Hemodynamic monitor for rapid, cost-effective assessment of peripheral vascular function

Worldwide, at least 200 million people are affected by peripheral vascular diseases (PVDs), including peripheral arterial disease (PAD), chronic venous insufficiency (CVI) and deep vein thrombosis (DVT). These diseases have considerable socioeconomic impacts due to their high prevalence, cost of investigation, treatment and their effects on quality of life. PVDs are often undiagnosed with up to 60% of patients with PVD remaining asymptomatic. Early diagnosis is essential for effective treatment and reducing socioeconomic costs, particularly in patients with diabetes where early endovascular treatment can prevent lower extremity amputation. However, available diagnostic methods simply do not meet the needs of clinicians. For example, duplex ultrasound or plethysmography are time-consuming methods, costly and require access to highly trained clinicians. Due to the cost and time requirements of such methods, they are often reserved for symptomatic patients. On the other hand, the Ankle Brachial Index (ABI) test is cheap but has poor sensitivity for those patients with diabetes and the elderly, both growing high-risk populations. There is an urgent need for new diagnostic tools to enable earlier intervention. Researchers at the MARCS Institute have developed a novel hemodynamic monitor platform named HeMo, specifically for the assessment of peripheral blood flow in the leg. This development aimed to provide a fast and low-cost diagnosis of both peripheral arterial disease and chronic venous insufficiency. This work first provides a comprehensive literature review of the existing non-invasive diagnostic devices developed since 1677 to highlight the need of development of a new blood monitoring tool. Second, it presents the simplified circuit of the HeMo device and provides series of pilot experiments with HeMo demonstrating its potential for diagnosis of both peripheral arterial disease and chronic venous insufficiency. Third, it presents a quantitative characterisation of the electrical behaviour of the electro-resistive band sensors with the development of an expansion/contraction simulator rig and using spectral analysis. The characterisation of the electro-resistive band was essential to understand the nonlinear electrical behaviour of such sensors and would be of interest for other users and uses of the electro-resistive band sensors. However, in another perspective this sinusoidal linear stretching movement and the presented method shows an example for the application of the presented rig, highlighting that the same technique could be used for characterisation of similar stretchable sensors. Fourth, it shows data from a healthy population, assessing the performance of HeMo compared to light reflection rheography (LRR sensor-VasoScreen 5000) for the assessment of venous function. Fifth, it presents human study data where the performance of HeMo is compared to photoplethysmography (PPG sensor-VasoScreen 5000) for the evaluation of the arterial function. Overall, the presented work here, steps toward development of the final version of a novel hemodynamic monitoring device, and its validation

