Long-Term Imaging Follow-up from the Management of Myelomeningocele Study.

BACKGROUND AND PURPOSE: Short-term results demonstrate that prenatal repair of a myelomeningocele is associated with a reduction in hydrocephalus and an increased likelihood of the reversal of Chiari II malformations compared with postnatal repair. The purpose of this study was to identify the long-term imaging findings at school age among subjects who underwent pre- versus postnatal repair of a myelomeningocele. MATERIALS AND METHODS: A subset of subjects enrolled in the Management of Myelomeningocele Study who underwent either prenatal (n = 66) or postnatal (n = 63) repair of a lumbosacral myelomeningocele and had follow-up brain MR imaging at school age were included. The prevalence of posterior fossa features of Chiari II malformation and supratentorial abnormalities and the change in these findings from fetal to school-age MR imaging were compared between the 2 groups. RESULTS: Prenatal repair of a myelomeningocele was associated with higher rates of normal location of fourth ventricle and lower rates of hindbrain herniation, cerebellar herniation, tectal beaking, brainstem distortion, and kinking at school age compared with postnatal repair (all P < .01). Supratentorial abnormalities, including corpus callosal abnormalities, gyral abnormalities, heterotopia, and hemorrhage, were not significantly different between the 2 groups (all P > .05). The rates of resolution of brainstem kinking, tectal beaking, cerebellar and hindbrain herniation, and normalization of fourth ventricle size from fetal to school age MR imaging were higher among the prenatal compared with postnatal surgery group (all, P < .02). CONCLUSIONS: Prenatal repair of a myelomeningocele is associated with persistent improvement in posterior fossa imaging findings of Chiari II malformation at school age compared with postnatal repair.

Development of Gestational Age-Based Fetal Brain and Intracranial Volume Reference Norms Using Deep Learning.

BACKGROUND AND PURPOSE: Fetal brain MR imaging interpretations are subjective and require subspecialty expertise. We aimed to develop a deep learning algorithm for automatically measuring intracranial and brain volumes of fetal brain MRIs across gestational ages. MATERIALS AND METHODS: This retrospective study included 246 patients with singleton pregnancies at 19-38 weeks gestation. A 3D U-Net was trained to segment the intracranial contents of 2D fetal brain MRIs in the axial, coronal, and sagittal planes. An additional 3D U-Net was trained to segment the brain from the output of the first model. Models were tested on MRIs of 10 patients (28 planes) via Dice coefficients and volume comparison with manual reference segmentations. Trained U-Nets were applied to 200 additional MRIs to develop normative reference intracranial and brain volumes across gestational ages and then to 9 pathologic fetal brains. RESULTS: Fetal intracranial and brain compartments were automatically segmented in a mean of 6.8 (SD, 1.2) seconds with median Dices score of 0.95 and 0.90, respectively (interquartile ranges, 0.91-0.96/0.89-0.91) on the test set. Correlation with manual volume measurements was high (Pearson r = 0.996, P < .001). Normative samples of intracranial and brain volumes across gestational ages were developed. Eight of 9 pathologic fetal intracranial volumes were automatically predicted to be >2 SDs from this age-specific reference mean. There were no effects of fetal sex, maternal diabetes, or maternal age on intracranial or brain volumes across gestational ages. CONCLUSIONS: Deep learning techniques can quickly and accurately quantify intracranial and brain volumes on clinical fetal brain MRIs and identify abnormal volumes on the basis of a normative reference standard.

Prenatal Diagnosis of Third and Fourth Branchial Apparatus Anomalies: Case Series and Comparison with Lymphatic Malformation.

BACKGROUND AND PURPOSE: Third and fourth branchial apparatus anomalies are rare congenital anomalies. The purpose of this study was to investigate imaging features of these lesions on fetal MR imaging in comparison with lymphatic malformations, the major competing differential diagnosis in these cases. MATERIALS AND METHODS: A retrospective review of our institutional fetal MR imaging database between 1997 and 2019 resulted in 4 patients with confirmed third and fourth branchial apparatus anomalies and 14 patients with confirmed lymphatic malformations. The imaging features were reviewed by consensus, and the Fisher exact test was used to evaluate statistically significant differences between these 2 populations. RESULTS: Four cases of third and fourth branchial apparatus anomalies were imaged at 29 weeks 1 day (range, 23 weeks 1 day to 33 weeks 4 days). All 4 cases demonstrated unilateral, unilocular cysts without reduced diffusion or hemorrhage and a medially directed beaked contour that tapered between the spine and airway at the level of the piriform sinus. Compared with 14 cases of fetal lymphatic malformations imaged at 27 weeks 6 days (range, 21 weeks 3 days to 34 weeks 6 days), third and fourth branchial apparatus cysts were significantly more likely to be unilocular (P < .005) and to have a medially beaked contour (P < .005). The combination of features of unilateral, unilocular, and medially beaked contour was observed only in the fetuses with third and fourth branchial apparatus cysts (P < .001). CONCLUSIONS: The presence of a left-sided unilocular cyst with a medially beaked contour tapering at the level of the piriform sinus suggests the diagnosis of third and fourth branchial apparatus anomaly. Accurate diagnosis in the prenatal period allows proper counseling, genetic work-up, and treatment, potentially sparing patients from recurrent infections and associated morbidity.

