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Optical coherence tomography angiography (OCTA) is a novel noninvasive imaging modality for visualization of retinal blood flow in the human retina. Using specific OCTA imaging biomarkers for the identification of pathologies, automated image segmentations of the blood vessels can improve subsequent analysis and diagnosis. We present a novel segmentation method for vessel density identification based on frequency representations of the image, in particular, using so-called Gabor filter banks. The algorithm is evaluated qualitatively and quantitatively on an OCTA image in-house data set from $10$ eyes acquired by a Cirrus HD-OCT device. Qualitatively, the segmentation outcomes received very good visual evaluation feedback by experts. Quantitatively, we compared the resulting vessel density values with automated in-built values provided by the device. The results underline the visual evaluation. For the evaluation of the FAZ identification substep, manual annotations of $2$ expert graders were used, showing that our results coincide well in visual and quantitative manners. Lastly, we suggest the computation of adaptive local vessel density maps that allow straightforward analysis of retinal blood flow in a local manner.

Segmenting anatomical structures such as the photoreceptor layer in retinal optical coherence tomography (OCT) scans is challenging in pathological scenarios. Supervised deep learning models trained with standard loss functions are usually able to characterize only the most common disease appeareance from a training set, resulting in suboptimal performance and poor generalization when dealing with unseen lesions. In this paper we propose to overcome this limitation by means of an augmented target loss function framework. We introduce a novel amplified-target loss that explicitly penalizes errors within the central area of the input images, based on the observation that most of the challenging disease appeareance is usually located in this area. We experimentally validated our approach using a data set with OCT scans of patients with macular diseases. We observe increased performance compared to the models that use only the standard losses. Our proposed loss function strongly supports the segmentation model to better distinguish photoreceptors in highly pathological scenarios., Comment: Accepted for publication at MICCAI-OMIA 2019

Optical coherence tomography (OCT) has become the most important imaging modality in ophthalmology. A substantial amount of research has recently been devoted to the development of machine learning (ML) models for the identification and quantification of pathological features in OCT images. Among the several sources of variability the ML models have to deal with, a major factor is the acquisition device, which can limit the ML model's generalizability. In this paper, we propose to reduce the image variability across different OCT devices (Spectralis and Cirrus) by using CycleGAN, an unsupervised unpaired image transformation algorithm. The usefulness of this approach is evaluated in the setting of retinal fluid segmentation, namely intraretinal cystoid fluid (IRC) and subretinal fluid (SRF). First, we train a segmentation model on images acquired with a source OCT device. Then we evaluate the model on (1) source, (2) target and (3) transformed versions of the target OCT images. The presented transformation strategy shows an F1 score of 0.4 (0.51) for IRC (SRF) segmentations. Compared with traditional transformation approaches, this means an F1 score gain of 0.2 (0.12)., Comment: * Contributed equally (order was defined by flipping a coin) --------------- Accepted for publication in the "IEEE International Symposium on Biomedical Imaging (ISBI) 2019"

In this paper, we introduce a Bayesian deep learning based model for segmenting the photoreceptor layer in pathological OCT scans. Our architecture provides accurate segmentations of the photoreceptor layer and produces pixel-wise epistemic uncertainty maps that highlight potential areas of pathologies or segmentation errors. We empirically evaluated this approach in two sets of pathological OCT scans of patients with age-related macular degeneration, retinal vein oclussion and diabetic macular edema, improving the performance of the baseline U-Net both in terms of the Dice index and the area under the precision/recall curve. We also observed that the uncertainty estimates were inversely correlated with the model performance, underlying its utility for highlighting areas where manual inspection/correction might be needed., Comment: Accepted for publication at IEEE International Symposium on Biomedical Imaging (ISBI) 2019

The use of orthogonal projections on high-dimensional input and target data in learning frameworks is studied. First, we investigate the relations between two standard objectives in dimension reduction, preservation of variance and of pairwise relative distances. Investigations of their asymptotic correlation as well as numerical experiments show that a projection does usually not satisfy both objectives at once. In a standard classification problem we determine projections on the input data that balance the objectives and compare subsequent results. Next, we extend our application of orthogonal projections to deep learning tasks and introduce a general framework of augmented target loss functions. These loss functions integrate additional information via transformations and projections of the target data. In two supervised learning problems, clinical image segmentation and music information classification, the application of our proposed augmented target loss functions increase the accuracy.

