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Combining neuroimaging datasets from multiple sites and scanners can help increase statistical power and thus provide greater insight into subtle neuroanatomical effects. However, site-specific effects pose a challenge by potentially obscuring the biological signal and introducing unwanted variance. Existing harmonization techniques, which use statistical models to remove such effects, have been shown to incompletely remove site effects while also failing to preserve biological variability. More recently, generative models using GANs or autoencoder-based approaches, have been proposed for site adjustment. However, such methods are known for instability during training or blurry image generation. In recent years, diffusion models have become increasingly popular for their ability to generate high-quality synthetic images. In this work, we introduce the disentangled diffusion autoencoder (DDAE), a novel diffusion model designed for controlling specific aspects of an image. We apply the DDAE to the task of harmonizing MR images by generating high-quality site-adjusted images that preserve biological variability. We use data from 7 different sites and demonstrate the DDAE's superiority in generating high-resolution, harmonized 2D MR images over previous approaches. As far as we are aware, this work marks the first diffusion-based model for site adjustment of neuroimaging data.

There has been a growing interest in recent years in modelling multiple modalities (or views) of data to for example, understand the relationship between modalities or to generate missing data. Multi-view autoencoders have gained significant traction for their adaptability and versatility in modelling multi-modal data, demonstrating an ability to tailor their approach to suit the characteristics of the data at hand. However, most multi-view autoencoders have inconsistent notation and are often implemented using different coding frameworks. To address this, we present a unified mathematical framework for multi-view autoencoders, consolidating their formulations. Moreover, we offer insights into the motivation and theoretical advantages of each model. To facilitate accessibility and practical use, we extend the documentation and functionality of the previously introduced \texttt{multi-view-AE} library. This library offers Python implementations of numerous multi-view autoencoder models, presented within a user-friendly framework. Through benchmarking experiments, we evaluate our implementations against previous ones, demonstrating comparable or superior performance. This work aims to establish a cohesive foundation for multi-modal modelling, serving as a valuable educational resource in the field.

A major challenge in imaging genetics and similar fields is to link high-dimensional data in one domain, e.g., genetic data, to high dimensional data in a second domain, e.g., brain imaging data. The standard approach in the area are mass univariate analyses across genetic factors and imaging phenotypes. That entails executing one genome-wide association study (GWAS) for each pre-defined imaging measure. Although this approach has been tremendously successful, one shortcoming is that phenotypes must be pre-defined. Consequently, effects that are not confined to pre-selected regions of interest or that reflect larger brain-wide patterns can easily be missed. In this work we introduce a Partial Least Squares (PLS)-based framework, which we term Cluster-Bootstrap PLS (CLUB-PLS), that can work with large input dimensions in both domains as well as with large sample sizes. One key factor of the framework is to use cluster bootstrap to provide robust statistics for single input features in both domains. We applied CLUB-PLS to investigating the genetic basis of surface area and cortical thickness in a sample of 33,000 subjects from the UK Biobank. We found 107 genome-wide significant locus-phenotype pairs that are linked to 386 different genes. We found that a vast majority of these loci could be technically validated at a high rate: using classic GWAS or Genome-Wide Inferred Statistics (GWIS) we found that 85 locus-phenotype pairs exceeded the genome-wide suggestive (P<1e-05) threshold., Comment: 12 pages, 4 Figures, 2 Tables

One of the challenges of studying common neurological disorders is disease heterogeneity including differences in causes, neuroimaging characteristics, comorbidities, or genetic variation. Normative modelling has become a popular method for studying such cohorts where the 'normal' behaviour of a physiological system is modelled and can be used at subject level to detect deviations relating to disease pathology. For many heterogeneous diseases, we expect to observe abnormalities across a range of neuroimaging and biological variables. However, thus far, normative models have largely been developed for studying a single imaging modality. We aim to develop a multi-modal normative modelling framework where abnormality is aggregated across variables of multiple modalities and is better able to detect deviations than uni-modal baselines. We propose two multi-modal VAE normative models to detect subject level deviations across T1 and DTI data. Our proposed models were better able to detect diseased individuals, capture disease severity, and correlate with patient cognition than baseline approaches. We also propose a multivariate latent deviation metric, measuring deviations from the joint latent space, which outperformed feature-based metrics.

When developing deep neural networks for segmenting intraoperative ultrasound images, several practical issues are encountered frequently, such as the presence of ultrasound frames that do not contain regions of interest and the high variance in ground-truth labels. In this study, we evaluate the utility of a pre-screening classification network prior to the segmentation network. Experimental results demonstrate that such a classifier, minimising frame classification errors, was able to directly impact the number of false positive and false negative frames. Importantly, the segmentation accuracy on the classifier-selected frames, that would be segmented, remains comparable to or better than those from standalone segmentation networks. Interestingly, the efficacy of the pre-screening classifier was affected by the sampling methods for training labels from multiple observers, a seemingly independent problem. We show experimentally that a previously proposed approach, combining random sampling and consensus labels, may need to be adapted to perform well in our application. Furthermore, this work aims to share practical experience in developing a machine learning application that assists highly variable interventional imaging for prostate cancer patients, to present robust and reproducible open-source implementations, and to report a set of comprehensive results and analysis comparing these practical, yet important, options in a real-world clinical application., Comment: Accepted to ASMUS@MICCAI 2021

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials., Comment: Presents final results of the TADPOLE competition. 60 pages, 7 tables, 14 figures

At this moment, databanks worldwide contain brain images of previously unimaginable numbers. Combined with developments in data science, these massive data provide the potential to better understand the genetic underpinnings of brain diseases. However, different datasets, which are stored at different institutions, cannot always be shared directly due to privacy and legal concerns, thus limiting the full exploitation of big data in the study of brain disorders. Here we propose a federated learning framework for securely accessing and meta-analyzing any biomedical data without sharing individual information. We illustrate our framework by investigating brain structural relationships across diseases and clinical cohorts. The framework is first tested on synthetic data and then applied to multi-centric, multi-database studies including ADNI, PPMI, MIRIAD and UK Biobank, showing the potential of the approach for further applications in distributed analysis of multi-centric cohorts, Comment: Federated learning, distributed databases, PCA, SVD, meta-analysis, brain disease