Static and dynamic responses to hyperoxia of normal placenta across gestation with T2*-weighted MRI sequences.

OBJECTIVES: T2*-weighted magnetic resonance imaging (MRI) sequences have been identified as non-invasive tools with which to study placental oxygenation in vivo. This study aimed to use these to investigate both static and dynamic responses to hyperoxia of the normal placenta across gestation. METHODS: We conducted a single-center prospective study including 52 uncomplicated pregnancies. Two T2*-weighted sequences (T2* relaxometry) were performed, one before and one after maternal hyperoxia. The distribution of placental T2* values was modeled by fitting a gamma probability density function (T2* ~ Γ α ß ), describing the structure of the histogram using the mean T2* value, the shape parameter (α) and the rate (ß). A dynamic acquisition (blood-oxygen-level-dependent (BOLD) MRI) was also performed before and during maternal oxygen supply, until placental oxygen saturation had been achieved. The signal change over time was modeled using a sigmoid function, to determine the intensity of enhancement (ΔBOLD (% with respect to baseline)), a temporal variation coefficient (λ (min-1), controlling the slope of the curve) and the maximum steepness (Vmax (% of placental enhancement/min)). RESULTS: The histogram analysis of the T2* values in normoxia showed a whole-placenta variation, with a decreasing linear trend in the mean T2* value (Pearson's correlation coefficient (R) = -0.83 (95% CI, -0.9 to -0.71), P < 0.001), along with an increasingly peaked and narrower distribution of T2* values with advancing gestation. After maternal hyperoxia, the mean T2* ratios (mean T2*hyperoxia/mean T2*baseline) were positively correlated with gestational age, while the other histogram parameters remained stable, suggesting a translation of the histogram towards higher values with a similar appearance after maternal hyperoxia. ΔBOLD showed a non-linear increase across gestation. Conversely, λ showed an inverted trend across gestation, with a weaker correlation (R = -0.33 (95% CI, -0.58 to -0.02), P = 0.04, R2 = 0.1). As a combination of ΔBOLD and λ, the changes in Vmax throughout gestation were influenced mainly by the changes in ΔBOLD and showed a positive non-linear correlation with gestational age. CONCLUSIONS: Our results suggest that the decrease in the T2* placental signal as gestation progresses does not reflect placental dysfunction. The BOLD dynamic signal change is representative of a free-diffusion model of oxygenation and highlights the increasing differences in oxygen saturation between mother and fetus as gestation progresses (ΔBOLD) and in the placental permeability to oxygen (λ). © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Quantitative fetal MRI with diffusion tensor imaging in cases with 'short' corpus callosum.

