The relation of 12 lead ECG to the cardiac anatomy: The normal CineECG.

Abstract Background The interpretation of the 12‑lead ECG is notoriously difficult and requires experts to distinguish normal from abnormal ECG waveforms. ECG waveforms depend on body build and electrode positions, both often different in males and females. To relate the ECG waveforms to cardiac anatomical structures is even more difficult. The novel CineECG algorithm enables a direct projection of the 12‑lead ECG to the cardiac anatomy by computing the mean location of cardiac activity over time. The aim of this study is to investigate the cardiac locations of the CineECG derived from standard 12‑lead ECGs of normal subjects. Methods In this study we used 6525 12‑lead ECG tracings labelled as normal obtained from the certified Physionet PTB XL Diagnostic ECG Database to construct the CineECG. All 12 lead ECGs were analyzed, and then divided by age groups (18–29,30-39,40-49,50-59,60-69,70–100 years) and by gender (male/female). For each ECG, we computed the CineECG within a generic 3D heart/torso model. Based on these CineECG's, the average normal cardiac location and direction for QRS, STpeak, and TpeakTend segments were determined. Results The CineECG direction for the QRS segment showed large variation towards the left free wall, whereas the STT segments were homogeneously directed towards the septal/apical region. The differences in the CineECG location for the QRS, STpeak, and TpeakTend between the age and gender groups were relatively small (maximally 10 mm at end T-wave), although between the gender groups minor differences were found in the 4 chamber direction angles (QRS 4°, STpeak 5°, and TpeakTend 8°) and LAO (QRS 1°, STpeak 13°, and TpeakTend 30°). Conclusion CineECG demonstrated to be a feasible and pragmatic solution for ECG waveform interpretation, relating the ECG directly to the cardiac anatomy. The variations in depolarization and repolarization CineECG were small within this group of normal healthy controls, both in cardiac location as well as in direction. CineECG may enable an easier discrimination between normal and abnormal QRS and T-wave morphologies, reducing the amount of expert training. Further studies are needed to prove whether novel CineECG can significantly contribute to the discrimination of normal versus abnormal ECG tracings

Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET).

BackgroundConventional scale production of small batches of PET tracers (e.g. for preclinical imaging) is an inefficient use of resources. Using O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), we demonstrate that simple microvolume radiosynthesis techniques can improve the efficiency of production by consuming tiny amounts of precursor, and maintaining high molar activity of the tracers even with low starting activity.ProceduresThe synthesis was carried out in microvolume droplets manipulated on a disposable patterned silicon "chip" affixed to a heater. A droplet of [18F]fluoride containing TBAHCO3 was first deposited onto a chip and dried at 100 °C. Subsequently, a droplet containing 60 nmol of precursor was added to the chip and the fluorination reaction was performed at 90 °C for 5 min. Removal of protecting groups was accomplished with a droplet of HCl heated at 90 °C for 3 min. Finally, the crude product was collected in a methanol-water mixture, purified via analytical-scale radio-HPLC and formulated in saline. As a demonstration, using [18F]FET produced on the chip, we prepared aliquots with different molar activities to explore the impact on preclinical PET imaging of tumor-bearing mice.ResultsThe microdroplet synthesis exhibited an overall decay-corrected radiochemical yield of 55 ± 7% (n = 4) after purification and formulation. When automated, the synthesis could be completed in 35 min. Starting with < 370 MBq of activity, ~ 150 MBq of [18F]FET could be produced, sufficient for multiple in vivo experiments, with high molar activities (48-119 GBq/μmol). The demonstration imaging study revealed the uptake of [18F]FET in subcutaneous tumors, but no significant differences in tumor uptake as a result of molar activity differences (ranging 0.37-48 GBq/μmol) were observed.ConclusionsA microdroplet synthesis of [18F]FET was developed demonstrating low reagent consumption, high yield, and high molar activity. The approach can be expanded to tracers other than [18F]FET, and adapted to produce higher quantities of the tracer sufficient for clinical PET imaging

