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This paper presents a multimodal deep learning framework that utilizes advanced image techniques to improve the performance of clinical analysis heavily dependent on routinely acquired standard images. More specifically, we develop a joint learning network that for the first time leverages the accuracy and reproducibility of myocardial strains obtained from Displacement Encoding with Stimulated Echo (DENSE) to guide the analysis of cine cardiac magnetic resonance (CMR) imaging in late mechanical activation (LMA) detection. An image registration network is utilized to acquire the knowledge of cardiac motions, an important feature estimator of strain values, from standard cine CMRs. Our framework consists of two major components: (i) a DENSE-supervised strain network leveraging latent motion features learned from a registration network to predict myocardial strains; and (ii) a LMA network taking advantage of the predicted strain for effective LMA detection. Experimental results show that our proposed work substantially improves the performance of strain analysis and LMA detection from cine CMR images, aligning more closely with the achievements of DENSE. 

Identifying regions of late mechanical activation (LMA) of the left ventricular (LV) myocardium is critical in determining the optimal pacing site for cardiac resynchronization therapy in patients with heart failure. Several deep learning-based approaches have been developed to predict 3D LMA maps of LV myocardium from a stack of sparse 2D cardiac magnetic resonance imaging (MRIs). However, these models often loosely consider the geometric shape structure of the myocardium. This makes the reconstructed activation maps suboptimal; hence leading to a reduced accuracy of predicting the late activating regions of hearts. In this paper, we propose to use shape-constrained diffusion models to better reconstruct a 3D LMA map, given a limited number of 2D cardiac MRI slices. In contrast to previous methods that primarily rely on spatial correlations of image intensities for 3D reconstruction, our model leverages object shape as priors learned from the training data to guide the reconstruction process. To achieve this, we develop a joint learning network that simultaneously learns a mean shape under deformation models. Each reconstructed image is then considered as a deformed variant of the mean shape. To validate the performance of our model, we train and test the proposed framework on a publicly available mesh dataset of 3D myocardium and compare it with state-of-the-art deep learning-based reconstruction models. Experimental results show that our model achieves superior performance in reconstructing the 3D LMA maps as compared to the state-of-the-art models. 

This paper presents a novel predictive model, MetaMorph, for metamorphic registration of images with appearance changes (i.e., caused by brain tumors). In contrast to previous learning-based registration methods that have little or no control over appearance-changes, our model introduces a new regularization that can effectively suppress the negative effects of appearance changing areas. In particular, we develop a piecewise regularization on the tangent space of diffeomorphic transformations (also known as initial velocity fields) via learned segmentation maps of abnormal regions. The geometric transformation and appearance changes are treated as joint tasks that are mutually beneficial. Our model MetaMorph is more robust and accurate when searching for an optimal registration solution under the guidance of segmentation, which in turn improves the segmentation performance by providing appropriately augmented training labels. We validate MetaMorph on real 3D human brain tumor magnetic resonance imaging (MRI) scans. Experimental results show that our model outperforms the state-of-the-art learning-based registration models. The proposed MetaMorph has great potential in various image-guided clinical interventions, e.g., real-time image-guided navigation systems for tumor removal surgery. 

The epithelial-mesenchymal transition (EMT) and the corresponding reverse process, mesenchymalepithelial transition (MET), are dynamic and reversible cellular programs orchestrated by many changes at both biochemical and morphological levels. A recent surge in identifying the molecular mechanisms underlying EMT/MET has led to the development of various mathematical models that have contributed to our improved understanding of dynamics at single-cell and population levels: (a) multi-stability—how many phenotypes can cells attain during an EMT/MET?, (b) reversibility/irreversibility—what time and/or concentration of an EMT inducer marks the “tipping point” when cells induced to undergo EMT cannot revert?, (c) symmetry in EMT/MET—do cells take the same path when reverting as theytook during the induction of EMT?, and (d) non-cell autonomous mechanisms—how does a cell undergoing EMT alter the tendency of its neighbors to undergo EMT? These dynamical traits may facilitate a heterogenous response within a cell population undergoing EMT/MET. Here, we present a few examples of designing different mathematical models that can contribute to decoding EMT/MET dynamics. Key words Mathematical modeling, Epithelial-mesenchymal plasticity, Nongenetic heterogeneity,Multi-stability, Epithelial-mesenchymal heterogeneity