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Register a new userMRI-based Alzheimers disease prediction via distilling the knowledge in multi-modal data
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Mild cognitive impairment (MCI) conversion prediction, i.e., identifying MCI patients of high risks converting to Alzheimers disease (AD), is essential for preventing or slowing the progression of AD. Although previous studies have shown that the fusion of multi-modal data can effectively improve the prediction accuracy, their applications are largely restricted by the limited availability or high cost of multi-modal data. Building an effective prediction model using only magnetic resonance imaging (MRI) remains a challenging research topic. In this work, we propose a multi-modal multi-instance distillation scheme, which aims to distill the knowledge learned from multi-modal data to an MRI-based network for MCI conversion prediction. In contrast to existing distillation algorithms, the proposed multi-instance probabilities demonstrate a superior capability of representing the complicated atrophy distributions, and can guide the MRI-based network to better explore the input MRI. To our best knowledge, this is the first study that attempts to improve an MRI-based prediction model by leveraging extra supervision distilled from multi-modal information. Experiments demonstrate the advantage of our framework, suggesting its potentials in the data-limited clinical settings.
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In recent years, many papers have reported state-of-the-art performance on Alzheimers Disease classification with MRI scans from the Alzheimers Disease Neuroimaging Initiative (ADNI) dataset using convolutional neural networks. However, we discover that when we split that data into training and testing sets at the subject level, we are not able to obtain similar performance, bringing the validity of many of the previous studies into question. Furthermore, we point out that previous works use different subsets of the ADNI data, making comparison across similar works tricky. In this study, we present the results of three splitting methods, discuss the motivations behind their validity, and report our results using all of the available subjects.
Medical imaging datasets are inherently high dimensional with large variability and low sample sizes that limit the effectiveness of deep learning algorithms. Recently, generative adversarial networks (GANs) with the ability to synthesize realist images have shown great potential as an alternative to standard data augmentation techniques. Our work focuses on cross-modality synthesis of fluorodeoxyglucose~(FDG) Positron Emission Tomography~(PET) scans from structural Magnetic Resonance~(MR) images using generative models to facilitate multi-modal diagnosis of Alzheimers disease (AD). Specifically, we propose a novel end-to-end, globally and locally aware image-to-image translation GAN (GLA-GAN) with a multi-path architecture that enforces both global structural integrity and fidelity to local details. We further supplement the standard adversarial loss with voxel-level intensity, multi-scale structural similarity (MS-SSIM) and region-of-interest (ROI) based loss components that reduce reconstruction error, enforce structural consistency at different scales and perceive variation in regional sensitivity to AD respectively. Experimental results demonstrate that our GLA-GAN not only generates synthesized FDG-PET scans with enhanced image quality but also superior clinical utility in improving AD diagnosis compared to state-of-the-art models. Finally, we attempt to interpret some of the internal units of the GAN that are closely related to this specific cross-modality generation task.
In clinical practice, magnetic resonance imaging (MRI) with multiple contrasts is usually acquired in a single study to assess different properties of the same region of interest in human body. The whole acquisition process can be accelerated by having one or more modalities under-sampled in the $k$-space. Recent researches demonstrate that, considering the redundancy between different contrasts or modalities, a target MRI modality under-sampled in the $k$-space can be more efficiently reconstructed with a fully-sampled MRI contrast as the reference modality. However, we find that the performance of the above multi-modal reconstruction can be negatively affected by subtle spatial misalignment between different contrasts, which is actually common in clinical practice. In this paper, to compensate for such spatial misalignment, we integrate the spatial alignment network with multi-modal reconstruction towards better reconstruction quality of the target modality. First, the spatial alignment network estimates the spatial misalignment between the fully-sampled reference and the under-sampled target images, and warps the reference image accordingly. Then, the aligned fully-sampled reference image joins the multi-modal reconstruction of the under-sampled target image. Also, considering the contrast difference between the target and the reference images, we particularly design the cross-modality-synthesis-based registration loss, in combination with the reconstruction loss, to jointly train the spatial alignment network and the reconstruction network. Experiments on both clinical MRI and multi-coil $k$-space raw data demonstrate the superiority and robustness of multi-modal MRI reconstruction empowered with our spatial alignment network. Our code is publicly available at url{https://github.com/woxuankai/SpatialAlignmentNetwork}.
Background: Although convolutional neural networks (CNN) achieve high diagnostic accuracy for detecting Alzheimers disease (AD) dementia based on magnetic resonance imaging (MRI) scans, they are not yet applied in clinical routine. One important reason for this is a lack of model comprehensibility. Recently developed visualization methods for deriving CNN relevance maps may help to fill this gap. We investigated whether models with higher accuracy also rely more on discriminative brain regions predefined by prior knowledge. Methods: We trained a CNN for the detection of AD in N=663 T1-weighted MRI scans of patients with dementia and amnestic mild cognitive impairment (MCI) and verified the accuracy of the models via cross-validation and in three independent samples including N=1655 cases. We evaluated the association of relevance scores and hippocampus volume to validate the clinical utility of this approach. To improve model comprehensibility, we implemented an interactive visualization of 3D CNN relevance maps. Results: Across three independent datasets, group separation showed high accuracy for AD dementia vs. controls (AUC$geq$0.92) and moderate accuracy for MCI vs. controls (AUC$approx$0.75). Relevance maps indicated that hippocampal atrophy was considered as the most informative factor for AD detection, with additional contributions from atrophy in other cortical and subcortical regions. Relevance scores within the hippocampus were highly correlated with hippocampal volumes (Pearsons r$approx$-0.86, p<0.001). Conclusion: The relevance maps highlighted atrophy in regions that we had hypothesized a priori. This strengthens the comprehensibility of the CNN models, which were trained in a purely data-driven manner based on the scans and diagnosis labels.
Current neuroimaging techniques provide paths to investigate the structure and function of the brain in vivo and have made great advances in understanding Alzheimers disease (AD). However, the group-level analyses prevalently used for investigation and understanding of the disease are not applicable for diagnosis of individuals. More recently, deep learning, which can efficiently analyze large-scale complex patterns in 3D brain images, has helped pave the way for computer-aided individual diagnosis by providing accurate and automated disease classification. Great progress has been made in classifying AD with deep learning models developed upon increasingly available structural MRI data. The lack of scale-matched functional neuroimaging data prevents such models from being further improved by observing functional changes in pathophysiology. Here we propose a potential solution by first learning a structural-to-functional transformation in brain MRI, and further synthesizing spatially matched functional images from large-scale structural scans. We evaluated our approach by building computational models to discriminate patients with AD from healthy normal subjects and demonstrated a performance boost after combining the structural and synthesized functional brain images into the same model. Furthermore, our regional analyses identified the temporal lobe to be the most predictive structural-region and the parieto-occipital lobe to be the most predictive functional-region of our model, which are both in concordance with previous group-level neuroimaging findings. Together, we demonstrate the potential of deep learning with large-scale structural and synthesized functional MRI to impact AD classification and to identify ADs neuroimaging signatures.
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