Towards Cognition-Guided Patient-Specific Numerical Simulation for Cardiac Surgery Assistance

Motivation. Patient-specific, knowledge-based, holistic surgical treatment planning is of utmost importance when dealing with complex surgery. Surgeons need to account for all available medical patient data, keep track of technical developments, and stay on top of current surgical expert knowledge to define a suitable surgical treatment strategy. There is a large potential for computer assistance, also, and in particular, regarding surgery simulation which gives surgeons the opportunity not only to plan but to simulate, too, some steps of an intervention and to forecast relevant surgical situations. Purpose. In this work, we particularly look at mitral valve reconstruction (MVR) surgery, which is to re-establish the functionality of an incompetent mitral valve (MV) through implantation of an artificial ring that reshapes the valvular morphology. We aim at supporting MVR by providing surgeons with biomechanical FEM-based MVR surgery simulations that enable them to assess the simulated behavior of the MV after an MVR. However, according to the above requirements, such surgery simulation is really beneficial to surgeons only if it is patient-specific, surgical expert knowledge-based, comprehensive in terms of the underlying model and the patient’s data, and if its setup and execution is fully automated and integrated into the surgical treatment workflow. Methods. This PhD work conducts research on simulation-enhanced, cognition-guided, patient-specific cardiac surgery assistance. First, we derive a biomechanical MV/MVR model and develop an FEM-based MVR surgery simulation using the FEM software toolkit HiFlow3. Following, we outline the functionality and features of the Medical Simulation Markup Language (MSML) and how it simplifies the biomechanical modeling workflow. It is then detailed, how, by means of the MSML and a set of dedicated MVR simulation reprocessing operators, patient-individual medical data can comprehensively be analyzed and processed in order for the fully automated setup of MVR simulation scenarios. Finally, the presented work is integrated into the cognitive system architecture of the joint research project Cognition-Guided Surgery. We particularly look at its semantic knowledge and data infrastructure as well as at the setup of its cognitive software components, which eventually facilitate cognition-guidance and patient-specifity for the overall simulation-enhanced MVR assistance pipeline. Results and Discussion. We have proposed and implemented, for the first time, a prototypic system for simulation-enhanced, cognition-guided, patient-specific cardiac surgery assistance. The overall system was evaluated in terms of functionality and performance. Through its cognitive, data-driven pipeline setup, medical patient data and surgical information is analyzed and processed comprehensively, efficiently and fully automatically, and the hence set-up simulation scenarios yield reliable, patient-specific MVR surgery simulation results. This indicates the system’s usability and applicability. The proposed work thus presents an important step towards a simulation-enhanced, cognition-guided, patient-specific cardiac surgery assistance, and can – once operative – be expected to significantly enhance MVR surgery. Concluding, we discuss possible further research contents and promising applications to build upon the presented work

Finite-element-method (FEM) model generation of time-resolved 3D echocardiographic geometry data for mitral-valve volumetry

INTRODUCTION: Mitral Valve (MV) 3D structural data can be easily obtained using standard transesophageal echocardiography (TEE) devices but quantitative pre- and intraoperative volume analysis of the MV is presently not feasible in the cardiac operation room (OR). Finite element method (FEM) modelling is necessary to carry out precise and individual volume analysis and in the future will form the basis for simulation of cardiac interventions. METHOD: With the present retrospective pilot study we describe a method to transfer MV geometric data to 3D Slicer 2 software, an open-source medical visualization and analysis software package. A newly developed software program (ROIExtract) allowed selection of a region-of-interest (ROI) from the TEE data and data transformation for use in 3D Slicer. FEM models for quantitative volumetric studies were generated. RESULTS: ROI selection permitted the visualization and calculations required to create a sequence of volume rendered models of the MV allowing time-based visualization of regional deformation. Quantitation of tissue volume, especially important in myxomatous degeneration can be carried out. Rendered volumes are shown in 3D as well as in time-resolved 4D animations. CONCLUSION: The visualization of the segmented MV may significantly enhance clinical interpretation. This method provides an infrastructure for the study of image guided assessment of clinical findings and surgical planning. For complete pre- and intraoperative 3D MV FEM analysis, three input elements are necessary: 1. time-gated, reality-based structural information, 2. continuous MV pressure and 3. instantaneous tissue elastance. The present process makes the first of these elements available. Volume defect analysis is essential to fully understand functional and geometrical dysfunction of but not limited to the valve. 3D Slicer was used for semi-automatic valve border detection and volume-rendering of clinical 3D echocardiographic data. FEM based models were also calculated. METHOD: A Philips/HP Sonos 5500 ultrasound device stores volume data as time-resolved 4D volume data sets. Data sets for three subjects were used. Since 3D Slicer does not process time-resolved data sets, we employed a standard movie maker to animate the individual time-based models and visualizations. Calculation time and model size were minimized. Pressures were also easily available. We speculate that calculation of instantaneous elastance may be possible using instantaneous pressure values and tissue deformation data derived from the animated FEM

