Integrated analysis of vascular and nonvascular changes from color retinal fundus image sequences.

Algorithms are presented for integrated analysis of both vascular and nonvascular changes observed in longitudinal time-series of color retinal fundus images, extending our prior work. A Bayesian model selection algorithm that combines color change information, and image understanding systems outputs in a novel manner is used to analyze vascular changes such as increase/decrease in width, and disappearance/appearance of vessels, as well as nonvascular changes such as appearance/disappearance of different kinds of lesions. The overall system is robust to false changes due to inter-image and intra-image nonuniform illumination, imaging artifacts such as dust particles in the optical path, alignment errors and outliers in the training-data. An expert observer validated the algorithms on 54 regions selected from 34 image pairs. The regions were selected such that they represented diverse types of vascular changes of interest, as well as no-change regions. The algorithm achieved a sensitivity of 82% and a 9% false positive rate for vascular changes. For the nonvascular changes, 97% sensitivity and a 10% false positive rate are achieved. The combined system is intended for diverse applications including computer-assisted retinal screening, image-reading centers, quantitative monitoring of disease onset and progression, assessment of treatment efficacy, and scoring clinical trials.

Robust detection and classification of longitudinal changes in color retinal fundus images for monitoring diabetic retinopathy.

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.

Predictive scheduling algorithms for real-time feature extraction and spatial referencing: application to retinal image sequences.

Real-time spatial referencing is an important alternative to tracking for designing spatially aware ophthalmic instrumentation for procedures such as laser photocoagulation and perimetry. It requires independent, fast registration of each image frame from a digital video stream (1024 x 1024 pixels) to a spatial map of the retina. Recently, we have introduced a spatial referencing algorithm that works in three primary steps: 1) tracing the retinal vasculature to extract image feature (landmarks); 2) invariant indexing to generate hypothesized landmark correspondences and initial transformations; and 3) alignment and verification steps to robustly estimate a 12-parameter quadratic spatial transformation between the image frame and the map. The goal of this paper is to introduce techniques to minimize the amount of computation for successful spatial referencing. The fundamental driving idea is to make feature extraction subservient to registration and, therefore, only produce the information needed for verified, accurate transformations. To this end, the image is analyzed along one-dimensional, vertical and horizontal grid lines to produce a regular sampling of the vasculature, needed for step 3) and to initiate step 1). Tracing of the vascular is then prioritized hierarchically to quickly extract landmarks and groups (constellations) of landmarks for indexing. Finally, the tracing and spatial referencing computations are integrated so that landmark constellations found by tracing are tested immediately. The resulting implementation is an order-of-magnitude faster with the same success rate. The average total computation time is 31.2 ms per image on a 2.2-GHz Pentium Xeon processor.

Robust model-based vasculature detection in noisy biomedical images.

This paper presents a set of algorithms for robust detection of vasculature in noisy retinal video images. Three methods are studied for effective handling of outliers. The first method is based on Huber's censored likelihood ratio test. The second is based on the use of a alpha-trimmed test statistic. The third is based on robust model selection algorithms. All of these algorithms rely on a mathematical model for the vasculature that accounts for the expected variations in intensity/texture profile, width, orientation, scale, and imaging noise. These unknown parameters are estimated implicitly within a robust detection and estimation framework. The proposed algorithms are also useful as nonlinear vessel enhancement filters. The proposed algorithms were evaluated over carefully constructed phantom images, where the ground truth is known a priori, as well as clinically recorded images for which the ground truth was manually compiled. A comparative evaluation of the proposed approaches is presented. Collectively, these methods outperformed prior approaches based on Chaudhuri et al. (1989) matched filtering, as well as the verification methods used by prior exploratory tracing algorithms, such as the work of Can et aL (1999). The Huber censored likelihood test yielded the best overall improvement, with a 145.7% improvement over the exploratory tracing algorithm, and a 43.7% improvement in detection rates over the matched filter.

Model-based method for improving the accuracy and repeatability of estimating vascular bifurcations and crossovers from retinal fundus images.

A model-based algorithm, termed exclusion region and position refinement (ERPR), is presented for improving the accuracy and repeatability of estimating the locations where vascular structures branch and cross over, in the context of human retinal images. The goal is two fold. First, accurate morphometry of branching and crossover points (landmarks) in neuronal/vascular structure is important to several areas of biology and medicine. Second, these points are valuable as landmarks for image registration, so improved accuracy and repeatability in estimating their locations and signatures leads to more reliable image registration for applications such as change detection and mosaicing. The ERPR algorithm is shown to reduce the median location error from 2.04 pixels down to 1.1 pixels, while improving the median spread (a measure of repeatability) from 2.09 pixels down to 1.05 pixels. Errors in estimating vessel orientations were similarly reduced from 7.2 degrees down to 3.8 degrees.

Automated retinal image analysis over the internet.

Retinal clinicians and researchers make extensive use of images, and the current emphasis is on digital imaging of the retinal fundus. The goal of this paper is to introduce a system, known as retinal image vessel extraction and registration system, which provides the community of retinal clinicians, researchers, and study directors an integrated suite of advanced digital retinal image analysis tools over the Internet. The capabilities include vasculature tracing and morphometry, joint (simultaneous) montaging of multiple retinal fields, cross-modality registration (color/red-free fundus photographs and fluorescein angiograms), and generation of flicker animations for visualization of changes from longitudinal image sequences. Each capability has been carefully validated in our previous research work. The integrated Internet-based system can enable significant advances in retina-related clinical diagnosis, visualization of the complete fundus at full resolution from multiple low-angle views, analysis of longitudinal changes, research on the retinal vasculature, and objective, quantitative computer-assisted scoring of clinical trials imagery. It could pave the way for future screening services from optometry facilities.