidelity information about the heart and cardiovascular system. These efforts aim to narrow the information gap between invasive measurements and their non-invasive counterpart in the field of cardiology.
Chapters 2 and 3 discuss the design and functionality of the components in the cuff-based system for high-resolution pulse waveform acquisition. The device proposed herein aims to improve wide-spread applicability of non-invasive pulse waveform analysis by addressing ease of measurement and result repeatability.
The challenge in this part of the project was the acquisition of a small pressure signal in a large operating range. We exploited our knowledge of fluid dynamics to design a pneumatic low pass filter to obtain the running mean pressure from a
pulsatile input signal. This component was combined with a differential pressure sensor to effectively capture a high-pass filtered version of the input signal. We mathematically showed that the pneumatic low pass filter’s behavior is governed by a set of equations that closely mimic the well-known electrical low pass filter.
From these set of equations we extracted the time constants of the model allowing the reader to redesign the components for an application of their interest. The filter characteristics were specified for a physiological application that would theoretically generalize well to the entire population. The shape friendly design was integrated into the device for high-resolution pulse waveform acquisition. Preliminary testing results showed the system is user friendly and highly mitigates operator errors.
The iterative design process culminated with a medical device that captures high- resolution pulse waveforms at distinct subject-specific pressure-flow conditions.
Chapters 4 and 5 discuss the human studies that were used to evaluate the device’s accuracy. The first human IRB study was performed at Caltech and re- cruited healthy volunteers for a quality control on the system. The study evaluated the reliability of the measurement and validated that within a healthy population pulse waveform parameters generate consistent results. The second human study was a multi site clinical study with individuals referred for left heart catheterization.
The study consisted of simultaneous recordings with an invasive catheter, the cuff measurement and an electrocardiogram; the study performed a measurement in the left ventricle followed by a measurement in the aorta. The clinical data from the catheter in the ascending aorta and the cuffmeasurement was analyzed to assess the capability of the brachial cuff to accurately measure central cardiovascular health.
The study revealed that our cuffwith sSBP hold pressure produces an high-fidelity representation of the central cardiovascular signal parameters. Chapters 3 and 4 also discuss the work done to study and conserve the dynamic modulation of the cardio- vascular pressure signal, one of the measurement aspects that is typically neglected in non-invasive systems. I introduce a novel method for signal calibration using the subject-specific oscillometric envelope function to preserve the dynamic breathing fluctuations. Evaluation against the pressure signal from the catheter showed the calculated fluctuations from the cuffare proportional to those measured invasively.
These results show that advances in cuff-based systems allow to accurately measure central cardiovascular parameters in a non-invasive and consistent manner.
Chapters 6 and 7 correlate the pulse pressure signal from the brachial cuffto left ventricular functions. Chapter 6 introduces a method to extract the pressure-sound
equivalent of the heart sounds from the brachial cuffmeasurement. These pressure vibrations are shown to originate from the forceful opening and the closing stretch- and-recoil behavior of the aortic valve. Left ventricular pressure gradients are found to be one of the determining physiological factors in the generation of these sounds.
The cuffpressure-sound waveform parameters followed the expected physiological behavior setting a first stepping stone towards the non-invasive characterization of the left ventricular contractile function. Future studies will target developing predictive models for the systolic and diastolic contractile function using cuffderived pressure- sound waveform parameters. In Chapter 7 we perform an observational study on the influence of breathing on the catheter signal in the left ventricular and the cuff parameters. Pressure fluctuations caused by physiological breathing were shown to produce measurable and equivalent effects in the left ventricle and the cuffsignal.
With the improvement of medical technologies, the dynamic components of the pressure time signal are starting to gain more attention in the cardiovascular space and we hope the steps presented in this analysis can further motivate their advance.
In summary, accurately characterizing left ventricular functions is a big step towards creating more informative non-invasive diagnostic tools.
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