The added value of high-resolution above coarse-resolution remote sensing images in crop yield forecasting: A case study in the Egyptian Nile Delta

Crop growth models play a major role in sustaining the world-wide food security. These models are used to simulate crop growth during the growing season, and the final crop yield at the end of the growing season, given the farmers’ management practices. At a more strategic level, these crop growth models play an important role to decision makers to take timely decisions regarding food import and/or export strategies. The simulation accuracy of crop growth models relies on the quality of the input data. Since crop yield forecasting applications are often applied over large areas that rely on a spatially distributed crop growth model, the uncertainty in the spatial variation of the input data increases. Remote sensing images are often used in crop growth models because remote sensing images provide spatially distributed input data to these models. These images are available in numerous spatial resolutions, where coarse resolution images are often freely available compared to the more expensive high-resolution images. Therefore, the objective of the current study was to evaluate the added value of high-resolution satellite imagery above coarse-resolution satellite imagery in crop yield forecasting

Disease-Specific Electrocardiographic Lead Positioning for Early Detection of Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by replacement of cardiomyocytes by fibrofatty tissue which can lead to ventricular arrhythmias, heart failure or sudden cardiac death. Genetic defects in desmosomal proteins, as plakophilin-2 (PKP2), are known to contribute to disease development. Current electrocardiographic (ECG) criteria for ARVC diagnosis only focus on right precordial leads, but sensitivity of current depolarization criteria is limited. This study aimed to identify additional depolarization criteria with most optimal lead configurations for early detection of ARVC in PKP2 pathogenic mutation carriers. In PKP2-positive ARVC patients (n=7), PKP2 pathogenic variant carriers (n=16) and control subjects without structural heart disease (n=9), 67-lead body surface potential maps (BSPM) were obtained. Terminal QRS-integrals were determined and quantitatively compared to controls using departure mapping. Significantly different terminal QRS-integrals were identified in lead 34 (conventional V3), 40 and 41 (conventional V4). To conclude, a clear distinction between ARVC patients, asymptomatic mutation carriers and healthy controls was observed

Universality of Entanglement and Quantum Computation Complexity

We study the universality of scaling of entanglement in Shor's factoring algorithm and in adiabatic quantum algorithms across a quantum phase transition for both the NP-complete Exact Cover problem as well as the Grover's problem. The analytic result for Shor's algorithm shows a linear scaling of the entropy in terms of the number of qubits, therefore difficulting the possibility of an efficient classical simulation protocol. A similar result is obtained numerically for the quantum adiabatic evolution Exact Cover algorithm, which also shows universality of the quantum phase transition the system evolves nearby. On the other hand, entanglement in Grover's adiabatic algorithm remains a bounded quantity even at the critical point. A classification of scaling of entanglement appears as a natural grading of the computational complexity of simulating quantum phase transitions.Comment: 30 pages, 17 figures, accepted for publication in PR

Non-invasive estimation of QLV from the standard 12-lead ECG in patients with left bundle branch block

Background: Cardiac resynchronization therapy (CRT) is a treatment for patients with heart failure and electrical dyssynchrony, i.e., left bundle branch block (LBBB) ECG pattern. CRT resynchronizes ventricular contraction with a right ventricle (RV) and a left ventricle (LV) pacemaker lead. Positioning the LV lead in the latest electrically activated region (measured from Q wave onset in the ECG to LV sensing by the left pacemaker electrode [QLV]) is associated with favorable outcome. However, optimal LV lead placement is limited by coronary venous anatomy and the inability to measure QLV non-invasively before implantation. We propose a novel non-invasive method for estimating QLV in sinus-rhythm from the standard 12-lead ECG. Methods: We obtained 12-lead ECG, LV electrograms and LV lead position in a standard LV 17-segment model from procedural recordings from 135 standard CRT recipients. QLV duration was measured post-operatively. Using a generic heart geometry and corresponding forward model for ECG computation, the electrical activation pattern of the heart was fitted to best match the 12-lead ECG in an iterative optimization procedure. This procedure initialized six activation sites associated with the His-Purkinje system. The initial timing of each site was based on the directions of the vectorcardiogram (VCG). Timing and position of the sites were then changed iteratively to improve the match between simulated and measured ECG. Noninvasive estimation of QLV was done by calculating the time difference between Q-onset on the computed ECG and the activation time corresponding to centroidal epicardial activation time of the segment where the LV electrode is positioned. The estimated QLV was compared to the measured QLV. Further, the distance between the actual LV position and the estimated LV position was computed from the generic ventricular model. Results: On average there was no difference between QLV measured from procedural recordings and non-invasive estimation of QLV ( [Formula: see text] ). Median distance between actual LV pacing site and the estimated pacing site was 18.6 mm (IQR 17.3 mm). Conclusion: Using the standard 12-lead ECG and a generic heart model it is possible to accurately estimate QLV. This method may potentially be used to support patient selection, optimize implant procedures, and to simulate optimal stimulation parameters prior to pacemaker implantation

