National Institute for Health Research Health Technology Assessment programme.

Background Ultrasonography has been the mainstay of antenatal screening programmes in the UK for many years. Technical factors and physical limitations may result in suboptimal images that can lead to incorrect diagnoses and inaccurate counselling and prognostic information being given to parents. Previous studies suggest that the addition of in utero magnetic resonance imaging (iuMRI) may improve diagnostic accuracy for fetal brain abnormalities. These studies have limitations, including a lack of an outcome reference diagnosis (ORD), which means that improvements could not be assessed accurately. Objectives To assess the diagnostic impact, acceptability and cost consequence of iuMRI among fetuses with a suspected fetal brain abnormality. Design A pragmatic, prospective, multicentre, cohort study with a health economics analysis and a sociological substudy. Setting Sixteen UK fetal medicine centres. Participants Pregnant women aged ≥ 16 years carrying a fetus (at least 18 weeks’ gestation) with a suspected brain abnormality detected on ultrasonography. Interventions Participants underwent iuMRI and the findings were reported to their referring fetal medicine clinician. Main outcome measures Pregnancy outcome was followed up and an ORD from postnatal imaging or postmortem autopsy/imaging collected when available. Developmental data from the Bayley Scales of Infant Development and questionnaires were collected from the surviving infants aged 2–3 years. Data on the management of the pregnancy before and after the iuMRI were collected to inform the economic evaluation. Two surveys collected data on patient acceptability of iuMRI and qualitative interviews with participants and health professionals were undertaken. Results The primary analysis consisted of 570 fetuses. The absolute diagnostic accuracies of ultrasonography and iuMRI were 68% and 93%, respectively [a difference of 25%, 95% confidence interval (CI) 21% to 29%]. The difference between ultrasonography and iuMRI increased with gestational age. In the 18–23 weeks group, the figures were 70% for ultrasonography and 92% for iuMRI (difference of 23%, 95% CI 18% to 27%); in the ≥ 24 weeks group, the figures were 65% for ultrasonography and 94% for iuMRI (difference of 29%, 95% CI 23% to 36%). Patient acceptability was high, with at least 95% of respondents stating that they would have iuMRI again in a similar situation. Health professional interviews suggested that iuMRI was acceptable to clinicians and that iuMRI was useful as an adjunct to ultrasonography, but not as a replacement. Across a range of scenarios, iuMRI resulted in additional costs compared with ultrasonography alone. The additional cost was consistently < £600 per patient and the cost per management decision appropriately changed was always < £3000. There is potential for reporting bias from the referring clinicians on the diagnostic and prognostic outcomes. Lower than anticipated follow-up rates at 3 years of age were observed. Conclusions iuMRI as an adjunct to ultrasonography significantly improves the diagnostic accuracy and confidence for the detection of fetal brain abnormalities. An evaluation of the use of iuMRI for cases of isolated microcephaly and the diagnosis of fetal spine abnormalities is recommended. Longer-term follow-up studies of children diagnosed with fetal brain abnormalities are required to fully assess the functional significance of the diagnoses. Trial registration Current Controlled Trials ISRCTN27626961. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 49. See the NIHR Journals Library website for further project information.

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 Measurement of fetal brain volume from iuMR imaging is a relatively new area of investigation and has been derived from motion corrected ultrafast 2D imaging but there is limited published data due to small sample sizes. Fetal brain volumes can be derived from 3D iuMR acquisitions with a high degree of reproducibility using freehand segmentation. Our work demonstrated a quadratic model provided best fit to describe the changes of fetal brain growth in relation to gestational age, increasing from a Mean value of 22.5 cm 3 to 274.7cm 3 between 18 and 36 weeks gestation.2

Purpose To describe the normal linear measurements of the skull (bi-parietal diameter and occipito-frontal diameter) and intracranial volumes (ventricular volume, brain parenchymal volume, extra-axial volume and total intra-cranial volume) in normal fetuses. Materials and methods We recruited pregnant women from low-risk pregnancies whose fetuses had normal ultrasound and in utero MR studies. All volunteers had in utero MR imaging on the same 1.5T MR scanner with a protocol consisting of routine and 3D steady-state volume imaging of the fetal brain. Linear measurements of the skull were made using the volume imaging. The 3D volume imaging also was manually segmented to delineate the intracranial compartments described above to determine quantitative values for each. Results Two hundred normal fetuses were studied with gestational ages between 18 and 37 weeks. The linear skull measurements made on in utero MR imaging closely correlate with published data from ultrasonography. The intracranial volume data is presented as graphs and as tabular summaries of 3rd, 10th, 50th, 90th and 97th centiles. Conclusion It is now possible to measure the volumes of the intracranial compartments in individual fetuses using ultrafast in utero MR techniques. Key Points • There are limitations in using the skull size of the fetus to comment on the state of the fetal brain. • Volumes for the intracranial compartments are presented, based on in utero MR imaging of the fetal brain between 18 and 37 weeks gestational age. • Those normative values can be used to assess fetuses with known or suspected structural brain abnormalities and may assist the differential diagnosis provided by visual assessment of routine iuMR studies. Electronic supplementary material The online version of this article (10.1007/s00330-018-5938-5) contains supplementary material, which is available to authorized users.

