Quantitative multi-energy micro-CT: A simulation and phantom study for simultaneous imaging of four different contrast materials using an energy integrating detector.

Emerging from the development of single-energy Computed Tomography (CT) and Dual-Energy Computed Tomography, Multi-Energy Computed Tomography (MECT) is a promising tool allowing advanced material and tissue decomposition and thereby enabling the use of multiple contrast materials in preclinical research. The scope of this work was to evaluate whether a usual preclinical micro-CT system is applicable for the decomposition of different materials using MECT together with a matrix-inversion method and how different changes of the measurement-environment affect the results. A matrix-inversion based algorithm to differentiate up to five materials (iodine, iron, barium, gadolinium, residual material) by applying four different acceleration voltages/energy levels was established. We carried out simulations using different ratios and concentrations (given in fractions of volume units, VU) of the four different materials (plus residual material) at different noise-levels for 30 keV, 40 keV, 50 keV, 60 keV, 80 keV and 100 keV (monochromatic). Our simulation results were then confirmed by using region of interest-based measurements in a phantom-study at corresponding acceleration voltages. Therefore, different mixtures of contrast materials were scanned using a micro-CT. Voxel wise evaluation of the phantom imaging data was conducted to confirm its usability for future imaging applications and to estimate the influence of varying noise-levels, scattering, artifacts and concentrations. The analysis of our simulations showed the smallest deviation of 0.01 (0.003-0.15) VU between given and calculated concentrations of the different contrast materials when using an energy-combination of 30 keV, 40 keV, 50 keV and 100 keV for MECT. Subsequent MECT phantom measurements, however, revealed a combination of acceleration voltages of 30 kV, 40 kV, 60 kV and 100 kV as most effective for performing material decomposition with a deviation of 0.28 (0-1.07) mg/ml. The feasibility of our voxelwise analyses using the proposed algorithm was then confirmed by the generation of phantom parameter-maps that matched the known contrast material concentrations. The results were mostly influenced by the noise-level and the concentrations used in the phantoms. MECT using a standard micro-CT combined with a matrix inversion method is feasible at four different imaging energies and allows the differentiation of mixtures of up to four contrast materials plus an additional residual material.

Determining of Ablation Zone in Ex Vivo Bovine Liver Using Time-Shift Measurements.

This study presents a measurement principle for determining the size of the ablation zone in MWA, which could ultimately form an alternative to more expensive monitoring approaches like CT. The measurement method is based on a microwave transmission measurement. A MWA is performed experimentally on ex vivo bovine liver to determine the ablation zone. This setup uses a custom slot applicator performing the MWA at an operating frequency of 2.45 GHz and a custom bowtie antenna measuring the waves transmitted from the applicator. Furthermore, a custom measurement probe is used to determine the dielectric properties. A time-shift analysis is used to determine the radial extent of the ablation zone. Several measurements are carried out with a power of 50 W for 10 min to show the reproducibility. The results show that this method can provide reproducible outcomes to determine the ablation zone with a maximum error of 4.11%.

Investigation of Microwave Ablation Process in Sweet Potatoes as Substitute Liver.

The microwave ablation technique to destroy cancer tissues in liver is practiced clinically and is the subject of ongoing research, e.g., ablation monitoring. For studies, liver tissue from cattle or pigs is often used as a substitute material. In this work, sweet potato is presented as an alternative material for microwave ablation experiments in liver due to similar material properties. Sweet potatoes as a substitute for liver have the advantages of better handling, easy procurement and stable material properties over time for microwave ablation experiments. The dielectric constant and electrical conductivity of sweet potato are characterized for temperature variation with the help of high-temperature dielectric probe. Furthermore, a test setup is presented for microwave ablation experiments in which a bowtie slot antenna matched to sweet potato is placed on its surface to directly receive the microwave power from a self-developed microwave applicator inserted into a sweet potato 4 cm below the surface antenna. A high-power source was used to excite the microwave powers up to 80 W and a spectrum analyzer was used to measure the signal received by the surface antenna. The experiments were performed in an anechoic chamber for safety reasons. Power at 50 W and 80 W was stimulated for a maximum of 600 s at the 2.45 GHz ISM band in different sweet potato experiments. A correlation is found between the power received by the surface antenna and rise of temperature inside sweet potato; relative received power drops from 1 at 76 ∘C to 0.6 at 88 ∘C (max. temperature) represents a 40% relative change in a 50 W microwave ablation experiment. The received power envelope at the surface antenna is between 10 mW and 32 mW during 50 W microwave ablation. Other important results for 10 min, 80 W microwave ablation include: a maximum ablation zone short axis diameter of 4.5 cm and a maximum ablation temperature reached at 99 ∘C, 3 mm away from the applicator's slot. The results are compared with the state of the art in microwave ablation in animal liver. The dielectric constant and electrical conductivity evolution of sweet potato with rising temperature is comparable to animal liver in 50-60 ∘C range. The reflection loss of self-developed applicator in sweet potato is below 15 dB which is equal to reflection loss in liver experiments for 600 s. The temperature rise for the first 90 s in sweet potato is 76 ∘C as compared to 73 ∘C in liver with 50 W microwave ablation. Similarly, with 80-75 W microwave ablation, for the first 60 s, the temperature is 98 ∘C in sweet potato as compared to 100 ∘C in liver. The ablation zone short-axis diameter after 600 s is 3.3 cm for 50 W microwave ablation in sweet potato as compared to 3.5 cm for 30 W microwave ablation in liver. The reasons for difference in microwave ablation results in sweet potato and animal liver are discussed. This is the first study to directly receive a signal from microwave applicator during a microwave ablation process with the help of a surface antenna. The work can be extended to multiple array antennas for microwave ablation monitoring.

