Abstract. Recently, the field of neuroimaging analysis has seen a large number of studies which u... more Abstract. Recently, the field of neuroimaging analysis has seen a large number of studies which use machine learning methods to make predictions about the progression of Alzheimer's Disease (AD) in mildly demented subjects. Among these, Multi-Kernel ...
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention, 2009
We study the problem of classifying mild Alzheimer's disease (AD) subjects from healthy indiv... more We study the problem of classifying mild Alzheimer's disease (AD) subjects from healthy individuals (controls) using multi-modal image data, to facilitate early identification of AD related pathologies. Several recent papers have demonstrated that such classification is possible with MR or PET images, using machine learning methods such as SVM and boosting. These algorithms learn the classifier using one type of image data. However, AD is not well characterized by one imaging modality alone, and analysis is typically performed using several image types--each measuring a different type of structural/functional characteristic. This paper explores the AD classification problem using multiple modalities simultaneously. The difficulty here is to assess the relevance of each modality (which cannot be assumed a priori), as well as to optimize the classifier. To tackle this problem, we utilize and adapt a recently developed idea called Multi-Kernel learning (MKL). Briefly, each imaging ...
Structural and functional brain images are playing an important role in helping us understand the... more Structural and functional brain images are playing an important role in helping us understand the changes associated with neurological disorders such as Alzheimer's disease (AD). Recent efforts have now started investigating their utility for diagnosis purposes. This line of research has shown promising results where methods from machine learning (such as Support Vector Machines) have been used to identify AD-related patterns from images, for use in diagnosing new individual subjects. In this paper, we propose a new framework for AD classification which makes use of the Linear Program (LP) boosting with novel additional regularization based on spatial "smoothness" in 3D image coordinate spaces. The algorithm formalizes the expectation that since the examples for training the classifier are images, the voxels eventually selected for specifying the decision boundary must constitute spatially contiguous chunks, i.e., "regions" must be preferred over isolated vox...
Proceedings / CVPR, IEEE Computer Society Conference on Computer Vision and Pattern Recognition. IEEE Computer Society Conference on Computer Vision and Pattern Recognition, 2010
We propose a new algorithm for learning kernels for variants of the Normalized Cuts (NCuts) objec... more We propose a new algorithm for learning kernels for variants of the Normalized Cuts (NCuts) objective - i.e., given a set of training examples with known partitions, how should a basis set of similarity functions be combined to induce NCuts favorable distributions. Such a procedure facilitates design of good affinity matrices. It also helps assess the importance of different feature types for discrimination. Rather than formulating the learning problem in terms of the spectral relaxation, the alternative we pursue here is to work in the original discrete setting (i.e., the relaxation occurs much later). We show that this strategy is useful - while the initial specification seems rather difficult to optimize efficiently, a set of manipulations reveal a related model which permits a nice SDP relaxation. A salient feature of our model is that the eventual problem size is only a function of the number of input kernels and not the training set size. This relaxation also allows strong opt...
Advances in neural information processing systems, 2012
Multiple Kernel Learning (MKL) generalizes SVMs to the setting where one simultaneously trains a ... more Multiple Kernel Learning (MKL) generalizes SVMs to the setting where one simultaneously trains a linear classifier and chooses an optimal combination of given base kernels. Model complexity is typically controlled using various norm regularizations on the base kernel mixing coefficients. Existing methods neither regularize nor exploit potentially useful information pertaining to how kernels in the input set 'interact'; that is, higher order kernel-pair relationships that can be easily obtained via unsupervised (similarity, geodesics), supervised (correlation in errors), or domain knowledge driven mechanisms (which features were used to construct the kernel?). We show that by substituting the norm penalty with an arbitrary quadratic function Q 0, one can impose a desired covariance structure on mixing weights, and use this as an inductive bias when learning the concept. This formulation significantly generalizes the widely used 1- and 2-norm MKL objectives. We explore the mod...
Advances in neural information processing systems, 2013
Multiple hypothesis testing is a significant problem in nearly all neuroimaging studies. In order... more Multiple hypothesis testing is a significant problem in nearly all neuroimaging studies. In order to correct for this phenomena, we require a reliable estimate of the Family-Wise Error Rate (FWER). The well known Bonferroni correction method, while simple to implement, is quite conservative, and can substantially under-power a study because it ignores dependencies between test statistics. Permutation testing, on the other hand, is an exact, non-parametric method of estimating the FWER for a given α-threshold, but for acceptably low thresholds the computational burden can be prohibitive. In this paper, we show that permutation testing in fact amounts to populating the columns of a very large matrix P. By analyzing the spectrum of this matrix, under certain conditions, we see that P has a low-rank plus a low-variance residual decomposition which makes it suitable for highly sub-sampled - on the order of 0.5% - matrix completion methods. Based on this observation, we propose a novel pe...