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of the foetal brain using a rapid 3D steady-state sequence. Br J Radiol 2013;86:20130168. FULL PAPER MRI of the foetal brain using a rapid 3D steady-state sequence P D GRIFFITHS, PhD Objective: To evaluate the capacity of a rapid T 2 weighted three-dimensional (3D) sequence to diagnose foetal brain abnormalities by comparing the results with current twodimensional (2D) methods. We have also made assessments of the estimates of energy deposition using those methods. Methods: 50 pregnant females were included in this study under the guidance of the institutional review board. All their foetuses had suspected brain abnormalities on antenatal ultrasonography or were at increased risk of a brain malformation based on the results of an earlier pregnancy. All the foetuses had a routine MR protocol that includes three orthogonal plane single-shot fast-spin echoes and 2D steady-state sequences. In addition, a 3D rapid steady-state sequence of the foetal brain was performed (acquisition time approximately 40 s), and the standard and 3D sequences were reported independently and the results were compared. The specific absorption rate (SAR) predicted by the scanner was recorded in 12 cases in order to estimate the energy deposited by the three sequences. Results: The 3D rapid steady-state sequences produced diagnostic-quality images in 41/50 (82%) cases. All the failures were in second trimester foetuses (9/26-35% failure rate). There was a discrepancy between the standard report and findings using the 3D sequence in 2/41 of the foetuses with good-quality 3D imaging. The predicted SAR deposition of the 3D steady-state sequences was comparable with the single-shot fast-spin echo sequence. Conclusion: Our initial assessments of a 3D rapid steadystate sequence to image the foetus are encouraging in terms of diagnostic information and acceptable energy deposition values. The high failure rate in second trimester foetuses probably relates to the greater mobility of the smaller foetuses, and improvements in the 3D sequence are required in terms of reduced acquisition time and higher resolution. Advances in knowledge:We have shown that 3D T 2 weighted images of the foetal brain can be acquired in a clinical setting and produce diagnostic-quality imaging in a high proportion of cases. The success rate in acquiring diagnostic-quality images is related to gestational age. Good-quality images were obtained in all third trimester foetuses but only in approximately two-thirds of second trimester foetuses. This probably reflects the problem of the greater mobility of second trimester foetuses. 3D T 2 weighted acquisitions have great potential for improving the antenatal diagnosis of foetal brain abnormalities and may reduce the time that a pregnant female needs to spend on the MR scanner.MRI of the foetus while in utero (iuMR) has become a valuable adjunct to antenatal ultrasonography over the past 10-15 years, particularly in cases of suspected brain pathology [1][2][3][4][5][6]. The most common approach to iuMR is to use sectional u...

Purpose To refine methods that assess structural brain abnormalities and calculate intracranial volumes in fetuses with congenital heart diseases (CHD) using in utero MR (iuMR) imaging. Our secondary objective was to assess the prevalence of brain abnormalities in this high-risk cohort and compare the brain volumes with normative values. Methods We performed iuMR on 16 pregnant women carrying a fetus with CHD and gestational age ≥ 28-week gestation and no brain abnormality on ultrasonography. All cases had fetal echocardiography by a pediatric cardiologist. Structural brain abnormalities on iuMR were recorded. Intracranial volumes were made from 3D FIESTA acquisitions following manual segmentation and the use of 3D Slicer software and were compared with normal fetuses. Z scores were calculated, and regression analyses were performed to look for differences between the normal and CHD fetuses. Results Successful 2D and 3D volume imaging was obtained in all 16 cases within a 30-min scan. Despite normal ultrasonography, 5/16 fetuses (31%) had structural brain abnormalities detected by iuMR (3 with ventriculomegaly, 2 with vermian hypoplasia). Brain volume, extra-axial volume, and total intracranial volume were statistically significantly reduced, while ventricular volumes were increased in the CHD cohort. Conclusion We have shown that it is possible to perform detailed 2D and 3D studies using iuMR that allow thorough investigation of all intracranial compartments in fetuses with CHD in a clinically appropriate scan time. Those fetuses have a high risk of structural brain abnormalities and smaller brain volumes even when brain ultrasonography is normal.