121 research outputs found
Prediction of treatment response from retinal OCT in patients with exudative age-related macular degeneration
Age related macular degeneration is a major cause of blindness and visual impairment in older adults. Its exudative form, where fluids leak into the macula, is especially damaging. The standard treatment involves injections of anti-VEGF (vascular endothelial growth factor) agents into the eye, which prevent further vascular growth and leakage, and can restore vision. These intravitreal injections have a risk of devastating complications including blindness from infection and are expensive. Optimizing the interval between injections in a patient specific manner is of great interest, as the retinal response is partially patient specific. In this paper we propose a machine learning approach to predict the retinal response at the end of a standardized 12-week induction phase of the treatment. From a longitudinal series of optical coherence tomography (OCT) images, a number of quantitative measurements are extracted, describing the underlying retinal structure and pathology and its response to initial treatment. After initial feature selection, the selected set of features is used to predict the treatment response status at the end of the induction phase using the support vector machine classifier. On a population of 30 patients, leave-one-out cross-validation showed the classification success rate of 87% of predicting whether the subject will show a response to the treatment at the next visit. The proposed methodology is a promising step towards the much needed image-guided prediction of patient-specific treatment response
Optical Coherence Tomography Noise Reduction Using Anisotropic Local Bivariate Gaussian Mixture Prior in 3D Complex Wavelet Domain
In this paper, MMSE estimator is employed for noise-free 3D OCT data recovery in 3D complex wavelet domain. Since the proposed distribution for noise-free data plays a key role in the performance of MMSE estimator, a priori distribution for the pdf of noise-free 3D complex wavelet coefficients is proposed which is able to model the main statistical properties of wavelets. We model the coefficients with a mixture of two bivariate Gaussian pdfs with local parameters which are able to capture the heavy-tailed property and inter- and intrascale dependencies of coefficients. In addition, based on the special structure of OCT images, we use an anisotropic windowing procedure for local parameters estimation that results in visual quality improvement. On this base, several OCT despeckling algorithms are obtained based on using Gaussian/two-sided Rayleigh noise distribution and homomorphic/nonhomomorphic model. In order to evaluate the performance of the proposed algorithm, we use 156 selected ROIs from 650 Γ 512 Γ 128 OCT dataset in the presence of wet AMD pathology. Our simulations show that the best MMSE estimator using local bivariate mixture prior is for the nonhomomorphic model in the presence of Gaussian noise which results in an improvement of 7.8 Β± 1.7 in CNR
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4D Graph-Based Segmentation for Reproducible and Sensitive Choroid Quantification From Longitudinal OCT Scans
Purpose Longitudinal imaging is becoming more commonplace for studies of disease progression, response to treatment, and healthy maturation. Accurate and reproducible quantification methods are desirable to fully mine the wealth of data in such datasets. However, most current retinal OCT segmentation methods are cross-sectional and fail to leverage the inherent context present in longitudinal sequences of images. Methods: We propose a novel graph-based method for segmentation of multiple three-dimensional (3D) scans over time (termed 3D + time or 4D). The usefulness of this approach in retinal imaging is illustrated in the segmentation of the choroidal surfaces from longitudinal optical coherence tomography (OCT) scans. A total of 3219 synthetic (3070) and patient (149) OCT images were segmented for validation of our approach. Results: The results show that the proposed 4D segmentation method is significantly more reproducible (P < 0.001) than the 3D approach and is significantly more sensitive to temporal changes (P < 0.0001) achieved by the substantial increase of measurement robustness. Conclusions: This is the first automated 4D method for jointly quantifying choroidal thickness in longitudinal OCT studies. Our method is robust to image noise and produces more reproducible choroidal thickness measurements than a sequence of independent 3D segmentations, without sacrificing sensitivity to temporal changes
Normalization of Voltage-Sensitive Dye Signal with Functional Activity Measures
In general, signal amplitude in optical imaging is normalized using the
well-established ΞF/F method, where functional activity is divided by
the total fluorescent light flux. This measure is used both directly, as a
measure of population activity, and indirectly, to quantify spatial and
spatiotemporal activity patterns. Despite its ubiquitous use, the stability and
accuracy of this measure has not been validated for voltage-sensitive dye
imaging of mammalian neocortex in vivo. In this report, we find
that this normalization can introduce dynamic biases. In particular, the
ΞF/F is influenced by dye staining quality, and the ratio is also
unstable over the course of experiments. As methods to record and analyze
optical imaging signals become more precise, such biases can have an
increasingly pernicious impact on the accuracy of findings, especially in the
comparison of cytoarchitechtonic areas, in area-of-activation measurements, and
in plasticity or developmental experiments. These dynamic biases of the
