Retinal microvascular complexity comparing mono- and multifractal dimensions in relation to cardiometabolic risk factors in a Middle Eastern population.

PURPOSE: Metrics that capture changes in the retinal microvascular structure are relevant in the context of cardiometabolic disease development. The microvascular topology is typically quantified using monofractals, although it obeys more complex multifractal rules. We study mono- and multifractals of the retinal microvasculature in relation to cardiometabolic factors. METHODS: The cross-sectional retrospective study used data from 3000 Middle Eastern participants in the Qatar Biobank. A total of 2333 fundus images (78%) passed quality control and were used for further analysis. The monofractal (Df ) and five multifractal metrics were associated with cardiometabolic factors using multiple linear regression and were studied in clinically relevant subgroups. RESULTS: Df and multifractals are lowered in function of age, and Df is lower in males compared to females. In models corrected for age and sex, Df is significantly associated with BMI, insulin, systolic blood pressure, glycated haemoglobin (HbA1c), albumin, LDL and total cholesterol concentrations. Multifractals are negatively associated with systolic and diastolic blood pressure, glucose and the WHO/ISH cardiovascular risk score. Df was higher, and multifractal curve asymmetry was lower in diabetic patients (HbA1c > 6.5%) compared to healthy individuals (HbA1c < 5.7%). Insulin resistance (insulin ≥ 23 mcU/mL) was associated with significantly lower Df values. CONCLUSION: One or more fractal metrics are in association with sex, age, BMI, systolic and diastolic blood pressure and biochemical blood measurements in a Middle Eastern population study. Follow-up studies aiming at investigating retinal microvascular changes in relation to cardiometabolic risk should analyse both monofractal and multifractal metrics for a more comprehensive microvascular picture.

Combination of snapshot hyperspectral retinal imaging and optical coherence tomography to identify Alzheimer's disease patients.

INTRODUCTION: The eye offers potential for the diagnosis of Alzheimer's disease (AD) with retinal imaging techniques being explored to quantify amyloid accumulation and aspects of neurodegeneration. To assess these changes, this proof-of-concept study combined hyperspectral imaging and optical coherence tomography to build a classification model to differentiate between AD patients and controls. METHODS: In a memory clinic setting, patients with a diagnosis of clinically probable AD (n = 10) or biomarker-proven AD (n = 7) and controls (n = 22) underwent non-invasive retinal imaging with an easy-to-use hyperspectral snapshot camera that collects information from 16 spectral bands (460-620 nm, 10-nm bandwidth) in one capture. The individuals were also imaged using optical coherence tomography for assessing retinal nerve fiber layer thickness (RNFL). Dedicated image preprocessing analysis was followed by machine learning to discriminate between both groups. RESULTS: Hyperspectral data and retinal nerve fiber layer thickness data were used in a linear discriminant classification model to discriminate between AD patients and controls. Nested leave-one-out cross-validation resulted in a fair accuracy, providing an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [0.60-0.89]). Inner loop results showed that the inclusion of the RNFL features resulted in an improvement of the area under the receiver operating characteristic curve: for the most informative region assessed, the average area under the receiver operating characteristic curve was 0.70 (95% confidence interval [0.55, 0.86]) and 0.79 (95% confidence interval [0.65, 0.93]), respectively. The robust statistics used in this study reduces the risk of overfitting and partly compensates for the limited sample size. CONCLUSIONS: This study in a memory-clinic-based cohort supports the potential of hyperspectral imaging and suggests an added value of combining retinal imaging modalities. Standardization and longitudinal data on fully amyloid-phenotyped cohorts are required to elucidate the relationship between retinal structure and cognitive function and to evaluate the robustness of the classification model.

Systematic Comparison of Heatmapping Techniques in Deep Learning in the Context of Diabetic Retinopathy Lesion Detection.

Purpose: Heatmapping techniques can support explainability of deep learning (DL) predictions in medical image analysis. However, individual techniques have been mainly applied in a descriptive way without an objective and systematic evaluation. We investigated comparative performances using diabetic retinopathy lesion detection as a benchmark task. Methods: The Indian Diabetic Retinopathy Image Dataset (IDRiD) publicly available database contains fundus images of diabetes patients with pixel level annotations of diabetic retinopathy (DR) lesions, the ground truth for this study. Three in advance trained DL models (ResNet50, VGG16 or InceptionV3) were used for DR detection in these images. Next, explainability was visualized with each of the 10 most used heatmapping techniques. The quantitative correspondence between the output of a heatmap and the ground truth was evaluated with the Explainability Consistency Score (ECS), a metric between 0 and 1, developed for this comparative task. Results: In case of the overall DR lesions detection, the ECS ranged from 0.21 to 0.51 for all model/heatmapping combinations. The highest score was for VGG16+Grad-CAM (ECS = 0.51; 95% confidence interval [CI]: [0.46; 0.55]). For individual lesions, VGG16+Grad-CAM performed best on hemorrhages and hard exudates. ResNet50+SmoothGrad performed best for soft exudates and ResNet50+Guided Backpropagation performed best for microaneurysms. Conclusions: Our empirical evaluation on the IDRiD database demonstrated that the combination DL model/heatmapping affects explainability when considering common DR lesions. Our approach found considerable disagreement between regions highlighted by heatmaps and expert annotations. Translational Relevance: We warrant a more systematic investigation and analysis of heatmaps for reliable explanation of image-based predictions of deep learning models.