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Fetal postmortem imaging: an overview of current


techniques and future perspectives
Xin Kang, MD, PhD; Andrew Carlin, MD; Mieke M. Cannie, MD, PhD; Teresa Cos Sanchez, MD; Jacques C. Jani, MD, PhD

F etal loss owing to miscarriage, still-


birth, or termination of pregnancy
is tragic for any family. Therefore,
Fetal death because of miscarriage, unexpected intrauterine fetal demise, or termination
of pregnancy is a traumatic event for any family. Despite advances in prenatal imaging
determining the cause of death or diag- and genetic diagnosis, conventional autopsy remains the gold standard because it can
nosis of fetal disease is essential to better provide additional information not available during fetal life in up to 40% of cases and this
understand and prevent such events, in by itself may change the recurrence risk and hence future counseling for parents.
addition to evaluating the risk of recur- However, conventional autopsy is negatively affected by procedures involving long
rence for future pregnancies.1,2 Routine reporting times because the fetal brain is prone to the effect of autolysis, which may
prenatal diagnosis has developed rapidly result in suboptimal examinations, particularly of the central nervous system. More
in the past 10 years because of im- importantly, fewer than 50%e60% of parents consent to invasive autopsy, mainly owing
provements in prenatal imaging3-12 and to the concerns about body disfigurement.
invasive and noninvasive prenatal ge- Consequently, this has led to the development of noninvasive perinatal virtual
netic testing,13-28 which has led to earlier autopsy using imaging techniques. Because a significant component of conven-
and more frequent diagnoses of fetal tional autopsy involves the anatomic examination of organs, imaging techniques
structural abnormalities and syndromic such as magnetic resonance imaging, ultrasound, and computed tomography are
diseases.4,29-33 Consequently, the current possible alternatives. With a parental acceptance rate of nearly 100%, imaging
usefulness of fetal postmortem exami- techniques as part of postmortem examination have become widely used in recent
nations could be questioned. However, years in some countries.
although the importance of the educa- Postmortem magnetic resonance imaging using 1.5-Tesla magnets is the most studied
tional role of autopsy is undervalued,34 technique and offers an overall diagnostic accuracy of 77%e94%. It is probably the best
recent series have shown that invasive choice as a virtual autopsy technique for fetuses >20 weeks’ gestation. However, for
autopsy provided additional findings in fetuses <20 weeks’ gestation, its performance is poor. The use of higher magnetic
16%e22% of cases in developed coun- resonance imaging magnetic fields such as 3-Tesla may slightly improve performance.
tries,29,30,35 including 1% of major Of note, in cases of fetal maceration, magnetic resonance imaging may offer diagnoses
findings, and revised the prenatal diag- in a proportion of brain lesions wherein conventional autopsy fails. Postmortem ultra-
nosis in 40% of cases in developing sound examination using a high-frequency probe offers overall sensitivity and specificity
countries,36 indicating that fetal post- of 67%e77% and 74%e90%, respectively, with the advantage of easy access and
affordability. The main difference between postmortem ultrasound and magnetic reso-
From the Departments of Obstetrics and nance imaging relates to their respective abilities to obtain images of sufficient quality for
Gynecology (Drs Kang, Carlin, Cos Sanchez, a confident diagnosis. The nondiagnostic rate using postmortem ultrasound ranges from
and Jani) and Radiology (Dr Cannie), University 17% to 30%, depending on the organ examined, whereas the nondiagnostic rate using
Hospital Brugmann, Université Libre de
Bruxelles, Brussels, Belgium; and the
postmortem magnetic resonance imaging in most situations is far less than 10%. For
Department of Radiology, UZ Brussel, Vrije fetuses 20 weeks’ gestation, microfocus computed tomography achieves close to
Universiteit Brussel, Brussels, Belgium (Dr 100% agreement with autopsy and is likely to be the technique of the future in this
Cannie). subgroup. The lack of histology has always been listed as 1 limitation of all postmortem
Received Feb. 18, 2020; revised April 19, 2020; imaging techniques. Image-guided needle tissue biopsy coupled with any postmortem
accepted April 28, 2020. imaging can overcome this limitation.
The Fetal Medicine Foundation Belgium partly In addition to describing the diagnostic accuracy and limitations of each imaging
funded the studies included in this review. The technology, we propose a novel, stepwise diagnostic approach and describe the possible
funding source had no involvement in the study
design, data gathering, data analysis, data
application of these techniques in clinical practice as an alternative or an adjunct or for
interpretation, or writing of the reports. triage to select cases that would specifically benefit from invasive examination, with the
The authors report no conflict of interest. aim of reducing parental distress and pathologist workload. The widespread use of
Corresponding author: Jacques Jani, MD, PhD.
postmortem fetal imaging is inevitable, meaning that hurdles such as specialized training
jackjani@hotmail.com and dedicated financing must be overcome to improve access to these newer, well-
0002-9378/$36.00 validated techniques.
ª 2020 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.ajog.2020.04.034 Key words: autopsy, congenital anomalies, diagnosis, management, micro-CT, mini-
mally invasive, MRI, postmortem, stillbirth, termination, ultrasound, virtual autopsy