Dynamic relationship between cardiac imaging and physiological measurements

PhD ThesisImpedance cardiography (ICG) is a non-invasive technique to measure the dynamic changes in electrical impedance of the thorax. Photoplethymgraphy (PPG) is an optical- based non-invasive physiological measurement technique used to detect the blood volume pulses in the microvascular bed of tissue. These two physiological measurements have potential clinical importance to enable simple and cost-efficient ways to examine cardiovascular function and provide surrogate or additional clinical information to the measures from cardiac imaging. However, because the origins of the characteristic waveforms of the impedance and pulse are still not well understood, the clinical applications of these two techniques are limited. There were two main aims in this study: 1) to obtain a better understanding of the origins of the pulsatile impedance changes and peripheral pulse by linking their characteristic features beat-by-beat to those from simultaneous echocardiograms; 2) to validate the clinical indices from ICG and PPG with those well-established echocardiographic indices. Physiological signals, including ECGs, impedance, the first derivative impedance and finger and ear pulses, were simultaneously recorded with echocardiograms from 30 male healthy subjects at rest. The timing sequence of cardiovascular events in a single cardiac cycle was reconstructed with the feature times obtained from the physiological measurements and images. The relations of the time features from the impedance with corresponding features from images and pulses were investigated. The relations of the time features from peripheral pulses with corresponding features from images were also investigated. Furthermore, clinical time indices measured from the impedance and pulse were validated with the reference to the echocardiograms. Finally, the effects of age, heart rate and blood pressure on the image and physiological measurements were examined. According to the reconstructed timing sequence, it was evident that the systolic waves of the thoracic impedance and peripheral pulse occurred following left ventricular ejection. The impedance started to fall 26 ms and the pulse arrived at the fingertip 162 ms after the aortic valve opened. A diastolic wave was observed during the ventricular passive filling phase on the impedance and pulse. The impedance started to recover during the late ventricular ejection phase when the peripheral pulse was rising up. While the pulsatile impedance changes were mainly correlated with valve movement, the derivative impedance (velocity of impedance change) was more correlated with aortic flow (velocity of blood 2 flow). The foot of the finger pulse was significantly correlated with aortic valve open (R = 0.361, P < 0.05), while its systolic peak was strongly correlated with the aortic valve 2 closing (R = 0.579, P < 0.001). Although the pulse had similar waveform shapes to the inverted impedance waveform, the associations between the time features of these two signals were weak. During the validation of potential clinical indices from ICG, significant correlation was found between the overall duration of the derivative impedance systolic wave (359 ms) and the left ventricular ejection time (LVET) measured by aortic valve open duration from M- 2 mode images (329 ms) (R = 0.324, P < 0.001). The overall duration from the finger pulse foot to notch (348 ms) was also significantly correlated with the LVET from M-mode 2 images (R = 0.461, P < 0.001). Therefore, both ICG and PPG had the potential to provide surrogates to the LVET measurement. Age influenced the cardiovascular diastolic function more than systolic function on normal subjects. With age increasing, the reduction of the left ventricular passive filling was compensated by active filling. The ratio of the passive filling duration to the active 2 filling duration decreased with age (R = 0.143, P < 0.05). The influence of age on the diastolic wave of the impedance signals was striking. The impedance diastolic wave disappeared gradually with age. The effects of age on the peripheral pulse were mainly on the shortened pulse foot transit time (PPT) and prolonged pulse rise time. The large artery f stiffness index (SI) increased with age. Most time intervals were prolonged with heart rate slowing down. The effects of systolic blood pressure were evident on pulse transit time and pulse diastolic rising time. Driven by higher systolic blood pressure, both PPT and rising f time decreased significantly (P < 0.001). In conclusion, from the analysis based on simultaneous physiological measurements and echocardiograms, both the pulsatile impedance changes and peripheral volume pulse were initiated by left ventricular ejection. The thoracic impedance changes reflected volume changes in the central great vessels, while the first derivative impedance was associated with the velocity of blood flow. Both ICG and PPG had the potential to provide surrogates for the measures of cardiac mechanical functions from images. The PPG technique also enabled the assessment of changes in vascular function caused by age.Institute of Cellular Medicine Newcastle Universit

Biomedical Signal and Image Processing

Written for senior-level and first year graduate students in biomedical signal and image processing, this book describes fundamental signal and image processing techniques that are used to process biomedical information. The book also discusses application of these techniques in the processing of some of the main biomedical signals and images, such as EEG, ECG, MRI, and CT. New features of this edition include the technical updating of each chapter along with the addition of many more examples, the majority of which are MATLAB based

Quantification of Blood Velocity and Vascular Wall Shear Rate From Ultrasound Radio Frequency Signals and Its Relationship to Vascular Mechanical Properties and Potential Clinical Applications.

