A novel automated approach of multi-modality retinal image registration and fusion

Biomedical image registration and fusion are usually scene dependent, and require intensive computational effort. A novel automated approach of feature-based control point detection and area-based registration and fusion of retinal images has been successfully designed and developed. The new algorithm, which is reliable and time-efficient, has an automatic adaptation from frame to frame with few tunable threshold parameters. The reference and the to-be-registered images are from two different modalities, i.e. angiogram grayscale images and fundus color images. The relative study of retinal images enhances the information on the fundus image by superimposing information contained in the angiogram image. Through the thesis research, two new contributions have been made to the biomedical image registration and fusion area. The first contribution is the automatic control point detection at the global direction change pixels using adaptive exploratory algorithm. Shape similarity criteria are employed to match the control points. The second contribution is the heuristic optimization algorithm that maximizes Mutual-Pixel-Count (MPC) objective function. The initially selected control points are adjusted during the optimization at the sub-pixel level. A global maxima equivalent result is achieved by calculating MPC local maxima with an efficient computation cost. The iteration stops either when MPC reaches the maximum value, or when the maximum allowable loop count is reached. To our knowledge, it is the first time that the MPC concept has been introduced into biomedical image fusion area as the measurement criteria for fusion accuracy. The fusion image is generated based on the current control point coordinates when the iteration stops. The comparative study of the presented automatic registration and fusion scheme against Centerline Control Point Detection Algorithm, Genetic Algorithm, RMSE objective function, and other existing data fusion approaches has shown the advantage of the new approach in terms of accuracy, efficiency, and novelty

Enhancing retinal images by nonlinear registration

Being able to image the human retina in high resolution opens a new era in many important fields, such as pharmacological research for retinal diseases, researches in human cognition, nervous system, metabolism and blood stream, to name a few. In this paper, we propose to share the knowledge acquired in the fields of optics and imaging in solar astrophysics in order to improve the retinal imaging at very high spatial resolution in the perspective to perform a medical diagnosis. The main purpose would be to assist health care practitioners by enhancing retinal images and detect abnormal features. We apply a nonlinear registration method using local correlation tracking to increase the field of view and follow structure evolutions using correlation techniques borrowed from solar astronomy technique expertise. Another purpose is to define the tracer of movements after analyzing local correlations to follow the proper motions of an image from one moment to another, such as changes in optical flows that would be of high interest in a medical diagnosis.Comment: 21 pages, 7 figures, submitted to Optics Communication

Tram-Line filtering for retinal vessel segmentation

The segmentation of the vascular network from retinal fundal images is a fundamental step in the analysis of the retina, and may be used for a number of purposes, including diagnosis of diabetic retinopathy. However, due to the variability of retinal images segmentation is difficult, particularly with images of diseased retina which include significant distractors. This paper introduces a non-linear filter for vascular segmentation, which is particularly robust against such distractors. We demonstrate results on the publicly-available STARE dataset, superior to Stare’s performance, with 57.2% of the vascular network (by length) successfully located, with 97.2% positive predictive value measured by vessel length, compared with 57% and 92.2% for Stare. The filter is also simple and computationally efficient

\u3cem\u3eIn vivo\u3c/em\u3e Imaging of Human Cone Photoreceptor Inner Segments

Purpose. An often overlooked prerequisite to cone photoreceptor gene therapy development is residual photoreceptor structure that can be rescued. While advances in adaptive optics (AO) retinal imaging have recently enabled direct visualization of individual cone and rod photoreceptors in the living human retina, these techniques largely detect strongly directionally-backscattered (waveguided) light from normal intact photoreceptors. This represents a major limitation in using existing AO imaging to quantify structure of remnant cones in degenerating retina. Methods. Photoreceptor inner segment structure was assessed with a novel AO scanning light ophthalmoscopy (AOSLO) differential phase technique, that we termed nonconfocal split-detector, in two healthy subjects and four subjects with achromatopsia. Ex vivo preparations of five healthy donor eyes were analyzed for comparison of inner segment diameter to that measured in vivo with split-detector AOSLO. Results. Nonconfocal split-detector AOSLO reveals the photoreceptor inner segment with or without the presence of a waveguiding outer segment. The diameter of inner segments measured in vivo is in good agreement with histology. A substantial number of foveal and parafoveal cone photoreceptors with apparently intact inner segments were identified in patients with the inherited disease achromatopsia. Conclusions. The application of nonconfocal split-detector to emerging human gene therapy trials will improve the potential of therapeutic success, by identifying patients with sufficient retained photoreceptor structure to benefit the most from intervention. Additionally, split-detector imaging may be useful for studies of other retinal degenerations such as AMD, retinitis pigmentosa, and choroideremia where the outer segment is lost before the remainder of the photoreceptor cell