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TABLE 1
Summary of published data concerning the diagnostic accuracy of postmortem magnetic resonance imaging
GA
(mean–SD or Analyzed ND MRI vs Accuracy Sensitivity Specificity
Author, y Study protocol n range) organs autopsy (%) (%) (%) (%) Conclusion
Brookes et al, 1.5-T vs autopsy, prospective, 20 15e39 Overall / 90 / / Total agreement was obtained in
199657 unselected fetuses, reporter not 8 of 20 cases. Autopsy provided
mentioned, design unclear more information in 8 of 20
cases. MRI provided more
information in 4 of 20 cases. In
90% of cases, the 2
examinations had similar clinical
significance.
Woodward et al, 1.5-T (3D) vs autopsy, prospective, 26 13e39 Overall / / 79b / MRI provided 79% detection of
199759 unselected fetuses, reported by 3 major malformations; 10 of 11
radiologists, blinded minor malformations were not
detected.
Huisman et al, 1.5-T vs autopsy, prospective, 10 14e32 / / / / / MRI confirmed every prenatal
200263 TOP, reported by 1 pediatric diagnosis for termination. All MRI
neuroradiologist and 1 general findings were confirmed by
radiologist, blinded autopsy. Autopsy provided
additional information relevant
for counseling in 2 cases.
Alderliesten et al, 1.0-T vs autopsy, prospective, 25 16e40 Overall / 68a 56a 93a MRI had higher acceptance, but
200364 unselected fetuses and neonates, the accuracy was insufficient to
reported by a single radiologist, recommend it as an alternative.
blinded
Griffiths et al, 1.5-T vs autopsy of the brain, 40 24 (14e42) Brain 0 vs 20 97 100 92 MRI would be useful for CNS
200365 prospective, unselected, reported postmortem examination.
by 1 pediatric neuroradiologist and
1 neonatal radiologist, unblinded
Breeze et al, 1.5-T vs autopsy, prospective, 30 16e39 Brain / / 88 96 MRI provided high confidence for
200668 unselected, reported by 1 pediatric CNS diagnoses but low
neuroradiologist and 2 pediatric confidence for the diagnoses of
radiologists, unblinded cardiac and abdominal
abnormalities.
Heart 25 100
Lungs 63 87
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020. (continued)

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TABLE 1
Summary of published data concerning the diagnostic accuracy of postmortem magnetic resonance imaging (continued)
GA
(mean–SD or Analyzed ND MRI vs Accuracy Sensitivity Specificity
Author, y Study protocol n range) organs autopsy (%) (%) (%) (%) Conclusion
Widjaja et al, 1.5-T vs autopsy for spine 41 14e42 Spine / / 100 97 MRI and autopsy were
200670 examination, prospective, 31 concordant in 10 of 11 abnormal
normal and 10 abnormal fetuses, cases. They were discordant for
reported by 2 neuroradiologists a case of diastematomyelia
and 1 fetal/neonatal radiologist, shown at MRI but not diagnosed
design unclear at autopsy.
Hagmann et al, 1.5-T vs autopsy for kidney 37 Unclear Kidney / / / / MRI identified 5 of 5 abnormal
200773 examinations, unclear design kidneys and 1 false positive.
Cohen et al, 1.5T vs autopsy for the 100 13e41 Brain / 60 / / MRI added valuable information
200876 examination of the brain, in 24 of 90 cases. Autopsy was
retrospective, unselected fetuses, superior to PMMRI in 12 of 90
reported by 1 neuroradiologist, cases,
design unclear
Thayyil et al, 9.4-T vs 1.5-T vs autopsy, 17 11e22 Brain 24 vs 76 100 1/1 3/3 9.4-T MRI was feasible for small
200978 prospective, unselected fetuses, fetuses <20 wk GA compared
reported by 4 specialist with 1.5-T PMMRI, which was
radiologists (CNS, cardiac, chest, not diagnostic in 78% of cases.
abdomen and musculoskeletal),
blinded
Body 35 vs 0 100 4/4 7/7
Votino et al, 1.5-T vs 3.T vs 9.4-T vs autopsy 24 11e22 Four / / 67 80 Seven of 8 major cardiac defects
MONTH 2020 American Journal of Obstetrics & Gynecology

201283 for fetal heart examination, chambers were identified using 9.4-T MRI
prospective, TOP and miscarriage in fetuses <20 wk GA.
<20 wk GA reported by 1 fetal MRI
specialist, blinded
Outflow tracts 75 100
b
Thayyil et al, 1.5-T plus MIA vs autopsy, 277 Unclear Overall 25 vs NA 49 / / MRI associated with ancillary
2013c,85 prospective, unselected, each examinations had high accuracy,
system reported by 4 specialists and could be an alternative to
radiologist, blinded conventional autopsy.

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185 24 35 vs NA 43b
92 >24 5 vs NA 63b
Sandaite et al, 3-T vs autopsy for fetal heart, 24 12e34 Heart / / 75 / 3-T MRI would be a valid
201489 prospective, fetuses with cardiac diagnostic tool for CHD in fetuses
defects, reported by a cardiac beyond 16 wk GA.
radiologist, blinded
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020. (continued)
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TABLE 1
Summary of published data concerning the diagnostic accuracy of postmortem magnetic resonance imaging (continued)
GA
(mean–SD or Analyzed ND MRI vs Accuracy Sensitivity Specificity
Author, y Study protocol n range) organs autopsy (%) (%) (%) (%) Conclusion
Arthurs et al, 1.5-T vs autopsy for MSK disease, 277 Unclear MSK 5 vs NA 94 59 99 MRI had good accuracy for
2014c,90 prospective, unselected, single exclusion of MSK abnormalities
reporter pediatric radiologist, but sensitivities are poor.
blinded
185 24 7 vs NA 94 69 100
92 >24 1 vs NA 92 17 98
Taylor et al, 1.5-T (3D T1 and T2) vs autopsy for 275 Unclear Heart 14 vs NA 94 83 95 Using 3D cardiac MRI as an
2014c,91 fetal heart, prospective, adjuvant might increase the yield
unselected, single reporter from invasive autopsy.
pediatric cardiovascular MR
radiologist, blinded
184 24 20 vs NA 95 82 96
91 >24 1 vs NA 93 83 94
Arthurs et al, 1.5-T vs autopsy, for fetal thorax 277 All Thorax 10 vs NA 81 33 93 MRI had poor detection rates for
2014c,94 prospective, unselected, reported intrathoracic pathologies
by several experienced perinatal/ (infections).
pediatric radiologists, blinded
185 24 15 vs NA 82 30 96
92 >24 0 vs NA 79 38 88
Arthurs et al, 1.5-T vs autopsy for fetal brain, 275 All Brain 12 vs 16 75 79 72 MRI had high accuracy for brain
2015c,95 prospective, unselected, reported abnormalities. MRI should be
by 1 of 3 pediatric performed routinely even when
neuroradiologists, blinded consent for classical autopsy has
been obtained.
183 24 19 vs 19 75 87 69
92 >24 9 vs 0 75 71 77
Arthurs et al 1.5-T vs autopsy for fetal 277 all Abdomen 10 vs 1 89 73 92 MRI had good overall accuracy,
2015c,96, abdomen, prospective, particularly for the detection of
unselected, reported by 1 of 2 renal abnormalities, but poor
pediatric/perinatal radiologists, diagnostic accuracy for intestinal
blinded abnormalities.
185 24 15 vs 3 91 77 95
>24

