Can different Catphan phantoms be used in a multi-centre audit of radiotherapy CT image quality?

PurposeTo determine the variation between Catphan image quality CT phantoms, specifically for use in a future multi-centre image quality audit.Method14 Catphan phantoms (models 503, 504 and 604) were scanned on a Canon Aquilion Prime CT scanner using a single scan protocol. Measurements were made of noise in the uniformity section, visibility of low contrast targets and contrast, x-ray attenuation and CT number for 5 materials in the sensitometry section. Scans were also acquired using one phantom and varying reconstruction field of view, image slice thickness, effective tube-current-time product and iterative reconstruction settings to determine how the degree of inter-phantom variability compared with the magnitude of changes from scan parameter alteration.ResultsAcross all phantoms the mean CT value in the uniformity section was 7.0 (SD 0.9) range: 4.9–8.1 HU. For the different materials the CT numbers were air: −1004 ± 5, Polymethylpentene: −190 ± 2, Polystyrene: −42 ± 2, Delrin: 321 ± 5 and Teflon: 898 ± 8 HU. Consistency of low contrast targets through visual scoring was good. Measured contrast was lower (p < 0.001) with more variability for 504 versus 604 models. All phantoms produced identical tube current settings with x-ray tube current modulation, indicating no x-ray attenuation differences. The degree of change in image quality metrics between phantoms was small compared with results when scan parameters were varied.ConclusionCatphan phantoms model 604 showed minimal differences and will be used for multi-centre inter-comparison work, with the consistency between phantoms appropriate for measuring possible variations in image quality.     

First detection and quantification of N-monomethylarginine,a structural isomer of N-monomethylarginine,in humans using MS

The l-arginine metabolites methylated at the guanidino moiety, such as N^G-monomethyl-l-arginine (LNMMA), asymmetric N^G,N^G-dimethyl-l-arginine (ADMA), and symmetric N^G,N^G'-dimethyl-l-arginine (SDMA), are long known to be present in human plasma. Far less is known about the structural isomer of LNMMA, N^δ-monomethyl-l-arginine (δ-MMA). In prior work, it has been detected in yeast proteins, but it has not been investigated in mammalian plasma or cells. In this work, we present a method for the simultaneous and unambiguous quantification of LNMMA and δ-MMA in human plasma that is capable of detecting δ-MMA separately from LNMMA. The method comprises a simple protein precipitation sample preparation, hydrophilic interaction liquid chromatography (HILIC) gradient elution on an unmodified silica column, and triple stage mass spectrometric detection. Stable isotope-labeled D₆-SDMA was used as internal standard. The calibration ranges were 25–1000 nmol/L for LNMMA and 5–350 nmol/L for δ-MMA. The intra- and inter-batch precision determinations resulted in relative standard deviations of less than 12% for both compounds with accuracies of less than 6% deviation from the expected values. In a pilot study enrolling 10 healthy volunteers, mean concentrations of 48.0 ± 7.4 nmol/L for LNMMA and 27.4 ± 7.7 nmol/L for δ-MMA were found.     

Quantification of isradipine in human plasma using LC–MS/MS for pharmacokinetic and bioequivalence study

A highly sensitive and rapid method for the analysis of isradipine in human plasma using liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) was developed. The procedure involves a simple liquid–liquid extraction of isradipine and amlodipine (IS, internal standard) with methyl-t-butyl ether after alkaline treatment and separation by RP-HPLC. Detection was performed by positive ion electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 372.1 → m/z 312.2 and m/z 408.8 → m/z 237.9, for quantification of isradipine and IS, respectively. The standard calibration curves showed good linearity within the range of 10 to 5000 pg/mL (r² ≥ 0.9998). The lower limit of quantitation (LLOQ) was 10 pg/mL. The retention times of isradipine (0.81 min) and IS (0.65 min) suggested the potential for high throughput of the proposed method. In addition, no significant metabolic compounds were found to interfere with the analysis. This method offered good precision and accuracy and was successfully applied for the pharmacokinetic and bioequivalence studies of 5 mg of sustained-release isradipine in 24 healthy Korean volunteers.     

