Influence of scatter reduction method and monochromatic beams on image quality and dose in mammography.

In mammography, the image contrast and dose delivered to the patient are determined by the x-ray spectrum and the scatter to primary ratio S/P. Thus the quality of the mammographic procedure is highly dependent on the choice of anode and filter material and on the method used to reduce the amount of scattered radiation reaching the detector. Synchrotron radiation is a useful tool to study the effect of beam energy on the optimization of the mammographic process because it delivers a high flux of monochromatic photons. Moreover, because the beam is naturally flat collimated in one direction, a slot can be used instead of a grid for scatter reduction. We have measured the ratio S/P and the transmission factors for grids and slots for monoenergetic synchrotron radiation. In this way the effect of beam energy and scatter rejection method were separated, and their respective importance for image quality and dose analyzed. Our results show that conventional mammographic spectra are not far from optimum and that the use of a slot instead of a grid has an important effect on the optimization of the mammographic process. We propose a simple numerical model to quantify this effect.

An active contour-based atlas registration model applied to automatic subthalamic nucleus targeting on MRI: method and validation.

This paper presents a new non parametric atlas registration framework, derived from the optical flow model and the active contour theory, applied to automatic subthalamic nucleus (STN) targeting in deep brain stimulation (DBS) surgery. In a previous work, we demonstrated that the STN position can be predicted based on the position of surrounding visible structures, namely the lateral and third ventricles. A STN targeting process can thus be obtained by registering these structures of interest between a brain atlas and the patient image. Here we aim to improve the results of the state of the art targeting methods and at the same time to reduce the computational time. Our simultaneous segmentation and registration model shows mean STN localization errors statistically similar to the most performing registration algorithms tested so far and to the targeting expert's variability. Moreover, the computational time of our registration method is much lower, which is a worthwhile improvement from a clinical point of view.

High b-value Diffusion-weighted Imaging: A Sensitive Method to Reveal White Matter Changes in Schizophrenia

Background: b-value is the parameter characterizing the intensity of the diffusion weighting during image acquisition. Data acquisition is usually performed with low b value (b~1000 s/mm2). Evidence shows that high b-values (b>2000 s/mm2) are more sensitive to the slow diffusion compartment (SDC) and maybe more sensitive in detecting white matter (WM) anomalies in schizophrenia.Methods: 12 male patients with schizophrenia (mean age 35 +/-3 years) and 16 healthy male controls matched for age were scanned with a low b-value (1000 s/mm2) and a high b-value (4000 s/mm2) protocol. Apparent diffusion coefficient (ADC) is a measure of the average diffusion distance of water molecules per time unit (mm2/s). ADC maps were generated for all individuals. 8 region of interests (frontal and parietal region bilaterally, centrum semi-ovale bilaterally and anterior and posterior corpus callosum) were manually traced blind to diagnosis.Results: ADC measures acquired with high b-value imaging were more sensitive in detecting differences between schizophrenia patients and healthy controls than low b-value imaging with a gain in significance by a factor of 20- 100 times despite the lower image Signal-to-noise ratio (SNR). Increased ADC was identified in patient's WM (p=0.00015) with major contributions from left and right centrum semi-ovale and to a lesser extent right parietal region.Conclusions: Our results may be related to the sensitivity of high b-value imaging to the SDC believed to reflect mainly the intra-axonal and myelin bound water pool. High b-value imaging might be more sensitive and specific to WM anomalies in schizophrenia than low b-value imaging

Determination of trimipramine and its demethylated and hydroxylated metabolites in plasma by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric (GC-MS) method has been developed, for the determination of trimipramine (TRI), desmethyltrimipramine (DTRI), didesmethyltrimipramine (DDTRI), 2-hydroxytrimipramine (2-OH-TRI) and 2-hydroxydesmethyltrimipramine (2-OH-DTRI). The method includes two derivatization steps with trifluoroacetic acid anhydride and N-methyl-N-(tert.-butyldimethyl silyl)trifluoroacetamide and the use of an SE-54 capillary silica column. The limits of quantitation were found to be 2 ng/ml for DTRI and 4 ng/ml for all other substances. Besides, methods have been optimized for the hydrolysis of the glucuronic acid conjugated metabolites. This specific detection method is useful, as polymedication is a usual practice in clinical situations, and its sensitivity allows its use for single-dose pharmacokinetic studies.

