Reference Standard Measurements Research Articles

Prospective deep learning-based quantitative assessment of coronary plaque by computed tomography angiography compared with intravascular ultrasound: the REVEALPLAQUE study.

Coronary computed tomography angiography provides non-invasive assessment of coronary stenosis severity and flow impairment. Automated artificial intelligence (AI) analysis may assist in precise quantification and characterization of coronary atherosclerosis, enabling patient-specific risk determination and management strategies. This multicentre international study compared an automated deep learning-based method for segmenting coronary atherosclerosis in coronary computed tomography angiography (CCTA) against the reference standard of intravascular ultrasound (IVUS). The study included clinically stable patients with known coronary artery disease from 15 centres in the USA and Japan. An AI-enabled plaque analysis was utilized to quantify and characterize total plaque (TPV), vessel, lumen, calcified plaque (CP), non-calcified plaque (NCP), and low-attenuation plaque (LAP) volumes derived from CCTA and compared with IVUS measurements in a blinded, core laboratory-adjudicated fashion. In 237 patients, 432 lesions were assessed; mean lesion length was 24.5 mm, and mean IVUS-TPV was 186.0 mm3. AI-enabled plaque analysis on CCTA showed strong correlation and high accuracy when compared with IVUS; correlation coefficient, slope, and Y intercept for TPV were 0.91, 0.99, and 1.87, respectively; for CP volume 0.91, 1.05, and 5.32, respectively; and for NCP volume 0.87, 0.98, and 15.24, respectively. Bland-Altman analysis demonstrated strong agreement with little bias for these measurements. AI-enabled CCTA quantification and characterization of atherosclerosis demonstrated strong agreement with IVUS reference standard measurements. This tool may prove effective for accurate evaluation of coronary atherosclerotic burden and cardiovascular risk assessment.

Development and Analysis of a Multi-Wavelength Near-Infrared Sensor for Monitoring Skin Hydration and Validation Using Monte Carlo Simulation

The monitoring of an individual’s hydration levels is a vital measurement required for the maintenance of a healthy skin barrier function as well as the avoidance of dehydration. The current commercial devices for this measure are typically based on electrical methodologies, such as capacitance, which allows for the extraction of skin hydration using the ionic balance deviations in the stratum corneum. The use of optical-based methods such as near-infrared spectroscopy (NIRS) has been recently explored for the measurement of skin hydration. Optical approaches have the ability to penetrate deeper into the skin layers and provide detailed information on the optical properties of present water bands. This paper presents the development of a multi-wavelength optical sensor and its capability of assessing skin hydration in an in vitro experiment utilizing porcine skin. Regression analysis of the results showed to be in line with standard reference measurements (R2 CV=0.952257), validating the accuracy of the developed sensor in measuring dermal water content. A Monte Carlo model of the human skin was also developed and simulated to predict the optical sensor’s performance at variable water concentrations. This model serves as a tool for validating the sensor measurement accuracy. The output from this model gave a standard expectation of the device, which agreed with trends seen in the in vitro work. This research strongly suggests that non-invasive (wearable) NIR based sensors could be used for the comprehensive assessment of skin hydration.

Dynamic Contrast-enhanced CT Lymphangiography to Quantify Thoracic Duct Lymphatic Flow.

Background CT lymphangiography has been used to image the lymphatic anatomy and assess lymphatic abnormalities. There is, however, a need to develop a method for quantification of lymphatic flow rate in the thoracic duct (TD). Purpose To develop and validate a TD lymphatic flow measurement technique using dynamic contrast-enhanced CT lymphangiography. Materials and Methods Lymphatic flow rate was measured with two techniques: a first-pass analysis technique based on a single compartment model and a thresholding technique distinguishing between opacified and nonopacified voxels within the TD. The measurements were validated in a swine animal model between November 2021 and September 2022. CT images were acquired at 100 kV and 200 mA using a fast-pitched helical scan mode covering the entire TD following contrast material injection into the bilateral inguinal lymph nodes. Two helical CT scans, acquired at the base and peak contrast enhancement of the TD, were used to measure lymphatic flow rate. A US flow probe surgically placed around the TD provided the reference standard measurement. CT lymphatic flow measurements were compared with the reference US flow probe measurements using regression and Bland-Altman analysis. Repeatability was determined using repeated flow measurements within approximately 10 minutes of each other. Results Eleven swine (10 male; mean weight, 43.6 kg ± 2.6 [SD]) were evaluated with 71 dynamic CT acquisitions. The lymphatic flow rates measured using the first-pass analysis and thresholding techniques were highly correlated with the reference US flow probe measurements (r = 0.99 and 0.91, respectively) and showed good agreement with the reference standard, with Bland-Altman analysis showing small mean differences of 0.04 and 0.05 mL/min, respectively. The first-pass analysis and thresholding techniques also showed good agreement for repeated flow measurements (r = 0.94 and 0.90, respectively), with small mean differences of 0.09 and 0.03 mL/min, respectively. Conclusion The first-pass analysis and thresholding techniques could be used to accurately and noninvasively quantify TD lymphatic flow using dynamic contrast-enhanced CT lymphangiography. © RSNA, 2023 See also the editorial by Choyke in this issue.