OBJECTIVES: It has been suggested previously that the presence of Probst bundles (PB) in cases with a short corpus callosum (SCC) on diffusion tensor imaging (DTI) may help to differentiate between corpus callosal (CC) dysplasia and a variant of normal CC development. The objectives of this study were to compare DTI parameters between cases of SCC vs normal CC and between cases of SCC with PB (SCC-PB+) vs SCC without PB (SCC-PB-). METHODS: This was a retrospective study of patients referred to the Necker Hospital in Paris, France, for magnetic resonance imaging (MRI) evaluation of an apparently isolated SCC detected by sonography between November 2016 and December 2022 (IRB: 00011928). MRI was performed using a 1.5-Tesla Signa system. T2-weighted axial and sagittal sequences of the fetal brain were used to measure the length and thickness of the CC. 16-direction DTI axial brain sequences were performed to identify the presence of PB and to generate quantitative imaging parameters (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) of the entire CC, genu, body and splenium. Cases in which other associated brain abnormalities were detected on MRI were excluded. Cases were matched for fetal gender and gestational age with controls in a 1:3 ratio. Control cases were normal fetuses included in the LUMIERE on the FETUS trial (NCT04142606) that underwent the same DTI evaluation of the brain. Comparisons between SCC and normal CC cases, and between SCC-PB+ and SCC-PB- cases were performed using ANOVA and adjusted for potential confounders using ANCOVA. RESULTS: Twenty-two SCC cases were included and compared with 66 fetuses with a normal CC. In 10/22 (45.5%) cases of SCC, PB were identified. As expected, dimensions of the CC were significantly smaller in SCC compared with normal CC cases (all P < 0.01). In SCC-PB+ vs SCC-PB- cases, FA values were significantly lower in the entire CC (median, 0.21 (range, 0.19-0.24) vs 0.24 (range, 0.22-0.28); P < 0.01), genu (median, 0.21 (range, 0.15-0.29) vs 0.24 (range, 0.17-0.29); P = 0.04), body (median, 0.21 (range, 0.18-0.23) vs 0.23 (range, 0.21-0.27); P = 0.04) and splenium (median, 0.22 (range, 0.16-0.30) vs 0.25 (range, 0.20-0.29); P = 0.03). ADC values were significantly higher in the entire CC, genu and body in SCC-PB+ vs SCC-PB- cases (all P < 0.05). In SCC-PB+ cases, all FA values were significantly lower, and ADC values in the CC body were significantly higher compared with normal CC cases (all P < 0.05). In SCC-PB- cases, there was no significant difference in FA and ADC compared with normal CC cases (all P > 0.05). CONCLUSIONS: Fetal DTI evaluation of the CC showed that FA values were significantly lower and ADC values tended to be significantly higher in SCC-PB+ compared with normal CC cases. This may highlight alterations of the white matter microstructure in SCC-PB+. In contrast, isolated SCC-PB- did not demonstrate significant changes in DTI parameters, strengthening the possibility that this is a normal CC variant. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Placental T2* and BOLD effect in response to hyperoxia in normal and growth-restricted pregnancies: multicenter cohort study.

OBJECTIVES: Blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI) facilitates the non-invasive in-vivo evaluation of placental oxygenation. The aims of this study were to identify and quantify a relative BOLD effect in response to hyperoxia in the human placenta and to compare it between pregnancies with and those without fetal growth restriction (FGR). METHODS: This was a prospective multicenter study (NCT02238301) of 19 pregnancies with FGR (estimated fetal weight (EFW) on ultrasound < 5th centile) and 75 non-FGR pregnancies (controls) recruited at two centers in Paris, France. Using a 1.5-Tesla MRI system, the same multi-echo gradient-recalled echo (GRE) sequences were performed at both centers to obtain placental T2* values at baseline and in hyperoxic conditions. The relative BOLD effect was calculated according to the equation 100 × (hyperoxic T2* - baseline T2*)/baseline T2*. Baseline T2* values and relative BOLD effect were compared according to EFW (FGR vs non-FGR), presence/absence of Doppler anomalies and birth weight (small-for-gestational age (SGA) vs non-SGA). RESULTS: We observed a relative BOLD effect in response to hyperoxia in the human placenta (median, 33.8% (interquartile range (IQR), 22.5-48.0%)). The relative BOLD effect did not differ significantly between pregnancies with and those without FGR (median, 34.4% (IQR, 24.1-48.5%) vs 33.7% (22.7-47.4%); P = 0.95). Baseline T2* Z-score adjusted for gestational age at MRI was significantly lower in FGR pregnancies compared with non-FGR pregnancies (median, -1.27 (IQR, -4.87 to -0.10) vs 0.33 (IQR, -0.81 to 1.02); P = 0.001). Baseline T2* Z-score was also significantly lower in those pregnancies that subsequently delivered a SGA neonate (n = 23) compared with those that delivered a non-SGA neonate (n = 62) (median, -0.75 (IQR, -3.48 to 0.29) vs 0.35 (IQR, -0.79 to 1.05); P = 0.01). CONCLUSIONS: Our study confirms a BOLD effect in the human placenta and that baseline T2* values are significantly lower in pregnancies with FGR. Further studies are needed to evaluate whether such parameters may detect placental insufficiency before it has a clinical impact on fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Corpus callosal reference ranges: systematic review of methodology of biometric chart construction and measurements obtained.

