Analysis of longitudinal shape variability via subject specific growth modeling

pre-printStatistical analysis of longitudinal imaging data is crucial for understanding normal anatomical development as well as disease progression. This fundamental task is challenging due to the difficulty in modeling longitudinal changes, such as growth, and comparing changes across different populations. We propose a new approach for analyzing shape variability over time, and for quantifying spatiotemporal population differences. Our approach estimates 4D anatomical growth models for a reference population (an average model) and for individuals in different groups. We define a reference 4D space for our analysis as the average population model and measure shape variability through diffeomorphisms that map the reference to the individuals. Conducting our analysis on this 4D space enables straightforward statistical analysis of deformations as they are parameterized by momenta vectors that are located at homologous locations in space and time. We evaluate our method on a synthetic shape database and clinical data from a study that seeks to quantify brain growth differences in infants at risk for autism

Brain structure in sagittal craniosynostosis

Craniosynostosis, the premature fusion of one or more cranial sutures, leads to grossly abnormal head shapes and pressure elevations within the brain caused by these deformities. To date, accepted treatments for craniosynostosis involve improving surgical skull shape aesthetics. However, the relationship between improved head shape and brain structure after surgery has not been yet established. Typically, clinical standard care involves the collection of diagnostic medical computed tomography (CT) imaging to evaluate the fused sutures and plan the surgical treatment. CT is known to provide very good reconstructions of the hard tissues in the skull but it fails to acquire good soft brain tissue contrast. This study intends to use magnetic resonance imaging to evaluate brain structure in a small dataset of sagittal craniosynostosis patients and thus quantify the effects of surgical intervention in overall brain structure. Very importantly, these effects are to be contrasted with normative shape, volume and brain structure databases. The work presented here wants to address gaps in clinical knowledge in craniosynostosis focusing on understanding the changes in brain volume and shape secondary to surgery, and compare those with normally developing children. This initial pilot study has the potential to add significant quality to the surgical care of a vulnerable patient population in whom we currently have limited understanding of brain developmental outcomes

Doctor of Philosophy

dissertationAn important aspect of medical research is the understanding of anatomy and its relation to function in the human body. For instance, identifying changes in the brain associated with cognitive decline helps in understanding the process of aging and age-related neurological disorders. The field of computational anatomy provides a rich mathematical setting for statistical analysis of complex geometrical structures seen in 3D medical images. At its core, computational anatomy is based on the representation of anatomical shape and its variability as elements of nonflat manifold of diffeomorphisms with an associated Riemannian structure. Although such manifolds effectively represent natural biological variability, intrinsic methods of statistical analysis within these spaces remain deficient at large. This dissertation contributes two critical missing pieces for statistics in diffeomorphisms: (1) multivariate regression models for cross-sectional study of shapes, and (2) generalization of classical Euclidean, mixed-effects models to manifolds for longitudinal studies. These models are based on the principle that statistics on manifold-valued information must respect the intrinsic geometry of that space. The multivariate regression methods provide statistical descriptors of the relationships of anatomy with clinical indicators. The novel theory of hierarchical geodesic models (HGMs) is developed as a natural generalization of hierarchical linear models (HLMs) to describe longitudinal data on curved manifolds. Using a hierarchy of geodesics, the HGMs address the challenge of modeling the shape-data with unbalanced designs typically arising as a result of follow-up medical studies. More generally, this research establishes a mathematical foundation to study dynamics of changes in anatomy and the associated clinical progression with time. This dissertation also provides efficient algorithms that utilize state-of-the-art high performance computing architectures to solve models on large-scale, longitudinal imaging data. These manifold-based methods are applied to predictive modeling of neurological disorders such as Alzheimer's disease. Overall, this dissertation enables clinicians and researchers to better utilize the structural information available in medical images

Analysis of Longitudinal Shape Variability via Subject Specific Growth Modeling

Abstract. Statistical analysis of longitudinal imaging data is crucial for understanding normal anatomical development as well as disease progression. This fundamental task is challenging due to the difficulty in modeling longitudinal changes, such as growth, and comparing changes across different populations. We propose a new approach for analyzing shape variability over time, and for quantifying spatiotemporal population differences. Our approach estimates 4D anatomical growth models for a reference population (an average model) and for individuals in different groups. We define a reference 4D space for our analysis as the average population model and measure shape variability through diffeomorphisms that map the reference to the individuals. Conducting our analysis on this 4D space enables straightforward statistical analysis of deformations as they are parameterized by momenta vectors that are located at homologous locations in space and time. We evaluate our method on a synthetic shape database and clinical data from a study that seeks to quantify brain growth differences in infants at risk for autism

Analysis of longitudinal shape variability via subject specific growth modeling.

International audienceStatistical analysis of longitudinal imaging data is crucial for understanding normal anatomical development as well as disease progression. This fundamental task is challenging due to the difficulty in modeling longitudinal changes, such as growth, and comparing changes across different populations. We propose a new approach for analyzing shape variability over time, and for quantifying spatiotemporal population differences. Our approach estimates 4D anatomical growth models for a reference population (an average model) and for individuals in different groups. We define a reference 4D space for our analysis as the average population model and measure shape variability through diffeomorphisms that map the reference to the individuals. Conducting our analysis on this 4D space enables straightforward statistical analysis of deformations as they are parameterized by momenta vectors that are located at homologous locations in space and time. We evaluate our method on a synthetic shape database and clinical data from a study that seeks to quantify brain growth differences in infants at risk for autism