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


  • A. C. G. Breeze,

    1. Division of Maternal-Fetal Medicine, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
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  • F. A. Jessop,

    1. Department of Paediatric & Perinatal Pathology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
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  • P. A. K. Set,

    1. Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
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  • A. L. Whitehead,

    1. Department of Paediatric & Perinatal Pathology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
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  • J. J. Cross,

    1. Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
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  • D. J. Lomas,

    1. Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
    2. University Department of Radiology, University of Cambridge School of Clinical Medicine, Cambridge, UK
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  • G. A. Hackett,

    1. Division of Maternal-Fetal Medicine, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
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  • I. Joubert,

    1. Magnetic Resonance Imaging and Spectroscopy Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
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  • C. C. Lees

    Corresponding author
    1. Division of Maternal-Fetal Medicine, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
    • Division of Maternal-Fetal Medicine, Addenbrooke's Hospital, Hills Road, Box 228, Cambridge, CB2 0QQ, UK

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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.


Forty-four fetuses underwent postmortem MRI and attempted percutaneous biopsy (using surface landmarks) of major fetal organs (liver, lung, heart, spleen, kidney, adrenal and thymus) following fetal death or termination for abnormality, prior to conventional autopsy, which was considered the ‘gold standard’. We compared significant findings of the two examinations for both diagnostic information and clinical significance. Ancillary investigations (such as radiographs and placental histology) were regarded as common to the two forms of autopsy.


In 21 cases conventional autopsy provided superior diagnostic information to that of MIA. In two cases the MIA provided superior diagnostic information to that of conventional autopsy, when autolysis prevented detailed examination of the fetal brain. In the remaining 21 cases, conventional autopsy and MIA provided equivalent diagnostic information. With regard to clinical significance, however, in 32 (72.7%) cases, the MIA provided information of at least equivalent clinical significance to that of conventional autopsy. In no case did the addition of percutaneous biopsies reveal information of additional clinical significance.


Although in some cases MRI may provide additional information, conventional perinatal autopsy remains the gold standard for the investigation of fetal death. The utility of adding percutaneous organ biopsies, without imaging guidance, to an MRI-based fetal autopsy remains unproven. Postmortem MRI, combined with ancillary investigations such as placental histology, external examination by a pathologist, cytogenetics and plain radiography provided information of equivalent clinical significance in the majority of cases. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.


Fetal and neonatal deaths, and major fetal abnormalities are common events in perinatal medicine, affecting 1–2% of pregnancies in the UK and many other industrialized countries1, 2. In such circumstances, the attending medical staff will often recommend to parents an autopsy and other investigations, in the hope that the findings may provide a cause of death, or an explanation of any congenital abnormalities, and help inform the best estimation of the risk of recurrence3, 4.

In recent years consent rates for perinatal autopsy have been in decline in many countries, and access to the services of a specialist pediatric pathologist may be limited by centralization in regional centers5. Recruitment into the speciality of pediatric pathology has been under threat, and adverse publicity regarding organ retention has harmed public confidence in pediatric pathology services. Clinicians may find it difficult to ask parents for an autopsy6, 7. A consequence of these events has been a growing interest in alternative methods of autopsy8. The most promising approach to date has been the use of postmortem imaging techniques, and in particular magnetic resonance imaging (MRI), as it appears to provide macroscopic information equivalent to that of conventional autopsy in many cases.

Some aspects of conventional autopsy cannot be replicated by postmortem MRI alone. For example, assessment of organ weight, an integral part of conventional perinatal autopsy, is not possible directly using postmortem MRI, though organ volume estimation is feasible9, 10. Another weakness in studies comparing conventional autopsy to postmortem MRI is the unavailability of organ tissue for microscopic examination from MRI postmortem. Some investigators have examined the feasibility of combining postmortem imaging with targeted biopsies in small series, for example following deaths due to neonatal encephalopathy11. However, whether the addition of percutaneous biopsies is valuable or feasible, in the majority of cases undergoing less invasive autopsy with MRI, has not yet been clearly demonstrated. In this study we investigated the comparability of an MRI-based minimally invasive autopsy (MIA), incorporating percutaneous organ biopsies, with conventional fetal autopsy. In doing this, we sought to assess whether such biopsies provide additional information that would change parental counseling or would modify the apparent cause of death.


