DTI of Opioid-Exposed Fetuses Using ComBat Harmonization: A Bi-Institutional Study.

BACKGROUND AND PURPOSE: The underlying mechanisms leading to altered cognitive, behavioral, and vision outcomes in children with prenatal opioid exposure are yet to be fully understood. Some studies suggest WM alterations in infants and children with prenatal opioid exposure; however, the time course of WM changes is unknown. We aimed to evaluate differences in diffusion tensor imaging MRI parameters in the brain between opioid exposed fetuses and normal controls. MATERIALS AND METHODS: This is a pilot, prospective cohort study in which subjects in the third trimester of pregnancy underwent fetal DTI of the brain with 20 noncolinear diffusion directions and a b-value of 500 s/mm2 at 2.5-mm isotropic resolution. RESULTS: The study included a total of 26 fetuses, 11 opioid-exposed (mean gestational age, 32.61 [SD, 2.35] weeks) and 15 unexposed controls (mean gestational age, 31.77 [SD, 1.68] weeks). After we adjusted for gestational age, fractional anisotropy values were significantly higher in opioid-exposed fetuses relative to controls in 8 WM tracts: the bilateral lemniscus (left: P = .017; right: P = .020), middle cerebellar peduncle (P = .027), left inferior cerebellar peduncle (P = .026), right sagittal stratum (P = .040), right fornix stria terminalis (P = .022), right inferior fronto-occipital fasciculus (P = .011), and the right uncinate fasciculus (P = .033). Significant alteration was also identified in other DTI indices involving a series of brain regions. CONCLUSIONS: Our data demonstrate initial evidence of cerebral WM microstructural differences between opioid-exposed fetuses and unexposed controls. Further studies in larger patient populations will be needed to fully understand these findings.

Prenatal Evaluation of Intracranial Hemorrhage on Fetal MRI: A Retrospective Review.

BACKGROUND AND PURPOSE: The evaluation and characterization of germinal matrix hemorrhages have been predominantly described on postnatal head sonography in premature neonates. However, germinal matrix hemorrhages that are seen in premature neonates can be also seen in fetuses of the same postconceptual age and are now more frequently encountered in the era of fetal MR imaging. Our aim was to examine and describe the MR imaging findings of fetuses with intracranial hemorrhage. MATERIALS AND METHODS: A retrospective review of diagnostic-quality fetal MRIs showing intracranial hemorrhage from January 2004 to May 2020 was performed. Images were reviewed by 2 radiologists, and imaging characteristics of fetal intracranial hemorrhages were documented. Corresponding postnatal imaging and clinical parameters were reviewed. RESULTS: One hundred seventy-seven fetuses with a mean gestational age of 25.73 (SD, 5.01) weeks were included. Germinal matrix hemorrhage was identified in 60.5% (107/177) and nongerminal matrix hemorrhage in 39.5% (70/177) of patients. Significantly increased ventricular size correlated with higher germinal matrix hemorrhage grade (P < .001). Fetal growth restriction was present in 21.3% (20/94) of our population, and there was no significant correlation with germinal matrix grade or type of intracranial hemorrhage. An increased incidence of neonatal death with grade III germinal matrix hemorrhages (P = .069) compared with other grades was identified; 23.2% (16/69) of the neonates required ventriculoperitoneal shunts, with an increased incidence in the nongerminal matrix hemorrhage group (P = .026). CONCLUSIONS: MR imaging has become a key tool in the diagnosis and characterization of intracranial hemorrhage in the fetus. Appropriate characterization is important for optimizing work-up, therapeutic approach, and prenatal counseling.

Evaluation of Posterior Fossa Biometric Measurements on Fetal MRI in the Evaluation of Dandy-Walker Continuum.

