Pathologist pupil dilation reflects experience level and difficulty in diagnosing medical images.

: Digital whole slide imaging allows pathologists to view slides on a computer screen instead of under a microscope. Digital viewing allows for real-time monitoring of pathologists' search behavior and neurophysiological responses during the diagnostic process. One particular neurophysiological measure, pupil diameter, could provide a basis for evaluating clinical competence during training or developing tools that support the diagnostic process. Prior research shows that pupil diameter is sensitive to cognitive load and arousal, and it switches between exploration and exploitation of a visual image. Different categories of lesions in pathology pose different levels of challenge, as indicated by diagnostic disagreement among pathologists. If pupil diameter is sensitive to the perceived difficulty in diagnosing biopsies, eye-tracking could potentially be used to identify biopsies that may benefit from a second opinion. : We measured case onset baseline-corrected (phasic) and uncorrected (tonic) pupil diameter in 90 pathologists who each viewed and diagnosed 14 digital breast biopsy cases that cover the diagnostic spectrum from benign to invasive breast cancer. Pupil data were extracted from the beginning of viewing and interpreting of each individual case. After removing 122 trials ( ) with poor eye-tracking quality, 1138 trials remained. We used multiple linear regression with robust standard error estimates to account for dependent observations within pathologists. : We found a positive association between the magnitude of phasic dilation and subject-centered difficulty ratings and between the magnitude of tonic dilation and untransformed difficulty ratings. When controlling for case diagnostic category, only the tonic-difficulty relationship persisted. : Results suggest that tonic pupil dilation may indicate overall arousal differences between pathologists as they interpret biopsy cases and could signal a need for additional training, experience, or automated decision aids. Phasic dilation is sensitive to characteristics of biopsies that tend to elicit higher difficulty ratings and could indicate a need for a second opinion.