Tube voltage-independent coronary calcium scoring on a first-generation dual-source photon-counting CT-a proof-of-principle phantom study.

To evaluate the accuracy of coronary artery calcium (CAC) scoring at various tube voltages and different monoenergetic image reconstructions on a first-generation dual-source photon-counting detector CT (PCD-CT). A commercially available anthropomorphic chest phantom with calcium inserts was scanned at different tube voltages (90 kV, Sn100kV, 120 kV, and Sn140kV) on a first-generation dual-source PCD-CT system with quantum technology using automatic exposure control with an image quality (IQ) level of 20. The same phantom was also scanned on a conventional energy-integrating detector CT (120 kV; weighted filtered back projection) for reference. Extension rings were used to emulate different patient sizes. Virtual monoenergetic images at 65 keV and 70 keV applying different levels of quantum iterative reconstruction (QIR) were reconstructed from the PCD-CT data sets. CAC scores were determined and compared to the reference. Radiation doses were noted. At an IQ level of 20, radiation doses ranged between 1.18 mGy and 4.64 mGy, depending on the tube voltage and phantom size. Imaging at 90 kV or Sn100kV was associated with a size-dependent radiation dose reduction between 23% and 48% compared to 120 kV. Tube voltage adapted image reconstructions with 65 keV and QIR 3 at 90 kV and with 70 keV and QIR 1 at Sn100kV allowed to calculate CAC scores comparable to conventional EID-CT scans with a percentage deviation of ≤ 5% for all phantom sizes. Our phantom study indicates that CAC scoring with dual-source PCD-CT is accurate at various tube voltages, offering the possibility of substantial radiation dose reduction.

Structured Digital Self-Assessment of Patient Anamnesis Prior to Computed Tomography: Performance Evaluation and Added Value.

The aim of this study was to evaluate the performance of a tablet-based, digitized structured self-assessment (DSSA) of patient anamnesis (PA) prior to computed tomography (CT). Of the 317 patients consecutively referred for CT, the majority (n = 294) was able to complete the tablet-based questionnaire, which consisted of 67 items covering social anamnesis, lifestyle factors (e.g., tobacco abuse), medical history (e.g., kidney diseases), current symptoms, and the usability of the system. Patients were able to mark unclear questions for a subsequent discussion with the radiologist. Critical issues for the CT examination were structured and automatically highlighted as "red flags" (RFs) in order to improve patient interaction. RFs and marked questions were highly prevalent (69.5% and 26%). Missing creatinine values (33.3%), kidney diseases (14.4%), thyroid diseases (10.6%), metformin (5.5%), claustrophobia (4.1%), allergic reactions to contrast agents (2.4%), and pathological TSH values (2.0%) were highlighted most frequently as RFs. Patient feedback regarding the comprehensibility of the questionnaire and the tablet usability was mainly positive (90.9%; 86.2%). With advanced age, however, patients provided more negative feedback for both (p = 0.007; p = 0.039). The time effort was less than 20 min for 85.1% of patients, and faster patients were significantly younger (p = 0.046). Overall, the DSSA of PA prior to CT shows a high success rate and is well accepted by most patients. RFs and marked questions were common and helped to focus patients' interactions and reporting towards decisive aspects.

Novel iterative reconstruction method with optimal dose usage for partially redundant CT-acquisition.

In CT imaging, a variety of applications exist which are strongly SNR limited. However, in some cases redundant data of the same body region provide additional quanta. Examples in dual energy CT, the spatial resolution has to be compromised to provide good SNR for material decomposition. However, the respective spectral dataset of the same body region provides additional quanta which might be utilized to improve SNR of each spectral component. Perfusion CT is a high dose application, and dose reduction is highly desirable. However, a meaningful evaluation of perfusion parameters might be impaired by noisy time frames. On the other hand, the SNR of the average of all time frames is extremely high.In redundant CT acquisitions, multiple image datasets can be reconstructed and averaged to composite image data. These composite image data, however, might be compromised with respect to contrast resolution and/or spatial resolution and/or temporal resolution. These observations bring us to the idea of transferring high SNR of composite image data to low SNR 'source' image data, while maintaining their resolution.It has been shown that the noise characteristics of CT image data can be improved by iterative reconstruction (Popescu et al 2012 Book of Abstracts, 2nd CT Meeting (Salt Lake City, UT) p 148). In case of data dependent Gaussian noise it can be modelled with image-based iterative reconstruction at least in an approximate manner (Bruder et al 2011 Proc. SPIE 7961 79610J). We present a generalized update equation in image space, consisting of a linear combination of the previous update, a correction term which is constrained by the source image data, and a regularization prior, which is initialized by the composite image data. This iterative reconstruction approach we call bimodal reconstruction (BMR). Based on simulation data it is shown that BMR can improve low contrast detectability, substantially reduces the noise power and has the potential to recover spatial resolution of the source image data.For different CT applications: dual energy imaging, liver imaging, spiral imaging, cardiac imaging, we show that SNR can efficiently be transferred from the composite image to the source image data at constant patient dose, while maintaining resolution properties of the source data.

