Conduit Artery Photoplethysmography and its Applications in the Assessment of Hemodynamic Condition

Elektroniskā versija nesatur pielikumusPromocijas darbā ir izstrādāta maģistrālo artēriju fotopletizmogrāfijas (APPG) metode hemodinamisko parametru novērtējumam. Pretstatot referentām metodēm, demonstrēta iespēja iegūt arteriālo elasticitāti raksturojošus parametrus, izmantojot APPG signāla formas analīzi (atvasinājuma un signāla formas aproksimācijas parametri) un ar APPG iegūtu pulsa izplatīšanās ātrumu unilaterālā gultnē. Izstrādāta APPG reģistrācijas standartizācija, mērījuma laikā nodrošinot optimālo sensora piespiedienu. Šis paņēmiens validēts ārējās ietekmes (sensora piespiediens) un hemodinamisko stāvokļu (perifērā vaskulārā pretestība) izmaiņās femorālā APPG signālā, identificējot būtiskākos faktorus APPG pielietojumos. Veikta APPG validācija asinsrites fizioloģijas un preklīniskā pētījumā demonstrējot APPG potenciālu pētniecībā un diagnostikā. Izstrādāts pulsa formas parametrizācijas paņēmiens, saistot fizioloģiskās un aproksimācijas modeļa komponentes. Atslēgas vārdi: maģistrālā artērija, fotopletizmogrāfija, arteriālā elasticitāte, metodes standartizācija, pulsa formas kvantifikācija, vazomocija, sepseThe doctoral thesis features the development of a conduit artery photoplethysmography technique (APPG) for the evaluation of hemodynamic parameters. Contrasting referent methods, the work demonstrates the possibility to receive parameters characterizing the arterial stiffness by means of APPG waveform analysis (derivation and waveform approximation parameters) and APPG obtained pulse wave velocity in a unilateral vascular bed. In this work APPG standardization technique was developed providing optimal probe contact pressure conditions. It was validated by altering the external factors (probe contact pressure) and hemodynamic conditions (peripheral vascular resistance) on the femoral APPG waveform identifying the key factors in APPG applications. The APPG validation in blood circulation physiology and a pre-clinical trial was performed demonstrating APPG potential in the extension of applications. An arterial waveform parameterization was developed relating the physiological wave to approximation model components. Keywords: conduit artery, photoplethysmography, arterial stiffness, method standardization, waveform parametrization, vasomotion, sepsi

Estimation of cardiovascular system parameters using noninvasive measurements

Mathematical models have been widely used to simulate the pulsatile flow of blood in a segment of an artery. These models contain several physiologically significant parameters, such as arterial diameter and arterial compliance, and for diseased arteries, parameters pertaining to arterial constrictions (stenoses). Generally these parameters are difficult to measure directly. The aim of the present study was to develop a suitable parameter estimation scheme, based on noninvasive measurements of flow and pressure in the arterial segment, to predict the stenosis parameters in the model. The mathematical model used in this study for pulsatile flow in a tube containing a simulated stenosis was solved with the finite-element method;In the first part of the study, a hydraulic model simulated pulsatile flow in a segment of an artery. Pulsatile pressure and flow waveforms were measured noninvasively by a phase-locked, ultrasonic echo-tracker, and a continuous-wave Doppler flowmeter, respectively. These waveforms compared well with corresponding directly measured waveforms;The method of ordinary least squares, incorporating the Gauss-Newton linearization scheme, was used to estimate the location and severity of a simulated stenosis introduced in the tube. Measured proximal flow and a lumped distal resistance were used as boundary conditions for the model, with a measured proximal pressure used for parameter optimization. The estimation scheme was first validated by model-to-model tests utilizing computer generated waveforms as input data. Subsequently, experimental data from the hydraulic model, which incorporated stenoses ranging in severity from 94.3% to 74.8%, were used as input to the estimation scheme. Estimates for the stenosis severity and location, based on noninvasive measurements of pressure and flow in the tube, compared well with the corresponding directly measured values, and also with estimates obtained with invasively measured data;Limited animal experiments were carried out in the second part of the study. Reasonable estimates of the severity of stenoses, artificially induced in the femoral arteries of dogs, were obtained for stenoses ranging in severity from 90% to 60%. These estimates were based on invasively measured flow and pressure waveforms in the femoral artery

