Synthetic MRI and MR Fingerprinting-Derived Relaxometry of Antenatal Human Brainstem Myelination: A Postmortem-Based Quantitative Imaging Study.

BACKGROUND AND PURPOSE: The radiologic evaluation of ongoing myelination is currently limited prenatally. Novel quantitative MR imaging modalities provide relaxometric properties that are linked to myelinogenesis. In this retrospective postmortem imaging study, the capability of Synthetic MR imaging and MR fingerprinting-derived relaxometry for tracking fetal myelin development was investigated. Moreover, the consistency of results for both MR approaches was analyzed. MATERIALS AND METHODS: In 26 cases, quantitative postmortem fetal brain MR data were available (gestational age range, 15 + 1 to 32 + 1; female/male ratio, 14/12). Relaxometric measurements (T1-/T2-relexation times) were determined in the medulla oblongata and the midbrain using Synthetic MR imaging/MR fingerprinting-specific postprocessing procedures (Synthetic MR imaging and MR Robust Quantitative Tool for MR fingerprinting). The Pearson correlations were applied to detect relationships between T1-relaxation times/T2-relaxation times metrics and gestational age at MR imaging. Intraclass correlation coefficients were calculated to assess the consistency of the results provided by both modalities. RESULTS: Both modalities provided quantitative data that revealed negative correlations with gestational age at MR imaging: Synthetic MR imaging-derived relaxation times (medulla oblongata [r = -0.459; P = .021]; midbrain [r = -0.413; P = .040]), T2-relaxation times (medulla oblongata [r = -0.625; P < .001]; midbrain [r = -0.571; P = .003]), and MR fingerprinting-derived T1-relaxation times (medulla oblongata [r = -0.433; P = .035]; midbrain [r = -0.386; P = .062]), and T2-relaxation times (medulla oblongata [r =-0.883; P < .001]; midbrain [r = -0.890; P < .001]).The intraclass correlation coefficient analysis for result consistency between both MR approaches ranged between 0.661 (95% CI, 0.351-0.841) (T2-relaxation times: medulla oblongata) and 0.920 (95% CI, 0.82-0.965) (T1-relaxation times: midbrain). CONCLUSIONS: There is a good-to-excellent consistency between postmortem Synthetic MR imaging and MR fingerprinting myelin quantifications in fetal brains older than 15 + 1 gestational age. The strong correlations between quantitative myelin metrics and gestational age indicate the potential of quantitative MR imaging to identify delayed or abnormal states of myelination at prenatal stages of cerebral development.

3T MRI signal intensity profiles and thicknesses of transient zones in human fetal brain at mid-gestation.

In this study we compare temporal lobe (TL) signal intensity (SI) profiles, along with the average thicknesses of the transient zones obtained from postmortem MRI (pMRI) scans and corresponding histological slices, to the frontal lobe (FL) SI and zone thicknesses, in normal fetal brains. The purpose was to assess the synchronization of the corticogenetic processes in different brain lobes. Nine postmortem human fetal brains without cerebral pathologies, from 19 to 24 weeks of gestation (GW) were analyzed on T2-weighted 3T pMRI, at the coronal level of the thalamus and basal ganglia. The SI profiles of the transient zones in the TL correlate well spatially and temporally to the signal intensity profile of the FL. During the examined period, in the TL, the intermediate and subventricular zone are about the size of the subplate zone (SP), while the superficial SP demonstrates the highest signal intensity. The correlation of the SI profiles and the distributions of the transient zones in the two brain lobes, indicates a time-aligned histogenesis during this narrow time window. The 3TpMRI enables an assessment of the regularity of lamination patterns in the fetal telencephalic wall, upon comparative evaluation of sizes of the transient developmental zones and the SI profiles of different cortical regions. A knowledge of normal vs. abnormal transient lamination patterns and the SI profiles is a prerequisite for further advancement of the MR diagnostic tools needed for early detection of developmental brain pathologies prenatally, especially mild white matter injuries such as lesions of TL due to prenatal cytomegalovirus infections, or cortical malformations.

Temporal changes in epidemiological profile and fetal indications for late termination of pregnancy: a retrospective single-center study.