Dose reduction in computed tomography of the chest: image quality of iterative reconstructions at a 50% radiation dose compared to filtered back projection at a 100% radiation dose.

PURPOSE: The aim of this study was to evaluate the potential of iterative reconstruction (IR) in chest computed tomography (CT) to reduce radiation exposure. The qualitative and quantitative image quality of standard reconstructions with filtered back projection (FBP) and half dose (HD) chest CT data reconstructed with FBP and IR was assessed. MATERIALS AND METHODS: 52 consecutive patients underwent contrast-enhanced chest CT on a dual-source CT system at 120 kV and automatic exposure control. The tube current was equally split on both tube detector systems. For the HD datasets, only data from one tube detector system was utilized. Thus, FD and HD data was available for each patient with a single scan. Three datasets were reconstructed from the raw data: standard full dose (FD) images applying FBP which served as a reference, HD images applying FBP and IR. Objective image quality analysis was performed by measuring the image noise in tissue and air. The subjective image quality was evaluated by 2 radiologists according to European guidelines. Additional assessment of artifacts, lesion conspicuity and edge sharpness was performed. RESULTS: Image noise did not differ significantly between HD-IR and FD-FBP (p = 0.254) but increased substantially in HD-FBP (p < 0.001). No statistically significant differences were found for the reproduction of anatomical and pathological structures between HD-IR and FD-FBP, subsegmental bronchi and bronchioli. The image quality of HD-FBP was rated inferior because of increased noise. CONCLUSION: A 50 % dose reduction in contrast-enhanced chest CT is feasible without a loss of diagnostic confidence if IR is used for image data reconstruction. Iterative reconstruction is another powerful tool to reduce radiation exposure and can be combined with other dose-saving techniques. KEY POINTS: • Iterative reconstructions allow for image noise and artifact reduction.• Comparable image data can thus be attained even at 50 % radiation dose.• Diagnostic confidence remains unaffected.

Reconstructions with identical filling (RIF) of the heart: a physiological approach to image reconstruction in coronary CT angiography.

OBJECTIVES: To compare image quality in coronary artery computed tomography angiography (cCTA) using reconstructions with automated phase detection and Reconstructions computed with Identical Filling of the heart (RIF). METHODS: Seventy-four patients underwent ECG-gated dual source CT (DSCT) between November 2009 and July 2010 for suspected coronary heart disease (n = 35), planning of transcatheter aortic valve replacement (n = 34) or evaluation of ventricular function (n = 5). Image data sets by the RIF formula and automated phase detection were computed and evaluated with the AHA 15-segment model and a 5-grade Likert scale (1: poor, 5: excellent quality). Subgroups regarding rhythm (sinus rhythm = SR; arrhythmia = ARR) and potential premedication were evaluated by a per-segment, per-vessel and per-patient analysis. RESULTS: RIF significantly improved image quality in 10 of 15 coronary segments (P < 0.05). More diagnostic segments were provided by RIF regarding the entire cohort (n = 693 vs. 590, P < 0.001) and all of the subgroups (e.g. ARR: n = 143 vs. 72, P < 0.001). In arrhythmic patients (n = 19), more diagnostic vessels (e.g. LAD: n = 10 vs. 3; P < 0.014) and complete data sets (n = 7 vs. 1; P < 0.001) were produced. CONCLUSIONS: RIF reconstruction is superior to automatic diastolic non-edited reconstructions, especially in arrhythmic patients. RIF theory provides a physiological approach for determining the optimal image reconstruction point in ECG-gated CT angiography. KEY POINTS: Conventional CT coronary angiography suffers from numerous artefacts in patients with irregular rhythms. Coronary computed tomography angiograms (cCTA) were reconstructed with identical cardiac filling (RIF). RIF reconstructions provide improved image quality compared to non-edited standard reconstructions. RIF theory links physiology with cardiac CT.

