title: Validation of automatic scanning of microscope slides in recovering rare cellular events: application for detection of fetal cells in maternal blood.
abstract: OBJECTIVE
  Detection of rare fetal cells (FCs) in the maternal circulation could be used for non-invasive prenatal diagnosis. Considering that FCs in maternal blood are present in extremely low frequency, manual scanning is cumbersome, time-consuming, and unsuitable for clinical applications. As an alternative, we optimized a custom-made classifier for automatic detection of FCs.
  
  
  METHODS
  Using MetaSystems' automated platform, we developed a robust detection algorithm and validated its efficiency on retrieval of rare XY cells in a pure population of XX cells. Slides were scanned for presence of predefined XY cells after fluorescence in situ hybridization (FISH) and primed in situ labeling (PRINS). Retrieval of FCs was also performed on samples from maternal blood.
  
  
  RESULTS
  The efficiency of detection of rare XY cells was 88% using FISH (117/133) in comparison with 78% (53/68) with PRINS. FC frequencies per 1 mL of maternal blood ranged from 3 to 6 FCs in normal pregnancies versus 13 to 21 FCs in Down syndrome pregnancies.
  
  
  CONCLUSIONS
  Automatic scanning was more efficient and consistent than manual scanning for detection of rare FCs and required considerably less operator time. Automatic scanning using FISH is more sensitive than that using PRINS. The study validates automatic scanning retrieval of FCs from maternal blood.
authors.affiliation: Division of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Emad
authors.forename: Eric F
authors.initials: EF
authors.lastname: Bouchard
authors.forename: Josée
authors.initials: J
authors.lastname: Lamoureux
authors.forename: Annie
authors.initials: A
authors.lastname: Ouellet
authors.forename: Aparajita
authors.initials: A
authors.lastname: Dutta
authors.forename: Uli
authors.initials: U
authors.lastname: Klingbeil
authors.forename: Régen
authors.initials: R
authors.lastname: Drouin
mesh_terms: D001773:Blood Cells / Q000166:cytology* / Q000473:pathology; D001330:Electronic Data Processing / Q000379:methods; D005260:Female; D005333:Fetus / Q000166:cytology*; D006403:Hematologic Tests / Q000379:methods; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping / Q000379:methods; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D020401:Primed In Situ Labeling; D012680:Sensitivity and Specificity