Calibration phantom-based prediction of CT lung nodule volume measurement performance.

Background: A calibration phantom-based method has been developed for predicting small lung nodule volume measurement bias and precision that is specific to a particular computed tomography (CT) scanner and acquisition protocol. Methods: The approach involves CT scanning a simple reference object with a specific acquisition protocol, analyzing the scan to estimate the fundamental imaging properties of the CT acquisition system, generating numerous simulated images of a target geometry using the fundamental imaging properties, measuring the simulated images with a standard nodule volume segmentation algorithm, and calculating bias and precision performance statistics from the resulting volume measurements. We evaluated the ability of this approach to predict volume measurement bias and precision of Teflon spheres (diameters =4.76, 6.36, and 7.94 mm) placed within an anthropomorphic chest phantom when using 3M Scotch Magic™ tape as the reference object. CT scanning of the spheres was performed with 0.625, 1.25, and 2.5 mm slice thickness and spacing. Results: The study demonstrated good agreement between predicted volumetric performance and observed volume measurement performance for both volumetric measurement bias and precision. The predicted and observed volume mean for all slice thicknesses was found to be 28% and 13% lower on average than the manufactured sphere volume, respectively. When restricted to 0.625 and 1.25 mm slice thickness scans, which are recommended for small lung nodule volume measurement, we found that the difference between predicted and observed volume coefficient of variation was less than 1.0 %. The approach also showed a resilience to varying CT image acquisition protocols, a critical capability when deploying in a real-world clinical setting. Conclusions: This is the first report of a calibration phantom-based method's ability to predict both small lung nodule volume measurement bias and precision. Volume measurement bias and precision for small lung nodules can be predicted using simple low-cost reference objects to estimate fundamental CT image characteristics and modeling and simulation techniques. The approach demonstrates an improved method for predicting task specific, clinically relevant measurement performance using advanced and fully automated image analysis techniques and low-cost reference objects.

QIBA guidance: Computed tomography imaging for COVID-19 quantitative imaging applications.

As the COVID-19 pandemic impacts global populations, computed tomography (CT) lung imaging is being used in many countries to help manage patient care as well as to rapidly identify potentially useful quantitative COVID-19 CT imaging biomarkers. Quantitative COVID-19 CT imaging applications, typically based on computer vision modeling and artificial intelligence algorithms, include the potential for better methods to assess COVID-19 extent and severity, assist with differential diagnosis of COVID-19 versus other respiratory conditions, and predict disease trajectory. To help accelerate the development of robust quantitative imaging algorithms and tools, it is critical that CT imaging is obtained following best practices of the quantitative lung CT imaging community. Toward this end, the Radiological Society of North America's (RSNA) Quantitative Imaging Biomarkers Alliance (QIBA) CT Lung Density Profile Committee and CT Small Lung Nodule Profile Committee developed a set of best practices to guide clinical sites using quantitative imaging solutions and to accelerate the international development of quantitative CT algorithms for COVID-19. This guidance document provides quantitative CT lung imaging recommendations for COVID-19 CT imaging, including recommended CT image acquisition settings for contemporary CT scanners. Additional best practice guidance is provided on scientific publication reporting of quantitative CT imaging methods and the importance of contributing COVID-19 CT imaging datasets to open science research databases.

Not all lightweight lead aprons and thyroid shields are alike.

OBJECTIVE: With the explosion of minimally invasive surgery, the use of fluoroscopy has significantly increased. Concurrently, there has been a demand for lighter weight aprons. The industry answered this call with the development of lightweight aprons. Our goal was to see whether lighter weight garments provide reduced protection. METHODS: Dry laboratory testing was performed in a standard X-ray room, using a standard fluoroscopy table and standard acrylic blocks. A commercial-grade pressurized ion chamber survey meter (Ludlum Model 9DP; Ludlum Measurements, Inc, Sweetwater, Tex) was used to detect gamma rays and X-rays above 25 keV. Nonlead aprons from several manufacturers were tested for scatter radiation penetration above the table at a fixed distance (3 feet) and compared with two standard 0.5-mm lead aprons of different manufacturers. RESULTS: Scatter measurements were made at 60 kVp and 70 kVp for pure lead (0.5 mm), mixed, and nonlead protective garments. Scatter penetration for the nonlead blends and barium aprons was 292% and 258%, respectively, at 60 kVp compared with the pure lead apron. At the higher beam quality of 70 kVp, the scatter penetration was 214% and 233% for the blend and barium aprons, respectively, compared with the pure lead apron. Our measurements demonstrate a noticeable difference in scatter reduction between pure lead and nonlead garments. Pure barium aprons and nonlead aprons from certain companies demonstrated scatter penetration that is inconsistent with the 0.5 mm of lead equivalence as claimed on the label. In addition, there was an incidental finding of a handful of lightweight aprons with significant tears along the seams, leaving large gaps in protection. Our study also demonstrates that several companies rate their lightweight garments as 0.5 mm lead equivalent, when actually only a small area on the chest and abdomen where the garment overlapped was 0.5 mm, leaving the rest of the garment with half the protection at 0.25 mm. CONCLUSIONS: Our reliance on protective lead garments to shield us from the biologic effects of radiation exposure and the inferiority of some lightweight garments necessitate a streamlining of the testing methods and transparency in data reporting by manufacturers.

