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UOG Journal Club: October 2012
  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)
Most                                                     High % can
 common                                                     be detected
abnormality                                                 by prenatal
  ≈ 0.8%                                                    ultrasound
                         Congenital
                            heart
                          disease
One of the                 (CHD)                              Improved
 leading                                                     ultrasound
causes of                                                        = 1st
  infant                                                      trimester
mortality                                                    diagnosis


 Hoffman and Kaplan S. J Am Coll Cardiol 2002; Lombardi et al. Ultrasound Obstet Gynecol 2007
Impact of early prenatal diagnosis of CHD

         Option of pregnancy
         termination

         Planned birth


         Improved neonatal outcome




                     Franklin et al. Heart 2002; Thayyil et al. Prenat Diagn 2010
Termination of pregnancy after early
    prenatal diagnosis of CHD



   Accurate               Proper
  postmortem            pregnancy
   diagnosis            counseling




                           Thayyil et al., Prenat Diagn 2010
Postmortem diagnosis
• 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

                    Cannie et al., Ultrasound Obstet Gynecol 2012; Brookes et al., Lancet 1996
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



                          Objective
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.




                                                Votino et al., Ultrasound Obstet Gynecol 2012
Subjects
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
Methods
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




                               Votino et al., Ultrasound Obstet Gynecol 2012
MRI postmortem evaluation
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



                                 Votino et al., Ultrasound Obstet Gynecol 2012
Invasive autopsy
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




                                   Votino et al., Ultrasound Obstet Gynecol 2012
Results: image quality




        1.5 T                    3.0 T                            9.4 T
   Ability to visualize different fetal heart structures (n=24)
        Situs    4 chamber Outflow tracts Aortic arch Systemic veins
1.5 T   62.5%      25.0%        0.0%           0.0%                   0.0%

3.0 T   70.8%      45.8%        4.2%           0.0%                   0.0%

9.4 T   100.0%    100.0%       100.0%         83.3%                  79.2%
                                          Votino et al., Ultrasound Obstet Gynecol 2012
Results: sensitivity in detecting CHD

                                      1.5 T 3.0 T       9.4 T  Autopsy
Retro-esophageal subclavian artery      0     0           0       1
Ventricular septal defect               0     0       1 (20%)     5
Atrioventricular septal defect          0     0       1 (50%)     2
Transposition of the great arteries     0     0       1 (100%)    1
Ventricular hypoplasia                  0     0       1 (50%)     2
Tetralogy of Fallot                     0     0       2 (100%)    2

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
Key findings

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




                                            Votino et al., Ultrasound Obstet Gynecol 2012
Limitations
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



                                           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?

                                             Votino et al., Ultrasound Obstet Gynecol 2012

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UOG Journal Club: Postmortem examination of human fetal hearts at or below 20 weeks’ gestation

  • 1. UOG Journal Club: October 2012 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)
  • 2. Most High % can common be detected abnormality by prenatal ≈ 0.8% ultrasound Congenital heart disease One of the (CHD) Improved leading ultrasound causes of = 1st infant trimester mortality diagnosis Hoffman and Kaplan S. J Am Coll Cardiol 2002; Lombardi et al. Ultrasound Obstet Gynecol 2007
  • 3. Impact of early prenatal diagnosis of CHD Option of pregnancy termination Planned birth Improved neonatal outcome Franklin et al. Heart 2002; Thayyil et al. Prenat Diagn 2010
  • 4. Termination of pregnancy after early prenatal diagnosis of CHD Accurate Proper postmortem pregnancy diagnosis counseling Thayyil et al., Prenat Diagn 2010
  • 5. Postmortem diagnosis • 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 Cannie et al., Ultrasound Obstet Gynecol 2012; Brookes et al., Lancet 1996
  • 6. 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 Objective 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. Votino et al., Ultrasound Obstet Gynecol 2012
  • 7. Subjects 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
  • 8. Methods 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 Votino et al., Ultrasound Obstet Gynecol 2012
  • 9. MRI postmortem evaluation 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 Votino et al., Ultrasound Obstet Gynecol 2012
  • 10. Invasive autopsy 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 Votino et al., Ultrasound Obstet Gynecol 2012
  • 11. Results: image quality 1.5 T 3.0 T 9.4 T Ability to visualize different fetal heart structures (n=24) Situs 4 chamber Outflow tracts Aortic arch Systemic veins 1.5 T 62.5% 25.0% 0.0% 0.0% 0.0% 3.0 T 70.8% 45.8% 4.2% 0.0% 0.0% 9.4 T 100.0% 100.0% 100.0% 83.3% 79.2% Votino et al., Ultrasound Obstet Gynecol 2012
  • 12. Results: sensitivity in detecting CHD 1.5 T 3.0 T 9.4 T Autopsy Retro-esophageal subclavian artery 0 0 0 1 Ventricular septal defect 0 0 1 (20%) 5 Atrioventricular septal defect 0 0 1 (50%) 2 Transposition of the great arteries 0 0 1 (100%) 1 Ventricular hypoplasia 0 0 1 (50%) 2 Tetralogy of Fallot 0 0 2 (100%) 2 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
  • 13. Key findings 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 Votino et al., Ultrasound Obstet Gynecol 2012
  • 14. Limitations 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 Votino et al., Ultrasound Obstet Gynecol 2012
  • 15. 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? Votino et al., Ultrasound Obstet Gynecol 2012