Background: Data driven stratification of patients into biologically informed subtypes holds promise for precision neuropsychiatry, yet neuroimaging-based clustering methods often fail to generalize across cohorts. While algorithmic innovations have focused on model complexity, the role of underlying dataset characteristics remains underexplored. We hypothesized that cluster separation, size imbalance, noise, and the direction and magnitude of disease-related effects in the input data critically determine both within-algorithm accuracy and reproducibility. Methods: We evaluated 4 widely used stratification algorithms, HYDRA, SuStaIn, SmileGAN, and SurrealGAN, on a suite of synthetic brain-morphometry cohorts derived from the Human Connectome Project Young Adult dataset. Three global transformation patterns were applied to 600 pseudo-patients against 508 controls, followed by 4 within-dataset variations varying cluster count (k=2-6), overlap, and effect magnitude. Algorithm performance was quantified by accuracy in recovering the known ground-truth clusters. Results: Across 122 synthetic scenarios, data complexity consistently outweighed algorithm choice in predicting stratification success. Well-separated clusters yielded high accuracy for all methods, whereas overlapping, unequal-sized, or subtle effects reduced accuracy by up to 50%. SuStaIn could not scale beyond 17 features, HYDRA's accuracy varied unpredictably with data heterogeneity. SmileGAN and SurrealGAN maintained robust pattern detection but did not assign discrete cluster labels to individuals. Conclusions: The study results demonstrate the impact of statistical properties of input data across algorithms and highlight the need for using realistic dataset distributions when new algorithms are being developed and suggest greater focus on data-centric strategies that actively shape and standardize the input distributions.
Automated feature extraction from MRI brain scans and diagnosis of Alzheimer's disease are ongoing challenges. With advances in 3D imaging technology, 3D data acquisition is becoming more viable and efficient than its 2D counterpart. Rather than using feature-based vectors, in this paper, for the first time, we suggest a pipeline to extract novel covariance-based descriptors from the cortical surface using the Ricci energy optimization. The covariance descriptors are components of the nonlinear manifold of symmetric positive-definite matrices, thus we focus on using the Gaussian radial basis function to apply manifold-based classification to the 3D shape problem. Applying this novel signature to the analysis of abnormal cortical brain morphometry allows for diagnosing Alzheimer's disease. Experimental studies performed on about two hundred 3D MRI brain models, gathered from Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset demonstrate the effectiveness of our descriptors in achieving remarkable classification accuracy.
With the rise of open data, identifiability of individuals based on 3D renderings obtained from routine structural magnetic resonance imaging (MRI) scans of the head has become a growing privacy concern. To protect subject privacy, several algorithms have been developed to de-identify imaging data using blurring, defacing or refacing. Completely removing facial structures provides the best re-identification protection but can significantly impact post-processing steps, like brain morphometry. As an alternative, refacing methods that replace individual facial structures with generic templates have a lower effect on the geometry and intensity distribution of original scans, and are able to provide more consistent post-processing results by the price of higher re-identification risk and computational complexity. In the current study, we propose a novel method for anonymised face generation for defaced 3D T1-weighted scans based on a 3D conditional generative adversarial network. To evaluate the performance of the proposed de-identification tool, a comparative study was conducted between several existing defacing and refacing tools, with two different segmentation algorithms (FAST and Morphobox). The aim was to evaluate (i) impact on brain morphometry reproducibility, (ii) re-identification risk, (iii) balance between (i) and (ii), and (iv) the processing time. The proposed method takes 9 seconds for face generation and is suitable for recovering consistent post-processing results after defacing.
For the first time, we propose using a multiple instance learning based convolution-free transformer model, called Multiple Instance Neuroimage Transformer (MINiT), for the classification of T1weighted (T1w) MRIs. We first present several variants of transformer models adopted for neuroimages. These models extract non-overlapping 3D blocks from the input volume and perform multi-headed self-attention on a sequence of their linear projections. MINiT, on the other hand, treats each of the non-overlapping 3D blocks of the input MRI as its own instance, splitting it further into non-overlapping 3D patches, on which multi-headed self-attention is computed. As a proof-of-concept, we evaluate the efficacy of our model by training it to identify sex from T1w-MRIs of two public datasets: Adolescent Brain Cognitive Development (ABCD) and the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA). The learned attention maps highlight voxels contributing to identifying sex differences in brain morphometry. The code is available at https://github.com/singlaayush/MINIT.
Motivation: Brain morphometry from magnetic resonance imaging (MRI) is a promising neuroimaging biomarker for the non-invasive diagnosis and monitoring of neurodegenerative and neurological disorders. Current tools for brain morphometry often come with a high computational burden, making them hard to use in clinical routine, where time is often an issue. We propose a deep learning-based approach to predict the volumes of anatomically delineated subcortical regions of interest (ROI), and mean thicknesses and curvatures of cortical parcellations directly from T1-weighted MRI. Advantages are the timely availability of results while maintaining a clinically relevant accuracy. Materials and Methods: An anonymized dataset of 574 subjects (443 healthy controls and 131 patients with epilepsy) was used for the supervised training of a convolutional neural network (CNN). A silver-standard ground truth was generated with FreeSurfer 6.0. Results: The CNN predicts a total of 165 morphometric measures directly from raw MR images. Analysis of the results using intraclass correlation coefficients showed, in general, good correlation with FreeSurfer generated ground truth data, with some of the regions nearly reaching human inter-rater performance (ICC > 0.75). Cortical thicknesses predicted by the CNN showed cross-sectional annual age-related gray matter atrophy rates both globally (thickness change of −0.004 mm/year) and regionally in agreement with the literature. A statistical test to dichotomize patients with epilepsy from healthy controls revealed similar effect sizes for structures affecting all subtypes as reported in a large-scale epilepsy study. Conclusions: We demonstrate the general feasibility of using deep learning to estimate human brain morphometry directly from T1-weighted MRI within seconds. A comparison of the results to other publications shows accuracies of comparable magnitudes for the subcortical volumes and cortical thicknesses.
Brain morphometry from magnetic resonance imaging (MRI) is a consolidated biomarker for many neurodegenerative diseases. Recent advances in this domain indicate that deep convolutional neural networks can infer morphometric measurements within a few seconds. Nevertheless, the accuracy of the devised model for insightful bio-markers (mean curvature and thickness) remains unsatisfactory. In this paper, we propose a more accurate and efficient neural network model for brain morphometry named HerstonNet. More specifically, we develop a 3D ResNet-based neural network to learn rich features directly from MRI, design a multi-scale regression scheme by predicting morphometric measures at feature maps of different resolutions, and leverage a robust optimization method to avoid poor quality minima and reduce the prediction variance. As a result, HerstonNet improves the existing approach by 24.30% in terms of intraclass correlation coefficient (agreement measure) to FreeSurfer silver-standards while maintaining a competitive run-time.
Sparse systems are usually parameterized by a tuning parameter that determines the sparsity of the system. How to choose the right tuning parameter is a fundamental and difficult problem in learning the sparse system. In this paper, by treating the the tuning parameter as an additional dimension, persistent homological structures over the parameter space is introduced and explored. The structures are then further exploited in speeding up the computation using the proposed soft-thresholding technique. The topological structures are further used as multivariate features in the tensor-based morphometry (TBM) in characterizing white matter alterations in children who have experienced severe early life stress and maltreatment. These analyses reveal that stress-exposed children exhibit more diffuse anatomical organization across the whole white matter region.