Explainable machine learning predictions to support personalized cardiology strategies.

Aims: A widely practiced intervention to modify cardiac health, the effect of physical activity on older adults is likely heterogeneous. While machine learning (ML) models that combine various systemic signals may aid in predictive modelling, the inability to rationalize predictions at a patient personalized level is a major shortcoming in the current field of ML. Methods and results: We applied a novel methodology, SHapley Additive exPlanations (SHAP), on a dataset of older adults n = 86 (mean age 72 ± 4 years) whose physical activity levels were studied alongside changes in their left ventricular (LV) structure. SHAP was tested to provide intelligible visualization on the magnitude of the impact of the features in their physical activity levels on their LV structure. As proof of concept, using repeated K-cross-validation on the train set (n = 68), we found the Random Forest Regressor with the most optimal hyperparameters, which achieved the lowest mean squared error. With the trained model, we evaluated its performance by reporting its mean absolute error and plotting the correlation on the test set (n = 18). Based on collective force plot, individually numbered patients are indicated on the horizontal axis, and each bandwidth implies the magnitude (i.e. effect) of physical parameters (higher in red; lower in blue) towards prediction of their LV structure. Conclusions: As a tool that identified specific features in physical activity that predicted cardiac structure on a per patient level, our findings support a role for explainable ML to be incorporated into personalized cardiology strategies.

Skin Lesion Analysis By Multi-Target Deep Neural Networks.

Automatic skin lesion analysis involves two critical steps: lesion segmentation and lesion classification. In this work, we propose a novel multi-target deep convolutional neural network (DCNN) to simultaneously tackle the problem of segmentation and classification. Based on U-Net and GoogleNet, a single model is constructed with three different targets of both lesion segmentation and two independent binary lesion classifications (i.e., melanoma detection and seborrheic keratosis identification), aiming to explore the differences and commonalities over different target models. We conduct experiments on dermoscopic images from the International Skin Imaging Collaboration (ISIC) 2017 Challenge. Results of our multi-target DCNN model demonstrates superiority over single model with one target only (such as U-net or GoogleNet), indicating its learning efficiency and potential for application in automatic skin lesion diagnosis. To the best of our knowledge, this work is the first demonstration for a single end-to-end deep neural network model that simultaneously handle both segmentation and classification in the field of skin lesion analysis.

Lipidomic Profiling of Lung Pleural Effusion Identifies Unique Metabotype for EGFR Mutants in Non-Small Cell Lung Cancer.

Cytology and histology forms the cornerstone for the diagnosis of non-small cell lung cancer (NSCLC) but obtaining sufficient tumour cells or tissue biopsies for these tests remains a challenge. We investigate the lipidome of lung pleural effusion (PE) for unique metabolic signatures to discriminate benign versus malignant PE and EGFR versus non-EGFR malignant subgroups to identify novel diagnostic markers that is independent of tumour cell availability. Using liquid chromatography mass spectrometry, we profiled the lipidomes of the PE of 30 benign and 41 malignant cases with or without EGFR mutation. Unsupervised principal component analysis revealed distinctive differences between the lipidomes of benign and malignant PE as well as between EGFR mutants and non-EGFR mutants. Docosapentaenoic acid and Docosahexaenoic acid gave superior sensitivity and specificity for detecting NSCLC when used singly. Additionally, several 20- and 22- carbon polyunsaturated fatty acids and phospholipid species were significantly elevated in the EGFR mutants compared to non-EGFR mutants. A 7-lipid panel showed great promise in the stratification of EGFR from non-EGFR malignant PE. Our data revealed novel lipid candidate markers in the non-cellular fraction of PE that holds potential to aid the diagnosis of benign, EGFR mutation positive and negative NSCLC.

Automatic 4D reconstruction of patient-specific cardiac mesh with 1-to-1 vertex correspondence from segmented contours lines.