This study evaluates a novel measurement method of determining vascular wall strain and wall shear rate, which are interrelated physiologic parameters fundamentally important in vascular disease. Wall strains during vascular wall dilation were performed using ultrasound 2D speckle tracking; vascular wall edges and vascular wall shear rate were determined using decorrelation based velocity measurement method for in-vitro and in-vivo flow measurement. These experiments and measurements were performed to investigate both the novel measurement methods as well as the relationship between the vascular wall shear rate and vascular wall dilation. First, this study measures arterial wall strains using the ultrasound radio-frequency (RF) signals. Strains in the arterial wall during arterial dilation (from diastole to systole) were determined using a 2D speckle tracking algorithm. These ultrasound results were compared with measurements of arterial strain as determined by finite-element analysis (FEA) models with and without the effects from surrounding tissue, which was represented by homogenous material with fixed elastic modulus. Under pressure equalization, the strain levels predicted by FEA model without surrounding tissue were considerably greater than the strain levels measured by both ultrasound and the FEA model with surrounding tissue. Second, this research aims to measure wall edges and wall shear rate for in-vitro flow experiment using decorrelation ultrasound based velocity measurement. The flow velocity was obtained by multiplying the speckle movement in two consecutive frames by the acoustic frame rate. The wall edge was determined using B-mode images and 2nd order gradient of flow velocity profiles. The wall shear rate was measured at the wall edge and evaluated by comparison with velocity gradients from parabolic flow velocity profile based on Poiseuille theory. Third, this research measures the vascular wall shear rate in the brachial artery for healthy and renal disease subjects using the decorrelation based ultrasound velocity measurement. The vascular wall shear rate and vascular diameter pre-, during- and post-vascular occlusion with pressure cuffs were compared for the healthy and renal disease subjects at top and bottom wall edges. The mean vascular wall shear rate change between pre- and post-vascular occlusion was significantly different for the healthy versus renal disease subjects.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91610/1/bigrain_1.pd

2-D and 3-D high frame-rate Pulse Wave Imaging for the characterization of focal vascular disease

Cardiovascular diseases are major causes of morbidity and mortality in Western-style populations. Atherosclerosis and Abdominal Aortic Aneurysms (AAAs) are two prevalent vascular diseases that may progress without symptoms and contribute to acute cardiovascular events such as stroke and AAA rupture, which are consistently among the leading causes of death worldwide. The imaging methods used in the diagnosis of these diseases, have been reported to present several limitations. Given that both are associated with mechanical changes in the arterial wall, imaging of the arterial mechanical properties may improve early disease detection and patient care. Pulse wave velocity (PWV) refers to the velocity at which arterial waves generated by ventricular ejection travel along the arterial tree. PWV is a surrogate marker of arterial stiffness linked to cardiovascular mortality. The foot-to-foot method that is typically used to calculate PWV suffers from errors of distance measurements and time-delay measurements. Additionally, a single PWV estimate is provided over a relatively long distance, thus inherently lacking the capability to provide regional arterial stiffness measurements. Pulse Wave Imaging (PWI) is a noninvasive, ultrasound-based technique for imaging the propagation of pulse waves along the wall of major arteries and providing a regional PWV value for the imaged artery. The aim of this work was to enable PWI to provide more localized PWV and stiffness measurements within the imaged arterial segment and to further extend it into a 2-D and 3-D technique for the detection and monitoring of focal vascular disease at high temporal and spatial resolution. The improved modality was integrated with blood flow imaging modalities aiming to render PWI a comprehensive methodology for the study of arterial biomechanics in vivo. Spatial information was increased with the introduction of piecewise PWI. This novel technique was used to measure PWV within small sub-regions of the imaged vessel in murine aneurysmal (n = 8) and atherosclerotic aortas (n = 11) in vivo. It provided PWV and stiffness maps while capturing the progressive arterial stiffening caused by atherosclerosis. PWI was further augmented with a sophisticated adaptive algorithm, enabling it to optimally partition the imaged artery into relatively homogeneous segments, automatically isolating arterial stiffness inhomogeneities. Adaptive PWI was validated in silicone phantoms consisting of segments of varying stiffness and then tested in murine aortas in vivo. Subsequently, the conventional tradeoff between spatial and temporal resolution was addressed with a plane wave compounding implementation of PWI, allowing the acquisition of full field of view frames at over 2000 Hz. A GPU-accelerated PWI post-processing framework was developed for the processing of the big bulk of generated data. The parameters of coherent compounding were optimized in vivo. The optimized sequences were then used in the clinic to assess the mechanical properties of atherosclerotic carotids (n=10) and carotids of patients after endarterectomy (n=7), a procedure to remove the plaque and restore blood flow to the brain. In the case of atherosclerotic patients undergoing carotid endarterectomy, the results were compared against the histology of the excised plaques. Investigation of the mechanical properties of plaques was also conducted for the first time with a high-frequency transducer (18.5 MHz). Additionally, 4-D PWI was introduced, utilizing high frame rate 3-D plane wave acquisitions with a 2-D matrix array transducer (16x16 elements, 2.5 MHz). A novel methodology for PWV estimation along the direction of pulse wave propagation was implemented and validated in silicone phantoms. 4-D PWI provided comprehensive views of the pulse wave propagation in a plaque phantom and the results were compared against conventional PWI. Finally, its feasibility was tested in the carotid arteries of healthy human subjects (n=6). PWVs derived in 3-D were within the physiological range and showed good agreement with the results of conventional PWI. Finally, PWI was integrated with flow imaging modalities (Color and Vector Doppler). Thus, full field-of-view, high frame-rate, simultaneous and co-localized imaging of the arterial wall dynamics and color flow as well as 2-D vector flow was implemented. The feasibility of both techniques was tested in healthy subjects (n=6) in vivo. The relationship between the timings of the flow and wall velocities was investigated at multiple locations of the imaged artery. Vector flow velocities were found to be aligned with the vessel’s centerline during peak systole in the common carotid artery and interesting flow patterns were revealed in the case of the carotid bifurcation Consequently, with the aforementioned improvements and the inclusion of 3-D imaging, PWI is expected to provide comprehensive information on the mechanical properties of pathological arteries, providing clinicians with a powerful tool for the early detection of vascular abnormalities undetectable on the B-mode, while also enabling the monitoring of fully developed vascular pathology and of the recovery of post-operated vessels

