Postmortem examination of human fetal hearts at or below 20 weeks’ gestation: a comparison of high-field MRI at 9.4 T with lower-field MRI magnets and stereomicroscopic autopsy C. Votino, J. Jani, M. Verhoye, M. Verhoye, B. Bessieres, Y. Fierens, V. Segers, A. Vorsselmans, X. Kang, T. Cos, W. Foulon, J. de Mey and M. Cannie. Volume 40, Issue 4, Date: October 2012, pages 437–444 Journal Club slides prepared by Dr Wellington P Martins (UOG Editor for Trainees) UOG Journal Club: October 2012

Congenital heart disease (CHD) Most common abnormality ≈ 0.8% One of the leading causes of infant mortality Improved ultrasound = 1 st trimester diagnosis High % can be detected by prenatal ultrasound Hoffman and Kaplan S. J Am Coll Cardiol 2002; Lombardi et al. Ultrasound Obstet Gynecol 2007

Franklin et al. Heart 2002; Thayyil et al. Prenat Diagn 2010 Option of pregnancy termination Planned birthImproved neonatal outcome Impact of early prenatal diagnosis of CHD

Thayyil et al., Prenat Diagn 2010 Accurate postmortem diagnosis Proper pregnancy counseling Termination of pregnancy after early prenatal diagnosis of CHD

Cannie et al., Ultrasound Obstet Gynecol 2012; Brookes et al., Lancet 1996 Conventional/invasive autopsy –Gold standard for postmortem diagnosis –Parents acceptance is poor Whole body MRI as an alternative –1.5 T MRI introduced a decade ago Limited use for CHD in small fetuses Relatively low resolution –9.4 T MRI has improved resolution Diagnostic accuracy almost equivalent to invasive autopsy Postmortem diagnosis

Votino et al., Ultrasound Obstet Gynecol 2012 To compare the diagnostic usefulness of high-field (9.4 T) with lower-field (1.5 T and 3.0 T) MRI against the gold standard of stereomicroscopic autopsy for the postmortem examination of the fetal heart in fetuses ≤ 20 weeks’ gestation. Objective Postmortem examination of human fetal hearts at or below 20 weeks’ gestation: a comparison of high-field MRI at 9.4 T with lower-field MRI magnets and stereomicroscopic autopsy Votino et al., UOG 2012

Fetuses ≤ 20 weeks, with any abnormality on prenatal ultrasound; parents opted for termination of pregnancy (TOP) (n=22) Fetuses ≤ 20 weeks, spontaneous miscarriage, heart beat detected when admitted to hospital (n=2). Total = 24 fetuses (14 normal and 10 with CHD) abnormal four-chamber view (n=9) abnormal outflow tracts (n=4) abnormal aortic arch (n=3) abnormal systemic venous return (n=2) Votino et al., Ultrasound Obstet Gynecol 2012 Subjects

Votino et al., Ultrasound Obstet Gynecol 2012 Fetuses were cryopreserved at −20ºC until MRI and stereomicroscopic invasive autopsy. The MRI scans were performed with: 1.5T whole-body magnet: Siemens Avanto 3.0T whole-body magnet: Philips Achieva 9.4T horizontal bore: Biospec 94/20 USR Methods

Votino et al., Ultrasound Obstet Gynecol 2012 MRI performed by three different operators blinded to the prenatal scan findings Single radiologist evaluated the MRIs 10 years’ experience in fetal and postmortem MRI Offline analysis of acquired volumes Following order: 1.5 T, 3.0 T, and 9.4 T 1-month delay between readings MRI postmortem evaluation

Votino et al., Ultrasound Obstet Gynecol 2012 Invasive autopsies were conducted and/or supervised by a single pathologist with 20 years’ experience in fetal pathology and 12 years in cardiac fetal pathology Unaware of results of prenatal scan and MRI findings Invasive autopsy

Votino et al., Ultrasound Obstet Gynecol T3.0 T9.4 T Ability to visualize different fetal heart structures (n=24) Situs4 chamberOutflow tractsAortic archSystemic veins 1.5 T 62.5%25.0%0.0% 3.0 T 70.8%45.8%4.2%0.0% 9.4 T 100.0% 83.3%79.2% Results: image quality

Votino et al., Ultrasound Obstet Gynecol T3.0 T9.4 TAutopsy Retro-esophageal subclavian artery 0001 Ventricular septal defect 001 (20%)5 Atrioventricular septal defect 001 (50%)2 Transposition of the great arteries 001 (100%)1 Ventricular hypoplasia 001 (50%)2 Tetralogy of Fallot 002 (100%)2 Results: sensitivity in detecting CHD 9.4 T MRI examination also diagnosed two cases of ventricular septal defect (VSD) not confirmed by invasive autopsy

Votino et al., Ultrasound Obstet Gynecol 2012 For the postmortem examination of the fetal heart before 20 weeks’ gestation: 1.5 T or 3.0 T MRI seem to be limited 9.4 T MRI seems to be able to detect major CHD However, its limited availability makes it less attractive for widespread clinical use Key findings

Votino et al., Ultrasound Obstet Gynecol 2012 Small sample size Only a small variety of CHD was examined Some fetuses were frozen/thawed before MRI This can possibly interfere with image quality Could compromise integrity of tissue structure Improved image quality for the fetal heart Only non-macerated fetuses were examined Limited the generalizability of the findings Ideal conditions will not always be possible Limitations

Votino et al., Ultrasound Obstet Gynecol 2012 Discussion points Is first-trimester ultrasound diagnosis of fetal congenital heart disease accurate enough to help parents decide on termination of pregnancy? Is the postmortem diagnostic confirmation necessary for future pregnancy counselling and management? Are the current imaging methods accurate/reliable for postmortem investigation of fetal congenital heart diseases? Is the accuracy of congenital heart disease by postmortem imaging methods better than that obtained by prenatal ultrasound? Is the conventional postmortem examination currently a well accepted procedure by parents? Is postmortem examination limited to imaging methods only more or less likely to be accepted by parents?