Following termination of pregnancy for fetal abnormality, miscarriage or stillbirth, 44 fetuses underwent postmortem MRI and attempted percutaneous biopsy of major fetal organs prior to conventional autopsy by a specialist perinatal pathologist. Ethical approval was given by the Cambridge Research Ethics Committee (Cambridge REC 02/004). Median gestational age was 21.5 (range, 16–40) weeks and median fetal weight recorded at autopsy was 346 (range, 61–3270) g. MRI techniques and sequences were as described previously by our group12, and are summarized in Table 1. A GE Signa 1.5T clinical MRI system (GE Healthcare, Milwaukee, WI, USA), with software release 11 was used, with different receiver coils (head, knee and wrist coils) selected according to the size of the fetus. Percutaneous organ biopsies were performed by an obstetric research fellow, using surface landmarks without imaging guidance, using a 16–18G Temno cutting biopsy needle (Cardinal Health, McGraw Park, IL, USA) as previously described13. The findings of percutaneous organ biopsy of 30 of these cases have been reported elsewhere13.

Table 1. Typical magnetic resonance imaging parameters for FSE-XL T2-weighted sequences in the three anatomical orthogonal planes
ParameterBody imagingHead imaging
  1. Coronal and sagittal sequences include both fetal head and body; separate axial sequences were performed for fetal head and body. NEX, number of excitations; TE, echo time; TR, repetition time.

TE effective (ms)102102
TR (ms)4000–650015 000
Echo train length13–2432
Bandwidth (kHz)20.8320.83
Field of view (cm)16–2812–16
Slice thickness (mm)2–3, no gap2, no gap
Matrix512 × 256, 384 × 256 for axial sequences256 × 256
NEXMinimum of 45
Phase field of view0.5 used to reduce time for axial and sagittal sequences0.75 for axial sequences
Scan time5–8 min for each plane7 min 30 s

Postmortem MRI studies of the body were reported by a pediatric radiologist, and a neuroradiologist with expertise in pediatric neuroradiology reported on the head and neck. The reporting radiologists were advised of the clinical history and prenatal ultrasound findings, when available. Radiologists reported studies using a standardized checklist12, and were ‘blind’ to the results of the conventional autopsy, which was performed subsequent to postmortem MRI.

Fetal autopsies were performed by two pediatric histopathologists, who had access to the clinical history and prenatal ultrasound findings, but who were blinded to the results of the postmortem MRI studies. Percutaneous needle biopsies were reported by whichever of the two pathologists had not performed the conventional autopsy.

The results of all investigations, including ancillary tests such as karyotype, maternal infection serology, plain radiography and placental histology were collated and then compared to identify which investigations provided the most clinically useful information about the cause of fetal death, or to facilitate the estimation of the risk of recurrence in those cases of structural fetal abnormality.

The clinical significance of the conventional autopsy findings was compared with that of MIA findings, in a manner similar to that previously described by Brookes et al.14 and by Thayyil et al.15, regarding ancillary investigations as common information for both the conventional autopsy and MIA. The two modalities were also compared in terms of diagnostic information, that is any macroscopic or histological finding where there was discordance between the techniques, i.e. macroscopic information at MRI and microscopic information from biopsies, in comparison with the macroscopic and histological findings at autopsy as the gold standard.


There were 21 cases of miscarriage and intrauterine fetal death (median gestational age 27 (range, 17–40) weeks; median fetal weight 500 (range, 93–3270) g), and 23 cases of termination for fetal abnormality (median gestational age 21 (range, 16–33) weeks; median fetal weight 330 (range, 61–2345) g).

Overall, MIA provided information of equal clinical significance to that of conventional autopsy in 32/44 (72.7%) cases (Table S1). Conventional autopsy was superior to MIA in 10/44 cases (22.7%) in terms of clinical significance (Table 2), and MIA was superior to conventional autopsy in two (4.5%) cases (Table 3). In these two cases, detailed neuropathological examination was not possible due to autolysis following fetal death, and postmortem MRI in both cases demonstrated structural brain malformations (see Table 3).

Table 2. Conventional and minimally invasive autopsy (MIA) findings in cases where conventional autopsy provided information of greater clinical significance
GA (weeks)Weight (g)Clinical history and US findingsSignificant MRI/biopsy i.e. MIA and autopsy findings (discrepant findings in italics) and diagnostic sensitivityCommon investigations (incl. karyotype, placenta, radiographs, TORCH)Clinical significance
  1. (A)CC, (absent) corpus callosum; ASD, atrial septal defect; AVSD, atrioventricular septal defect; CMV, cytomegalovirus; GA, gestational age; HPE, holoprosencephaly; IHC, interhemispheric cyst; incl., including; IUD, intrauterine death; MCDK, multicystic dysplastic kidneys; MRI, magnetic resonance imaging; NEC, necropsy (conventional postmortem); PVH, periventricular hemorrhage; RVOT, right ventricular outflow tract; SGA, small-for-gestational age; SOD, septo-optic dysplasia; TGA, transposition of great arteries; TORCH, toxoplasma, rubella and cytomegalovirus serology; US, ultrasound; VSD, ventricular septal defect; VM, ventriculomegaly.

