Computer-aided diagnosis tools for Retinopathy of Prematurity (ROP) base their decisions on handcrafted retinal features that highly correlate with expert diagnoses, such as arterial and venous curvature, tortuosity and dilation. Deep learning leads to performance comparable to those of expert physicians, albeit not ensuring that the same clinical factors are learned in the deep representations. In this paper, we investigate the relationship between the handcrafted and the deep learning features in the context of ROP diagnosis. Average statistics on the handcrafted features for each input image were expressed as retinal concept measures. Three disease severity grades, i.e. normal, pre-plus and plus, were classified by a deep convolutional neural network. Regression Concept Vectors (RCV) were computed in the network feature space for each retinal concept measure. Relevant concept measures were identified by bidirectional relevance scores for the normal and plus classes. Results show that the curvature, diameter and tortuosity of the segmented vessels are indeed relevant to the classification. Among the potential applications of this method, the analysis of borderline cases between the classes and of network faults, in particular, can be used to improve the performance.
Several digital reference objects (DROs) for DCE-MRI have been created to test the accuracy of pharmacokinetic modeling software under a variety of different noise conditions. However, there are few DROs that mimic the anatomical distribution of voxels found in real data, and similarly few DROs that are based on both malignant and normal tissue. We propose a series of DROs for modeling K<sub>trans</sub> and V<sub>e</sub> derived from a publically-available RIDER DCEMRI dataset of 19 patients with gliomas. For each patient’s DCE-MRI data, we generate K<sub>trans</sub> and V<sub>e</sub> parameter maps using an algorithm validated on the QIBA Tofts model phantoms. These parameter maps are denoised, and then used to generate noiseless time-intensity curves for each of the original voxels. This is accomplished by reversing the Tofts model to generate concentration-times curves from K<sub>trans</sub> and V<sub>e</sub> inputs, and subsequently converting those curves into intensity values by normalizing to each patient’s average pre-bolus image intensity. The result is a noiseless DRO in the shape of the original patient data with known ground-truth K<sub>trans</sub> and V<sub>e</sub> values. We make this dataset publically available for download for all 19 patients of the original RIDER dataset.
Retinopathy of prematurity (ROP) is a disease that affects premature infants, where abnormal growth of the retinal blood vessels can lead to blindness unless treated accordingly. Infants considered at risk of severe ROP are monitored for symptoms of plus disease, characterized by arterial tortuosity and venous dilation at the posterior pole, with a standard photographic definition. Disagreement among ROP experts in diagnosing plus disease has driven the development of computer-based methods that classify images based on hand-crafted features extracted from the vasculature. However, most of these approaches are semi-automated, which are time-consuming and subject to variability. In contrast, deep learning is a fully automated approach that has shown great promise in a wide variety of domains, including medical genetics, informatics and imaging. Convolutional neural networks (CNNs) are deep networks which learn rich representations of disease features that are highly robust to variations in acquisition and image quality. In this study, we utilized a U-Net architecture to perform vessel segmentation and then a GoogLeNet to perform disease classification. The classifier was trained on 3,000 retinal images and validated on an independent test set of patients with different observed progressions and treatments. We show that our fully automated algorithm can be used to monitor the progression of plus disease over multiple patient visits with results that are consistent with the experts’ consensus diagnosis. Future work will aim to further validate the method on larger cohorts of patients to assess its applicability within the clinic as a treatment monitoring tool.
In the last five years, advances in processing power and computational efficiency in graphical processing units have catalyzed dozens of deep neural network segmentation algorithms for a variety of target tissues and malignancies. However, few of these algorithms preconfigure any biological context of their chosen segmentation tissues, instead relying on the neural network’s optimizer to develop such associations de novo. We present a novel method for applying deep neural networks to the problem of glioma tissue segmentation that takes into account the structured nature of gliomas – edematous tissue surrounding mutually-exclusive regions of enhancing and non-enhancing tumor. We trained separate deep neural networks with a 3D U-Net architecture in a tree structure to create segmentations for edema, non-enhancing tumor, and enhancing tumor regions. Specifically, training was configured such that the whole tumor region including edema was predicted first, and its output segmentation was fed as input into separate models to predict enhancing and non-enhancing tumor. We trained our model on publicly available pre- and post-contrast T1 images, T2 images, and FLAIR images, and validated our trained model on patient data from an ongoing clinical trial.