Predicting Thioflavin Fluorescence Of Retinal Amyloid Deposits Associated With Alzheimer'S Disease From Their Polarimetric Properties

Purpose: To use machine learning in those with brain amyloid to predict thioflavin fluorescence (indicative of amyloid) of retinal deposits from their interactions with polarized light.Methods: We imaged 933 retinal deposits in 28 subjects with post mortem evidence of brain amyloid using thioflavin fluorescence and polarization sensitive microscopy. Means and standard deviations of 14 polarimetric properties were input to machine learning algorithms. Two oversampling strategies were applied to overcome data imbalance. Three machine learning algorithms: linear discriminant analysis, supporting vector machine, and random forest (RF) were trained to predict thioflavin positive deposits. For each method; accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve were computed.Results: For the polarimetric positive deposits, using 1 oversampling method, RF had the highest area under the receiver operating characteristic curve (0.986), which was not different from that with the second oversampling method. RF had 95% accuracy, 94% sensitivity, and 97% specificity. After including deposits with no polarimetric signals, polarimetry correctly predicted 93% of thioflavin positive deposits. Linear retardance and linear anisotropy were the dominant polarimetric properties in RF with 1 oversampling method, and no polarimetric properties were dominant in the second method.Conclusions: Thioflavin positivity of retinal amyloid deposits can be predicted from their images in polarized light. Polarimetry is a promising dye-free method of detecting amyloid deposits in ex vivo retinal tissue. Further testing is required for translation to live eye imaging.Translational Relevance: This dye-free method distinguishes retinal amyloid deposits, a promising biomarker of Alzheimer's disease, in human retinas imaged with polarimetry.