17113Nasal bone hypoplasia,MIA apparently normalApparently normal femaleNEC > MIA
   hypoplastic left heart, cysticAutopsy: nasal bone hypoplasia, aortic coarctation  
   hygromata, echogenic bowel and tubular hypoplasia, dysmorphism, cystic  
   Diagnostic sensitivity: autopsy > MIA  
21396Bilateral multicystic kidneys,MIA: multicystic kidneys, hypoplastic lungs, renal46,XYNEC > MIA
   anhydramnios biopsy inadequate  
   Autopsy: bilateral MCDK on histology, hypoplastic lungs, postural anomalies  
   Diagnostic sensitivity: autopsy > MIA  
20330Gross VM ± semilobar HPE,MIA: enlarged lateral ventricles, likely SOD/lobarApparently normalNEC > MIA
   oligohydramnios; kidneys and HPE, multiple spinal anomalies, collapsed bladder,  
   bladder appeared present, single femur visualized, hypoplastic kidneys, mild ascites, large pericardial  
   absent tibiae, fibulae and feet, abnormal effusions, heart displaced to right, suspected  
   pelvic rim, multiple vertebral anomalies univentricular heart, TGA, ASD  
   suspected TGAAutopsy: dysmorphism, no anus or external genitalia, single lower limb, rudimentary foot, right lung with abnormal middle lobe, no lower urogenital tract, single left-sided cystic kidney, blind-ending small intestine, scoliosis, normal heart, HPE (middle interhemispheric/lobar form), abnormal brainstem  
   Diagnostic sensitivity: autopsy > MIA  
23567US: midline supratentorial cyst;MRI: ACC, interhemispheric cyst, segmentation46,XX; reactive CMVNEC > MIA
   In-utero fetal MRI: ACC with abnormal anomaly at T12 suspected hemivertebra serology 
   left parietal cortexAutopsy: closed-lip schizencephaly, remote polymicrogyria, subcortical nodular heterotopy, IHC with arachnoid and choroid plexus elements, absent CC  
   Diagnostic sensitivity: autopsy > MIA  
21354.7US showed an AVSD and anMIA: suspected ASD, small RVOT, very small right-sided46,XYNEC > MIA
   echogenic focus, mild PVH of uncertain significance  
   polyhydramniosAutopsy: dysmorphism, AVSD with aortic override  
    and stenotic pulmonary valve, tracheo-esophageal fistula  
   Diagnostic sensitivity: autopsy > MIA  
22311.2VSD, talipesMIA: small lungs, micrognathia, mild cervicothoracic scoliosis, suspected midline cleft hard palate46,XXNEC > MIA
   Autopsy: dysmorphic fetus with unilateral single palmar creases, VSD, two lobes in right lung, unilateral talipes, apparently absent adrenal glands  
   Diagnostic sensitivity: autopsy > MIA  
27997IUD following threatenedMRI: apparently normal, no biopsies available46,XXNEC > MIA
   preterm labor, raisedAutopsy: normally formed fetus, chronic Cause of death provided
   inflammatory markers inflammatory infiltrate in lung  by lung block histology
   Diagnostic sensitivity: autopsy > MIA  
19145Unbooked pregnancy,MRI: HPE normal cerebellum, pons and medullaApparently normalNEC > MIA
   miscarriage at 19 weeks, no US scans rotation of intestineAutopsy: HPE, premaxillary agenesis, cleft lip and palate, right lung absent middle lobe, incomplete  
   Diagnostic sensitivity: autopsy > MIA  
392786Apparently normalMRI: narrow thorax, small lungs with heterogeneous signal, small thymus, no thymus biopsy available46 + 21NEC > MIA
   Autopsy: dysmorphic, SGA, small lungs, narrow thorax, single left palmar crease, perimembranous VSD, large cystic Hassall's corpuscles in thymus No definite cause of death identified
   Diagnostic sensitivity: autopsy > MIA  
1661Right-sided parietalMRI: anencephaly46,XYNEC > MIA
   encephaloceleAutopsy: occipital encephalocele  
   Diagnostic sensitivity: autopsy > MIA  
Table 3. Conventional and minimally invasive autopsy (MIA) findings in cases where less-invasive autopsy provided information of greater clinical significance
GA (weeks)Weight (g)Clinical history and US findingsSignificant MRI/biopsy and autopsy findings (discrepant findings in italics) and diagnostic sensitivityCommon investigations (incl. karyotype, placenta, radiographs, TORCH)Clinical significance
  1. CC, corpus callosum; CNS, central nervous system; GA, gestational age; incl., including; MCA, middle cerebral artery; MRI, magnetic resonance imaging; NEC, necropsy (conventional postmortem); TORCH, Toxoplasma, Rubella and Cytomegalovirus serology; US, ultrasound; VM, ventriculomegaly.