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92 0 vs 0 85 65 89
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020. (continued)
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TABLE 1
Summary of published data concerning the diagnostic accuracy of postmortem magnetic resonance imaging (continued)
GA
(mean–SD or Analyzed ND MRI vs Accuracy Sensitivity Specificity
Author, y Study protocol n range) organs autopsy (%) (%) (%) (%) Conclusion
Vullo et al, 1.5-T vs autopsy, prospective, 15 21e38 / / / / / Concordant findings were
2016102 stillbirth, reported by 2 obtained in all 8 normal cases
radiologists, blinded and all 7 abnormal cases with
MRI.
Arthurs et al, 1.5-T vs CT, prospective, 53 All Overall 5 vs 2 59 43 100 CT had limited value in
201698 unselected, reported by 3 postmortem imaging. MRI
neuroradiologists, 1 cardiac should be the modality of choice
radiologist, 3 body radiologists, 1 for fetal postmortem imaging.
MSK radiologist, blinded
Brain 15 vs NA 64 79 58
Heart 8 vs NA 92 100 90
Thorax 15 vs NA 82 38 92
Abdomen 11 vs NA 92 67 97
MSK 4 vs NA 94 50 100
35 24 Overall 11 vs NA 52 40 100
(19.352.55)
Brain 23 vs NA 59 83 52
Heart 11 vs NA 87 100 86
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Thorax 23 vs NA 82 20 96
Abdomen 17 vs NA 90 40 100
MSK 6 vs NA 94 60 100
18 >24 Overall 0 vs NA 72 50 100
(33.145.24)
Brain 0 vs NA 72 75 70
Heart 0 vs NA 100 100 100
Thorax 0 vs NA 83 67 87

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Abdomen 0 vs NA 94 100 93
MSK 0 vs NA 94 0 100
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020. (continued)
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TABLE 1
Summary of published data concerning the diagnostic accuracy of postmortem magnetic resonance imaging (continued)
GA
(mean–SD or Analyzed ND MRI vs Accuracy Sensitivity Specificity
Author, y Study protocol n range) organs autopsy (%) (%) (%) (%) Conclusion
b b b
Kang et al, 1.5-T vs 3-T vs autopsy, 92 12e41 Overall 10 vs 11 77 52 87 3-T MRI had better confidence
2017104 prospective, unselected score and overall diagnostic
population, reported by 1 perinatal accuracy than 1.5-T MRI,
and 1 pediatric radiologist with particularly for the thorax, heart,
consensus, blinded and abdomen of fetuses < 20
wk.
Brain 6 vs 42 81b 83b 90b
Heart 12 vs 7 81b 48b 95b
Thorax 10 vs 4 81b 44b 90b
Abdomen 18 vs 1 67b 56b 73b
MSK 7 vs 4 81b 58b 89b
32 20 Overall 30 vs NA 55b
35b
65b
Brain 19 vs NA 56b 100b 50b
Heart 37 vs NA 52b 23b 79b
Thorax 32 vs NA 54b 13b 50b
Abdomen 48 vs NA 39b 50b 32b
b b
MSK 21 vs NA 68 50 75b
60 >20 Overall 0 vs NA 87b 62b 97b
Brain 0 vs NA 92b 81b 100b
Heart 0 vs NA 94b 75b 100b
Thorax 0 vs 0 93b 70b 98b
b b
Abdomen 2 vs 0 82 60 93b
MSK 0 vs 0 87b 63b 96b
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020. (continued)

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TABLE 1
Summary of published data concerning the diagnostic accuracy of postmortem magnetic resonance imaging (continued)
GA
(mean–SD or Analyzed ND MRI vs Accuracy Sensitivity Specificity
Author, y Study protocol n range) organs autopsy (%) (%) (%) (%) Conclusion
Ashwin et al, 1.5-T vs autopsy, prospective, 201 25.17.7 Overall 7 vs 3 90 92 83 MRI could be reported by a single
2017103 unselected, single reporter after radiologist after a learning
training period, blinded period.
Brain 17 vs NA 92 94 90
Heart 10 vs NA 93 60 97
Thorax 5 vs NA 94 82 95
Abdomen 7 vs NA 89 90 89
MSK 1 vs NA 91 67 99
Shruthi et al, 3D 1.5-T vs autopsy, prospective, 43 20 Whole body / / 78 100 MRI could be an acceptable
201836 fetuses 20 wk GA, exclusion of alternative to conventional
ND autopsies, reported by 3 fetal autopsy. Postmortem MRI was
radiologists with <1-y experience more acceptable to parents and
in postmortem MRI, blinded can provide additional diagnostic
information on brain and spinal
cord malformations.
Brain 93 99
Heart 61 100
Lungs 91 100
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Abdomen 81 100
Kidney 96 100
MSK 67 100
Kang et al, 3-T MRI vs postmortem ultrasound 160 13e41 Brain 4 vs 64 82 79 84 MRI provided more diagnostic
2019110 vs autopsy, prospective, examination. When MRI and
unselected population, reported by postmortem ultrasound were
1 pediatric and 1 fetal radiologist, both diagnostic, they offered
blinded similar diagnostic accuracy.
Heart 4 vs 0 90 65 100