Breast glandularity and mean glandular dose assessment using a deep learning framework: Virtual patients study

PurposeBreast dosimetry in mammography is an important aspect of radioprotection since women are exposed periodically to ionizing radiation due to breast cancer screening programs. Mean glandular dose (MGD) is the standard quantity employed for the establishment of dose reference levels in retrospective population studies. However, MGD calculations requires breast glandularity estimation. This work proposes a deep learning framework for volume glandular fraction (VGF) estimations based on mammography images, which in turn are converted to glandularity values for MGD calculations.Methods208 virtual breast phantoms were generated and compressed computationally. The mammography images were obtained with Monte Carlo simulations (MC-GPU code) and a ray-tracing algorithm was employed for labeling the training data. The architectures of the neural networks are based on the XNet and multilayer perceptron, adapted for each task. The network predictions were compared with the ground truth using the coefficient of determination (r²).ResultsThe results have shown a good agreement for inner breast segmentation (r² = 0.999), breast volume prediction (r² = 0.982) and VGF prediction (r² = 0.935). Moreover, the DgN coefficients using the predicted VGF for the virtual population differ on average 1.3% from the ground truth values. Afterwards with the obtained DgN coefficients, the MGD values were estimated from exposure factors extracted from the DICOM header of a clinical cohort, with median(75 percentile) values of 1.91(2.45) mGy.ConclusionWe successfully implemented a deep learning framework for VGF and MGD calculations for virtual breast phantoms.     

High throughput film dosimetry in homogeneous and heterogeneous media for a small animal irradiator

PurposeWe have established a high-throughput Gafchromic film dosimetry protocol for narrow kilovoltage beams in homogeneous and heterogeneous media for small-animal radiotherapy applications. The kV beam characterization is based on extensive Gafchromic film dosimetry data acquired in homogeneous and heterogeneous media. An empirical model is used for parameterization of depth and off-axis dependence of measured data.MethodsWe have modified previously published methods of film dosimetry to suit the specific tasks of the study. Unlike film protocols used in previous studies, our protocol employs simultaneous multi-channel scanning and analysis of up to nine Gafchromic films per scan. A scanner and background correction were implemented to improve accuracy of the measurements. Measurements were taken in homogeneous and inhomogeneous phantoms at 220 kVp and a field size of 5 × 5 mm². The results were compared against Monte Carlo simulations.ResultsDose differences caused by variations in background signal were effectively removed by the corrections applied. Measurements in homogeneous phantoms were used to empirically characterize beam data in homogeneous and heterogeneous media. Film measurements in inhomogeneous phantoms and their empirical parameterization differed by about 2%–3%. The model differed from MC by about 1% (water, lung) to 7% (bone). Good agreement was found for measured and modelled off-axis ratios.ConclusionsEBT2 films are a valuable tool for characterization of narrow kV beams, though care must be taken to eliminate disturbances caused by varying background signals. The usefulness of the empirical beam model in interpretation and parameterization of film data was demonstrated.     

Comparaison de six méthodes de segmentation du volume tumoral sur la 18F-FDG TEP-TDM avec le volume de référence anatomopathologique dans les cancers bronchopulmonaires non à petites cellules

The ¹⁸F-FDG TEP has demonstrated its importance in oncology, for initial extension and efficacy of antitumoral therapeutics. Several studies have attempted to prove its utility to define tumoral volumes for conformational radiotherapy in nonsmall cell lung cancers. Some authors have suggested the use of threshold of tumor intensity uptake with 40 or 50% of maximal intensity. Black et al. have determined contouring with linear regression formula of mean semi-quantitative index of tumor uptake (standard uptake value): SUV_threshold = 0.307 SUV_average + 0.588. Nestlé et al. have taken into account the background noise intensity and mean intensity of the tumor: I_threshold = β I_average + I_noise with β = 0.15. Our study was done in collaboration with Inserm U618 team and has compared volumes defined on PETscan defined according to different methods based on intensity or SUV to the tumour volume determined on CT scan by radiophysicist. We have compared those volumes with histological volume that we considered for reference. Four patients have been included. They had ¹⁸F-FDG PETscan followed by complete tumoral removal surgery. Specific histological procedure allowed to define complete size of the tumor in reexpanded lung. Comparatively to pathology, the volumes obtained using I_max 40 and I_max 50 are all underestimated. The volumes defined by Black's et al. method are underevaluated for the two largest tumours (15.8% to 22%) and overestimated for the two smallest ones (17.9 to 82.9%). Nestlé's et al. method, using β = 0.15, correctly estimates two tumor volumes over 2 cm, but overestimates the two small tumors (79.6 to 124%). Finally, the corrected Nestlé's et al. formula (using β = 0.264) overestimates three tumours. Volumes defined on CT scan by radiophysicist are correct for one lesion, underestimated for one and overestimated for two other ones (44 and 179.5%). Nestlé's et al. method seems to be the most accurate for tumours over 2 cm of diameter. Today no method can correctly estimate the volume of smaller tumours. To improve those segmentation approaches, partial volume effect correction needs to be implemented for small tumours or tumours close to mediastinal local extension. The main indication of segmentation based on FDG PET is tumour greater than 2 cm for which treatment will be radiotherapy alone or radiotherapy associated with chemotherapy. Our study is important because it compares the different methods described in the literature with the reference histological volume of the tumor, which is the only way to validate tumor segmentation method.     

