title: Novel fluorescein angiography-based computer-aided algorithm for assessment of retinal vessel permeability.
abstract: OBJECTIVE
  To present a novel method for quantitative assessment of retinal vessel permeability using a fluorescein angiography-based computer algorithm.
  
  
  METHODS
  Twenty-one subjects (13 with diabetic retinopathy, 8 healthy volunteers) underwent fluorescein angiography (FA). Image pre-processing included removal of non-retinal and noisy images and registration to achieve spatial and temporal pixel-based analysis. Permeability was assessed for each pixel by computing intensity kinetics normalized to arterial values. A linear curve was fitted and the slope value was assigned, color-coded and displayed. The initial FA studies and the computed permeability maps were interpreted in a masked and randomized manner by three experienced ophthalmologists for statistical validation of diagnosis accuracy and efficacy.
  
  
  RESULTS
  Permeability maps were successfully generated for all subjects. For healthy volunteers permeability values showed a normal distribution with a comparable range between subjects. Based on the mean cumulative histogram for the healthy population a threshold (99.5%) for pathological permeability was determined. Clear differences were found between patients and healthy subjects in the number and spatial distribution of pixels with pathological vascular leakage. The computed maps improved the discrimination between patients and healthy subjects, achieved sensitivity and specificity of 0.974 and 0.833 respectively, and significantly improved the consensus among raters for the localization of pathological regions.
  
  
  CONCLUSIONS
  The new algorithm allows quantification of retinal vessel permeability and provides objective, more sensitive and accurate evaluation than the present subjective clinical diagnosis. Future studies with a larger patients' cohort and different retinal pathologies are awaited to further validate this new approach and its role in diagnosis and treatment follow-up. Successful evaluation of vasculature permeability may be used for the early diagnosis of brain microvascular pathology and potentially predict associated neurological sequelae. Finally, the algorithm could be implemented for intraoperative evaluation of micovascular integrity in other organs or during animal experiments.
authors.affiliation: Department of Physiology and Neurobiology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Serlin
authors.forename: Geva
authors.initials: G
authors.lastname: Tal
authors.forename: Yoash
authors.initials: Y
authors.lastname: Chassidim
authors.forename: Yisrael
authors.initials: Y
authors.lastname: Parmet
authors.forename: Oren
authors.initials: O
authors.lastname: Tomkins
authors.forename: Boris
authors.initials: B
authors.lastname: Knyazer
authors.forename: Alon
authors.initials: A
authors.lastname: Friedman
authors.forename: Jaime
authors.initials: J
authors.lastname: Levy
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D002138:Calibration; D002199:Capillary Permeability; D016022:Case-Control Studies; D003930:Diabetic Retinopathy / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005451:Fluorescein Angiography / Q000379:methods*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D012160:Retina / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology*; D012680:Sensitivity and Specificity