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Thorax 5 vs 0 85 41 99
Abdomen 3 vs 0 82 58 92
Spine 0 vs 0 99 83 100
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020. (continued)
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TABLE 1
Summary of published data concerning the diagnostic accuracy of postmortem magnetic resonance imaging (continued)
GA
(mean–SD or Analyzed ND MRI vs Accuracy Sensitivity Specificity
Author, y Study protocol n range) organs autopsy (%) (%) (%) (%) Conclusion
Staicu et al, 7-T MRI vs stereomicroscopic 9 9e13 Overall / / 95 98 7-T MRI could be considered a
2019111 autopsy, prospective, unselected safe alternative to autopsy.
populations, reported by 1
pediatric/fetal radiologist and 2
embryologists, blinded.
Brain 100 100
Face 100 100
Thorax plus 100 94
heart
Digestive 77 100
Urogenital 100 100
Skeleton 100 95
Shelmerdine et al, 1.5 eT postmortem MRI vs 81 14e41 Overall 16 94 79 98 Where postmortem MRI and
2019113 prenatal ultrasound vs autopsy, prenatal ultrasound were
retrospective review, unselected concordant, there was little
population, reported by 1 of 2 additional yield from autopsy
pediatric radiologists
Brain 2 85 80 89
Heart 9 92 43 97
Thorax 1 97 80 100
Abdomen 1 96 80 100
MSK 2 97 90 100
3D, three-dimensional; CHD, coronary heart disease; CNS, central nervous system; CT, computed tomography; GA, gestational age; MIA, minimally invasive autopsy; MRI, magnetic resonance imaging; MSK, musculoskeletal; n, number of cases; NA, not applicable;
ND, nondiagnostic; PM, postmortem; SD, standard deviation; TOP, termination of pregnancy.
a
Only major malformations were included for analysis; b Inclusion of ND MRI; c Different study but same patient cohort.
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020.

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TABLE 2
Current 3-T postmortem MRI Magnetom Avanto (Siemens, Erlangen, Germany) parameters used in our center
Parameter 2D T2 spin echo 3D T2 spin echo
Voxel dimension (mm) 0.470.581.2 0.450.450.45
TE (ms) 80 210
TR (ms) 1000e17,000 1500
Averages 5 1e5
Intersection gap (mm) 0 0
A knee-coil (16 channels) or a body coil (32 channels) is selected depending on the size of the body part studied.
2D, two-dimensional; 3D, dimensional; TE, echo time; TR, repetition time.
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020.

mortem examinations still have an help guide clinicians through this lower quality autopsy and increased
important role to play.37 complex process. waiting times for the full autopsy
However, because of the worldwide report.38 The fetal condition may also
declining consent rate for invasive au- Challenges of Conventional Autopsy challenge the pathologist’s skills
topsy, different noninvasive postmor- The current gold standard for fetal particularly in cases of maceration39 or
tem imaging techniques have emerged. postmortem examination is invasive when the fetus is small.30 However,
The selection of procedures to propose autopsy, which comprises an external the main challenge of conventional
in cases of fetal loss may become un- examination, systematic dissections of autopsy is the low and declining con-
clear. Therefore, in this study, we pro- internal organs including the brain, sent rate, which is approximately 5%
vide an overview of all possible and histopathologic analysis. Unfor- e60% worldwide.40-46 Cultural and
postmortem imaging techniques and tunately, experienced qualified fetal religious beliefs and the invasiveness
suggest a clinical decision pathway to pathologists are scarce, which leads to of the technique have been proffered

FIGURE 1
Severe cystic encephalopathy at 34 weeks

Coronal view of the brain in a fetus of 34-week gestational age with severe cystic encephalopathy (arrow) using 3-T postmortem magnetic resonance
imaging T2 spin-echo sequences (A) compared with postmortem ultrasound (B).
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020.

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listed the published diagnostic accuracy


