Automated multi-subject fiber clustering of mouse brain using dominant sets

Mapping of structural and functional connectivity may provide deeper understanding of brain function and disfunction. Diffusion Magnetic Resonance Imaging (DMRI) is a powerful technique to non-invasively delineate white matter (WM) tracts and to obtain a three-dimensional description of the structural architecture of the brain. However, DMRI tractography methods produce highly multi-dimensional datasets whose interpretation requires advanced analytical tools. Indeed, manual identification of specific neuroanatomical tracts based on prior anatomical knowledge is time-consuming and prone to operator-induced bias. Here we propose an automatic multi-subject fiber clustering method that enables retrieval of group-wise WM fiber bundles. In order to account for variance across subjects, we developed a multi-subject approach based on a method known as Dominant Sets algorithm, via an intra- and cross-subject clustering. The intra-subject step allows us to reduce the complexity of the raw tractography data, thus obtaining homogeneous neuroanatomically-plausible bundles in each diffusion space. The cross-subject step, characterized by a proper space-invariant metric in the original diffusion space, enables the identification of the same WM bundles across multiple subjects without any prior neuroanatomical knowledge. Quantitative analysis was conducted comparing our algorithm with spectral clustering and affinity propagation methods on synthetic dataset. We also performed qualitative analysis on mouse brain tractography retrieving significant WM structures. The approach serves the final goal of detecting WM bundles at a population level, thus paving the way to the study of the WM organization across groups.Mapping of structural and functional connectivity may provide deeper understanding of brain function and disfunction. Diffusion Magnetic Resonance Imaging (DMRI) is a powerful technique to non-invasively delineate white matter (WM) tracts and to obtain a three-dimensional description of the structural architecture of the brain. However, DMRI tractography methods produce highly multi-dimensional datasets whose interpretation requires advanced analytical tools. Indeed, manual identification of specific neuroanatomical tracts based on prior anatomical knowledge is time-consuming and prone to operator-induced bias. Here we propose an automatic multi-subject fiber clustering method that enables retrieval of group-wise WM fiber bundles. In order to account for variance across subjects, we developed a multi-subject approach based on a method known as Dominant Sets algorithm, via an intra-and cross-subject clustering. The intra-subject step allows us to reduce the complexity of the raw tractography data, thus obtaining homogeneous neuroanatomically-plausible bundles in each diffusion space. The cross-subject step, characterized by a proper space-invariant metric in the original diffusion space, enables the identification of the same WM bundles across multiple subjects without any prior neuroanatomical knowledge. Quantitative analysis was conducted comparing our algorithm with spectral clustering and affinity propagation methods on synthetic dataset. We also performed qualitative analysis on mouse brain tractography retrieving significant WM structures. The approach serves the final goal of detecting WM bundles at a population level, thus paving the way to the study of the WM organization across groups

Anatomically-Informed Multiple Linear Assignment Problems for White Matter Bundle Segmentation

Segmenting white matter bundles from human tractograms is a task of interest for several applications. Current methods for bundle segmentation consider either only prior knowledge about the relative anatomical position of a bundle, or only its geometrical properties. Our aim is to improve the results of segmentation by proposing a method that takes into account information about both the underlying anatomy and the geometry of bundles at the same time. To achieve this goal, we extend a state-of-the-art example-based method based on the Linear Assignment Problem (LAP) by including prior anatomical information within the optimization process. The proposed method shows a significant improvement with respect to the original method, in particular on small bundles

Development of High Angular Resolution Diffusion Imaging Analysis Paradigms for the Investigation of Neuropathology

Diffusion weighted magnetic resonance imaging (DW-MRI), provides unique insight into the microstructure of neural white matter tissue, allowing researchers to more fully investigate white matter disorders. The abundance of clinical research projects incorporating DW-MRI into their acquisition protocols speaks to the value this information lends to the study of neurological disease. However, the most widespread DW-MRI technique, diffusion tensor imaging (DTI), possesses serious limitations which restrict its utility in regions of complex white matter. Fueled by advances in DW-MRI acquisition protocols and technologies, a group of exciting new DW-MRI models, developed to address these concerns, are now becoming available to clinical researchers. The emergence of these new imaging techniques, categorized as high angular resolution diffusion imaging (HARDI), has generated the need for sophisticated computational neuroanatomic techniques able to account for the high dimensionality and structure of HARDI data. The goal of this thesis is the development of such techniques utilizing prominent HARDI data models. Specifically, methodologies for spatial normalization, population atlas building and structural connectivity have been developed and validated. These methods form the core of a comprehensive analysis paradigm allowing the investigation of local white matter microarcitecture, as well as, systemic properties of neuronal connectivity. The application of this framework to the study of schizophrenia and the autism spectrum disorders demonstrate its sensitivity sublte differences in white matter organization, as well as, its applicability to large population DW-MRI studies