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2009
Diffusion Tensor Imaging (DTI) provides unique information about the underlying tissue structure ... more Diffusion Tensor Imaging (DTI) provides unique information about the underlying tissue structure of brain white matter in vivo, including both the geometry of fiber bundles as well as quantitative information about tissue properties as characterized by measures such as tensor orientation, anisotropy, and size. Our objective in this paper is to evaluate the utility of shape representations of white matter tracts extracted from DTI data for classification of clinically different population groups (here autistic vs control). As a first step, our algorithm extracts fiber bundles passing through approximately marked regions of interest on affinely aligned brain volumes. The subsequent analysis is entirely based on the geometric modeling of the extracted tracts. A key advantage of using such an abstraction is that it allows us to capture invariant features of brains allowing for efficient large sample size studies. We demonstrate that with the use of an appropriate representation of the t...
Advances in neural information processing systems, 2010
We study the problem of segmenting specific white matter structures of interest from Diffusion Te... more We study the problem of segmenting specific white matter structures of interest from Diffusion Tensor (DT-MR) images of the human brain. This is an important requirement in many Neuroimaging studies: for instance, to evaluate whether a brain structure exhibits group level differences as a function of disease in a set of images. Typically, interactive expert guided segmentation has been the method of choice for such applications, but this is tedious for large datasets common today. To address this problem, we endow an image segmentation algorithm with "advice" encoding some global characteristics of the region(s) we want to extract. This is accomplished by constructing (using expert-segmented images) an epitome of a specific region - as a histogram over a bag of 'words' (e.g., suitable feature descriptors). Now, given such a representation, the problem reduces to segmenting a new brain image with additional constraints that enforce consistency between the segmented ...
Alzheimer&amp... more Alzheimer's Disease (AD) and other neurodegenerative diseases affect over 20 million people worldwide, and this number is projected to significantly increase in the coming decades. Proposed imaging-based markers have shown steadily improving levels of sensitivity/specificity in classifying individual subjects as AD or normal. Several of these efforts have utilized statistical machine learning techniques, using brain images as input, as means of deriving such AD-related markers. A common characteristic of this line of research is a focus on either (1) using a single imaging modality for classification, or (2) incorporating several modalities, but reporting separate results for each. One strategy to improve on the success of these methods is to leverage all available imaging modalities together in a single automated learning framework. The rationale is that some subjects may show signs of pathology in one modality but not in another-by combining all available images a clearer view of the progression of disease pathology will emerge. Our method is based on the Multi-Kernel Learning (MKL) framework, which allows the inclusion of an arbitrary number of views of the data in a maximum margin, kernel learning framework. The principal innovation behind MKL is that it learns an optimal combination of kernel (similarity) matrices while simultaneously training a classifier. In classification experiments MKL outperformed an SVM trained on all available features by 3%-4%. We are especially interested in whether such markers are capable of identifying early signs of the disease. To address this question, we have examined whether our multi-modal disease marker (MMDM) can predict conversion from Mild Cognitive Impairment (MCI) to AD. Our experiments reveal that this measure shows significant group differences between MCI subjects who progressed to AD, and those who remained stable for 3 years. These differences were most significant in MMDMs based on imaging data. We also discuss the relationship between our MMDM and an individual's conversion from MCI to AD.
Precise detection and quantification of white matter hyperintensities (WMH) observed in T2-weight... more Precise detection and quantification of white matter hyperintensities (WMH) observed in T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Images (MRI) is of substantial interest in aging, and age-related neurological disorders such as Alzheimer's disease (AD). This is mainly because WMH may reflect co-morbid neural injury or cerebral vascular disease burden. WMH in the older population may be small, diffuse, and irregular in shape, and sufficiently heterogeneous within and across subjects. Here, we pose hyperintensity detection as a supervised inference problem and adapt two learning models, specifically, Support Vector Machines and Random Forests, for this task. Using texture features engineered by texton filter banks, we provide a suite of effective segmentation methods for this problem. Through extensive evaluations on healthy middle-aged and older adults who vary in AD risk, we show that our methods are reliable and robust in segmenting hyperintense regions. A measure of hyperintensity accumulation, referred to as normalized effective WMH volume, is shown to be associated with dementia in older adults and parental family history in cognitively normal subjects. We provide an open source library for hyperintensity detection and accumulation (interfaced with existing neuroimaging tools), that can be adapted for segmentation problems in other neuroimaging studies.
