A. C. G. Breeze

Minimally‐invasive fetal autopsy using magnetic resonance imaging and percutaneous organ biopsies: clinical value and comparison to conventional autopsy

Autopsy is an important investigation following fetal death or termination for fetal abnormality. Postmortem magnetic resonance imaging (MRI) can provide macroscopic information of comparable quality to that of conventional autopsy in the event of perinatal death. It does not provide tissue for histological examination, which may limit the quality of counseling for recurrence risks and elucidation of the cause of death. We sought to examine the comparability and clinical value of a combination of postmortem MRI and percutaneous fetal organ biopsies (minimally invasive autopsy (MIA)) with conventional fetal autopsy.

Feasibility of percutaneous organ biopsy as part of a minimally invasive perinatal autopsy.

To determine the feasibility of percutaneous fetal organ biopsies in the context of a ‘minimally invasive’ perinatal autopsy after stillbirth and termination for abnormality is the aim of this study. We assessed successful biopsy rate and the proportion adequate for histological examination in 30 fetuses undergoing organ sampling before autopsy. The relationship between gestational age, body weight, death–biopsy interval, operator experience and successful biopsy rate was investigated. Significant findings from conventional block histology were compared with corresponding percutaneous biopsies. Of 210 organ biopsies attempted from seven target organs, 107 were obtained, of which 94 were adequate for pathological comment. The median delivery–autopsy interval was 4 (range 2–11) days. Adequate samples were obtained from the lung in 86% cases (95% CI 68, 96%), liver 76% (95% CI 56, 90%) and less frequently for the myocardium, kidney, adrenal, thymus and spleen. There was no relationship between biopsy success and time to biopsy, gestational age, body weight and user experience. No histological abnormalities found at autopsy were diagnosed from needle biopsies. Although targeted percutaneous biopsies appear feasible for some organs, fewer than 50% of all biopsies are adequate for histological examination. This technique cannot be considered to provide useful clinical information as part of a ‘minimally invasive’ perinatal autopsy.

Use of a confidence scale in reporting postmortem fetal magnetic resonance imaging

Postmortem magnetic resonance imaging (MRI) may be an alternative to conventional autopsy. However, it is unclear how confident radiologists are in reporting such studies. We sought to determine the confidence with which radiologists report on various fetal organs by developing a scale to express their confidence of normality and abnormality, and to place this in the context of a pathological diagnosis of whether the organ was in fact normal or abnormal.

Attitudes to perinatal postmortem: parental views about research participation

Objective To study parental attitudes to participating in questionnaire research about perinatal postmortem immediately after late miscarriage, stillbirth and termination for fetal abnormality. Design Prospective self-completion questionnaire. Setting UK fetal medicine and delivery unit. Patients 35 women and their partners after second or third trimester pregnancy loss, making decisions about having a postmortem. Methods Participants were asked to complete a questionnaire about postmortem decision-making which included questions about their attitudes to taking part in research. Prior to giving full approval for the study, the Research Ethics Committee (REC) requested feedback after 10 questionnaires had been returned. Results Responses from the first 10 participants were positive about the research and the REC allowed the study to continue. 31 questionnaires were received from parents of 17 babies (49% of those asked; 16 from mothers, 15 from fathers). Of the 22 participants who answered a question about the impact of participating in this research, 73% stated that completing the questionnaire had helped them feel better about the decision whether or not to consent to postmortem and none reported any adverse effect of completing the questionnaire. Additional comments made by 19 participants supported this finding. Conclusion Research into this sensitive area of perinatal medicine where there is a poor outcome is possible and is indeed well received by many parents. RECs should not automatically take a negative stance towards studies of this type.

OP06.04: Postmortem fetal lung volumetry using MRI and comparison to lung weights at autopsy

Introduction: Prediction of pulmonary hypoplasia remains difficult. At autopsy, pathologists use the lung weight/body weight ratio to diagnose pulmonary hypoplasia. Estimating lung volumes in utero could aid management when pulmonary hypoplasia is suspected. We measured fetal lung volumes on post mortem MRI. By comparing these volumes to organ weights at autopsy, we estimated fetal lung densities. This may allow prenatal calculation of lung weights in future. Methods: 21 fetuses underwent postmortem MRI at 1.5T prior to conventional autopsy with parental consent. Fetal weights ranged from 113–3270 g, with gestational ages of 17–40 weeks. T2-weighted sequences were used. Conventional autopsies were performed to RCPath guidelines. Lung volumes were independently estimated by two researchers using the ANALYZE (BIR, Mayo Foundation) software package’s stereology tool. Organ volumes for each observer were compared to autopsy organ weights, and the reciprocal of the gradients and R2 values were calculated. Inter-observer agreement was assessed using BlandAltman analysis. Results: There was high linear correlation between estimated lung volume and actual lung weights (R2 > 0.98 for both observers). The reciprocal of the gradient gave an average lung density of 1.15 g/cm3 which corresponds closely to the density of non-aerated adult lung (1.04–1.09). Bland-Altman analysis demonstrated good interobserver agreement, which appeared to improve with increasing organ size. Conclusions: Ex utero fetal lung volume measurements are highly correlated to lung weight at autopsy, with a calculated density that corresponds well to published figures. The technique has low interobserver variability and provides non-invasive information about fetal lung development when conventional autopsy is declined. It may also prove of value in the prenatal assessment of lung development.

