Ali Can

Over the past decade, dramatic increases in computational power and improvement in image analysis algorithms have allowed the development of powerful computer-assisted analytical approaches to radiological data. With the recent advent of whole slide digital scanners, tissue histopathology slides can now be digitized and stored in digital image form. Consequently, digitized tissue histopathology has now become amenable to the application of computerized image analysis and machine learning techniques. Analogous to the role of computer-assisted diagnosis (CAD) algorithms in medical imaging to complement the opinion of a radiologist, CAD algorithms have begun to be developed for disease detection, diagnosis, and prognosis prediction to complement the opinion of the pathologist. In this paper, we review the recent state of the art CAD technology for digitized histopathology. This paper also briefly describes the development and application of novel image analysis technology for a few specific histopathology related problems being pursued in the United States and Europe.

Algorithms are presented for rapid, automatic, robust, adaptive, and accurate tracing of retinal vasculature and analysis of intersections and crossovers. This method improves upon prior work in several ways: 1) automatic adaptation from frame to frame without manual initialization/adjustment, with few tunable parameters; 2) robust operation on image sequences exhibiting natural variability, poor and varying imaging conditions, including over/under-exposure, low contrast, and artifacts such as glare; 3) does not require the vasculature to be connected, so it can handle partial views; and 4) operation is efficient enough for use on unspecialized hardware, and amenable to deadline-driven computing, being able to produce a rapidly and monotonically improving sequence of usable partial results. Increased computation can be traded for superior tracing performance. Its efficiency comes from direct processing on gray-level data without any preprocessing, and from processing only a minimally necessary fraction of pixels in an exploratory manner, avoiding low-level image-wide operations such as thresholding, edge detection, and morphological processing. These properties make the algorithm suited to real-time, on-line (live) processing and is being applied to computer-assisted laser retinal surgery.

This paper describes a robust hierarchical algorithm for fully-automatic registration of a pair of images of the curved human retina photographed by a fundus microscope. Accurate registration is essential for mosaic synthesis, change detection, and design of computer-aided instrumentation. Central to the algorithm is a 12-parameter interimage transformation derived by modeling the retina as a rigid quadratic surface with unknown parameters. The parameters are estimated by matching vascular landmarks by recursively tracing the blood vessel structure. The parameter estimation technique, which could be generalized to other applications, is a hierarchy of models and methods, making the algorithm robust to unmatchable image features and mismatches between features caused by large interframe motions. Experiments involving 3,000 image pairs from 16 different healthy eyes were performed. Final registration errors less than a pixel are routinely achieved. The speed, accuracy, and ability to handle small overlaps compare favorably with retinal image registration techniques published in the literature.

A fully automated approach is presented for robust detection and classification of changes in longitudinal time-series of color retinal fundus images of diabetic retinopathy. The method is robust to: 1) spatial variations in illumination resulting from instrument limitations and changes both within, and between patient visits; 2) imaging artifacts such as dust particles; 3) outliers in the training data; 4) segmentation and alignment errors. Robustness to illumination variation is achieved by a novel iterative algorithm to estimate the reflectance of the retina exploiting automatically extracted segmentations of the retinal vasculature, optic disk, fovea, and pathologies. Robustness to dust artifacts is achieved by exploiting their spectral characteristics, enabling application to film-based, as well as digital imaging systems. False changes from alignment errors are minimized by subpixel accuracy registration using a 12-parameter transformation that accounts for unknown retinal curvature and camera parameters. Bayesian detection and classification algorithms are used to generate a color-coded output that is readily inspected. A multiobserver validation on 43 image pairs from 22 eyes involving nonproliferative and proliferative diabetic retinopathies, showed a 97% change detection rate, a 3% miss rate, and a 10% false alarm rate. The performance in correctly classifying the changes was 99.3%. A self-consistency metric, and an error factor were developed to measure performance over more than two periods. The average self consistency was 94% and the error factor was 0.06%. Although this study focuses on diabetic changes, the proposed techniques have broader applicability in ophthalmology.