Brain age identification from diffusion MRI synergistically predicts neurodegenerative disease

Estimated brain age from magnetic resonance image (MRI) and its deviation from chronological age can provide early insights into potential neurodegenerative diseases, supporting early detection and implementation of prevention strategies. Diffusion MRI (dMRI), a widely used modality for brain age estimation, presents an opportunity to build an earlier biomarker for neurodegenerative disease prediction because it captures subtle microstructural changes that precede more perceptible macrostructural changes. However, the coexistence of macro- and micro-structural information in dMRI raises the question of whether current dMRI-based brain age estimation models are leveraging the intended microstructural information or if they inadvertently rely on the macrostructural information. To develop a microstructure-specific brain age, we propose a method for brain age identification from dMRI that minimizes the model's use of macrostructural information by non-rigidly registering all images to a standard template. Imaging data from 13,398 participants across 12 datasets were used for the training and evaluation. We compare our brain age models, trained with and without macrostructural information minimized, with an architecturally similar T1-weighted (T1w) MRI-based brain age model and two state-of-the-art T1w MRI-based brain age models that primarily use macrostructural information. We observe difference between our dMRI-based brain age and T1w MRI-based brain age across stages of neurodegeneration, with dMRI-based brain age being older than T1w MRI-based brain age in participants transitioning from cognitively normal (CN) to mild cognitive impairment (MCI), but younger in participants already diagnosed with Alzheimer's disease (AD). Approximately 4 years before MCI diagnosis, dMRI-based brain age yields better performance than T1w MRI-based brain ages in predicting transition from CN to MCI.

World of Forms: Deformable Geometric Templates for One-Shot Surface Meshing in Coronary CT Angiography

Deep learning-based medical image segmentation and surface mesh generation typically involve a sequential pipeline from image to segmentation to meshes, often requiring large training datasets while making limited use of prior geometric knowledge. This may lead to topological inconsistencies and suboptimal performance in low-data regimes. To address these challenges, we propose a data-efficient deep learning method for direct 3D anatomical object surface meshing using geometric priors. Our approach employs a multi-resolution graph neural network that operates on a prior geometric template which is deformed to fit object boundaries of interest. We show how different templates may be used for the different surface meshing targets, and introduce a novel masked autoencoder pretraining strategy for 3D spherical data. The proposed method outperforms nnUNet in a one-shot setting for segmentation of the pericardium, left ventricle (LV) cavity and the LV myocardium. Similarly, the method outperforms other lumen segmentation operating on multi-planar reformatted images. Results further indicate that mesh quality is on par with or improves upon marching cubes post-processing of voxel mask predictions, while remaining flexible in the choice of mesh triangulation prior, thus paving the way for more accurate and topologically consistent 3D medical object surface meshing.

ATOMMIC: An Advanced Toolbox for Multitask Medical Imaging Consistency to facilitate Artificial Intelligence applications from acquisition to analysis in Magnetic Resonance Imaging

AI is revolutionizing MRI along the acquisition and processing chain. Advanced AI frameworks have been developed to apply AI in various successive tasks, such as image reconstruction, quantitative parameter map estimation, and image segmentation. Existing frameworks are often designed to perform tasks independently or are focused on specific models or datasets, limiting generalization. We introduce ATOMMIC, an open-source toolbox that streamlines AI applications for accelerated MRI reconstruction and analysis. ATOMMIC implements several tasks using DL networks and enables MultiTask Learning (MTL) to perform related tasks integrated, targeting generalization in the MRI domain. We first review the current state of AI frameworks for MRI through a comprehensive literature search and by parsing 12,479 GitHub repositories. We benchmark 25 DL models on eight publicly available datasets to present distinct applications of ATOMMIC on accelerated MRI reconstruction, image segmentation, quantitative parameter map estimation, and joint accelerated MRI reconstruction and image segmentation utilizing MTL. Our findings demonstrate that ATOMMIC is the only MTL framework with harmonized complex-valued and real-valued data support. Evaluations on single tasks show that physics-based models, which enforce data consistency by leveraging the physical properties of MRI, outperform other models in reconstructing highly accelerated acquisitions. Physics-based models that produce high reconstruction quality can accurately estimate quantitative parameter maps. When high-performing reconstruction models are combined with robust segmentation networks utilizing MTL, performance is improved in both tasks. ATOMMIC facilitates MRI reconstruction and analysis by standardizing workflows, enhancing data interoperability, integrating unique features like MTL, and effectively benchmarking DL models.