Computational fluid dynamics indicators to improve cardiovascular pathologies

In recent years, the study of computational hemodynamics within anatomically complex vascular regions has generated great interest among clinicians. The progress in computational fluid dynamics, image processing and high-performance computing haveallowed us to identify the candidate vascular regions for the appearance of cardiovascular diseases and to predict how this disease may evolve. Medicine currently uses a paradigm called diagnosis. In this thesis we attempt to introduce into medicine the predictive paradigm that has been used in engineering for many years. The objective of this thesis is therefore to develop predictive models based on diagnostic indicators for cardiovascular pathologies. We try to predict the evolution of aortic abdominal aneurysm, aortic coarctation and coronary artery disease in a personalized way for each patient. To understand how the cardiovascular pathology will evolve and when it will become a health risk, it is necessary to develop new technologies by merging medical imaging and computational science. We propose diagnostic indicators that can improve the diagnosis and predict the evolution of the disease more efficiently than the methods used until now. In particular, a new methodology for computing diagnostic indicators based on computational hemodynamics and medical imaging is proposed. We have worked with data of anonymous patients to create real predictive technology that will allow us to continue advancing in personalized medicine and generate more sustainable health systems. However, our final aim is to achieve an impact at a clinical level. Several groups have tried to create predictive models for cardiovascular pathologies, but they have not yet begun to use them in clinical practice. Our objective is to go further and obtain predictive variables to be used practically in the clinical field. It is to be hoped that in the future extremely precise databases of all of our anatomy and physiology will be available to doctors. These data can be used for predictive models to improve diagnosis or to improve therapies or personalized treatments.En els últims anys, l'estudi de l'hemodinàmica computacional en regions vasculars anatòmicament complexes ha generat un gran interès entre els clínics. El progrés obtingut en la dinàmica de fluids computacional, en el processament d'imatges i en la computació d'alt rendiment ha permès identificar regions vasculars on poden aparèixer malalties cardiovasculars, així com predir-ne l'evolució. Actualment, la medicina utilitza un paradigma anomenat diagnòstic. En aquesta tesi s'intenta introduir en la medicina el paradigma predictiu utilitzat des de fa molts anys en l'enginyeria. Per tant, aquesta tesi té com a objectiu desenvolupar models predictius basats en indicadors de diagnòstic de patologies cardiovasculars. Tractem de predir l'evolució de l'aneurisma d'aorta abdominal, la coartació aòrtica i la malaltia coronària de forma personalitzada per a cada pacient. Per entendre com la patologia cardiovascular evolucionarà i quan suposarà un risc per a la salut, cal desenvolupar noves tecnologies mitjançant la combinació de les imatges mèdiques i la ciència computacional. Proposem uns indicadors que poden millorar el diagnòstic i predir l'evolució de la malaltia de manera més eficient que els mètodes utilitzats fins ara. En particular, es proposa una nova metodologia per al càlcul dels indicadors de diagnòstic basada en l'hemodinàmica computacional i les imatges mèdiques. Hem treballat amb dades de pacients anònims per crear una tecnologia predictiva real que ens permetrà seguir avançant en la medicina personalitzada i generar sistemes de salut més sostenibles. Però el nostre objectiu final és aconseguir un impacte en l¿àmbit clínic. Diversos grups han tractat de crear models predictius per a les patologies cardiovasculars, però encara no han començat a utilitzar-les en la pràctica clínica. El nostre objectiu és anar més enllà i obtenir variables predictives que es puguin utilitzar de forma pràctica en el camp clínic. Es pot preveure que en el futur tots els metges disposaran de bases de dades molt precises de tota la nostra anatomia i fisiologia. Aquestes dades es poden utilitzar en els models predictius per millorar el diagnòstic o per millorar teràpies o tractaments personalitzats.Postprint (published version