Polymicrogyria in a fetus with human parvovirus B19 infection: a case with radiologic-pathologic correlation.

We report the prenatal magnetic resonance imaging (MRI) appearance of polymicrogyria with pathologic correlation in a fetus with congenital parvovirus B19 infection. Prenatal ultrasound revealed non-immune hydrops, but detected no fetal brain abnormalities. A subsequent fetal MRI scan performed at 23 weeks' gestation demonstrated bilateral polymicrogyria, which was confirmed at autopsy. To our knowledge, prenatal diagnosis of polymicrogyria in association with congenital parvovirus B19 infection has not been previously described. This case provides further evidence for brain abnormalities resulting from congenital parvovirus B19 infection, and suggests that fetal neuroimaging with MRI would be of value in suspected cases of congenital parvovirus infection.

Diffusion-weighted imaging in fetuses with severe congenital heart defects.

Fetal diffusion MR imaging was performed in 3 fetuses with CHD. ADC values in the periatrial WM, thalamus, and basal ganglia were compared with those in a control population of fetuses. Diffusivity in the periatrial WM and thalamus was higher for the fetuses with CHD compared with controls. These observations support the finding of abnormal in utero brain development in fetuses with CHD.

3D global and regional patterns of human fetal subplate growth determined in utero.

The waiting period of subplate evolution is a critical phase for the proper formation of neural connections in the brain. During this time, which corresponds to 15 to 24 postconceptual weeks (PCW) in the human fetus, thalamocortical and cortico-cortical afferents wait in and are in part guided by molecules embedded in the extracellular matrix of the subplate. Recent advances in fetal MRI techniques now allow us to study the developing brain anatomy in 3D from in utero imaging. We describe a reliable segmentation protocol to delineate the boundaries of the subplate from T2-W MRI. The reliability of the protocol was evaluated in terms of intra-rater reproducibility on a subset of the subjects. We also present the first 3D quantitative analyses of temporal changes in subplate volume, thickness, and contrast from 18 to 24 PCW. Our analysis shows that firstly, global subplate volume increases in proportion with the supratentorial volume; the subplate remained approximately one-third of supratentorial volume. Secondly, we found both global and regional growth in subplate thickness and a linear increase in the median and maximum subplate thickness through the waiting period. Furthermore, we found that posterior regions--specifically the occipital pole, ventral occipito-temporal region, and planum temporale--of the developing brain underwent the most statistically significant increases in subplate thickness. During this period, the thickest region was the developing somatosensory/motor cortex. The subplate growth patterns reported here may be used as a baseline for comparison to abnormal fetal brain development.

Diffusion-weighted imaging in fetuses with unilateral cortical malformations and callosal agenesis.

DWI was performed in fetuses with callosal agenesis and unilateral cortical malformations. ADC values were retrospectively measured in the developing white matter underlying the cortical malformation and compared with the corresponding contralateral white matter. In all 3 patients, ADC values were lower under the areas of cortical malformation compared with the normal contralateral side. Our findings suggest that there are structural differences in the developing white matter underlying areas of cortical malformation.

Normative apparent diffusion coefficient values in the developing fetal brain.