A LC-tandem MS assay for the simultaneous measurement of new antiretroviral agents: Raltegravir, maraviroc, darunavir, and etravirine.

Raltegravir (RAL), maraviroc (MVC), darunavir (DRV), and etravirine (ETV) are new antiretroviral agents with significant potential for drug interactions. This work describes a sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of plasma drug levels. Single-step extraction of RAL, MVC, DRV, ETV and RTV from plasma (100 microl) is performed by protein precipitation using 600 microl of acetonitrile, after the addition of 100 microl darunavir-d(9) (DRV-d(9)) at 1000 ng/ml in MeOH/H(2)O 50/50 as internal standard (I.S.). The mixture is vortexed, sonicated for 10 min, vortex-mixed again and centrifuged. An aliquot of supernatant (150 microl) is diluted 1:1 with a mixture of 20 mM ammonium acetate/MeOH 40/60 and 10 microl is injected onto a 2.1 x 50 mm Waters Atlantis-dC18 3 microm analytical column. Chromatographic separations are performed using a gradient program with 2 mM ammonium acetate containing 0.1% formic acid and acetonitrile with 0.1% formic acid. Analytes quantification is performed by electrospray ionisation-triple quadrupole mass spectrometry using the selected reaction monitoring detection in the positive mode. The method has been validated over the clinically relevant concentrations ranging from 12.5 to 5000 ng/ml, 2.5 to 1000 ng/ml, 25 to 10,000 ng/ml, 10 to 4000 ng/ml, and 5 to 2000 ng/ml for RAL, MRV, DRV, ETV and RTV, respectively. The extraction recovery for all antiretroviral drugs is always above 91%. The method is precise, with mean inter-day CV% within 5.1-9.8%, and accurate (range of inter-day deviation from nominal values -3.3 to +5.1%). In addition our method enables the simultaneous assessment of raltegravir-glucuronide. This is the first analytical method allowing the simultaneous assay of antiretroviral agents targeted to four different steps of HIV replication. The proposed method is suitable for the Therapeutic Drug Monitoring Service of these new regimen combinations administered as salvage therapy to patients having experienced treatment failure, and for whom exposure, tolerance and adherence assessments are critical.

Iterative statistical reconstruction method: A new way to reduce dose in pediatric cardiac CT

Purpose: Although several approaches have been already used to reduce radiation dose, CT doses are still among the high doses in radio-diagnostic. Recently, General Electric introduced a new imaging reconstruction technique, adaptive statistical iterative reconstruction (ASIR), allows to taking into account the statistical fluctuation of noise. The benefits of ASIR method were assessed through classic metrics and the evaluations of cardiac structures by radiologists. Methods and materials: A 64-row CT (MDCT) was employed. Catphan600 phantom acquisitions and 10 routine-dose CT examinations performed at 80 kVp were reconstructed with FBP and with 50% of ASIR. Six radiologists then assessed the visibility of main cardiac structures using the visual grading analysis (VGA) method. Results: On phantoms, for a constant value of SD (25 HU), CTDIvol is divided by 2 (8 mGy to 4 mGy) when 50% of ASIR is used. At constant CTDIvol, MTF medium frequencies were also significantly improved. First results indicated that clinical images reconstructed with ASIR had a better overall image quality compared with conventional reconstruction. This means that at constant image quality the radiation dose can be strongly reduced. Conclusion: The first results of this study shown that the ASIR method improves the image quality on phantoms by decreasing noise and improving resolution with respect to the classical one. Moreover, the benefit obtained is higher at lower doses. In clinical environment, a dose reduction can still be expected on 80 kVp low dose pediatric protocols using 50% of iterative reconstruction. Best ASIR percentage as a function of cardiac structures and detailed protocols will be presented for cardiac examinations.