PURPOSE: To explore whether epidemiological shifts regarding reproduction and pregnancy have influenced the spectrum of indications for late termination of singleton pregnancies (TOP) above 17 weeks of gestation and to evaluate temporal changes in maternal demographics and fetal indications over the last 16 years. METHODS: Retrospective single-center cohort study involving all late TOPs preceded by feticide between 1 January 2004 and 31 December 2019 at a tertiary referral hospital in Austria. Outcome variables were retrieved and a time trend assessed between two 8-year intervals (2004-2011 versus 2012-2019). RESULTS: Between January 2004 and December 2019, a total of 209 singleton pregnancies (50.7% male; 46.9% female fetuses, 2.4% no disclosed sex) were terminated medically at a median gestational age of 25+1 (17+3-37+1) weeks at our institution. Predominant conditions legally justifying the late medical abortion were abnormaltities of the brain/central nervous system (n = 83; 39.7%), chromosomal aberrations (n = 33; 15.8%), complex malformations (n = 31; 4.8%) and abnormaltities of the musculosceletal system including diaphragmatic hernias (n = 18; 8.6%), as reflected by the ICD-10-categories "Congenital malformation of the central nervous system", "Other congenital malformations" and "Chromosomal abnormalities". No changes were observed with regards to maternal age (30.1 ± 5.9 vs. 31.0 ± 6.0 years; p = 0.315) nor frequency of assisted reproductive technologies (7.0% vs. 8.5%; p = 0.550). Despite a 2.5-fold increase in incidence of late TOPs, no epidemiological changes in maternal or fetal characteristics were observed over the last 16 years. CONCLUSION: Population profile and indications for late TOPs followed by feticide remain unchanged over time.

Developmental Differences Between the Limbic and Neocortical Telencephalic Wall: An Intrasubject Slice-Matched 3 T MRI-Histological Correlative Study in Humans.

The purpose of the study was to investigate the interrelation of the signal intensities and thicknesses of the transient developmental zones in the cingulate and neocortical telencephalic wall, using T2-weighted 3 T-magnetic resonance imaging (MRI) and histological scans from the same brain hemisphere. The study encompassed 24 postmortem fetal brains (15-35 postconceptional weeks, PCW). The measurements were performed using Fiji and NDP.view2. We found that T2w MR signal-intensity curves show a specific regional and developmental stage profile already at 15 PCW. The MRI-histological correlation reveals that the subventricular-intermediate zone (SVZ-IZ) contributes the most to the regional differences in the MRI-profile and zone thicknesses, growing by a factor of 2.01 in the cingulate, and 1.78 in the neocortical wall. The interrelations of zone or wall thicknesses, obtained by both methods, disclose a different rate and extent of shrinkage per region (highest in neocortical subplate and SVZ-IZ) and stage (highest in the early second half of fetal development), distorting the zones' proportion in histological sections. This intrasubject, slice-matched, 3 T correlative MRI-histological study provides important information about regional development of the cortical wall, critical for the design of MRI criteria for prenatal brain monitoring and early detection of cortical or other brain pathologies in human fetuses.

Genetic diagnosis and clinical evaluation of severe fetal akinesia syndrome.

OBJECTIVE: In this retrospective study, we describe the clinical course, ultrasound findings and genetic investigations of fetuses affected by fetal akinesia. MATERIALS AND METHODS: We enrolled 22 eukaryotic fetuses of 18 families, diagnosed with fetal akinesia between 2008 and 2016 at the Department of Obstetrics and Feto-Maternal Medicine at the Medical University of Vienna. Routine genetic evaluation included karyotyping and chromosomal microarray analysis. Retrospectively, exome sequencing was performed in the index case of 11 families, if stored DNA was available. Confirmation analyses and genetic diagnosis of siblings were performed by using Sanger sequencing. RESULTS: Whole exome sequencing identified pathogenic variants of CNTN1, RYR1, NEB, GLDN, HRAS and TNNT3 in six cases of 11 families. In three of these families, the variants were confirmed in the respective sibling. CONCLUSIONS: The present study demonstrates a high diagnostic yield of exome sequencing in fetuses affected by akinesia syndrome, especially if family history is positive. Still, in a large part the underlying genetic cause remained unknown, whereas precise clinical evaluation in combination with exome sequencing shows to be the best tool to find the disease causing variants.

The Subplate Layers: The Superficial and Deep Subplate Can be Discriminated on 3 Tesla Human Fetal Postmortem MRI.