Modeling the His-Purkinje Effect in Non-invasive Estimation of Endocardial and Epicardial Ventricular Activation

Inverse electrocardiography (iECG) estimates epi- and endocardial electrical activity from body surface potentials maps (BSPM). In individuals at risk for cardiomyopathy, non-invasive estimation of normal ventricular activation may provide valuable information to aid risk stratification to prevent sudden cardiac death. However, multiple simultaneous activation wavefronts initiated by the His-Purkinje system, severely complicate iECG. To improve the estimation of normal ventricular activation, the iECG method should accurately mimic the effect of the His-Purkinje system, which is not taken into account in the previously published multi-focal iECG. Therefore, we introduce the novel multi-wave iECG method and report on its performance. Multi-wave iECG and multi-focal iECG were tested in four patients undergoing invasive electro-anatomical mapping during normal ventricular activation. In each subject, 67-electrode BSPM were recorded and used as input for both iECG methods. The iECG and invasive local activation timing (LAT) maps were compared. Median epicardial inter-map correlation coefficient (CC) between invasive LAT maps and estimated multi-wave iECG versus multi-focal iECG was 0.61 versus 0.31. Endocardial inter-map CC was 0.54 respectively 0.22. Modeling the His-Purkinje system resulted in a physiologically realistic and robust non-invasive estimation of normal ventricular activation, which might enable the early detection of cardiac disease during normal sinus rhythm

5-HT7 receptors in Alzheimer's disease

Even though the involvement of serotonin (5-hydroxytryptamine; 5-HT) and its receptors in Alzheimer’s disease (AD) is widely accepted, data on the expression and the role of 5-HT7 receptors in AD is relatively limited. Therefore, the objective of the present work was to study the expression of serotonergic 5-HT7 receptors in postmortem samples of AD brains and correlate it with neurotransmitter levels, cognition and behavior. The study population consisted of clinically well-characterized and neuropathologically confirmed AD patients (n = 42) and age-matched control subjects (n = 18). Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and high-performance liquid chromatography were performed on Brodmann area (BA) 7, BA10, BA22, BA24, hippocampus, amygdala, thalamus and cerebellum to measure mRNA levels of 5-HT7 receptors (HTR7), as well as the concentrations of various monoamine neurotransmitters and their metabolites. Decreased levels of HTR7 mRNA were observed in BA10. A significant association was observed between HTR7 levels in BA10 and BEHAVE-AD cluster B (hallucinations) (rs(28) = 0.444, P < 0.05). In addition, a negative correlation was observed between HTR7 levels in BA10 and both MHPG concentrations in this brain region (rs(45) = -0.311; P < 0.05), and DOPAC levels in the amygdala (rs(42) = -0.311; P < 0.05). Quite sur- prisingly, no association was found between HTR7 levels and cognitive status. Altogether, this study supports the notion of the involvement of 5-HT7 receptors in psychotic symptoms in AD, suggesting the interest of testing antagonist acting at this receptor to specifically treat psychotic symptoms in this illness