Prediction of Treatment Response to Neoadjuvant Chemotherapy for Breast Cancer via Early Changes in Tumor Heterogeneity Captured by DCE-MRI Registration.

We analyzed DCE-MR images from 132 women with locally advanced breast cancer from the I-SPY1 trial to evaluate changes of intra-tumor heterogeneity for augmenting early prediction of pathologic complete response (pCR) and recurrence-free survival (RFS) after neoadjuvant chemotherapy (NAC). Utilizing image registration, voxel-wise changes including tumor deformations and changes in DCE-MRI kinetic features were computed to characterize heterogeneous changes within the tumor. Using five-fold cross-validation, logistic regression and Cox regression were performed to model pCR and RFS, respectively. The extracted imaging features were evaluated in augmenting established predictors, including functional tumor volume (FTV) and histopathologic and demographic factors, using the area under the curve (AUC) and the C-statistic as performance measures. The extracted voxel-wise features were also compared to analogous conventional aggregated features to evaluate the potential advantage of voxel-wise analysis. Voxel-wise features improved prediction of pCR (AUC = 0.78 (±0.03) vs 0.71 (±0.04), p < 0.05 and RFS (C-statistic = 0.76 ( ± 0.05), vs 0.63 ( ± 0.01)), p < 0.05, while models based on analogous aggregate imaging features did not show appreciable performance changes (p > 0.05). Furthermore, all selected voxel-wise features demonstrated significant association with outcome (p < 0.05). Thus, precise measures of voxel-wise changes in tumor heterogeneity extracted from registered DCE-MRI scans can improve early prediction of neoadjuvant treatment outcomes in locally advanced breast cancer

Control-Group Feature Normalization for Multivariate Pattern Analysis Using the Support Vector Machine

Normalization of feature vector values is a common practice in machine learning. Generally, each feature value is standardized to the unit hypercube or by normalizing to zero mean and unit variance. Classification decisions based on support vector machines (SVMs) or by other methods are sensitive to the specific normalization used on the features. In the context of multivariate pattern analysis using neuroimaging data, standardization effectively up- and down-weights features based on their individual variability. Since the standard approach uses the entire data set to guide the normalization it utilizes the total variability of these features. This total variation is inevitably dependent on the amount of marginal separation between groups. Thus, such a normalization may attenuate the separability of the data in high dimensional space. In this work we propose an alternate approach that uses an estimate of the control-group standard deviation to normalize features before training. We also show that control-based normalization provides better interpretation with respect to the estimated multivariate disease pattern and improves the classifier performance in many cases

Multiscale 3D Shape Analysis using Spherical Wavelets

©2005 Springer. The original publication is available at www.springerlink.com: http://dx.doi.org/10.1007/11566489_57DOI: 10.1007/11566489_57Shape priors attempt to represent biological variations within a population. When variations are global, Principal Component Analysis (PCA) can be used to learn major modes of variation, even from a limited training set. However, when significant local variations exist, PCA typically cannot represent such variations from a small training set. To address this issue, we present a novel algorithm that learns shape variations from data at multiple scales and locations using spherical wavelets and spectral graph partitioning. Our results show that when the training set is small, our algorithm significantly improves the approximation of shapes in a testing set over PCA, which tends to oversmooth data

Multilinear Wavelets: A Statistical Shape Space for Human Faces

We present a statistical model for $3$D human faces in varying expression, which decomposes the surface of the face using a wavelet transform, and learns many localized, decorrelated multilinear models on the resulting coefficients. Using this model we are able to reconstruct faces from noisy and occluded $3$D face scans, and facial motion sequences. Accurate reconstruction of face shape is important for applications such as tele-presence and gaming. The localized and multi-scale nature of our model allows for recovery of fine-scale detail while retaining robustness to severe noise and occlusion, and is computationally efficient and scalable. We validate these properties experimentally on challenging data in the form of static scans and motion sequences. We show that in comparison to a global multilinear model, our model better preserves fine detail and is computationally faster, while in comparison to a localized PCA model, our model better handles variation in expression, is faster, and allows us to fix identity parameters for a given subject.Comment: 10 pages, 7 figures; accepted to ECCV 201

IS MRI-BASED VOLUME A MEDIATOR OF THE ASSOCIATION OF CUMULATIVE LEAD DOSE WITH COGNITIVE FUNCTION?

This work considers the pathway through which past occupational lead exposure impacts cognitive function using cross-sectional data. It is motivated by studies linking cumulative lead dose with brain volumes, volumes with cognitive function, and lead dose with cognitive function. It is hypothesized that the brain regions associated with lead mediate a portion of the association between lead dose and cognitive function. The data were derived from an ongoing study of 513 former organolead manufacturing workers. Using MRIs, a novel analysis was performed to investigate Mediation. Volumes associated with cognitive function and lead dose were derived using registered images and used in a subsequent mediation analysis. Cumulative lead dose was associated with adverse function in the visuo-construction, executive functioning and eye-hand coordination domains. Of these, there was strong evidence of volumetric mediation of lead’s effect on cognition in the visuo-construction domain, a moderate amount for eye-hand coordination, and limited evidence for executive functioning. A second path analysis based approach was also performed. To address the possibility that chance associations explained these findings, a permuted analysis was conducted, the results of which support the mediation inferences. The approach to the evaluation of volumetric mediation may have general applicability in epidemiologic neuroimaging settings

FUNCTIONAL PRINCIPAL COMPONENTS MODEL FOR HIGH-DIMENSIONAL BRAIN IMAGING

We establish a fundamental equivalence between singular value decomposition (SVD) and functional principal components analysis (FPCA) models. The constructive relationship allows to deploy the numerical efficiency of SVD to fully estimate the components of FPCA, even for extremely high-dimensional functional objects, such as brain images. As an example, a functional mixed effect model is fitted to high-resolution morphometric (RAVENS) images. The main directions of morphometric variation in brain volumes are identified and discussed

Addressing Confounding in Predictive Models with an Application to Neuroimaging

Understanding structural changes in the brain that are caused by a particular disease is a major goal of neuroimaging research. Multivariate pattern analysis (MVPA) comprises a collection of tools that can be used to understand complex disease effects across the brain. We discuss several important issues that must be considered when analyzing data from neuroimaging studies using MVPA. In particular, we focus on the consequences of confounding by non-imaging variables such as age and sex on the results of MVPA. After reviewing current practice to address confounding in neuroimaging studies, we propose an alternative approach based on inverse probability weighting. Although the proposed method is motivated by neuroimaging applications, it is broadly applicable to many problems in machine learning and predictive modeling. We demonstrate the advantages of our approach on simulated and real data examples