BACKGROUND AND PURPOSE: Dandy-Walker malformation, vermian hypoplasia, and Blake pouch remnant represent a continuum of anomalies and are common reasons for referral for fetal MR imaging. This study aimed to determine biometric measurements that quantitatively delineate these 3 posterior fossa phenotypes. MATERIALS AND METHODS: Our single-center institutional review board approved a retrospective analysis of all fetal MRIs for posterior fossa malformations, including Dandy-Walker malformation, vermian hypoplasia, and Blake pouch remnant. Measurements included the anterior-to-posterior pons, craniocaudal and anterior-to-posterior vermis, lateral ventricle size, and tegmentovermian and posterior fossa angles. Measurements were compared with normal biometry and also between each subgroup. RESULTS: Thirty-three fetuses met the criteria and were included in the study. Seven were designated as having Dandy-Walker malformation; 16, vermian hypoplasia; and 10, Blake pouch remnant. No significant group interactions with adjusted mean gestational age for tegmentovermian and posterior fossa angles were observed. The tegmentovermian angle was significantly higher in Dandy-Walker malformation (109.5° [SD, 20.2°]) compared with vermian hypoplasia (52.13° [SD, 18.8°]) and Blake pouch remnant (32.1° [SD, 17.9°]), regardless of gestational age. Lateral ventricle sizes were significantly higher in Dandy-Walker malformation at a mean of ≥23.1 weeks' gestational age compared with vermian hypoplasia and Blake pouch remnant. The anterior-to-posterior and craniocaudal vermes were significantly smaller in Dandy-Walker malformation compared with vermian hypoplasia and Blake pouch remnant at mean of ≥23.1 weeks' gestational age. CONCLUSIONS: Dandy-Walker malformation can be described in relation to vermian hypoplasia and Blake pouch remnant by an increased tegmentovermian angle; however, other potential qualifying biometric measurements are more helpful at ≥23.1 weeks' gestational age. Because they fall along the same spectrum of abnormalities, the difficulty in distinguishing these entities from one another makes precise morphologic and biometric descriptions important.

White Matter Injury and Structural Anomalies in Infants with Prenatal Opioid Exposure.

Previous studies have not found structural injury or brain malformations in infants and children with prenatal opioid exposure. As part of an ongoing study evaluating neuroimaging in infants with prenatal opioid exposure, we reviewed structural brain MR imaging in 20 term infants with prenatal opioid exposure and 20 term controls at 4-8 weeks of age. We found that 8 of the 20 opioid-exposed infants had punctate white matter lesions or white matter signal abnormality on structural MR imaging, and 2 of the opioid-exposed infants had a septopreoptic fusion anomaly. No controls had white matter injury or structural malformations. Our findings underscore the importance of clinical neurodevelopmental follow-up and the need for more comprehensive imaging and long-term outcomes research following prenatal opioid exposure.

Clinical, Neuroimaging, and Electrographic Predictors of Phenobarbital Failure in Newborns With Hypoxic Ischemic Encephalopathy and Seizures.

BACKGROUND: Many neonates with hypoxic ischemic encephalopathy and seizures do not respond to the first line antiepileptic drug, phenobarbital. Little is known about what factors are associated with its failure. OBJECTIVE: To examine factors associated with failure of phenobarbital therapy in neonates with hypoxic ischemic encephalopathy and seizures. DESIGN/METHODS: A single-center retrospective review of 50 term (>35 weeks) neonates with hypoxic ischemic encephalopathy and seizures treated with phenobarbital as the first-line antiepileptic. Neonates were classified into either responders (n = 30) or nonresponders (n = 20). Nonresponse was defined as continued seizures after maximum dosing of phenobarbital or an additional antiepileptic. Subjects with acceptable magnetic resonance imaging (MRI) scans obtained within 2 weeks of birth were included in the study and rated using an MRI injury scoring system. Charts were reviewed for demographic, clinical, and laboratory variables. Resuscitation and seizure scores were also calculated. Electroencephalographic (EEG) background activity was reviewed in 2 different time epochs (12-24 hours and 24-36 hours of life) and graded as per ACNS guidelines. RESULTS: There were no significant group differences in demographic, clinical, and laboratory variables except nonresponders, who had higher mean seizure score (P = .01) and significantly more injury on MRI scan for white matter (P = .004), parenchymal cortex (P = .027), and watershed (P = .009) regions. Neonates with moderately abnormal or severely abnormal background EEG responded poorly to phenobarbital. CONCLUSION: In the presence of above factors, one can anticipate that additional antiepileptic medication may be needed. These data also support that larger studies should be done to look prospectively at using alternative agents first line in patients with severe injury.

Spinal Imaging Findings of Open Spinal Dysraphisms on Fetal and Postnatal MRI.

