Drusen detection in retro-mode imaging by a scanning laser ophthalmoscope

Purpose: The Nidek F-10 is a scanning laser ophthalmoscope that is capable of a novel fundus imaging technique, so-called ‘retro-mode’ imaging. The standard method of imaging drusen in age-related macular degeneration (AMD) is by fundus photography. The aim of the study was to assess drusen quantification using retro-mode imaging. Methods: Stereoscopic fundus photographs and retro-mode images were captured in 31 eyes of 20 patients with varying stages of AMD. Two experienced masked retinal graders independently assessed images for the number and size of drusen, using purpose-designed software. Drusen were further assessed in a subset of eight patients using optical coherence tomography (OCT) imaging. Results: Drusen observed by fundus photography (mean 33.5) were significantly fewer in number than subretinal deposits seen in retro-mode (mean 81.6; p < 0.001). The predominant deposit diameter was on average 5 µm smaller in retro-mode imaging than in fundus photography (p = 0.004). Agreement between graders for both types of imaging was substantial for number of deposits (weighted ? = 0.69) and moderate for size of deposits (weighted ? = 0.42). Retro-mode deposits corresponded to drusen on OCT imaging in all eight patients. Conclusion: The subretinal deposits detected by retro-mode imaging were consistent with the appearance of drusen on OCT imaging; however, a larger longitudinal study would be required to confirm this finding. Retro-mode imaging detected significantly more deposits than conventional colour fundus photography. Retro-mode imaging provides a rapid non-invasive technique, useful in monitoring subtle changes and progression of AMD, which may be useful in monitoring the response of drusen to future therapeutic interventions.

Retinal drusen detection using the Nidek F-10 SLO in retro-mode

Presentaton Purpose:We conducted a small study to assess the novel, retro - mode imaging technique of the NIDEK F-10 scanning laser ophthalmoscope, for detecting and quantifying retinal drusen. Methods:Fundus photographs of 4 eyes of 2 patients taken in retro-mode on the Nidek F-10 SLO were graded independently by 6,experienced, masked fundus graders for the presence of retinal drusen , and compared to stereo colour fundus photographs taken with a Topcon TRC-50DX camera. Results:The mean number of retinal drusen detected in retro mode was 142.96+/- 60.8, range 63-265, and on colour fundus photography mean of 66.6+/-32.6, range 26-177. All observers independently detected approximately twice as many drusen on retro-mode than colour fundus photography (p<0.0001, Student’s paired t-test) . The statistical significance of interobserver variation in drusen detection was p=0.07 on colour fundus photography , and p=0.02 on retro mode ( ANOVA) . Conclusions:The retro-mode of the F-10 camera uses infrared laser and an aperture with a modified central stop, with the aperture deviated laterally from the confocal light path. This forms a pseudo -3D image which is a new means of detecting abnomalites in the deeper retinal layers. Retro-mode imaging of retinal drusen using the F-10 Nidek SLO is a highly sensitive technique for detecting and quantifying retinal drusen , and detected twice as many drusen than colour fundus photography. This small pilot study suggests that this novel type of imaging may have a role in the future detection and analysis of retinal drusen, a field that is likely to become increasingly important in future AMD prevention studies.

OCT evaluation of visible and subthreshold retinal photocoagulation using 532nm laser

Presentation Purpose:We conducted a study to determine if the spectral domain optical coherence tomography (SD-OCT) could be used as a tool to assess effective delivery of threshold and subthreshold laser burns created using 532nm green wavelength laser. Methods:10 patients planned for panretinal photocoagulation (PRP) for proliferative diabetic retinopathy were included in this study. Before initiating the full PRP, a row of moderately white laser burns as used for conventional PRP was created using 532 nm laser set at threshold power for 0.1 second with 300 microns spot size. Further rows of laser burns were created by altering the duration and power settings on the laser device. The area of the retina irradiated with laser was imaged using the Topcon SD-OCT within a few minutes of laser treatment. Results:Laser burns created using threshold power were seen on the OCT scan in all cases as a homogenous diffuse increase in reflectivity extending across the full thickness of retina (Fig 1). Retinal burns created by lowering the duration of laser pulse to 0.01s were barely visible ophthalmoscopically but were clearly detectable on the OCT scan as a localised, well-defined area of increased tissue reflectivity (Fig 2). Conclusions:OCT is a useful to tool to assess the delivery of laser burns created using the 532 nm green laser. Burns of a subthreshold intensity that may not be visible ophthalmoscopically result in retinal changes that are clearly detectable on OCT imaging. Further studies would be needed to assess the clinical effectiveness of subthreshold laser treatment for retinal vascular diseases using the 532 nm green laser.