Abstract. Recently, the field of neuroimaging analysis has seen a large number of studies which u... more Abstract. Recently, the field of neuroimaging analysis has seen a large number of studies which use machine learning methods to make predictions about the progression of Alzheimer's Disease (AD) in mildly demented subjects. Among these, Multi-Kernel ...
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention, 2009
We study the problem of classifying mild Alzheimer's disease (AD) subjects from healthy indiv... more We study the problem of classifying mild Alzheimer's disease (AD) subjects from healthy individuals (controls) using multi-modal image data, to facilitate early identification of AD related pathologies. Several recent papers have demonstrated that such classification is possible with MR or PET images, using machine learning methods such as SVM and boosting. These algorithms learn the classifier using one type of image data. However, AD is not well characterized by one imaging modality alone, and analysis is typically performed using several image types--each measuring a different type of structural/functional characteristic. This paper explores the AD classification problem using multiple modalities simultaneously. The difficulty here is to assess the relevance of each modality (which cannot be assumed a priori), as well as to optimize the classifier. To tackle this problem, we utilize and adapt a recently developed idea called Multi-Kernel learning (MKL). Briefly, each imaging ...
Structural and functional brain images are playing an important role in helping us understand the... more Structural and functional brain images are playing an important role in helping us understand the changes associated with neurological disorders such as Alzheimer's disease (AD). Recent efforts have now started investigating their utility for diagnosis purposes. This line of research has shown promising results where methods from machine learning (such as Support Vector Machines) have been used to identify AD-related patterns from images, for use in diagnosing new individual subjects. In this paper, we propose a new framework for AD classification which makes use of the Linear Program (LP) boosting with novel additional regularization based on spatial "smoothness" in 3D image coordinate spaces. The algorithm formalizes the expectation that since the examples for training the classifier are images, the voxels eventually selected for specifying the decision boundary must constitute spatially contiguous chunks, i.e., "regions" must be preferred over isolated vox...
Proceedings / CVPR, IEEE Computer Society Conference on Computer Vision and Pattern Recognition. IEEE Computer Society Conference on Computer Vision and Pattern Recognition, 2010
We propose a new algorithm for learning kernels for variants of the Normalized Cuts (NCuts) objec... more We propose a new algorithm for learning kernels for variants of the Normalized Cuts (NCuts) objective - i.e., given a set of training examples with known partitions, how should a basis set of similarity functions be combined to induce NCuts favorable distributions. Such a procedure facilitates design of good affinity matrices. It also helps assess the importance of different feature types for discrimination. Rather than formulating the learning problem in terms of the spectral relaxation, the alternative we pursue here is to work in the original discrete setting (i.e., the relaxation occurs much later). We show that this strategy is useful - while the initial specification seems rather difficult to optimize efficiently, a set of manipulations reveal a related model which permits a nice SDP relaxation. A salient feature of our model is that the eventual problem size is only a function of the number of input kernels and not the training set size. This relaxation also allows strong opt...
Advances in neural information processing systems, 2012
Multiple Kernel Learning (MKL) generalizes SVMs to the setting where one simultaneously trains a ... more Multiple Kernel Learning (MKL) generalizes SVMs to the setting where one simultaneously trains a linear classifier and chooses an optimal combination of given base kernels. Model complexity is typically controlled using various norm regularizations on the base kernel mixing coefficients. Existing methods neither regularize nor exploit potentially useful information pertaining to how kernels in the input set 'interact'; that is, higher order kernel-pair relationships that can be easily obtained via unsupervised (similarity, geodesics), supervised (correlation in errors), or domain knowledge driven mechanisms (which features were used to construct the kernel?). We show that by substituting the norm penalty with an arbitrary quadratic function Q 0, one can impose a desired covariance structure on mixing weights, and use this as an inductive bias when learning the concept. This formulation significantly generalizes the widely used 1- and 2-norm MKL objectives. We explore the mod...
Advances in neural information processing systems, 2013
Multiple hypothesis testing is a significant problem in nearly all neuroimaging studies. In order... more Multiple hypothesis testing is a significant problem in nearly all neuroimaging studies. In order to correct for this phenomena, we require a reliable estimate of the Family-Wise Error Rate (FWER). The well known Bonferroni correction method, while simple to implement, is quite conservative, and can substantially under-power a study because it ignores dependencies between test statistics. Permutation testing, on the other hand, is an exact, non-parametric method of estimating the FWER for a given α-threshold, but for acceptably low thresholds the computational burden can be prohibitive. In this paper, we show that permutation testing in fact amounts to populating the columns of a very large matrix P. By analyzing the spectrum of this matrix, under certain conditions, we see that P has a low-rank plus a low-variance residual decomposition which makes it suitable for highly sub-sampled - on the order of 0.5% - matrix completion methods. Based on this observation, we propose a novel pe...