OBJECTIVE: Adequate reference ranges of size of the corpus callosum (CC) are necessary to improve characterization of CC abnormalities and parental counseling. The objective of this study was to evaluate the methodology used in studies developing references charts for CC biometry. METHODS: We conducted a systematic review of studies on fetal CC biometry using a set of predefined quality criteria of study design, statistical analysis and reporting methods. We included observational studies whose primary aim was to create ultrasound or magnetic resonance imaging charts for CC size in a normal population of fetuses. Studies were scored against a predefined set of independently agreed methodological criteria, and an overall quality score was given for each study. RESULTS: Twelve studies met the inclusion criteria. Quality scores ranged between 17.4% and 95.7%. The greatest potential for bias was noted for the following items: sample selection and sample-size calculation, as only 17% of the studies were population-based and had consecutive or random recruitment of patients and with a justification of the sample size; number of measurements obtained for CC biometry, as only 17% of the studies performed more than one measurement per fetus and per scan; and description of characteristics of the study population, as only 8% of the studies clearly reported a minimum dataset of demographic characteristics. CONCLUSIONS: Our review demonstrates substantial heterogeneity in methods and final biometric values of the fetal CC across the evaluated studies. The use of uniform methodology of the highest quality is essential in order to define a 'short' CC and provide appropriate parental counseling. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Diffusion tensor imaging of fetal spinal cord: feasibility and gestational-age-related changes.

OBJECTIVES: Diffusion tensor imaging (DTI) of the fetal brain is a relatively new technique that allows evaluation of white matter tracts of the central nervous system throughout pregnancy, as well as in certain pathological conditions. The objectives of this study were to evaluate the feasibility of DTI of the spinal cord in utero and to examine gestational-age (GA)-related changes in DTI parameters during pregnancy. METHODS: This was a prospective study conducted between December 2021 and June 2022 in the LUMIERE Platform, Necker-Enfants Malades Hospital, Paris, France, as part of the LUMIERE SUR LE FETUS trial. Women with a pregnancy between 18 and 36 weeks of gestation without fetal or maternal abnormality were eligible for inclusion. Sagittal diffusion-weighted scans of the fetal spine were acquired, without sedation, using a 1.5-Tesla magnetic resonance imaging scanner. The imaging parameters were as follows: 15 non-collinear direction diffusion-weighted magnetic-pulsed gradients with a b-value 700 s/mm2 and one B0 image without diffusion-weighting; slice thickness, 3 mm; field of view (FOV), 36 mm; phase FOV, 1.00; voxel size, 4.5 × 2.8 × 3 mm3 ; number of slices, 7-10; repetition time, 2800 ms; echo time, minimum; and total acquisition time, 2.3 min. DTI parameters, including fractional anisotropy (FA) and apparent diffusion coefficient (ADC), were extracted at the cervical, upper thoracic, lower thoracic and lumbar levels of the spinal cord. Cases with motion degradation and those with aberrant reconstruction of the spinal cord on tractography were excluded. Pearson's correlation analysis was performed to evaluate GA-related changes of DTI parameters during pregnancy. RESULTS: During the study period, 42 pregnant women were included at a median GA of 29.3 (range, 22.0-35.7) weeks. Five (11.9%) patients were not included in the analysis because of fetal movement. Two (4.8%) patients with aberrant tractography reconstruction were also excluded from analysis. Acquisition of DTI parameters was feasible in all remaining cases (35/35). Increasing GA correlated with increasing FA averaged over the entire fetal spinal cord (r, 0.37; P < 0.01), as well as at the individual cervical (r, 0.519; P < 0.01), upper thoracic (r, 0.468; P < 0.01), lower thoracic (r, 0.425; P = 0.02) and lumbar (r, 0.427; P = 0.02) levels. There was no correlation between GA and ADC averaged over the entire spinal cord (r, 0.01; P = 0.99) or at the individual cervical (r, -0.109; P = 0.56), upper thoracic (r, -0.226; P = 0.22), lower thoracic (r, -0.052; P = 0.78) or lumbar (r, -0.11; P = 0.95) levels. CONCLUSIONS: This study shows that DTI of the spinal cord is feasible in normal fetuses in typical clinical practice and allows extraction of DTI parameters of the spinal cord. There is a significant GA-related change in FA in the fetal spinal cord during pregnancy, which may result from decreasing water content as observed during myelination of fiber tracts occurring in utero. This study may serve as a basis for further investigation of DTI in the fetus, including research into its potential in pathological conditions that impact spinal cord development. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Diffusion tensor imaging of fetal brain: principles, potential and limitations of promising technique.

