LaTiM: Longitudinal representation learning in continuous-time models to predict disease progression

This work proposes a novel framework for analyzing disease progression using time-aware neural ordinary differential equations (NODE). We introduce a "time-aware head" in a framework trained through self-supervised learning (SSL) to leverage temporal information in latent space for data augmentation. This approach effectively integrates NODEs with SSL, offering significant performance improvements compared to traditional methods that lack explicit temporal integration. We demonstrate the effectiveness of our strategy for diabetic retinopathy progression prediction using the OPHDIAT database. Compared to the baseline, all NODE architectures achieve statistically significant improvements in area under the ROC curve (AUC) and Kappa metrics, highlighting the efficacy of pre-training with SSL-inspired approaches. Additionally, our framework promotes stable training for NODEs, a commonly encountered challenge in time-aware modeling.

L-MAE: Longitudinal masked auto-encoder with time and severity-aware encoding for diabetic retinopathy progression prediction

Pre-training strategies based on self-supervised learning (SSL) have proven to be effective pretext tasks for many downstream tasks in computer vision. Due to the significant disparity between medical and natural images, the application of typical SSL is not straightforward in medical imaging. Additionally, those pretext tasks often lack context, which is critical for computer-aided clinical decision support. In this paper, we developed a longitudinal masked auto-encoder (MAE) based on the well-known Transformer-based MAE. In particular, we explored the importance of time-aware position embedding as well as disease progression-aware masking. Taking into account the time between examinations instead of just scheduling them offers the benefit of capturing temporal changes and trends. The masking strategy, for its part, evolves during follow-up to better capture pathological changes, ensuring a more accurate assessment of disease progression. Using OPHDIAT, a large follow-up screening dataset targeting diabetic retinopathy (DR), we evaluated the pre-trained weights on a longitudinal task, which is to predict the severity label of the next visit within 3 years based on the past time series examinations. Our results demonstrated the relevancy of both time-aware position embedding and masking strategies based on disease progression knowledge. Compared to popular baseline models and standard longitudinal Transformers, these simple yet effective extensions significantly enhance the predictive ability of deep classification models.

DISCOVER: 2-D Multiview Summarization of Optical Coherence Tomography Angiography for Automatic Diabetic Retinopathy Diagnosis

Diabetic Retinopathy (DR), an ocular complication of diabetes, is a leading cause of blindness worldwide. Traditionally, DR is monitored using Color Fundus Photography (CFP), a widespread 2-D imaging modality. However, DR classifications based on CFP have poor predictive power, resulting in suboptimal DR management. Optical Coherence Tomography Angiography (OCTA) is a recent 3-D imaging modality offering enhanced structural and functional information (blood flow) with a wider field of view. This paper investigates automatic DR severity assessment using 3-D OCTA. A straightforward solution to this task is a 3-D neural network classifier. However, 3-D architectures have numerous parameters and typically require many training samples. A lighter solution consists in using 2-D neural network classifiers processing 2-D en-face (or frontal) projections and/or 2-D cross-sectional slices. Such an approach mimics the way ophthalmologists analyze OCTA acquisitions: 1) en-face flow maps are often used to detect avascular zones and neovascularization, and 2) cross-sectional slices are commonly analyzed to detect macular edemas, for instance. However, arbitrary data reduction or selection might result in information loss. Two complementary strategies are thus proposed to optimally summarize OCTA volumes with 2-D images: 1) a parametric en-face projection optimized through deep learning and 2) a cross-sectional slice selection process controlled through gradient-based attribution. The full summarization and DR classification pipeline is trained from end to end. The automatic 2-D summary can be displayed in a viewer or printed in a report to support the decision. We show that the proposed 2-D summarization and classification pipeline outperforms direct 3-D classification with the advantage of improved interpretability.

LMT: Longitudinal Mixing Training, a Framework to Predict Disease Progression from a Single Image

Longitudinal imaging is able to capture both static anatomical structures and dynamic changes in disease progression toward earlier and better patient-specific pathology management. However, conventional approaches rarely take advantage of longitudinal information for detection and prediction purposes, especially for Diabetic Retinopathy (DR). In the past years, Mix-up training and pretext tasks with longitudinal context have effectively enhanced DR classification results and captured disease progression. In the meantime, a novel type of neural network named Neural Ordinary Differential Equation (NODE) has been proposed for solving ordinary differential equations, with a neural network treated as a black box. By definition, NODE is well suited for solving time-related problems. In this paper, we propose to combine these three aspects to detect and predict DR progression. Our framework, Longitudinal Mixing Training (LMT), can be considered both as a regularizer and as a pretext task that encodes the disease progression in the latent space. Additionally, we evaluate the trained model weights on a downstream task with a longitudinal context using standard and longitudinal pretext tasks. We introduce a new way to train time-aware models using $t_{mix}$, a weighted average time between two consecutive examinations. We compare our approach to standard mixing training on DR classification using OPHDIAT a longitudinal retinal Color Fundus Photographs (CFP) dataset. We were able to predict whether an eye would develop a severe DR in the following visit using a single image, with an AUC of 0.798 compared to baseline results of 0.641. Our results indicate that our longitudinal pretext task can learn the progression of DR disease and that introducing $t_{mix}$ augmentation is beneficial for time-aware models.