Direct derivatization and gas chromatography-tandem mass spectrometry identification of nerve agent biomarkers in urine samples.

Rapid determination of nerve agent biomarkers at low-ppb levels in urine samples was achieved by direct derivatization and sample analysis using gas chromatography-tandem mass spectrometry. The studied biomarkers were alkylphosphonic acids (APAs), as they are specific hydrolysis products of organophosphorus nerve agents that can be used to verify nerve agent exposure. The sample preparation technique employed involves rapid direct derivatization (5min) of acidified urine samples (25µL) using a highly fluorinated phenyldiazomethane reagent [1-(diazomethyl)-3,5-bis(trifluoromethyl)benzene]. The derivatization conditions were optimized using statistical experimental design and multivariate data analysis. The APA derivatives were analyzed by GC-MS and MS/MS using negative ion chemical ionization. The selectivity and sensitivity of analyses performed by low and high resolution single ion monitoring MS-mode were compared with those performed by multiple reaction monitoring MS/MS-mode. The MS/MS technique offered the greatest sensitivity and selectivity of the tested mass spectrometric techniques, with limits of detection ranging from 0.5 to 1ng APAs/mL of urine. The method's robustness was evaluated using urine samples from the OPCW 2nd biomedical confidence building exercise and all APAs present in the samples were conclusively identified. The method thus offers excellent performance and is viable for the simultaneous trace determination of a wide range of nerve agent markers.

Determination of S-2-(N,N-diisopropylaminoethyl)- and S-2-(N,N-diethylaminoethyl) methylphosphonothiolate, nerve agent markers, in water samples using strong anion-exchange disk extraction, in vial trimethylsilylation, and gas chromatography-mass spectrometry analysis.

Since the establishment of the Chemical Weapons Convention in 1997, the development of analytical methods for unambiguous identification of large numbers of chemicals related to chemical warfare agents has attracted increased interest. The analytically challenging, zwitterionic S-2-(N,N-diisopropylaminoethyl) methylphosphonothiolate (EA-2192), a highly toxic degradation marker of the nerve agent VX, has been reported to resist trimethylsilylation or to result in an unacceptably high limit of detection in GC-MS analysis. In the present study, the problem is demonstrated to be associated with the presence of salt, which hinders trimethysilylation. EA-2192 was extracted from aqueous samples by use of a strong anion-exchange disk, derivatized as a trimethylsilyl derivative via in vial solid-phase trimethylsilylation and identified by GC-MS. The limits of detection were 10 ng/mL and 100 ng/mL (in a water sample) for SIM and SCAN mode respectively. The analytical method was found to be repeatable with relative standard deviation <10%. The performance of the method was evaluated using a proficiency test sample and environmental samples (spiked river water and Baltic Bay water) and compared with the commonly used evaporation-silylation method. The disk method displayed good tolerance to the presence of salt and the spiked EA-2192 was conclusively identified in all matrices. In addition, the applicability of the method was further demonstrated for other selected hydrolysis products of VX and Russian VX, namely S-2-(N,N-diethylaminoethyl) methylphosphonothiolate, ethyl methylphosphonic acid, methylphosphonic acid, and isobutyl methylphosphonic acid. For the synthesis of reference compounds, EA-2192 and its analog from degradation of the Russian VX isomer, the present methods were improved by using a polymer-bound base, resulting in >90% purity based on (1)H NMR. Based on the current results and earlier work on alkylphosphonic acids using the same method, we conclude that the method is a viable choice for the simultaneous determination of a wide range of degradation products of nerve agents - zwitterionic, monoacid, diacid, and monothioacid chemicals - with excellent performance.

An isomer-specific high-energy collision-induced dissociation MS/MS database for forensic applications: a proof-of-concept on chemical warfare agent markers.