Imaging of the human fundus in the clinical setting:past present and future

The human fundus is a complex structure that can be easily visualized and the world of ophthalmology is going through a golden era of new and exciting fundus imaging techniques; recent advances in technology have allowed a significant improvement in the imaging modalities clinicians have available to formulate a diagnostic and treatment plan for the patient, but there is constant on-going work to improve current technology and create new ideas in order to gather as much information as possible from the human fundus. In this article we shall summarize the imaging techniques available in the standard medical retina clinic (i.e. not limited to the research lab) and delineate the technologies that we believe will have a significant impact on the way clinicians will assess retinal and choroidal pathology in the not too distant future.

Optical imaging of retina in response to grating stimuli in cats

We examined the intrinsic signals in response to grating stimuli in order to determine whether the light-evoked intrinsic signals of the retina are due to changes in the photoreceptor activities induced by the image projected on to the retina or are due to neural activities of the inner retina. The retinas of the left eye of 12 cats under general anesthesia were examined by a functional imaging fundus camera. Near infrared light was used to monitor the reflectance changes (RCs) of the retina. Vertical grating were used to stimulate the retina at 4 Hz. The spatial frequencies of the gratings were 0.05, 0.11, 0.22, 0.43, 0.86, 1.73, and 3.46 cycles/degree (cpd). Ten images were averaged and used to analyze the RCs to obtain the peak value (PV) of a two dimensional fast Fourier transfer of the RCs. The wavefront aberrations (WA) were measured with a compact wavefront aberrometer and the spatial modulation transfer function (MTF) of the eye was calculated. The retinal reflectance image had a grating pattern. The PV of the spatial sensitivity curve was highest at low spatial frequencies (0.05 and 0.11 cpd), and the sensitivity decreased steeply with an increase in the spatial frequency. RCs were not detectable at 3.46 cpd. The MTF decreased gradually with increases in the spatial frequencies and was 0.68 at 3.46 cpd. The reflectance pattern of the retinal intrinsic signal elicited by grating stimuli of different spatial frequencies was different from that of the MTF. This suggests that the intrinsic signal represents not only the response of the photoreceptors but also other neuronal or vascular changes in the retina.

The impact of flash intensity on retinal vessel oxygen saturation measurements using dual wavelength oximetry

PURPOSE. To establish the optimal flash settings for retinal vessel oxygen saturation parameters using dual-wavelength imaging in a multiethnic group. METHODS. Twelve healthy young subjects (mean age 32 years [SD 7]; three Mediterranean, two South Asian, and seven Caucasian individuals) underwent retinal vessel oxygen saturation measurements using dual-wavelength oximetry, noncontact tonometry, and manual sphygmomanometry. In order to evaluate the impact of flash intensity, we obtained three images (fundus camera angle 30°, ONH centered) per flash setting. Flash settings of the fundus camera were increased in steps of 2 (initial setting of 6 and the final of 22), which reflect logarithmic increasing intensities from 13.5 to 214 Watt seconds (Ws). RESULTS. Flash settings below 27 Ws were too low to obtain saturation measurements, whereas flash settings of more than 214 Ws resulted in overexposed images. Retinal arteriolar and venular oxygen saturation was comparable at flash settings of 27 to 76 Ws (arterioles' range: 85%-92%; venules' range: 45%-53%). Higher flash settings lead to increased saturation measurements in both retinal arterioles (up to 110%) and venules (up to 92%), with a more pronounced increase in venules. CONCLUSIONS. Flash intensity has a significant impact on retinal vessel oxygen saturation measurements using dual-wavelength retinal oximetry. High flash intensities lead to supranormal oxygen saturation measurements with a magnified effect in retinal venules compared with arteries. In addition to even retinal illumination, the correct flash setting is of paramount importance for clinical acquisition of images in retinal oximetry. We recommend flash settings between 27 to 76 Ws. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