Human brain development is a complex process that begins in the third week of gestation. During early development, the fetal brain undergoes dynamic morphological changes. These changes result from events such as neurogenesis, neuronal migration, synapse formation, axonal growth and myelination. Disruption of any of these processes is thought to be responsible for a wide array of different pathologies. Recent advances in magnetic resonance imaging, especially diffusion-weighted imaging and diffusion tensor imaging (DTI), have enabled characterization and evaluation of brain development in utero. In this review, aimed at practitioners involved in fetal medicine and high-risk pregnancies, we provide a comprehensive overview of fetal DTI studies focusing on characterization of early normal brain development as well as evaluation of brain pathology in utero. We also discuss the reliability and limitations of fetal brain DTI. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Feasibility and Added Value of Fetal DTI Tractography in the Evaluation of an Isolated Short Corpus Callosum: Preliminary Results.

BACKGROUND AND PURPOSE: Prognosis of isolated short corpus callosum is challenging. Our aim was to assess whether fetal DTI tractography can distinguish callosal dysplasia from variants of normal callosal development in fetuses with an isolated short corpus callosum. MATERIALS AND METHODS: This was a retrospective study of 37 cases referred for fetal DTI at 30.4 weeks (range, 25-34 weeks) because of an isolated short corpus callosum less than the 5th percentile by sonography at 26 weeks (range, 22-31 weeks). Tractography quality, the presence of Probst bundles, dysmorphic frontal horns, callosal length (internal cranial occipitofrontal dimension/length of the corpus callosum ratio), and callosal thickness were assessed. Cytogenetic data and neurodevelopmental follow-up were systematically reviewed. RESULTS: Thirty-three of 37 fetal DTIs distinguished the 2 groups: those with Probst bundles (Probst bundles+) in 13/33 cases (40%) and without Probst bundles (Probst bundles-) in 20/33 cases (60%). Internal cranial occipitofrontal dimension/length of the corpus callosum was significantly higher in Probst bundles+ than in Probst bundles-, with a threshold value determined at 3.75 for a sensitivity of 92% (95% CI, 77%-100%) and specificity of 85% (95% CI, 63%-100%). Callosal lipomas (4/4) were all in the Probst bundles- group. More genetic anomalies were found in the Probst bundles+ than in Probst bundles- group (23% versus 10%, P = .08). CONCLUSIONS: Fetal DTI, combined with anatomic, cytogenetic, and clinical characteristics could suggest the possibility of classifying an isolated short corpus callosum as callosal dysplasia and a variant of normal callosal development.

Prenatal diagnosis and outcome of fetuses with isolated agenesis of septum pellucidum: cohort study and meta-analysis.