Computer modeling and signal analysis of cardiovascular physiology

This dissertation aims to study cardiovascular physiology from the cellular level to the whole heart level to the body level using numerical approaches. A mathematical model was developed to describe electromechanical interaction in the heart. The model integrates cardio-electrophysiology and cardiac mechanics through excitation-induced contraction and deformation-induced currents. A finite element based parallel simulation scheme was developed to investigate coupled electrical and mechanical functions. The developed model and numerical scheme were utilized to study cardiovascular dynamics at cellular, tissue and organ levels. The influence of ion channel blockade on cardiac alternans was investigated. It was found that the channel blocker may significantly change the critical pacing period corresponding to the onset of alternans as well as the alternans’ amplitude. The influence of electro-mechanical coupling on cardiac alternans was also investigated. The study supported the earlier assumptions that discordant alternans is induced by the interaction of conduction velocity and action potential duration restitution at high pacing rates. However, mechanical contraction may influence the spatial pattern and onset of discordant alternans. Computer algorithms were developed for analysis of human physiology. The 12-lead electrocardiography (ECG) is the gold standard for diagnosis of various cardiac abnormalities. However, disturbances and mistakes may modify physiological waves in ECG and lead to wrong diagnoses. This dissertation developed advanced signal analysis techniques and computer software to detect and suppress artifacts and errors in ECG. These algorithms can help to improve the quality of health care when integrated into medical devices or services. Moreover, computer algorithms were developed to predict patient mortality in intensive care units using various physiological measures. Models and analysis techniques developed here may help to improve the quality of health care

A systematic review of the prediction of hospital length of stay:Towards a unified framework

Hospital length of stay of patients is a crucial factor for the effective planning and management of hospital resources. There is considerable interest in predicting the LoS of patients in order to improve patient care, control hospital costs and increase service efficiency. This paper presents an extensive review of the literature, examining the approaches employed for the prediction of LoS in terms of their merits and shortcomings. In order to address some of these problems, a unified framework is proposed to better generalise the approaches that are being used to predict length of stay. This includes the investigation of the types of routinely collected data used in the problem as well as recommendations to ensure robust and meaningful knowledge modelling. This unified common framework enables the direct comparison of results between length of stay prediction approaches and will ensure that such approaches can be used across several hospital environments. A literature search was conducted in PubMed, Google Scholar and Web of Science from 1970 until 2019 to identify LoS surveys which review the literature. 32 Surveys were identified, from these 32 surveys, 220 papers were manually identified to be relevant to LoS prediction. After removing duplicates, and exploring the reference list of studies included for review, 93 studies remained. Despite the continuing efforts to predict and reduce the LoS of patients, current research in this domain remains ad-hoc; as such, the model tuning and data preprocessing steps are too specific and result in a large proportion of the current prediction mechanisms being restricted to the hospital that they were employed in. Adopting a unified framework for the prediction of LoS could yield a more reliable estimate of the LoS as a unified framework enables the direct comparison of length of stay methods. Additional research is also required to explore novel methods such as fuzzy systems which could build upon the success of current models as well as further exploration of black-box approaches and model interpretability

Predictive analytics framework for electronic health records with machine learning advancements : optimising hospital resources utilisation with predictive and epidemiological models

