Morphology and function: from fetal brain image to childhood outcomes
Authors: Andrea Righini
Journal: The Lancet Child & Adolescent Health (2019)

In the past two decades, intrauterine MRI (iuMRI) has been widely applied in clinical and research settings.1Levine D Barnes PD Robertson RR Wong G Mehta TS Fast MR imaging of fetal central nervous system abnormalities.Radiology. 2003; 229: 51-61Crossref PubMed Scopus (181) Google Scholar, 2Glenn OA Cuneo AA Barkovich AJ et al.Malformations of cortical development: diagnostic accuracy of fetal MR imaging.Radiology. 2012; 263: 843-855Crossref PubMed Scopus (55) Google Scholar, 3Conte G Parazzini C Falanga G et al.Diagnostic value of prenatal MR imaging in the detection of brain malformations in fetuses before the 26th week of gestational age.AJNR Am J Neuroradiol. 2016; 37: 946-951Crossref Scopus (20) Google Scholar In particular, the high tissue contrast and multiplanar view of MRI helped to open a new window to important, yet previously neglected, prenatal medicine territories, such as the early development phase of cortical anomalies, acute brain parenchyma injuries (ie, ischaemia), or anomalies of the brainstem. Several studies have reported that iuMRI might provide additional information beyond that of ultrasonography in 5% to more than 40% of cases.4Jarvis D Mooney C Cohen J et al.A systematic review and meta-analysis to determine the contribution of mr imaging to the diagnosis of foetal brain abnormalities in utero.Eur Radiol. 2017; 27: 2367-2380Crossref PubMed Scopus (36) Google Scholar The wide variability in findings can likely be attributed to differences in cohort characteristics and in local clinical practice, such as the involvement or absence of dedicated specialists (ie, neuroultrasonographers or paediatric fetal neuroradiologists). The MERIDIAN study5Griffiths PD Bradburn M Campbell MJ et al.Use of MRI in the diagnosis of fetal brain abnormalities in utero (MERIDIAN): a multicentre, prospective cohort study.Lancet. 2017; 389: 538-546Summary Full Text Full Text PDF PubMed Scopus (173) Google Scholar compared iuMRI with ultrasonography in the largest cohort to date. The study has shown an overall remarkable improvement in prenatal neuroimaging workup using iuMRI. However, in spite of these achievements, there remains a gap in prenatal medicine between the ability to collect novel neuroimaging findings and to provide reliable mid-term to long-term neurological prognosis. Anthony Hart and colleagues' report, published in The Lancet Child & Adolescent Health,6Hart AR Embleton ND Bradburn M et al.Accuracy of in-utero MRI to detect fetal brain abnormalities and prognosticate developmental outcome: postnatal follow-up of the MERIDIAN cohort.Lancet Child Adolesc Health. 2019; (published online Nov 27)https://doi.org/10.1016/S2352-4642(19)30349-9Scopus (15) Google Scholar based on the original cohort of the MERIDIAN study, provides novel quantitative data about this gap. Despite a substantial case dropoff, the results from this large cohort indicate how overall the prediction based on prenatal imaging judgment was not confirmed at the 3-year clinical check-up in 20–30% of participants. Such drawback affected ultrasonography and iuMRI, although each method in a different manner, depending on the severity of the prenatal picture. In the fetuses with more severe findings, both ultrasonography and iuMRI were as good as one another at predicting childhood outcomes, but about 10–40% of cases were still misjudged, depending on whether aborted ones were also included; such failures are a matter of concern. Although an unknown fraction of the misjudged cases might still develop major neurological anomalies after 3 years (ie, drug-resistant epilepsy), the risk of terminating the gestation of individuals with normal or close to normal neurological outcome is not negligible. At the other extreme, iuMRI did better than ultrasonography in predicting mild developmental impairment. This result is expected, especially by those who have followed the rise of iuMRI. Since its early days, the perception has been that some conditions that had been considered high risk on the basis of ultrasonography (ie, the so-called Dandy–Walker-like malformation or spectrum) might receive a more reassuring result with the advent of iuMRI, if only because iuMRI can rule out additional findings. Nevertheless, the data show how also in the mild category more than 20% of cases were misjudged. Finally, Hart and colleagues found an unexpectedly high percentage of abnormal outcomes in children with mild isolated ventriculomegaly (a dominant issue in prenatal diagnosis): more than double the number traditionally reported. There might be patient inclusion biases behind this—ie, the number of prenatally detectable genetic abnormalities. However, it is likely that minor associated anomalies might be overlooked, such as subtle ventricular dysmorphism, mild opecularisation reduction, or brain mantle layering subtle anomalies. Such findings might be easily overlooked even in postnatal imaging. The discrepancy between prenatal imaging and postnatal clinical results is likely to have several explanations. That morphology may not predict function is a well known axiom in child neurology, and this is even more relevant when morphology itself is rapidly changing as in the case of the fetal brain. The gap between morphology and function should filled by adding genomic, proteomic, biochemistry, and environmental data to prognostication. The most effective strategy to reduce the gap would most probably be to concentrate expertise in selected centres. This concentration of expertise would allow obstetrician-ultrasonographers, geneticists, paediatric neuroradiologists, neurologists, and neurosurgeons to play a synergic role in each case. Such synergy would also facilitate the creation of research protocols, which should aim to establish prognosis at least for the most common diagnoses: isolated mild ventriculomegaly, isolated corpus callosum agenesis, isolated septum pellucidum agenesis, isolated upwards rotation of cerebellar vermis, isolated focal cortical malformations, mildly reduced opercularisation. The term isolated should be clearly defined for each protocol. To add accuracy to the morphology side of the axiom, new quantitative methods such as volume-rendering quantifications, diffusion tensor imaging, and functional MRI should be added to such protocols.7Jarvis D Griffiths PD Clinical applications of 3D volume MR imaging of the fetal brain in utero.Prenat Diagn. 2017; 37: 556-565Crossref Scopus (6) Google Scholar, 8Kasprian G Brugger PC Weber M et al.In utero tractography of fetal white matter development.Neuroimage. 2008; 43: 213-224Crossref PubMed Scopus (167) Google Scholar, 9Moore RJ Vadeyar S Fulford J et al.Antenatal determination of fetal brain activity in response to an acoustic stimulus using functional magnetic resonance imaging.Hum Brain Mapp. 2001; 12: 94-99Crossref PubMed Scopus (73) Google Scholar The fundamental message from Hart and colleagues' work is a warning against overconfidence in the sole use of iuMRI-based prognostication. Considering that this work was limited to 3 years of follow-up, our knowledge of outcomes in school-age children is currently unexplored territory. I declare no competing interests. Accuracy of in-utero MRI to detect fetal brain abnormalities and prognosticate developmental outcome: postnatal follow-up of the MERIDIAN cohortiuMRI remains the optimal tool to identify fetal brain abnormalities. It is less accurate when used to predict developmental outcome, although better than ultrasonography for identifying children with normal outcome. Further work is needed to determine how the prognostic abilities of iuMRI can be improved. Full-Text PDF Open Access