BACKGROUND AND PURPOSE: Previous studies of diffusion-weighted imaging (DWI) in fetuses are limited. Because of the need for normative data for comparison with young fetuses and preterm neonates with suspected brain abnormalities, we studied apparent diffusion coefficient (ADC) values in a population of singleton, nonsedated, healthy fetuses. MATERIALS AND METHODS: DWI was performed in 28 singleton nonsedated fetuses with normal or questionably abnormal results on sonography and normal fetal MR imaging results; 10 fetuses also had a second fetal MR imaging, which included DWI. ADC values in the periatrial white matter (WM), frontal WM, thalamus, basal ganglia, cerebellum, and pons were plotted against gestational age and analyzed with linear regression. We compared mean ADC in different regions using the Tukey Honestly Significant Difference test. We also compared rates of decline in ADC with increasing gestational age across different areas by using the t test with multiple comparisons correction. Neurodevelopmental outcome was assessed. RESULTS: Median gestational age was 24.28 weeks (range, 21-33.43 weeks). Results of all fetal MR imaging examinations were normal, including 1 fetus with a normal variant of a cavum velum interpositum. ADC values were highest in the frontal and periatrial WM and lowest in the thalamus and pons. ADC declined with increasing gestational age in periatrial WM (P = .0003), thalamus (P < .0001), basal ganglia (P = .0035), cerebellum (P < .0001), and pons (P = .024). Frontal WM ADC did not significantly change with gestational age. ADC declined fastest in the cerebellum, followed by the thalamus. CONCLUSIONS: Regional differences in nonsedated fetal ADC values and their evolution with gestational age likely reflect differences in brain maturation and are similar to published data in premature neonates.

Agenesis of the corpus callosum: an MR imaging analysis of associated abnormalities in the fetus.

BACKGROUND AND PURPOSE: Anomalies associated with callosal agenesis (ACC) found postnatally have been well documented. However, to our knowledge, no detailed MR imaging analysis of associated anomalies has been reported in a large cohort of fetuses with ACC. This study will assess those anomalies and compare them with postnatal cohorts of ACC, to identify associated fetal brain abnormalities that may give insight into etiology and outcome. MATERIALS AND METHODS: All cases of ACC diagnosed on fetal MR imaging during an 11-year period were retrospectively reviewed, including fetal MR imaging, postnatal MR imaging, and autopsy findings. Neurodevelopmental outcome was classified as poor in children with seizures and/or severe neurodevelopmental impairment or in cases of neonatal death. RESULTS: Twenty-nine cases of ACC were identified. Median gestational age was 26.14 weeks (range, 19.71-36.43 weeks). Twenty-three fetuses had delayed sulcation and/or too-numerous cortical infoldings (abnormal morphology). Fifteen fetuses had cerebellar and/or brain stem abnormalities. Fetal MR imaging findings suggested a genetic syndrome in 5 fetuses and an acquired etiology or genetic/metabolic disorder in 2 fetuses. Findings were confirmed in 8 cases with postnatal MR imaging, except for delayed sulcation and small vermis, and in 4 cases with autopsy, except for periventricular nodular heterotopia and abnormalities in areas not examined by autopsy. Neurodevelopmental outcome was good in 7 and poor in 9 children. Abnormal sulcal morphology and/or infratentorial abnormalities were present in those with poor outcome and absent in those with good outcome. CONCLUSIONS: ACC is infrequently isolated in fetuses. Abnormal sulcation is common and suggests more diffuse white matter dysgenesis in these fetuses.

Vanishing MS T2-bright lesions before puberty: a distinct MRI phenotype?

BACKGROUND: Multiple sclerosis (MS) onset before puberty may have a distinct clinical presentation. Pediatric patients with MS may less often meet MRI diagnostic criteria for adults. Whether initial MRI presentation is distinct in prepubertal patients is unknown. METHODS: We queried the UCSF MS database for pediatric patients with MS (onset or=11 years) pediatric MS. The next available brain MRI scan was used to evaluate lesion resolution. RESULTS: Thirteen children with EOPMS (median age 8.90 years, range [3.58-10.98], 38% girls) and 18 with LOPMS (median age 14.47 years, range [11.78-18.00], 61% girls) were identified. While the overall number of T2-bright lesions was similar in the two groups, patients with EOPMS had fewer well-defined ovoid T2-bright lesions (median = 7, range [0-29] vs 21.5, [4-100]; p = 0.004) and more often had confluent lesions (31% of patients vs 0%; p = 0.02) on their first MRI compared with patients with LOPMS. Ninety-two percent of patients with EOPMS had a reduction in the number of T2-bright lesions on the second scan compared to 29% of patients with LOPMS (p = 0.002). CONCLUSIONS: The distinct prepubertal multiple sclerosis (MS) MRI phenotype suggests that underlying biologic processes may differ in earlier-onset pediatric MS compared to later-onset pediatric MS. These findings may delay diagnosis in that age range. MRI criteria for MS diagnosis may need to be revised before puberty.

Diffusion tensor imaging of the pyramidal tracts in infants with motor dysfunction.