The primary aim of this thesis was to investigate the feasibility and robustness of predictive machine-learning models in the context of improving hospital resources’ utilisation with data- driven approaches and predicting hospitalisation with hospital quality assessment metrics such as length of stay. The length of stay predictions includes the validity of the proposed methodological predictive framework on each hospital’s electronic health records data source. In this thesis, we relied on electronic health records (EHRs) to drive a data-driven predictive inpatient length of stay (LOS) research framework that suits the most demanding hospital facilities for hospital resources’ utilisation context. The thesis focused on the viability of the methodological predictive length of stay approaches on dynamic and demanding healthcare facilities and hospital settings such as the intensive care units and the emergency departments. While the hospital length of stay predictions are (internal) healthcare inpatients outcomes assessment at the time of admission to discharge, the thesis also considered (external) factors outside hospital control, such as forecasting future hospitalisations from the spread of infectious communicable disease during pandemics. The internal and external splits are the thesis’ main contributions. Therefore, the thesis evaluated the public health measures during events of uncertainty (e.g. pandemics) and measured the effect of non-pharmaceutical intervention during outbreaks on future hospitalised cases. This approach is the first contribution in the literature to examine the epidemiological curves’ effect using simulation models to project the future hospitalisations on their strong potential to impact hospital beds’ availability and stress hospital workflow and workers, to the best of our knowledge. The main research commonalities between chapters are the usefulness of ensembles learning models in the context of LOS for hospital resources utilisation. The ensembles learning models anticipate better predictive performance by combining several base models to produce an optimal predictive model. These predictive models explored the internal LOS for various chronic and acute conditions using data-driven approaches to determine the most accurate and powerful predicted outcomes. This eventually helps to achieve desired outcomes for hospital professionals who are working in hospital settings

In-Vitro and In-Silico Investigations of Alternative Surgical Techniques for Single Ventricular Disease

Single ventricle (SV) anomalies account for one-fourth of all cases of congenital Heart disease. The conventional second and third stage i.e. Comprehensive stage II and Fontan procedure of the existing three-staged surgical approach serving as a palliative treatment for this anomaly, entails multiple complications and achieves a survival rate of 50%. Hence, to reduce the morbidity and mortality rate associated with the second and third stages of the existing palliative procedure, the novel alternative techniques called “Hybrid Comprehensive Stage II” (HCSII), and a “Self-powered Fontan circulation” have been proposed. The goal of this research is to conduct in-vitro investigations to validate computational and clinical findings on these proposed novel surgical techniques. The research involves the development of a benchtop study of HCSII and self-powered Fontan circulation

Interpretable Mechanistic and Machine Learning Models for Pre-dicting Cardiac Remodeling from Biochemical and Biomechanical Features

Biochemical and biomechanical signals drive cardiac remodeling, resulting in altered heart physiology and the precursor for several cardiac diseases, the leading cause of death for most racial groups in the USA. Reversing cardiac remodeling requires medication and device-assisted treatment such as Cardiac Resynchronization Therapy (CRT), but current interventions produce highly variable responses from patient to patient. Mechanistic modeling and Machine learning (ML) approaches have the functionality to aid diagnosis and therapy selection using various input features. Moreover, \u27Interpretable\u27 machine learning methods have helped make machine learning models fairer and more suited for clinical application. The overarching objective of this doctoral work is to develop computational models that combine an extensive array of clinically measured biochemical and biomechanical variables to enable more accurate identification of heart failure patients prone to respond positively to therapeutic interventions. In the first aim, we built an ensemble ML classification algorithm using previously acquired data from the SMART-AV CRT clinical trial. Our classification algorithm incorporated 26 patient demographic and medical history variables, 12 biomarker variables, and 18 LV functional variables, yielding correct CRT response prediction in 71% of patients. In the second aim, we employed a machine learning-based method to infer the fibrosis-related gene regulatory network from RNA-seq data from the MAGNet cohort of heart failure patients. This network identified significant interactions between transcription factors and cell synthesis outputs related to cardiac fibrosis - a critical driver of heart failure. Novel filtering methods helped us prioritize the most critical regulatory interactions of mechanistic forward simulations. In the third aim, we developed a logic-based model for the mechanistic network of cardiac fibrosis, integrating the gene regulatory network derived from aim two into a previously constructed cardiac fibrosis signaling network model. This integrated model implemented biochemical and biomechanical reactions as ordinary differential equations based on normalized Hill functions. The model elucidated the semi-quantitative behavior of cardiac fibrosis signaling complexity by capturing multi-pathway crosstalk and feedback loops. Perturbation analysis predicted the most critical nodes in the mechanistic model. Patient-specific simulations helped identify which biochemical species highly correlate with clinical measures of patient cardiac function