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In this paper, we present and validate a framework, based on deformable image registration, for automatic processing of serial three-dimensional CT images used in image-guided radiation therapy. A major assumption in deformable image registration has been that, if two images are being registered, every point of one image corresponds appropriately to some point in the other. For intra-treatment images of the prostate, however, this assumption is violated by the variable presence of bowel gas. The framework presented here explicitly extends previous deformable image registration algorithms to accommodate such regions in the image for which no correspondence exists. We show how to use our registration technique as a tool for organ segmentation, and present a statistical analysis of this segmentation method, validating it by comparison with multiple human raters. We also show how the deformable registration technique can be used to determine the dosimetric effect of a given plan in the presence of non-rigid tissue motion. In addition to dose accumulation, we describe a method for estimating the biological effects of tissue motion using a linear-quadratic model. This work is described in the context of a prostate treatment protocol, but it is of general applicability.

Regression analysis is a powerful tool for the study of changes in a dependent variable as a function of an independent regressor variable, and in particular it is applicable to the study of anatomical growth and shape change. When the underlying process can be modeled by parameters in a Euclidean space, classical regression techniques [15,38] are applicable and have been studied extensively. However, recent work suggests that attempts to describe anatomical shapes using flat Euclidean spaces undermines our ability to represent natural biological variability [10,12].In this paper we develop a method for regression analysis of general, manifoldvalued data. Specifically, we extend Nadaraya-Watson kernel regression by recasting the regression problem in terms of Fréchet expectation. Although this method is quite general, our driving problem is the study anatomical shape change as a function of age from random design image data.We demonstrate our method by analyzing shape change in the brain from a random design dataset of MR images of 97 healthy adults ranging in age from 20 to 79 years. To study the small scale changes in anatomy, we use the infinite dimensional manifold of diffeomorphic transformations, with an associated metric. We regress a representative anatomical shape, as a function of age, from this population.

Regression analysis is a powerful tool for the study of changes in a dependent variable as a function of an independent regressor variable, and in particular it is applicable to the study of anatomical growth and shape change. When the underlying process can be modeled by parameters in a Euclidean space, classical regression techniques (Hardle, Applied Nonparametric Regression, 1990; Wand and Jones, Kernel Smoothing, 1995) are applicable and have been studied extensively. However, recent work suggests that attempts to describe anatomical shapes using flat Euclidean spaces undermines our ability to represent natural biological variability (Fletcher et al.In this paper we develop a method for regression analysis of general, manifold-valued data. Specifically, we extend Nadaraya-Watson kernel regression by recasting the regression problem in terms of Fréchet expectation. Although this method is quite general, our driving problem is the study anatomical shape change as a function of age from random design image data.We demonstrate our method by analyzing shape change in the brain from a random design dataset of MR images of 97 healthy adults ranging in age from 20 to 79 years.To study the small scale changes in anatomy, we use the infinite dimensional manifold of diffeomorphic transformations, with an associated metric. We regress a representative anatomical shape, as a function of age, from this population.

In this paper, we present a Bayesian framework for both generating inter-subject large deformation transformations between two multi-modal image sets of the brain and for forming multi-class brain atlases. In this framework, the estimated transformations are generated using maximal information about the underlying neuroanatomy present in each of the different modalities. This modality independent registration framework is achieved by jointly estimating the posterior probabilities associated with the multi-modal image sets and the high-dimensional registration transformations mapping these posteriors. To maximally use the information present in all the modalities for registration, Kullback-Leibler divergence between the estimated posteriors is minimized. Registration results for image sets composed of multi-modal MR images of healthy adult human brains are presented. Atlas formation results are presented for a population of five infant human brains.