| Congenital heart disease(CHD)is an innate deformity with a prevalence of approximately 0.6-0.8%in live neonates,it is the most common type of congenital malformations and birth defects.The placenta is a vital organ that provides oxygen and nutrients,discharges wastes,secretion of hormones and barrier to the invasion of foreign microorganisms or toxins,which are critical for normal fetal neurodevelopment.The placenta and fetal heart share key developmental pathways and develop in parallel,which known as the placenta-heart axis,suggesting that any harmful defects in them would likely result in abnormal development of both heart and placenta.Besides,the placenta-heart-brain connection affects each other with genetic genetics,hemodynamics,structure,or microstructure.Measuring fetal cerebral venous blood oxygen saturation(SvO2)can help assess fetal oxygen extraction fraction,oxygen consumption and brain oxygen metabolism rate;measuring brain volume,cortical thickness,sulcal depth and mean curvature can help understand the fetal brain development;Intravoxel incoherent motion(IVIM)can reflect tissue microcapillary perfusion and tissue diffusivity.Therefore,this study aims(1)To investigate the early changes SvO2 in fetuses with complex CHD and normal pregnancies across gestational age by quantitative susceptibility mapping(QSM)in utero;(2)To explore early changes of the hemodynamics,brain volume and different brain regions’ cortical development in fetuses with complex CHD;and(3)To assess placental perfusion in fetuses with complex CHD and normal pregnancy.Part 1 Brain venous blood oxygenation assessed by quantitative susceptibility mapping in fetuses with congenital heart disease and in normal pregnanciesBackground and purpose:Congenital heart disease(CHD)in fetuses can change the brain’s hemodynamics and blood oxygen level,resulting in impaired neurodevelopment.The aim of this study was to investigate the early changes(gestational age(GA):2030 weeks)of venous blood oxygen saturation(SvO2)in fetuses with complex CHD(SvO2CHD)and normal pregnancies(SvO2Normal)across GA by quantitative susceptibility mapping(QSM)in utero.Methods:In this study,in vivo 3D susceptibility-weighted imaging(SWI)was performed in 83 normal fetuses(GA:30.5±3.8 weeks,range 21.6-37,9 weeks)and 22 fetuses with CHD(GA:26.0±2.0 weeks,range 23.0-29.6 weeks).QSM images were reconstructed from the SWI phase images to quantify the SvO2 of the superior sagittal sinus(SSS).The association between SvO2 and GA was assessed for both CHD and normal fetuses using a linear regression model.In addition,we compared the SvO2 between CHD and GA-matched normal fetuses(GA:20-30 weeks)using covariance analyses.Results:The SvO2Normal demonstrated a downward trend across GA(p<0.001).Thirtytwo GA-matched normal fetuses(GA:26.8±2.1 weeks)were selected to compare the SvO2 difference with CHD fetuses.The GA-matched SvO2Normal did not change significantly with GA(p=0.064).However,SvO2CHD decreased as GA advanced(p=0.015).The SvO2CHD(71.7±9.4%)indicated no significant difference with that in GAmatched SvO2Normal(71.6±9.7%)after the effects of GA were excluded(p=0.535).Conclusions:The SvO2Normal showed a downward trend with increasing GA.SSS SvO2 measured in GA 20 to 30 weeks showed no difference in the CHD-fetuses but also show a downward trend with increasing GA.Part 2 Hemodynamics,brain volume and cortical development in fetuses with complex congenital heart diseaseObjective:Neonatal brain MRI studies have demonstrated evidence that brain development is delayed in congenital heart disease(CHD)before corrective surgery,including smaller brain volumes in mixed CHD types in the third trimester.Impaired frontal lobe growth has also recently been shown in fetuses with CHD.However,little is known about the hemodynamics changes,the timing of altered brain volume,and the different brain regions’ cortical development in these patients.The purpose of this study was to investigate early changes(20-30 weeks)of the hemodynamics,brain volume and different brain regions’ cortical development in fetuses with complex CHD.Materials and Methods:In this prospective study,pregnant women with singleton pregnancies with complex CHD between 20 and 30 weeks gestation(n=23)and healthy gestational age(GA)-matched controls(n=25)were enrolled.The Doppler examinations were performed on GE voluson E8 system.A specialized and experienced sonographer measured umbilical artery pulsation index(UA-PI),and the middle cerebral artery pulsation index(MCA-PI).The cerebroplacental ratio(CPR)was calculated as a ratio between MCA-PI and UA-PI.Fetal brain MR images were acquired on a 3T MR scanner(MAGNETOM Skyra,Siemens Healthcare,Erlangen,Germany)with an 18-channel body coil.Free-breathing T2-weighted half-Fourier single-shot turbo spin echo(T2-HASTE)images were obtained in orthogonal axial,coronal,sagittal planes.The preprocessing,including brain extraction,signal inhomogeneity correction,slice-to-volume registration,super-resolution reconstruction was performed using the NiftyMIC6,and the multiple orthogonal 2D stacks were reconstructed into high-resolution of 0.8×4.8×4.8 mm3 3D volume by