An Information Theory Model for Optimizing Quantitative Magnetic Resonance Imaging Acquisitions

Quantitative magnetic resonance imaging (qMRI) is a powerful group of imaging techniques with a growing number of clinical applications, including synthetic image generation in post-processing, automatic segmentation, and diagnosis of disease from quantitative parameter values. Currently, acquisition parameter selection is performed empirically for quantitative MRI. Tuning parameters for different scan times, tissues, and resolutions requires some measure of trial and error. There is an opportunity to quantitatively optimize these acquisition parameters in order to maximize image quality and the reliability of the previously mentioned methods which follow image acquisition. The objective of this work is to introduce and evaluate a quantitative method for selecting parameters that minimize image variability. An information theory framework was developed for this purpose and applied to a 3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse (3D-QALAS) signal model for synthetic MRI. In this framework, mutual information is used to measure the information gained by a measurement as a function of acquisition parameters, quantifying the information content of the acquisition parameters and allowing informed parameter selection. The information theory framework was tested on synthetic data generated from a representative mathematical phantom, measurements acquired on a qMRI multiparametric imaging standard phantom, and in vivo measurements in a human brain. The application of this information theory framework resulted in successful parameter optimization with respect to mutual information. Both the phantom and in vivo measurements showed that higher mutual information calculated by the model correlated with smaller standard deviation in the reconstructed parametric maps. With this framework, optimal acquisition parameters can be selected to improve image quality, image repeatability, or scan time. This method could reduce the time and labor necessary to achieve images of the desired quality. Making an informed acquisition parameter selection reduces uncertainty in the imaging output and optimizes information gain within the bounds of clinical constraints

Analyzing hierarchical multi-view MRI data with StaPLR: An application to Alzheimer's disease classification

Multi-view data refers to a setting where features are divided into feature sets, for example because they correspond to different sources. Stacked penalized logistic regression (StaPLR) is a recently introduced method that can be used for classification and automatically selecting the views that are most important for prediction. We introduce an extension of this method to a setting where the data has a hierarchical multi-view structure. We also introduce a new view importance measure for StaPLR, which allows us to compare the importance of views at any level of the hierarchy. We apply our extended StaPLR algorithm to Alzheimer's disease classification where different MRI measures have been calculated from three scan types: structural MRI, diffusion-weighted MRI, and resting-state fMRI. StaPLR can identify which scan types and which derived MRI measures are most important for classification, and it outperforms elastic net regression in classification performance.Comment: 36 pages, 9 figures. Accepted manuscrip

Emerging Techniques in Breast MRI

As indicated throughout this chapter, there is a constant effort to move to more sensitive, specific, and quantitative methods for characterizing breast tissue via magnetic resonance imaging (MRI). In the present chapter, we focus on six emerging techniques that seek to quantitatively interrogate the physiological and biochemical properties of the breast. At the physiological scale, we present an overview of ultrafast dynamic contrast-enhanced MRI and magnetic resonance elastography which provide remarkable insights into the vascular and mechanical properties of tissue, respectively. Moving to the biochemical scale, magnetization transfer, chemical exchange saturation transfer, and spectroscopy (both “conventional” and hyperpolarized) methods all provide unique, noninvasive, insights into tumor metabolism. Given the breadth and depth of information that can be obtained in a single MRI session, methods of data synthesis and interpretation must also be developed. Thus, we conclude the chapter with an introduction to two very different, though complementary, methods of data analysis: (1) radiomics and habitat imaging, and (2) mechanism-based mathematical modeling

Diagnostic classification of childhood cancer using multiscale transcriptomics

The causes of pediatric cancers’ distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types

Combining network neuroscience and machine learning to discover neurocognitive subgroups in aging individuals at risk of or diagnosed with Alzheimer’s disease