Deep Learning for Automatic Strain Quantification in Arrhythmogenic Right Ventricular Cardiomyopathy

Quantification of cardiac motion with cine Cardiac Magnetic Resonance Imaging (CMRI) is an integral part of arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis. Yet, the expert evaluation of motion abnormalities with CMRI is a challenging task. To automatically assess cardiac motion, we register CMRIs from different time points of the cardiac cycle using Implicit Neural Representations (INRs) and perform a biomechanically informed regularization inspired by the myocardial incompressibility assumption. To enhance the registration performance, our method first rectifies the inter-slice misalignment inherent to CMRI by performing a rigid registration guided by the long-axis views, and then increases the through-plane resolution using an unsupervised deep learning super-resolution approach. Finally, we propose to synergically combine information from short-axis and 4-chamber long-axis views, along with an initialization to incorporate information from multiple cardiac time points. Thereafter, to quantify cardiac motion, we calculate global and segmental strain over a cardiac cycle and compute the peak strain. The evaluation of the method is performed on a dataset of cine CMRI scans from 47 ARVC patients and 67 controls. Our results show that inter-slice alignment and generation of super-resolved volumes combined with joint analysis of the two cardiac views, notably improves registration performance. Furthermore, the proposed initialization yields more physiologically plausible registrations. The significant differences in the peak strain, discerned between the ARVC patients and healthy controls suggest that automated motion quantification methods may assist in diagnosis and provide further understanding of disease-specific alterations of cardiac motion.

Predicting Age from White Matter Diffusivity with Residual Learning

Imaging findings inconsistent with those expected at specific chronological age ranges may serve as early indicators of neurological disorders and increased mortality risk. Estimation of chronological age, and deviations from expected results, from structural MRI data has become an important task for developing biomarkers that are sensitive to such deviations. Complementary to structural analysis, diffusion tensor imaging (DTI) has proven effective in identifying age-related microstructural changes within the brain white matter, thereby presenting itself as a promising additional modality for brain age prediction. Although early studies have sought to harness DTI's advantages for age estimation, there is no evidence that the success of this prediction is owed to the unique microstructural and diffusivity features that DTI provides, rather than the macrostructural features that are also available in DTI data. Therefore, we seek to develop white-matter-specific age estimation to capture deviations from normal white matter aging. Specifically, we deliberately disregard the macrostructural information when predicting age from DTI scalar images, using two distinct methods. The first method relies on extracting only microstructural features from regions of interest. The second applies 3D residual neural networks (ResNets) to learn features directly from the images, which are non-linearly registered and warped to a template to minimize macrostructural variations. When tested on unseen data, the first method yields mean absolute error (MAE) of 6.11 years for cognitively normal participants and MAE of 6.62 years for cognitively impaired participants, while the second method achieves MAE of 4.69 years for cognitively normal participants and MAE of 4.96 years for cognitively impaired participants. We find that the ResNet model captures subtler, non-macrostructural features for brain age prediction.

Automatic Coronary Artery Plaque Quantification and CAD-RADS Prediction using Mesh Priors

Coronary artery disease (CAD) remains the leading cause of death worldwide. Patients with suspected CAD undergo coronary CT angiography (CCTA) to evaluate the risk of cardiovascular events and determine the treatment. Clinical analysis of coronary arteries in CCTA comprises the identification of atherosclerotic plaque, as well as the grading of any coronary artery stenosis typically obtained through the CAD-Reporting and Data System (CAD-RADS). This requires analysis of the coronary lumen and plaque. While voxel-wise segmentation is a commonly used approach in various segmentation tasks, it does not guarantee topologically plausible shapes. To address this, in this work, we propose to directly infer surface meshes for coronary artery lumen and plaque based on a centerline prior and use it in the downstream task of CAD-RADS scoring. The method is developed and evaluated using a total of 2407 CCTA scans. Our method achieved lesion-wise volume intraclass correlation coefficients of 0.98, 0.79, and 0.85 for calcified, non-calcified, and total plaque volume respectively. Patient-level CAD-RADS categorization was evaluated on a representative hold-out test set of 300 scans, for which the achieved linearly weighted kappa ($\kappa$) was 0.75. CAD-RADS categorization on the set of 658 scans from another hospital and scanner led to a $\kappa$ of 0.71. The results demonstrate that direct inference of coronary artery meshes for lumen and plaque is feasible, and allows for the automated prediction of routinely performed CAD-RADS categorization.

Robust deformable image registration using cycle-consistent implicit representations

Recent works in medical image registration have proposed the use of Implicit Neural Representations, demonstrating performance that rivals state-of-the-art learning-based methods. However, these implicit representations need to be optimized for each new image pair, which is a stochastic process that may fail to converge to a global minimum. To improve robustness, we propose a deformable registration method using pairs of cycle-consistent Implicit Neural Representations: each implicit representation is linked to a second implicit representation that estimates the opposite transformation, causing each network to act as a regularizer for its paired opposite. During inference, we generate multiple deformation estimates by numerically inverting the paired backward transformation and evaluating the consensus of the optimized pair. This consensus improves registration accuracy over using a single representation and results in a robust uncertainty metric that can be used for automatic quality control. We evaluate our method with a 4D lung CT dataset. The proposed cycle-consistent optimization method reduces the optimization failure rate from 2.4% to 0.0% compared to the current state-of-the-art. The proposed inference method improves landmark accuracy by 4.5% and the proposed uncertainty metric detects all instances where the registration method fails to converge to a correct solution. We verify the generalizability of these results to other data using a centerline propagation task in abdominal 4D MRI, where our method achieves a 46% improvement in propagation consistency compared with single-INR registration and demonstrates a strong correlation between the proposed uncertainty metric and registration accuracy.

