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Micro-computed tomography: a new diagnostic tool in postmortem assessment of brain anatomy in small fetuses

  • Diagnostic Neuroradiology
  • Published:
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Abstract

Purpose

The aim of our study was to evaluate the postmortem micro-CT anatomy of early fetal human fetal brains, either in situ or isolated.

Methods

We studied 12 ex vivo specimens, 9 whole human fetuses (9–18 GW), and 3 isolated samples (16–26 GW).

Specimens were fixed in formalin, then immersed in Lugol solution. Images were evaluated by two neuroradiologists. The depiction of CNS structures was defined based on the comparison between micro-CT images and a reference histologic anatomical Atlas of human brain development.

Results

Micro-CT provided informative high-resolution brain images in all cases, with the exception of one case (9 weeks) due to advanced maceration. All major CNS structures (i.e., brain hemispheres, layering, ventricles, germinal neuroepithelium, basal ganglia, corpus callosum, major cranial nerves, and structures of the head and neck) were recognizable.

Conclusions

Micro-CT imaging of the early fetal brain is feasible and provides high-quality images that correlate with the histological Atlas of the human brain, offering multiplanar and volumetric images that can be stored and shared for clinical, teaching, and research purposes.

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Abbreviations

Micro-CT:

Micro-focus computed tomography

GA:

Gestational age

GZ:

Germinal neuroepithelium or zone

GE:

Ganglionic eminence

IZ:

Intermediate zone

SP:

Subplate

CP:

Cortical plate

MZ:

Marginal zone

References

  1. Engels AC, Joyeux L, Brantner C, De Keersmaecker B, De Catte L, Baud D, Deprest J, Van Mieghem T (2016) Sonographic detection of central nervous system defects in the first trimester of pregnancy. Prenat Diagn 36:266–273. https://doi.org/10.1002/pd.4770

    Article  CAS  PubMed  Google Scholar 

  2. Syngelaki A, Chelemen T, Dagklis T, Allan L, Nicolaides KH (2011) Challenges in the diagnosis of fetal non-chromosomal abnormalities at 11-13 weeks. Prenat Diagn 31:90–102. https://doi.org/10.1002/pd.2642

    Article  PubMed  Google Scholar 

  3. Katorza E, Achiron R (2012) Early pregnancy scanning for fetal anomalies--the new standard? Clin Obstet Gynecol 55:199–216. https://doi.org/10.1097/GRF.0b013e3182446ae9

    Article  PubMed  Google Scholar 

  4. Volpe P, Contro E, Fanelli T, Muto B, Pilu G, Gentile M (2016) Appearance of fetal posterior fossa at 11-14 weeks in fetuses with Dandy-Walker malformation or chromosomal anomalies. Ultrasound Obstet Gynecol 47:720–725. https://doi.org/10.1002/uog.14883

    Article  CAS  PubMed  Google Scholar 

  5. Contro E, Volpe P, De Musso F, Muto B, Ghi T, De Robertis V, Pilu G (2014) Open fourth ventricle prior to 20 weeks’ gestation: a benign finding? Ultrasound Obstet Gynecol 43:154–158. https://doi.org/10.1002/uog.13227

    Article  CAS  PubMed  Google Scholar 

  6. Arthurs OJ, Thayyil S, Pauliah SS, Jacques TS, Chong WK, Gunny R, Saunders D, Addison S, Lally P, Cady E, Jones R, Norman W, Scott R, Robertson NJ, Wade A, Chitty L, Taylor AM, Sebire NJ, Group MRIAS (MaRIAS) C (2015) Diagnostic accuracy and limitations of post-mortem MRI for neurological abnormalities in fetuses and children. Clin Radiol 70:872–880. https://doi.org/10.1016/j.crad.2015.04.008

