Computational fluid dynamics modelling in cardiovascular medicine

This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length-And time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, populationaveraged data. Model integration is progressively moving towards 'digital patient' or 'virtual physiological human' representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education-And service-related challenges

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

Haemodynamic optimization of cardiac resynchronization therapy

Heart failure carries a very poor prognosis, unless treated with the appropriate pharmacological agents which, have been evaluated in large randomized clinical trials and have demonstrated improvements in morbidity and mortality of this cohort of patients. A significant proportion of these patients develop conduction abnormalities involving both the atrioventricular node and also the specialised conduction tissue (bundle of His and Purkinje fibers) of the ventricular myocardium which is most commonly evidenced by the presence of a wide QRS, typically left bundle branch block. The net effect of these conduction abnormalities is inefficient filling and contraction of the left ventricle. The presence of these conduction abnormalities is an additional strong marker of poor prognosis. Over the last 15 years pacing treatments have been developed aimed at mitigating the conduction disease. Large scale randomized multicentre trials have repeatedly demonstrated the effectiveness of cardiac pacing, officially recognized as cardiac resynchronization therapy (CRT). This mode of pacing therapy has undoubtedly had a positive impact on both the morbidity and mortality of these patients. Despite the large advancement in the management of heart failure patients by pacing therapies, a significant proportion of patients (30%) being offered CRT are classed as non-responders. Many explanations have been put forward for the lack of response. The presence of scar at the pacing site with failure to capture or delayed capture of myocardium, too much left ventricular scar therefore minimal contractile response, incorrect pacing site due to often limited anatomical options of lead placement and insufficient programming i.e optimization, of pacemaker settings such as the AV and VV delay are just some of the suggested areas perceived to be responsible for the lack of patients’ response to cardiac resynchronization therapy. The effect of optimization of pacemaker settings is a field that has been investigated extensively in the last decade. Disappointingly, current methods of assessing the effect of optimization of pacemaker settings on several haemodynamic parameters, such as cardiac output and blood pressure, are marred with very poor reproducibility, so measurement of any effect of optimization is close to being meaningless. Moreover, detailed understanding of the effects of CRT on coronary physiology and cardiac mechanoenergetics is equally, disappointingly, lacking. In this thesis, I investigated the acute effects of cardiac resynchronization therapy and AV optimization on coronary physiology and cardiac mechanoenergetics. This was accomplished using very detailed and demanding series of invasive catheterization studies. I used novel analytical mathematical techniques, such as wave intensity analysis, which have been developed locally and this provided a unique insight of the important physiological entities defining coronary physiology and cardiac mechanics. I explored in detail the application and reliability of photoplethysmography as a tool for non-invasive optimization of the AV delay. Photoplethysmography has the potential of miniaturization and therefore implantation alongside pacemaker devices. I compared current optimization techniques (Echocardiography and ECG) of VV delay against beat-to-beat blood pressure using the Finometer device and defined the criteria that a technique requires if such a technique can be used meaningfully for the optimization of pacemaker settings both in clinical practice and in clinical trials. Finally, I investigated the impact of atrial pacing and heart rate on the optimal AV delay and attempted to characterize the mechanisms underlying any changes of the optimal AV delay under these varying patient and pacing states. In this thesis I found that optimization of AV delay of cardiac resynchronization therapy not only improved cardiac contraction and external cardiac work, but also cardiac relaxation and coronary blood flow, when compared against LBBB. I found that most of the increase in coronary blood flow occurred during diastole and that the predominant drive for this was ventricular microcirculatory suction as evidenced by the increased intracoronary diastolic backward-travelling decompression wave. I showed that non-invasive haemodynamic optimization using the plethysmograph signal of an inexpensive pulse oximeter is as reliable as using the Finometer. Appropriate processing of the oximetric signal improved the reproducibility of the optimal AV delay. The advantage of this technology is that it might be miniaturized and implanted to provide automated optimization. In this thesis I found that other commonly used modalities of VV optimization such as echocardiography and ECG lack internal validity as opposed to non-invasive haemodynamic optimization using blood pressure. This finding will encourage avoidance of internally invalid modalities, which may cause more harm than good. In this thesis I found that the sensed and paced optimal AV delays have, on average, a bigger difference than the one assumed by the device manufacturers and clinicians. As a significant proportion of patients will be atrially paced, especially during exercise, optimization during this mode of pacing is equally crucial as it is during atrial sensing. Finally, I found that the optimal AV delay decreases with increasing heart rate, and the slope of this is within the range of existing pacemaker algorithms used for rate adaptation of AV delay, strengthening the argument for the rate adaptation to be programmed on.Imperial Users Onl

Grid simulation services for the medical community

The first part of this paper presents a selection of medical simulation applications, including image reconstruction, near real-time registration for neuro-surgery, enhanced dose distribution calculation for radio-therapy, inhaled drug delivery prediction, plastic surgery planning and cardio-vascular system simulation. The latter two topics are discussed in some detail. In the second part, we show how such services can be made available to the clinical practitioner using Grid technology. We discuss the developments and experience made during the EU project GEMSS, which provides reliable, efficient, secure and lawful medical Grid services

The baseline instantaneous wave-free ratio as an index of coronary disease severity: relationship with fractional flow reserve and coronary flow reserve

Over the last 30 years the development of invasive methods to directly measure the haemodynamic impact of individual coronary stenoses on blood flow has enabled the identification of vessel-specific and lesion-specific ischaemia. Fractional flow reserve (FFR) is the most commonly used technique, largely due to the simplification brought by its pressure-only methodology. Despite the evidence accumulated demonstrating the benefits of FFR-guided decisions, its adoption remains low worldwide (6-8%) and a large proportion of patients with coronary artery disease (CAD) still undergo percutaneous interventions without any objective evidence of myocardial ischaemia. This is partly due to FFR’s reliance on the induction of coronary hyperaemia, a methodological step which adds time, cost and inconvenience for patients and clinicians. Recently, our group presented a novel invasive pressure-only methodology, the instantaneous wave-free ratio (iFR), which differs from FFR as it can be calculated at baseline, without the need for vasodilator administration. In its initial validation studies, iFR demonstrated a close diagnostic agreement with FFR and with invasive coronary flow. In this thesis, I will present a series of studies which aim to further evaluate the utility of iFR as an index coronary stenosis severity. Firstly, I will explore its diagnostic relationship with FFR in details and present a novel methodology to measure classification agreement between methods of clinical measurement. Secondly, I will evaluate the merits of utilising iFR and FFR in a common diagnostic pathway and quantify the potential benefits of such a strategy to spare patients from the need for vasodilator administration. Finally, I will investigate the relationship between pressure-only indices (iFR and FFR) and coronary flow reserve, an extensively validated marker of prognosis in coronary disease.Open Acces