FIGURE 2
of postmortem MRI using autopsy as
Undifferentiated kidneys and volvulus at 30 weeks gold standard in Table 1, excluding case
reports, anatomic and developmental
studies, and studies describing technical
applications.
1.5-Tesla (T) and 3-T magnets are
commonly used in clinical practice,
whereas high-field magnets at 7-Tor 9.4-
T are mainly reserved for research,
particularly for studies on normal hu-
man fetal development,114-123 and T2
sequences are generally preferred
because of their excellent tissue
contrast.81 The selected coils should be
as small as possible, usually determined
by the size of the fetus. The image signal
can be enhanced by placing the fetuses in
saline bags, and very small fetuses can be
examined inside a 60-cc syringe filled
with saline or isotonic solution.87,89,104
Usually, an acquisition time of less than
60 minutes is adequate enough to obtain
images of sufficient quality for whole-
body examinations. Typical 3-T post-
mortem MRI parameters used at our
center are described in Table 2.
The main advantage of postmortem
MRI lies in the detection of brain lesions,
where sensitivity and specificity range
79%e94% and 90%e99%, respectively,
in recent series and negative predictive
3-T postmortem magnetic resonance imaging and ultrasound of a fetus of 30-week gestational age values of more than 90% have been
after intrauterine fetal demise with undifferentiated large kidney (A, magnetic resonance imaging achieved (Figure 1).36,95,103,104,110,113
[MRI]; B, ultrasound) and dilated bowels presenting a “whirlpool sign” suggesting the diagnosis of Even where there is maceration, which
volvulus (C, MRI; D, ultrasound). is frequently associated with non-
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020. diagnostic neuropathology, MRI is still
capable of providing crucial clinical in-
as explanations for this low take-up 99%.44,51,52 Furthermore, compared with formation.85,95,104 Furthermore, it may
rate. classical autopsy, where the body can only be that apparently false-positive results
be examined once, imaging data can produced by MRI can sometimes relate
Fetal Postmortem Imaging easily be stored, transmitted to experts, or to true malformations that were unde-
Procedures reconstructed in any plane and even used tected by neuropathology. Therefore,
Recent advances in clinical imaging to create a three-dimensional (3D) pro- fetal brain postmortem MRI is already
accompanied by improved accessibility totype for education and further part of routine postmortem examination
and the development of minimally analysis.53,54 in some centers.88,93,95
invasive surgical procedures, such as For abdominal malformations, post-
needle biopsy and laparoscopy, have Postmortem Magnetic Resonance mortem MRI offers an acceptable sensi-
created a new range of possibilities for Imaging tivity of 56%e90% with a specificity of
postmortem examinations.47-50 Postmortem magnetic resonance imag- 73%e100% and a reported negative
Healthcare professionals and grieving ing (MRI) is the most studied fetal predictive value of 90%.36,96,103,104,110,113
parents find the less and, in some cases, postmortem imaging technique.36,53-113 3-T MRI frequently produces more
the noninvasive nature of these tech- It provides accurate fetal organ weight diagnostic examinations than 1.5-T MRI
niques easier to propose and accept, estimation75,77,82 and an overall diag- and has a higher concordance rate with
which has led to an improvement in nostic accuracy of 77%e94% in recent autopsy, particularly for fetuses <20
consent rates between 80% and published series.36,103,104,110,113 We have weeks gestational age (GA). Intestinal

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particularly for small fetuses <20 weeks


FIGURE 3
GA.104 However, its overall sensitivity is
Massive hydrops at 28 weeks not significantly improved because in-
fections, abnormal lung lobulations, and
tracheal-esophageal fistula are more
difficult to diagnose using both 1.5-T
and 3-T MRIs.57,85,94,104
Cardiac lesions are also challenging
with postmortem MRI. Radiologists are
less confident in cardiac diagnosis using
this method,51,68 which has an overall
48%e65% sensitivity, 95%e100% spec-
ificity, and 5%e13% rate of non-
diagnostic examinations (Figures 5 and
6).36,103,104,110,113 3-T MRI is preferred
over 1.5-T MRI because it provides more
diagnostic results with increased accu-
racy, reaching a sensitivity and specificity
of 75% and 100%, respectively, for fetuses
Coronal (A) and axial (B) postmortem magnetic resonance imaging of a fetus of 28-week gestational >20 weeks GA.87,89,104 3D T2 sequences
age after intrauterine fetal demise with a prenatal history of nonimmune hydrops showing massive enable the visualization of cardiac struc-
ascites and pericardial effusion, cardiomegaly, and lung hypoplasia (*) tures in any plane and facilitate the
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020. identification of complex malforma-
tions.91,97 The radiologist’s expertise also
malformations such as Meckel’s divertic- For noncardiac thoracic abnormal- plays an important role: sensitivity was
ulum and malrotation and pancreatic ities, postmortem MRI has a lower improved to more than 90% when the
abnormality are typically missed on sensitivity of 41%e82% with a speci- images were reported by a pediatric car-
postmortem MRI, in contrast with an ficity of 95%e100% and a reported diac MRI specialist or following a dedi-
excellent detection of renal lesions negative predictive value of 80% cated learning period.91,97,103
(Figures 2e4).96,104 However, these (Figures 3 and 5).94,103,104,110,113 The use The main challenge for postmortem
missed diagnoses correspond to minor of a 3-T magnet MRI produces more MRI using the currently available mag-
findings and may not influence the final diagnostic examinations and has a better nets is the adequate visualization of fe-
diagnosis. concordance rate with autopsy, tuses <20 weeks GA. The 3-T MRI

FIGURE 4
Bicornuate uterus at 23 weeks

Coronal view of the pelvis of a fetus of 23-week gestational age fetus showing a bicornuate uterus (arrows showing each uterine horn) using 3-T
postmortem magnetic resonance imaging (A) and ultrasound (B).
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020.

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Furness et al124 first described almost