    Article  CAS  PubMed  Google Scholar 

  7. Gilbert-Barness E, Spicer DE, Steffensen TS (2014) Handbook of pediatric autopsy pathology. Springer

  8. Connolly AJ, Finkbeiner WE, Ursell PC, Richard L, Davis M (2016) Autopsy pathology: a manual and atlas. Elsevier

  9. Lombardi CM, Zambelli V, Botta G, Moltrasio F, Cattoretti G, Lucchini V, Fesslova V, Cuttin MS (2014) Postmortem microcomputed tomography (micro-CT) of small fetuses and hearts. Ultrasound Obstet Gynecol 44:600–609. https://doi.org/10.1002/uog.13330

    Article  CAS  PubMed  Google Scholar 

  10. Thayyil S, Sebire NJ, Chitty LS, Wade A, Chong W, Olsen O, Gunny RS, Offiah AC, Owens CM, Saunders DE, Scott RJ, Jones R, Norman W, Addison S, Bainbridge A, Cady EB, De VE, Robertson NJ, Taylor AM (2013) Post-mortem MRI versus conventional autopsy in fetuses and children: a prospective validation study. Lancet 382:223–233. https://doi.org/10.1016/S0140-6736(13)60134-8

    Article  PubMed  Google Scholar 

  11. Hutchinson JC, Arthurs OJ, Ashworth MT, Ramsey AT, Mifsud W, Lombardi CM, Sebire NJ (2016) Clinical utility of postmortem microcomputed tomography of the fetal heart: diagnostic imaging vs macroscopic dissection. Ultrasound Obstet Gynecol 47:58–64. https://doi.org/10.1002/uog.15764

    Article  CAS  PubMed  Google Scholar 

  12. Lewis C, Hill M, Arthurs O, Hutchinson C, Chitty L, Sebire N (2018) Factors affecting uptake of postmortem examination in the prenatal, perinatal and paediatric setting. BJOG An Int J Obstet Gynaecol 125:172–181. https://doi.org/10.1111/1471-0528.14600

    Article  CAS  Google Scholar 

  13. Thayyil S, Cleary JO, Sebire NJ, Scott RJ, Chong K, Gunny R, Owens CM, Olsen OE, Offiah AC, Parks HG, Chitty LS, Price AN, Yousry TA, Robertson NJ, Lythgoe MF, Taylor AM (2009) Post-mortem examination of human fetuses: a comparison of whole-body high-field MRI at 9.4 T with conventional MRI and invasive autopsy. Lancet (London, England) 374:467–475. https://doi.org/10.1016/S0140-6736(09)60913-2

    Article  Google Scholar 

  14. Scola E, Conte G, Palumbo G, Avignone S, Cinnante CM, Boito S, Persico N, Rizzuti T, Triulzi F (2018) High resolution post-mortem MRI of non-fixed in situ foetal brain in the second trimester of gestation: Normal foetal brain development. Eur Radiol 28:363–371. https://doi.org/10.1007/s00330-017-4965-y

    Article  PubMed  Google Scholar 

  15. Kang X, Cannie MM, Arthurs OJ, Segers V, Fourneau C, Bevilacqua E, Cos Sanchez T, Sebire NJ, Jani JC (2017) Post-mortem whole-body magnetic resonance imaging of human fetuses: a comparison of 3-T vs. 1.5-T MR imaging with classical autopsy. Eur Radiol 27:3542–3553. https://doi.org/10.1007/s00330-016-4725-4

    Article  PubMed  Google Scholar 

  16. Metscher BD (2009) MicroCT for developmental biology: a versatile tool for high-contrast 3D imaging at histological resolutions. Dev Dyn 238:632–640. https://doi.org/10.1002/dvdy.21857

    Article  PubMed  Google Scholar 

  17. Hutchinson JC, Barrett H, Ramsey AT, Haig IG, Guy A, Sebire NJ, Arthurs OJ (2016) Virtual pathological examination of the human fetal kidney using micro-CT. Ultrasound Obstet Gynecol 48:663–665. https://doi.org/10.1002/uog.15859

    Article  CAS  PubMed  Google Scholar 

  18. Hutchinson JC, Kang X, Shelmerdine SC, Segers V, Lombardi CM, Cannie MM, Sebire NJ, Jani JC, Arthurs OJ (2018) Postmortem microfocus computed tomography for early gestation fetuses: a validation study against conventional autopsy. Am J Obstet Gynecol 218:445.e1–445.e12. https://doi.org/10.1016/j.ajog.2018.01.040

