| The development of the vertebral body begins at the 6th week of embryonic development,and three primary ossification centers can be seen in the vertebral body at 7-8 weeks.The primary ossification centers of the cervical,thoracic,lumbar and sacral vertebral bodies are initially formed at the 21-week.The development of fetal vertebral ossification center is an important index to judge the gestational age and evaluate the maturity of fetal development.It is an important part of prenatal examination and the premise of diagnosis of vertebral malformation.Fetal vertebral development malformation refers to congenital scoliosis and kyphosis caused by abnormal or asymmetric development of the vertebral body at 4-6 weeks of gestation,and the incidence rate is about 1/1000-2000.Common congenital vertebral malformations were caused by a failure of formation,by failure of segmentation,mixed or other abnormalities that affect normal development of vertebrae.The prognosis of vertebral malformation is related to the type,location,number and concomitant abnormality.Therefore,accurate prenatal diagnosis is particularly important for prenatal consultation,risk stratification and postnatal follow-up planning.Magnetic resonance imaging(MRI)is an important way to evaluate spinal development due to its advantages of high tissue contrast,high spatial resolution and large imaging field.However,the analysis of fetal vertebral ossification center development by MRI is limited to specimens.But formalin soaked specimens may cause protein denaturation and tissue dehydration,and the bone structure may decalcify if stored for a long time,which cannot truly reflect the development of intrauterine fetal vertebrae.Ultrasound(US)is the first-line for intrauterine fetal development assessment and prenatal screening.However,certain fetal and/or maternal factors(amniotic fluid,position,placenta previa,maternal abdominal scar,or maternal obesity,etc.)can adversely affect the image quality of US and reduce the detection rate of malformations.At present,the diagnostic accuracy of fetal vertebral anomalies by US is low,especially when isolated vertebral anomalies without scoliosis.With the development of ultra-fast T2-weighted sequences(single-shot Turbo spin echo),MRI is increasingly used as an adjunct to assess the development of the fetus.It is worth mentioning that the optimized Susceptibility Weighted Imaging(SWI)sequence makes use of the strong diamagnetic sensitivity characteristic of bone structure(calcium)to form a good contrast between bone and soft tissue and better outline the fetal bone structure.So the imaging quality of intrauterine fetal bony spine has been greatly improved,which makes it possible to evaluate the development of fetal vertebrae and improve the diagnosis rate of malformation with MRI.At present,little is known about the quantitative analysis with MRI to monitor the development of fetal vertebrae in intrauterine,and the diagnostic analysis of MRI for fetal vertebral anomalies has not been reported.Therefore,in this study,morphological parameters of intrauterine fetal vertebral ossification center were measured by MRI to determine MRI reference values and the diagnostic accuracy and confidence of MRI in the diagnosis of fetal vertebral anomalies were further evaluated based on a large sample of follow-up data.Part 1 MRI assessment of fetal vertebral developmentPurpose:MRI was used to measure the morphological parameters of the fetal vertebral centrum ossification centers(COC)of the fourth cervical vertebra(C4),sixth thoracic vertebra(T6),third lumbar vertebra(L3)and first sacral vertebra(S1)in the middle-late gestational ages,and to plot the growth and development trajectory of the vertebrae,providing MRI age-specific reference values for fetal vertebrae in vivo.Materials and methodsParticipants:This study was approved by our Institutional Review Board,and all the participants provided written informed consent.Inclusion criteria were(ⅰ)fetuses had no evidence of intrauterine growth