Quantitative diffusion MRI with application to multiple sclerosis

Diffusion MRI (dMRI) is a uniquely non-invasive probe of biological tissue properties, increasingly able to provide access to ever more intricate structural and microstructural tissue information. Imaging biomarkers that reveal pathological alterations can help advance our knowledge of complex neurological disorders such as multiple sclerosis (MS), but depend on both high quality image data and robust post-processing pipelines. The overarching aim of this thesis was to develop methods to improve the characterisation of brain tissue structure and microstructure using dMRI. Two distinct avenues were explored. In the first approach, network science and graph theory were used to identify core human brain networks with improved sensitivity to subtle pathological damage. A novel consensus subnetwork was derived using graph partitioning techniques to select nodes based on independent measures of centrality, and was better able to explain cognitive impairment in relapsing-remitting MS patients than either full brain or default mode networks. The influence of edge weighting scheme on graph characteristics was explored in a separate study, which contributes to the connectomics field by demonstrating how study outcomes can be affected by an aspect of network design often overlooked. The second avenue investigated the influence of image artefacts and noise on the accuracy and precision of microstructural tissue parameters. Correction methods for the echo planar imaging (EPI) Nyquist ghost artefact were systematically evaluated for the first time in high b-value dMRI, and the outcomes were used to develop a new 2D phase-corrected reconstruction framework with simultaneous channel-wise noise reduction appropriate for dMRI. The technique was demonstrated to alleviate biases associated with Nyquist ghosting and image noise in dMRI biomarkers, but has broader applications in other imaging protocols that utilise the EPI readout. I truly hope the research in this thesis will influence and inspire future work in the wider MR community

A Survey on Generative Diffusion Model

Deep learning shows excellent potential in generation tasks thanks to deep latent representation. Generative models are classes of models that can generate observations randomly concerning certain implied parameters. Recently, the diffusion Model has become a rising class of generative models by its power-generating ability. Nowadays, great achievements have been reached. More applications except for computer vision, speech generation, bioinformatics, and natural language processing are to be explored in this field. However, the diffusion model has its genuine drawback of a slow generation process, single data types, low likelihood, and the inability for dimension reduction. They are leading to many enhanced works. This survey makes a summary of the field of the diffusion model. We first state the main problem with two landmark works -- DDPM and DSM, and a unified landmark work -- Score SDE. Then, we present improved techniques for existing problems in the diffusion-based model field, including speed-up improvement For model speed-up improvement, data structure diversification, likelihood optimization, and dimension reduction. Regarding existing models, we also provide a benchmark of FID score, IS, and NLL according to specific NFE. Moreover, applications with diffusion models are introduced including computer vision, sequence modeling, audio, and AI for science. Finally, there is a summarization of this field together with limitations \& further directions. The summation of existing well-classified methods is in our Github:https://github.com/chq1155/A-Survey-on-Generative-Diffusion-Model

Normative values of the topological metrics of the structural connectome: A multi-site reproducibility study across the Italian Neuroscience network

Purpose: The use of topological metrics to derive quantitative descriptors from structural connectomes is receiving increasing attention but deserves specific studies to investigate their reproducibility and variability in the clinical context. This work exploits the harmonization of diffusion-weighted acquisition for neuroimaging data performed by the Italian Neuroscience and Neurorehabilitation Network initiative to obtain normative values of topological metrics and to investigate their reproducibility and variability across centers. / Methods: Different topological metrics, at global and local level, were calculated on multishell diffusion-weighted data acquired at high-field (e.g. 3 T) Magnetic Resonance Imaging scanners in 13 different centers, following the harmonization of the acquisition protocol, on young and healthy adults. A “traveling brains” dataset acquired on a subgroup of subjects at 3 different centers was also analyzed as reference data. All data were processed following a common processing pipeline that includes data pre-processing, tractography, generation of structural connectomes and calculation of graph-based metrics. The results were evaluated both with statistical analysis of variability and consistency among sites with the traveling brains range. In addition, inter-site reproducibility was assessed in terms of intra-class correlation variability. / Results: The results show an inter-center and inter-subject variability of <10%, except for “clustering coefficient” (variability of 30%). Statistical analysis identifies significant differences among sites, as expected given the wide range of scanners’ hardware. / Conclusions: The results show low variability of connectivity topological metrics across sites running a harmonised protocol

Graph Priors, Optimal Transport, and Deep Learning in Biomedical Discovery

Recent advances in biomedical data collection allows the collection of massive datasets measuring thousands of features in thousands to millions of individual cells. This data has the potential to advance our understanding of biological mechanisms at a previously impossible resolution. However, there are few methods to understand data of this scale and type. While neural networks have made tremendous progress on supervised learning problems, there is still much work to be done in making them useful for discovery in data with more difficult to represent supervision. The flexibility and expressiveness of neural networks is sometimes a hindrance in these less supervised domains, as is the case when extracting knowledge from biomedical data. One type of prior knowledge that is more common in biological data comes in the form of geometric constraints. In this thesis, we aim to leverage this geometric knowledge to create scalable and interpretable models to understand this data. Encoding geometric priors into neural network and graph models allows us to characterize the models’ solutions as they relate to the fields of graph signal processing and optimal transport. These links allow us to understand and interpret this datatype. We divide this work into three sections. The first borrows concepts from graph signal processing to construct more interpretable and performant neural networks by constraining and structuring the architecture. The second borrows from the theory of optimal transport to perform anomaly detection and trajectory inference efficiently and with theoretical guarantees. The third examines how to compare distributions over an underlying manifold, which can be used to understand how different perturbations or conditions relate. For this we design an efficient approximation of optimal transport based on diffusion over a joint cell graph. Together, these works utilize our prior understanding of the data geometry to create more useful models of the data. We apply these methods to molecular graphs, images, single-cell sequencing, and health record data