BACKGROUND AND PURPOSE: Fetal MRI has become a valuable tool in the evaluation of open spinal dysraphisms making studies comparing prenatal and postnatal MRI findings increasingly important. Our aim was to determine the accuracy of predicting the level of the spinal dysraphic defect of open spinal dysraphisms on fetal MR imaging and to report additional findings observed when comparing fetal and postnatal MR imaging of the spine in this population. MATERIALS AND METHODS: A single-center retrospective analysis was performed of fetal MRIs with open spinal dysraphisms from 2004 through 2016 with available diagnostic postnatal spine MR imaging. Images were reviewed by 2 board-certified fellowship-trained pediatric neuroradiologists. Corresponding clinical/operative reports were reviewed. RESULTS: One hundred nineteen fetal MRIs of open spinal dysraphisms were included. The level of the osseous defect between fetal and postnatal MR imaging was concordant in 42.9% (51/119) of cases and was 1 level different in 39% (47/119) of cases. On postnatal MR imaging, type II split cord malformation was seen in 8.4% (10/119) of cases, with only 50% (5/10) of these cases identified prospectively on fetal MR imaging. Syrinx was noted in 3% (4/119) of prenatal studies, all cervical, all confirmed on postnatal MR imaging. CONCLUSIONS: Fetal MR imaging is accurate in detecting the level of the spinal dysraphic defect, which has an impact on prenatal counseling, neurologic outcomes, and eligibility for fetal surgery. In addition, fetal MR imaging is limited in its ability to detect split cord malformations in patients with open spinal dysraphisms. Although rare, fetal MR imaging has a high specificity for detection of cervical spinal cord syrinx.

Prenatal Factors Associated with Postnatal Brain Injury in Infants with Congenital Diaphragmatic Hernia.

BACKGROUND AND PURPOSE: Approximately 60% of infants with congenital diaphragmatic hernia have evidence of brain injury on postnatal MR imaging. It is unclear whether any brain injury is present before birth. In this study, we evaluated fetal MR imaging findings of brain injury and the association of congenital diaphragmatic hernia severity with postnatal brain injury. MATERIALS AND METHODS: Fetal MR imaging and postnatal brain MR imaging were retrospectively evaluated in 36 cases of congenital diaphragmatic hernia (from 2009 to 2014) by 2 pediatric neuroradiologists. Brain injury on postnatal MR imaging and brain injury and congenital diaphragmatic hernia severity on fetal MR imaging were recorded. Correlations between brain abnormalities on fetal and postnatal brain MR imaging were analyzed. Postnatal brain injury findings correlating with the severity of congenital diaphragmatic hernia were also assessed. RESULTS: On fetal MR imaging, enlarged extra-axial spaces (61%), venous sinus distention (21%), and ventriculomegaly (6%) were identified. No maturational delay, intracranial hemorrhage, or brain parenchymal injury was identified on fetal MR imaging. On postnatal MR imaging, 67% of infants had evidence of abnormality, commonly, enlarged extra-axial spaces (44%). Right-sided congenital diaphragmatic hernia was associated with a greater postnatal brain injury score (P = .05). Low observed-to-expected lung volume was associated with postnatal white matter injury (P = .005) and a greater postnatal brain injury score (P = .008). Lack of liver herniation was associated with normal postnatal brain MR imaging findings (P = .03). CONCLUSIONS: Fetal lung hypoplasia is associated with postnatal brain injury in congenital diaphragmatic hernia, suggesting that the severity of lung disease and associated treatments affect brain health as well. We found no evidence of prenatal brain parenchymal injury or maturational delay.

Hindbrain Herniation in Chiari II Malformation on Fetal and Postnatal MRI.