The subplate (SP) is a transient structure of the human fetal brain that becomes the most prominent layer of the developing pallium during the late second trimester. It is important in the formation of thalamocortical and cortico-cortical connections. The SP is vulnerable in perinatal brain injury and may play a role in complex neurodevelopmental disorders, such as schizophrenia and autism. Nine postmortem fetal human brains (19-24 GW) were imaged on a 3 Tesla MR scanner and the T2-w images in the frontal and temporal lobes were compared, in each case, with the histological slices of the same brain. The brains were confirmed to be without any brain pathology. The purpose of this study was to demonstrate that the superficial SP (sSP) and deep SP (dSP) can be discriminated on postmortem MR images. More specifically, we aimed to clarify that the observable, thin, hyperintense layer below the cortical plate in the upper SP portion on T2-weighted MR images has an anatomical correspondence to the histologically established sSP. Therefore, the distinction between the sSP and dSP layers, using clinically available MR imaging methodology, is possible in postmortem MRI and can help in the imaging interpretation of the fetal cerebral layers.

Lumbar Intervertebral Disc Degeneration as a Common Incidental Finding in Young Pregnant Women as Observed on Prenatal Magnetic Resonance Imaging.

Background: Obstetric imaging, subserving fetal evaluation, may yield incidental maternal findings. Based on prenatal magnetic resonance (MR) imaging, this study aims to investigate incidental intervertebral disc degeneration and displacement in young, pregnant women. Methods: This retrospective study included the sagittal 1.5 Tesla, T2-weighted lumbar spine images of 943 pregnant Central Europeans (age range, 18-47 years), who initially had undergone MR imaging because of sonographically suspected fetal abnormalities. Qualitatively, 4715 lumbar intervertebral discs were evaluated for degeneration using a modified Pfirrmann MR classification (nondegenerated, low-grade, moderate, and high-grade degeneration), as well as for displacement. In addition to descriptive statistics, an ordinal regression analysis was performed to analyze the relationship between degeneration and the women's age, and body weight. Results: With regard to the highest degree of degeneration in each woman, 578 (61.3%) showed low-grade, 211 (22.4%) moderate, and 154 (16.3%) high-grade degeneration, and no woman had entirely nondegenerated discs. For the span from 18 to 47 years of age, moderate and high-grade degeneration increased from 6.7% to 36.7% and from 13.3% to 22.4%, respectively. Of 943 women, 57 (6%) had disc displacements, of which 97% were in conjunction with high-grade degeneration. There was a statistically significant relationship (p < 0.001) between degeneration and age, and between degeneration and body weight. Conclusions: In young pregnant women, lumbar intervertebral disc degeneration is a ubiquitous, incidental finding, increasing from the late second decade of life onward, which may be part of physiological aging, as opposed to a small percentage of incidental disc displacements.

Perinatal outcomes of infants with congenital limb malformations: an observational study from a tertiary referral center in Central Europe.

BACKGROUND: Congenital limb malformations are rare, and their perinatal outcomes are not well described. This study analyzed the perinatal outcomes of infants with congenital limb malformations. METHODS: All infants with congenital limb malformations who underwent prenatal assessment and delivery at our tertiary referral center from 2004 through 2017 were retrospectively identified. Neonatal outcome parameters were assessed, and the predictors of worse perinatal outcomes were determined. RESULTS: One hundred twenty-four cases of congenital limb malformations were identified, of which 104 (83.9%) were analyzed. The upper limb was affected in 15 patients (14.4%), the lower limb in 49 (47.1%), and both limbs in 40 (38.5%) patients. A fetal syndrome was identified in 66 patients (63.5%); clubfoot and longitudinal reduction defects were the most frequent malformations. In total, 38 patients (36.5%) underwent termination, seven (6.7%) had stillbirth, and 59 (56.7%) had live-born delivery. Rates of preterm delivery and transfer to the Neonatal Intensive Care Unit were 42.4 and 25.4%, respectively. Localization of the malformation was a determinant of perinatal outcome (P = .006) and preterm delivery (P = .046). CONCLUSIONS: Congenital limb malformations frequently occur bilaterally and are associated with poor perinatal outcomes, including high rates of stillbirth and preterm delivery. Multidisciplinary care and referral to a perinatal center are warranted.

Echo-planar FLAIR Sequence Improves Subplate Visualization in Fetal MRI of the Brain.