A feasible and automatic free tool for T1 and ECV mapping

PurposeCardiac magnetic resonance (CMR) is a useful non-invasive tool for characterizing tissues and detecting myocardial fibrosis and edema. Estimation of extracellular volume fraction (ECV) using T1 sequences is emerging as an accurate biomarker in cardiac diseases associated with diffuse fibrosis. In this study, automatic software for T1 and ECV map generation consisting of an executable file was developed and validated using phantom and human data.MethodsT1 mapping was performed in phantoms and 30 subjects (22 patients and 8 healthy subjects) on a 1.5T MR scanner using the modified Look-Locker inversion-recovery (MOLLI) sequence prototype before and 15 min after contrast agent administration. T1 maps were generated using a Fast Nonlinear Least Squares algorithm. Myocardial ECV maps were generated using both pre- and post-contrast T1 image registration and automatic extraction of blood relaxation rates.ResultsUsing our software, pre- and post-contrast T1 maps were obtained in phantoms and healthy subjects resulting in a robust and reliable quantification as compared to reference software. Coregistration of pre- and post-contrast images improved the quality of ECV maps. Mean ECV value in healthy subjects was 24.5% ± 2.5%.ConclusionsThis study demonstrated that it is possible to obtain accurate T1 maps and informative ECV maps using our software. Pixel-wise ECV maps obtained with this automatic software made it possible to visualize and evaluate the extent and severity of ECV alterations.     

Simultaneous quantification of venlafaxine and O-desmethylvenlafaxine in human plasma by ultra performance liquid chromatography–tandem mass spectrometry and its application in a pharmacokinetic study

A rapid, selective and sensitive ultra performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method was developed to simultaneously determine venlafaxine (VEN) and O-desmethylvenlafaxine (ODV) in human plasma. Sample pretreatment involved a one-step extraction with diethyl ether of 0.5 mL plasma. The separation was carried out on an ACQUITY UPLC? BEH C₁₈ column with 10 mmol/L ammonium acetate and methanol as the mobile phase at a flow rate of 0.30 mL/min. The detection was performed on a triple–quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. The linear calibration curves for VEN and ODV were both obtained in the concentration range of 0.200–200 ng/mL (r² ≥ 0.99) with the lower limit of quantification (LLOQ) of 0.200 ng/mL. The intra- and inter-day precision (relative standard deviation, R.S.D.) values were less than 13% and the accuracy (relative error, R.E.) was within ±5.3% and ±3.6% for VEN and ODV. The method herein described was superior to previous methods in sensitivity and sample throughput and successfully applied to clinical pharmacokinetic study of venlafaxine sustained-release capsule in healthy male volunteers after oral administration.     

Metabolic Characterization of All-Trans-Retinoic Acid (ATRA)–Induced Craniofacial Development of Murine Embryos Using In Vivo Proton Magnetic Resonance Spectroscopy

Aim

To characterize the abnormal metabolic profile of all-trans-retinoic acid (ATRA)–induced craniofacial development in mouse embryos using proton magnetic resonance spectroscopy (¹H-MRS).

Methods

Timed-pregnant mice were treated by oral gavage on the morning of embryonic gestation day 11 (E11) with all-trans-retinoic acid (ATRA). Dosing solutions were adjusted by maternal body weight to provide 30, 70, or 100 mg/kg RA. The control group was given an equivalent volume of the carrier alone. Using an Agilent 7.0 T MR system and a combination of surface coil coils, a 3 mm×3 mm×3 mm ¹H-MRS voxel was selected along the embryonic craniofacial tissue. ¹H-MRS was performed with a single-voxel method using PRESS sequence and analyzed using LCModel software. Hematoxylin and eosin was used to detect and confirm cleft palate.