restriction,chromosomal abnormality;(ⅱ)fetuses showed normal development indicated by US;(ⅲ)pregnant women have no gestational diabetes,hypertension and other pregnancy complications.Exclusion criteria included women with contraindications to MRI,poor image quality and incomplete image sequences,last menstrual period unknown.Imaging acquisition:The MRI examinations were performed on a 1.5-T MR system and the protocols included HASTE,TrueFISP,and SWI in the axial,coronal,and sagittal planes,respectively and T1WI in sagtial plane.Image interpretation:The following morphometric parameters of the C4、T6、L3、SI vertebrae COC were measured:transverse diameter,sagittal diameter,height,cross-sectional area and volume.To assess within-subject repeatability,the research performed the measurements three times under the same conditions but at different times,and the mean of the three measurements were used.Analyzed the measured values and established regression equations.Statistical analysis:The ICC was used to assess the intra-observer agreement for the measurements.Pearson correlations were used to correlate the C4,T6,L3,S1 COC measurements with GA.Linear and nonlinear regression analysis was used to derive the bestfit curve for each parameters versus gestational age.A P-value(two-tailed)of less than 0.05 was considered representative of a significant difference.ResultsParticipant characteristics:A total of 127 participants were recruited,mean age 28.7±5.8y,mean GA 29.4±3.9w.Of these,C4 COC was 30,mean GA 29.9 ± 3.8w,range 25-38w;T6 COC was 58,mean GA 29.0±3.5w,range 21-38w;L3 COC was 92,mean GA 29.3±3.9w,range 21-39w;S1 COC was 62,mean GA 29.7±3.8w,range 23-39w.Intra-observer reliability:The ICC tests showed excellent inter-observer agreement for all measurements(P<0.05).MRI Features of fetal vertebral centrum ossification center:Fetal spine in utero with global curvature was kyphosis,presenting two primary curves(thoracic and sacral kyphosis)and two secondary curves(cervical and lumbar lordosis);the vertebral body shape is regular in round,oval,or square.Morphometric parameters characteristics of fetal vertebral centrum ossification center:The morphological parameters of C4,T6,L3 and S1 COC increased with the GA(P<0.001);L3 had the largest absolute growth,while C4 had the smallest.The growth peak of the volume of C4,L3 and S1 COC was 33-36w,and T6 vertebral ossification center was 25-28w.Morphometric parameters growth curve of fetal vertebral centrum ossification center:The growth of C4 COC were according to the following equation with GA:the sagittal diameter(mm)=0.0161×GA2-0.72×GA+11.03(R2=0.9379,P<0.001);the transverse diameter(mm)=0.0185×GA2-0.824×GA+12.43(R2=0.9425,P<0.001);the height(mm)=0.0035×GA2-0.0657×GA+1.746,(R2=0.9522,P<0.001);the area(mm2)=0.1436×GA2-7.1754×GA+95.92(R2=0.9574,P<0.001);the volume(mm3)=1.4439×GA2-76.372×GA+1038.7(R2=0.9815,P<0.001);The growth of T6 COC were according to the following equation with GA:the sagittal diameter(mm)=0.0118×GA1.816(R2=0.9146,P<0.001);the transverse diameter(mm)=0.0195×GA1.7277(R2.0.9232,P<0.001);the height(mm)=0.0409×GA1.3793(R2=0.8494,P<0.001);the area(mm2)=0.0627×GA2-0.8339×GA-3.9837(R2=0.9433,P<0.001);the volume(mm3)=1.5769×GA2-64.45×GA+695.86(R2=0.9609,P<0.001):The growth of L3 COC were according to the following equation with GA:the sagittal diameter(mm)=0.0046×GA2+0.1275×GA-1.1467(R2=0.9097,P<0.001);the transverse diameter(mm)=0.0207×GA2-0.6825×GA+10.663(R2=0.9162,P<0.001);the height(mm)=0.0071×GA2-0.0915×GA+2.217(R2=0.914,P<0.001);the area(mm2)=0.2792×GA211.536×GA+138.56(R2=0.9415,P<0.001);the volune(mm3)=6.3819×GA2-309.31×GA+3885.5(R2=0.9483,P<0.001);The growth of S1 COC were according to the following equation with GA:the sagittal diameter(mm)=0.2557×GA-1.7959(R2=0.9047,P<0.001);the transverse diameter(mm)=0.5111×GA-7.5792(R2=0.911,P<0.001);the height(mm)=0.2756×GA-3.0909(R2=0.9222,P<0.001);the area(mm2)=0.128×GA2-3.7928×GA+31.429(R2=0.9304,P<0.001);the volume(mm3)=2.9197×GA2-135.61×GA+1666.4(R2=0.9643,P<0.001)ConclusionThis study