BACKGROUND AND PURPOSE: As the practice of in utero repair of myelomeningoceles becomes more prevalent, knowledge of the expected MR imaging findings has become increasingly important. Our aim was to examine neuroimaging findings with a focus on hindbrain herniation and ventricular size in fetuses with open spinal dysraphism and to compare them with postnatal imaging features in groups undergoing prenatal-versus-postnatal repair. MATERIALS AND METHODS: Single-center retrospective analysis was performed on MRIs of fetuses with open spinal dysraphism from January 2004 through July 2015 with available postnatal imaging. One hundred two fetuses were included. Reports from available fetal ultrasound were also examined. Images were reviewed by 2 board-certified fellowship-trained pediatric neuroradiologists. Descriptive analyses were performed to demonstrate the distribution of the imaging findings. RESULTS: Thirty-two of 102 (31.3%) fetuses underwent in utero repair of open spinal dysraphism; 68.6% (70/102) underwent postnatal repair. Ninety-four of 102 (92.2%) fetuses had cerebellar ectopia. Of those who underwent prenatal repair (26 grade 3, 6 grade 2), 81.3% (26/32) had resolved cerebellar ectopia postnatally. Of those who had severe cerebellar ectopia (grade 3) that underwent postnatal repair, 65.5% (36/55) remained grade 3, while the remaining 34.5% (19/55) improved to grade 2. The degree of postnatal lateral ventriculomegaly in those that underwent prenatal repair (20.3 ± 5.6 mm) was not significantly different from that in those that underwent postnatal repair (21.5 ± 10.2 mm, P = .53). Increased Chiari grade was significantly correlated with decreased head size for gestational age on fetal sonography (P = .0054). CONCLUSIONS: In fetuses with open spinal dysraphism and severe Chiari II malformation that do not undergo prenatal repair, most have no change in the severity of cerebellar ectopia/Chiari grade. However, in fetuses that undergo in utero repair, most have resolved cerebellar ectopia postnatally.

Correlation of MRI Brain Injury Findings with Neonatal Clinical Factors in Infants with Congenital Diaphragmatic Hernia.

BACKGROUND AND PURPOSE: Infants with congenital diaphragmatic hernia are reported to have evidence of brain MR imaging abnormalities. Our study aimed to identify perinatal clinical factors in infants with congenital diaphragmatic hernia that are associated with evidence of brain injury on MR imaging performed before hospital discharge. MATERIALS AND METHODS: MRIs performed before hospital discharge in infants with congenital diaphragmatic hernia were scored for brain injury by 2 pediatric neuroradiologists. Perinatal variables and clinical variables from the neonatal intensive care unit stay were analyzed for potential associations with brain MR imaging findings. RESULTS: Fifty-three infants with congenital diaphragmatic hernia (31 boys) were included. At least 1 abnormality was seen on MR imaging in 32 infants (60%). The most common MR imaging findings were enlarged extra-axial spaces (36%), intraventricular hemorrhage (23%), ventriculomegaly (19%), white matter injury (17%), and cerebellar hemorrhage (17%). The MR imaging brain injury score was associated with extracorporeal membrane oxygenation (P = .0001), lack of oral feeding at discharge (P = .012), use of inotropes (P = .027), and gastrostomy tube placement before hospital discharge (P = .024). The MR imaging brain injury score was also associated with a large diaphragmatic defect size (P = .011). CONCLUSIONS: Most infants with congenital diaphragmatic hernia have at least 1 abnormality identified on MR imaging of the brain performed before discharge. The main predictors of brain injury in this population are a requirement for extracorporeal membrane oxygenation, large diaphragmatic defect size, and lack of oral feeding at discharge.

Identification and management of neonatal skull fractures.

OBJECTIVE: Suspected skull fractures in the neonate are uncommon and present a management dilemma. We hypothesized that skull fractures are more common than reported in the literature and that few infants require any intervention. STUDY DESIGN: We retrospectively reviewed the charts of 21 infants referred to our level IV Neonatal Intensive Care Unit for possible skull fracture over a 3-year period after birth trauma, suspicious findings on clinical exam, or accidental falls in the birth hospital. RESULTS: Skull films at the birth hospital were unreliable for fracture in 23% of cases. Seven of nine infants with accidental falls had fracture on computed tomography scan. Only three infants required neurosurgical intervention, all after severe birth trauma associated with instrumentation. CONCLUSION: Skull fractures are more common than previously reported in neonates after accidental falls, but few infants with skull fractures require neurosurgical intervention.

Evaluation of Subependymal Gray Matter Heterotopias on Fetal MRI.