Background The cortical plate (future cortex) is readily identifiable in utero at MRI. However, MRI evaluation of the remaining brain layers is limited by the poor T2 contrast between the subplate and the underlying intermediate zone (IZ). Purpose To compare the delineation of fetal brain lamination between T2-weighted single-shot fast spin-echo (SSFSE) and echo-planar imaging (EPI) fluid-attenuated inversion recovery (FLAIR) images, and to quantify differences in the depiction of brain layering between the two sequences. Materials and Methods Consecutive fetal brain MRI examinations performed between January 2014 and March 2018 with T2-weighted SSFSE and EPI-FLAIR images were reviewed. Two neuroradiologists evaluated the visibility of brain layers by using a three-point grading system, and findings were compared by using the sign test. One rater performed region-of-interest analysis in the cortical plate (CP), subplate (gyral crest and sulcal bottom), and IZ. Signal intensity (SI) ratios between adjacent brain compartments were calculated and compared by using the paired t test. Reader agreement was assessed by using weighted κ values. Results A total of 259 MRI examinations (mean gestational age [GA], 26.9 weeks ± 5.6) were included in the qualitative analysis, and 72 MRI examinations (mean GA, 27.4 weeks ± 5.5) were included in the quantitative analysis. Subplate identification on EPI-FLAIR images was superior to that on T2-weighted SSFSE images (subplate visualization [complete + partial]: frontal lobe, n = 243 vs n = 117; temporal lobe, n = 244 vs n = 137; parietal lobe n = 240 vs n = 93; and occipital lobe, n = 241 vs n = 97, respectively; P < .001), with higher interrater reliability (κ = 0.91-0.95 for EPI-FLAIR images and 0.80-0.87 for T2-weighted SSFSE images). SI ratios between the IZ and subplate were significantly higher on EPI-FLAIR images in all lobes (EPI-FLAIR images: 1.6-2.1; T2-weighted SSFSE images:1.2-1.2; P < .001). Subplate-to-CP ratios were not statistically significant between the two sequences (EPI-FLAIR:1.8-2.4; T2-weighted SSFSE: 2.0-2.2; P < .001). Conclusion The echo-planar fluid-attenuated inversion recovery sequence improves visualization of fetal brain lamination compared with the T2-weighted single-shot fast spin-echo sequence, as established by quantitative and qualitative methods. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Rossi in this issue.

Value of increased nuchal translucency in the era of noninvasive prenatal testing with cell-free DNA.

OBJECTIVE: To assess the value of increased nuchal translucency (NT) at first-trimester screening (FTS) despite the superiority of noninvasive prenatal testing with cell-free DNA (cfDNA) for the detection of fetal aneuploidies. METHODS: Retrospective analysis of all FTS data from 2005 to 2015 in our department. Only cases with increased NT and euploid karyotype were considered eligible for inclusion. Abnormal findings, diagnostic work-up, and perinatal outcomes were assessed. RESULTS: Of 18 084 FTS results, 460 (2.5%) showed increased fetal NT, of which 242 (52.6%) underwent invasive karyotyping and 179 (74.0%) had an aneuploidy. Of the remaining 63 cases, 61 (96.8%) showed an additional sonographic finding at FTS and25 (78.1%) had a major anomaly at the second trimester organ scan. The outcome was termination of pregnancy in 28 (44.4%) cases, fetal demise in 5 (7.9%), delivery of an infant with malformation in 21 (33.3%), and delivery of a healthy infant in 7 (11.1%) cases. CONCLUSION: All cases with increased NT would have been detected by cfDNA or by a major sonographic anomaly not later than the second trimester. Routine use of cfDNA, a basic sonogram, and an organ scan could reduce unnecessary work-up and anxiety.

Fetal Survival in Second-Trimester Termination of Pregnancy Without Feticide.

OBJECTIVE: To evaluate the rate of live birth and the duration of survival after termination of pregnancy without feticide. METHODS: We conducted a retrospective analysis of 241 terminations of pregnancy without feticide for fetal anomalies or genetic abnormalities between 20 0/7 and 24 0/7 weeks of gestation at a single tertiary care referral center in Europe between February 2003 and May 2017. A multivariate binary regression model was used to evaluate factors associated with live birth. RESULTS: Pregnancies were terminated at a mean gestational age of 22.1±1.1 completed weeks of gestation. Median birth weight was 440 g (range 141-1,890 g). Live birth occurred in 122 cases (50.6%, 95% CI 44.4-56.8); median survival time was 32 minutes (range 1-267 minutes). Factors associated with live birth were gestational age at labor induction (odds ratio 1.41, 95% CI 1.01-2.01; P=.049) and fetal anomalies (P=.046). CONCLUSION: After termination of pregnancy without feticide between 20 0/7 and 24 0/7 weeks of gestation, the live birth rate was 50.6% (95% CI 44.4-56.8). A lower gestational age at labor induction and the presence of skeletal, cerebral, renal, or multiple fetal anomalies increased the chance of stillbirth.