Pre- and Perioperative Assessment of Right Ventricular Afterload to Determine Chronic Right Ventricular Failure Post-implant of Durable Left Ventricular Assist Device: Feasibility and Clinical System Development

Patients suffering from end-stage heart failure refractory to optimal medical treatment may require a durable left ventricular assist device (LVAD) as a bridge to transplant or as destination therapy. Unfortunately, as many as 40% of LVAD recipients experience right ventricular failure (RVF) post-implant. RVF post- implant results in a decrease in survival to transplant or continued support, and an increase in hospital stay. In the most severe RVF cases, mechanical circulatory support (MCS) for the right ventricle (RV) is needed. Short-term RV MCS is available; however, no durable RVAD currently exists. To date, research has focused mainly on predicting cases of RVF which occur immediately following LVAD implant or within the first 30 post-operative days. However, chronic RVF may also occur in subjects beyond one month. In the clinical setting, echocardiography (echo) and right heart catheterization (RHC) are standard methods used to provide imaging and hemodynamic data for physicians. RHC reports resistance faced by the RV using only mean pressure and mean flow. However, it does not account for the oscillatory component of pulsatile blood flow generated during the cardiac cycle. Pulmonary vascular impedance (PVZ) completely characterizes the RV afterload by measuring both steady and oscillatory components in the frequency domain. Unfortunately, PVZ has not been used in the clinical setting due to technical limitations and cost-prohibitive equipment. In this study, we attempted to calculate PVZ using signals obtained via standard of care echo and RHC, available before and during LVAD implantation. PVZ spectra were then used to determine if there is a difference in RV afterload based on RVF outcome within one year of implant. Results ultimately showed that there was no difference in afterload between groups. Though no difference in PVZ was found, the study showed that PVZ calculation is possible and may be of benefit to other patients. Following completion of the initial study, a graphically driven, software-based system was developed to calculate PVZ using only standard of care data from electronic health records. The software facilitates rapid assessment of PVZ in a manner that is intuitive to those who work in the clinical setting