OBJECTIVE: To determine if diffusion tensor imaging (DTI) metrics of the pyramidal tracts correlate with motor outcome in infants presenting with motor dysfunction. METHODS: DTI tractography of the pyramidal tracts was performed in 21 patients with clinical motor dysfunction who were less than 30 months of age and in 22 age-matched controls. We plotted tract-specific DTI metrics (fractional anisotropy, parallel diffusivity, transverse diffusivity, and mean diffusivity) against age for the controls and generated normative curves. For each patient, we calculated the deviation from the normative curves. Patients returned for a neurodevelopmental evaluation when they were over 36 months of age, and motor outcome measures were performed. We analyzed the association between normative deviation in DTI metrics and motor outcome measures using linear and logistic regression models. RESULTS: Normative deviation in fractional anisotropy and transverse diffusivity were significantly correlated with all measures of motor outcome. Lower fractional anisotropy and higher transverse diffusivity compared to controls were associated with worse motor outcome. Furthermore, children who were eventually diagnosed with permanent motor dysfunction had lower fractional anisotropy and higher transverse diffusivity compared with those whose motor dysfunction normalized. CONCLUSIONS: Diffusion tensor imaging metrics correlate with motor outcome in infants presenting with motor dysfunction. The identification of a quantitative imaging marker that can be applied to infants at the time of clinical presentation has implications for the evaluation of early motor dysfunction.

Diffusion tensor MR imaging tractography of the pyramidal tracts correlates with clinical motor function in children with congenital hemiparesis.

BACKGROUND AND PURPOSE: Children with congenital hemiparesis have greater asymmetry in diffusion parameters of the pyramidal tracts compared with control subjects. We hypothesized that the asymmetry correlates with the severity of hemiparesis and that diffusion metrics would be abnormal in the affected tracts and normal in the unaffected tracts. MATERIALS AND METHODS: Fifteen patients with congenital hemiparesis and 17 age-matched control subjects were studied with diffusion tensor MR imaging tractography. Hemipareses were scored as mild, moderate, or severe. We measured tract-specific diffusion parameters (fractional anisotropy, mean, and directional diffusion coefficients) of the pyramidal tracts. We compared tract-specific parameters and asymmetry between the right and left tracts of the differing severity groups and control subjects. RESULTS: We observed many different causes of congenital hemiparesis including venous infarction, arterial infarction, and polymicrogyria. Clinical severity of hemiparesis correlated with asymmetry in fractional anisotropy (P < .0001), transverse diffusivity (P < .0001), and mean diffusivity (P < .03). With increasing severity of hemiparesis, fractional anisotropy decreased (P < .0001) and transverse diffusivity (P < .0001) and mean diffusivity (P < .02) increased in the affected pyramidal tract compared with controls. Diffusion metrics in the unaffected tract were similar to those in the control subjects. CONCLUSION: Asymmetry in fractional anisotropy, transverse diffusivity, and mean diffusivity, as well as the degree of abnormality in the actual values of the affected pyramidal tracts themselves, correlates with the severity of motor dysfunction in infants and children with congenital hemiparesis from different causes. This suggests that abnormalities detected by diffusion tensor MR imaging tractography in the affected pyramidal tract are related to the functional ability of the affected pyramidal tract, regardless of the etiology of motor dysfunction.

Magnetic resonance imaging of the fetal brain and spine: an increasingly important tool in prenatal diagnosis: part 2.

Fetal MR imaging is an increasingly available technique used to evaluate the fetal brain and spine. This is made possible by recent advances in technology, such as rapid pulse sequences, parallel imaging, and advances in coil design. This provides a unique opportunity to evaluate processes that cannot be approached by any other current imaging technique, and it affords a unique opportunity for studying in vivo brain development and early diagnosis of congenital abnormalities inadequately visualized or undetectable by prenatal sonography. This 2-part review summarizes some of the latest developments in MR imaging of the fetal brain and spine and its application to prenatal diagnosis. The first part discussed the utility, safety, and technical aspects of fetal MR imaging; the appearance of normal fetal brain development; and the role of fetal MR imaging in the evaluation of fetal ventriculomegaly. In this second part, we focus on additional clinical applications of fetal MR imaging, including suspected abnormalities of the corpus callosum, malformations of cortical development, and spine abnormalities.

Magnetic resonance imaging of the fetal brain and spine: an increasingly important tool in prenatal diagnosis, part 1.

