Objective To document longitudinal changes in brain development in fetuses with congenital diaphragmatic hernia (CDH). Design Retrospective cohort study Setting Single tertiary fetal surgery center Population Fetuses with isolated CDH and at least two MRI-examinations (n=42 fetuses). Fifty-six fetuses who underwent MRI for a condition not interfering with fetal brain development or fetuses from healthy volunteers served as controls. Methods Biometry included biparietal and fronto-occipital diameter, ventricular atrial width, transcerebellar diameter, head circumference and width of the extra-axial space. Cortical maturation was assessed using a qualitative and quantitative grading system. 3D volumes were segmented for white matter, intra-axial and extra-axial cerebrospinal fluid and cerebellum. Main outcome measures Brain development on MRI with subjective and objective assessment. Results The mean GA at first MRI was 28.0 ± 2.1 wks and at the second 33.2 ± 1.3 wks. The mean GA in controls was 30.7 ± 4.2 wks. At 28 weeks CDH fetuses displayed abnormal maturation grading (p<0.003) and fissure depth (p<0.05). By 33 wks, the brain grading indices were still abnormal (p<0.01), but fissure depth measurements were in the normal range (p>0.05). Also, the extra-axial fluid and the ventricular volume were increased (resp. p 0.0054 and p 0.0243). There was no difference in white matter or cerebellum volume (p>0.05). Conclusions Brain development in CDH fetuses around 28 weeks appears to be delayed. This is less prominent at 33 weeks. In addition, there was an increase in ventricular and extra-axial space volume in the third trimester.

Abstract Objective:Evaluate deformable slice-to-volume registration (DSVR) to calculate 3D-segmented total lung volume (TLV) in fetuses with congenital diaphragmatic hernia, congenital lung lesions and healthy controls, with comparison to 2D-manual segmentation. Design:Pilot study Setting:Regional fetal medicine referral centre Sample:Fetal MRIs performed for clinical indications (abnormal cases) or as research participants (healthy controls) Methods:Sixteen MRI datasets of fetuses (22-32 weeks GA). Diagnosis: CDH(n=5), CPAM(n=2), CDH with BPS(n=1) and healthy control(n=8). DSVR was used for reconstruction of 3D isotropic (0.85 mm) volumes of fetal body followed by semi-automated lung segmentation. The resulting 3D TLV were compared to the traditional 2D-based volumetry, and a normogram of DSVR-derived fetal lung volumes from 100 cases was produced. Main Outcome Measures:Concordance with 2D-volumetry assessed with Bland-Altman analysis, results of segmentations presented visually. Observed/Expected values were calculated for abnormal cases based upon the normogram. Results:DSVR-derived TLV values have high correlation with the 2D-based measurements but with a consistently lower volume; bias -1.44cm3 [95% limits: -2.6 to -0.3] with improved resolution able to exclude hilar structures even in severe motion corruption or in cases of lung hypoplasia. Conclusions:Application of DSVR for fetal MRI provides a solution for analysis of motion corrupted scans and does not suffer from the interpolation error inherent in 2D-segmentation as per current clinical practice. It increases information content of acquired data in terms of visualising organs in 3D space and quantification of volumes, which we believe will have important value for counselling and surgical planning. Keywords:Fetal MRI; congenital diaphragmatic hernia; CPAM; lung volume