Repeatability of \u3cem\u3eIn Vivo\u3c/em\u3e Parafoveal Cone Density and Spacing Measurements

Purpose. To assess the repeatability and measurement error associated with cone density and nearest neighbor distance (NND) estimates in images of the parafoveal cone mosaic obtained with an adaptive optics scanning light ophthalmoscope (AOSLO).Methods. Twenty-one participants with no known ocular pathology were recruited. Four retinal locations, approximately 0.65[degrees] eccentricity from the center of fixation, were imaged 10 times in randomized order with an AOSLO. Cone coordinates in each image were identified using an automated algorithm (with or without manual correction) from which cone density and NND were calculated. Owing to naturally occurring fixational instability, the 10 images recorded from a given location did not overlap entirely. We thus analyzed each image set both before and after alignment.Results. Automated estimates of cone density on the unaligned image sets showed a coefficient of repeatability of 11,769 cones/mm2 (17.1%). The primary reason for this variability appears to be fixational instability, as aligning the 10 images to include the exact same retinal area results in an improved repeatability of 4358 cones/mm2 (6.4%) using completely automated cone identification software. Repeatability improved further by manually identifying cones missed by the automated algorithm, with a coefficient of repeatability of 1967 cones/mm2 (2.7%). NND showed improved repeatability and was generally insensitive to the undersampling by the automated algorithm.Conclusions. As our data were collected in a young, healthy population, this likely represents a best-case estimate for corresponding measurements in patients with retinal disease. Similar studies need to be carried out on other imaging systems (including those using different imaging modalities, wavefront correction technology, and/or image analysis software), as repeatability would be expected to be highly sensitive to initial image quality and the performance of cone identification algorithms. Separate studies addressing intersession repeatability and interobserver reliability are also needed

In vivo imaging reveals transient microglia recruitment and functional recovery of photoreceptor signaling after injury.

Microglia respond to damage and microenvironmental changes within the central nervous system by morphologically transforming and migrating to the lesion, but the real-time behavior of populations of these resident immune cells and the neurons they support have seldom been observed simultaneously. Here, we have used in vivo high-resolution optical coherence tomography (OCT) and scanning laser ophthalmoscopy with and without adaptive optics to quantify the 3D distribution and dynamics of microglia in the living retina before and after local damage to photoreceptors. Following photoreceptor injury, microglia migrated both laterally and vertically through the retina over many hours, forming a tight cluster within the area of visible damage that resolved over 2 wk. In vivo OCT optophysiological assessment revealed that the photoreceptors occupying the damaged region lost all light-driven signaling during the period of microglia recruitment. Remarkably, photoreceptors recovered function to near-baseline levels after the microglia had departed the injury locus. These results demonstrate the spatiotemporal dynamics of microglia engagement and restoration of neuronal function during tissue remodeling and highlight the need for mechanistic studies that consider the temporal and structural dynamics of neuron-microglia interactions in vivo

Assessing Retinal Structure In Complete Congenital Stationary Night Blindness and Oguchi Disease

Purpose To examine retinal structure and changes in photoreceptor intensity after dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease. Design Prospective, observational case series. Methods We recruited 3 patients with complete congenital stationary night blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by mutations in GRK1, and 1 normal control. Retinal thickness was measured from optical coherence tomography images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the patients after a period of dark adaptation and examined layer reflectivity on optical coherence tomography in a patient with Oguchi disease under light- and dark-adapted conditions. Results Retinal thickness was reduced in the parafoveal region in patients with GRM6 mutations as a result of decreased thickness of the inner retinal layers. All patients had normal photoreceptor density at all locations analyzed. On removal from dark adaptation, the intensity of the rods (but not cones) in the patients with Oguchi disease gradually and significantly increased. In 1 Oguchi disease patient, the outer segment layer contrast on optical coherence tomography was 4-fold higher under dark-adapted versus light-adapted conditions. Conclusions The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. Our finding that rods, but not cones, change intensity after dark adaptation suggests that fundus changes in Oguchi disease are the result of changes within the rods as opposed to changes at a different retinal locus