OBJECTIVE: To evaluate the postnatal outcome of children with a prenatal diagnosis of apparently isolated agenesis of the septum pellucidum (ASP). METHODS: A retrospective cohort study of cases of prenatally diagnosed ASP followed in two tertiary centers and a meta-analysis combining data from the cohort study with data from published studies identified in a systematic review were carried out. Only cases with apparently isolated ASP on antenatal ultrasound and/or magnetic resonance imaging and with available postnatal follow-up data were considered eligible for inclusion. The following outcomes were analyzed: incidence of chromosomal anomalies, agreement between antenatal and postnatal findings, overall incidence of septo-optic dysplasia (SOD) and incidence of major neurological disability (motor, language, coordination or behavioral disorder or epilepsy) in non-SOD children. The incidence of SOD in infants with apparently normal optic pathways on antenatal imaging was also evaluated. RESULTS: Fifteen cases of isolated ASP, with median postnatal follow-up of 36 months (range, 12-60 months), were selected from the two centers. Six previously published studies met the inclusion criteria for the systematic review and a total of 78 cases were eligible for the analysis, including the 15 cases from our series. Genetic tests were carried out antenatally in 30 fetuses, of which two had an abnormal result (pooled proportion, 9.0% (95% CI, 1.8-20.7%); I2 = 0%). Additional or discordant imaging findings were noted postnatally in 9/70 (pooled proportion, 13.7% (95% CI, 3.5-29.0%); I2 = 63.9%) cases. Of all 78 neonates with available follow-up, SOD was diagnosed postnatally in 14 (pooled proportion, 19.4% (95% CI, 8.6-33.2%); I2 = 51.2%). In 60 cases, the optic pathways were considered to be normal on antenatal imaging, and six of these (pooled proportion, 9.1% (95% CI, 1.1-24.0%); I2 = 62.0%) were diagnosed postnatally with SOD. Of the 46 infants with available neurological follow-up who were not affected by SOD, a major neurological disability was diagnosed in three (pooled proportion, 6.5% (95% CI, 0.5-18.6%); I2 = 40.1%). CONCLUSIONS: In the vast majority of cases with a prenatal diagnosis of apparently isolated ASP, the prognosis is favorable. However, an additional anomaly is detected after birth in about 14% of cases and has a negative impact on clinical outcome. Detailed antenatal assessment of the brain and optic pathways is strongly recommended in order to identify the presence of associated anomalies. Antenatal visualization of apparently normal optic pathways does not rule out SOD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Heterogeneity in defining fetal corpus callosal pathology: systematic review.

OBJECTIVE: Fetal anomalies of the corpus callosum (CC) have been reported in the prenatal imaging literature since 1985, and, especially when isolated, pose challenges for both the patient and fetal medicine specialist. The purpose of this study was to review systematically the literature on prenatally diagnosed abnormalities of the CC, focusing on the terminology used to describe abnormalities other than complete agenesis of the CC, and to assess the heterogeneity of the nomenclature and definitions used. METHODS: This study was conducted in accordance with the PRISMA statement for reporting systematic reviews. A literature search was performed to identify prospective or retrospective case series or cohort studies, published in English, French, Italian, German or Spanish, reporting fetal imaging findings and describing anomalies of the CC. Quality and risk of bias of the studies were evaluated using the Newcastle-Ottawa scale and a modification of the scale developed by Conde-Agudelo et al. for other fetal imaging studies. The data extracted included the number of patients, the number of different anomalies identified, the descriptive names of the anomalies, and, where applicable, the definitions of the anomalies, the number of cases of each type of anomaly and the biometric charts used. Secondary tests used to confirm the diagnosis, as well as the postnatal or post-termination tests used to ascertain the diagnosis, were also recorded. RESULTS: The search identified 998 records, and, after review of titles and abstracts and full review of 45 papers, 27 studies were included initially in the review, of which 24 were included in the final analysis. These 24 studies had a broad range of quality and risk of bias and represented 1135 cases of CC anomalies, of which 49% were complete agenesis and the remainder were described using the term partial agenesis or nine other terms, of which five had more than one definition. CONCLUSIONS: In comparison to the postnatal literature, in the prenatal literature there is much greater heterogeneity in the nomenclature and definition of CC anomalies other than complete agenesis. This heterogeneity and lack of standard definitions in the prenatal literature make it difficult to develop large multicenter pooled cohorts of patients who can be followed in order to develop a better understanding of the genetic associations and neurodevelopmental and psychological outcomes of patients with CC anomalies. As this information is important to improve counseling of these patients, a good first step towards this goal would be to develop a simpler categorization of prenatal CC anomalies that matches better the postnatal literature. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.