Result

¹H-MRS revealed elevated choline levels in embryonic craniofacial tissue in the RA70 and RA100 groups compared to controls (P<0.05). Increased choline levels were also found in the RA70 and RA100 groups compared with the RA30 group (P<0.01). High intra-myocellular lipids at 1.30 ppm (IMCL13) in the RA100 group compared to the RA30 group were found (P<0.01). There were no significant changes in taurine, intra-myocellular lipids at 2.10 ppm (IMCL21), and extra-myocellular lipids at 2.30 ppm (EMCL23). Cleft palate formation was observed in all fetuses carried by mice administered 70 and 100 mg/kg RA.

Conclusions

This novel study suggests that the elevated choline and lipid levels found by ¹H-MRS may represent early biomarkers of craniofacial defects. Further studies will determine performance of this test and pathogenetic mechanisms of craniofacial malformation.     

Capillary electrophoresis determination of thiopurine methyl transferase activity in erythrocytes

Thiopurine S-methyltransferase (TPMT) catalyzes methylation of thiopurine drugs (e.g. 6-mercaptopurine, azathioprine). Decreased activity of TPMT is associated with hematopoietic toxicity after administration of standard doses of the drugs. We developed capillary electrophoretic method for determination of TPMT enzyme activity in erythrocytes. Limit of quantification of the method is 1.5 μmol/L (S/N = 6). The recovery of 6-methylmercaptopurine was 87.5–94.8%, imprecision value (as CV, n = 10) was 1.68% (within-day) and 2.53% (between-day). Erythrocyte TPMT activities were measured in 60 healthy adult volunteers.     

Stable-isotope dilution GC–MS approach for nitrite quantification in human whole blood,erythrocytes, and plasma using pentafluorobenzyl bromide derivatization: Nitrite distribution in human blood

Previously, we reported on the usefulness of pentafluorobenzyl bromide (PFB-Br) for the simultaneous derivatization and quantitative determination of nitrite and nitrate in various biological fluids by GC–MS using their ¹⁵N-labelled analogues as internal standards. As nitrite may be distributed unevenly in plasma and blood cells, its quantification in whole blood rather than in plasma or serum may be the most appropriate approach to determine nitrite concentration in the circulation. So far, GC–MS methods based on PFB-Br derivatization failed to measure nitrite in whole blood and erythrocytes because of rapid nitrite loss by oxidation and other unknown reactions during derivatization. The present article reports optimized and validated procedures for sample preparation and nitrite derivatization which allow for reliable quantification of nitrite in human whole blood and erythrocytes. Essential measures for stabilizing nitrite in these samples include sample cooling (0–4 °C), hemoglobin (Hb) removal by precipitation with acetone and short derivatization of the Hb-free supernatant (5 min, 50 °C). Potassium ferricyanide (K₃Fe(CN)₆) is useful in preventing Hb-caused nitrite loss, however, this chemical is not absolutely required in the present method. Our results show that accurate GC–MS quantification of nitrite as PFB derivative is feasible virtually in every biological matrix with similar accuracy and precision. In EDTA-anticoagulated venous blood of 10 healthy young volunteers, endogenous nitrite concentration was measured to be 486 ± 280 nM in whole blood, 672 ± 496 nM in plasma (C_P), and 620 ± 350 nM in erythrocytes (C_E). The C_E-to-C_P ratio was 0.993 ± 0.188 indicating almost even distribution of endogenous nitrite between plasma and erythrocytes. By contrast, the major fraction of nitrite added to whole blood remained in plasma. The present GC–MS method is useful to investigate distribution and metabolism of endogenous and exogenous nitrite in blood compartments under basal conditions and during hyperemia.     