FIGURE 5
30 years ago a technique for performing
Pulmonary hypoplasia at 31 weeks postmortem ultrasound on fetal viscera
in a water bath or after gelatin prepara-
tion. Only recently has a feasibility study
been conducted on fetuses. This single-
reporter unblinded study showed a
sensitivity of 86%e91% and a specificity
of 87%e95% for postmortem ultra-
sound using transducers at a maximum
of between 9 and 18 MHz.125 However,
when postmortem ultrasound was per-
formed blindly and by multiple opera-
tors, it demonstrated lower accuracy
with overall sensitivities and specificities
of 67%e77% and 74%e90%, respec-
tively (Table 3).110,126,127
Abdominal organs, in particular the
kidneys, are the easiest to assess with
postmortem ultrasound, which en-
courages its use for future ultrasound-
guided postmortem biopsy studies
(Figures 2e4). Conversely, cardiac
anatomy is more difficult to assess
because postmortem intracardiac blood
clots have echogenicities very similar to
Axial views of 3-T postmortem magnetic resonance imaging of the thorax of a fetus of 31-week those of the myometrium, and artifacts
gestational age terminated for pulmonary hypoplasia showing normal right lung (*) with right arising from the presence of air in the
main bronchus (arrow) and agenesis of the left lung and left main bronchus. cardiac chambers are frequently
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020. encountered after feticide by intracar-
diac injections (Figure 6).128,129 An
additional limitation of postmortem
demonstrates higher quality imaging Solution Inc) for examination of the ultrasound is its higher nondiagnostic
with better tissue contrast than 1.5-T head and extremities. We anticipate that examinations rate of 17%e30% than
MRI. This enabled 3-T MRI to provide access to these newer 7-T MRI machines the 3%e5% nondiagnostic rate of
a higher success rate of about 60% than will progressively improve, making their postmortem MRI for fetuses >20 weeks
success rate of less than 10% for 1.5-T.104 use in routine clinical practice a realistic GA.110 Finally, discrepancies between
However, the overall accuracy obtained possibility in the future. However, single-operator and multiple-operator
is only 55%, and the diagnostic rate for further studies with large sample sizes studies may indicate that postmortem
fetuses 16 weeks GA is even worse. are needed to explore the use of these ultrasound performance is operator
Furthermore, our experience of staining powerful machines for fetal postmortem dependent and that the learning effect
fetuses with gadolinium-based 3-T MRI examination, as all previously published should be investigated in further
was also unsuccessful.112 These results data on fetal high-field MRI used studies.
suggest that spatial resolution is subop- experimental machines with small-bore
timal when using 1.5-Tand 3-T MRIs for diameters of 20e30 cm.78,83,111 Postmortem Computed Tomography
the examination of small fetuses. High- Scan and X-Ray Examination
field MRI at 9.4-T or 7-T has shown Postmortem Ultrasound Routine fetal postmortem x-ray exami-
higher sensitivity and specificity in small Ultrasound is less expensive and more nations or babygrams are routinely per-
sample studies.78,83,111 However, access widely available even in developing formed as an adjunct to invasive autopsy
to these machines is currently restricted countries compared with MRI. High- in many centers. However, this practice
because they are only available in rela- frequency transducers provide high- has been proven to be neither diagnos-
tively few centers for research purposes resolution images particularly when the tically useful nor cost-effective in a
only. The US Food and Drug Adminis- targeted organ is near, as is the case in the retrospective study.130 It should only be
tration and the European Union have postmortem setting, wherein the fetus is used in selected cases of prenatally sus-
recently approved a 7-T MRI device examined by direct contact with the pected skeletal abnormalities or when a
(Magnetom Terra, Siemens Medical transducer (Figure 1). pathologist needs to include or exclude

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FIGURE 6
Tetralogy of Fallot at 32 weeks

Axial and coronal view of the heart of a fetus of 32-week gestational age terminated for Tetralogy of Fallot and microdeletion 22q11 using 3-T
postmortem magnetic resonance imaging (A, C) and ultrasound (B, D) showing thymus agenesis in which a blood clot related to termination (open
arrow), pulmonary artery atresia (arrow), and right-sided aorta crossing ventricular septal defect are seen (*).
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020.

specific features after external in- and may have value in the diagnosis of because it offers high-resolution images
spections.130-132 complex cardiac malformations after without disruption and handling.136,137
Fetal postmortem computed tomog- intracardiac injection of contrast, but the Recently, new applications of micro-
raphy (CT) scan has excellent diagnostic diagnostic accuracy of this method is yet CT in medicine have been investigated,
value for musculoskeletal abnormal- to be confirmed.134,135 including human fetal postmortem ex-
ities,98,133 with only a 0.3% reduction in amination following preparation with
detection rate compared with an x-ray Postmortem Microfocus Computed formalin and potassium triiodide stain-
examination.130 However, without Tomography ing.138-145 The first studies evaluated the
contrast, it yields a low success rate for Microfocus computed tomography (mi- feasibility of micro-CT for the exami-
the examination of the brain and thor- cro-CT) is a newly described technology nation of isolated organs, such as the
acoabdominal organs compared with offering submicron voxel-level resolu- heart and kidneys, and demonstrated
postmortem MRI.98 Whole-body fetal tion. It has been used for small animal very good agreement with invasive au-
postmortem CT angiography is feasible studies, in archeology, and in industry topsy results.138-140 Whole-body fetal

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14 American Journal of Obstetrics & Gynecology MONTH 2020

TABLE 3
Summary of published data concerning the diagnostic accuracy of postmortem ultrasound
Accuracy Sensitivity Specificity
Author, year Study protocol n GA Analyzed organs ND (%) (%) (%) (%) Conclusion
Votino et al, Ultrasound vs autopsy, prospective, 88 11e40 Brain 5 / 91 87 Ultrasound was feasible from 11 wk
2018125 unselected population, single reporter, of GA with high sensitivity and
unblinded specificity
Thoraxa 2 89 93
Abdomen 2 86 95
Tuchtan et al, Ultrasound vs autopsy, prospective, 75 15e38 Brain / / 82 98 Ultrasound showed high sensitivity
2018127 unselective population, single reporter, and specificity for fetal structural
blinded abnormalities with exception of
congenital cardiac structures.
Heart 18 100
Thorax 75 100
Abdomen 68 100
Kang et al, Ultrasound vs autopsy, prospective, 123 13e42 Overall 16 78 75 83 Ultrasound provided diagnostically
2019126 unselected population, 5 reporters, acceptable accuracy for fetal brain
blinded and abdominal organs.
Brain 19 73 62 78
Heart 20 75 50 81
Thorax 17 72 26 81
Abdomen 15 72 61 76
86 20 Overall 12 81 77 90
Brain 19 69 62 74
Heart 17 79 65 83
Thorax 11 76 29 87
Abdomen 14 72 57 77
37 <20 Overall 24 70 67 74
Brain 17 83 NA 83
Heart 27 65 0 77
Thorax 32 65 0 69
Abdomen 19 73 71 73

ajog.org
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020. (continued)
ajog.org Expert Review

scanning is also feasible after iodine


staining.138 A recent study comparing

Ultrasound was more frequently ND

techniques have similar accuracy.


