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We present an open-source software pipeline to create patient-specific left atrial (LA) models with fibre orientations and a fibrosis map, suitable for electrophysiology simulations. The semi-automatic pipeline takes as input a contrast enhanced magnetic resonance angiogram, and a late gadolinium enhanced (LGE) contrast magnetic resonance (CMR). Five operators were allocated 20 cases each from a set of 50 CMR datasets to create a total of 100 models to evaluate inter/intra-operator variability. Each output model consisted of (1) a labelled surface mesh open at the pulmonary veins (PV) and mitral valve (MV), (2) fibre orientations mapped from a diffusion tensor MRI human atlas, (3) fibrosis map from the LGE-CMR scan, and (4) simulation of local activation time (LAT) and phase singularity (PS) mapping. We evaluated reproducibility in our pipeline by comparing agreement in shape of the output meshes, fibrosis distribution in the LA body, and fibre orientations; simulations outputs were evaluated comparing total activation times of LAT maps, mean conduction velocity (CV), and structural similarity index measure (SSIM) of PS maps. Our workflow allows a single model to be created in 16.72 +/- 12.25 minutes. Results in this abstract are reported as inter/intra. Shape only differed noticeably with users' selection of the MV and the length of the PV from the ostia to the distal end; fibrosis agreement (0.91/0.99 ICC) and fibre orientation agreement (60.63/71.77 %) were high. LAT maps showed good agreement, the median of the absolute difference of the total activation times was 2.02ms/1.37ms. The average of the mean CV difference was -4.04mm/s / 2.1mm/s. PS maps showed a moderately good agreement with SSIM of 0.648/0.608. Although we found notable differences in the models due to user input, our tests show that operator variability was comparable to that of image resolution or fibre estimation., Comment: 17 pages, 7 figures, submitted for review at Journal of Computers in Biology and Medicine (in press)

Catheter ablation is currently the only curative treatment for scar-related ventricular tachycardias (VTs). However, not only are ablation procedures long, with relatively high risk, but success rates are punitively low, with frequent VT recurrence. Personalized in-silico approaches have the opportunity to address these limitations. However, state-of-the-art reaction diffusion (R-D) simulations of VT induction and subsequent circuits used for in-silico ablation target identification require long execution times, along with vast computational resources, which are incompatible with the clinical workflow. Here, we present the Virtual Induction and Treatment of Arrhythmias (VITA), a novel, rapid and fully automated computational approach that uses reaction-Eikonal methodology to induce VT and identify subsequent ablation targets. The rationale for VITA is based on finding isosurfaces associated with an activation wavefront that splits in the ventricles due to the presence of an isolated isthmus of conduction within the scar; once identified, each isthmus may be assessed for their vulnerability to sustain a reentrant circuit, and the corresponding exit site automatically identified for potential ablation targeting. VITA was tested on a virtual cohort of 7 post-infarcted porcine hearts and the results compared to R-D simulations. Using only a standard desktop machine, VITA could detect all scar-related VTs, simulating activation time maps and ECGs (for clinical comparison) as well as computing ablation targets in 48 minutes. The comparable VTs probed by the R-D simulations took 68.5 hours on 256 cores of high-performance computing infrastructure. The set of lesions computed by VITA was shown to render the ventricular model VT-free. VITA could be used in near real-time as a complementary modality aiding in clinical decision-making in the treatment of post-infarction VTs.

In patients with atrial fibrillation, local activation time (LAT) maps are routinely used for characterising patient pathophysiology. The gradient of LAT maps can be used to calculate conduction velocity (CV), which directly relates to material conductivity and may provide an important measure of atrial substrate properties. Including uncertainty in CV calculations would help with interpreting the reliability of these measurements. Here, we build upon a recent insight into reduced-rank Gaussian processes (GP) to perform probabilistic interpolation of uncertain LAT directly on human atrial manifolds. Our Gaussian Process Manifold Interpolation (GPMI) method accounts for the topology of the atria, and allows for calculation of statistics for predicted CV. We demonstrate our method on two clinical cases, and perform validation against a simulated ground truth. CV uncertainty depends on data density, wave propagation direction, and CV magnitude. GPMI is suitable for probabilistic interpolation of other uncertain quantities on non-Euclidean manifolds.

Pulmonary vein isolation (PVI) is a common procedure for the treatment of atrial fibrillation (AF). A successful isolation produces a continuous lesion (scar) completely encircling the veins that stops activation waves from propagating to the atrial body. Unfortunately, the encircling lesion is often incomplete, becoming a combination of scar and gaps of healthy tissue. These gaps are potential causes of AF recurrence, which requires a redo of the isolation procedure. Late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) is a non-invasive method that may also be used to detect gaps, but it is currently a time-consuming process, prone to high inter-observer variability. In this paper, we present a method to semi-automatically identify and quantify ablation gaps. Gap quantification is performed through minimum path search in a graph where every node is a scar patch and the edges are the geodesic distances between patches. We propose the Relative Gap Measure (RGM) to estimate the percentage of gap around a vein, which is defined as the ratio of the overall gap length and the total length of the path that encircles the vein. Additionally, an advanced version of the RGM has been developed to integrate gap quantification estimates from different scar segmentation techniques into a single figure-of-merit. Population-based statistical and regional analysis of gap distribution was performed using a standardised parcellation of the left atrium. We have evaluated our method on synthetic and clinical data from 50 AF patients who underwent PVI with radiofrequency ablation. The population-based analysis concluded that the left superior PV is more prone to lesion gaps while the left inferior PV tends to have less gaps (p<0.05 in both cases), in the processed data. This type of information can be very useful for the optimization and objective assessment of PVI interventions.

We describe TrustBase, an architecture that provides certificate-based authentication as an operating system service. TrustBase enforces best practices for certificate validation for all applications and transparently enables existing applications to be strengthened against failures of the CA system. The TrustBase system allows simple deployment of authentication systems that harden the CA system. This enables system administrators, for example, to require certificate revocation checks on all TLS connections, or require STARTTLS for email servers that support it. TrustBase is the first system that is able to secure all TLS traffic, using an approach compatible with all operating systems. We design and evaluate a prototype implementation of TrustBase on Linux, evaluate its security, and demonstrate that it has negligible overhead and universal compatibility with applications. To demonstrate the utility of TrustBase, we have developed six authentication services that strengthen certificate validation for all applications., Comment: 15 pages, 4 figures

The use of TLS proxies to intercept encrypted traffic is controversial since the same mechanism can be used for both benevolent purposes, such as protecting against malware, and for malicious purposes, such as identity theft or warrantless government surveillance. To understand the prevalence and uses of these proxies, we build a TLS proxy measurement tool and deploy it via Google AdWords campaigns. We generate 15.2 million certificate tests across two large-scale measurement studies. We find that 1 in 250 TLS connections are TLS-proxied. The majority of these proxies appear to be benevolent, however we identify over 3,600 cases where eight malware products are using this technology nefariously. We also find numerous instances of negligent, duplicitous, and suspicious behavior, some of which degrade security for users without their knowledge. Distinguishing these types of practices is challenging in practice, indicating a need for transparency and user awareness.