An operator formulation of the multiscale finite-volume method with correction function

The multiscale finite-volume (MSFV) method has been derived to efficiently solve large problems with spatially varying coefficients. The fine-scale problem is subdivided into local problems that can be solved separately and are coupled by a global problem. This algorithm, in consequence, shares some characteristics with two-level domain decomposition (DD) methods. However, the MSFV algorithm is different in that it incorporates a flux reconstruction step, which delivers a fine-scale mass conservative flux field without the need for iterating. This is achieved by the use of two overlapping coarse grids. The recently introduced correction function allows for a consistent handling of source terms, which makes the MSFV method a flexible algorithm that is applicable to a wide spectrum of problems. It is demonstrated that the MSFV operator, used to compute an approximate pressure solution, can be equivalently constructed by writing the Schur complement with a tangential approximation of a single-cell overlapping grid and incorporation of appropriate coarse-scale mass-balance equations.

Determination of the Enantiomers of Mianserin and its Metabolites in Plasma by Capillary Electrophoresis After Liquid-Liquid Extraction and On-Column Sample Preconcentration

Capillary electrophoresis has drawn considerable attention in the past few years, particularly in the field of chiral separations because of its high separation efficiency. However, its routine use in therapeutic drug monitoring is hampered by its low sensitivity due to a short optical path. We have developed a capillary zone electrophoresis (CZE) method using 2mM of hydroxypropyl-β-cyclodextrin as a chiral selector, which allows base-to-base separation of the enantiomers of mianserin (MIA), desmethylmianserin (DMIA), and 8-hydroxymianserin (OHMIA). Through the use of an on-column sample concentration step after liquid-liquid extraction from plasma and through the presence of an internal standard, the quantitation limits were found to be 5 ng/mL for each enantiomer of MIA and DMIA and 15 ng/mL for each enantiomer of OHMIA. To our knowledge, this is the first published CE method that allows its use for therapeutic monitoring of antidepressants due to its sensitivity down to the low nanogram range. The variability of the assays, as assessed by the coefficients of variation (CV) measured at two concentrations for each substance, ranged from 2 to 14% for the intraday (eight replicates) and from 5 to 14% for the interday (eight replicates) experiments. The deviations from the theoretical concentrations, which represent the accuracy of the method, were all within 12.5%. A linear response was obtained for all compounds within the range of concentrations used for the calibration curves (10-150 ng/mL for each enantiomer of MIA and DMIA and 20-300 ng/mL for each enantiomer of OHMIA). Good correlations were calculated between [(R) + (S)]-MIA and DMIA concentrations measured in plasma samples of 20 patients by a nonchiral gas chromatography method and CZE, and between the (R)- and (S)-concentrations of MIA and DMIA measured in plasma samples of 37 patients by a previously described chiral high-performance liquid chromatography method and CZE. Finally, no interference was noted from more than 20 other psychotropic drugs. Thus, this method, which is both sensitive and selective, can be routinely used for therapeutic monitoring of the enantiomers of MIA and its metabolites. It could be very useful due to the demonstrated interindividual variability of the stereoselective metabolism of MIA.

Molecular identification of an endemic Alpine mammal, Apodemus alpicola, using a PCR-based RFLP method

The ability of a PCR-based restriction fragment length polymorphism (RFLP) analysis of the cytochrome b (mtDNA) to distinguish Apodemus alpicola from two other Apodemus species was investigated. The partial sequencing of the cytochrome b allowed the identification of one enzyme as being potentially diagnostic. This was supported by an analysis of 131 specimens previously identified using morphometric and/or allozymic data, indicating that the PCR-based RFLP method provides a rapid and reliable tool for distinguishing A. alpicola from its two co-occurring congenerics. The method is applicable to samples taken in the field for ecological studies, and could easily be adapted to the identification of museum samples.

