Faculty of Biological Sciences

Dr Eleftheria Pervolaraki

BSc(Hons), Portsmouth; MSc, Leicester; PhD, Cardiff
Visiting Research Fellow
School of Biomedical Sciences

Contact:  Garstang 7.53, +44(0) 113 34 31869, email address for  

You can read more about Dr Pervolaraki's interests here:
http://vtea.leeds.ac.uk/
http://rsfs.royalsocietypublishing.org/content/3/2.cover-expansion
http://www.leeds.ac.uk/news/article/3368/human_heart_development_slower_than_other_mammals
http://www.vph-institute.org/news/developed-computational-imaging-tools-for-representing-foetal-heart-through-gestation.html

Research Interests

Bioimaging and modelling of human cardiac foetal and neonatal development; enabling early diagnosis of disorders and evaluation of their treatment.

Background:

The development of the human heart is poorly understood, principally as research thus far has been employing animal models. I have recently shown that data generated from animal models does not describe human foetal cardiac development, because of differences between species. This fundamental lack of knowledge has serious clinical consequences when we try to assess normal and abnormal foetal development. I lead a novel research effort to make ground-breaking discoveries in three areas: (i) the development of structure and architecture of the human heart via the use of MRI, (ii) the development of human cardiac activity as detected and measured with non-invasive electrophysiological recordings (ECGs), and (iii) integrating all of the data into a comprehensive predictive tool to be used by clinicians working on the development of the human heart and its disorders.

 

Reconstruction of 3D geometry and ventricular wall architecture of human hearts during gestation: 

I have developed specialised MRI protocols and applied them to reconstruct the 3D structure of human foetal hearts from 14 to 20 weeks gestational age. An imaging protocol (FLASH MRI) combined with a clinically used contrast agent (gadolinium) has been used to reconstruct the geometry and principal structures (vessels, atria, ventricles, coronary arteries and Purkinje fibres) of the whole heart. Although the cardiac chambers develop by week 12, the transmural architecture of the ventricular walls does not appear until week 20 (Fig 1c). A more organised and defined structure with canonical cellular organisation was apparent in gestational week 20, when tractography (the mapping of fibres across the tissue) became possible (Fig 1b). Tractographic methods prior to the 18th week of gestation have failed to provide great details due to the lack of clear organisation. This organisation is important for effective cardiac contractions and can be used to produce propagation maps within the heart during normal sinus rhythm (NSR) and foetal arrhythmias (Fig 1d).

Figure 2: Human foetal electrophysiological models: (a) Signal taken from a foetal electrocardiogram (fECG) showing normal sinus rhythm (fNSR) and ventricular tachycardia (fVT) from which the ECG characteristics were extracted (QT in black square, PR in blue diamonds and QR in red triangles). (b) Computed fNSR at 25 weeks gestational age for a variety of cardiac cells. (c) Congenital heart block (CHB) computed with a spatially uniform reduction in GCaL. (d) Computed self-terminating arrhythmia and persistent re-entrant propagation.

 

Models of ventricular electrophysiology informed by foetal and neonatal ECGs:

A pilot study (in collaboration with Dr Nigel Simpson) on pregnant volunteers (Fig 2a) has revealed quantitative characteristics of the foetal ECG. Using the ECG data, I have been able to study (Fig 2a) RR intervals, providing pacemaking rates, PR and QR intervals, providing indices of propagation times, and QT intervals, providing an index of ventricular action potential duration (APD) and its restitution. These foetal intervals were used to construct cardiac models at normal sinus rhythm (fNSR; Fig 2b) of cell types including: sinoatrial node (SAN), atrial (ATR), atrio-ventricular node (AVN), Purkinje fibres (PF) and ventricular. The ability to compute normal sinus rhythm has allowed the construction of initial computational models of the foetal heart during pathophysiological conditions, including congenital heart block (Fig 2c) and foetal arrhythmias, either self-terminating or persistent (Fig 2d).

Figure 2: Human foetal electrophysiological models: (a) Signal taken from a foetal electrocardiogram (fECG) showing normal sinus rhythm (fNSR) and ventricular tachycardia (fVT) from which the ECG characteristics were extracted (QT in black square, PR in blue diamonds and QR in red triangles). (b) Computed fNSR at 25 weeks gestational age for a variety of cardiac cells. (c) Congenital heart block (CHB) computed with a spatially uniform reduction in GCaL. (d) Computed self-terminating arrhythmia and persistent re-entrant propagation.