In vivo microvascular oximetry using multispectral imaging

This thesis describes the application of multispectral imaging to several novel oximetry applications. Chapter 1 motivates optical microvascular oximetry, outlines oxygen transport in the body, describes the theory of oximetry, and describes the challenges associated with in vivo oximetry, in particular imaging through tissue. Chapter 2 reviews various imaging techniques for quantitative in vivo oximetry of the microvasculature, including multispectral and hyperspectral imaging, photoacoustic imaging, optical coherence tomography, and laser speckle techniques. Chapter 3 describes a two-wavelength oximetry study of two microvascular beds in the anterior segment of the eye: the bulbar conjunctival and episcleral microvasculature. This study reveals previously unseen oxygen diffusion from ambient air into the bulbar conjunctival microvasculature, altering the oxygen saturation of the bulbar conjunctiva. The response of the bulbar conjunctival and episcleral microvascular beds to acute mild hypoxia is quantified and the rate at which oxygen diffuses into bulbar conjunctival vessels is measured. Chapter 4 describes the development and application of a highly novel non-invasive retinal angiography technique: Oximetric Ratio Contrast Angiography (ORCA). ORCA requires only multispectral imaging and a small perturbation of blood oxygen saturation to produce angiographic sequences. A pilot study of ORCA in human subjects was conducted. This study demonstrates that ORCA can produce angiographic sequences with features such as sequential vessel filling and laminar flow. The application and challenges of ORCA are discussed, with emphasis on comparison with other angiography techniques, such as fluorescein angiography. Chapter 5 describes the development of a multispectral microscope for oximetry in the spinal cord dorsal vein of rats. Measurements of blood oxygen saturation are made in the dorsal vein of both healthy rats, and in rats with the Experimental autoimmune encephalomyelitis (EAE) disease model of multiple sclerosis. The venous blood oxygen saturation of EAE disease model rats was found to be significantly lower than that of healthy controls, indicating increased oxygen uptake from blood in the EAE disease model of multiple sclerosis. Chapter 6 describes the development of video-rate red eye oximetry; a technique which could enable stand-off oximetry of the blood-supply of the eye with high temporal resolution. The various challenges associated with video-rate red eye oximetry are investigated and their influence quantified. The eventual aim of this research is to track circulating deoxygenation perturbations as they arrive in both eyes, which could provide a screening method for carotid artery stenosis, which is major risk-factor for stroke. However, due to time constraints, it was not possible to thoroughly investigate if video-rate red eye can detect such perturbations. Directions and recommendations for future research are outlined.

Advancing Bag-of-visual-words Representations For Lesion Classification In Retinal Images.

Diabetic Retinopathy (DR) is a complication of diabetes that can lead to blindness if not readily discovered. Automated screening algorithms have the potential to improve identification of patients who need further medical attention. However, the identification of lesions must be accurate to be useful for clinical application. The bag-of-visual-words (BoVW) algorithm employs a maximum-margin classifier in a flexible framework that is able to detect the most common DR-related lesions such as microaneurysms, cotton-wool spots and hard exudates. BoVW allows to bypass the need for pre- and post-processing of the retinographic images, as well as the need of specific ad hoc techniques for identification of each type of lesion. An extensive evaluation of the BoVW model, using three large retinograph datasets (DR1, DR2 and Messidor) with different resolution and collected by different healthcare personnel, was performed. The results demonstrate that the BoVW classification approach can identify different lesions within an image without having to utilize different algorithms for each lesion reducing processing time and providing a more flexible diagnostic system. Our BoVW scheme is based on sparse low-level feature detection with a Speeded-Up Robust Features (SURF) local descriptor, and mid-level features based on semi-soft coding with max pooling. The best BoVW representation for retinal image classification was an area under the receiver operating characteristic curve (AUC-ROC) of 97.8% (exudates) and 93.5% (red lesions), applying a cross-dataset validation protocol. To assess the accuracy for detecting cases that require referral within one year, the sparse extraction technique associated with semi-soft coding and max pooling obtained an AUC of 94.2 ± 2.0%, outperforming current methods. Those results indicate that, for retinal image classification tasks in clinical practice, BoVW is equal and, in some instances, surpasses results obtained using dense detection (widely believed to be the best choice in many vision problems) for the low-level descriptors.

