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 being 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 observe 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.

This paper introduces CompressedMediQ, a novel hybrid quantum-classical machine learning pipeline specifically developed to address the computational challenges associated with high-dimensional multi-class neuroimaging data analysis. Standard neuroimaging datasets, such as 4D MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Neuroimaging in Frontotemporal Dementia (NIFD), present significant hurdles due to their vast size and complexity. CompressedMediQ integrates classical high-performance computing (HPC) nodes for advanced MRI pre-processing and Convolutional Neural Network (CNN)-PCA-based feature extraction and reduction, addressing the limited-qubit availability for quantum data encoding in the NISQ (Noisy Intermediate-Scale Quantum) era. This is followed by Quantum Support Vector Machine (QSVM) classification. By utilizing quantum kernel methods, the pipeline optimizes feature mapping and classification, enhancing data separability and outperforming traditional neuroimaging analysis techniques. Experimental results highlight the pipeline's superior accuracy in dementia staging, validating the practical use of quantum machine learning in clinical diagnostics. Despite the limitations of NISQ devices, this proof-of-concept demonstrates the transformative potential of quantum-enhanced learning, paving the way for scalable and precise diagnostic tools in healthcare and signal processing.

In this project, we have explored machine learning approaches for predicting hearing loss thresholds on the brain's gray matter 3D images. We have solved the problem statement in two phases. In the first phase, we used a 3D CNN model to reduce high-dimensional input into latent space and decode it into an original image to represent the input in rich feature space. In the second phase, we utilized this model to reduce input into rich features and used these features to train standard machine learning models for predicting hearing thresholds. We have experimented with autoencoders and variational autoencoders in the first phase for dimensionality reduction and explored random forest, XGBoost and multi-layer perceptron for regressing the thresholds. We split the given data set into training and testing sets and achieved an 8.80 range and 22.57 range for PT500 and PT4000 on the test set, respectively. We got the lowest RMSE using multi-layer perceptron among the other models. Our approach leverages the unique capabilities of VAEs to capture complex, non-linear relationships within high-dimensional neuroimaging data. We rigorously evaluated the models using various metrics, focusing on the root mean squared error (RMSE). The results highlight the efficacy of the multi-layer neural network model, which outperformed other techniques in terms of accuracy. This project advances the application of data mining in medical diagnostics and enhances our understanding of age-related hearing loss through innovative machine-learning frameworks.

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 vector of base kernel mixing coefficients. Existing methods, however, 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 \succeq 0, one can impose a desired covariance structure on mixing coefficient selection, and use this as an inductive bias when learning the concept. This formulation significantly generalizes the widely used 1- and 2-norm MKL objectives.

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 being 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 observe 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.

A model can be considered as transparent when it (or all parts of it) can be fully understood as such, or when the learning process is understandable. A natural and common candidate that fits, at first sight, these criteria is the linear regression algorithm, where coefficients are usually seen as the individual contributions of the input features. Another candidate is the decision tree approach where model predictions can be broken down into a series of understandable operations. One can reasonably consider these models as transparent: one can easily identify the features that were used to take the decision. However, one may need to be cautious not to push too far the medical interpretation.

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 vector of base kernel mixing coefficients. Existing methods, however, 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 \succeq 0, one can impose a desired covariance structure on mixing coefficient selection, and use this as an inductive bias when learning the concept. This formulation significantly generalizes the widely used 1- and 2-norm MKL objectives.

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 being 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 observe 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.

In the 70s a novel branch of statistics emerged focusing its effort in selecting a function in the pattern recognition problem, which fulfils a definite relationship between the quality of the approximation and its complexity. These data-driven approaches are mainly devoted to problems of estimating dependencies with limited sample sizes and comprise all the empirical out-of sample generalization approaches, e.g. cross validation (CV) approaches. Although the latter are \emph{not designed for testing competing hypothesis or comparing different models} in neuroimaging, there are a number of theoretical developments within this theory which could be employed to derive a Statistical Agnostic (non-parametric) Mapping (SAM) at voxel or multi-voxel level. Moreover, SAMs could relieve i) the problem of instability in limited sample sizes when estimating the actual risk via the CV approaches, e.g. large error bars, and provide ii) an alternative way of Family-wise-error (FWE) corrected p-value maps in inferential statistics for hypothesis testing. In this sense, we propose a novel framework in neuroimaging based on concentration inequalities, which results in (i) a rigorous development for model validation with a small sample/dimension ratio, and (ii) a less-conservative procedure than FWE p-value correction, to determine the brain significance maps from the inferences made using small upper bounds of the actual risk.

Traditional voxel-level multiple testing procedures in neuroimaging, mostly $p$-value based, often ignore the spatial correlations among neighboring voxels and thus suffer from substantial loss of power. We extend the local-significance-index based procedure originally developed for the hidden Markov chain models, which aims to minimize the false nondiscovery rate subject to a constraint on the false discovery rate, to three-dimensional neuroimaging data using a hidden Markov random field model. A generalized expectation-maximization algorithm for maximizing the penalized likelihood is proposed for estimating the model parameters. Extensive simulations show that the proposed approach is more powerful than conventional false discovery rate procedures. We apply the method to the comparison between mild cognitive impairment, a disease status with increased risk of developing Alzheimer's or another dementia, and normal controls in the FDG-PET imaging study of the Alzheimer's Disease Neuroimaging Initiative.