 

Current Projects

Collaborators:

Professor Arun V Holden (Leeds)

Professor Ed White (Leeds)

Professor Martyn Paley (Sheffield)

Professor Barrie Hayes-Gill (Monica Healthcare Ltd)

Professor Richard A Anderson (Edinburgh, MRC Centre for Reproductive Health)

Dr Al Benson (Leeds)

Dr James Dachtler (Durham)

 

Studentship information

Undergraduate project topics:

  • Foetal cardiac arrhythmias: a possible mechanism for the 60% of preterm stillbirths that have no apparent cause on autopsy.
  • Quantitative analysis of diffusion tensor magnetic resonance imaging data of the developing heart.
  • 3D reconstruction of human cardiac geometry during development, using MRI datasets.

See also:

Pervolaraki E, Anderson RA, Benson AP, Hayes-Gill B, Holden AV, Moore BJR, Paley MN, Zhang H Antenatal architecture and activity of the human heart Interface Focus 3 -, 2013
DOI:10.1098/rsfs.2012.0065
View abstract

Temple IP, Logantha SJRJ, Absi M, Zhang Y, Pervolaraki E, Yanni J, Atkinson A, Petkova M, Quigley GM, Castro S, Drinkhill M, Schneider H, Monfredi O, Cartwright E, Zi M, Yamanushi TT, Mahadevan VS, Gurney AM, White E, Zhang H, Hart G, Boyett MR, Dobrzynski H Atrioventricular Node Dysfunction and Ion Channel Transcriptome in Pulmonary Hypertension Circulation: Arrhythmia and Electrophysiology 9 -, 2016
DOI:10.1161/CIRCEP.115.003432
View abstract

Atkinson L, Basharat A, Benson AP, Colman MA, Holden AV, Kagugube GW, Pervolaraki E Computational modelling of cardiac electrophysiological changes in malarial fever, 2016
View abstract

Pervolaraki E, Drinkhill M, Fowler E, Stones R, White E The beta 1-Adrenergic Receptor Blocker, Metoprolol, Improves Survival and Electrical Remodeling in Rats with Pulmonary Artery Hypertension, 2016

Hodgson S, Holden AV, Benson AP, Pervolaraki E Congenital heart block in a one-dimensional computational model of the human fetal heart, 2015

Benson AP, Hayes-Gill B, Holden AV, Matthews R, Naz A, Page S, Pervolaraki E, Spofford E, Tayebjee M Self-terminating re-entrant cardiac arrhythmias: Quantitative characterization Computing in Cardiology 42 641-644, 2015
DOI:10.1109/CIC.2015.7410992
View abstract

Pervolaraki E, Hodgson S, Holden AV, Benson AP Towards computational modelling of the human foetal electrocardiogram: normal sinus rhythm and congenital heart block. Europace 16 758-765, 2014
DOI:10.1093/europace/eut377
View abstract

Benson AP, Bleakley A, Hodgson S, Holden AV, Pelech N, Palkhi E, Pervolaraki E, Whitfield C Computational modeling of human fetal normal sinus rhythm and arrhythmia Computing in Cardiology 40 37-40, 2013
View abstract

Pervolaraki E, Holden AV Spatiotemporal patterning of uterine excitation patterns in human labour. Biosystems 112 63-72, 2013
DOI:10.1016/j.biosystems.2013.03.012
View abstract

Aslanidi OV, Al-Owais M, Benson AP, Colman M, Garratt CJ, Gilbert SH, Greenwood JP, Holden AV, Kharche S, Kinnell E, Pervolaraki E, Plein S, Stott J, Zhang H Virtual tissue engineering of the human atrium: modelling pharmacological actions on atrial arrhythmogenesis. Eur J Pharm Sci 46 209-221, 2012
DOI:10.1016/j.ejps.2011.08.014
View abstract

Pervolaraki E, Holden AV Human uterine excitation patterns leading to labour: Synchronization or propagation? Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 7223 LNCS 162-176, 2012
DOI:10.1007/978-3-642-28792-3_21
View abstract

Wright N, Glazewski S, Hardingham N, Phillips K, Pervolaraki E, Fox K Laminar analysis of the role of GluR1 in experience-dependent and synaptic depression in barrel cortex. Nat Neurosci 11 1140-1142, 2008
DOI:10.1038/nn.2188
View abstract

Biktasheva IV, Anderson RA, Holden AV, Pervolaraki E, Wen F Cardiac re-entry dynamics&self-termination in DT-MRI based model of Human Foetal Heart Chaos -,
View abstract

Marcinkevics R, O'Neill J, Law H, Pervolaraki E, Hogarth A, Russell CR, Stegemann B, Holden AV, Tayebjee MH Multichannel ECG diagnostics for the diagnosis of arrhythmogenic right ventricular dysplasia EP-Europace -,
View abstract