Dementia is a complicated medical condition that negatively impacts an individual’s mental and physical well-being, increasing the risk of early mortality. The risk of developing dementia increases with age, although rates vary according to several factors, such as sex, race, and genetics. While Alzheimer’s disease (AD), the most common form of dementia, is often associated with episodic memory impairment, individuals with AD can present with diverse cognitive profiles. Similarly, heterogeneous subgroups of typically aging individuals may show impairments in both general and specific forms of attention, memory, and/or executive functioning. Individual variation in cognitive impairments experienced by aging individuals, and resistance or resilience to cognitive decline, can be linked to functional brain network organization and communication capacity. This study aimed to disentangle shared and unique aspects of cognitive impairment and functional network topology seen in healthy aging, early-stage or preclinical dementia, and AD. Specifically, Aim 1 sought to establish if weighted metrics that index redundancy in unthresholded functional brain networks, as a proxy of brain and cognitive reserve, support general and/or specific forms of cognition. Aim 2 sought to establish whether a combination of core demographic risk factors (age, sex, and education), cognitive measures, and weighted functional network metrics could accurately distinguish otherwise cognitively normal individuals (CN), from CN who will convert to AD (AD-C), and individuals diagnosed with AD, using supervised machine learning. Aim 3 specifically sought to quantify the presence of data-driven neurocognitive subgroups utilizing a combination of unsupervised and supervised machine learning. In the present study, redundancy-based metrics (global communicability and global clustering coefficient) were not predictive of overall cognitive functioning, nor were they the most informative predictors when attempting to distinguish between CN, AD-C, and AD participants using machine learning. When classifying older individuals with and without AD, neuropsychological measures were more informative than metrics assessing global network topology, including redundancy-based measures. Finally, while this study failed to identify cognitive subgroups previously reported in MCI and AD participants, AD converters correctly classified or misclassified as AD showed diverging neurocognitive profiles and may represent a subset of individuals with primarily executive, as opposed to memory-related impairments, respectively.Doctor of Philosoph

Analyzing hierarchical multi-view MRI data with StaPLR: an application to Alzheimer's disease classification

Multivariate analysis of psychological dat

Analyzing hierarchical multi-view MRI Data With StaPLR An Application to Alzheimer's disease classification: an application to Alzheimer's disease classification

Multi-view data refers to a setting where features are divided into feature sets, for example because they correspond to different sources. Stacked penalized logistic regression (StaPLR) is a recently introduced method that can be used for classification and automatically selecting the views that are most important for prediction. We introduce an extension of this method to a setting where the data has a hierarchical multi-view structure. We also introduce a new view importance measure for StaPLR, which allows us to compare the importance of views at any level of the hierarchy. We apply our extended StaPLR algorithm to Alzheimer's disease classification where different MRI measures have been calculated from three scan types: structural MRI, diffusion-weighted MRI, and resting-state fMRI. StaPLR can identify which scan types and which derived MRI measures are most important for classification, and it outperforms elastic net regression in classification performance. Horizon 2020(H2020)101041064Multivariate analysis of psychological dat

Reverse Engineering the Human Brain: An Evolutionary Computation Approach to the Analysis of fMRI

The field of neuroimaging has truly become data rich, and as such, novel analytical methods capable of gleaning meaningful information from large stores of imaging data are in high demand. Those methods that might also be applicable on the level of individual subjects, and thus potentially useful clinically, are of special interest. In this dissertation we introduce just such a method, called nonlinear functional mapping (NFM), and demonstrate its application in the analysis of resting state fMRI (functional Magnetic Resonance Imaging) from a 242-subject subset of the IMAGEN project, a European study of risk-taking behavior in adolescents that includes longitudinal phenotypic, behavioral, genetic, and neuroimaging data. Functional mapping employs a computational technique inspired by biological evolution to discover and mathematically characterize interactions among ROI (regions of interest), without making linear or univariate assumptions. Statistics of the resulting interaction relationships comport with recent independent work, constituting a preliminary cross-validation. Furthermore, nonlinear terms are ubiquitous in the models generated by NFM, suggesting that some of the interactions characterized here are not discoverable by standard linear methods of analysis. One such nonlinear interaction is discussed in the context of a direct comparison with a procedure involving pairwise correlation, designed to be an analogous linear version of functional mapping. Another such interaction suggests a novel distinction in brain function between drinking and non-drinking adolescents: a tighter coupling of ROI associated with emotion, reward, and interceptive processes such as thirst, among drinkers. Finally, we outline many improvements and extensions of the methodology to reduce computational expense, complement other analytical tools like graph-theoretic analysis, and possibly allow for voxel level functional mapping to eliminate the necessity of ROI selection