Parameter Estimation of Ion Current Formulations Requires Hybrid Optimization Approach to Be Both Accurate and Reliable

Computational models of cardiac electrophysiology provided insights into arrhythmogenesis and paved the way toward tailored therapies in the last years. To fully leverage in silico models in future research, these models need to be adapted to reflect pathologies, genetic alterations, or pharmacological effects, however. A common approach is to leave the structure of established models unaltered and estimate the values of a set of parameters. Today’s high-throughput patch clamp data acquisition methods require robust, unsupervised algorithms that estimate parameters both accurately and reliably. In this work, two classes of optimization approaches are evaluated: gradient-based trust-region-reflective and derivative-free particle swarm algorithms. Using synthetic input data and different ion current formulations from the Courtemanche et al. electrophysiological model of human atrial myocytes, we show that neither of the two schemes alone succeeds to meet all requirements. Sequential combination of the two algorithms did improve the performance to some extent but not satisfactorily. Thus, we propose a novel hybrid approach coupling the two algorithms in each iteration. This hybrid approach yielded very accurate estimates with minimal dependency on the initial guess using synthetic input data for which a ground truth parameter set exists. When applied to measured data, the hybrid approach yielded the best fit, again with minimal variation. Using the proposed algorithm, a single run is sufficient to estimate the parameters. The degree of superiority over the other investigated algorithms in terms of accuracy and robustness depended on the type of current. In contrast to the non-hybrid approaches, the proposed method proved to be optimal for data of arbitrary signal to noise ratio. The hybrid algorithm proposed in this work provides an important tool to integrate experimental data into computational models both accurately and robustly allowing to assess the often non-intuitive consequences of ion channel-level changes on higher levels of integration

Cherenkov Diffraction Radiation Emissions from Single Electrons and Positrons on a Fused Silica Radiator

Beam diagnostics are crucial for smooth accelerator operations. Many techniques rely on instrumentation in which the beam properties are significantly affected by the measurement. Novel approaches aim to use Cherenkov Diffraction Radiation (ChDR) for non-invasive diagnostics. Unlike regular Cherenkov Radiation, the charged particles do not have to move inside of the medium, but it is sufficient for them to move in its vicinity as long as they are faster than the speed of light in the medium. Changes to the beam properties due to ChDR measurements are consequently negligible. To examine ChDR emission under different conditions, we placed a fused silica radiator in the DESY II Test Beam. We observed a linear increase in ChDR intensity for electron and positron momenta between 1 GeV/c and 5 GeV/c. Additionally, we found that electrons produce significantly more ChDR than positrons for increasing particle momenta. The results suggest a need for further research into the ChDR generation by electrons and positrons and may find application in the design of future beam diagnostic devices

Behind the Scenes:The Two-Weeks Stay of Beamline for Schools Winning Students at DESY

In a previous paper1 the BL4S science competition has been presented from the technical point of view. This paper focuses on the organizational aspects of the period that the winning teams spent at DESY to perform their experiments. Together with a description of the event, this paper provides the unique point of view of the participants

European Journal of Nuclear Medicine and Molecular Imaging / Quantitative assessment of atherosclerotic plaques on 18F-FDG PET/MRI : comparison with a PET/CT hybrid system

Purpose PET with 18F-FDG has the potential to assess vascular macrophage metabolism. 18F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel 18F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of 18F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques. Methods The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with 18F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUVmax) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated. Results Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUVmax values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3 0.6 vs. 3.1 0.6; P < 0.01), but were significantly correlated between PET/CT and PET/MRI (Spearmans r = 0.67, P < 0.01). In contrast, TBRmax values of plaque lesions were similar on PET/MRI and on PET/CT (2.2 0.3 vs. 2.2 0.3; P = 0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearmans r = 0.73, P < 0.01). Considering the increasing trend in SUVmax and TBRmax values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBRmax values may also be expected with PET/MRI compared with PET/CT. Conclusion SUVmax and TBRmax values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUVmax and TBRmax with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI.KLI 382(VLID)346802

'Hydra' by Ann Savageau (image)

Spring Issuehttp://deepblue.lib.umich.edu/bitstream/2027.42/61137/1/3001.pd