23587Dandy–Walker malformation on US and fetal MRIMIA: likely agenesis CC, small cerebellum, adrenal hemorrhage46,XXMIA > NEC
   Autopsy: maceration prevented neuropathology  
   Diagnostic sensitivity: MIA > autopsy  
22275Fetal hydrops, normal MCA Doppler, maternal TORCH screen normalMIA: hydrops, small thymus, hypoplastic lungs, suspected dysgenesis CC, borderline VM, small cerebellum and brainstem46,XYMIA > NEC, no cause for hydrops/fetal death identified at either
   Autopsy: edematous tissues, small thymus, autolyzed CNS  
   Diagnostic sensitivity: MIA > autopsy  

In those 32 cases where MIA and conventional autopsy were clinically equivalent, there were 11 cases in which autopsy provided additional diagnostic information compared with MIA. However, this additional information was unlikely to impact on parental counseling. In the remaining 21/32 cases, both MIA and conventional autopsy provided equivalent diagnostic information, which in some cases meant both failed to explain fetal death, or that ancillary tests (such as plain radiography, cytogenetics or placental histology) provided the key information.

In the 10 cases where conventional autopsy was superior to MIA for clinical significance, there were four cases of cardiac anomalies at autopsy that were not clearly seen at MRI (including one fetus with a tracheo-esophageal fistula, not detected on MRI), one case in which a cardiac anomaly suspected at MRI was excluded at autopsy (false positive diagnosis) in a fetus with multiple structural anomalies (sirenomelia sequence), and one case with abnormal lung lobation and incomplete bowel rotation that was undetected on MRI. In one case, detailed neuropathology revealed additional central nervous system (CNS) anomalies (schizencephaly with polymicrogyria) in a fetus with agenesis of the corpus callosum and an interhemispheric cyst. In one case, lung block histology helped provide the cause of fetal death, but no lung biopsy was available from MIA, and in another case renal block histology confirmed that enlarged cystic kidneys seen on ultrasound scan were due to multicystic renal dysplasia. In the same case, percutaneous renal biopsy from the MIA was inadequate for pathological comment.


We report on the comparability of MIA—i.e. whole-body postmortem MRI and percutaneous biopsies—with conventional autopsy. Previous reports have concentrated on comparing the macroscopic information provided by MRI with the macroscopic and microscopic information of conventional autopsy, or focused on specific organ systems14, 16–20. By adding biopsies, we hoped to address the lack of histological information associated with postmortem MRI.

Most reports have concluded that a minority of perinatal autopsies provide additional diagnostic information or information that modifies care or parental counseling21, 22. This may diminish the perceived value of autopsy to clinicians and parents, and may therefore have contributed to falling autopsy rates6, 7. Other reports have, however, demonstrated that a significant proportion of autopsies (27% of cases in which there were fetal anomalies but a normal karyotype4) will provide new information, and parents should therefore be encouraged to give permission for autopsy, while less invasive investigations might provide some information for parents unwilling to do so23.

In the present study in 72.7% of cases, an MIA based on postmortem MRI, percutaneous sampling of major fetal organs, external examination and ancillary tests (cytogenetics, placental histology and radiographs) provided information of equivalent clinical significance to conventional autopsy. This concurs with some previous reports14, 18, 20 and is better than the percentage given in others17.

We report discrepancies between conventional autopsy and postmortem MRI. These are due to difficulties in resolving small anatomical structures using conventional 1.5 T sequences, postmortem distortion of anatomy, or unfamiliarity with the appearances of ‘normal’ anatomy at MRI. While some discrepancies could be described as false-positive findings, autopsy also revealed additional true anomalies undetected on MRI. Previous reports highlighted difficulties in assessing cardiac anomalies on postmortem MRI in particular, which these data confirm. Further, gastrointestinal tract anomalies (tracheo-esophageal fistula and bowel malrotation) and thoracic abnormalities (abnormal lung lobation) may also go undetected.