fetal whole-body micro-CTwith invasive
compared with MRI. But when a
autopsy in 20 fetuses of 11e21 weeks’
diagnosis is achievable, both
GA found an overall sensitivity of 93.8%
and specificity of 100% with an agree-
ment of 97% (Figure 7).142 The perfor-
mance of micro-CT was not limited by
Conclusion

early GA, and accurate imaging can even


be obtained for human embryos.142,145
Furthermore, the iodine staining can
easily be removed with a solution of so-
Specificity

dium thiosulfate pentahydrate, and no


adverse effects have been found on either
100

93
99
86
97

subsequent invasive autopsy or histo-


(%)

logic examinations.139,142
Sensitivity

Micro-CT may also have some advan-


tages compared with invasive autopsy: it
(%)

seems to yield fewer nondiagnostic results


71

70
32
62
83
Summary of published data concerning the diagnostic accuracy of postmortem ultrasound (continued)

and offers a permanent 3D record of the


anatomy of the studied organ with reso-
Accuracy

lution comparable with that of low-power


(%)

histologic examinations.142,145,146 The


86

86
83
80
97

dataset obtained offers the potential for


unlimited review and slicing at different
Analyzed organs ND (%)

angles compared with a standard invasive


2
27

31
17
24

autopsy, wherein careless dissection may


harm the specimen and lead to an incor-
rect diagnosis.139 Micro-CT therefore
represents a promising alternative to
b
Abdomen

invasive autopsy for small fetuses <20


b
Thorax

Spineb
Heartb
b
Brain

weeks’ GA, at a developmental stage when


postmortem MRI and ultrasound are less
satisfactory.85,104,126
13e41

However, larger fetuses beyond 21


GA

GA, gestational age; MRI, magnetic resonance imaging; n, number of cases; ND, nondiagnostic.

weeks’ GA are more challenging for


autopsy, 92

micro-CT for a variety of reasons. First,


118 body

autopsy

homogeneous and sufficient penetration


brain

of iodine is more difficult to obtain with


n

larger fetuses. Second, micro-CT scanners


have fixed radiation sources with the
prospective, unselected population, 4
Ultrasound vs 3-T MRI vs autopsy,

specimen mounted vertically on an


Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020.

adjustable rotating platform that modifies


the “radiation source-to-object” and “ob-
Thorax including heart; b Exclusion of ND ultrasound.

ject-to-detector” distance to yield a higher


image resolution (less than 1-micron
voxels) (Figures 7e9).146 Although the
Author, year Study protocol

reporters, blind

fetal tissue is fixed with formalin, the


vertical fetal body can collapse slightly
during the 20- to 30-minute scanning
period, which may cause imaging artifacts.
Consequently, the fetal body must be
Kang et al,

completely immobilized during the scan,


TABLE 3

2019110

which is more difficult to achieve with


larger fetuses. Further studies are therefore
a

required to validate the role of micro-CT

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preferences. Concerns about the inva-


FIGURE 7
siveness of the procedures, funeral de-
Microfocus computed tomography images of a fetus of 13-week lays, and religious considerations have
gestational age terminated for trisomy 18 been considered as possible explanations
for the low consent rate of traditional
autopsy.44,51 However, when the poten-
tial benefits of autopsy are correctly
explained by fetal medicine specialists or
fetal pathologists, bereaved parents can
overcome most of their concerns and
fears, leading to an increase in the con-
sent rate.51,147,148 Furthermore, the
emotional distress in these situations
also affects healthcare professionals.
Therefore, education of midwives and
obstetricians regarding the value of au-
topsy and the possibility for, and the
limitations of, less invasive alternatives is
recommended to further increase the
number of fetal postmortem
examinations.52,148
When invasive autopsy is declined,
health professionals should counsel
parents on the benefit of less invasive
autopsy, including ancillary in-
vestigations such as fetal body external
examination, placental pathology, ge-
netic tests, and imaging techniques. In
A, Sagittal view of the whole fetus showing detail anatomy including diaphragm (open arrow) and fact, such minimally invasive procedures
esophagus (arrow). B, Axial view of the thorax at the level of cardiac 4-chambers showing hypoplasia increased the concordance rate of 1.5-T
of the right ventricle (*). C, Illustration of the fetus inside the microfocus computed tomography postmortem MRI from 40%e60% to
machine, mounted vertically on a rotating platform (a) with a fixed radiation source (b). 95%,85 suggesting that these procedures
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020. may improve the reported results of
other imaging techniques. In principle,
the choice of imaging technology should
in fetal postmortem examination, experience in postmortem imaging. A initially be based on local availability,
improve the staining protocol, and learning curve is expected for teams who because performing any examination
develop novel techniques to immobilize start to implement these techniques. will always be preferable to nothing and,
fetuses during scanning. Second, despite the relatively high where different imaging technologies are
number of fetal malformations included available, fetal GA and the targeted organ
Limitation of Postmortem Imaging in the studies, it is impossible to cover all should guide the selection of imaging
and Postmortem Imaging Studies fetal pathologies because some of them techniques based on image resolution
The absence of histology data has always are extremely rare. Finally, the imple- and diagnostic accuracy. Hence in prac-
been listed as a limitation of all postmor- mentation of postmortem imaging tice, for fetuses beyond 20 weeks, MRI is
tem imaging procedures. However, less before autopsy may have increased the preferred because of its higher success
invasive systematic biopsy methods have delay between delivery and autopsy in rate compared with CT and ultra-
been described such as transcutaneous some cases, exacerbating the effect of sound.98,110 3-T magnets are favored
needle and laparoscopy-assisted biopsy,47- maceration. However, this effect is ex- because of better image quality and
50
with a likely higher parental acceptance pected to be small if the fetuses are stored diagnostic accuracy for cardiac malfor-
than invasive autopsy.44 in cold chambers at 4 C while waiting mations.104 For fetuses <20 weeks, high-
Caution is also needed when general- for postmortem examinations. field MRI and micro-CT are the best
izing the previously described diagnostic options.78,111,142 However, these scan-
accuracy for all imaging methods. First, Clinical Implications: The Choice of ners are not currently widely available in
the reported data came, in most cases, Postmortem Procedures clinical practice. Consequently, high-
from the postmortem imaging expert The most important factor in the choice frequency ultrasound and MRI are
center, with more than 10 years’ of postmortem procedures is parental possible alternatives, with a preference

