Imaging techniques that allow diagnosis of fetal malformations have had a major impact on the management of pregnancy and of the neonate and infant, no more so than in cases of suspected fetal brain anomalies. Sonography has for some time been the primary fetal imaging technique and remains the screening technique of choice. However, fetal sonography has limited specificity, and false-positive diagnoses of posterior fossa anomalies are well described [9
]. In our study, fetal MRI added diagnostic specificity for the diagnosis of posterior fossa anomalies when compared with screening fetal sonography in the community, with approximately 30% of such diagnoses by fetal sonography being excluded by fetal MRI. However, despite the apparent strengths of fetal MRI, neuropathology studies have raised concerns about the accuracy of fetal MRI for the diagnosis of brain anomalies [8
]. The populations in these pathology studies are likely biased toward severe cases that undergo fetal autopsy. Few studies have compared the accuracy of fetal MRI with that of postnatal MRI for the diagnosis of brain malformations in general [23
In our study, the first to our knowledge focusing on fetuses with posterior fossa anomalies surviving pregnancy, fetal MRI showed limitations in both sensitivity and specificity when compared with postnatal MRI. The accuracy with which fetal MRI predicted findings on postnatal MRI in cases of posterior fossa anomalies was modest at best, with only 60% of prenatal diagnoses confirmed postnatally.
There are several possible reasons for the limited ability described in this study of fetal MRI diagnosis of posterior fossa lesions to predict findings on postnatal MRI. The use of MRI for imaging the fetus is relatively new, at least in the United States, and although it represents a major advance in fetal diagnosis, many technical challenges remain, including limited pulse sequence options and low signal-to-noise ratios. In recent years, advances in MRI technology, such as faster scanning times, have improved but have not yet overcome the challenges of tissue resolution of in utero structures. Furthermore, although significantly reduced by ultrafast MR techniques, fetal motion artifact may still affect image quality and the ability to obtain a true sagittal image.
The issue of tissue resolution is particularly limiting for small structures such as the brainstem and vermis. This limitation of MRI was evident in our study, in which one quarter of the infants undergoing postnatal MRI had “new” posterior fossa lesions detected including brainstem hypoplasia, superior vermian dysplasia, and posterior fossa hemorrhage. In addition, small cerebral lesions (e.g., heterotopias) not noted on fetal MRI but seen on postnatal images may have major prognostic importance. These lesions may be too small to diagnose by MRI early in gestation. Conversely, in 15% of our cases, fetal MRI diagnoses could not be confirmed by postnatal MRI. Of note, in almost all cases in which a fetal posterior fossa anomaly was excluded by postnatal MRI, the fetal diagnosis was isolated inferior vermian hypoplasia. These findings corroborate our recent report that isolated inferior vermian hypoplasia may be overdiagnosed by second-trimester fetal MRI [7
]. Similarly, a recent study comparing fetal MRI diagnosis of posterior fossa anomalies with results at fetal autopsy showed that vermian hypoplasia diagnosed by fetal MRI could not be confirmed by neuropathology studies in 30% of the cases [21
]; of note, these false-positive MRI diagnoses were made after 30 weeks’ gestation [21
]. In our study, one third of terminated pregnancies had isolated inferior vermian hypoplasia. Together, these findings suggest that caution is warranted during counseling for inferior vermian hypoplasia, particularly if the lesion is an isolated finding, because a good outcome is to be expected in the majority of cases [7
Beyond the technical limitations of in utero tissue resolution by MRI, there are a number of important factors that likely underlie the discrepancies between fetal and postnatal MRI in cases of posterior fossa anomalies. One major limitation is our incomplete understanding of the normal temporal and structural range of fetal brain development, which may compromise reliable interpretation of the more subtle posterior fossa anomalies. Concerns regarding the limited resolution of fetal MRI in the posterior fossa have been raised by others, showing a delay of up to 5 weeks between known anatomic stages of development [26
] and those detected by fetal MRI [27
]. In our study, early gestational age at the time of fetal MRI was a significant predictor of discrepancy between the fetal and postnatal MRI posterior fossa findings. This is not surprising when considering the protracted time line of cerebellar development. Although the cerebellum is one of the first brain structures to begin development, at around 4 weeks of gestation, it is one of the last to reach its mature configuration, many months after birth [28
]. In fact, during the middle and late fetal periods, the cerebellum undergoes particularly rapid changes in size and differentiation [1
]. For example, cerebellar transverse diameter doubles in size during the second half of gestation [29
]. The rapid growth is the result of important developmental processes that may be vulnerable to genetic and environmental insults capable of derailing the developmental program.
In our study, the likelihood of discrepancy between fetal and postnatal MRI studies decreased over the 5-year study period. Although the interpretation of fetal studies at our center is performed by experienced fetal ultrasonologists and by pediatric neuroradiologists in cases of suspected brain anomaly, the advent of fetal MRI at our center is relatively recent. Therefore, improved correlation between fetal and postnatal studies may possibly be in part due to the accumulation over time of experience in the application and interpretation of fetal MRI.
Given the critical role of brain function in long-term quality of life, the interpretation of fetal brain structure by MRI is often a pivotal determinant in difficult parental decisions about the future of the fetus when a fetal anomaly is suspected. Previous studies have described the current limitations of MRI in the diagnosis of fetal brain anomalies [7
], and our study supports these findings in cases of suspected fetal posterior fossa abnormalities. Clinicians are often called on to make accurate predictions of fetal outcome against a background “ticking clock” for legal termination of pregnancy, despite the technical limitations of fetal MRI at this stage of gestation when many important developmental events are yet to occur. Our current and previous [2
] findings should be carefully considered when predicting postnatal brain structure by MRI in cases of suspected fetal posterior fossa abnormality. Furthermore, unlike the data of other investigators [23
], our data strongly emphasize the importance of performing postnatal MRI studies in all cases of posterior fossa anomaly suspected by fetal MRI.
Our study has several potential limitations. First, the overall goal of the study was to examine—from the counseling physician’s perspective—the current diagnostic accuracy in a major referral center of fetal MRI for posterior fossa anomalies. For this reason, we did not perform repeated blinded MRI interpretations to assess intra- and interreader reliability. Instead, we used the clinical diagnosis made by our pediatric neuroradiologists at the time of the prenatal and postnatal MRI studies. Second, given the large number of heterogeneous diagnostic groups in our cohort, our data did not have sufficient power to allow us to pursue more targeted analyses to evaluate the diagnostic accuracy of every posterior fossa lesion. In addition, because the cases with normal findings on fetal MRI studies did not undergo postnatal MRI studies, we are unable in this retrospective study to comment on the specificity of fetal MRI. Finally, this study focused on the structural diagnostic accuracy of fetal MRI and did not address the predicted and actual long-term functional outcomes. Those goals are part of a current ongoing study.
In conclusion, antenatal MRI has advanced our ability to define major posterior fossa anomalies in the fetus. However, from the perspective of the clinician counseling parents during the gestational period when critical decisions are often made, important limitations of the technique and its interpretation persist and need to be considered carefully. Our findings strongly support the need for postnatal MRI follow-up in cases with suspected pos terior fossa anomalies by fetal MRI. Overcoming the current limitations of fetal MRI in this population will require not only further developments in the0 technique but also greater understanding of the temporal and structural variations in the development of posterior fossa structures. Such advances in our understanding will be facilitated by large prospective studies using serial and quantitative MRI in both the healthy fetus and in the fetus with suspected posterior fossa abnormalities.