Ultrasound-based non invasive intracranial pressure

Intracranial pressure (ICP) is an important monitoring modality in the clinical management of several neurological diseases carrying the intrinsic risk of potentially lethal intracranial hypertension (ICH). Considering that the brain is in an enclosed compartment, ICH leads to brain hypoperfusion and eventually ischaemia followed by irreversible neuronal damage. Traumatic brain injury (TBI), for instance, is a condition in which ICH is strongly associated with unfavourable outcome and death. Although ICP can guide patient management in neurocritical care settings, this parameter is not commonly monitored in many clinical conditions outside this environment. The invasive character of the standard methods for ICP assessment and their associated risks to the patient (like infections, brain tissue lesions, haemorrhage) contribute to this scenario. Such risks have prevented ICP assessment in a broad range of diseases like in patients with risk of coagulopathy, as well as in other conditions in which invasive assessment is not considered or outweighed by the risks of the procedure. Provided that knowledge of ICP can be crucial for the successful management of patients in many sub-critical conditions, non-invasive estimation of ICP (nICP) may be helpful when indications for invasive ICP assessment are not met and when it is not immediately available or even contraindicated. Several methods for non-invasive assessment of ICP (nICP) have been described so far. Transcranial Doppler (TCD), for instance, is primarily a technique for diagnosing various intracranial vascular disorders such as emboli, stenosis, or vasospasm, but has been broadly utilised for non-invasive ICP monitoring due to its ability to detect changes in cerebral blood flow velocity derived from ICP variations. Moreover, TCD allows monitoring of these parameters as they may change in time. Optic nerve sheath diameter ultrasonography (ONSD) is another non-invasive tool which gained interest in the last years. The optic nerve sheath is in continuous with the subarachnoid space, and when ICP increased, the diameter of ONSD enlarges proportionally to ICP. The focus of this thesis is on the assessment, applications and development of ultrasoundbased for nICP assessment in different clinical conditions where this parameter is relevant but in many circumstances not considered, including TBI and other neurological diseases ULTRASOUND BASED NON-INVASIVE INTRACRANIAL PRESSURE 17 associated with impairment of cerebral blood flow circulation. As main results, ONSD and TCD-based non-invasive methods could replicate changes in direct ICP across time confidently, and could provide reasonable accuracy in comparison to the standard invasive techniques. These findings support the use of ultrasound based non-invasive ICP methods in a variety of clinical conditions requiring management of intracranial pressure and brain perfusion. More importantly, the low costs associated with nICP methods, ultrasound machines are widely available medical devices, could contribute to its widespread use as a reliable alternative for ICP monitoring in everyday clinical practice

Estimation of wall shear stress using 4D flow cardiovascular MRI and computational fluid dynamics

Electronic version of an article published as Journal of mechanics in medicine and biology, 0, 1750046 (2016), 16 pages. DOI:10.1142/S0219519417500464 © World Scientific Publishing CompanyIn the last few years, wall shear stress (WSS) has arisen as a new diagnostic indicator in patients with arterial disease. There is a substantial evidence that the WSS plays a significant role, together with hemodynamic indicators, in initiation and progression of the vascular diseases. Estimation of WSS values, therefore, may be of clinical significance and the methods employed for its measurement are crucial for clinical community. Recently, four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has been widely used in a number of applications for visualization and quantification of blood flow, and although the sensitivity to blood flow measurement has increased, it is not yet able to provide an accurate three-dimensional (3D) WSS distribution. The aim of this work is to evaluate the aortic blood flow features and the associated WSS by the combination of 4D flow cardiovascular magnetic resonance (4D CMR) and computational fluid dynamics technique. In particular, in this work, we used the 4D CMR to obtain the spatial domain and the boundary conditions needed to estimate the WSS within the entire thoracic aorta using computational fluid dynamics. Similar WSS distributions were found for cases simulated. A sensitivity analysis was done to check the accuracy of the method. 4D CMR begins to be a reliable tool to estimate the WSS within the entire thoracic aorta using computational fluid dynamics. The combination of both techniques may provide the ideal tool to help tackle these and other problems related to wall shear estimation.Peer ReviewedPostprint (author's final draft

Toward simultaneous flow and pressure assessment in large arteries using non-invasive ultrasound