Study Of The Homogeneity Of Drug Loaded In Polymeric Films Using Near-infrared Chemical Imaging And Split-plot Design.

Split-plot design (SPD) and near-infrared chemical imaging were used to study the homogeneity of the drug paracetamol loaded in films and prepared from mixtures of the biocompatible polymers hydroxypropyl methylcellulose, polyvinylpyrrolidone, and polyethyleneglycol. The study was split into two parts: a partial least-squares (PLS) model was developed for a pixel-to-pixel quantification of the drug loaded into films. Afterwards, a SPD was developed to study the influence of the polymeric composition of films and the two process conditions related to their preparation (percentage of the drug in the formulations and curing temperature) on the homogeneity of the drug dispersed in the polymeric matrix. Chemical images of each formulation of the SPD were obtained by pixel-to-pixel predictions of the drug using the PLS model of the first part, and macropixel analyses were performed for each image to obtain the y-responses (homogeneity parameter). The design was modeled using PLS regression, allowing only the most relevant factors to remain in the final model. The interpretation of the SPD was enhanced by utilizing the orthogonal PLS algorithm, where the y-orthogonal variations in the design were separated from the y-correlated variation.

Feasibility And Reproducibility Of Diffusion-weighted Magnetic Resonance Imaging Of The Fetal Brain In Twin-twin Transfusion Syndrome.

The aim of this study is to test the feasibility and reproducibility of diffusion-weighted magnetic resonance imaging (DW-MRI) evaluations of the fetal brains in cases of twin-twin transfusion syndrome (TTTS). From May 2011 to June 2012, 24 patients with severe TTTS underwent MRI scans for evaluation of the fetal brains. Datasets were analyzed offline on axial DW images and apparent diffusion coefficient (ADC) maps by two radiologists. The subjective evaluation was described as the absence or presence of water diffusion restriction. The objective evaluation was performed by the placement of 20-mm(2) circular regions of interest on the DW image and ADC maps. Subjective interobserver agreement was assessed by the kappa correlation coefficient. Objective intraobserver and interobserver agreements were assessed by proportionate Bland-Altman tests. Seventy-four DW-MRI scans were performed. Sixty of them (81.1%) were considered to be of good quality. Agreement between the radiologists was 100% for the absence or presence of diffusion restriction of water. For both intraobserver and interobserver agreement of ADC measurements, proportionate Bland-Altman tests showed average percentage differences of less than 1.5% and 95% CI of less than 18% for all sites evaluated. Our data demonstrate that DW-MRI evaluation of the fetal brain in TTTS is feasible and reproducible.

Effects Of Misalignments In The Retinal Nerve Fiber Layer Thickness Measurements With Spectral Domain Optical Coherence Tomography.

Purpose. To investigate misalignments (MAs) on retinal nerve fiber layer thickness (RNFLT) measurements obtained with Cirrus(©) SD-OCT. Methods. This was a retrospective, observational, cross-sectional study. Twenty-seven healthy and 29 glaucomatous eyes of 56 individuals with one normal exam and another showing MA were included. MAs were defined as an improper alignment of vertical vessels in the en face image. MAs were classified in complete MA (CMA) and partial MA (PMA), according to their site: 1 (superior, outside the measurement ring (MR)), 2 (superior, within MR), 3 (inferior, within MR), and 4 (inferior, outside MR). We compared RNFLT measurements of aligned versus misaligned exams in all 4 sectors, in the superior area (sectors 1 + 2), inferior area (sectors 3 + 4), and within the measurement ring (sectors 2 + 3). Results. RNFLT measurements at 12 clock-hour of eyes with MAs in the superior area (sectors 1 + 2) were significantly lower than those obtained in the same eyes without MAs (P = 0.043). No significant difference was found in other areas (sectors 1 + 2 + 3 + 4, sectors 3 + 4, and sectors 2 + 3). Conclusion. SD-OCT scans with superior MAs may present lower superior RNFLT measurements compared to aligned exams.

