Deep spectral learning for label-free optical imaging oximetry with uncertainty quantification

Measurement of blood oxygen saturation (sO2) by optical imaging oximetry provides invaluable insight into local tissue functions and metabolism. Despite different embodiments and modalities, all label-free optical-imaging oximetry techniques utilize the same principle of sO2-dependent spectral contrast from haemoglobin. Traditional approaches for quantifying sO2 often rely on analytical models that are fitted by the spectral measurements. These approaches in practice suffer from uncertainties due to biological variability, tissue geometry, light scattering, systemic spectral bias, and variations in the experimental conditions. Here, we propose a new data-driven approach, termed deep spectral learning (DSL), to achieve oximetry that is highly robust to experimental variations and, more importantly, able to provide uncertainty quantification for each sO2 prediction. To demonstrate the robustness and generalizability of DSL, we analyse data from two visible light optical coherence tomography (vis-OCT) setups across two separate in vivo experiments on rat retinas. Predictions made by DSL are highly adaptive to experimental variabilities as well as the depth-dependent backscattering spectra. Two neural-network-based models are tested and compared with the traditional least-squares fitting (LSF) method. The DSL-predicted sO2 shows significantly lower mean-square errors than those of the LSF. For the first time, we have demonstrated en face maps of retinal oximetry along with a pixel-wise confidence assessment. Our DSL overcomes several limitations of traditional approaches and provides a more flexible, robust, and reliable deep learning approach for in vivo non-invasive label-free optical oximetry.R01 CA224911 - NCI NIH HHS; R01 CA232015 - NCI NIH HHS; R01 NS108464 - NINDS NIH HHS; R21 EY029412 - NEI NIH HHSAccepted manuscrip

Deep learning-based improvement for the outcomes of glaucoma clinical trials

Glaucoma is the leading cause of irreversible blindness worldwide. It is a progressive optic neuropathy in which retinal ganglion cell (RGC) axon loss, probably as a consequence of damage at the optic disc, causes a loss of vision, predominantly affecting the mid-peripheral visual field (VF). Glaucoma results in a decrease in vision-related quality of life and, therefore, early detection and evaluation of disease progression rates is crucial in order to assess the risk of functional impairment and to establish sound treatment strategies. The aim of my research is to improve glaucoma diagnosis by enhancing state of the art analyses of glaucoma clinical trial outcomes using advanced analytical methods. This knowledge would also help better design and analyse clinical trials, providing evidence for re-evaluating existing medications, facilitating diagnosis and suggesting novel disease management. To facilitate my objective methodology, this thesis provides the following contributions: (i) I developed deep learning-based super-resolution (SR) techniques for optical coherence tomography (OCT) image enhancement and demonstrated that using super-resolved images improves the statistical power of clinical trials, (ii) I developed a deep learning algorithm for segmentation of retinal OCT images, showing that the methodology consistently produces more accurate segmentations than state-of-the-art networks, (iii) I developed a deep learning framework for refining the relationship between structural and functional measurements and demonstrated that the mapping is significantly improved over previous techniques, iv) I developed a probabilistic method and demonstrated that glaucomatous disc haemorrhages are influenced by a possible systemic factor that makes both eyes bleed simultaneously. v) I recalculated VF slopes, using the retinal never fiber layer thickness (RNFLT) from the super-resolved OCT as a Bayesian prior and demonstrated that use of VF rates with the Bayesian prior as the outcome measure leads to a reduction in the sample size required to distinguish treatment arms in a clinical trial

Trustworthy clinical AI solutions: a unified review of uncertainty quantification in deep learning models for medical image analysis

The full acceptance of Deep Learning (DL) models in the clinical field is rather low with respect to the quantity of high-performing solutions reported in the literature. Particularly, end users are reluctant to rely on the rough predictions of DL models. Uncertainty quantification methods have been proposed in the literature as a potential response to reduce the rough decision provided by the DL black box and thus increase the interpretability and the acceptability of the result by the final user. In this review, we propose an overview of the existing methods to quantify uncertainty associated to DL predictions. We focus on applications to medical image analysis, which present specific challenges due to the high dimensionality of images and their quality variability, as well as constraints associated to real-life clinical routine. We then discuss the evaluation protocols to validate the relevance of uncertainty estimates. Finally, we highlight the open challenges of uncertainty quantification in the medical field