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FIGURE 8
Sequential slice in a volume obtained using microfocus computed tomography in a fetus of 13-week gestational
age terminated for trisomy 18

Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020.

toward MRI in cases of suspected brain imaging as a first-line examination could postmortem imaging as first-line exami-
malformations.110 also change the a priori risk in the case of nation. Furthermore, as postmortem
Postmortem imaging can also be an discovery of fetal abnormalities, which imaging is more easily accepted, more
adjunct to full or partial autopsy in might encourage parents to be more fetuses would have postmortem exami-
certain cases. Babygrams are recom- accepting of an invasive autopsy. nations, maybe conducted for additional
mended in cases of suspected skeletal We therefore propose a stepwise diag- findings and modifications of recurrence
abnormalities on prenatal ultrasound or nostic approach to fetal postmortem ex- risk, which would lead to better man-
external examinations.130,132 MRI can aminations (Figure 10). This decision tree agement of subsequent pregnancies and
improve the detection of central nervous takes into account parents’ desire, pre- probably a reduction of parental stress.
system abnormalities, particularly when natal history, fetal GA, and locally avail- Furthermore, the cost related to the pre-
maceration is present, and should be able resources. The objective was to vention of future pregnancy loss and the
proposed routinely before autopsy in produce an algorithm based on the best improvement of parental psychological
future guidelines.85,93,95,104,149,150 For currently available evidence, which may status must be considered. Therefore, the
small fetuses <20 weeks and when reduce parental distress by restricting in- efficacy of our proposition and the cost-
complex cardiac malformations are sus- dications for invasive autopsy, thereby effectiveness of postmortem imaging
pected, micro-CT may provide addi- reserving precious resources for cases need to be validated in future prospective
tional findings by scanning the whole where invasive autopsy is strongly indi- studies.
fetus or only the heart in isolation.139,142 cated. Another advantage of this Before implementing routine post-
In addition to these 2 clinical appli- approach would be a reduction in waiting mortem imaging techniques such as
cations, postmortem imaging may serve times for the full reports. However, the postmortem MRI, postmortem ultra-
as a first-line screening examination that cost-effectiveness of our algorithm and sound, or micro-CT in routine clinical
could be used as a form of triage for fetal virtual autopsy are unknown. In 1 practice, several issues need to be
further invasive autopsy in future study concerning adults’ virtual autopsy, addressed. For instance, these tech-
guidelines. The Magnetic Resonance MRI with CT and biopsies produced an niques first need to be recognized as
Imaging Autopsy Study (MaRIAS) estimated cost of $1497 compared with part of routine fetal postmortem ex-
already suggested a stepwise procedure $2274 for invasive autopsy.151 Therefore, amination by national public health
using minimally invasive autopsy that this algorithm would probably allow a services, thus removing any organiza-
would reduce the indications for autopsy reduction of postmortem examination tional or financial obstacles to acces-
in 40% of cases with more than 99% cost, as it would likely reduce the indica- sibility.93 Although such recognition
agreement with autopsy.85 The use of tion for invasive autopsy with exists in the United Kingdom and in

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FIGURE 9
Microfocus computed tomography images of normal anatomy in a fetus of 13-week gestational age

A, Axial view of the brain at the level of the developing thalamus (T) and cerebellum (C) showing the different layers in the cortex (arrow). B, Axial view at
the level of the eyes and choanes. C, Coronal view at the level of the lungs showing normal lung lobulation (3 right lobes and 2 left lobes). The position of
the liver (L) and the stomach (S) demonstrate the normal laterality.
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020.

the Netherlands,149,150 in many other report the postmortem imaging and then be used to facilitate parental
countries, invasive autopsy is the only minimally invasive autopsy? Pediatric counseling.
recognized postmortem examination. radiologists have an excellent knowl-
Another important consideration is edge of imaging technology but have Conclusion
the need to minimize the delay be- less experience for earlier-gestation Postmortem imaging techniques, such as
tween the performance of the chosen fetuses and their associated malfor- MRI, have proven their benefit as alter-
adjunctive imaging technique and the mations. Fetal medicine specialists and natives or adjuncts to invasive autopsy.
invasive autopsy. This relative urgency pathologists have in-depth knowledge Postmortem ultrasound is also helpful
is constrained by the availability of of fetal malformations but have less when MRI is not available. The newly
postmortem ultrasound operators and experience in dysmorphology and in described micro-CT opens up a whole
access to MRI machines, which already the diagnoses of genetic disorders. new area of possibilities for the post-
function at maximum capacity in Therefore, we recommend multidis- mortem examination of small fetuses
many centers. One must also consider ciplinary fetal postmortem working and warrants further investigation.
the emotional impact of handling groups, including radiologists, fetal Now is the time for those responsible
deceased fetuses, particularly for the medicine specialists, pathologists, and for clinical commissioning and man-
radiographers and radiologists who geneticists, jointly responsible for agement of public health finance to
are not regularly confronted by such producing a single unified postmor- incorporate postmortem imaging into
situations.149 Finally, who should tem report, whose conclusions would routine clinical practice.

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FIGURE 10
Proposed stepwise diagnostic approach for fetal postmortem examination

CT, computed tomography; GA, gestational age; MRI, magnetic resonance imaging; NIPT, Noninvasive prenatal testing; PM, postmortem; US, ultrasound.
Kang. Fetal postmortem imaging. Am J Obstet Gynecol 2020.

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