1st Supervisor: Enrico De Vita, King’s College London
2nd Supervisor: Jana Hutter, King’s College London
Clinical Champion: Mary Rutherford, King’s College London
Additional Supervisor: Jo Hajnal, King’s College London
Aim of the PhD Project:
We recently proposed a prototype Arterial spin labelling method to visualise maternal blood delivery to the placenta (placental perfusion) with MRI.
We aim to further optimise this method making it quantitative and to efficiently combine it with other quantitative MRI techniques, in particular diffusion, oxygenation related (T2*) measurements and angiography to further elucidate placental blood flow dynamics within the placenta.
Project Description / Background:
The placenta is key to successful pregnancies as it ensures the supply of oxygen to the growing fetus. Major pregnancy complications, e.g. fetal growth restriction (FGR), significantly contributing to fetal mortality and morbidity and lifelong complications, are linked to placental insufficiency.
However, slow fetal growth is the endpoint of a cascade of events, i.e. altered maternal inflow, reduced tissue perfusion, damaged microstructure to finally decreased oxygen uptake – none of which can be assessed by ultrasound.
Recently, MRI successfully detected deviations in these functional steps within the placental core. Promising results from our institution include in-vivo visualization of maternal vessels [Jackson 2019], placental micro-structure [Slator 2018] and oxygen concentration [Hutter 2019a].
We have also recently implemented a velocity selective arterial spin labelling protocol (VSASL)
Allowing the qualitative visualisation of placental perfusion [Hutter 2019b].
We aim to develop an integrated and robust MRI test of placental function from maternal vasculature to delivery of oxygen to the fetus quantitatively and non-invasively during pregnancy.
As the time available for the examination of the placenta is limited to ensuring maternal comfort, we will then aim to combine the different techniques into one joint scan; this will provide a time-efficient comprehensive assessment of placental function and early detection of at-risk pregnancies in clinically acceptable acquisition times
We will test the following hypotheses:
- Reliable perfusion measurements can be obtained, after 20 weeks gestation, resilient to fetal motion and able to visualise the placental functional units, irrespective of placental position in the uterus.
- The simultaneous acquisition of highly localised perfusion, oxygenation and microstructural data, together with vascular anatomy can provide a novel window into placental function that can be used to identify and characterise placental insufficiency.
- The joint acquisition leads to increased sensitivity to early changes associated with fetal growth restriction.
MRI sequences will include:
(a) The integrated perfusion-oxygenation-microstructure scan. This is based on a successfully developed joint microstructure-oxygenation scan which will be extended using a velocity selective arterial spin labelling (VSASL) module. The initial part of this project will focus on further developing and optimising this module with respect to spatial resolution and VSASL specific parameters such as orientation of velocity labelling, threshold for velocity labelling and post-labelling delay; importantly the relation between such parameters and reproducibility will be explored. This preliminary work will result in a robust protocol for the rest of the study.
(b) a recently developed method for MR-angiography providing vascular information insensitive to motion.
(c) Routine clinical morphological imaging to provide an anatomical reference for the functional data.
Multi-modality data will undergo motion correction and outlier rejection following established pipelines. Perfusion quantification will follow established formulae for VSASL. Voxelwise and placental-lobule averaged values from different parametric maps will then be computed, statistically correlated with gestational age at scan and compared between groups (patients vs healthy controls).
Required candidate background: The candidate will have an academic background in Physics, Engineering, Maths or a similarly relevant subject with a strong interest in pregnancy/fetal development and aspirations to contribute to novel advances in diagnostic imaging techniques.
- Hutter J, Slator PJ, Jackson L, Gomes ADS, Ho A, Story L, O’Muircheartaigh J, Teixeira RPAG, Chappell LC, Alexander DC, Rutherford MA, Hajnal JV. Multi-modal functional MRI to explore placental function over gestation. Magn Reson Med. 2019 Feb;81(2):1191-1204
- Hutter J, Harteveld AA, Jackson LH, Franklin S, Bos C, van Osch MJP, O’Muircheartaigh J, Ho A, Chappell L, Hajnal JV, Rutherford M, De Vita E, Perfusion and apparent oxygenation in the human placenta (PERFOX). Magn Reson Med. 2019 Aug 21. doi: 10.1002/mrm.27950
- Jackson et al., Joint placental angiography with perfusion and apparent oxygenation mapping, ISMRM 2019.
- Slator PJ, Hutter J, McCabe L, Gomes ADS, Price AN, Panagiotaki E, Rutherford MA, Hajnal JV, Alexander DC, Placenta microstructure and microcirculation imaging with diffusion MRI. Magn Reson Med. 2018 Aug;80(2):756-766.