Longitudinal Self-supervised Learning Using Neural Ordinary Differential Equation

Longitudinal analysis in medical imaging is crucial to investigate the progressive changes in anatomical structures or disease progression over time. In recent years, a novel class of algorithms has emerged with the goal of learning disease progression in a self-supervised manner, using either pairs of consecutive images or time series of images. By capturing temporal patterns without external labels or supervision, longitudinal self-supervised learning (LSSL) has become a promising avenue. To better understand this core method, we explore in this paper the LSSL algorithm under different scenarios. The original LSSL is embedded in an auto-encoder (AE) structure. However, conventional self-supervised strategies are usually implemented in a Siamese-like manner. Therefore, (as a first novelty) in this study, we explore the use of Siamese-like LSSL. Another new core framework named neural ordinary differential equation (NODE). NODE is a neural network architecture that learns the dynamics of ordinary differential equations (ODE) through the use of neural networks. Many temporal systems can be described by ODE, including modeling disease progression. We believe that there is an interesting connection to make between LSSL and NODE. This paper aims at providing a better understanding of those core algorithms for learning the disease progression with the mentioned change. In our different experiments, we employ a longitudinal dataset, named OPHDIAT, targeting diabetic retinopathy (DR) follow-up. Our results demonstrate the application of LSSL without including a reconstruction term, as well as the potential of incorporating NODE in conjunction with LSSL.

Improved Automatic Diabetic Retinopathy Severity Classification Using Deep Multimodal Fusion of UWF-CFP and OCTA Images

Diabetic Retinopathy (DR), a prevalent and severe complication of diabetes, affects millions of individuals globally, underscoring the need for accurate and timely diagnosis. Recent advancements in imaging technologies, such as Ultra-WideField Color Fundus Photography (UWF-CFP) imaging and Optical Coherence Tomography Angiography (OCTA), provide opportunities for the early detection of DR but also pose significant challenges given the disparate nature of the data they produce. This study introduces a novel multimodal approach that leverages these imaging modalities to notably enhance DR classification. Our approach integrates 2D UWF-CFP images and 3D high-resolution 6x6 mm$^3$ OCTA (both structure and flow) images using a fusion of ResNet50 and 3D-ResNet50 models, with Squeeze-and-Excitation (SE) blocks to amplify relevant features. Additionally, to increase the model's generalization capabilities, a multimodal extension of Manifold Mixup, applied to concatenated multimodal features, is implemented. Experimental results demonstrate a remarkable enhancement in DR classification performance with the proposed multimodal approach compared to methods relying on a single modality only. The methodology laid out in this work holds substantial promise for facilitating more accurate, early detection of DR, potentially improving clinical outcomes for patients.

Segmentation, Classification, and Quality Assessment of UW-OCTA Images for the Diagnosis of Diabetic Retinopathy

Diabetic Retinopathy (DR) is a severe complication of diabetes that can cause blindness. Although effective treatments exist (notably laser) to slow the progression of the disease and prevent blindness, the best treatment remains prevention through regular check-ups (at least once a year) with an ophthalmologist. Optical Coherence Tomography Angiography (OCTA) allows for the visualization of the retinal vascularization, and the choroid at the microvascular level in great detail. This allows doctors to diagnose DR with more precision. In recent years, algorithms for DR diagnosis have emerged along with the development of deep learning and the improvement of computer hardware. However, these usually focus on retina photography. There are no current methods that can automatically analyze DR using Ultra-Wide OCTA (UW-OCTA). The Diabetic Retinopathy Analysis Challenge 2022 (DRAC22) provides a standardized UW-OCTA dataset to train and test the effectiveness of various algorithms on three tasks: lesions segmentation, quality assessment, and DR grading. In this paper, we will present our solutions for the three tasks of the DRAC22 challenge. The obtained results are promising and have allowed us to position ourselves in the TOP 5 of the segmentation task, the TOP 4 of the quality assessment task, and the TOP 3 of the DR grading task. The code is available at \url{https://github.com/Mostafa-EHD/Diabetic_Retinopathy_OCTA}.

Detection of diabetic retinopathy using longitudinal self-supervised learning

Longitudinal imaging is able to capture both static anatomical structures and dynamic changes in disease progression towards earlier and better patient-specific pathology management. However, conventional approaches for detecting diabetic retinopathy (DR) rarely take advantage of longitudinal information to improve DR analysis. In this work, we investigate the benefit of exploiting self-supervised learning with a longitudinal nature for DR diagnosis purposes. We compare different longitudinal self-supervised learning (LSSL) methods to model the disease progression from longitudinal retinal color fundus photographs (CFP) to detect early DR severity changes using a pair of consecutive exams. The experiments were conducted on a longitudinal DR screening dataset with or without those trained encoders (LSSL) acting as a longitudinal pretext task. Results achieve an AUC of 0.875 for the baseline (model trained from scratch) and an AUC of 0.96 (95% CI: 0.9593-0.9655 DeLong test) with a p-value < 2.2e-16 on early fusion using a simple ResNet alike architecture with frozen LSSL weights, suggesting that the LSSL latent space enables to encode the dynamic of DR progression.