For more information please contact Prof. dr. Piet Claus, tel.: +3216349017, mail: firstname.lastname@example.org.
You can apply for this job no later than September 10, 2019 via the online application tool.
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The project will be conducted in the Lab on Cardiovascular Imaging and Dynamics (supervised by prof. P. Claus, promoter) and Nuclear Medicine (supervised by prof. O. Gheysens, co-promoter) in close collaboration with the Laboratory of Experimental Cardiology (profs. R. Willems and K. Sipido). During the project other (international) collaborators will be involved. Both labs are internationally oriented and are part of the Department of Cardiovascular Sciences. The department has a long tradition of translational and multidisciplinary research, with PI from basic science, such as cardiovascular biology to engeneering and physics to clinical scientists involved in research in the academic hospital.
Sudden Cardiac Death (SCD) is the second leading cause of death after all cancers combined in Western society. The incidence of SCD is estimated to be as high as 400 000 deaths/year in Europe. Lethal ventricular arrhythmia such as ventricular tachycardia (VT) and ventricular fibrillation (VF) underlie the vast majority of unexpected sudden cardiac deaths (SCD).
Up to 70% of these SCDs are related to myocardial ischemia, infarction and subsequent heart failure as an underlying structural cardiac abnormality (ischemic cardiomyopathy, ICMP).
Moreover, theoccurrence of SCD varies in time similar to variations of blood pressure suggesting a pro-arrhythmic effect of fluctuations in afterload. We demonstrated previously in experimental models that an acute blood pressure increase resulted in an abrupt left ventricular pressure decline, which had a profound effect on myocardial mechanics with enhanced post-systolic shortening and coincided with induced transient depolarizations and pressure-induced premature beats (PIPB).
In this project we want to elucidate the mechanisms of the origin of PIPBs and toprovide evidence that these PIPBs arising from the myocardial infarct borderzone can trigger VA in ICMP. We hypothesize that the activation of stretchactivated non-selective cation channels and the mechano-sensitivity of Ca2+signaling are responsible for this mechano-electrical coupling and that the border zone of an infarct is a specific “area at risk” for the genesis of these PIPBs because of the increased strain on this region, increased oxidative stress and regional changes in cardiac innervation. With specific pharmacological tools, merging of cardiac activation maps with information derived from simultaneous MRI and PET imaging using specific tracers we will investigate the pathophysiologic and regional origin of these PIPBs as triggers for VA in ICMP.
The specific PhD project
The specific aim of this PhD project is to develop processing pipelines to combine extensive imaging and electrophysiology data into anatomically accurate models of the ischemic heart, suited for further use in computational analyses. Challenges are the multiple resolutions of the different imaging and electrophysiological data. The further development of a multiscale bi-ventricular model, with details of fibrotic tissue (from ex-vivo scans), innervation of the infarct border zone (from PET imaging), tissue deformation (from MRI or ultrasound), electrical activation from single beat non-contact as well as contact mapping, should allow for a comprehensive evaluation and provide insight into infarct border zone remodelling. Depending on progress further analyses will consist of simulating mechano-electrical feedback. Hereto, we will implement these models in existing dedicated cardiovascular modelling software. There will be a close collaboration with the basic and clinical PhD students for data gathering in an animal model of ICMP.
We are looking for a highly motivated young researcher with a Master degree (or equivalent) in Biomedical Engineering,Physics, Mechanical Engineering, Applied Mathematics, Computational Science, or related disciplines, willing to study and do research at the leading edge of biomedical engineering. Experience with computer sciences and having proven programming skills are important.
Candidates should have excellent teamwork and communication skills and should be enthusiastic about collaborating with a diverse range of local and international partners. We expect them to be fluent in English as this will be the language used to interrelate with the different partners.
On the basis of this project, a training plan will be set up by selecting the best training opportunities in the PhD program of KULeuven and available initiatives within our collaborator's labs. Physiology training will be organized depending on the needs and background of the researcher and the project and you are expected to join and lead discussion groups.
Our research group wants to focus on translational research integrating engineering/physics with physiology, working closely together with the academic clinical center. Therefore, our group provides methodologies and offers support for clinical and basic researchers to help to define the research approach from the basic understanding of the disease towards the clinical study; to select/design the appropriate investigational tools to assess the relevant physiological parameters; and to interpret the results and relate them to the pathophysiological knowledge. Therefore, willingness to invest into learning pathophysiology is a must.
We offer a 4 year PhD fellowship in an interdisciplinary and international academic environment.