Ultrageluid wordt in de kliniek vaak toegepast om op een niet-invasieve manier geometrische eigenschappen van grote vaten, zoals diameter en wanddikte en hemodynamische variabelen zoals bloedstroomsnelheid te bepalen. Om biomechanische parameters en hemodynamische variabelen die karakteristiek zijn voor de ontwikkeling van hart en vaatziekten, zoals compliantie en impedantie, te bepalen, is de bepaling van geometrie en bloedstroomsnelheid alleen onvoldoende. Daarvoor is een gelijktijdige en bij voorkeur niet invasieve meting van debiet en druk vereist. Met de huidige ultrageluidstechnieken is het onmogelijk om gelijktijdig debiet en druk nauwkeurig te bepalen. Debiet wordt vaak bepaald aan de hand van twee metingen: een diametermeting (geluidsbundel loodrecht op het vat) en een meting van de maximale axiale bloedstroomsnelheid met behulp van Doppler ultrageluid (geluidsbundel onder een hoek met het vat). Door een theoretische snelheidsverdeling aan te nemen, bijvoorbeeld een Poiseuille of Womersley profiel, wordt hieruit vervolgens het debiet berekend. In-vivo zijn vaten zelden recht: vaten zijn taps toelopend, gekromd en hebben vertakkingen. Dientengevolge zijn er secundaire snelheidscomponenten aanwezig die de axiale snelheidverdeling be¨invloeden. Dit resulteert in asymmetrische axiale snelheidsverdelingen. Omdat de aangenomen snelheidsverdelingen slechts geldig zijn voor rechte vaten, geeft een dusdanige bepaling een onnauwkeurige afschatting van het debiet. Verder is het onmogelijk om gelijktijdig met de snelheidsmeting nauwkeurig de wandbeweging te bepalen, waardoor de debietmeting nog verder verslechtert en het gelijktijdig bepalen van druk uit wandbeweging en debiet onmogelijk wordt. In dit onderzoek worden Particle Image Velocimetry (PIV) gebaseerde algoritmen toegepast op RF-data die verkregen zijn met behulp van een commercieel beschikbaar, voor klinische toepassing goedgekeurd ultrageluidssysteem. Dit maakt het mogelijk om snelheidscomponenten loodrecht op de ultrageluidbundel, en dus gelijktijdig wandpositie en axiale snelheid nauwkeurig te meten. Deze snelheidsmeettechniek is gevalideerd door metingen van het snelheidsprofiel in een experimentele opstelling te vergelijken met resultaten van computational fluid dynamics (CFD) berekeningen, voor stationaire en instationaire stromingen in een recht vat. Er werd een goede overeenstemming gevonden voor het axiale snelheidsprofiel. Integratie van het gemeten axiale snelheidsprofiel leverde een nauwkeurige afschatting van het debiet op. Omdat in de praktijk de meeste vaten gekromd zijn is de snelheids meetmethode vervolgens gevalideerd voor toepassing op stromingen in dit soort geometrieën. In de experimentele opstelling zijn axiale snelheidsprofielen gemeten voor stationaire en instationaire stroming in kromme buizen. Opnieuw zijn de gemeten profielen vergeleken met resultaten van CFD-berekeningen. Ook hier werd een goede overeenstemming gevonden tussen de gemeten profielen en de met behulp van CFD berekende snelheidsprofielen. Om nauwkeurig debiet te bepalen op basis van de gemeten asymmetrische axiale snelheidsprofielen, is een analytische en een op CFD gebaseerde studie gedaan naar stroming in kromme vaten. Deze studie heeft geresulteerd in de cos ¿-methode. Toepassing van de cos ¿-methode op de gemeten asymmetrische axiale profielen gaf een nauwkeurige afschatting van het debiet, voor stationaire en instationaire flow. Vergeleken met de huidig toegepaste afschattingsmethode voor het debiet werd een grote verbetering gevonden. Voor een fysiologisch relevant debiet gaf de cos ¿-methode een gemiddelde afwijking van 5% ten opzichte van het referentiedebiet terwijl deze voor de huidig toegepaste Poiseuille en Womersley benaderingen gelijk was aan 20%. Tenslotte is getracht om de lokale druk te bepalen uit enkel een niet-invasieve ultrageluidsmeting door een meting van de diameter te combineren met een gelijktijdige bepaling van de lokale compliantie. De lokale compliantie is bepaald door de lokale golfsnelheid (PWV) te meten. Verschillende methoden om lokaal de PWV te meten zijn getest in de experimentele opstelling. Hieruit bleek dat de QA-methode, een methode waarbij de lokale PWV bepaald wordt uit de verhouding tussen veranderingen in debiet en veranderingen in oppervlak van de dwarsdoorsnede van het vat, het mogelijk maakt om lokaal nauwkeurig PWV te meten. Door de PWV meting te combineren met een gelijktijdige meting van de diameter werd de lokale druk nauwkeurig afgeschat. Dit geeft aan dat het haalbaar is om op een niet-invasieve manier in-vivo druk te meten met behulp van ultrageluid. Hoewel de meettechnieken besproken in deze studie alleen getest zijn voor toepassing in een gecontroleerde experimentele omgeving, zijn de vooruitzichten voor klinische toepassing veelbelovend. De gepresenteerde methoden maken het mogelijk om de toestand van het vaatbed nauwkeuriger te bepalen, waardoor in de toekomst informatie verkregen kan worden over het effect van therapeutische ingrepen en factoren ge¨identificeerd kunnen worden die karakteristiek zijn voor de ontwikkeling van hart- en vaatziekten