showed that the growth and development of C4,T6,L3 and S1 COC in the middlelate pregnancy had a good correlation with gestational age,providing reference values of MRI and may be useful in the prenatal diagnosis of fetal vertebral anomalies.Part 2 Utility of magnetic resonance imaging for evaluation of fetal vertebral abnormalities and postnatal outcomePurposeThe purpose of this study was to determine whether the accuracy and confidence of diagnosing fetal vertebral anomalies are improved with MRI.We also assessed whether or not fetal MRI provided additional information in diagnosing fetal vertebral anomalies.MethodsParticipant characteristics:A total of 269 second or third trimester pregnant women carrying a fetus with suspected vertebral anomalies(screened by US)were recruited to the study between December 2015 and January 2021,mean age,27.2±4.2y,mean GA,28.0±3.3w.Imaging acquisition:The 3 planes of imaging commonly used to assess the fetal spine from the cervical region through the coccyx included the coronal,parasagittal,and transverse planes.Fetal MRI examinations were performed within 3 days of the anomalous US findings.The scanning sequences and planes were same as part Ⅰ.Image interpretation:In all cases,postnatal or postmortem imaging findings were used as reference standards.Comparisons of diagnostic accuracy and consistency were made between MRI and ultrasound for the identification of fetal vertebral anomalies.The score-based weighted average analysis was used to assess whether MRI had improved diagnosis confidence in fetal vertebral anomalies.Statistical analysis:McNemar’s paired binomial test,chi-square test,or Fisher’s exact test were used to compare the diagnostic ability between MRI and ultrasound.One sample t-tests were carried out to test the hypothesis that the expected calculated scores were zero.ResultsParticipant characteristics and follow-up results:A total of 127 participants were recruited between December 2015 and January 2021,mean age 29.8±4.3y,mean GA 28.2±3.8.Of the 127 pregnant women,116 cases carried pregnancies to term(mean GA,28±4w),and 11 cases resulted in a termination of pregnancy(mean GA,27±3w).Fetus were found with vertebral anomalies in 63.8%(81/127)cases and proved to be negative in 36.2%(46/127)after follow ups.The diagnostic comparison between ultrasound and MRI:The diagnostic accuracy of the vertebral anomalies between ultrasound and MRI were 46.9%(38/81)vs.84.0%(68/81)in deformity group;19.6%(9/46)vs.97.8%(45/46)in negative group and 37.0%(47/127)vs.89.0%in overall sample,for MRI(difference,37.1%;95%CI 27-48;P<.001),increased by 37.1%(95%CI,27-48;P<0.001),78.2%(95%CI,66-90;P<0.001),52.0%(95%CI,4361;P<0.001)respectively.The consistency comparison between ultrasound and MRI:MRI and ultrasound were concordant and correct in 36.2%(46/127)of the fetuses,provided additional information in 16.5%(21/127)of the fetuses,and corrected ultrasound diagnoses in 36.2%(46/127)of the fetuses;both MRI and ultrasound were not consistent with postnatal findings in 10.2%(13/127)and the remaining one fetus(0.8%,1/127)which was diagnosed correctly in ultrasound but failed in MRI.The diagnostic confidence assessment of MRI:Diagnoses were reported with high confidence by MRI in 95.3%(121/127)of the cases compared with 73.2%(93/127)using ultrasound.The incorrect rate of ultrasound and MRI in high diganositic confidence was 44.9%(57/127)and 9.4%(12/127),respectively.The score-based weighted average analysis results showed MRI increased diagnostic confidence(mean confidence difference+1.535,95%CI:1.20-1.87,P<0.001).Conclusions:Fetal vertebral MRI improved the accuracy and confidence of diagnosing fetal vertebral anomalies.This finding indicated that fetal MRI supplements the information provided by ultrasound and leads us to propose that MRI may be a good complement in selected fetus when ultrasound could not make a definite diagnosis or is in doubt to better inform prenatal counseling and management decisions. |
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