Design and Simulation Analysis of a 17 Element Spiral Antenna Array for Brain Imaging.

In this paper, a simple Archemedian spiral antenna fed by a 6-section exponential impedance transformer cum parallel-strip to microstrip balun is presented. Antenna and the balun are designed for ultra wide-band (UWB) (1.6-12 GHz) frequency range. Using this antenna, a 17 element array helmet is simulated in 3-5 GHz band, around CST voxel model of human brain with a 1 cm blood-clot introduced in it. A comparison of difference in reflection loss with and without tumor for various antenna positions is carried out.

Deorphaning pyrrolopyrazines as potent multi-target antimalarial agents.

The discovery of pyrrolopyrazines as potent antimalarial agents is presented, with the most effective compounds exhibiting EC50 values in the low nanomolar range against asexual blood stages of Plasmodium falciparum in human red blood cells, and Plasmodium berghei liver schizonts, with negligible HepG2 cytotoxicity. Their potential mode of action is uncovered by predicting macromolecular targets through avant-garde computer modeling. The consensus prediction method suggested a functional resemblance between ligand binding sites in non-homologous target proteins, linking the observed parasite elimination to IspD, an enzyme from the non-mevalonate pathway of isoprenoid biosynthesis, and multi-kinase inhibition. Further computational analysis suggested essential P. falciparum kinases as likely targets of our lead compound. The results obtained validate our methodology for ligand- and structure-based target prediction, expand the bioinformatics toolbox for proteome mining, and provide unique access to deciphering polypharmacological effects of bioactive chemical agents.

Activity quantification combining conjugate-view planar scintigraphies and SPECT/CT data for patient-specific 3-D dosimetry in radionuclide therapy.

PURPOSE: Three-dimensional dosimetry based on quantitative SPECT/CT has potential advantages over planar approaches, but may be impractical due to acquisition durations. We combine one SPECT/CT with improved quantification of multiple planar scintigraphies to shorten acquisitions. METHODS: A hybrid 2-D/3-D quantification technique is proposed, using SPECT/CT information for robust planar image quantification and creating virtual SPECTs out of conjugate-view planar scintigraphies; these are included in a 3-D absorbed dose calculation. A projection model simulates photon attenuation and scatter as well as camera and collimator effects. Planar and SPECT calibration techniques are described, offering multiple pathways of deriving calibration factors for hybrid quantification. Model, phantom and patient data are used to validate the approach on a per-organ basis, and the similarity of real and virtual SPECTs, and of planar images and virtual SPECT projections, is assessed using linear regression analysis. RESULTS: Organ overlap, background activity and organ geometry are accounted for in the algorithm. Hybrid time-activity curves yield the same information as those derived from a conventional SPECT evaluation. Where correct values are known, hybrid quantification errors are less than 16% for all but two compartments (SPECT/CT 23%). Under partial volume effects, hybrid quantification can provide more robust results than SPECT/CT. The mean correlation coefficient of 3-D data is 0.962 (2-D 0.934). As a consequence of good activity quantification performance, good agreement of absorbed dose estimates and dose-volume histograms with reference results is achieved. CONCLUSION: The proposed activity quantification method for 2-D scintigraphies can speed up SPECT/CT-based 3-D dosimetry without losing accuracy.

Simultaneous reconstruction of activity and attenuation for PET/MR.

