X-ray computed tomography (CT) reconstruction from a sparse number of views is a useful way to reduce either the radiation dose or the acquisition time, for example in fixed-gantry CT systems; however, this results in an ill-posed inverse problem whose solution is typically computationally demanding. Approximate message passing (AMP) techniques represent the state of the art for solving undersampling compressed sensing problems with random linear measurements, but there are still not clear solutions on how AMP should be modified and how it performs with real world problems. This paper investigates the question of whether we can employ an AMP framework for real sparse view CT imaging. The proposed algorithm for approximate inference in tomographic reconstruction incorporates a number of advances from within the AMP community, resulting in the denoising generalized approximate message passing CT algorithm (D-GAMP-CT). Specifically, this exploits the use of sophisticated image denoisers to regularize the reconstruction. While in order to reduce the probability of divergence the (Radon) system and the Poisson nonlinear noise model are treated separately, exploiting the existence of efficient preconditioners for the former and the generalized noise modeling in GAMP for the latter. Experiments with simulated and real CT baggage scans confirm that the performance of the proposed algorithm outperforms statistical CT optimization solvers.

This paper describes a new, physically interpretable, fully automatic algorithm for removal of tissue autofluorescence (AF) from fluorescence microscopy images, by non-negative matrix factorization. Measurement of signal intensities from the concentration of certain fluorescent reporter molecules at each location within a sample of biological tissue is confounded by fluorescence produced by the tissue itself (autofluorescence). Spectral mixing models use mixing coefficients to specify how much fluorescence from each source is present and unmixing algorithms separate the two fluorescent sources. Current spectral unmixing methods for AF removal often require a priori knowledge of mixing coefficients. Those which do not, such as principal component analysis, generate negative mixing coefficients that are not physically meaningful. Non-negative matrix factorization constrains mixing coefficients to be non-negative, and has been used for spectral unmixing, but not AF removal. This paper describes a novel non-negative matrix factorization algorithm which separates fluorescent images into true signal and AF components utilizing an estimate of the dark current. We also present a test-bed, based on fluorescent beads, to compare the performance of different AF removal algorithms. Our algorithm out-performed previous state of the art on validation images.

Quantifying expression levels of proteins with sub cellular resolution is critical to many applications ranging from biomarker discovery to treatment planning. In this paper, we present a fully automated method and a new metric that quantifies the expression of target proteins in immunohisto-chemically stained tissue microarray (TMA) samples. The proposed metric is superior to existing intensity or ratio-based methods. We compared performance with the majority decision of a group of 19 observers scoring estrogen receptor (ER) status, achieving a detection rate of 96% with 90% specificity. The presented methods will accelerate the processes of biomarker discovery and transitioning of biomarkers from research bench to clinical utility.

This paper presents a method to exploit rank statistics to improve fully automatic tracing of neurons from noisy digital confocal microscope images. Previously proposed exploratory tracing (vectorization) algorithms work by recursively following the neuronal topology, guided by responses of multiple directional correlation kernels. These algorithms were found to fail when the data was of lower quality (noisier, less contrast, weak signal, or more discontinuous structures). This type of data is commonly encountered in the study of neuronal growth on microfabricated surfaces. We show that by partitioning the correlation kernels in the tracing algorithm into multiple subkernels, and using the median of their responses as the guiding criterion improves the tracing precision from 41% to 89% for low-quality data, with a 5% improvement in recall. Improved handling was observed for artifacts such as discontinuities and/or hollowness of structures. The new algorithms require slightly higher amounts of computation, but are still acceptably fast, typically consuming less than 2 seconds on a personal computer (Pentium III, 500 MHz, 128 MB). They produce labeling for all somas present in the field, and a graph-theoretic representation of all dendritic/axonal structures that can be edited. Topological and size measurements such as area, length, and tortuosity are derived readily. The efficiency, accuracy, and fully-automated nature of the proposed method makes it attractive for large-scale applications such as high-throughput assays in the pharmaceutical industry, and study of neuron growth on nano/micro-fabricated structures. A careful quantitative validation of the proposed algorithms is provided against manually derived tracing, using a performance measure that combines the precision and recall metrics.

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.

An algorithm for constructing image mosaics from multiple, uncalibrated, weak-perspective views of the human retina is presented and analyzed. It builds on an algorithm for registering pairs of retinal images using a noninvertible, 12-parameter, quadratic image transformation model and hierarchical, robust estimation. The major innovation presented is a linear, feature-based, noniterative method for jointly estimating consistent transformations of all images onto the mosaic "anchor image." Constraints for this estimation are derived from pairwise registration both directly with the anchor image and indirectly between pairs of nonanchor images. An incremental, graph-based technique constructs the set of registered image pairs used in the solution. The estimation technique allows images that do not overlap the anchor frame to be successfully mosaiced, a valuable capability for mosaicing images of the retinal periphery. Experimental analysis on data sets from 16 eyes shows the average overall median transformation error in final mosaic to be 0.76 pixels. The technique is simpler, more accurate, and offers broader coverage than previously published methods.

Methods are presented for increasing the coverage and accuracy of image mosaics constructed from multiple, uncalibrated, weak-perspective views of the human retina. Extending our previous algorithm for registering pairs of images using a non-invertible, 12-parameter, quadratic image transformation model and a hierarchical, robust estimation technique, two important innovations are presented. The first is a linear, non-iterative method for jointly estimating the transformations of all images onto the mosaic. This employs constraints derived from pairwise matching between the non-mosaic image frames. It allows the transformations to be estimated for images that do not overlap the mosaic anchor frame, and results in mutually consistent transformations for all images. This means the mosaics can cover a much broader area of the retinal surface, even though the transformation model is not closed under composition. This capability is particularly valuable for mosaicing the retinal periphery in the context of diseases such as AIDS/CMV. The second innovation is a method to improve the accuracy of the pairwise matches as well as the joint estimation by refining the feature locations and by adding new features based on the transformation estimates themselves. For matching image frames of size 1024/spl times/1024, this cuts the registration error from the range of 1 to 3 pixels to about 0.55 pixels. The overall transformation error in final mosaic construction is 0.80 pixels based on experiments over a large set of eyes.

This paper describes computer vision algorithms to assist in retinal laser surgery, which is widely used to treat leading blindness causing conditions but only has a 50% success rate, mostly due to a lack of spatial mapping and reckoning capabilities in current instruments. The novel technique described here automatically constructs a composite (mosaic) image of the retina from a sequence of incomplete views. This mosaic will be useful to ophthalmologists for both diagnosis and surgery. The new technique goes beyond published methods in both the medical and computer vision literatures because it is fully automated, models the patient-dependent curvature of the retina, handles large interframe motions, and does not require calibration. At the heart of the technique is a 12-parameter image transformation model derived by modeling the retina as a quadratic surface and assuming a weak perspective camera, and rigid motion. Estimating the parameters of this transformation model requires robustness to unmatchable image features and mismatches between features caused by large interframe motions. The described estimation technique is a hierarchy of models and methods: the initial match set is pruned based on a 0th order transformation estimated using a similarity-weighted histogram; a 1st order affine transformation is estimated using the reduced match set and least-median of squares; and the final, 2nd order 12-parameter transformation is estimated using an M-estimator initialized from the 1st order results. Initial experimental results show the method to be robust and accurate in accounting for the unknown retinal curvature in a fully automatic manner while preserving image details.

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.