A simple gas chromatography method for the analysis of monoethanolamine in air

A simple method determining airborne monoethanolamine has been developed. Monoethanolamine determination has traditionally been difficult due to analytical separation problems. Even in recent sophisticated methods, this difficulty remains as the major issue often resulting in time-consuming sample preparations. Impregnated glass fiber filters were used for sampling. Desorption of monoethanolamine was followed by capillary GC analysis and nitrogen phosphorous selective detection. Separation was achieved using a specific column for monoethanolamines (35% diphenyl and 65% dimethyl polysiloxane). The internal standard was quinoline. Derivatization steps were not needed. The calibration range was 0.5-80 μg/mL with a good correlation (R(2) = 0.996). Averaged overall precisions and accuracies were 4.8% and -7.8% for intraday (n = 30), and 10.5% and -5.9% for interday (n = 72). Mean recovery from spiked filters was 92.8% for the intraday variation, and 94.1% for the interday variation. Monoethanolamine on stored spiked filters was stable for at least 4 weeks at 5°C. This newly developed method was used among professional cleaners and air concentrations (n = 4) were 0.42 and 0.17 mg/m(3) for personal and 0.23 and 0.43 mg/m(3) for stationary measurements. The monoethanolamine air concentration method described here was simple, sensitive, and convenient both in terms of sampling and analytical analysis.

A comparative study on inter and intralaboratory reproducibility of renin measurement with a conventional enzymatic method and a new chemiluminescent assay of immunoreactive renin.

BACKGROUND: The activity of the renin-angiotensin system is usually evaluated as plasma renin activity (PRA, ngAI/ml per h) but the reproducibility of this enzymatic assay is notoriously scarce. We compared the inter and intralaboratory reproducibilities of PRA with those of a new automated chemiluminescent assay, which allows the direct quantification of immunoreactive renin [chemiluminescent immunoreactive renin (CLIR), microU/ml]. METHODS: Aliquots from six pool plasmas of patients with very low to very high PRA levels were measured in 12 centres with both the enzymatic and the direct assays. The same methods were applied to three control plasma preparations with known renin content. RESULTS: In pool plasmas, mean PRA values ranged from 0.14 +/- 0.08 to 18.9 +/- 4.1 ngAI/ml per h, whereas those of CLIR ranged from 4.2 +/- 1.7 to 436 +/- 47 microU/ml. In control plasmas, mean values of PRA and of CLIR were always within the expected range. Overall, there was a significant correlation between the two methods (r = 0.73, P < 0.01). Similar correlations were found in plasmas subdivided in those with low, intermediate and high PRA. However, the coefficients of variation among laboratories found for PRA were always higher than those of CLIR, ranging from 59.4 to 17.1% for PRA, and from 41.0 to 10.7% for CLIR (P < 0.01). Also, the mean intralaboratory variability was higher for PRA than for CLIR, being respectively, 8.5 and 4.5% (P < 0.01). CONCLUSION: The measurement of renin with the chemiluminescent method is a reliable alternative to PRA, having the advantage of a superior inter and intralaboratory reproducibility.

A Multi-SNP Locus-Association Method Reveals a Substantial Fraction of the Missing Heritability.

There are many known examples of multiple semi-independent associations at individual loci; such associations might arise either because of true allelic heterogeneity or because of imperfect tagging of an unobserved causal variant. This phenomenon is of great importance in monogenic traits but has not yet been systematically investigated and quantified in complex-trait genome-wide association studies (GWASs). Here, we describe a multi-SNP association method that estimates the effect of loci harboring multiple association signals by using GWAS summary statistics. Applying the method to a large anthropometric GWAS meta-analysis (from the Genetic Investigation of Anthropometric Traits consortium study), we show that for height, body mass index (BMI), and waist-to-hip ratio (WHR), 3%, 2%, and 1%, respectively, of additional phenotypic variance can be explained on top of the previously reported 10% (height), 1.5% (BMI), and 1% (WHR). The method also permitted a substantial increase (by up to 50%) in the number of loci that replicate in a discovery-validation design. Specifically, we identified 74 loci at which the multi-SNP, a linear combination of SNPs, explains significantly more variance than does the best individual SNP. A detailed analysis of multi-SNPs shows that most of the additional variability explained is derived from SNPs that are not in linkage disequilibrium with the lead SNP, suggesting a major contribution of allelic heterogeneity to the missing heritability.