OP03.03: Diagnostic sensitivity and clinical value of prenatal ultrasound, post-mortem magnetic resonance imaging and conventional autopsy for late miscarriage and stillbirth

Down syndrome risk. Of the 56 cases of trisomy 21 (1,2%), 25 were males and 31 females (P = 0,74). Detection rate for trisomy 21 was 84% in males and 87% in females (P=0,8). Free beta HCGMoM, NTMoM and PAPPAMoM were not significantly different between male and female trisomy 21 fetuses. Conclusions: There is a trend towards female fetuses having a higher chance of increased risk at the combined test. There are no gender differences in the detection rate of trisomy 21. Whether risk assessment protocols need to become gender specific needs further investigation.

OP03.02: Diagnostic sensitivity and clinical value of prenatal ultrasound, post‐mortem magnetic resonance imaging and conventional autopsy in structural fetal abnormality

Down syndrome risk. Of the 56 cases of trisomy 21 (1,2%), 25 were males and 31 females (P = 0,74). Detection rate for trisomy 21 was 84% in males and 87% in females (P=0,8). Free beta HCGMoM, NTMoM and PAPPAMoM were not significantly different between male and female trisomy 21 fetuses. Conclusions: There is a trend towards female fetuses having a higher chance of increased risk at the combined test. There are no gender differences in the detection rate of trisomy 21. Whether risk assessment protocols need to become gender specific needs further investigation.

OC50: Use of a confidence scale in reporting normal and abnormal fetal anatomy on postmortem MRI

Objective: To compare three dimensional ultrasound (3D-US) and magnetic resonance imaging (MRI) in the assessment of lung volumes in fetuses with congenital diaphragmatic hernia (CDH). Methods: Left and right lung volumes were measured using the 30◦ Virtual Organ Computer-aided AnaLysis 3D-US and the multiplan T2 WI MRI technique on a total of 78 fetuses with CDH at 18–38 (median 28) weeks of gestation. Measurements with both methods were done within 4 hours from each other. Regression analysis was used to determine the significance of association between the two methods. Results: There were 67 fetuses with left-sided and 11 with right-sided CDH. Intrathoracic herniation of the liver was observed in 66 of the examinations. In all 78 cases it was possible to visualize and measure both ipsiand contralateral lungs by MRI. In contrast, with 3D-US all contralateral lungs but 44% of ipsilateral lungs (n = 34) could not be adequately visualized. For contralateral lungs there was a significant association between 3D-US and MRI measurements (r = 0.86; p < 0.001). 3D-US volumes were on average 26% lower than those obtained by MRI, independent of lung size, site of CDH or the presence of intrathoracic herniation of the liver. The mean deficit in the measured volume in fetuses with CDH compared to the appropriate normal mean for gestation by the same method and established in previous studies, was not significantly different for 3D-US and MRI. For ipsilateral lungs where both methods yielded a result (56%) there was a much poorer association between 3D-US and MRI (r = 0.39; p < 0.05). Moreover, 3D-US volumes were on average 22% higher than those obtained by MRI. Conclusions: In the assumption that MRI provides an accurate measurement of fetal lungs, in CDH 3D-US provides a reliable measurement of the contralateral but not of the ipsilateral lung.

P09.03: What is the value of MRI post-mortem in pregnancy loss? Results from a pilot study

This study was to develop fetal growth curves and percentile growth charts for a Jamaican population. 499 jamaican women of African descent were enrolled in a prospective study from the maternity clinic of the University Hospital of the West Indies., Kingston, Jamaica. The women had serial scans between 14–37 weeks’ gestation to measure fetal growth. The measurements performed were BPD, HC, AC and FL. A total of 2574 scans were performed (mean 5.2 per woman). The data was used to plot centile growth charts for the Jamaican fetus. Birthweights vary between ethnic groups so must fetal growth. At present fetal growth in Jamaica is assessed using charts based on Caucasian populations. Fetal growth charts derived from this data would more accurately predict the at-risk fetus and hence improve obstetric care.

OC099: How well is normal fetal anatomy visualised at post‐mortem MRI?

Dynamic 3D ultrasound imaging of the fetal heart is difficult due to the absence of ECG signal for synchronization between loops. In this work we introduce tissue Doppler gating (TDOG), a technique in which tissue Doppler data dedicated to compute a gating signal are acquired. We have applied this cardiac gating method to dynamic 3D reconstructions of the heart of 8 fetuses aged 20 to 24 weeks. The gating signal was derived from the amplitude and frequency contents of the tissue Doppler signal. The reliability of the tissue Doppler gating signal for fetal cardiac cycle detection was experimentally investigated by continuous wave spectral Doppler of the umbilical artery. Each recording consisted of a 2D sector scan, trans-abdominally and slowly tilted by the operator, covering the fetal heart over 40 cardiac cycles. The total angle of the sweep was estimatedby recording a separate loop through the centre of the heart, in the elevation direction of the sweep. 3D reconstruction and visualization were performed with the EchoPAC-3D software from GE Medical Systems. Synchronization of B-mode cine-loops with the tissue Doppler gating signal proved to be sufficiently accurate for reconstruction of highquality dynamic 3D data. We show one example of a B-mode recording with 96 frames per second during 20 seconds. The reconstruction consists of 31 volumes, each with 49 tilted frames. The sampling distances were approximately 0.15 mm in the beam direction, 0.33–0.37 mm azimuth and 0.45–0.51 mm elevation. We generated a complete set of classical 2D views – such as fourchamber, three-vessel and short-axis views as well as views of the ascending aorta, aortic and ductal arches and IVC and SVC with high image quality adequate for clinical use. This study demonstrates the feasibility of tissue Doppler gated high frame 3D ultrasound imaging of the fetal heart with current ultrasound systems. The method is suitable for real time application in future ultrasound systems.