Pressure drop and recovery in cases of cardiovascular disease: a computational study

The presence of disease in the cardiovascular system results in changes in flow and pressure patterns. Increased resistance to the flow observed in cases of aortic valve and coronary artery disease can have as a consequence abnormally high pressure gradients, which may lead to overexertion of the heart muscle, limited tissue perfusion and tissue damage. In the past, computational fluid dynamics (CFD) methods have been used coupled with medical imaging data to study haemodynamics, and it has been shown that CFD has great potential as a way to study patient-specific cases of cardiovascular disease in vivo, non-invasively, in great detail and at low cost. CFD can be particularly useful in evaluating the effectiveness of new diagnostic and treatment techniques, especially at early ‘concept’ stages. The main aim of this thesis is to use CFD to investigate the relationship between pressure and flow in cases of disease in the coronary arteries and the aortic valve, with the purpose of helping improve diagnosis and treatment, respectively. A transitional flow CFD model is used to investigate the phenomenon of pressure recovery in idealised models of aortic valve stenosis. Energy lost as turbulence in the wake of a diseased valve hinders pressure recovery, which occurs naturally when no energy losses are observed. A “concept” study testing the potential of a device that could maximise pressure recovery to reduce the pressure load on the heart muscle was conducted. The results indicate that, under certain conditions, such a device could prove useful. Fully patient-specific CFD studies of the coronary arteries are fewer than studies in larger vessels, mostly due to past limitations in the imaging and velocity data quality. A new method to reconstruct coronary anatomy from optical coherence tomography (OCT) data is presented in the thesis. The resulting models were combined with invasively acquired pressure and flow velocity data in transient CFD simulations, in order to test the ability of CFD to match the invasively measured pressure drop. A positive correlation and no bias were found between the calculated and measured results. The use of lower resolution reconstruction methods resulted in no correlation between the calculated and measured results, highlighting the importance of anatomical accuracy in the effectiveness of the CFD model. However, it was considered imperative that the limitations of CFD in predicting pressure gradients be further explored. It was found that the CFD-derived pressure drop is sensitive to changes in the volumetric flow rate, while bench-top experiments showed that the estimation of volumetric flow rate from invasively measured velocity data is subject to errors and uncertainties that may have a random effect on the CFD pressure result. This study demonstrated that the relationship between geometry, pressure and flow can be used to evaluate new diagnostic and treatment methods. In the case of aortic stenosis, further experimental work is required to turn the concept of a pressure recovery device into a potential clinical tool. In the coronary study it was shown that, though CFD has great power as a study tool, its limitations, especially those pertaining to the volumetric flow rate boundary condition, must be further studied and become fully understood before CFD can be reliably used to aid diagnosis in clinical practice.Open Acces

Development, Validation, and Clinical Application of a Numerical Model for Pulse Wave Velocity Propagation in a Cardiovascular System with Application to Noninvasive Blood Pressure Measurements

High blood pressure blood pressure is an important risk factor for cardiovascular disease and affects almost one-third of the U.S. adult population. Historical cuff-less non-invasive techniques used to monitor blood pressure are not accurate and highlight the need for first principal models. The first model is a one-dimensional model for pulse wave velocity (PWV) propagation in compliant arteries that accounts for nonlinear fluids in a linear elastic thin walled vessel. The results indicate an inverse quadratic relationship (R^2=.99) between ejection time and PWV, with ejection time dominating the PWV shifts (12%). The second model predicts the general relationship between PWV and blood pressure with a rigorous account of nonlinearities in the fluid dynamics, blood vessel elasticity, and finite dynamic deformation of a membrane type thin anisotropic wall. The nonlinear model achieves the best match with the experimental data. To retrieve individual vascular information of a patient, the inverse problem of hemodynamics is presented, calculating local orthotropic hyperelastic properties of the arterial wall. The final model examines the impact of the thick arterial wall with different material properties in the radial direction. For a hypertensive subject the thick wall model provides improved accuracy up to 8.4% in PWV prediction over its thin wall counterpart. This translates to nearly 20% improvement in blood pressure prediction based on a PWV measure. The models highlight flow velocity is additive to the classic pressure wave, suggesting flow velocity correction may be important for cuff-less, non-invasive blood pressure measures. Systolic flow correction of the measured PWV improves the R2 correlation to systolic blood pressure from 0.81 to 0.92 for the mongrel dog study, and 0.34 to 0.88 for the human subjects study. The algorithms and insight resulting from this work can enable the development of an integrated microsystem for cuff-less, non-invasive blood pressure monitoring