Advanced Monte Carlo Simulation and Machine Learning for Frequency Domain Optical Coherence Tomography

Optical Coherence Tomography(OCT) is a popular, rapidly growing imaging technique with an increasing number of bio medical applications due to its noninvasive nature. However, there are three major challenges in understanding and improving an OCT system: (1) Obtaining an OCT image is not easy. It either takes a real medical experiment or requires days of computer simulation. Without much data, it is difficult to study the physical processes underlying OCT imaging of different objects simply because there aren't many imaged objects. (2) Interpretation of an OCT image is also hard. This challenge is more profound than it appears. For instance, it would require a trained expert to tell from an OCT image of human skin whether there is a lesion or not. This is expensive in its own right, but even the expert cannot be sure about the exact size of the lesion or the width of the various skin layers. The take away message is that analyzing an OCT image even from a high level would usually require a trained expert, and pixel level interpretation is simply unrealistic. The reason is simple: we have OCT images but not their underlying ground truth structure, so there is nothing to learn from. (3) The imaging depth of OCT is very limited (millimeter or sub millimeter on human tissues) While OCT utilizes infrared light for illumination to stay noninvasive, the downside of this is that photons at such long wavelengths can only penetrate a limited depth into the tissue before getting back scattered. To image a particular region of a tissue, photons first need to reach that region. As a result, OCT signals from deeper regions of the tissue are both weak (since few photons reached there) and distorted (due to multiple scatterings of the contributing photons) This fact alone makes OCT images very hard to interpret. This thesis addresses the above challenges by successfully developing an advanced Monte Carlo simulation platform which is 10000 times faster than the state of the art simulator in the literature, bringing down the simulation time from 360 hours to a single minute. This powerful simulation tool not only enables us to efficiently generate as many OCT images of objects with arbitrary structure and shape as we want on a common desktop computer, but it also provides us the underlying ground truth of the simulated images at the same time because we dictate them at the beginning of the simulation. This is one of the key contributions of this thesis. What allows us to build such a powerful simulation tool includes a thorough understanding of the signal formation process, clever implementation of the importance sampling/photon splitting procedure, efficient use of a voxel based mesh system in determining photon mesh interception, and a parallel computation of different A scans that consist a full OCT image, among other programming and mathematical tricks, which will be explained in detail later in the thesis. Next we aim at the inverse problem: given an OCT image, predict/reconstruct its ground truth structure on a pixel level. By solving this problem we would be able to interpret an OCT image completely and precisely without the help from a trained expert. It turns out that we can do much better. For simple structures we are able to reconstruct the ground truth of an OCT image more than 98% correctly, and for more complicated structures (e.g. a multi layered brain structure) we are looking at 93% We achieved this through extensive uses of Machine Learning. The success of the Monte Carlo simulation already puts us in a great position by providing us with a great deal of data (effectively unlimited) in the form of (image, truth) pairs. Through a transformation of the high dimensional response variable, we convert the learning task into a multi output multi class classification problem and a multi output regression problem. We then build a hierarchy architecture of machine learning models (committee of experts) and train different parts of the architecture with specifically designed data sets. In prediction, an unseen OCT image first goes through a classification model to determine its structure (e.g. the number and the types of layers present in the image) then the image is handed to a regression model that is trained specifically for that particular structure to predict the length of the different layers and by doing so reconstruct the ground truth of the image. We also demonstrate that ideas from Deep Learning can be useful to further improve the performance. It is worth pointing out that solving the inverse problem automatically improves the imaging depth, since previously the lower half of an OCT image (i.e. greater depth) can be hardly seen but now becomes fully resolved. Interestingly, although OCT signals consisting the lower half of the image are weak, messy, and uninterpretable to human eyes, they still carry enough information which when fed into a well trained machine learning model spits out precisely the true structure of the object being imaged. This is just another case where Artificial Intelligence (AI) outperforms human. To the best knowledge of the author, this thesis is not only a success but also the first attempt to reconstruct an OCT image at a pixel level. To even give a try on this kind of task, it would require fully annotated OCT images and a lot of them (hundreds or even thousands) This is clearly impossible without a powerful simulation tool like the one developed in this thesis.