Work Package 1: Surgical planning and visualisation

Professor Tom Vercauteren, Dr Andrew Melbourne, Professor David Atkinson, Professor David Hawkes

About this work package

Advances in Fetal Therapy and Surgery

As part of this project, we are developing new imaging technology using MRI and microCT to measure placenta function and to help to guide planned interventions, such as for twin-to-twin transfusion syndrome, congenital diaphragmatic hernia and myelomeningocele. Technology developed by close interaction between clinicians and engineers at University College London (UCL), Katholieke Universitet Leuven (KUL) and King’s College London can offer more accurate monitoring of placenta function. The multidisciplinary collaboration of clinicians and engineers allows us to combine clinical relevance with technical competence and thus make better informed decisions about improvements to procedures which can be lifesaving and have life-long impact.

Magnetic Resonance Imaging – an attractive field

The role of Magnetic Resonance Imaging (MRI) in medical imaging research goes far beyond the acquisition of static structural images. Different techniques have been developed for many other applications, most notably the brain, to provide information on tissue microstructure and function.

A key area of MR research is the measurement of the vascular properties of tissue. The gold-standard technique for this uses an injected para-magnetic contrast agent that makes it generally unsuitable for fetal and maternal clinical MRI. However, there are several non-invasive competing modalities for flow and perfusion measurement.

New capabilities in hardware and software are enabling us to apply these imaging techniques during pregnancy in new and exciting ways but each of these techniques requires substantial image post-processing and correction of motion artefacts. At UCL, we develop the software that can take these large numbers of images and extract the most useful biological information from the data. The combination of images with different MR contrasts represents fertile ground for developing our understanding of the most fascinating of biological organs. Applied to the placenta, a combination of flow and perfusion imaging techniques will hopefully reveal much about the working efficiency of the placental tissue and help us to better monitor the wellbeing of the baby.

Micro CT – exploring below the placenta surface

Despite the availability of the postnatal placenta for study, little is known about the three-dimensional structure of the fetoplacental vascular tree, due to the small size of vessels and complexity of branching structure. Micro-CT can capture this data in 3D volumes and opens a new window into our understanding of the vascular structure in normal pregnancy, and in major obstetric disorders, including fetal growth restriction, pre-eclampsia and complicated twin pregnancies.

The major vessels of the placenta can be perfused with radiopaque contrast agents so that the vessel structure is revealed on using Micro-CT with isotropic voxel sizes reaching beyond 0.01mm at high, but reasonable, magnification. Micro-CT of the placenta allows the three dimensional chorionic and deep branching vessel structure to be captured and quantified. Automatic analysis software can be used to analyse the branching vessel tree and help us to better understand the important features of this vastly complicated organ.

A positive outlook

This is a very exciting time for the management of pregnancies complicated by placental insufficiency. Other researchers at UCLH are developing the first treatment for the condition, which uses gene therapy to increase the maternal blood flow to the womb (the EVERREST project). The imaging techniques we are developing as a part of this work package will improve our knowledge of a poorly understood organ and improve our ability to assess placental function. This will allow us to measure the response to treatment, and understand the effect it has on placental function and the growth of the baby. The challenge is great, but we are working hard to improve technology that will help reduce stillbirths and neonatal deaths, and improve long-term outcomes for affected babies.

One of Work Package 1’s key successes has been the development of new technology that has revealed new information about the placenta.