    Article  Google Scholar 

  19. Thayyil S (2011) Less invasive autopsy: an evidenced based approach. Arch Dis Child 96:681–687. https://doi.org/10.1136/adc.2009.165704

    Article  PubMed  Google Scholar 

  20. De Crespigny A, Bou-reslan H, Nishimura MC, Phillips H, Richard A, Carano D, Arceuil HED (2009) 3D microCT of the postmortem brain. J Neurosci Methods 171:207–213. https://doi.org/10.1016/j.jneumeth.2008.03.006.3D

    Article  Google Scholar 

  21. Dobrivojević M, Bohaček I, Erjavec I, Gorup D, Gajović S (2013) Computed microtomography visualization and quantification of mouse ischemic brain lesion by nonionic radio contrast agents. Croat Med J 54:3–11. https://doi.org/10.3325/cmj.2013.54.3

    Article  PubMed  PubMed Central  Google Scholar 

  22. Gignac PM, Kley NJ, Clarke JA, Colbert MW, Morhardt AC, Cerio D, Cost IN, Cox PG, Daza JD, Early CM, Echols MS, Henkelman RM, Herdina AN, Holliday CM, Li Z, Mahlow K, Merchant S, Müller J, Orsbon CP, Paluh DJ, Thies ML, Tsai HP, Witmer LM (2016) Diffusible iodine-based contrast-enhanced computed tomography (diceCT): an emerging tool for rapid, high-resolution, 3-D imaging of metazoan soft tissues. J Anat 228:889–909. https://doi.org/10.1111/joa.12449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Degenhardt K, Wright AC, Horng D, Padmanabhan A, Epstein JA (2010) Rapid 3D phenotyping of cardiovascular development in mouse embryos by micro-CT with iodine staining. Circ Cardiovasc Imaging 3:314–322. https://doi.org/10.1161/CIRCIMAGING.109.918482

    Article  PubMed  PubMed Central  Google Scholar 

  24. Li Z, Clarke JA, Ketcham RA, Colbert MW, Yan F (2015) An investigation of the efficacy and mechanism of contrast-enhanced X-ray computed tomography utilizing iodine for large specimens through experimental and simulation approaches. BMC Physiol 15(5). https://doi.org/10.1186/s12899-015-0019-3

  25. Kostovic I, Vasung L (2009) Insights from in vitro fetal magnetic resonance imaging of cerebral development. Semin Perinatol 33:220–233. https://doi.org/10.1053/j.semperi.2009.04.003

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Neuroradiology, Grande Ospedale Metropolitano Niguarda, Milan, Italy

    Sophie Lombardi

  2. Neuroradiology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Elisa Scola & Fabio Triulzi

  3. Department of Radiology, Ospedale San Gerardo, Monza, Italy

    Davide Ippolito

  4. Department of Health Sciences, Università di Milano-Bicocca, Milan, Italy

    Vanessa Zambelli

  5. Azienda Ospedaliera Città della Salute e delle Scienze di Torino, Presidio Ospedaliero OIRM-Sant’Anna, Turin, Italy

    Giovanni Botta

  6. Department of Pathology, San Gerardo Hospital, Monza, Italy

    Serena Cuttin

  7. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy

    Fabio Triulzi

  8. Department of Radiology-Studio Diagnostico Eco, Vimercate, Italy

    Claudio M. Lombardi

Authors
  1. Sophie Lombardi
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  2. Elisa Scola
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  4. Vanessa Zambelli
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Corresponding author

Correspondence to Sophie Lombardi.

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No funding was received for this study.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.

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For this type of retrospective study formal consent is not required.

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Lombardi, S., Scola, E., Ippolito, D. et al. Micro-computed tomography: a new diagnostic tool in postmortem assessment of brain anatomy in small fetuses. Neuroradiology 61, 737–746 (2019). https://doi.org/10.1007/s00234-019-02168-2

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  • DOI: https://doi.org/10.1007/s00234-019-02168-2

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