A-383 A Novel Lateral Flow Immunoassay for Health Biomarker and Immunosuppressive Drug Monitoring in Fingerstick Blood in a Point-of-Care Setting

Abstract Background Rapid, CLIA-waived quantitative testing can help eliminate delays in receiving care, improve telemedicine, enhance the management of chronic diseases and clinical trials, and reduce healthcare costs. Intelligent Optical Systems has developed an innovative Enhanced Lateral Flow Assay (ELFA) platform and partnered with the University of California, Irvine Nephrology Division and Wake Forest Institute for Regenerative Medicine for the clinical validation of the assay. The ELFA platform quantitatively measures the immunosuppressive drug tacrolimus (TAC), and health biomarkers such as proinflammatory cytokines IL6, IL8, matrix metalloproteinase-3 (MMP3), glial fibrillary acidic protein (GFAP, an indicator of traumatic brain injury), and cystatin C (CysC, an indicator of kidney function) from fingerstick blood at the point of care. The testing panel is continuously expanding. Methods The ELFA platform is an in vitro, quantitative, single plex or multiplexed lateral flow immunoassay that consists of three main components: (i) simple fingerstick whole blood sampling kit; (ii) lateral flow test strip with running buffer and dried fluorescent labeled affinity reagents; and (iii) miniaturized readout device that can be further developed with a controlled user interface, enabling untrained users to easily record results and instantly transmit them to the physician. Depending on the analytes, the ELFA point-of-care platform has undergone bench testing or clinical validation studies, including: (1) Single plex for TAC: Clinical validation using 5 uL of capillary fingerstick whole blood from kidney transplant recipients (KTR, n = 50) compared to standard LC-MS/MS laboratory method. (2) Multiplexed ELFA for TAC, IL6, and MMP3: In vitro assessment of limit of detection (LoD), detection range, specificity, and repeatability (n = 5) with 10 uL spiked whole blood. (3) Single plex ELFA for GFAP, IL8, and CysC: In vitro determination of the LoD, detection range, CV%, and correlation of spiked and estimated analyte levels with 10 uL of spiked whole blood. For all analytes, a 4-parameter logistic calibration curve with n = 3 for each level of analyte was constructed to determine the LoD, detection range, and CV%. Pearson correlation and Bland-Altman analysis were applied to correlate and compare data between spiked and estimated levels, or between ELFA and standard lab test methods. Results Study (1) demonstrated excellent correlation between ELFA and LC-MS/MS, with a correlation coefficient r-value of 0.89, and at 95% limit of agreement, a mean difference of 0.7 ng/mL in the clinically compared samples from 50 KTRs. Study (2) showed an LoD and range of detection of 2 ng/mL to 20 ng/mL, 1 ng/mL to 5 ng/mL, and 10 ng/mL to 200 ng/mL for the multiplexed detection of TAC, IL6, and MMP3, respectively. The repeatability assessment showed a <10%CV for all analytes. Study (3) showed an LoD and range of detection of 1 ng/mL to 10 ng/mL, 0.5 ng/mL to 5 ng/mL, and 0 to 5 mg/L for GFAP, IL8, and CysC, respectively. Conclusion The ELFA platform delivers minimally invasive, convenient sampling in a POC device using capillary fingerstick blood, and provides accurate, rapid measurements of TAC, which demonstrate good repeatability and strong correlation against LC-MS standard reference measurements.

Clinical assessment of a point-of-care assay to determine protective vaccinal antibody titers to canine viral diseases

Guidelines recommend that dogs are vaccinated for canine distemper virus (CDV), canine parvovirus (CPV), and canine adenovirus (CAV) every 3 years. Alternatively, their antibody titers are measured and vaccines given when titers fall below a protective threshold. In this study, a point-of-care (POC) assay was compared to hemagglutination inhibition (for CPV) and virus neutralization (for CAV and CDV) assays to predict the need for revaccination Ninety-two dogs presented for vaccination were enrolled. The POC assay indicated protective titers against CDV in 79/80, CPV in 89/90, and CAV in 91/91 dogs with reference standard antibody measurements that were over a protective threshold. The sensitivity of the POC assay for to detect protective concentrations of CDV antibodies was 99% (95% confidence interval [CI 95%], 93.3–99.9%). Ten dogs were falsely considered protected against CDV by the POC assay with a specificity of 17% (CI 95%, 3.0–44.8%). The sensitivity of the POC assay for protective concentrations of CPV titers was 99% (CI 95%, 93.9–99.9%). The sensitivity of the POC assay to detect protective concentrations of CAV antibodies was 100% (CI 95%, 95.9–100%). Only classifying high-positive CDV and CPV titers on the POC assay as protective improved assay specificity to 100%, but sensitivity decreased to 51% and 76% respectively. This POC assay had a high sensitivity for the detection of protective antibody titers; however, some dogs were falsely categorized as protected, especially for CDV.