Medical investigations targeting a quantitative analysis of the position emission tomography (PET) images require the incorporation of additional knowledge about the photon attenuation distribution in the patient. Today, energy range adapted attenuation maps derived from computer tomography (CT) scans are used to effectively compensate for image quality degrading effects, such as attenuation and scatter. Replacing CT by magnetic resonance (MR) is considered as the next evolutionary step in the field of hybrid imaging systems. However, unlike CT, MR does not measure the photon attenuation and thus does not provide an easy access to this valuable information. Hence, many research groups currently investigate different technologies for MR-based attenuation correction (MR-AC). Typically, these approaches are based on techniques such as special acquisition sequences (alone or in combination with subsequent image processing), anatomical atlas registration, or pattern recognition techniques using a data base of MR and corresponding CT images. We propose a generic iterative reconstruction approach to simultaneously estimate the local tracer concentration and the attenuation distribution using the segmented MR image as anatomical reference. Instead of applying predefined attenuation values to specific anatomical regions or tissue types, the gamma attenuation at 511 keV is determined from the PET emission data. In particular, our approach uses a maximum-likelihood estimation for the activity and a gradient-ascent based algorithm for the attenuation distribution. The adverse effects of scattered and accidental gamma coincidences on the quantitative accuracy of PET, as well as artifacts caused by the inherent crosstalk between activity and attenuation estimation are efficiently reduced using enhanced decay event localization provided by time-of-flight PET, accurate correction for accidental coincidences, and a reduced number of unknown attenuation coefficients. First results achieved with measured whole body PET data and reference segmentation from CT showed an absolute mean difference of 0.005 cm⁻¹ (< 20%) in the lungs, 0.0009 cm⁻¹ (< 2%) in case of fat, and 0.0015 cm⁻¹ (< 2%) for muscles and blood. The proposed method indicates a robust and reliable alternative to other MR-AC approaches targeting patient specific quantitative analysis in time-of-flight PET/MR.

Significant progress in predicting the crystal structures of small organic molecules--a report on the fourth blind test.

We report on the organization and outcome of the fourth blind test of crystal structure prediction, an international collaborative project organized to evaluate the present state in computational methods of predicting the crystal structures of small organic molecules. There were 14 research groups which took part, using a variety of methods to generate and rank the most likely crystal structures for four target systems: three single-component crystal structures and a 1:1 cocrystal. Participants were challenged to predict the crystal structures of the four systems, given only their molecular diagrams, while the recently determined but as-yet unpublished crystal structures were withheld by an independent referee. Three predictions were allowed for each system. The results demonstrate a dramatic improvement in rates of success over previous blind tests; in total, there were 13 successful predictions and, for each of the four targets, at least two groups correctly predicted the observed crystal structure. The successes include one participating group who correctly predicted all four crystal structures as their first ranked choice, albeit at a considerable computational expense. The results reflect important improvements in modelling methods and suggest that, at least for the small and fairly rigid types of molecules included in this blind test, such calculations can be constructively applied to help understand crystallization and polymorphism of organic molecules.

Synthesis and characterization of hydroxy-functionalized models for the active site in Fe-only-hydrogenases.

The reactions of DL-1,4-disulfanylbutane-2,3-diol and 1,3-disulfanylpropan-2-ol with dodecacarbonyltriiron have been investigated. As main products, the iron complexes 1 and 2 were isolated and characterized by spectroscopic methods, as well as single crystal X-ray analysis. Additionally, the unusually large bond angles in the dithiolato bridge was investigated via density-functional theory (DFT) calculations. Moreover, the electrochemical features have been studied by cyclic voltammetry.

Crystal structure prediction of small organic molecules: a second blind test.

The first collaborative workshop on crystal structure prediction (CSP1999) has been followed by a second workshop (CSP2001) held at the Cambridge Crystallographic Data Centre. The 17 participants were given only the chemical diagram for three organic molecules and were invited to test their prediction programs within a range of named common space groups. Several different computer programs were used, using the methodology wherein a molecular model is used to construct theoretical crystal structures in given space groups, and prediction is usually based on the minimum calculated lattice energy. A maximum of three predictions were allowed per molecule. The results showed two correct predictions for the first molecule, four for the second molecule and none for the third molecule (which had torsional flexibility). The correct structure was often present in the sorted low-energy lists from the participants but at a ranking position greater than three. The use of non-indexed powder diffraction data was investigated in a secondary test, after completion of the ab initio submissions. Although no one method can be said to be completely reliable, this workshop gives an objective measure of the success and failure of current methodologies.