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2009
Diffusion Tensor Imaging (DTI) provides unique information about the underlying tissue structure ... more Diffusion Tensor Imaging (DTI) provides unique information about the underlying tissue structure of brain white matter in vivo, including both the geometry of fiber bundles as well as quantitative information about tissue properties as characterized by measures such as tensor orientation, anisotropy, and size. Our objective in this paper is to evaluate the utility of shape representations of white matter tracts extracted from DTI data for classification of clinically different population groups (here autistic vs control). As a first step, our algorithm extracts fiber bundles passing through approximately marked regions of interest on affinely aligned brain volumes. The subsequent analysis is entirely based on the geometric modeling of the extracted tracts. A key advantage of using such an abstraction is that it allows us to capture invariant features of brains allowing for efficient large sample size studies. We demonstrate that with the use of an appropriate representation of the t...
Advances in neural information processing systems, 2010
We study the problem of segmenting specific white matter structures of interest from Diffusion Te... more We study the problem of segmenting specific white matter structures of interest from Diffusion Tensor (DT-MR) images of the human brain. This is an important requirement in many Neuroimaging studies: for instance, to evaluate whether a brain structure exhibits group level differences as a function of disease in a set of images. Typically, interactive expert guided segmentation has been the method of choice for such applications, but this is tedious for large datasets common today. To address this problem, we endow an image segmentation algorithm with "advice" encoding some global characteristics of the region(s) we want to extract. This is accomplished by constructing (using expert-segmented images) an epitome of a specific region - as a histogram over a bag of 'words' (e.g., suitable feature descriptors). Now, given such a representation, the problem reduces to segmenting a new brain image with additional constraints that enforce consistency between the segmented ...
Alzheimer&amp... more Alzheimer's Disease (AD) and other neurodegenerative diseases affect over 20 million people worldwide, and this number is projected to significantly increase in the coming decades. Proposed imaging-based markers have shown steadily improving levels of sensitivity/specificity in classifying individual subjects as AD or normal. Several of these efforts have utilized statistical machine learning techniques, using brain images as input, as means of deriving such AD-related markers. A common characteristic of this line of research is a focus on either (1) using a single imaging modality for classification, or (2) incorporating several modalities, but reporting separate results for each. One strategy to improve on the success of these methods is to leverage all available imaging modalities together in a single automated learning framework. The rationale is that some subjects may show signs of pathology in one modality but not in another-by combining all available images a clearer view of the progression of disease pathology will emerge. Our method is based on the Multi-Kernel Learning (MKL) framework, which allows the inclusion of an arbitrary number of views of the data in a maximum margin, kernel learning framework. The principal innovation behind MKL is that it learns an optimal combination of kernel (similarity) matrices while simultaneously training a classifier. In classification experiments MKL outperformed an SVM trained on all available features by 3%-4%. We are especially interested in whether such markers are capable of identifying early signs of the disease. To address this question, we have examined whether our multi-modal disease marker (MMDM) can predict conversion from Mild Cognitive Impairment (MCI) to AD. Our experiments reveal that this measure shows significant group differences between MCI subjects who progressed to AD, and those who remained stable for 3 years. These differences were most significant in MMDMs based on imaging data. We also discuss the relationship between our MMDM and an individual's conversion from MCI to AD.
Precise detection and quantification of white matter hyperintensities (WMH) observed in T2-weight... more Precise detection and quantification of white matter hyperintensities (WMH) observed in T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Images (MRI) is of substantial interest in aging, and age-related neurological disorders such as Alzheimer's disease (AD). This is mainly because WMH may reflect co-morbid neural injury or cerebral vascular disease burden. WMH in the older population may be small, diffuse, and irregular in shape, and sufficiently heterogeneous within and across subjects. Here, we pose hyperintensity detection as a supervised inference problem and adapt two learning models, specifically, Support Vector Machines and Random Forests, for this task. Using texture features engineered by texton filter banks, we provide a suite of effective segmentation methods for this problem. Through extensive evaluations on healthy middle-aged and older adults who vary in AD risk, we show that our methods are reliable and robust in segmenting hyperintense regions. A measure of hyperintensity accumulation, referred to as normalized effective WMH volume, is shown to be associated with dementia in older adults and parental family history in cognitively normal subjects. We provide an open source library for hyperintensity detection and accumulation (interfaced with existing neuroimaging tools), that can be adapted for segmentation problems in other neuroimaging studies.
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Papers by Chris Hinrichs