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Non-invasive advanced imaging biomarkers to improve optimal timing of interventions in tetralogy of fallot

PGR-P-193

Key facts

Type of research degree
4 year PhD
Application deadline
Ongoing deadline
Country eligibility
International (outside UK)
Funding
Non-funded
Supervisors
Dr Malenka Bissell and Professor Sven Plein
Schools
School of Medicine
Research groups/institutes
Leeds Institute of Cardiovascular and Metabolic Medicine
<h2 class="heading hide-accessible">Summary</h2>

Congenital heart disease is an expanding specialty as the majority of children with congenital heart disease now survive well into adulthood. After initial surgical management in childhood many patients remain stable in their teens but often further surgical interventions become necessary in adulthood. Active surveillance and early re-intervention to prevent irreversible damage are key management strategies. However, bioprosthetic and other non-bioprosthetic material have a limited life span and intervention too early in the disease process will lead to added surgeries, added risks and potential complications over the patients&amp;rsquo; lifetime. Therefore careful timing of further intervention is essential. Cardiovascular Magnetic Resonance (CMR) has evolved as an invaluable tool in assessing patients for interventions. CMR gives highly reproducible measurements which are indexed to body surface area. This does however assume that as children reach adulthood and their heart size has reached adult size, they stop growing in height and weight not accounting for obese patients. Therefore additional non-invasive imaging biomarkers are necessary to better define advanced, more precise and body size independent parameters to guide optimal timing of intervention.

<h2 class="heading hide-accessible">Full description</h2>

<h3>The main research question:</h3> <p>When is the optimal time to intervene in tetralogy of fallot allowing for post-operative normalisation of volume and function without intervening too early creating additional future interventions in a patient&rsquo;s lifetime?</p> <h3>Hypothesis</h3> <ul> <li>Right ventricular impairment can be predicted at an earlier stage using advanced haemodynamic and myocardial energetic imaging biomarkers enabling optimisation of timing of intervention in tetralogy of fallot</li> <li>Advanced imaging biomarkers can be used independent of body habitus and optimise timing of intervention further in obese patients</li> <li>Ventricular interdependence is a contributor to disease progression in right ventricular heart disease in tetralogy of fallot and early changes in the left ventricle may better inform timing of intervention than assessment of the right ventricle alone.</li> <li>Advanced imaging biomarkers can differentiate between the volume loaded and the pressure loaded right ventricle</li> </ul> <h2>Project design</h2> <p>This project is looking at a very interesting group of patients with tetralogy of fallot which to date have not been studied in a larger cohort using advanced imaging biomarkers.&nbsp;</p> <p>Recruitment for this study is already underway by our congenital cardiac research nurse. The study groups we recruiting are:</p> <p>1) Tetralogy of fallot patients currently undergoing intervention/surgery such as pulmonary valve replacement or pulmonary artery stenting</p> <p>2) Children and young adults of varying age groups who have repaired tetralogy of fallot and are well</p> <p>3) Age and sex matched healthy volunteers.</p> <p>All participants attend for a research CMR scan where we acquire standard and advanced imaging data such as 4D flow MRI.</p> <p>4D flow MRI is a very versatile CMR technique and a multitude of different parameters can be analysed and assessed by using commercially available and research specific analysis platforms. This PhD project will start with providing comprehensive training in standard and advanced CMR analysis.</p> <p>Initial work will involve analysing healthy volunteer datasets to establish optimal image resolution, analysis technique and reporting standards for these parameters. Furthermore this work will define normal values for these novel parameters. The 4D flow MRI parameters will then be assessed in the patient cohort before and after pulmonary valve replacement/pulmonary artery stent placement. Promising parameters that show a change after valve replacement will then be assessed in the well tetralogy of fallot group as comparison. Further subgroup analysis will include comparing patients with a volume loaded right heart compared to a pressure loaded heart. This data will then be compared to cardiac catheter data.</p> <p>Statistical analysis will include evaluation of the 4D flow MRI parameters to assess whether these may help plan timing of interventions.</p> <h3>Potential of research for patient care</h3> <p>Risk assessment by cardiac imaging is well established for many adult cardiovascular diseases, and is already routinely used for monitoring and management decisions. We hope our study will add new understanding to current practice by developing new advanced imaging biomarkers for the paediatric and adult congenital heart disease population. This will hopefully lead to improved patient selection and improved timing for interventional/surgical procedures in these patients which will improve their long term survival.</p> <p><strong>References</strong></p> <p>(1) Hirtler D, Garcia J, Barker AJ, Geiger J. Assessment of intracardiac flow and vorticity in the right heart of patients after repair of tetralogy of Fallot by flow-sensitive 4D MRI. Eur Radiol 2016 Jan 8.</p> <p>(2) Fogel MA, Pawlowski T, Keller MS, Cohen MS, Goldmuntz E, Diaz L, et al. The Cardiovascular Effects of Obesity on Ventricular Function and Mass in Patients after Tetralogy of Fallot Repair. J Pediatr 2015 Aug;167(2):325-30.e1.</p> <p>(3) Geiger J, Markl M, Jung B, Grohmann J, Stiller B, Langer M, et al. 4D-MR flow analysis in patients after repair for tetralogy of Fallot. Eur Radiol 2011 Aug;21(8):1651-1657.</p> <p>(4) Geva T. Repaired tetralogy of Fallot: the roles of cardiovascular magnetic resonance in evaluating pathophysiology and for pulmonary valve replacement decision support. J Cardiovasc Magn Reson 2011 Jan 20;13:9-429X-13-9.</p>

<h2 class="heading">How to apply</h2>

<p>Please note these are not standalone projects and applicants must apply to the PhD academy directly.</p> <p>Applications can be made at any time. To apply for this project applicants should complete a<a href="https://medicinehealth.leeds.ac.uk/downloads/download/129/faculty_graduate_school_-_application_form"> Faculty Application Form</a> and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>We also require 2 academic references to support your application. Please ask your referees to send these <a href="https://medicinehealth.leeds.ac.uk/downloads/download/130/faculty_graduate_school_-_scholarship_reference_form">references</a> on your behalf, directly to <a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p> <p>If you have already applied for other projects using the Faculty Application Form this academic session you do not need to complete this form again. Instead you should email fmhgrad to inform us you would like to be considered for this project.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject may also be required in some areas of the Faculty. For entry requirements for all other research degrees we offer, please contact us.

<h2 class="heading heading--sm">English language requirements</h2>

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Medicine and Health minimum requirements in IELTS and TOEFL tests for PhD, MSc, MPhil, MD are: &acirc;&euro;&cent; British Council IELTS - score of 7.0 overall, with no element less than 6.5 &acirc;&euro;&cent; TOEFL iBT - overall score of 100 with the listening and reading element no less than 22, writing element no less than 23 and the speaking element no less than 24.

<h2 class="heading">Contact details</h2>

<p>For further information please contact the Graduate School Office<br /> e:&nbsp;<a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a>, t: +44 (0)113 343 8221</p>


<h3 class="heading heading--sm">Linked research areas</h3>