Title: Magnetic resonance imaging to enhance the diagnosis of fetal developmental brain abnormalities in utero
Funder: Department of Health and Social Care

Abstract: The objective of this research is to assess MRI as a technology to aid in the prenatal diagnosis of fetal developmental brain abnormalities. The study will recruit 750 pregnant women from 18 weeks gestation onwards where the fetus is known or suspected of having some form of developmental brain abnormality based on antenatal ultrasound examination. Study participants will receive their clinical care in one of 15 collaborating fetal medicine units drawing from a large and varied geographic and socio-economic referral area in England and Scotland. The study is designed primarily to assess the diagnostic accuracy of MRI along with the related aspect of diagnostic confidence. The clinical impact of MRI in this context will also be assessed both quantitatively, as changes in clinical management, and qualitatively by assessing the impact of the 'new technique' on the clinicians who interact with the pregnant women. In parallel, the opinions of the women included in the study will be sought in order to assess perceptions of MRI on acceptability and decision making. Finally, health economic modelling will be performed for the specific changes in management attributable to the inclusion of MRI in the diagnostic pathway. The work is centred at the Academic Unit of Radiology, University of Sheffield. The MRI examination itself will be performed either in Sheffield, or a local collaborating centre. The aim is to deliver a programme of research able to inform fetal medicine practice within the United Kingdom in five years from the start of the study. The study will provide evidence relevant to a range of health policy options, for instance service delivery based on gestational age (before and after 24 weeks) or for specific types of suspected brain abnormality. The results should also provide some indication of the clinical and patient acceptability of centralised versus regional MRI services.

Lay abstract: This study plans to explore the possible value of including magnetic resonance (MR) imaging in the assessment of pregnant women whose fetus may have a developmental brain abnormality. This covers a wide range of problems but the most common pathologies are likely to be; ventriculomegaly (enlargement of the fluid containing spaces within the brain), agenesis of the corpus callosum (the hemispheres of the brain do not connect properly) and Dandy-Walker spectrum disorders (problems with how the cerebellum forms). All of these are associated with a risk of poor outcome for the baby although the risk is highly variable and depends on making an accurate and complete anatomical diagnosis. Hospitals in Britain offer ultrasound scans to screen for these types of problems and if a concern is raised a more detailed ultrasound examination is performed by an expert in fetal medicine. There is growing evidence that the accuracy and certainty of diagnosis of fetal brain problems can be improved by performing fetal MR imaging to supplement the information gained on ultrasound. This should improve the quality of information available to the women. MR imaging has revolutionized the detection of brain abnormalities in adults and children, and we will attempt to prove that this is the same for developmental brain problems of the fetus. When a new technology or diagnostic application is introduced the assessment pathway usually follows: - Technical performance - Diagnostic performance - Diagnostic impact - Therapeutic impact - Impact on health The Academic Unit of Radiology, University of Sheffield is the lead group in this application and has a proven track record for assessing MR-based diagnostic interventions by these mechanisms in a wide range of brain pathology including fetal imaging. The following is a summary of the status of using MR for problems of the fetal brain: Technical performance: It has been possible to image the fetus with 'ultrafast' MR imaging for approximately 15 years. Technical advancements are being made continually but it is possible now to produce good quality images that are anatomically robust in a reliable fashion. Our group was heavily involved in this development work. Diagnostic performance: Many groups, including our own, have shown improved diagnostic accuracy when MR imaging is included in the diagnostic process for fetal brain abnormalities. The vast majority (if not all) studies performed so far have had significant selection bias or have intentionally concentrated on pathology sub-groups. That approach, although providing valuable data, may not be generally applicable. Diagnostic impact: This refers to changes in diagnostic confidence and possible displacement of existing diagnostic procedures. There is no intention to replace ultrasound by fetal MR as a screening method or as the first line of detailed assessment by any group known to us in the field. It is possible that the widespread introduction of fetal MR at some point in the future may reduce the number of detailed ultrasound examinations the woman receives before a confident diagnosis is achieved. This issue should be studied in terms of health economics. There is no prima facia data to support the contention that feto-medicine experts believe the results of fetal brain MR over ultrasound and this is also an important line of study. Therapeutic impact: i.e. do the results of fetal MR contribute to changes in management. As far as we are aware our group has performed the only formal study on this issue to date on fetuses with ventriculomegaly (manuscript in press). That study did show significant effects on management in a high proportion of cases, such as whether to consider termination of pregnancy or not. Impact on health: It is not known how this imaging contributes to improvements in health on a societal basis. The views of the woman on how fetal MR contributed to her decision making, and her acceptance of the process, have not been studied in detail to date. A health economic assessment is also necessary in order to provide information to healthcare providers and our study includes this. Our proposal is a logical extension of our earlier work and is directed at reinforcing the data about the improved diagnostic performance of fetal MR and to provide novel information around diagnostic impact, therapeutic impact and impact on health. We plan to do this by performing a large, population-based study recruiting from a large number of pre-existing collaborating centres in England and Scotland. We will bring in health professionals with a wide range of expertise in order to plan, execute and report on the study.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL;REPRODUCTIVE HEALTH AND CHILDBIRTH