Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Multiparametric Magnetic Resonance Imaging Artificial Intelligence Pipeline for Oropharyngeal Cancer Radiotherapy Treatment Guidance

Oropharyngeal cancer (OPC) is a widespread disease and one of the few domestic cancers that is rising in incidence. Radiographic images are crucial for assessment of OPC and aid in radiotherapy (RT) treatment. However, RT planning with conventional imaging approaches requires operator-dependent tumor segmentation, which is the primary source of treatment error. Further, OPC expresses differential tumor/node mid-RT response (rapid response) rates, resulting in significant differences between planned and delivered RT dose. Finally, clinical outcomes for OPC patients can also be variable, which warrants the investigation of prognostic models. Multiparametric MRI (mpMRI) techniques that incorporate simultaneous anatomical and functional information coupled to artificial intelligence (AI) approaches could improve clinical decision support for OPC by providing immediately actionable clinical rationale for adaptive RT planning. If tumors could be reproducibly segmented, rapid response could be classified, and prognosis could be reliably determined, overall patient outcomes would be optimized to improve the therapeutic index as a function of more risk-adapted RT volumes. Consequently, there is an unmet need for automated and reproducible imaging which can simultaneously segment tumors and provide predictive value for actionable RT adaptation. This dissertation primarily seeks to explore and optimize image processing, tumor segmentation, and patient outcomes in OPC through a combination of advanced imaging techniques and AI algorithms. In the first specific aim of this dissertation, we develop and evaluate mpMRI pre-processing techniques for use in downstream segmentation, response prediction, and outcome prediction pipelines. Various MRI intensity standardization and registration approaches were systematically compared and benchmarked. Moreover, synthetic image algorithms were developed to decrease MRI scan time in an effort to optimize our AI pipelines. We demonstrated that proper intensity standardization and image registration can improve mpMRI quality for use in AI algorithms, and developed a novel method to decrease mpMRI acquisition time. Subsequently, in the second specific aim of this dissertation, we investigated underlying questions regarding the implementation of RT-related auto-segmentation. Firstly, we quantified interobserver variability for an unprecedented large number of observers for various radiotherapy structures in several disease sites (with a particular emphasis on OPC) using a novel crowdsourcing platform. We then trained an AI algorithm on a series of extant matched mpMRI datasets to segment OPC primary tumors. Moreover, we validated and compared our best model\u27s performance to clinical expert observers. We demonstrated that AI-based mpMRI OPC tumor auto-segmentation offers decreased variability and comparable accuracy to clinical experts, and certain mpMRI input channel combinations could further improve performance. Finally, in the third specific aim of this dissertation, we predicted OPC primary tumor mid-therapy (rapid) treatment response and prognostic outcomes. Using co-registered pre-therapy and mid-therapy primary tumor manual segmentations of OPC patients, we generated and characterized treatment sensitive and treatment resistant pre-RT sub-volumes. These sub-volumes were used to train an AI algorithm to predict individual voxel-wise treatment resistance. Additionally, we developed an AI algorithm to predict OPC patient progression free survival using pre-therapy imaging from an international data science competition (ranking 1st place), and then translated these approaches to mpMRI data. We demonstrated AI models could be used to predict rapid response and prognostic outcomes using pre-therapy imaging, which could help guide treatment adaptation, though further work is needed. In summary, the completion of these aims facilitates the development of an image-guided fully automated OPC clinical decision support tool. The resultant deliverables from this project will positively impact patients by enabling optimized therapeutic interventions in OPC. Future work should consider investigating additional imaging timepoints, imaging modalities, uncertainty quantification, perceptual and ethical considerations, and prospective studies for eventual clinical implementation. A dynamic version of this dissertation is publicly available and assigned a digital object identifier through Figshare (doi: 10.6084/m9.figshare.22141871)

Deep Learning of Unified Region, Edge, and Contour Models for Automated Image Segmentation

Image segmentation is a fundamental and challenging problem in computer vision with applications spanning multiple areas, such as medical imaging, remote sensing, and autonomous vehicles. Recently, convolutional neural networks (CNNs) have gained traction in the design of automated segmentation pipelines. Although CNN-based models are adept at learning abstract features from raw image data, their performance is dependent on the availability and size of suitable training datasets. Additionally, these models are often unable to capture the details of object boundaries and generalize poorly to unseen classes. In this thesis, we devise novel methodologies that address these issues and establish robust representation learning frameworks for fully-automatic semantic segmentation in medical imaging and mainstream computer vision. In particular, our contributions include (1) state-of-the-art 2D and 3D image segmentation networks for computer vision and medical image analysis, (2) an end-to-end trainable image segmentation framework that unifies CNNs and active contour models with learnable parameters for fast and robust object delineation, (3) a novel approach for disentangling edge and texture processing in segmentation networks, and (4) a novel few-shot learning model in both supervised settings and semi-supervised settings where synergies between latent and image spaces are leveraged to learn to segment images given limited training data.Comment: PhD dissertation, UCLA, 202

Advancing Pancreas Segmentation in Multi-protocol MRI Volumes using Hausdorff-Sine Loss Function

Computing pancreatic morphology in 3D radiological scans could provide significant insight about a medical condition. However, segmenting the pancreas in magnetic resonance imaging (MRI) remains challenging due to high inter-patient variability. Also, the resolution and speed of MRI scanning present artefacts that blur the pancreas bound- aries between overlapping anatomical structures. This paper proposes a dual-stage automatic segmentation method: 1) a deep neural network is trained to address the problem of vague organ boundaries in high class-imbalanced data. This network integrates a novel loss function to rigorously optimise boundary delineation using the modified Hausdorff metric and a sinusoidal component; 2) Given a test MRI volume, the output of the trained network predicts a sequence of targeted 2D pan- creas classes that are reconstructed as a volumetric binary mask. An energy-minimisation approach fuses a learned digital contrast model to suppress the intensities of non-pancreas classes, which, combined with the binary volume performs a refined segmentation in 3D while reveal- ing dense boundary detail. Experiments are performed on two diverse MRI datasets containing 180 and 120 scans, in which the proposed ap- proach achieves a mean Dice score of 84.1 ± 4.6% and 85.7 ± 2.3%, respectively. This approach is statistically stable and outperforms state- of-the-art methods on MRI