Prenatal diagnosis of congenital upper limb differences: a current concept review.

Congenital upper limb differences are frequently associated with complex syndromes. Ultrasonography is considered as the first-line diagnostic modality, and fetal MRI can be useful to further evaluate ill-defined areas. Genetic and non-invasive prenatal testing help to identify the underlying genetic disorder. The diagnostic assessment is a multidisciplinary task that should involve early prenatal consultations with specialists involved in case management and treatment planning. Obstetricians, geneticists, radiologists, psychologists and dedicated surgeons are needed to provide good parental education, prenatal and postnatal care, and successful outcomes. The purpose of this review is to provide an overview of the clinicopathologic background, current diagnostic and imaging procedures in affected fetuses.

Fetal diffusion tensor quantification of brainstem pathology in Chiari II malformation.

OBJECTIVES: This prenatal MRI study evaluated the potential of diffusion tensor imaging (DTI) metrics to identify changes in the midbrain of fetuses with Chiari II malformations compared to fetuses with mild ventriculomegaly, hydrocephalus and normal CNS development. METHODS: Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated from a region of interest (ROI) in the midbrain of 46 fetuses with normal CNS, 15 with Chiari II malformations, eight with hydrocephalus and 12 with mild ventriculomegaly. Fetuses with different diagnoses were compared group-wise after age-matching. Axial T2W-FSE sequences and single-shot echo planar DTI sequences (16 non-collinear diffusion gradient-encoding directions, b-values of 0 and 700 s/mm(2), 1.5 Tesla) were evaluated retrospectively. RESULTS: In Chiari II malformations, FA was significantly higher than in age-matched fetuses with a normal CNS (p = .003), while ADC was not significantly different. No differences in DTI metrics between normal controls and fetuses with hydrocephalus or vetriculomegaly were detected. CONCLUSIONS: DTI can detect and quantify parenchymal alterations of the fetal midbrain in Chiari II malformations. Therefore, in cases of enlarged fetal ventricles, FA of the fetal midbrain may contribute to the differentiation between Chiari II malformation and other entities. KEY POINTS: • FA in the fetal midbrain is elevated in Chiari II malformations. • FA is not elevated in hydrocephalus and mild ventriculomegaly without Chiari II. • Measuring FA may help distinguish different causes for enlarged ventricles prenatally. • Elevated FA may aid in the diagnosis of open neural tube defects. • Elevated FA might contribute to stratification for prenatal surgery in Chiari II.

Isolated Short Fetal Femur Length in the Second Trimester and the Association with Adverse Perinatal Outcome: Experiences from a Tertiary Referral Center.

OBJECTIVE: To determine the association between isolated mid-trimester short fetal femur length and adverse perinatal outcome. METHODS: This is a retrospective cohort study of patients with singleton gestations routinely assessed by second trimester ultrasound examination during 2006-2013. A fetal isolated short femur was defined as a femur length (FL) below the 5th percentile in a fetus with an abdominal circumference greater than the 10th percentile. Cases of aneuploidy, skeletal dysplasia and major anomalies were excluded. Primary outcomes of interest included the risk of small for gestational age neonates, low birth weight and preterm birth (PTB). Secondary outcome parameters were a 5-min Apgar score less than 7 and a neonatal intensive care unit admission. A control group of 200 fetuses with FL ≥ 5th percentile was used to compare primary and secondary outcome parameters within both groups. Chi-square and Student's t-tests were used where appropriate. RESULTS: Out of 608 eligible patients with a short FL, 117 met the inclusion criteria. Isolated short FL was associated with an increased risk for small for gestational age (19.7% versus 8.0%, p = 0.002) neonates, low birth weight (23.9% versus 8.5%, p<0.001), PTB (19.7% versus 6.0%, p<0.001) and neonatal intensive care unit admissions (13.7% versus 3.5%, p = 0.001). The incidence of a 5-min Apgar score less than 7 was similar in both groups. CONCLUSION: Isolated short FL is associated with a subsequent delivery of small for gestational age and Low birth weight neonates as well as an increased risk for PTB. This information should be considered when counseling patients after mid-trimester isolated short FL is diagnosed.