Dr Andrew Melbourne

Work package tasks

Fetal US and MRI Acquisition

The main imaging modalities for surgical planning and guidance during fetal procedures are MRI and 2D/3D ultrasound. The initial focus of this WP was therefore the optimisation of acquisition protocols together with radiologists and clinical experts at UCH and UZ Leuven to improve the quality of the images and ensure accurate 3D reconstruction models. To achieve this, we have developed two open-source software packages:

  • GIFT-Grab, which allows the acquisition, processing and encoding of video streams from medical devices in real time;
  • GIFT-Cloud, which can be easily integrated with the IT systems of hospitals and universities to upload automatically anonymised MRI and ultrasound images into a secure server for data sharing.
Multi-modal preoperative computational modelling and visualisation

This task focuses on developing novel algorithms for automatic segmentation and 3D reconstruction of fetal anatomy from MRI images. So far, we have developed two techniques with high potential for clinical translation:

  • High-resolution volume reconstruction from multiple motion-corrupted stacks of 2D slices plays an increasing role in fetal brain MRI studies. Currently existing reconstruction methods are time-consuming and often require user interactions to localise and extract the brain from several stacks of 2D slices. In response to these issues, we have developed an automatic fetal brain reconstruction method based on machine learning. The technique can be applied to different parts of the fetal anatomy and the 3D reconstructions can be used to better visualise pathologies and aid diagnosis as well as surgical planning. 
  • Segmentation of the placenta from fetal MRI is challenging due to sparse acquisition, inter-slice motion, and the widely varying position and shape of the placenta between pregnant women. To overcome these issues, we have developed a minimally interactive framework that combines multiple volumes acquired in different views to obtain accurate segmentation of the placenta. In the first phase, a minimally interactive slice-by-slice propagation method called Slic-Seg (add link to Open Source Software page) is used to obtain an initial segmentation from a single motion-corrupted sparse volume image. In the second phase, to take advantage of the complementary resolution in multiple volumes acquired in different views, an iterative method is used to refine the initial segmentations using inter-slice and inter-image consistency. Accurate and fast segmentation allows to measure placenta size and assess its location, which aids the diagnosis of placenta abnormalities. 
Advanced Computational Imaging for Surgical Support
The role of ultrasound is severely limited by the field of view and relatively few contrast mechanisms when compared to MRI. We develop advanced computational imaging techniques for extracting novel measurements of perfusion and structure from both the placenta and the fetus and we have applied these to early-onset fetal growth restriction.
Specifically, longitudinal MRI of placenta function in complicated twin pregnancies, such as those affected by twin-to-twin transfusion syndrome, is likely to provide useful guidance for surgical planning and follow-up. As fetal surgery in complicated twin pregnancies can compromise placental and brain function, leading to selective fetal growth restriction and brain damage, this imaging will provide better short-term further assessment of surgical outcome.
Accurate measurement of perfusion and multi-modal modelling of placental vascularisation also aids the management of pathological placentae. We have developed our own optimised technique for assessing placental vascularisation ex vivo to do this.

Post-surgery, advanced imaging helps inform patient follow-up and can be compared and contrasted with pre-surgical imaging data. In the fetus, we make use of our own in-house technology for 3D reconstruction from multiple 2D stacks of images to analyse the shape of various features relevant to pathology.

Sign up for our studies

We are currently recruiting volunteers for a study about fetal MRI to improve prenatal diagnosis and therapy.

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Key publications

MRI Measurement of Placental Perfusion and Oxygen Saturation in Early Onset Fetal Growth Restriction.  Aughwane, R. et al. (2020). BJOG An International Journal of Obstetrics and Gynaecology, 1471-0528.16387. doi: 10.1111/1471-0528.16387

Separating fetal and maternal placenta circulations using multi parametric MRI. Melbourne, A. (2018). Magnetic Resonance in Medicine. doi: 10.1002/mrm.27406

Placental MRI and its application to fetal intervention. Aughwane, R. et al. (2019). Prenatal Diagnosis. doi: 10.1002/pd.5526

Micro-CT and histological investigation of the spatial pattern of feto-placental vascular density. Aughwane, R. et al. (2019). Placenta. doi: 10.1007/s11548-020-02166-3 Open Access

An automated framework for localization, segmentation and super-resolution reconstruction of fetal brain MRI. Ebner, M. et al. (2020). Neuroimagedoi: 10.1016/j.neuroimage.2019.116324