Solid-phase supported synthesis: a possibility for rapid scale-up of chemical reactions.

The direct scale-up of a solid-phase synthesis has been demonstrated with 4-(2-amino-6-phenylpyrimidin-4-yl)benzamide and an arylsulfonamido-substituted hydroxamic acid derivative as examples. These compounds were obtained through combinatorial chemistry and solution-phase synthesis was used in parallel to provide a comparison. By applying highly loaded polystyrene-derived resins as the solid support, a good ratio between the product and the starting resin is achieved. We have demonstrated that the synthesis can be scaled up directly on the solid support, successfully providing the desired compounds easily and quickly in sufficient quantities for early development demands.

Desbutyl-benflumetol, a novel antimalarial compound: in vitro activity in fresh isolates of Plasmodium falciparum from Thailand.

Desbutyl-benflumetol (DBB) is a novel antimalarial compound closely related to benflumetol (lumefantrine), of which it is a putative metabolite. The in vitro response of Plasmodium falciparum to DBB was studied in Mae Hong Son and Mae Sot, in northwest Thailand, in 1997 and 1998. In total, 155 fresh isolates were successfully tested using the World Health Organization standard in vitro microtest system (Mark II). The mean 50% effective concentration (EC(50)) and 90% effective concentration of DBB were 6.36 and 31.09 nmol/liter, respectively. The comparison of the activity of DBB and benflumetol yielded a highly significant potency ratio of 4.52, corresponding to a more than four times higher efficacy of DBB. A considerable potency difference was found between isolates from Mae Hong Son and those from Mae Sot, reflecting lesser sensitivity in the area with marked resistance to mefloquine and quinine. This observation is also supported by a highly significant activity correlation with benflumetol (P < 0.001) and to a similar degree with mefloquine (P < 0.001), reflecting a close relationship of DBB with the class II aryl amino alcohol blood schizontocides. A less distinct association was also found with artemisinin, which was significant only at the EC(50) level, and there was no correlation at all with chloroquine. DBB is a promising antimalarial compound that merits further investigation in order to define its practical therapeutic potential.

Organic process research and development--fifth international conference.

The development of antitumor and antifungal drugs, compounds to treat obesity, urge incontinence, glaucoma and retinopathy were the focus of presentations, although details of biological activity and clinical performance were not reported. Gram-to-ton-scale preparation was discussed in chemical and engineering detail, with an emphasis on route development and optimization. General considerations included high-throughput optimization using statistical and automatic laboratory tools, downscaling, and the fruitful interaction between chemists and engineers to detect and prevent potential scale-up problems as early as possible, ie, the 'bottom-up approach' to design direct drop processes for the simple and economic isolation of reaction products, cost calculations as decisive instruments for route selection and second-generation processes and the various approaches to generate enantiomerically pure compounds.

Antiparasitics - a review of the recent patent literature.

A total of 45 patents relating to chemical substances with antiparasitic activity appeared during the last quarter of 1999 and the first quarter of 2000. While ten were concerned with specific formulations of registered drugs, nine alluded to the antiparasitc activity in a general way but without substantiating such effect. The majority of the 26 remaining patents reflected the further exploration of chemical groups with known antiparasitic activity. All patents covering antimalarials relate to artemisinin analogs, some of which may offer pharmacodynamic advantages over currently available commercial products. Only two patents concern candidate compounds against human and animal infections by members of the Trypanosomatidae family. In contrast, ectoparasitoses of livestock animals received greater attention with new developments in the area of avermectins, nodulosporins, marcfortines and paraherquamides, with pyrazole analogs obviously reflecting a major veterinary medical interest. As a result of molecular biological research, two new approaches to antiparasitic therapy were identified and two new screening methods were developed for application in antiparasitic and antifungal screening.

Fluoroolefin isosteres.

Replacement of the amide bond in the peptide backbone can improve the activity, stability, or bioavailability of the resultant unnatural peptide (1). Amide bond surrogates cannot only impart peptidase resistance, but can also facilitate conformational control of the target peptide. Although the alkene ψ[C=C] isostere is an accurate mimic of the steric demand, bond lengths, and bond angles of the amide bond (2-6), it also permits construction of both the (E) and (Z) cis- and trans-) isomers independently. Unlike the amide bond, which has some degree of flexibility, the ψ[C=C] isostere is conformational fixed (7-8). The ψ[CF=C] isostere retains these attributes, but accurately mimics the electronic features of the amide bond (9-11) to include dipole moment, charge distribution, and electrostatic potential.