Near real-time magnetic particle imaging for visual assessment of vascular stenosis in a phantom model

PurposeThis study aimed to investigate the potential of magnetic particle imaging (MPI) to quantify artificial stenoses in vessel phantoms in near real-time.MethodsCustom-made stenosis phantoms with different degrees of stenosis (0%, 25%, 50%, 75%, and 100%; length 40 mm, inner diameter 8 mm, Polyoxymethylene) were filled with diluted Ferucarbotran (superparamagnetic iron-oxide nanoparticle (SPION) tracer agent, 500 mmol (Fe)/l). A traveling wave MPI scanner (spatial resolution ~ 2 mm, gradient strength ~ 1.5 T/m, field of view: 65 mm length and 29 mm diameter, frequencies f₁ = 1050 Hz and f₂ = 12150 Hz) was used to acquire images of the phantoms (200 ms total acquisition time per image, 10 averages). Standardized grey scaling was used for comparability. All measured stenoses (n = 80) were graded manually using a dedicated software tool.ResultsMPI allowed for accurate visualization of stenoses at a frame rate of 5 frames per second. Less severe stenoses were detected more precisely than higher-grade stenoses and came with smaller standard deviations. In particular, the 0%, 25%, 50%, 75%, and 100% stenosis phantom were measured as 3.7 ± 2.7% (mean ± standard deviation), 18.6 ± 1.8%, 52.8 ± 3.7%, 77.8 ± 14.8% and 100 ± 0%. Geometrical distortions occurred around the center of the high-grade stenosis and led to higher standard deviations compared to lower grade stenoses. In the frame of this study the MPI signal depended linearly on the SPION concentration down to 0.05 mmol (Fe)/l.ConclusionNear real-time MPI accurately visualized and quantified different stenosis grades in vascular phantoms.     

Combined in-silico and in-vitro experiments support acid-base equilibrium as a tool to estimate the localization depth of 4-nitrophenol within a phospholipid bilayer

The interaction and location of 4-nitrophenol (PNP) in biomembranes are relevant in the bioaccumulation and potentiation of the intensive toxic effects of this persistent organic pollutant. In this work, in-silico analyses predicted that, in a fluid phospholipid bilayer, the minimum energy of the protonated (PNPH) and deprotonated (PNP^?) species is located within the glycerol and choline region, respectively. This was experimentally confirmed by acid-base equilibrium experiments and theory, allowing the estimation of the mean location of PNP within a bilayer region with a dielectric constant D = 50.6 compatible with the phosphate/choline moiety of egg-yolk phosphatidylcholine unilamellar (EPC) vesicles. The comparison with the D = 43.2 value obtained in Triton X-100 micelles allow predicting a mean surface potential of ψ = 25.37 mV for the EPC-water interface. Changes in the chemical shifts and longitudinal relaxation times of EPC hydrogens by ¹H NMR confirm the deeper location of the PNPH within the glycerol region and at the choline region (PNP^?) at higher pH. Intermolecular PNP^?EPC dipolar interactions within the choline region was also demonstrated at pH 10.2 using ROESY experiments. Additional information was obtained trough ³¹P NMR, that detected an increase in the anisotropy at the membrane interface after insertion of PNP which probably act as a bridge between choline moieties rigidizing the crystalline structure at that spot. Concluding, here we provide experimental support to the “pH-piston hypothesis” proposed some decades ago in the pharmaceutical field, and that reinforce the importance of the environmental conditions (e.g. pH) to modulate the bioavailability of this highly toxic pollutant.     

A Simple and Highly Sensitive Method for Magnetic Nanoparticle Quantitation Using H-NMR Spectroscopy

Iron oxide superparamagnetic nanoparticles (SPIONs) have drawn significant attention because of their potential impact on medical diagnosis and therapy. However, the difficulty of achieving reliable and standardized quantification of these nanoparticles has limited the uniform study of nanoparticle systems. Current measurement techniques have limited sensitivity, and are sophisticated and subject to individual instrumental settings. Here, a characterization method using proton nuclear magnetic resonance (¹H-NMR) spectroscopy is presented that can quantify SPIONs regardless of surface modification. In addition to routine quantification of SPIONs during nanoparticle development, the method can also be used with in vitro nanoparticle assays and potentially with tissue samples for biodistribution studies. Specifically, measurement of water relaxivity shifts (R₁ or R₂) of dissolved SPION samples is correlated with nanoparticle concentration. Unmodified and dextran- and poly(ethylene glycol)-coated SPIONs gave linear correlations between SPION concentration and R₁ and R₂ relaxivities over five orders of magnitude, to below 10 ppb iron. Quantification of SPION concentration was also demonstrated in the presence of RAW 264.7 macrophage cells. A linear correlation between the SPION concentration and relaxivities was observed to <10 ng Fe/mL. This method is a rapid and inexpensive approach for quantitation of SPIONs and exhibits a number of advantages over many of the current methods for quantitative SPION analysis.     

