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Register a new userRetinal Microvasculature as Biomarker for Diabetes and Cardiovascular Diseases
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Purpose: To demonstrate that retinal microvasculature per se is a reliable biomarker for Diabetic Retinopathy (DR) and, by extension, cardiovascular diseases. Methods: Deep Learning Convolutional Neural Networks (CNN) applied to color fundus images for semantic segmentation of the blood vessels and severity classification on both vascular and full images. Vessel reconstruction through harmonic descriptors is also used as a smoothing and de-noising tool. The mathematical background of the theory is also outlined. Results: For diabetic patients, at least 93.8% of DR No-Refer vs. Refer classification can be related to vasculature defects. As for the Non-Sight Threatening vs. Sight Threatening case, the ratio is as high as 96.7%. Conclusion: In the case of DR, most of the disease biomarkers are related topologically to the vasculature. Translational Relevance: Experiments conducted on eye blood vasculature reconstruction as a biomarker shows a strong correlation between vasculature shape and later stages of DR.
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The aortic vessel tree is composed of the aorta and its branching arteries, and plays a key role in supplying the whole body with blood. Aortic diseases, like aneurysms or dissections, can lead to an aortic rupture, whose treatment with open surgery is highly risky. Therefore, patients commonly undergo drug treatment under constant monitoring, which requires regular inspections of the vessels through imaging. The standard imaging modality for diagnosis and monitoring is computed tomography (CT), which can provide a detailed picture of the aorta and its branching vessels if combined with a contrast agent, resulting in a CT angiography (CTA). Optimally, the whole aortic vessel tree geometry from consecutive CTAs, are overlaid and compared. This allows to not only detect changes in the aorta, but also more peripheral vessel tree changes, caused by the primary pathology or newly developed. When performed manually, this reconstruction requires slice by slice contouring, which could easily take a whole day for a single aortic vessel tree and, hence, is not feasible in clinical practice. Automatic or semi-automatic vessel tree segmentation algorithms, on the other hand, can complete this task in a fraction of the manual execution time and run in parallel to the clinical routine of the clinicians. In this paper, we systematically review computing techniques for the automatic and semi-automatic segmentation of the aortic vessel tree. The review concludes with an in-depth discussion on how close these state-of-the-art approaches are to an application in clinical practice and how active this research field is, taking into account the number of publications, datasets and challenges.
Purpose: Optical Coherence Tomography Angiography (OCT-A) permits visualization of the changes to the retinal circulation due to diabetic retinopathy (DR), a microvascular complication of diabetes. We demonstrate accurate segmentation of the vascular morphology for the superficial capillary plexus and deep vascular complex (SCP and DVC) using a convolutional neural network (CNN) for quantitative analysis. Methods: Retinal OCT-A with a 6x6mm field of view (FOV) were acquired using a Zeiss PlexElite. Multiple-volume acquisition and averaging enhanced the vessel network contrast used for training the CNN. We used transfer learning from a CNN trained on 76 images from smaller FOVs of the SCP acquired using different OCT systems. Quantitative analysis of perfusion was performed on the automated vessel segmentations in representative patients with DR. Results: The automated segmentations of the OCT-A images maintained the hierarchical branching and lobular morphologies of the SCP and DVC, respectively. The network segmented the SCP with an accuracy of 0.8599, and a Dice index of 0.8618. For the DVC, the accuracy was 0.7986, and the Dice index was 0.8139. The inter-rater comparisons for the SCP had an accuracy and Dice index of 0.8300 and 0.6700, respectively, and 0.6874 and 0.7416 for the DVC. Conclusions: Transfer learning reduces the amount of manually-annotated images required, while producing high quality automatic segmentations of the SCP and DVC. Using high quality training data preserves the characteristic appearance of the capillary networks in each layer. Translational Relevance: Accurate retinal microvasculature segmentation with the CNN results in improved perfusion analysis in diabetic retinopathy.
Though deep learning has shown successful performance in classifying the label and severity stage of certain diseases, most of them give few explanations on how to make predictions. Inspired by Kochs Postulates, the foundation in evidence-based medicine (EBM) to identify the pathogen, we propose to exploit the interpretability of deep learning application in medical diagnosis. By determining and isolating the neuron activation patterns on which diabetic retinopathy (DR) detector relies to make decisions, we demonstrate the direct relation between the isolated neuron activation and lesions for a pathological explanation. To be specific, we first define novel pathological descriptors using activated neurons of the DR detector to encode both spatial and appearance information of lesions. Then, to visualize the symptom encoded in the descriptor, we propose Patho-GAN, a new network to synthesize medically plausible retinal images. By manipulating these descriptors, we could even arbitrarily control the position, quantity, and categories of generated lesions. We also show that our synthesized images carry the symptoms directly related to diabetic retinopathy diagnosis. Our generated images are both qualitatively and quantitatively superior to the ones by previous methods. Besides, compared to existing methods that take hours to generate an image, our second level speed endows the potential to be an effective solution for data augmentation.
Diabetes-related retinal conditions can be detected by examining the posterior of the eye. By contrast, examining the anterior of the eye can reveal conditions affecting the front of the eye, such as changes to the eyelids, cornea, or crystalline lens. In this work, we studied whether external photographs of the front of the eye can reveal insights into both diabetic retinal diseases and blood glucose control. We developed a deep learning system (DLS) using external eye photographs of 145,832 patients with diabetes from 301 diabetic retinopathy (DR) screening sites in one US state, and evaluated the DLS on three validation sets containing images from 198 sites in 18 other US states. In validation set A (n=27,415 patients, all undilated), the DLS detected poor blood glucose control (HbA1c > 9%) with an area under receiver operating characteristic curve (AUC) of 70.2; moderate-or-worse DR with an AUC of 75.3; diabetic macular edema with an AUC of 78.0; and vision-threatening DR with an AUC of 79.4. For all 4 prediction tasks, the DLSs AUC was higher (p<0.001) than using available self-reported baseline characteristics (age, sex, race/ethnicity, years with diabetes). In terms of positive predictive value, the predicted top 5% of patients had a 67% chance of having HbA1c > 9%, and a 20% chance of having vision threatening diabetic retinopathy. The results generalized to dilated pupils (validation set B, 5,058 patients) and to a different screening service (validation set C, 10,402 patients). Our results indicate that external eye photographs contain information useful for healthcare providers managing patients with diabetes, and may help prioritize patients for in-person screening. Further work is needed to validate these findings on different devices and patient populations (those without diabetes) to evaluate its utility for remote diagnosis and management.
Chest radiography (CXR) is the most widely-used thoracic clinical imaging modality and is crucial for guiding the management of cardiothoracic conditions. The detection of specific CXR findings has been the main focus of several artificial intelligence (AI) systems. However, the wide range of possible CXR abnormalities makes it impractical to build specific systems to detect every possible condition. In this work, we developed and evaluated an AI system to classify CXRs as normal or abnormal. For development, we used a de-identified dataset of 248,445 patients from a multi-city hospital network in India. To assess generalizability, we evaluated our system using 6 international datasets from India, China, and the United States. Of these datasets, 4 focused on diseases that the AI was not trained to detect: 2 datasets with tuberculosis and 2 datasets with coronavirus disease 2019. Our results suggest that the AI system generalizes to new patient populations and abnormalities. In a simulated workflow where the AI system prioritized abnormal cases, the turnaround time for abnormal cases reduced by 7-28%. These results represent an important step towards evaluating whether AI can be safely used to flag cases in a general setting where previously unseen abnormalities exist.
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