Normal mandibular growth and diagnosis of micrognathia at prenatal MRI.

OBJECTIVE: The aim of this article is to present reference data for fetal mandibular growth on magnetic resonance imaging, enabling the diagnosis of micrognathia. METHODS: Retrospectively, on 355 magnetic resonance scans of apparently facially normal fetuses [gestational age (GA), 20-36 weeks], mandibular anterior-posterior diameter (APD = mandibular size), inferior facial angle (IFA = mandibular position), and jaw index (APD normalized to biparietal diameter) were correlated with GA by Pearson correlation. APD-age relationship was modeled. A receding chin was subjectively determined. Ten fetuses with mandibular anomalies were compared with normal fetuses. RESULTS: For GA, APD showed high correlation (r = 0.850; P < 0.001), IFA (r = 0.086; P = 0.119) no correlation, and jaw index (r = -0.139; P = 0.018) weak correlation. APD-age relationship was expressed by the following: APD = 0.281 + 0.989 * GA (r(2) = 0.723). A receding chin was identified in 7/10 abnormal fetuses. APD, IFA, and jaw index of abnormal and normal fetuses were significantly different (P < 0.001). In 10/10 abnormal fetuses, IFA was <50.0°; in 7/10, jaw index was less than the fifth percentile (micrognathia); in 3/10, jaw index was at low normal range (retrognathia). CONCLUSIONS: Subjective identification of micrognathia may be limited. Reference data provide quantitative evaluation of mandibular size and position. An IFA <50° reflects micrognathia or retrognathia; a jaw index less than the fifth percentile suggests micrognathia.

Isolated single umbilical artery: evaluating the risk of adverse pregnancy outcome.

OBJECTIVE: To evaluate if isolated single umbilical artery (SUA) diagnosed on second-trimester ultrasound has an independent risk association with adverse pregnancy outcomes. STUDY DESIGN: We compared 136 singleton pregnancies with isolated SUA with 500 consecutive singleton pregnancies with a three-vessel cord (3 VC). Pregnancies complicated by chromosomal abnormalities and other congenital malformations were excluded. The rates of intrauterine growth restriction (IUGR) defined as birth weight less than the 3rd percentile, small for gestational age (SGA) fetuses, defined as a birth weight lower than the 10th percentile and the incidence of very preterm deliveries before 34 weeks of gestation were compared between the two groups. Multivariable logistic regression analysis was performed to evaluate the risk association between SUA and adverse pregnancy outcomes, while controlling for potential confounders. RESULTS: Fetuses with isolated SUA had significantly lower birth weight (2942.5 ± 783.7 vs. 3243.7 ± 585.6 g, p = 0.002), and were delivered at an earlier gestational age (38.7 ± 3.4 vs. 39.5 ± 2.2 weeks, p < 0.001), when compared to fetuses with a 3 VC. Fetuses with isolated SUA were at higher risk for IUGR (15.4% vs. 1.8%, p < 0.001), SGA (20.6% vs. 4.4%, p < 0.001) and very preterm delivery (6.6% vs. 1.4%, p = 0.002). Using a multiple logistic regression model, isolated SUA was shown to be an independent risk factor for IUGR (adjusted OR = 11.3, 95% CI 4.8-25.6; p < 0.001) and very preterm delivery (adjusted OR = 5.0, 95% CI 1.8-13.8; p = 0.002). CONCLUSIONS: The presence of isolated SUA is independently associated with an increased risk for IUGR, SGA and very preterm delivery.

Validation of In utero Tractography of Human Fetal Commissural and Internal Capsule Fibers with Histological Structure Tensor Analysis.