ΞF/F method may, to an extent, be mitigated by a novel method of
normalization, ΞF/ΞFepileptiform. This normalization
uses as a reference the measured activity of epileptiform spikes elicited by
global disinhibition with bicuculline methiodide. Since this normalization is
based on a functional measure, i.e. the signal amplitude of
βhypersynchronizedβ bursts of activity in the cortical
network, it is less influenced by staining of non-functional elements. We
demonstrate that such a functional measure can better represent the amplitude of
population mass action, and discuss alternative functional normalizations based
on the amplitude of synchronized spontaneous sleep-like activity. These findings
demonstrate that the traditional ΞF/F normalization of voltage-sensitive
dye signals can introduce pernicious inaccuracies in the quantification of
neural population activity. They further suggest that normalization-independent
metrics such as waveform propagation patterns, oscillations in single detectors,
and phase relationships between detector pairs may better capture the biological
information which is obtained by high-sensitivity imaging
Imaging the Impact of Chemically Inducible Proteins on Cellular Dynamics In Vivo
The analysis of dynamic events in the tumor microenvironment during cancer progression is limited by the complexity of current in vivo imaging models. This is coupled with an inability to rapidly modulate and visualize protein activity in real time and to understand the consequence of these perturbations in vivo. We developed an intravital imaging approach that allows the rapid induction and subsequent depletion of target protein levels within human cancer xenografts while assessing the impact on cell behavior and morphology in real time. A conditionally stabilized fluorescent E-cadherin chimera was expressed in metastatic breast cancer cells, and the impact of E-cadherin induction and depletion was visualized using real-time confocal microscopy in a xenograft avian embryo model. We demonstrate the assessment of protein localization, cell morphology and migration in cells undergoing epithelial-mesenchymal and mesenchymal-epithelial transitions in breast tumors. This technique allows for precise control over protein activity in vivo while permitting the temporal analysis of dynamic biophysical parameters
Sch9 regulates ribosome biogenesis via Stb3, Dot6 and Tod6 and the histone deacetylase complex RPD3L
Three Repeat Isoforms of Tau Inhibit Assembly of Four Repeat Tau Filaments
Tauopathies are defined by assembly of the microtubule associated protein tau into filamentous tangles and classified by the predominant tau isoform within these aggregates. The major isoforms are determined by alternative mRNA splicing of exon 10 generating tau with three (3R) or four (4R) βΌ32 amino acid imperfect repeats in the microtubule binding domain. In normal adult brains there is an approximately equimolar ratio of 3R and 4R tau which is altered by several disease-causing mutations in the tau gene. We hypothesized that when 4R and 3R tau isoforms are not at equimolar ratios aggregation is favored. Here we provide evidence for the first time that the combination of 3R and 4R tau isoforms results in less in vitro heparin induced polymerization than with 4R preparations alone. This effect was independent of reducing conditions and the presence of alternatively spliced exons 2 and 3 N-terminal inserts. The addition of even small amounts of 3R to 4R tau assembly reactions significantly decreased 4R assembly. Together these findings suggest that co-expression of 3R and 4R tau isoforms reduce tau filament assembly and that 3R tau isoforms inhibit 4R tau assembly. Expression of equimolar amounts of 3R and 4R tau in adult humans may be necessary to maintain proper neuronal microtubule dynamics and to prevent abnormal tau filament assembly. Importantly, these findings indicate that disruption of the normal equimolar 3R to 4R ratio may be sufficient to drive tau aggregation and that restoration of the tau isoform balance may have important therapeutic implications in tauopathies
Defects in the Outer Limiting Membrane Are Associated with Rosette Development in the Nrlβ/β Retina
The neural retinal leucine zipper (Nrl) knockout mouse is a widely used model to study cone photoreceptor development, physiology, and molecular biology in the absence of rods. In the Nrlβ/β retina, rods are converted into functional cone-like cells. The Nrlβ/β retina is characterized by large undulations of the outer nuclear layer (ONL) commonly known as rosettes. Here we explore the mechanism of rosette development in the Nrlβ/β retina. We report that rosettes first appear at postnatal day (P)8, and that the structure of nascent rosettes is morphologically distinct from what is seen in the adult retina. The lumen of these nascent rosettes contains a population of aberrant cells protruding into the subretinal space that induce infolding of the ONL. Morphologically adult rosettes do not contain any cell bodies and are first detected at P15. The cells found in nascent rosettes are photoreceptors in origin but lack inner and outer segments. We show that the adherens junctions between photoreceptors and MΓΌller glia which comprise the retinal outer limiting membrane (OLM) are not uniformly formed in the Nrlβ/β retina and thus allow protrusion of a population of developing photoreceptors into the subretinal space where their maturation becomes delayed. These data suggest that the rosettes of the Nrlβ/β retina arise due to defects in the OLM and delayed maturation of a subset of photoreceptors, and that rods may play an important role in the proper formation of the OLM
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