Assessment of the relationship between myocardial microstructure and microvascular perfusion using cardiac magnetic resonance: novel imaging biomarker

PGR-P-178

Key facts

Type of research degree: 4 year PhD
Application deadline: Ongoing deadline
Country eligibility: International (outside UK)
Funding: Non-funded
Supervisors: Dr Erica Dall'Armellina and Dr Irvin Teh
Additional supervisors: Sven Plein, Jurgen Schneider
Schools: School of Medicine
Research groups/institutes: Leeds Institute of Cardiovascular and Metabolic Medicine

<h2 class="heading hide-accessible">Summary</h2>

The spatial interaction between the vessels and the arrangement of the cardiomyocytes is crucial to maintain an efficient delivery of oxygen to the cells. Current imaging techniques allow for the assessment of myocardial blood flow as indirect measurement of perfusion but lack to quantify the actual efficiency of oxygen delivery in the context of the 3D myocardial architecture.

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

Knowledge of this interrelationship is particularly crucial in cardiac disease such as hypertrophic cardiomyopathy (HCM), which is characterized by cardiomyocytes disarray and myocardial perfusion abnormalities due to dysfunction of the microcirculation. Recent technical developments in diffusion-weighted Magnetic Resonance Imaging could potentially allow for investigating the perfusion system in relation to cardiomyocyte architecture in more detail and provide new biomarkers of cardiac disease. This proposal aims to establish a novel diffusion weighted technique (i.e. Intra-Voxel Incoherent Motion – IVIM) to assess myocardial perfusion in relation to the myocardial micro-architecture. We propose to validate the technique on the isolated perfused rat heart; we will then establish baseline parameters and reproducibility in volunteers. We finally will investigate the clinical utility of the IVIM biomarkers in HCM patients, although novel IVIM biomarkers may also allow for more accurate risk stratification in other cardiac diseases. <h3>References:</h3> Maron, B.J. and M.S. Maron,Lancet, 2013. 381. Maron, B.J. and M.S. Maron,The American Journal of Cardiology, 2016. 118(12): p. 1897-1907. Maron, B.J., et al.,Circulation, 2000. 102(8): p. 858-64. Maron, M.S., et al.,Journal of the American College of Cardiology, 2016. 67(12): p. 1399-1409. Elliott, P.M., et al.,European Heart Journal, 2014. 35(39): p. 2733-2779. Hughes, S.E.,Histopathology, 2004. 44. Raphael, C.E., et al.,Journal of the American College of Cardiology, 2016. 68(15): p. 1651-1660. Cecchi, F., et al.,New England Journal of Medicine, 2003. 349(11): p. 1027-1035. Ismail, T.F., et al.,J Cardiovasc Magn Reson, 2014. 16: p. 49. Petersen, S.E., et al.,Circulation, 2007. 115(18): p. 2418-25. Basso, C., et al.,Hum Pathol, 2000. 31(8): p. 988-98. Harris, K.M., et al.,Circulation, 2006. 114(3): p. 216-25. Maron, M.S., et al.,Circulation: Heart Failure, 2008. 1(3): p. 184. O‘Hanlon, R., et al.,Journal of the American College of Cardiology, 2010. 56(11): p. 867-874. Green, J.J., et al.,JACC: Cardiovascular Imaging, 2012. 5(4): p. 370-377. Adabag, A.S., et al.,Journal of the American College of Cardiology, 2008. 51(14): p. 1369-1374. Maron, M.S., et al.,J Am Coll Cardiol, 2009. 54. Camici, P.G., I. Olivotto, and O.E. Rimoldi,Journal of Molecular and Cellular Cardiology. 52(4): p. 857-864. Knaapen, P., et al.,American Journal of Physiology - Heart and Circulatory Physiology, 2008. 294(2): p. H986. Lockie, T., et al.,Journal of the American College of Cardiology, 2011. 57(1): p. 70-75. Kellman, P., et al.,J Cardiovasc Magn Reson, 2017. 19(1): p. 43. Engblom, H., et al.,J Cardiovasc Magn Reson, 2017. 19(1): p. 78. Henkelman, R.M.,Magn Reson Med, 1990. 16(3): p. 470-5. Tunnicliffe, E.M., et al.,J Cardiovasc Magn Reson, 2014. 16: p. 31. Nielles-Vallespin, S., et al.,J Am Coll Cardiol, 2017. 69(6): p. 661-676. Teh, I., et al.,Sci Rep, 2016. 6: p. 30573. McGill, L.A., et al.,J Cardiovasc Magn Reson, 2012. 14. Ferreira, P.F., et al.,Journal of Cardiovascular Magnetic Resonance, 2014. 16(1): p. 87. Le Bihan, D., et al.,Radiology, 1988. 168(2): p. 497-505. Le Bihan, D., et al.,Radiology, 1986. 161(2): p. 401-7. Bihan, D.L. and R. Turner,Magnetic Resonance in Medicine, 1992. 27(1): p. 171-178. Le Bihan, D.,Radiology, 2008. 249(3): p. 748-52. Spinner, G.R., et al.,J Cardiovasc Magn Reson, 2017. 19(1): p. 85. Moulin, K., et al.,Magn Reson Med, 2016. 76(1): p. 70-82. Delattre, B.M., et al.,Investigative radiology, 2012. 47(11): p. 662-70. Callot, V., et al.,Magn Reson Med, 2003. 50(3): p. 531-40. Abdullah, O.M., et al.,Magnetic Resonance in Medicine, 2016. 76(4): p. 1252-1262. Scott, A.D., et al.,Magn Reson Med, 2015. 74(2): p. 420-30. McClymont, D., I. Teh, and J.E. Schneider,J Cardiovasc Magn Reson, 2017. 19(1): p. 90. Stoeck, C.T., et al.,Magnetic Resonance in Medicine, 2016. 75(4): p. 1669-1676. Lohezic, M., et al.,Progress in Biophysics and Molecular Biology, 2014. 115(2): p. 213-225.

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

Please note these are not standalone projects and applicants must apply to the PhD academy directly. Applications can be made at any time. You should complete an <a href="https://medicinehealth.leeds.ac.uk/faculty-graduate-school/doc/apply-2">online application form</a> and attach the following documentation to support your application.  <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks (or marks so far if still studying)</li> <li>Evidence that you meet the programme’s minimum English language requirements (if applicable, see requirement below)</li> <li>Evidence of funding to support your studies</li> </ul> To help us identify that you are applying for this project please ensure you provide the following information on your application form; <ul> <li>Select PhD in Cardiovascular and Metabolic Disease as your programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul>

<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 minimum requirements for this programme in IELTS and TOEFL tests are: • British Council IELTS - score of 7.0 overall, with no element less than 6.5 • 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>

For further information please contact the Faculty Graduate School e:<a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a>