The identification and quantification of markers in medical images is critical for diagnosis, prognosis, and disease management. Supervised machine learning enables the detection and exploitation of findings that are known a priori after annotation of training examples by experts. However, supervision does not scale well, due to the amount of necessary training examples, and the limitation of the marker vocabulary to known entities. In this proof-of-concept study, we propose unsupervised identification of anomalies as candidates for markers in retinal Optical Coherence Tomography (OCT) imaging data without a constraint to a priori definitions. We identify and categorize marker candidates occurring frequently in the data, and demonstrate that these markers show predictive value in the task of detecting disease. A careful qualitative analysis of the identified data driven markers reveals how their quantifiable occurrence aligns with our current understanding of disease course, in early- and late age-related macular degeneration (AMD) patients. A multi-scale deep denoising autoencoder is trained on healthy images, and a one-class support vector machine identifies anomalies in new data. Clustering in the anomalies identifies stable categories. Using these markers to classify healthy-, early AMD- and late AMD cases yields an accuracy of 81.40%. In a second binary classification experiment on a publicly available data set (healthy vs. intermediate AMD) the model achieves an area under the ROC curve of 0.944., Comment: Accepted for publication in IEEE Transactions on Medical Imaging, 2018

PURPOSE: Establishing and obtaining consistent quantitative indices of retinal thickness from a variety of clinically used Spectral-Domain Optical Coherence Tomography scanners. DESIGN: Retinal images from five Spectral-Domain Optical Coherence Tomography scanners were used to determine total retinal thickness with scanner-specific correction factors establishing consistency of thickness measurement across devices. PARTICIPANTS: 55 Fovea-centered Spectral-Domain Optical Coherence Tomography volumes from eleven subjects were analyzed, obtained from Cirrus HD-OCT, RS-3000, Heidelberg Spectralis, RTVue and Topcon2000, seven subjects with retinal diseases and four normal controls. METHOD: The Iowa Reference Algorithm measured total retinal thickness. Nonlinear model of total retinal thickness measurement comparisons was derived and used for device-specific comparisons. Bland-Altman plots and pairwise predictive equations yielded pairwise scanner-specific differences. Mendel test determined whether measurement biases were constant for each scanner pair. RESULTS: Mendel test revealed that all pairwise scanner differences of total retinal thickness were constant across the cohort (p=0.992). Individual measurements can thus be bias-corrected and the Iowa Reference Algorithm serve as a scanner-agnostic independent standard of total retinal thickness across the five tested SD-OCT scanners. CONCLUSIONS: Combination of the Iowa Reference Algorithm with scanner-specific bias correction yields cross-scanner consistency of total retinal thickness measurements, facilitating scanning-device independent quantitative assessment of total retinal thickness, longitudinal follow-up quantification without requiring patients to be imaged on the same scanner model, and allowing for multi-center studies with heterogeneous device utilization when using the Iowa Reference Algorithm., Comment: 14 pages, 5 tables, 5 figures

The identification and quantification of markers in medical images is critical for diagnosis, prognosis and management of patients in clinical practice. Supervised- or weakly supervised training enables the detection of findings that are known a priori. It does not scale well, and a priori definition limits the vocabulary of markers to known entities reducing the accuracy of diagnosis and prognosis. Here, we propose the identification of anomalies in large-scale medical imaging data using healthy examples as a reference. We detect and categorize candidates for anomaly findings untypical for the observed data. A deep convolutional autoencoder is trained on healthy retinal images. The learned model generates a new feature representation, and the distribution of healthy retinal patches is estimated by a one-class support vector machine. Results demonstrate that we can identify pathologic regions in images without using expert annotations. A subsequent clustering categorizes findings into clinically meaningful classes. In addition the learned features outperform standard embedding approaches in a classification task., Comment: Extended Abstract, Accepted for NIPS 2016 Workshop "Machine Learning for Health"