Analytical variation concerning total 25-hydroxyvitamin D measurement, where are we now? A DEQAS review of current assay performance

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes serum samples globally, on a quarterly basis, to assess participants’ performance of specific methods for 25-hydroxyvitamin D (25OHD) and other vitamin D metabolites. In this review an assessment of the state of the art in the performance of 25OHD methods is presented. This assessment is based on an analysis of data submitted by scheme participants for the 2021/22 distribution cycle, which comprised of four distributions each containing five DEQAS samples. These distributions enabled the assessment of performance across a wide concentration range and included samples containing endogenous 25OHD2. Overall analytical performance continues to improve, but there is still significant method variation and bias in some automated methods. These automated methods continue to be challenged in measuring 25OHD at the extremes of the measuring range and in the presence of 25OHD2. LC-MS/MS methods still show superior performance with regards to bias, but are out-performed by some automated methods in terms of assay variability. Through participating in an accuracy based EQA scheme, such as DEQAS, laboratories are able to assess the accuracy of their methods in comparison to a gold standard reference measurement procedure. It is crucial for all laboratories to be aware of the performance and limitations of their 25OHD assays and to educate their users accordingly in order to ensure reliable assessment of vitamin D status.

Monitoring Respiratory Effort and Lung-distending Pressure Noninvasively during Mechanical Ventilation: Ready for Prime Time.

Monitoring Respiratory Effort and Lung-distending Pressure Noninvasively during Mechanical Ventilation: Ready for Prime Time.

A novel echocardiographic estimate of pulmonary vascular resistance employing the hydraulic analogy to Ohm's law.

Assessment of pulmonary vascular resistance (PVR) is critical for accurate diagnosis and optimal pharmacotherapy in pulmonary hypertension. We aimed to test the diagnostic performance of a novel, Doppler-based method to evaluate PVR based on Ohm's law (PVRecho) using pragmatic estimates of pulmonary capillary wedge pressure (PCWP). Simultaneous right heart catheterization (RHC) and echocardiography was performed in a derivation cohort of 111 patients in sinus rhythm referred for PH evaluation and PVRecho independently validated in 238 patients. PVRecho was calculated using pulmonary artery mean pressure estimates (PAMPecho) obtained from peak tricuspid gradient employing a fixed right atrial pressure estimate, PCWPecho was estimated as 10 or 20mmHg using age-related mitral E/A cut-offs and cardiac output from left ventricular outflow. In the derivation cohort, both PAMPecho and PCWPecho estimates demonstrated excellent agreement with catheterization measurements. PVRecho was highly feasible, demonstrated negligible bias and excellent agreement with PVRRHC (Bias=-0.58, SD 2.2mmHg) and outperformed the Abbas method to identify PVRRHC>3WU (AUC=0.85 vs. 0.70; p=0.02). In the validation cohort, PVRecho preserved good invasive agreement with negligible bias, displayed strong diagnostic performance (AUC=0.84) and significant ability to distinguish isolated post-capillary from combined post- and pre-capillary pulmonary hypertension (PH) subgroups (AUC=0.77). PVRecho based on Ohm's law employing pragmatic estimates of PCWPecho demonstrates excellent agreement with invasive reference standard measurements and strong diagnostic ability to identify elevated PVRRHC. This novel approach may be useful during therapy selection to distinguish PH hemodynamic subgroups.

24-Hour ambulatory blood pressure monitoring 7years after intensive care unit admission.

Children who develop acute kidney injury (AKI) in the pediatric intensive care unit (PICU) may be at higher risk of long-term chronic kidney disease and hypertension. The objectives of this study were to determine the prevalence of post-discharge hypertension and albuminuria using reference-standard measurements in children admitted to the PICU, and evaluate their association with AKI. Single-center longitudinal cohort study of children admitted to the PICU from 2005 to 2010 with 7-8years of follow-up (n = 207). Patients were excluded if they had pre-existing chronic kidney disease, were deceased, lived > 3.5-h drive away, were unwilling/unable to provide consent/assent, or had a clotting disorder. AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine definition. Office blood pressure was evaluated using age, sex, and height-based percentiles. Hypertension was defined using 24-h ambulatory blood pressure monitoring (ABPM). Albuminuria was defined as first morning urine albumin:creatinine ratio ≥ 30mg/g. Prevalence of blood pressure outcomes was calculated. The association between AKI and outcomes was evaluated using multivariable regression. Sixty of 207 (29%) children developed AKI during PICU admission. Overall, 6% had albuminuria and 21% had elevated office blood pressure or worse. One-hundred-and-seventy-seven (86%) patients had successful ABPM data. Of these, 10 (6%) had white coat, 18 (10%) had masked, and 5 (3%) had ambulatory hypertension. There was no statistically significant difference in outcomes across AKI stages. Blood pressure abnormalities are common in children 7years after PICU admission. Future studies with longer follow-up are needed to further evaluate the association between AKI and hypertension. A higher-resolution version of the graphical abstract is available as Supplementary information.