Deep Learning-Based Prediction of Fractional Flow Reserve along the Coronary Artery

Functionally significant coronary artery disease (CAD) is caused by plaque buildup in the coronary arteries, potentially leading to narrowing of the arterial lumen, i.e. coronary stenosis, that significantly obstructs blood flow to the myocardium. The current reference for establishing the presence of a functionally significant stenosis is invasive fractional flow reserve (FFR) measurement. To avoid invasive measurements, non-invasive prediction of FFR from coronary CT angiography (CCTA) has emerged. For this, machine learning approaches, characterized by fast inference, are increasingly developed. However, these methods predict a single FFR value per artery i.e. they don't provide information about the stenosis location or treatment strategy. We propose a deep learning-based method to predict the FFR along the artery from CCTA scans. This study includes CCTA images of 110 patients who underwent invasive FFR pullback measurement in 112 arteries. First, a multi planar reconstruction (MPR) of the artery is fed to a variational autoencoder to characterize the artery, i.e. through the lumen area and unsupervised artery encodings. Thereafter, a convolutional neural network (CNN) predicts the FFR along the artery. The CNN is supervised by multiple loss functions, notably a loss function inspired by the Earth Mover's Distance (EMD) to predict the correct location of FFR drops and a histogram-based loss to explicitly supervise the slope of the FFR curve. To train and evaluate our model, eight-fold cross-validation was performed. The resulting FFR curves show good agreement with the reference allowing the distinction between diffuse and focal CAD distributions in most cases. Quantitative evaluation yielded a mean absolute difference in the area under the FFR pullback curve (AUPC) of 1.7. The method may pave the way towards fast, accurate, automatic prediction of FFR along the artery from CCTA.

Generative Models for Reproducible Coronary Calcium Scoring

Purpose: Coronary artery calcium (CAC) score, i.e. the amount of CAC quantified in CT, is a strong and independent predictor of coronary heart disease (CHD) events. However, CAC scoring suffers from limited interscan reproducibility, which is mainly due to the clinical definition requiring application of a fixed intensity level threshold for segmentation of calcifications. This limitation is especially pronounced in non-ECG-synchronized CT where lesions are more impacted by cardiac motion and partial volume effects. Therefore, we propose a CAC quantification method that does not require a threshold for segmentation of CAC. Approach: Our method utilizes a generative adversarial network where a CT with CAC is decomposed into an image without CAC and an image showing only CAC. The method, using a CycleGAN, was trained using 626 low-dose chest CTs and 514 radiotherapy treatment planning CTs. Interscan reproducibility was compared to clinical calcium scoring in radiotherapy treatment planning CTs of 1,662 patients, each having two scans. Results: A lower relative interscan difference in CAC mass was achieved by the proposed method: 47% compared to 89% manual clinical calcium scoring. The intraclass correlation coefficient of Agatston scores was 0.96 for the proposed method compared to 0.91 for automatic clinical calcium scoring. Conclusions: The increased interscan reproducibility achieved by our method may lead to increased reliability of CHD risk categorization and improved accuracy of CHD event prediction.

Autoencoding Low-Resolution MRI for Semantically Smooth Interpolation of Anisotropic MRI

High-resolution medical images are beneficial for analysis but their acquisition may not always be feasible. Alternatively, high-resolution images can be created from low-resolution acquisitions using conventional upsampling methods, but such methods cannot exploit high-level contextual information contained in the images. Recently, better performing deep-learning based super-resolution methods have been introduced. However, these methods are limited by their supervised character, i.e. they require high-resolution examples for training. Instead, we propose an unsupervised deep learning semantic interpolation approach that synthesizes new intermediate slices from encoded low-resolution examples. To achieve semantically smooth interpolation in through-plane direction, the method exploits the latent space generated by autoencoders. To generate new intermediate slices, latent space encodings of two spatially adjacent slices are combined using their convex combination. Subsequently, the combined encoding is decoded to an intermediate slice. To constrain the model, a notion of semantic similarity is defined for a given dataset. For this, a new loss is introduced that exploits the spatial relationship between slices of the same volume. During training, an existing in-between slice is generated using a convex combination of its neighboring slice encodings. The method was trained and evaluated using publicly available cardiac cine, neonatal brain and adult brain MRI scans. In all evaluations, the new method produces significantly better results in terms of Structural Similarity Index Measure and Peak Signal-to-Noise Ratio (p< 0.001 using one-sided Wilcoxon signed-rank test) than a cubic B-spline interpolation approach. Given the unsupervised nature of the method, high-resolution training data is not required and hence, the method can be readily applied in clinical settings.