Fetal MR imaging is an increasingly available technique used to evaluate the fetal brain and spine. This is made possible by recent advances in technology, such as rapid pulse sequences, parallel imaging and advances in coil design. This provides a unique opportunity to evaluate processes that cannot be approached by any other current imaging technique and affords a unique opportunity for studying in vivo brain development and early diagnosis of congenital abnormalities inadequately visualized or undetectable by prenatal sonography. This 2-part review summarizes some of the latest developments in MR imaging of the fetal brain and spine and its application to prenatal diagnosis. This first part discusses the utility, safety, and technical aspects of fetal MR imaging, the appearance of normal fetal brain development, and the role of fetal MR imaging in the evaluation of fetal ventriculomegaly. The second part focuses on additional clinical applications of fetal MR imaging, including suspected abnormalities of the corpus callosum, malformations of cortical development, and spine abnormalities.

MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy.

BACKGROUND: Although the imaging, spectroscopic, and diffusion characteristics of brains of infants with neonatal encephalopathy have been described, the time course during which these changes evolve is not clear. The results of sequential MR imaging studies--including anatomic MR imaging, proton MR spectroscopy, and diffusion tensor imaging (DTI)--of 10 patients enrolled prospectively in a study of neonatal encephalopathy are reported to help to clarify the time course of changes in different brain regions during the first 2 weeks of life. METHODS: Ten neonates were prospectively enrolled in a study of the evolution of MR findings in neonatal encephalopathy and were studied 2 (8 patients) or 3 (2 patients) times within the first 2 weeks of life. The MR examination included spin-echo T1 and T2-weighted images, DTI, and long echo time (288 milliseconds) proton MR spectroscopy. Diffusion parameters (diffusivity [D(av)], fractional anisotropy [FA], and individual eigenvalues) were calculated for 10 1-cm2 regions of interest in each hemisphere that were placed based on anatomic landmarks. D(av) and FA were then measured manually in the same areas on a workstation. Metabolite ratios (NAA/Ch, Cr/Ch, Cr/NAA, Lac/Ch, and Lac/NAA) were calculated in 7 regions of interest. Imaging appearance, diffusion parameters, and metabolite ratios were then evaluated longitudinally (comparing with other studies on the same patient at different times) and cross-sectionally (comparing all studies performed on the same postnatal day). RESULTS: In most of the patients a characteristic evolution of DTI and MR spectroscopy parameters was seen during the first 2 weeks after birth. Although the anatomic images were normal or nearly normal on the first 2 days after birth in most patients, abnormalities were detected on DTI (both visually and by quantitative interrogation of D(av) maps) and proton MR spectroscopy (abnormal metabolite ratios). These parameters tended to worsen until about day 5 and then normalize, though in several patients abnormal metabolite ratios persisted. Of interest, as areas of abnormal diffusivity pseudonormalized within one region of the brain they would develop in other areas. Therefore, the pattern of injury looked very different when imaging was performed at different times during this evolution. CONCLUSION: Patterns of injury detected by standard anatomic imaging sequences, DTI sequences, and proton MR spectroscopy varied considerably during the first 2 weeks after injury. The appearance of new areas of reduced diffusion simultaneous with the pseudonormalization of areas that had reduced diffusion at earlier times can result in an entirely different pattern of injury on diffusivity maps acquired at different time points. Awareness of these evolving patterns is essential if studies are performed and interpreted during this critical period of time.

Evaluation of femur length during the second and third trimesters in fetuses with myelomeningocele.

OBJECTIVES: To determine if the femur length of fetuses with myelomeningocele is shorter in the second and third trimesters compared with that of normal fetuses. METHODS: We retrospectively collected measurements of femur length, head circumference, biparietal diameter and abdominal circumference from detailed obstetric ultrasound studies performed during the second and third trimesters in 31 fetuses with myelomeningocele and 43 fetuses with no detectable anomaly. The gestational age predicted by each parameter (based on Hadlock's tables) was compared with the true gestational age (based on last menstrual period), using the ANCOVA test to determine if there was a statistically significant difference between the two groups of fetuses. RESULTS: There was no significant difference in femur length (P = 0.60) or in abdominal circumference (P = 0.85) between fetuses with myelomeningocele and normal fetuses. Fetuses with myelomeningocele did have a significantly lower biparietal diameter and head circumference (P < or = 0.001). CONCLUSIONS: Myelomeningocele is not associated with reduced femur length in the second and third trimesters, suggesting that the known postnatal lower extremity foreshortening in patients with myelomeningocele develops late in gestation or after birth.

MRI shows abnormal white matter maturation in classical holoprosencephaly.

In an attempt to assess white matter maturation in holoprosencephaly (HPE), MRI scans of 47 patients with HPE were retrospectively reviewed. White matter maturation was delayed in 25/47 patients, including 24/29 patients with classic HPE who were