Ryne A. Didier

Background: Progressive ventriculomegaly and the resulting irreversible brain damage may be mitigated through timely diversion prenatal intervention. While ventriculosubgaleal shunt (VSGS) is commonly performed postnatally in premature infants, in utero placement is unexplored. Objectives: We evaluated the feasibility of intrauterine placement of VSGS using a fetal lamb obstructive hydrocephalus model. Study Design: Hydrocephalus was induced in 14 fetal lambs by injecting 1–1.5 mL of BioGlueⓇ into the cisterna magna between Days 80 and 90 of gestation. Ten to 16 days later, ultrasound was performed to confirm hydrocephalus. Afterward, VSGS was surgically placed by creating a fetal subgaleal pocket, inserting a standard ventricular catheter, tunneling under the scalp, and securing with a silk suture, with the other end into a lateral ventricle. Near term, the ewes were sacrificed. Hysterotomy was performed to extract the lambs. Lambs were evaluated through gross inspection. Postmortem magnetic resonance imaging and pathology evaluations were performed. To assess the presence of activated microglia and astroglia, selected brain sections were immuno‐stained with ionized calcium‐binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), respectively. Results: Ten ewes with 14 fetuses (four twins) underwent hydrocephalus induction (median 86 days) by maternal laparotomy and either hysterotomy (two out of 14) or transuterine (12 out of 14) methods. Two fetuses were found demised at the time of shunt placement; hydrocephalus was confirmed in 11/12 surviving fetuses (three severe, four moderates, and four mild). A VSGS was successfully placed in all 12 surviving fetuses (median 104 days) employing open uterus fetal surgery. After shunt placement, one case died immediately from severe hydrocephalus, three were aborted, and one intrauterine fetal demise was found during cesarean delivery. Of the remaining seven lambs, seven out of seven VSGS remained under the scalp without catheter migration, and all demonstrated full scalp healing. Pathologic analyses by gross and histological methods confirmed typical hydrocephalic changes, including altered and denuded ependyma. However, more than half of the catheters were macroscopically obstructed with tissue debris and fibrin (four out of seven). Conclusion: Prenatal placement of the VSGS was technically successful in all cases, meaning the shunt could be inserted in 100% of fetuses. Survival to cesarean delivery was 58% (seven out of 12). Among survivors, no hardware migration or scalp breakdown occurred. Future studies should further explore the safety of the shunt.

Background: Children with congenital heart disease (CHD) demonstrate long-term neurodevelopmental impairments. We investigated contrast-enhanced ultrasound (CEUS) cerebral perfusion in a fetal animal model exposed to sub-physiologic oxygen at equivalent levels observed in human fetuses with CHD. Methods: Fifteen fetal lambs [hypoxic animals (n = 9) and normoxic controls (n = 6)] maintained in an extrauterine environment underwent periodic brain CEUS. Perfusion parameters including microvascular flow velocity (MFV), transit time, and microvascular blood flow (MBF) were extrapolated from a standardized plane; regions of interest (ROI) included whole brain, central/thalami, and peripheral parenchymal analyses. Daily echocardiographic parameters and middle cerebral artery (MCA) pulsatility indices (PIs) were obtained. Results: Hypoxic lambs demonstrated decreased MFV, increased transit time, and decreased MBF (p = 0.026, p = 0.016, and p < 0.001, respectively) by whole brain analyses. MFV and transit time were relatively preserved in the central/thalami (p = 0.11, p = 0.08, p = 0.012, respectively) with differences in the peripheral parenchyma (all p < 0.001). In general, cardiac variables did not correlate with cerebral CEUS perfusion parameters. Hypoxic animals demonstrated decreased MCA PI compared to controls (0.65 vs. 0.78, respectively; p = 0.027). Conclusion: Aberrations in CEUS perfusion parameters suggest that in environments of prolonged hypoxia, there are regional microvascular differences incompletely characterized by MCA interrogation offering insights into fetal conditions which may contribute to patient outcomes. Impact: This work utilizes CEUS to study cerebral microvascular perfusion in a unique fetal animal model subjected to chronic hypoxic conditions equal to fetuses with congenital heart disease. CEUS demonstrates altered parameters with regional differences that are incompletely characterized by MCA Doppler values. These findings show that routine MCA Doppler interrogation may be inadequate in assessing microvascular perfusion differences. To our knowledge, this study is the first to utilize CEUS to assess microvascular perfusion in this model. The results offer insight into underlying conditions and physiological changes which may contribute to known neurodevelopmental impairments in those with congenital heart disease.