We propose an automatic algorithm for the reconstruction of patient-specific cardiac mesh models with 1-to-1 vertex correspondence. In this framework, a series of 3D meshes depicting the endocardial surface of the heart at each time step is constructed, based on a set of border delineated magnetic resonance imaging (MRI) data of the whole cardiac cycle. The key contribution in this work involves a novel reconstruction technique to generate a 4D (i.e., spatial-temporal) model of the heart with 1-to-1 vertex mapping throughout the time frames. The reconstructed 3D model from the first time step is used as a base template model and then deformed to fit the segmented contours from the subsequent time steps. A method to determine a tree-based connectivity relationship is proposed to ensure robust mapping during mesh deformation. The novel feature is the ability to handle intra- and inter-frame 2D topology changes of the contours, which manifests as a series of merging and splitting of contours when the images are viewed either in a spatial or temporal sequence. Our algorithm has been tested on five acquisitions of cardiac MRI and can successfully reconstruct the full 4D heart model in around 30 minutes per subject. The generated 4D heart model conforms very well with the input segmented contours and the mesh element shape is of reasonably good quality. The work is important in the support of downstream computational simulation activities.

Segmentation of biomedical images using active contour model with robust image feature and shape prior.

In this article, a new level set model is proposed for the segmentation of biomedical images. The image energy of the proposed model is derived from a robust image gradient feature which gives the active contour a global representation of the geometric configuration, making it more robust in dealing with image noise, weak edges, and initial configurations. Statistical shape information is incorporated using nonparametric shape density distribution, which allows the shape model to handle relatively large shape variations. The segmentation of various shapes from both synthetic and real images depict the robustness and efficiency of the proposed method.

Left ventricle segmentation by dynamic shape constrained random walks.

Accurate and robust extraction of the left ventricle (LV) cavity is a key step for quantitative analysis of cardiac functions. In this study, we propose an improved LV cavity segmentation method that incorporates a dynamic shape constraint into the weighting function of the random walks algorithm. The method involves an iterative process that updates an intermediate result to the desired solution. The shape constraint restricts the solution space of the segmentation result, such that the robustness of the algorithm is increased to handle misleading information that emanates from noise, weak boundaries, and clutter. Our experiments on real cardiac magnetic resonance images demonstrate that the proposed method obtains better segmentation performance than standard method.

Reconstructing patient-specific cardiac models from contours via Delaunay triangulation and graph-cuts.

This study proposes a novel method to reconstruct the left cardiac structure from contours. Given the contours representing left ventricle (LV), left atrium (LA), and aorta (AO), re-orientation, contour matching, extrapolation, and interpolation are performed sequentially. The processed data are then reconstructed via a variational method. The weighted minimal surface model is revised to handle the multi-phase cases, which happens at the LV-LA-AO junction. A Delaunay-based tetrahedral mesh is generated to discretize the domain while the max-flow/min-cut algorithm is utilized as the minimization tool. The reconstructed model including LV, LA, and AO structure is extracted from the mesh and post-processed further. Numerical examples show the robustness and effectiveness of the proposed method.

Geometrically induced force interaction for three-dimensional deformable models.

In this paper, we propose a novel 3-D deformable model that is based upon a geometrically induced external force field which can be conveniently generalized to arbitrary dimensions. This external force field is based upon hypothesized interactions between the relative geometries of the deformable model and the object boundary characterized by image gradient. The evolution of the deformable model is solved using the level set method so that topological changes are handled automatically. The relative geometrical configurations between the deformable model and the object boundaries contribute to a dynamic vector force field that changes accordingly as the deformable model evolves. The geometrically induced dynamic interaction force has been shown to greatly improve the deformable model performance in acquiring complex geometries and highly concave boundaries, and it gives the deformable model a high invariancy in initialization configurations. The voxel interactions across the whole image domain provide a global view of the object boundary representation, giving the external force a long attraction range. The bidirectionality of the external force field allows the new deformable model to deal with arbitrary cross-boundary initializations, and facilitates the handling of weak edges and broken boundaries. In addition, we show that by enhancing the geometrical interaction field with a nonlocal edge-preserving algorithm, the new deformable model can effectively overcome image noise. We provide a comparative study on the segmentation of various geometries with different topologies from both synthetic and real images, and show that the proposed method achieves significant improvements against existing image gradient techniques.

