Design of HIFU treatment plans using an evolutionary strategy

High Intensity Focused Ultrasound (HIFU) is an emerging technique for non-invasive cancer treatment where malignant tissue is destroyed by thermal ablation. Since one ablation only allows a small region of tissue to be destroyed, a series of ablations has to be conducted to treat larger volumes. To maximize the treatment outcome and prevent injuries such as skin burns, complex preoperative treatment planning is carried out to determine the focal position and sonication time for each ablation. Here, we present an evolutionary strategy to design HIFU treatment plans using a map of patient specific material properties and a realistic thermal model. The proposed strategy allows high-quality treatment plans to be designed, with the average volume of mistreated and under-treated tissue not exceeding 0.1 %

Preliminary plasma spectrometric analyses for selected elements in some geothermal waters from Cerro Prieto, Mexico

Water samples collected from geothermal power production wells at Cerro Prieto, Mexico, were analyzed for selected elements by dc argon plasma emission spectroscopy. Spectral interferences due to the presence of high concentrations of Ca, Si, Na and K in these waters affected the apparent concentration values obtained. These effects were evaluated and correction techniques were developed and applied to the analytical values. Precipitates present in the samples at the time of analysis adversely affected the accuracy, precision and interpretability of the data

Ultrasonography-based motion tracking for MRgFUS

Non-invasive treatment of moving organs like liver and kidney with high intensity focused ultrasound (HIFU/FUS) is challenging. The highly precise HIFU ablation requires real-time knowledge of tumor position with mm precision. The aim of this work was to build up a magnetic resonance imaging compatible tracking device using diagnostic ultrasound imaging for MR guided FUS (MRgFUS). The hardware of the developed US-tracking system comprises the ultrasound beam former with a screen directly placed in front of the MR-magnet, a linear and a special ultrasound tracking probe. The tracking probe (2x64 element phased array) can acquire two perpendicularly oriented US-image planes for quasi 3D tracking. The US-data are sent to a workstation in the console room of the MRI scanner which controls the whole tracking device. The tracking software (Sonoplan II) analyzes the ultrasound image stream and calculates the actual position of pre-defined contours. Beside the 2D-translation, the tracking algorithm analyzes the rotation as well as the 2D scaling of the contour. The developed US-tracking system proved MR-compatibility in 1.5 and 3 T MR-systems and enabled simultaneous MR-and US-imaging and motion tracking. In the next step, the tracking system will be combined with an MRgFUS unit

The influence of underlying assumptions on evaluating the relative merits of concentration-controlled and dose-controlled trials

The objective of this study was to assess the relative performances of concentration-controlled trial (CCT) and dose-controlled clinical trial (DCT) designs with varying (i) interindividual variability (IIV) in clearance (CL), (ii) relative clinical importance of rejection and infection episodes, (iii) parameter values for the concentration-effect relationships, (iv) interindividual covariance between exposure and effect relationships, and (v) nonlinearity of the concentration-effect relationship. Different scenarios were simulated and analyzed for DCT and CCT designs, and these were compared with respect to bias, prediction, and power. The DCT design showed superiority across all the scenarios studied, with regard to precision and bias in parameter estimates, precision and bias in the estimate of optimal exposure, and bias in prediction of the therapeutic benefit at estimated optimal exposure. However, when a pharmacokinetic-pharmacodynamic (PKPD) covariance in the parameters was considered, either the variance-equivalent concentration-controlled trial (VCCT) or the DCT was the more useful design. Across a number of scenarios, the DCT design is the more informative one. © 2009 American Society for Clinical Pharmacology and Therapeutics

Hydrochemistry and energy storage in aquifers

This volume of the series Proceedings and Information of the TNO Committee on Hydrological Research (CHO-TNO) contains the contributions as presented on the 48th technical meeting of the CHO-TNO, "Hydrochemistry and energy storage in aquifers". During this symposium recent results have been presented on research which has been conducted within the framework of Annex VI of the International Energy Agency (IEA); Environmental and Chemical Aspects of Thermal Energy Storage in Aquifers and Research and Development of Water Treatment Methods. The Dutch contribution within the IEA framework is coordinated and sponsored by the Netherlands Agency for Energy and the Environment (NOVEM BV) in the Dutch research program: National Research Program on Geothermal Energy and Energy Storage in Aquifers (NOAA)

Allosteric modulation of proteinase 3 activity by anti-neutrophil cytoplasmic antibodies in granulomatosis with polyangiitis.

Anti-neutrophil cytoplasmic antibodies (ANCA) with proteinase 3 (PR3) specificity are a useful laboratory biomarker for the diagnosis of Granulomatosis with Polyangiitis (GPA) and are believed to be implicated in the pathogenesis. It has been repeatedly suggested that disease activity of GPA is more closely related to the appearance and rise of PR3-inhibiting ANCA than to an increase of total ANCA. Previous studies on a limited number of patient samples, however, have yielded inconclusive results. To overcome the previous methodological limitations, we established a new ultrasensitive method to quantify the inhibitory capacity of PR3-ANCA using small volumes of plasma from patients with GPA. A large collection of longitudinally-collected samples from the Wegener Granulomatosis Etanercept Trial (WGET) became available to us to determine the functional effects of ANCA on PR3 in comparison to clinical disease manifestations. In these patient samples we not only detected PR3-ANCA with inhibitory capacity, but also PR3-ANCA with enhancing effects on PR3 activity. However no correlation of these activity-modulating PR3-ANCA with disease activity at either the time of enrollment or over the course of disease was found. Only patients with pulmonary involvement, especially patients with nodule formation in the respiratory tract, showed a slight, but not significant, decrease of inhibitory capacity. Epitope mapping of the activity-modulating PR3-ANCA revealed a binding on the active site surface of PR3. Yet these ANCA were able to bind to PR3 with an occupied active site cleft, indicating an allosteric mechanism of inhibition. The recently described signal ratio between the MCPR3-3 and MCPR3-2 capture ELISA was consistent with the binding of activity-modulating ANCA to the active site surface. Evidence for a shared epitope between activity-modulating PR3-ANCA and MCPR3-7, however, was very limited, suggesting that a majority of PR3-ANCA species do not inhibit PR3 by the same mechanism as previously reported for MCPR3-7