BACKGROUND AND PURPOSE: Recent advances in fetal MR imaging technology have enabled acquisition of diagnostic images in the early second trimester. Interpretation of these examinations is limited by a lack of familiarity with the developmental changes that occur during these early stages of growth. This study aimed to characterize normal fetal brain growth between the 12th and 20th weeks of gestational age. MATERIALS AND METHODS: This study was conducted as an observational retrospective analysis. Data were obtained from a tertiary care center’s PACS database. All fetuses included had late fetal MR imaging (>20 weeks) or postnatal MR imaging, which confirmed normality. Each MR image was manually segmented, with ROIs placed to calculate the volume of the supratentorial parenchyma, brainstem, cerebellum, ventricular CSF, and extra-axial CSF. A linear regression analysis was used to evaluate gestational age as a predictor of the volume of each structure. RESULTS: Thirty-one subjects with a mean gestational age of 17.23 weeks (range, 12–19 weeks) were studied. There was a positive, significant association between gestational age and intracranial, supratentorial parenchyma; brainstem cerebellum; intraventricular CSF; and extra-axial CSF volumes (P < .001). Growth was fastest in the supratentorial parenchyma and extra-axial CSF. Fetal sex was not associated with the volume in any of the ROIs. CONCLUSIONS: This study demonstrates distinct trajectories for the major compartments of the fetal brain in the early second trimester. The fastest growth rates were observed in the supratentorial brain and extra-axial CSF.

Background Intracranial pressure (ICP) monitoring in children currently requires invasive techniques. Subharmonic aided pressure estimation (SHAPE) uses contrast-enhanced ultrasound (CEUS) to measure intravascular and interstitial pressure, but utility in ICP measurements has yet to be explored. Objective The objective of this study was to investigate SHAPE as a novel tool for noninvasive ICP measurements in fetal lambs. Materials and methods Eighteen fetal lambs at 107–139 days gestational age (term = 145 days) underwent subdural ICP catheter placement. The brain was imaged in the coronal plane in CEUS mode optimized for SHAPE, while infusing an US contrast agent into the fetal circulation. After SHAPE calibration, saline was infused via the subdural catheter to increase ICP. Five-second SHAPE cine clips were obtained at various ICPs. Subharmonic intensity values of the whole brain and thalami were correlated with ICP values using mixed effects linear regression analyses and the strength of the relationship was evaluated by Spearman’s rank-order correlation. Results Forty-nine experiments produced 723 datapoints, including SHAPE intensity values and mean ICP measurements. There was a statistically significant inverse relationship between SHAPE intensity values and ICP measurements in the whole brain and thalami (median rho value − 0.58 and − 0.56, respectively). Conclusion SHAPE intensity values of the brain demonstrate an inverse and statistically significant correlation with in vivo ICP measurements in an animal model.

Introduction: The aim of the study was to determine if markers of donor placental insufficiency and recipient cardiac dysfunction increase the risk for single fetal demise (SFD) after laser for twin-twin transfusion syndrome (TTTS). Methods: Single-center retrospective review of patients who had laser for TTTS. Risk factors for donor and recipient demise within 1 week were compared in pregnancies with SFD and pregnancies with dual survival using χ2 or Fisher’s exact test. Multivariate logistic regression was then performed. Results: Of 398 procedures, 305 (76.6%) had dual survival, 36 (9.0%) had donor demise, 28 (7.0%) had recipient demise, and 9 (2.3%) had dual demise. The remaining 20 (5.0%) patients had complicated courses with pregnancy loss or further intervention. In the 64 pregnancies with SFD, 29 (81%) in the donor group and 20 (71%) in the recipient group occurred in the first postoperative week. For the donor demise group, estimated fetal weight (EFW) 30% did not increase the risk for donor demise except in cases that also had umbilical artery absent or reversed end diastolic flow (AREDF). Donor AREDF was the only independent risk factor for early donor demise. For the recipient demise group, recipient abnormal venous Dopplers were associated with increased risk while EFW discordance >25% was associated with decreased risk of recipient loss. Discussion/Conclusion: In our cohort, donor growth restriction did not increase the risk of early donor demise after laser unless there was also donor AREDF. Donor AREDF was an independent risk factor for donor demise likely due to the severity of placental insufficiency. Abnormal recipient venous Doppler indices increased the risk of early recipient loss while a large intertwin discordance decreased the risk. This may be explained by profound overload in cases with recipient abnormal venous Doppler velocimetry and a lower risk of substantial fluid shifts from a relatively smaller donor territory when there is a large discordance.