NiftyMIC.The high-resolution 3D-reconstructed fetal brains were then segmented into cortical grey matter(cGM),cerebellum,lateral ventricle,and lobe regions using atlas-based segmentation with the unbiased symmetric diffeomorphic deformable registration(SyN)algorithm.The CRL atlas was chosen as the reference.Segmentations were manually refined by the experts,and total brain volume(TBV),parenchyma volume(PV),cerebellar volume(CBV),brainstem volume(BV),lateral ventricles volume(LVV),cGM volume(cGMV)and external cerebrospinal fluid spaces volume(eCSFV)were computed.The cortical white matter surface and pial surface were reconstructed by dHCP-structural-pipeline,which was modified to adapt to our fetal data(originally defined for neonates).Vertex-wise cortical indicators,including the thickness,mean curvature,and sulcal depth were computed during the reconstruction of cortical surfaces.And then we mapped the regional segmentation results in volume space to the surface space using workbench command(https://humanconnectome.org/software/workbench-command).Each vertex-wise indicator of different lobe regions was calculated respectively.The association between volumes across GA was assessed with a linear regression model between CHD and normal fetuses.Comparisons of the brain volume,sulcal depth,cortical thickness,and curvature were conducted using analysis of covariance.False-discovery rates(FDR,α=0.05)correction was used for multiple testing.Results:There was no significant difference in GA between the CHD and Normal group(25.52±1.74 weeks,26.05±2.16weeks,respectively,p=0.37).In the CHD group,the UA-PI was significantly higher than that in the normal group(1.08±0.13,0.97±0.14,respectively,p=0.024).The MCA-PI and the CPR showed no significant difference between the two groups(p=0.149,0.340,respectively).The TBV,PV,cGMV,CBV,LVV and eCSFV all showed an upward tendency and statistically significant trend across GA.Besides,the TBV,PV,cGMV,CBV,BSV in the CHD group were all smaller than that in the normal group(all p<0.05)after the FDR correction.However,the LVV and eCSFV showed no significant difference between the two groups(both p>0.05).The surface area of the cortical plate in CHD fetuses was lower than in normal fetuses across GAs(p=0.02)but showed no statistical significance after FDR correction(p=0.44).The sulcal depth,cortical thickness,and curvature values of all the brain lobes showed no difference between the two groups(all p>0.05).Conclusion:This study demonstrates that fetuses with complex CHD have abnormally higher UA-PI,smaller brain volumes(TBV,PV,CBV,LVV,CSF,cGMV)as early as 20-30 weeks.However,the thickness,mean curvature,and sulcal depth at different brain lobes in the CHD group showed no statistical difference from the normal group.In addition,the changes of UA-PI and CPR in the CHD group may be a marker of impaired fetal growth velocity.Combining these findings,this study suggests that UAPI and fetal MRI maybe an early biomarker to evaluate brain development in fetuses with CHD.Part 3.Placental perfusion in Fetuses with congenital heart disease and healthy pregnancy assessed with intravoxel incoherent motion imagingObjective:To assess placental function using intravoxel incoherent motion(IVIM)in pregnant women with a fetus diagnosed with congenital heart disease(CHD)and gestational age(GA)matched healthy controls.Materials and Methods:This prospective study enrolled pregnant women with a fetus diagnosed with CHD and GA-matched healthy controls between January 2019 to June 2020 consecutively.Participants underwent MRI of the placenta by using an IVIM sequence.One specialized and experienced radiologist measured the IVIM parameters,including apparent diffusion coefficient(ADC),diffusion coefficient(D),pseudodiffusion coefficient(D*),and pseudoperfusion fraction(f).The ADC,D,D*and f values in CHD group were compared with those in control group using the covariance analyses.Results:A total of 29 pregnant women with a fetus with CHD(GA:27.26±3.80w)and 47 healthy gestational age-matched controls(GA:26.86±3.09 w)were included.During the second trimester,there were no significant difference in the ADC(1984.18±186.06×10-6mm2/s,1938.10±125.13×10-6mm2/s,p=0.833)、D(1672.10±163.66×10-6mm2/s,1593.87±99.38×10-6mm2/s,p=0.411)、D*(17.12±1.87×103mm2/s,16.71±1.60×10-3mm2/s,p=0.859)and f(35.88±5.13%,35.99±4.26%,p=0.682)values between the CHD and normal group.During the third trimester,the mean f values were significantly lower in the CHD group compared with the normal pregnancy group(31.20±3.08%vs.33.86±3.73%,p=0.030)and there were no significant difference in the ADC(1984.18 ±186.06×10-6mm2/s,1938.10±125.13x 10-6mm2/s,p=0.833),D(1672.10±163.66×10-6mm2/s,1593.87±99.38×10-6mm2/s,p=0.411),D*(17.12±1.87×10-3mm2/s,16.71±1.60×10-3mm2/s,p=0.859)values between the CHD and normal group.Conclusion:Assessment of microvessel perfusion of the placenta based on IVIM is feasible.Compared to healthy placenta controls,pregnant women with a fetus diagnosed with CHD were characterized by lower f during the third trimester but showed no difference during the second trimester. |
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