3D Normal Coordinate Systems for Cortical Areas

A surface-based diffeomorphic algorithm to generate 3D coordinate grids in the cortical ribbon is described. In the grid, normal coordinate lines are generated by the diffeomorphic evolution from the grey/white (inner) surface to the grey/csf (outer) surface. Specifically, the cortical ribbon is described by two triangulated surfaces with open boundaries. Conceptually, the inner surface sits on top of the white matter structure and the outer on top of the gray matter. It is assumed that the cortical ribbon consists of cortical columns which are orthogonal to the white matter surface. This might be viewed as a consequence of the development of the columns in the embryo. It is also assumed that the columns are orthogonal to the outer surface so that the resultant vector field is orthogonal to the evolving surface. Then the distance of the normal lines from the vector field such that the inner surface evolves diffeomorphically towards the outer one can be construed as a measure of thickness. Applications are described for the auditory cortices in human adults and cats with normal hearing or hearing loss. The approach offers great potential for cortical morphometry

Longitudinal imaging highlights preferential basal ganglia circuit atrophy in Huntington's disease

Huntington's disease is caused by a CAG repeat expansion in the Huntingtin gene (HTT), coding for polyglutamine in the Huntingtin protein, with longer CAG repeats causing earlier age of onset. The variable 'Age' × ('CAG'-L), where 'Age' is the current age of the individual, 'CAG' is the repeat length and L is a constant (reflecting an approximation of the threshold), termed the 'CAG Age Product' (CAP) enables the consideration of many individuals with different CAG repeat expansions at the same time for analysis of any variable and graphing using the CAG Age Product score as the X axis. Structural MRI studies have showed that progressive striatal atrophy begins many years prior to the onset of diagnosable motor Huntington's disease, confirmed by longitudinal multicentre studies on three continents, including PREDICT-HD, TRACK-HD and IMAGE-HD. However, previous studies have not clarified the relationship between striatal atrophy, atrophy of other basal ganglia structures, and atrophy of other brain regions. The present study has analysed all three longitudinal datasets together using a single image segmentation algorithm and combining data from a large number of subjects across a range of CAG Age Product score. In addition, we have used a strategy of normalizing regional atrophy to atrophy of the whole brain, in order to determine which regions may undergo preferential degeneration. This made possible the detailed characterization of regional brain atrophy in relation to CAG Age Product score. There is dramatic selective atrophy of regions involved in the basal ganglia circuit-caudate, putamen, nucleus accumbens, globus pallidus and substantia nigra. Most other regions of the brain appear to have slower but steady degeneration. These results support (but certainly do not prove) the hypothesis of circuit-based spread of pathology in Huntington's disease, possibly due to spread of mutant Htt protein, though other connection-based mechanisms are possible. Therapeutic targets related to prion-like spread of pathology or other mechanisms may be suggested. In addition, they have implications for current neurosurgical therapeutic approaches, since delivery of therapeutic agents solely to the caudate and putamen may miss other structures affected early, such as nucleus accumbens and output nuclei of the striatum, the substantia nigra and the globus pallidus

Morphology And Mechanics Of Cortical Folding Associated With Auditory Deprivation

Hearing loss is increasingly becoming a common disabling condition that affects the global population. Functional and structural changes occur in the developing auditory cortex after the onset of auditory deprivation. This study aims at measuring and modeling these changes, which can help understand the pathology of hearing loss and support research on treatment. Specifically, it describes a pipeline of automatically extracting inner and outer cortical surfaces from MRI images and measuring morphological metrics. Then, a two-component finite element mechanical model mimicking gray matter and white matter is used to investigate the causes of measured structural differences between cats with normal hearing and hearing loss. Mechanical parameters, such as shear and bulk modulus, are varied with a view to studying their influence on cortical folding patterns. Compared to hearing cats, cats with hearing loss have decreased cortical curvature and folding index, and increased thickness. By varying the shear modulus and bulk modulus of the gray and white matter at different locations, the mechanical model reveals distinct stable folding patterns. Specific combinations of parameters and locations lead to changes in curvature, folding index, and thickness. The methods used in this study can also be extended to examine cortical morphological characteristics associated with other abnormalities in the developing brain

Preclinical Alzheimer's Disease in the Entorhinal and Transentorhinal Cortex

Research on biomarkers of Alzheimer's disease has been shifting focus toward identifying changes in the preclinical stage, a stage prior to the emergence of cognitive deficits. Advances in the field of computational anatomy leverages noisy, longitudinal data for more sensitive and robust detection of shape differences. In particular, cortical thickness measures have been shown to be a sensitive marker of change. In this work, we introduce a pipeline for quantifying cortical thickness and develop three models to study the earliest changes detected from structural MRI. First, we investigate where grey matter atrophy occurs with great spatial resolution using a new cortical thickness metric and a mixed effects model of group differences. Next, we determine when grey matter atrophy begins using a piece-wise linear mixed effects model of atrophy. Finally, we characterize early progression of the disease in an individual using a subject-specific model of atrophy spread

On Model-based Diffeomorphic Shape Evolution and Diffeomorphic Shape Registration

Shape registration is fundamental in many applications. However, the shape registration problem is usually ill posed unless further information is provided. In this dissertation, we examine a scenario when one of the two shapes to be registered is assumed to have evolved from the other shape according to a known model. The shape registration problem is then formulated as a variational problem subject to the dynamics of the shape evolution model. We provide sufficient conditions on models so that diffeomorphic shape evolution and diffeomorphic shape registration are guaranteed theoretically. In addition, we illustrate this model-based registration by applications of piecewise-rigid motion and biological atrophy. Numerical experiments of the two applications are presented with a GPU-accelerated implementation