We concur with previous reports that postmortem MRI has advantages, particularly in assessing the fetal CNS in situ, which often proves difficult at autopsy19, 24. In two cases neuropathology was not possible due to autolysis (commonly arising following fetal death or fetocide). Similarly, examining the unfixed brain when parents decline retention for detailed examination may limit diagnostic yield. MRI may be extremely valuable in such circumstances19.

Three cases with CNS anomalies suspected on ultrasound underwent in-utero fetal MRI. Although fetal MRI often provided additional information, significantly changing the ultrasound diagnosis25, 26 it did not always agree with the final autopsy diagnosis, or with postmortem MRI. Postmortem MRI should offer advantages over in-utero MRI, as there is little restriction on acquisition time, no motion artifact, and receiver coils can be placed closer to the region of interest. When detailed neuropathology is possible, it may provide information beyond that currently feasible with postmortem MRI. Parents should therefore be encouraged to consent if CNS anomalies are suspected on prenatal imaging, even when postmortem MRI is available as a clinical service.

Developments in postmortem MRI may obviate some difficulties encountered with small fetuses and some structures such as the heart. In 17 fetuses imaged at both 1.5 and 9.4 T, using a 9.4 T magnet resulted in fewer nondiagnostic examinations15. Significant problems remained in examining the fetal brain and trunk (with 50% and 75% of examinations nondiagnostic) when there was a prolonged interval between fetal death and imaging.

In these cases drawn from those seen at a tertiary unit, there is little evidence of incremental benefit of percutaneous biopsies over information provided by postmortem MRI alone. It remains plausible that percutaneous organ sampling is valuable in some cases: in unexplained fetal death, biopsies might reveal evidence of infection and biopsies of selected fetal organs may provide a histological diagnosis when anomalies are detected on prenatal ultrasound or postmortem MRI16. In one case, the typical appearances of multicystic renal dysplasia were present on both ultrasound and postmortem MRI though percutaneous renal biopsy was diagnostically inadequate. We have previously reported that fetal renal biopsies apparently adequate for histopathological comment are obtained in only half of the cases without imaging guidance, whereas adequate samples can usually be obtained from the liver and lung13. In some cases within our study, the lack of such histological information could adversely impact on parental counseling. Therefore if sampling of an organ is critical for providing an explanation, open sampling or imaging guidance, perhaps using MRI-compatible needles, is advised8, 27. Our data suggest that the lack of microscopic information provided by MRI alone is unlikely to diminish the quality of counseling in many cases of termination for fetal abnormality or fetal death. In the context of neonatal or infant death, obtaining samples from a number of organs for histological examination is likely to be beneficial, as these deaths are less likely to be complicated by structural anomalies amenable to detection by MRI.

Where fetuses have chromosomal anomalies, autopsy information is unlikely to modify parental counseling about recurrence risk, but a minority of parents may request it to validate their decision-making. Abnormal karyotype does not necessarily explain a fetal death although it may help clinicians and parents plan for future pregnancies. Our inclusion of these fetuses provides a wide spectrum of structural fetal anomalies for examining the diagnostic capabilities of postmortem MRI. However, in many cases with a normal karyotype, the failure of MRI to detect structural anomalies that would be identified at autopsy could adversely impact on parental counseling, or restrict the direction of further genetic testing. Skeletal dysplasias also represent cases where other investigations (e.g. plain radiography) usually provide the key diagnostic information. In such cases postmortem MRI is unlikely to offer additional information, although it may provide evidence of pulmonary hypoplasia9.

In conclusion, we present a comparison of MIA based on postmortem MRI with percutaneous biopsies of major fetal organs with conventional autopsy. Conventional autopsy will often provide information of superior clinical significance to that of MIA. However our data suggest that an examination based on postmortem MRI, external examination by a specialist perinatal pathologist, with ancillary investigations including placental histology, X-ray skeletal survey and cytogenetics, often provides equivalent information when parents decline conventional autopsy. Studies specifically with imaging-directed biopsies may clarify whether MIA is a realistic alternative for parents and clinicians. In the meantime, conventional autopsy remains the gold standard for investigating fetal death.


The following supporting information may be found in the online version of this article.

Table S1 Conventional and minimally invasive autopsy findings in cases with clinically equivalent information obtained from the two modalities.


This study was supported by the Addenbrooke's Charitable Trust, which had no role in the study design; A.C.G.B's salary was part-funded by Cambridge Fetal Care. We acknowledge the assistance of the pediatric pathology service staff of Addenbrooke's Hospital: N. Wood, G. Kenyon, S. Brown and M. Macer. Nick Coleman of the Hutchison/MRC Research Centre provided valuable advice during study design.