BACKGROUND AND PURPOSE: Subependymal grey matter heterotopias are seen in a high proportion of children with Chiari II malformation and are potentially clinically relevant. However, despite its growing use, there is little in the literature describing its detection on fetal MRI. Our aim was to evaluate the accuracy in diagnosing subependymal gray matter heterotopias in fetuses with spinal dysraphism on fetal MR imaging. MATERIALS AND METHODS: This study is a retrospective analysis of 203 fetal MRIs performed at a single institution for spinal dysraphism during a 10-year period. Corresponding obstetric sonography, postnatal imaging, and clinical/operative reports were reviewed. RESULTS: Of the fetal MRIs reviewed, 95 fetuses were included in our analysis; 23.2% (22/95) were suspected of having subependymal gray matter heterotopias on fetal MR imaging prospectively. However, only 50% (11/22) of these cases were confirmed on postnatal brain MR imaging. On postnatal brain MR imaging, 28.4% (27/95) demonstrated imaging findings consistent with subependymal gray matter heterotopia. Only 40.7% (11/27) of these cases were prospectively diagnosed on fetal MR imaging. CONCLUSIONS: Fetal MR imaging is limited in its ability to identify subependymal gray matter heterotopias in fetuses with spinal dysraphism. It is believed that this limitation relates to a combination of factors, including artifacts from fetal motion, the very small size of fetal neuroanatomy, differences in imaging techniques, and, possibly, irregularity related to denudation of the ependyma/subependyma in the presence of spinal dysraphism and/or stretching of the germinal matrix in ventriculomegaly.

Fetal and postnatal brain MRI in premature infants with twin-twin transfusion syndrome.

OBJECTIVE: To describe the findings on fetal and postnatal magnetic resonance imaging (MRI) in premature infants with twin-twin transfusion syndrome (TTTS) and to determine whether currently used staging systems and other fetal and postnatal factors correlate with brain injury in this population. STUDY DESIGN: We performed a prospective study of 22 premature infants with TTTS whose mothers had fetal MRIs. Postnatal brain MRI was performed at term equivalent age (38 to 44 weeks) and medical records were reviewed. Brain injury was scored on fetal and postnatal MRIs using an injury scale incorporating hemorrhagic and nonhemorrhagic injury. RESULT: The median (range) gestational age (GA) was 31 weeks (26 to 35) and birth weight (BW) was 1296 g (762 to 2330). In all, 5/22 patients (23%) had brain injury seen on fetal MRI and 15/22 patients (68%) had brain injury seen on postnatal MRI. Quintero stage was the only predictor variable that was significantly correlated with the total brain injury score (P=0.05). CONCLUSION: Postnatal brain injury in premature infants with TTTS is correlated with Quintero stage. GA and BW are not predictive of brain injury in this cohort of infants.

Contribution of magnetic resonance imaging to prenatal differential diagnosis of renal tumors: report of two cases and review of the literature.

Enlargement of a kidney on prenatal imaging is usually due to hydronephrosis or cystic renal disease, and much less often results from solid tumors such as mesoblastic nephroma, Wilms' tumor, nephroblastomatosis, renal sarcoma, and angiomyolipoma. All can be diagnosed by ultrasound. Magnetic resonance imaging is useful not only in confirming the presence of a renal mass, but also in the evaluation of the contralateral kidney for subtle abnormalities. We present one case each of Wilms' tumor and mesoblastic nephroma, both detected on antenatal ultrasound and further studied with fetal magnetic resonance imaging.

Doppler contrast sonography for detecting reduced perfusion in experimental ischemia of prepubertal rabbit testes.

RATIONALE AND OBJECTIVES: We examined whether the intravenous (IV) Doppler ultrasound contrast agent SHU 508 would improve the detection of reduced perfusion of rabbit testes when normal flow was otherwise difficult to detect. METHODS: Seventeen anesthetized prepubertal rabbits underwent random unilateral spermatic cord ligation and a contralateral sham operation. Immediate, blinded, and systematic color Doppler examination of each pair of testes was recorded before and after IV administration of 1 ml (300 mg) SHU 508, a gas-containing microparticle. Recorded examinations were reviewed by two pediatric radiologists who were unaware of experimental conditions and who graded intratesticular flow. RESULTS: For 34 pairs of observations (17 animals x 2 observers), intratesticular flow was absent in the sham-operated testes in 18 precontrast and two postcontrast images. The false-positive rate in this group decreased from 53% to 6%. This improvement in the detection of normal blood flow was statistically significant. The absence of flow in the ischemic testis was not significantly different before or after contrast agent administration. CONCLUSION: IV SHU 508 enhances color Doppler ultrasound detection of flow not otherwise evident in prepubertal rabbit testes. Doppler ultrasound contrast agents may be used in a setting of suspected torsion when routine Doppler sonography is indeterminate.