Combining Shape and Learning for Medical Image Analysis

Automatic methods with the ability to make accurate, fast and robust assessments of medical images are highly requested in medical research and clinical care. Excellent automatic algorithms are characterized by speed, allowing for scalability, and an accuracy comparable to an expert radiologist. They should produce morphologically and physiologically plausible results while generalizing well to unseen and rare anatomies. Still, there are few, if any, applications where today\u27s automatic methods succeed to meet these requirements.\ua0The focus of this thesis is two tasks essential for enabling automatic medical image assessment, medical image segmentation and medical image registration. Medical image registration, i.e. aligning two separate medical images, is used as an important sub-routine in many image analysis tools as well as in image fusion, disease progress tracking and population statistics. Medical image segmentation, i.e. delineating anatomically or physiologically meaningful boundaries, is used for both diagnostic and visualization purposes in a wide range of applications, e.g. in computer-aided diagnosis and surgery.The thesis comprises five papers addressing medical image registration and/or segmentation for a diverse set of applications and modalities, i.e. pericardium segmentation in cardiac CTA, brain region parcellation in MRI, multi-organ segmentation in CT, heart ventricle segmentation in cardiac ultrasound and tau PET registration. The five papers propose competitive registration and segmentation methods enabled by machine learning techniques, e.g. random decision forests and convolutional neural networks, as well as by shape modelling, e.g. multi-atlas segmentation and conditional random fields

MAD: Modality Agnostic Distance Measure for Image Registration

Multi-modal image registration is a crucial pre-processing step in many medical applications. However, it is a challenging task due to the complex intensity relationships between different imaging modalities, which can result in large discrepancy in image appearance. The success of multi-modal image registration, whether it is conventional or learning based, is predicated upon the choice of an appropriate distance (or similarity) measure. Particularly, deep learning registration algorithms lack in accuracy or even fail completely when attempting to register data from an "unseen" modality. In this work, we present Modality Agnostic Distance (MAD), a deep image distance}] measure that utilises random convolutions to learn the inherent geometry of the images while being robust to large appearance changes. Random convolutions are geometry-preserving modules which we use to simulate an infinite number of synthetic modalities alleviating the need for aligned paired data during training. We can therefore train MAD on a mono-modal dataset and successfully apply it to a multi-modal dataset. We demonstrate that not only can MAD affinely register multi-modal images successfully, but it has also a larger capture range than traditional measures such as Mutual Information and Normalised Gradient Fields

A Statistical Model for Simultaneous Template Estimation, Bias Correction, and Registration of 3D Brain Images

Template estimation plays a crucial role in computational anatomy since it provides reference frames for performing statistical analysis of the underlying anatomical population variability. While building models for template estimation, variability in sites and image acquisition protocols need to be accounted for. To account for such variability, we propose a generative template estimation model that makes simultaneous inference of both bias fields in individual images, deformations for image registration, and variance hyperparameters. In contrast, existing maximum a posterori based methods need to rely on either bias-invariant similarity measures or robust image normalization. Results on synthetic and real brain MRI images demonstrate the capability of the model to capture heterogeneity in intensities and provide a reliable template estimation from registration

Most Likely Separation of Intensity and Warping Effects in Image Registration

This paper introduces a class of mixed-effects models for joint modeling of spatially correlated intensity variation and warping variation in 2D images. Spatially correlated intensity variation and warp variation are modeled as random effects, resulting in a nonlinear mixed-effects model that enables simultaneous estimation of template and model parameters by optimization of the likelihood function. We propose an algorithm for fitting the model which alternates estimation of variance parameters and image registration. This approach avoids the potential estimation bias in the template estimate that arises when treating registration as a preprocessing step. We apply the model to datasets of facial images and 2D brain magnetic resonance images to illustrate the simultaneous estimation and prediction of intensity and warp effects

Diffeomorphic density registration

In this book chapter we study the Riemannian Geometry of the density registration problem: Given two densities (not necessarily probability densities) defined on a smooth finite dimensional manifold find a diffeomorphism which transforms one to the other. This problem is motivated by the medical imaging application of tracking organ motion due to respiration in Thoracic CT imaging where the fundamental physical property of conservation of mass naturally leads to modeling CT attenuation as a density. We will study the intimate link between the Riemannian metrics on the space of diffeomorphisms and those on the space of densities. We finally develop novel computationally efficient algorithms and demonstrate there applicability for registering RCCT thoracic imaging.Comment: 23 pages, 6 Figures, Chapter for a Book on Medical Image Analysi

Adversarial Deformation Regularization for Training Image Registration Neural Networks

We describe an adversarial learning approach to constrain convolutional neural network training for image registration, replacing heuristic smoothness measures of displacement fields often used in these tasks. Using minimally-invasive prostate cancer intervention as an example application, we demonstrate the feasibility of utilizing biomechanical simulations to regularize a weakly-supervised anatomical-label-driven registration network for aligning pre-procedural magnetic resonance (MR) and 3D intra-procedural transrectal ultrasound (TRUS) images. A discriminator network is optimized to distinguish the registration-predicted displacement fields from the motion data simulated by finite element analysis. During training, the registration network simultaneously aims to maximize similarity between anatomical labels that drives image alignment and to minimize an adversarial generator loss that measures divergence between the predicted- and simulated deformation. The end-to-end trained network enables efficient and fully-automated registration that only requires an MR and TRUS image pair as input, without anatomical labels or simulated data during inference. 108 pairs of labelled MR and TRUS images from 76 prostate cancer patients and 71,500 nonlinear finite-element simulations from 143 different patients were used for this study. We show that, with only gland segmentation as training labels, the proposed method can help predict physically plausible deformation without any other smoothness penalty. Based on cross-validation experiments using 834 pairs of independent validation landmarks, the proposed adversarial-regularized registration achieved a target registration error of 6.3 mm that is significantly lower than those from several other regularization methods.Comment: Accepted to MICCAI 201

Prior-based Coregistration and Cosegmentation

We propose a modular and scalable framework for dense coregistration and cosegmentation with two key characteristics: first, we substitute ground truth data with the semantic map output of a classifier; second, we combine this output with population deformable registration to improve both alignment and segmentation. Our approach deforms all volumes towards consensus, taking into account image similarities and label consistency. Our pipeline can incorporate any classifier and similarity metric. Results on two datasets, containing annotations of challenging brain structures, demonstrate the potential of our method.Comment: The first two authors contributed equall