Spectra database search has become the most popular technique for the identification of unknown chemicals, minimizing the need for authentic reference chemicals. In the present study, an isomer-specific high-energy collision-induced dissociation (CID) MS/MS spectra database of 12 isomeric O-hexyl methylphosphonic acids (degradation markers of nerve agents) was created. Phosphonate anions were produced by the electrospray ionization of phosphonic acids or negative-ion chemical ionization of their fluorinated derivatives and were analysed in a hybrid magnetic-sector-time-of-flight tandem mass spectrometer. A centre-of-mass energy (E(com)) of 65 eV led to an optimal sequential carbon-carbon bond breakage, which was interpreted in terms of charge remote fragmentation. The proposed mechanism is discussed in comparison with the routinely used low-energy CID MS/MS. Even-mass (odd-electron) charge remote fragmentation ion series were diagnostic of the O-alkyl chain structure and can be used to interpret unknown spectra. Together with the odd-mass ion series, they formed highly reproducible, isomer-specific spectra that gave significantly higher database matches and probability factors (by 1.5 times) than did the EI MS spectra of the trimethylsilyl derivatives of the same isomers. In addition, ionization by negative-ion chemical ionization and electrospray ionization resulted in similar spectra, which further highlights the general potential of the high-energy CID MS/MS technique.

Direct derivatization and rapid GC-MS screening of nerve agent markers in aqueous samples.

A rapid screening and identification method based on derivatization and gas chromatography mass spectrometry (GC-MS) has been developed for the detection of alkylphosphonic acids (APAs), the degradation products of organophosphorus nerve agents. The novel method described involves rapid (5 min) and direct derivatization of 25 microL aqueous sample using highly fluorinated phenyldiazomethane reagents (e.g., 1-(diazomethyl)-3,5-bis(trifluoromethyl)benzene). The APA derivatives are then screened by GC-MS negative ion chemical ionization (NICI) and identified by electron ionization (EI) mode. The conditions for the derivatization were optimized using statistical experimental design and multivariate data analysis. Method robustness was evaluated using aqueous samples from an official OPCW Proficiency Test and all APAs present in the sample were conclusively identified. Limits of detection for rapid screening using SIM NICI were between 5 and 10 ng/mL APA in aqueous sample, and for identification using full scan EI 100 ng/mL.

Combination of solid phase extraction and in vial solid phase derivatization using a strong anion exchange disk for the determination of nerve agent markers.

Alkylphosphonic acids (APAs) are degradation products and chemical markers of organophosphorous (OP) nerve agents (chemical warfare agents). Anion exchange disk-based solid phase extraction (SPE) has been combined with in vial solid phase derivatization (SPD) and GC-MS analysis for the determination of APAs in aqueous samples. The optimization of critical method parameters, such as the SPD reaction, was achieved using statistical experimental design and multivariate data analysis. The optimized method achieved quantitative recoveries in the range from 83% to 101% (n=13, RSD from 4% to 10%). The method was sensitive, with LODs in SIM mode of 0.14 ppb, and demonstrated excellent linearity with an average R(2)>or=0.99 over the concentration range of 0.07-1.4 ppm in full scan mode and from 0.14 ppb to 14 ppb in SIM mode. For forensic applications, aqueous samples containing APAs at concentrations exceeding 14 ppb were concentrated and target analytes were successfully identified by spectral library and retention index matching. Method robustness was evaluated using aqueous samples from the official OPCW Proficiency Test (round 19) and all APAs present in the sample were conclusively identified. The SPE disk retained the underivatized APAs in a stable condition for extended periods of time. No significant losses of APAs from the disk were observed over a 36-day period. Overall, the method is well suited to the qualitative and quantitative analysis of degradation markers of OP nerve agents in aqueous matrices with simplicity, a low risk of cross-contamination and trace level sensitivity.

Imaging the pregnant patient for nonobstetric conditions: algorithms and radiation dose considerations.

Use of diagnostic imaging studies for evaluation of pregnant patients with medical conditions not related to pregnancy poses a persistent and recurring dilemma. Although a theoretical risk of carcinogenesis exists, there are no known risks for development of congenital malformations or mental retardation in a fetus exposed to ionizing radiation at the levels typically used for diagnostic imaging. An understanding of the effects of ionizing radiation on the fetus at different gestational stages and the estimated exposure dose received by the fetus from various imaging modalities facilitates appropriate choices for diagnostic imaging of pregnant patients with nonobstetric conditions. Other aspects of imaging besides radiation (ie, contrast agents) also carry potential for fetal injury and must be taken into consideration. Imaging algorithms based on a review of the current literature have been developed for specific nonobstetric conditions: pulmonary embolism, acute appendicitis, urolithiasis, biliary disease, and trauma. Imaging modalities that do not use ionizing radiation (ie, ultrasonography and magnetic resonance imaging) are preferred for pregnant patients. If ionizing radiation is used, one must adhere to the principle of using a dose that is as low as reasonably achievable after a discussion of risks versus benefits with the patient.