Left ventricular regional wall curvedness and wall stress in patients with ischemic dilated cardiomyopathy.

Geometric remodeling of the left ventricle (LV) after myocardial infarction is associated with changes in myocardial wall stress. The objective of this study was to determine the regional curvatures and wall stress based on three-dimensional (3-D) reconstructions of the LV using MRI. Ten patients with ischemic dilated cardiomyopathy (IDCM) and 10 normal subjects underwent MRI scan. The IDCM patients also underwent delayed gadolinium-enhancement imaging to delineate the extent of myocardial infarct. Regional curvedness, local radii of curvature, and wall thickness were calculated. The percent curvedness change between end diastole and end systole was also calculated. In normal heart, a short- and long-axis two-dimensional analysis showed a 41 +/- 11% and 45 +/- 12% increase of the mean of peak systolic wall stress between basal and apical sections, respectively. However, 3-D analysis showed no significant difference in peak systolic wall stress from basal and apical sections (P = 0.298, ANOVA). LV shape differed between IDCM patients and normal subjects in several ways: LV shape was more spherical (sphericity index = 0.62 +/- 0.08 vs. 0.52 +/- 0.06, P < 0.05), curvedness at end diastole (mean for 16 segments = 0.034 +/- 0.0056 vs. 0.040 +/- 0.0071 mm(-1), P < 0.001) and end systole (mean for 16 segments = 0.037 +/- 0.0068 vs. 0.067 +/- 0.020 mm(-1), P < 0.001) was affected by infarction, and peak systolic wall stress was significantly increased at each segment in IDCM patients. The 3-D quantification of regional wall stress by cardiac MRI provides more precise evaluation of cardiac mechanics. Identification of regional curvedness and wall stresses helps delineate the mechanisms of LV remodeling in IDCM and may help guide therapeutic LV restoration.

A curvature-based approach for left ventricular shape analysis from cardiac magnetic resonance imaging.

It is believed that left ventricular (LV) regional shape is indicative of LV regional function, and cardiac pathologies are often associated with regional alterations in ventricular shape. In this article, we present a set of procedures for evaluating regional LV surface shape from anatomically accurate models reconstructed from cardiac magnetic resonance (MR) images. LV surface curvatures are computed using local surface fitting method, which enables us to assess regional LV shape and its variation. Comparisons are made between normal and diseased hearts. It is illustrated that LV surface curvatures at different regions of the normal heart are higher than those of the diseased heart. Also, the normal heart experiences a larger change in regional curvedness during contraction than the diseased heart. It is believed that with a wide range of dataset being evaluated, this approach will provide a new and efficient way of quantifying LV regional function.

Analysis of left ventricular surface deformation during isovolumic contraction.

The rapid pressure built-up in the left ventricular (LV) cavity is mainly due to the contraction of the helically oriented myocardial fibers, and its associated wall deformation. In this paper, we recover and elucidate the left ventricular wall motion during isovolumic contraction using a shape-based tracking approach. In particular, the LV surface properties are derived by means of local surface fitting, and the point-correspondences between successive time frames are determined using a thin plate bending model. Results show that the LV motion during isovolumic contraction is largely contributed by the twisting action of the LV.

Regional assessment of left ventricular surface shape from magnetic resonance imaging.

Left ventricular functional abnormalities are postulated to be associated with regional modification of surface curvature. This study describes the computation of the differential properties of the LV surface via an analytic approach using local surface fitting. Quantification was implemented with cine magnetic resonance imaging (MRI), which was used as the source to derive 3D wire-frame models and the related shape descriptors. Based on these shape descriptors, the shape of LV could be represented in both static and dynamic manners. These may have implications for diverse cardiac diseases.