Diffusion tensor imaging (DTI) and tractography offer the unique possibility to visualize the developing white matter macroanatomy of the human fetal brain in vivo and in utero and are currently under investigation for their potential use in the diagnosis of developmental pathologies of the human central nervous system. However, in order to establish in utero DTI as a clinical imaging tool, an independent comparison between macroscopic imaging and microscopic histology data in the same subject is needed. The present study aimed to cross-validate normal as well as abnormal in utero tractography results of commissural and internal capsule fibers in human fetal brains using postmortem histological structure tensor (ST) analysis. In utero tractography findings from two structurally unremarkable and five abnormal fetal brains were compared to the results of postmortem ST analysis applied to digitalized whole hemisphere sections of the same subjects. An approach to perform ST-based deterministic tractography in histological sections was implemented to overcome limitations in correlating in utero tractography to postmortem histology data. ST analysis and histology-based tractography of fetal brain sections enabled the direct assessment of the anisotropic organization and main fiber orientation of fetal telencephalic layers on a micro- and macroscopic scale, and validated in utero tractography results of corpus callosum and internal capsule fiber tracts. Cross-validation of abnormal in utero tractography results could be achieved in four subjects with agenesis of the corpus callosum (ACC) and in two cases with malformations of internal capsule fibers. In addition, potential limitations of current DTI-based in utero tractography could be demonstrated in several brain regions. Combining the three-dimensional nature of DTI-based in utero tractography with the microscopic resolution provided by histological ST analysis may ultimately facilitate a more complete morphologic characterization of axon guidance disorders at prenatal stages of human brain development.

MR-based morphometry of the posterior fossa in fetuses with neural tube defects of the spine.

OBJECTIVES: In cases of "spina bifida," a detailed prenatal imaging assessment of the exact morphology of neural tube defects (NTD) is often limited. Due to the diverse clinical prognosis and prenatal treatment options, imaging parameters that support the prenatal differentiation between open and closed neural tube defects (ONTDs and CNTDs) are required. This fetal MR study aims to evaluate the clivus-supraocciput angle (CSA) and the maximum transverse diameter of the posterior fossa (TDPF) as morphometric parameters to aid in the reliable diagnosis of either ONTDs or CNTDs. METHODS: The TDPF and the CSA of 238 fetuses (20-37 GW, mean: 28.36 GW) with a normal central nervous system, 44 with ONTDS, and 13 with CNTDs (18-37 GW, mean: 24.3 GW) were retrospectively measured using T2-weighted 1.5 Tesla MR -sequences. RESULTS: Normal fetuses showed a significant increase in the TDPF (r = .956; p<.001) and CSA (r = .714; p<.001) with gestational age. In ONTDs the CSA was significantly smaller (p<.001) than in normal controls and CNTDs, whereas in CNTDs the CSA was not significantly smaller than in controls (p = .160). In both ONTDs and in CNTDs the TDPF was significantly different from controls (p<.001). CONCLUSIONS: The skull base morphology in fetuses with ONTDs differs significantly from cases with CNTDs and normal controls. This is the first study to show that the CSA changes during gestation and that it is a reliable imaging biomarker to distinguish between ONTDs and CNTDs, independent of the morphology of the spinal defect.

Risk of inferior vena cava compression syndrome during fetal MRI in the supine position - a retrospective analysis.

OBJECTIVES: Inferior vena cava compression syndrome (VCCS) is a serious complication of supine fetal magnetic resonance imaging (MRI) examinations, particularly during late gestation. This morphologic study correlated the occurrence of VCCS with the grade of inferior vena cava (IVC) compression. MATERIALS AND METHODS: There were 56 fetal MRI in the supine position [median gestational weeks (GW) 27+4] and 16 fetal MRI in the lateral position (median GW 30+6) retrospectively analyzed. The grade of maternal IVC compression was determined by the maximal anterior-posterior diameter (DAP) at the level of L4/L5. Fetal head position and right-sided uterus volume were analyzed. Clinical VCCS-related symptoms during fetal MRI were assessed. RESULTS: A noncompressed IVC was present in 1.8% (n=1) and a DAP of 5 to <10 mm in 33.3% (n=19) and 1 to <5 mm in 64.9% (n=36). The DAP was independent of fetal head position (P=0.99) and showed no significant correlation with gestational age (r=0.33). IVC compression increased with right-sided uterus volume (r=-0.328; P=0.014). There was a significant difference in DAP in the lateral position compared with the supine position (P<0.001). Clinical assessment revealed no symptoms of VCCS in any woman. CONCLUSIONS: The presented data support the concept of physiologic compensation for significantly reduced venous backflow in the supine position during the second and third trimesters of pregnancy.

Fetal eye movements on magnetic resonance imaging.

OBJECTIVES: Eye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed. METHODS: Dynamic SSFP sequences were acquired in 72 singleton fetuses (17-40 GW, three age groups [17-23 GW, 24-32 GW, 33-40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid. RESULTS: In 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded. Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3-45%. CONCLUSIONS: In human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations.