Digital imaging, including the use of artificial intelligence, has been increasingly applied to investigate the placenta and its related pathology. However, there has been no comprehensive review of this body of work to date. The aim of this study was to therefore review the literature regarding digital pathology of the placenta. A systematic literature search was conducted in several electronic databases. Studies involving the application of digital imaging and artificial intelligence techniques to human placental samples were retrieved and analyzed. Relevant articles were categorized by digital image technique and their relevance to studying normal and diseased placenta. Of 2008 retrieved articles, 279 were included. Digital imaging research related to the placenta was often coupled with immunohistochemistry, confocal microscopy, 3D reconstruction, and/or deep learning algorithms. By significantly increasing pathologists’ ability to recognize potentially prognostic relevant features and by lessening inter-observer variability, published data overall indicate that the application of digital pathology to placental and perinatal diseases, along with clinical and radiology correlation, has great potential to improve fetal and maternal health care including the selection of targeted therapy in high-risk pregnancy.
RedlineRW. Classification of placental lesions. Am J Obstet Gynecol. 2015;213(4 Suppl):S21-S28. doi:10.1016/j.ajog.2015.05.056
2.
HuppertzB. Placental pathology in pregnancy complications. Thromb Res. 2011;127:S96-S99. doi:10.1016/S0049-3848(11)70026-3
3.
SalafiaCMVintzileosAM. Why all placentas should be examined by a pathologist in 1990. Am J Obstet Gynecol. 1990;163(4 Pt 1):1282-1293. doi:10.1016/0002-9378(90)90708-f
4.
SillsASteigmanCOunpraseuthSTOdiboISandlinATMagannEF. Pathologic examination of the placenta: recommended versus observed practice in a university hospital. Int J Womens Health. 2013;5:309-312. doi:10.2147/IJWH.S45095
5.
CurtinWMKraussSMetlayLAKatzmanPJ. Pathologic examination of the placenta and observed practice. Obstet Gynecol. 2007;109(1):35-41. doi:10.1097/01.AOG.0000247646.19979.9f
6.
RedlineRW. The clinical implications of placental diagnoses. Semin Perinatol. 2015;39(1):2-8. doi:10.1053/j.semperi.2014.10.002
7.
KhongTYMooneyEEArielI, et al. Sampling and definitions of placental lesions: Amsterdam placental workshop group consensus statement. Arch Pathol Lab Med. 2016;140(7):698-713. doi:10.5858/arpa.2015-0225-CC
8.
TizhooshHRPantanowitzL. Artificial intelligence and digital pathology: challenges and opportunities. J Pathol Inform. 2018;9:38. doi:10.4103/jpi.jpi_53_18
9.
ZarellaMDBowmanDAeffnerF, et al. A Practical guide to whole slide imaging: a white paper from the digital pathology association. Arch Pathol Lab Med. 2019;143(2):222-234. doi:10.5858/arpa.2018-0343-RA
10.
AbelsEPantanowitzL. Current state of the regulatory trajectory for whole slide imaging devices in the USA. J Pathol Inform. 2017;8:23. doi:10.4103/jpi.jpi_11_17
11.
PantanowitzLSinardJHHenricksWH, et al. Validating whole slide imaging for diagnostic purposes in pathology: guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med. 2013;137(12):1710-1722. doi:10.5858/arpa.2013-0093-CP
12.
GriffinJTreanorD. Digital pathology in clinical use: where are we now and what is holding us back?Histopathology. 2017;70(1):134-145. doi:10.1111/his.12993
13.
EccherAGirolamiIBrunelliM, et al. Digital pathology for second opinion consultation and donor assessment during organ procurement: review of the literature and guidance for deployment in transplant practice. Transplant Rev (Orlando). 2020;34(4):100562. doi:10.1016/j.trre.2020.100562
14.
NeriFEccherARigottiP, et al. Advantages of using a web-based digital platform for kidney preimplantation biopsies. J Pathol Inform. 2021;12:41. doi:10.4103/jpi.jpi_23_21
15.
BauerTWSlawRJ. Validating whole-slide imaging for consultation diagnoses in surgical pathology. Arch Pathol Lab Med. 2014;138(11):1459-1465. doi:10.5858/arpa.2013-0541-OA
16.
GoacherERandellRWilliamsBTreanorD. The diagnostic concordance of whole slide imaging and light microscopy: a systematic review. Arch Pathol Lab Med. 2017;141(1):151-161. doi:10.5858/arpa.2016-0025-RA
17.
BrunelliMBeccariSColombariR, et al. iPathology cockpit diagnostic station: validation according to College of American Pathologists Pathology and Laboratory Quality Center recommendation at the Hospital Trust and University of Verona. Diagn Pathol. 2014;9Suppl 1:S12. doi:10.1186/1746-1596-9-S1-S12
18.
GirolamiIPantanowitzLMarlettaS, et al. Diagnostic concordance between whole slide imaging and conventional light microscopy in cytopathology: a systematic review. Cancer Cytopathol. 2020;128(1):17-28. doi:10.1002/cncy.22195
19.
GirolamiIMarlettaSPantanowitzL, et al. Impact of image analysis and artificial intelligence in thyroid pathology, with particular reference to cytological aspects. Cytopathology. 2020;31(5):432-444. doi:10.1111/cyt.12828
20.
EccherAGirolamiI. Current state of whole slide imaging use in cytopathology: pros and pitfalls. Cytopathology. 2020;31(5):372-378. doi:10.1111/cyt.12806
21.
CimaLBrunelliMParwaniA, et al. Validation of remote digital frozen sections for cancer and transplant intraoperative services. J Pathol Inform. 2018;9:34. doi:10.4103/jpi.jpi_52_18
22.
EccherANeilDCiangherottiA, et al. Digital reporting of whole-slide images is safe and suitable for assessing organ quality in preimplantation renal biopsies. Hum Pathol. 2016;47(1):115-120. doi:10.1016/j.humpath.2015.09.012
23.
SantoniccoNMarlettaSPantanowitzL, et al. Impact of mobile devices on cancer diagnosis in cytology. Diagn Cytopathol. 2022;50(1):34-45. doi:10.1002/dc.24890
24.
LiberatiAAltmanDGTetzlaffJ, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700. doi:10.1136/bmj.b2700
25.
StroupDFBerlinJAMortonSC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008-2012. doi:10.1001/jama.283.15.2008
26.
OuzzaniMHammadyHFedorowiczZElmagarmidA. Rayyan-a web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210. doi:10.1186/s13643-016-0384-4
27.
NaickerTKhedunSMMoodleyJPijnenborgR. Quantitative analysis of trophoblast invasion in preeclampsia. Acta Obstet Gynecol Scand. 2003;82(8):722-729. doi:10.1034/j.1600-0412.2003.00220.x
28.
SzaboSXuYRomeroR, et al. Changes of placental syndecan-1 expression in preeclampsia and HELLP syndrome. Virchows Arch. 2013;463(3):445-458. doi:10.1007/s00428-013-1426-0
29.
BhallaAStonePRLiddellHSZanderigoAChamleyLW. Comparison of the expression of human leukocyte antigen (HLA)-G and HLA-E in women with normal pregnancy and those with recurrent miscarriage. Reproduction. 2006;131(3):583-589. doi:10.1530/rep.1.00892
30.
SchonkerenDvan der HoornM-LKhedoeP, et al. Differential distribution and phenotype of decidual macrophages in preeclamptic versus control pregnancies. Am J Pathol. 2011;178(2):709-717. doi:10.1016/j.ajpath.2010.10.011
31.
AlahakoonTIZhangWArbuckleSZhangKLeeV. Reduced angiogenic factor expression in intrauterine fetal growth restriction using semiquantitative immunohistochemistry and digital image analysis. J Obstet Gynaecol Res. 2018;44(5):861-872. doi:10.1111/jog.13592
32.
MoodleyMMoodleyJNaickerT. Evaluation of placental chorionic villi histone 2A expression in HIV-infected women with pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 2020;245:127-133. doi:10.1016/j.ejogrb.2019.12.025
33.
SingalSSNygardKGrattonRJanssonTGuptaMB. Increased insulin-like growth factor binding protein-1 phosphorylation in decidualized stromal mesenchymal cells in human intrauterine growth restriction placentas. J Histochem Cytochem. 2018;66(9):617-630. doi:10.1369/0022155418772574
34.
ChantraineFBlacherSBerndtS, et al. Abnormal vascular architecture at the placental-maternal interface in placenta increta. Am J Obstet Gynecol. 2012;207(3):188.e1-188.e9. doi:10.1016/j.ajog.2012.06.083
35.
PtacekISmithAGarrodA, et al. Quantitative assessment of placental morphology may identify specific causes of stillbirth. BMC Clin Pathol. 2016;16:1. doi:10.1186/s12907-016-0023-y
36.
WarranderLKBatraGBernataviciusG, et al. Maternal perception of reduced fetal movements is associated with altered placental structure and function. PLoS One. 2012;7(4):e34851. doi:10.1371/journal.pone.0034851
37.
GarrodABatraGPtacekIHeazellAEP. Duration and method of tissue storage alters placental morphology - implications for clinical and research practice. Placenta. 2013;34(11):1116-1119. doi:10.1016/j.placenta.2013.07.067
38.
MalyAGoshenGSelaJPinelisAStarkMMalyB. Histomorphometric study of placental villi vascular volume in toxemia and diabetes. Hum Pathol. 2005;36(10):1074-1079. doi:10.1016/j.humpath.2005.07.021
39.
GilioDBMiranda CorrêaRRSouza de Oliveira GuimarãesC, et al. Analysis of placenta vascularization in patients with uterine altered artery Doppler flow velocity exams. J Obstet Gynaecol Res. 2009;35(4):648-653. doi:10.1111/j.1447-0756.2008.00952.x
40.
Swiderska-ChadajZMarkiewiczTKoktyszRCierniakS. Image processing methods for the structural detection and gradation of placental villi. Comput Biol Med. 2018;100:259-269. doi:10.1016/j.compbiomed.2017.08.004
41.
KidronDVainerIFisherYSharonyR. Automated image analysis of placental villi and syncytial knots in histological sections. Placenta. 2017;53:113-118. doi:10.1016/j.placenta.2017.04.004
42.
MukherjeeAChanADCKeatingS, et al. The placental distal villous hypoplasia pattern: interobserver agreement and automated fractal dimension as an objective metric. Pediatr Dev Pathol. 2016;19(1):31-36. doi:10.2350/15-03-1619-OA.1
43.
ClymerDKostadinovSCatovJ, et al. Decidual vasculopathy identification in whole slide images using multiresolution hierarchical convolutional neural networks. Am J Pathol. 2020;190(10):2111-2122. doi:10.1016/j.ajpath.2020.06.014
44.
MobadersanyPCooperLADGoldsteinJA. GestAltNet: aggregation and attention to improve deep learning of gestational age from placental whole-slide images. Lab Invest. 2021;101(7):942-951. doi:10.1038/s41374-021-00579-5
45.
MayhewTM. Morphomics: an integral part of systems biology of the human placenta. Placenta. 2015;36(4):329-340. doi:10.1016/j.placenta.2015.01.001
46.
MayhewTMJoyCFHaasJD. Structure-function correlation in the human placenta: the morphometric diffusing capacity for oxygen at full term. J Anat. 1984;139(Pt 4):691-708.
47.
HeidariZMahmoudzadeh-SaghebHNaroueiMSheibakN. Effects of gestational diabetes mellitus on stereological parameters and extravillous trophoblast cells of placenta compared to the control group. J Obstet Gynaecol. 2019;39(7):928-933. doi:10.1080/01443615.2019.1578948
48.
HeidariZMahmoudzadeh-SaghebHSheibakN. Quantitative changes of extravillous trophoblast cells in heavy smoker mothers compared with healthy controls. Reprod Fertil Dev. 2018;30(2):409-414. doi:10.1071/RD17041
49.
HeidariZSakhavarNMahmoudzadeh-SaghebHEzazi-BojnourdiT. Stereological analysis of human placenta in cases of placenta previa in comparison with normally implanted controls. J Reprod Infertil. 2015;16(2):90-95.
50.
HeidariZMahmoudzadeh-SaghebHSheibakNNourzaeiN. Quantitative changes of extravillous trophoblast cells in placentas of systemic lupus erythematosus patients. J Obstet Gynaecol. 2017;37(6):746-751. doi:10.1080/01443615.2017.1306695
51.
AhenkorahJTetteh-QuarcooPBNuamahMA, et al. The impact of plasmodium infection on placental histomorphology: a stereological preliminary study. Infect Dis Obstet Gynecol. 2019;2019:2094560. doi:10.1155/2019/2094560
52.
DaayanaSBakerPCrockerI. An image analysis technique for the investigation of variations in placental morphology in pregnancies complicated by preeclampsia with and without intrauterine growth restriction. J Soc Gynecol Investig. 2004;11(8):545-552. doi:10.1016/j.jsgi.2004.06.009
53.
EgborMAnsariTMorrisNGreenCJSibbonsPD. Morphometric placental villous and vascular abnormalities in early- and late-onset pre-eclampsia with and without fetal growth restriction. BJOG. 2006;113(5):580-589. doi:10.1111/j.1471-0528.2006.00882.x
54.
OdiboAOZhongYLongtineM, et al. First-trimester serum analytes, biophysical tests and the association with pathological morphometry in the placenta of pregnancies with preeclampsia and fetal growth restriction. Placenta. 2011;32(4):333-338. doi:10.1016/j.placenta.2011.01.016
55.
GüvenDAltunkaynakBZAltunGAlkanIKocakI. Histomorphometric changes in the placenta and umbilical cord during complications of pregnancy. Biotech Histochem. 2018;93(3):198-210. doi:10.1080/10520295.2017.1410993
56.
WiddowsKKingdomJCPAnsariT. Double immuno-labelling of proliferating villous cytotrophoblasts in thick paraffin sections: integrating immuno-histochemistry and stereology in the human placenta. Placenta. 2009;30(8):735-738. doi:10.1016/j.placenta.2009.05.007
57.
KurtogluEAltunkaynakBZAydinI, et al. Role of vascular endothelial growth factor and placental growth factor expression on placenta structure in pre-eclamptic pregnancy. J Obstet Gynaecol Res. 2015;41(10):1533-1540. doi:10.1111/jog.12751
58.
McCarthyROrsiNMTreanorD, et al. Three-dimensional digital reconstruction of human placental villus architecture in normal and complicated pregnancies. Eur J Obstet Gynecol Reprod Biol. 2016;197:130-135. doi:10.1016/j.ejogrb.2015.12.015
59.
LongtineMSChenBOdiboAOZhongYNelsonDM. Caspase-mediated apoptosis of trophoblasts in term human placental villi is restricted to cytotrophoblasts and absent from the multinucleated syncytiotrophoblast. Reproduction. 2012;143(1):107-121. doi:10.1530/REP-11-0340
60.
Plitman MayoRCharnock-JonesDSBurtonGJOyenML. Three-dimensional modeling of human placental terminal villi. Placenta. 2016;43:54-60. doi:10.1016/j.placenta.2016.05.001
61.
MerzGSchwenkVShahR, et al. Three-dimensional rendering and analysis of immunolabeled, clarified human placental villous vascular networks. J Vis Exp. 2018;133:57099. doi:10.3791/57099
62.
JirkovskáMJanácekJKalábJKubínováL. Three-dimensional arrangement of the capillary bed and its relationship to microrheology in the terminal villi of normal term placenta. Placenta. 2008;29(10):892-897. doi:10.1016/j.placenta.2008.07.004
63.
MerzGSchwenkVShahRGNecaisePSalafiaCM. Clarification and 3-D visualization of immunolabeled human placenta villi. Placenta. 2017;53:36-39. doi:10.1016/j.placenta.2017.03.015
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