Intraventricular Mass Lesions At Magnetic Resonance Imaging: Iconographic Essay - Part 1.

The present essay is illustrated with magnetic resonance images obtained at the authors' institution over the past 15 years and discusses the main imaging findings of intraventricular tumor-like lesions (ependymoma, pilocytic astrocytoma, central neurocytoma, ganglioglioma, choroid plexus papilloma, primitive neuroectodermal tumors, meningioma, epidermoid tumor). Such lesions represent a subgroup of intracranial lesions with unique characteristics and some image patterns that may facilitate the differential diagnosis.

Intraventricular Mass Lesions At Magnetic Resonance Imaging: Iconographic Essay - Part 2.

The present essay is illustrated with magnetic resonance images obtained at the authors' institution over the past 15 years and discusses the main imaging findings of intraventricular tumor-like lesions (colloid cyst, oligodendroglioma, astroblastoma, lipoma, cavernoma) and of inflammatory/infectious lesions (neurocysticercosis and an atypical presentation of neurohistoplasmosis). Such lesions represent a subgroup of intracranial lesions with unique characteristics and some imaging patterns that may facilitate the differential diagnosis.

Two-dimensional Ultrasound And Ultrasound Elastography Imaging Of Trigger Points In Women With Myofascial Pain Syndrome Treated By Acupuncture And Electroacupuncture: A Double-blinded Randomized Controlled Pilot Study.

Chronic pain has been often associated with myofascial pain syndrome (MPS), which is determined by myofascial trigger points (MTrP). New features have been tested for MTrP diagnosis. The aim of this study was to evaluate two-dimensional ultrasonography (2D US) and ultrasound elastography (UE) images and elastograms of upper trapezius MTrP during electroacupuncture (EA) and acupuncture (AC) treatment. 24 women participated, aged between 20 and 40 years (M ± SD = 27.33 ± 5.05) with a body mass index ranging from 18.03 to 27.59 kg/m2 (22.59 ± 3.11), a regular menstrual cycle, at least one active MTrP at both right (RTPz) and left trapezius (LTPz) and local or referred pain for up to six months. Subjects were randomized into EA and AC treatment groups and the control sham AC (SHAM) group. Intensity of pain was assessed by visual analogue scale; MTrP mean area and strain ratio (SR) by 2D US and UE. A significant decrease of intensity in general, RTPz, and LTPz pain was observed in the EA group (p = 0.027; p < 0.001; p = 0.005, respectively) and in general pain in the AC group (p < 0.001). Decreased MTrP area in RTPz and LTPz were observed in AC (p < 0.001) and EA groups (RTPz, p = 0.003; LTPz, p = 0.005). Post-treatment SR in RTPz and LTPz was lower than pre-treatment in both treatment groups. 2D US and UE effectively characterized MTrP and surrounding tissue, pointing to the possibility of objective confirmation of subjective EA and AC treatment effects.

Detection Of Explosives On The Surface Of Banknotes By Raman Hyperspectral Imaging And Independent Component Analysis.

The aim of this study was to develop a methodology using Raman hyperspectral imaging and chemometric methods for identification of pre- and post-blast explosive residues on banknote surfaces. The explosives studied were of military, commercial and propellant uses. After the acquisition of the hyperspectral imaging, independent component analysis (ICA) was applied to extract the pure spectra and the distribution of the corresponding image constituents. The performance of the methodology was evaluated by the explained variance and the lack of fit of the models, by comparing the ICA recovered spectra with the reference spectra using correlation coefficients and by the presence of rotational ambiguity in the ICA solutions. The methodology was applied to forensic samples to solve an automated teller machine explosion case. Independent component analysis proved to be a suitable method of resolving curves, achieving equivalent performance with the multivariate curve resolution with alternating least squares (MCR-ALS) method. At low concentrations, MCR-ALS presents some limitations, as it did not provide the correct solution. The detection limit of the methodology presented in this study was 50μgcm(-2).