The Use of Magnetic Resonance Spectroscopy as a Tool for the Measurement of Bi-hemispheric Transcranial Electric Stimulation Effects on Primary Motor Cortex Metabolism

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has been increasingly used over the past decade in the treatment of neurological and psychiatric disorders such as stroke and depression. Yet, the mechanisms underlying its ability to modulate brain excitability to improve clinical symptoms remains poorly understood ³³. To help improve this understanding, proton magnetic resonance spectroscopy (¹H-MRS) can be used as it allows the in vivo quantification of brain metabolites such as γ-aminobutyric acid (GABA) and glutamate in a region-specific manner ⁴¹. In fact, a recent study demonstrated that ¹H-MRS is indeed a powerful means to better understand the effects of tDCS on neurotransmitter concentration ³⁴. This article aims to describe the complete protocol for combining tDCS (NeuroConn MR compatible stimulator) with ¹H-MRS at 3 T using a MEGA-PRESS sequence. We will describe the impact of a protocol that has shown great promise for the treatment of motor dysfunctions after stroke, which consists of bilateral stimulation of primary motor cortices ^27,30,31. Methodological factors to consider and possible modifications to the protocol are also discussed.     

Monte Carlo simulation of the dose distribution of ICRP adult reference computational phantoms for acquisitions with a 320 detector-row cone-beam CT scanner

PurposeThe purpose of this study was to develop and validate a Monte Carlo (MC) simulation tool for patient dose assessment for a 320 detector-row CT scanner, based on the recommendations of International Commission on Radiological Protection (ICRP). Additionally, the simulation was applied on four clinical acquisition protocols, with and without automatic tube current modulation (TCM).MethodsThe MC simulation was based on EGS4 code and was developed specifically for a 320 detector-row cone-beam CT scanner. The ICRP adult reference phantoms were used as patient models. Dose measurements were performed free-in-air and also in four CTDI phantoms: 150 mm and 350 mm long CT head and CT body phantoms. The MC program was validated by comparing simulations results with these actual measurements acquired under the same conditions. The measurements agreed with the simulations across all conditions within 5%. Patient dose assessment was performed for four clinical axial acquisitions using the ICRP adult reference phantoms, one of them using TCM.ResultsThe results were nearly always lower than those obtained from other dose calculator tools or published in other studies, which were obtained using mathematical phantoms in different CT systems. For the protocol with TCM organ doses were reduced by between 28 and 36%, compared to the results obtained using a fixed mA value.ConclusionsThe developed simulation program provides a useful tool for assessing doses in a 320 detector-row cone-beam CT scanner using ICRP adult reference computational phantoms and is ready to be applied to more complex protocols.     

The effect of tumour geometry on the quantification accuracy of planar 123I phantom images

IntroductionAccurate activity quantification is applied in radiation dosimetry. Planar images are important for quantification of whole-body images, enabling assessment of biodistribution from radionuclide administrations. We evaluated the effect of tumour geometry on quantification accuracy of ¹²³I planar phantom studies, including various tumour sizes, tumour-liver distances and two tumour-background ratios.Methods and materialsAn in-house manufactured abdominal phantom was equipped with a liver, different size cylindrical tumours, and a rod for tumour-liver distance variation. The geometric mean method with scatter and attenuation corrections was used for image processing. Scatter and attenuation corrections were made using the triple energy window scatter correction technique and a printed transmission sheet source, respectively. Region definitions for tumour activity distribution compensated for the partial volume effect (PVE). Activity measured in the dose calibrator served as reference for determining quantification accuracy.ResultsThe smallest tumour had the largest percentage deviation with an average activity underestimation of 34.6 ± 1.2%. Activity values for the largest tumour were overestimated by 3.1 ± 3.0%. PVE compensation improved quantification accuracy for all tumour sizes yielding accuracies of <12.4%. Scatter contribution to the tumours from the liver had minimal effect on quantification accuracy at tumour-liver distances >3 cm. With PVE compensation, increased tumour-background ratio resulted in a percentage increase of up to 26.3%.ConclusionWhen applying relevant corrections for scatter, attenuation and PVE without background activity, quantification accuracy of <13% was obtained. We demonstrated the successful implementation of a practical technique to obtain quantitative information from ¹²³I planar images.     