Population-wise consistent segmentation of diffusion weighted magnetic resonance images

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2008.Includes bibliographical references (p. 161-167).In this thesis, we investigate unsupervised and semi-supervised methods to construct anatomical atlases and segment medical images. We propose an integrated registration and clustering algorithm to compute an anatomical atlas of fiber-bundles as well as deep gray matter structures from a population of diffusion tensor MR images (DT-MRI). We refer to this algorithm as "Consistency Clustering" since the outputs of the algorithm include population-wise consistent segmentations and correspondence between the subjects. The consistency is ensured through using a single anatomical model for the whole population, which is similar to the atlases used by experts for manual labeling. We experiment with both parametric and non-parametric models for the gray matter and white matter segmentation problems, each model resulting in a different kind of atlas. Consistent population-wise segmentations require development of several integrated algorithms for clustering, registration, atlas-building and outlier rejection. In this thesis we develop, implement and evaluate these tools individually and together as a population-wise segmentation tool. Together, Consistency Clustering enables automatic atlas construction in DT-MRI for a population, either normal or affected by a neural disorder. Consistency Clustering also provides the user the choice to include prior knowledge through a few labeled subjects (semi-supervised) or compute an anatomical atlas in a completely data driven manner (unsupervised). Furthermore, resulting anatomical models are compact representations of populations and can be used for population-wise morphometry. We implement and evaluate these methods using in vivo DT-MRI datasets. We investigate the benefits of population-wise segmentation as opposed to individually segmenting subjects, as well as effects of noise and initialization on the segmentations.by Ulas Ziyan.Ph.D

Nonlinear tube-fitting for the analysis of anatomical and functional structures

We are concerned with the estimation of the exterior surface and interior summaries of tube-shaped anatomical structures. This interest is motivated by two distinct scientific goals, one dealing with the distribution of HIV microbicide in the colon and the other with measuring degradation in white-matter tracts in the brain. Our problem is posed as the estimation of the support of a distribution in three dimensions from a sample from that distribution, possibly measured with error. We propose a novel tube-fitting algorithm to construct such estimators. Further, we conduct a simulation study to aid in the choice of a key parameter of the algorithm, and we test our algorithm with validation study tailored to the motivating data sets. Finally, we apply the tube-fitting algorithm to a colon image produced by single photon emission computed tomography (SPECT) and to a white-matter tract image produced using diffusion tensor imaging (DTI).Comment: Published in at http://dx.doi.org/10.1214/10-AOAS384 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Application of neuroanatomical features to tractography clustering: Neural Features to Fiber Clustering

Diffusion tensor imaging allows unprecedented insight into brain neural connectivity in vivo by allowing reconstruction of neuronal tracts via captured patterns of water diffusion in white matter microstructures. However, tractography algorithms often output hundreds of thousands of fibers, rendering subsequent data analysis intractable. As a remedy, fiber clustering techniques are able to group fibers into dozens of bundles and thus facilitate analyses. Most existing fiber clustering methods rely on geometrical information of fibers, by viewing them as curves in 3D Euclidean space. The important neuroanatomical aspect of fibers, however, is ignored. In this article, the neuroanatomical information of each fiber is encapsulated in the associativity vector, which functions as the unique “fingerprint” of the fiber. Specifically, each entry in the associativity vector describes the relationship between the fiber and a certain anatomical ROI in a fuzzy manner. The value of the entry approaches 1 if the fiber is spatially related to the ROI at high confidence; on the contrary, the value drops closer to 0. The confidence of the ROI is calculated by diffusing the ROI according to the underlying fibers from tractography. In particular, we have adopted the fast marching method for simulation of ROI diffusion. Using the associativity vectors of fibers, we further model fibers as observations sampled from multivariate Gaussian mixtures in the feature space. To group all fibers into relevant major bundles, an expectation-maximization clustering approach is employed. Experimental results indicate that our method results in anatomically meaningful bundles that are highly consistent across subjects