Standardized sample preparation phases for a quantitative measurement of plasma peptidome profiling by MALDI-TOF

A growing body of literature defines MALDI-TOF MS as a technique for studying plasma and serum, thus enabling the detection of proteins, and the generation of reproducible protein profile mass spectra, potentially able to discriminate correctly different biological systems.In this work, the different steps of the pre-analytical phase that may affect the reproducibility of plasma proteome analysis have been carefully considered.The results showed that the method is highly accurate (9.1%) and precise (8.9%) and the calibration curve for the ACTH (18–39), in human plasma, gave a good correlation coefficient (r > 0.99 and r² > 0.98). The limit of detection (LOD) and the limit of quantification (LOQ), relative intensity, were of 0.5 × 10^?9 M and 1.0 × 10^?9 M respectively.Thus, an assay has been developed for the detection of low-abundant and low molecular weight proteins, from human plasma, aiming at the identification of new potential biomarkers. The method was tested on plasma from patients with a first diagnosis of pelvic mass. Statistical analysis of plasma profile generated a sub-profile of 17 peptides with their relative abundance able to discriminate patients bearing malignant or benign tumors. The sensitivity and specificity were 85.7% and 80.0% respectively.     

Validation of a commercial TPS based on the VMC++ Monte Carlo code for electron beams: Commissioning and dosimetric comparison with EGSnrc in homogeneous and heterogeneous phantoms

The aim of the present work was the validation of the VMC⁺⁺ Monte Carlo (MC) engine implemented in the Oncentra Masterplan (OMTPS) and used to calculate the dose distribution produced by the electron beams (energy 5-12 MeV) generated by the linear accelerator (linac) Primus (Siemens), shaped by a digital variable applicator (DEVA). The BEAMnrc/DOSXYZnrc (EGSnrc package) MC model of the linac head was used as a benchmark.Commissioning results for both MC codes were evaluated by means of 1D Gamma Analysis (2%, 2 mm), calculated with a home-made Matlab (The MathWorks) program, comparing the calculations with the measured profiles. The results of the commissioning of OMTPS were good [average gamma index (γ) > 97%]; some mismatches were found with large beams (size ≥ 15 cm). The optimization of the BEAMnrc model required to increase the beam exit window to match the calculated and measured profiles (final average γ > 98%).Then OMTPS dose distribution maps were compared with DOSXYZnrc with a 2D Gamma Analysis (3%, 3 mm), in 3 virtual water phantoms: (a) with an air step, (b) with an air insert, and (c) with a bone insert.The OMTPD and EGSnrc dose distributions with the air-water step phantom were in very high agreement (γ ∼ 99%), while for heterogeneous phantoms there were differences of about 9% in the air insert and of about 10–15% in the bone region. This is due to the Masterplan implementation of VMC⁺⁺ which reports the dose as “dose to water”, instead of “dose to medium”.     

qNMR: An applicable method for the determination of dimethyltryptamine in ayahuasca,a psychoactive plant preparation

Ayahuasca is an Amazonian plant beverage obtained by infusing the pounded stems of Banisteriopsis caapi in combination with the leaves of Psychotria viridis. P. viridis contains the psychedelic indole N,N-dimethyltryptamine (DMT). This association has a wide range of use in religious rituals around the world. In the present work, an easy, fast and non-destructive method by Nuclear Magnetic Resonance of proton (¹H NMR) for quantification of DMT in ayahuasca samples was developed and validated. 2,5-Dimethoxybenzaldehyde (DMBO) was used as internal standard (IS). For this purpose, the area ratios produced by protons of DMT (N(CH₃)₂) at 2.70 ppm, singlet, (6H) and for DMBO (Ar(OCH₃)₂) at 3.80 and 3.89 ppm, doublet, (6H) were used for quantification. The lower limit of quantification (LLOQ) was 12.5 μg/mL and a good intra-assay precision was also obtained (relative standard deviation < 5.1%). The present ¹H NMR method is not time consuming and can be readily applied to monitor this tryptamine in plant preparations. We believe that qNMR can be used for identification and quantification of many plant-based products and metabolites with important advantages, while comparing with other analytical techniques.