Validation of watershed-based segmentation of the cartilage surface from sequential CT arthrography scans.

This study investigated the utility of a 2-dimensional watershed algorithm for identifying the cartilage surface in computed tomography (CT) arthrograms of the knee up to 33 minutes after an intra-articular iohexol injection as boundary blurring increased. A 2D watershed algorithm was applied to CT arthrograms of 3 bovine stifle joints taken 3, 8, 18, and 33 minutes after iohexol injection and used to segment tibial cartilage. Thickness measurements were compared to a reference standard thickness measurement and the 3-minute time point scan. 77.2% of cartilage thickness measurements were within 0.2 mm (1 voxel) of the thickness calculated in the reference scan at the 3-minute time point. 42% fewer voxels could be segmented from the 33-minute scan than the 3-minute scan due to diffusion of the contrast agent out of the joint space and into the cartilage, leading to blurring of the cartilage boundary. The traced watershed lines were closer to the location of the cartilage surface in areas where tissues were in direct contact with each other (cartilage-cartilage or cartilage-meniscus contact). The use of watershed dam lines to guide cartilage segmentation shows promise for identifying cartilage boundaries from CT arthrograms in areas where soft tissues are in direct contact with each other.

Measurement of uni-planar and sport specific trunk motion using magneto-inertial measurement units: The concurrent validity of Noraxon and Xsens systems relative to a retro-reflective system

BackgroundThere is a range of magneto-inertial measurement unit (MIMU) systems commercially available, however sensor specifications and fusion methods vary considerably between manufacturers. Such variability can influence the concurrent validity of MIMUs relative to reference standard measurement devices. Different MIMUs have been compared during static or low-velocity conditions, with higher-velocity movements assessed in robotic-based studies. However, there is a need for the concurrent validity of higher-velocity movements to be established in human-based studies. Research questionThis study aimed to assess the concurrent validity of two commercial MIMU systems (Noraxon and Xsens), relative to a ‘gold-standard’ retro-reflective motion capture system, when measuring trunk angles during uni-planar range of motion (ROM) and cricket bowling, which involves high-speed, multi-planar movements. MethodsFor this criterion-based validity study, both MIMU systems incorporated comparable sensor specifications and employed Kalman filter sensor fusion algorithms. The MIMU based angles were compared with angles derived from concurrently captured three-dimensional retro-reflective data for 10 fast-medium bowlers. Statistical parametric mapping and root mean squared differences (RMSD) were computed for both MIMU systems. ResultsOne-dimensional statistical parametric mapping showed no significant differences for angles from both MIMU systems when compared with retro-reflective based angle outputs. The MIMU systems produced ROM RMSDs between 1.4 ± 1.0° and 2.6 ± 1.5°. One system displayed RMSDs between 4.6 ± 1.4° and 7.4 ± 1.9° during bowling, indicating functionally relevant differences to retro-reflective derived angles. There were some small but statistically significant differences in RMSDs between the MIMU systems. SignificanceMIMU-based angle accuracy is poorer during high-speed, multi-planar movement than uni-planar tasks. Comparable MIMU systems can produce varying measurements during ROM and bowling tasks. It is likely that varying sample rates and sensor fusion algorithm parameters contributed to the differences.

Evaluation of a flash glucose monitoring system in nondiabetic dogs with rapidly changing blood glucose concentrations.

BackgroundA flash glucose monitoring system (FGMS; FreeStyle Libre) is useful for monitoring hypoglycemic dogs with diabetes.ObjectiveTo assess the utility of this FGMS in dogs with induced hypoglycemia and rapid fluctuations in blood glucose (BG) concentrations.AnimalsTwenty‐four apparently healthy research (n = 10) and teaching (n = 14) dogs.MethodsProspective, observational study performed in tandem with a teaching laboratory. Regular insulin was administered to dogs and resulting hypoglycemia was corrected. Before insulin administration and every 10 minutes over a 90‐minute period, serial measurements of interstitial glucose (IG) with FGMS and BG with a portable blood glucose meter (PBGM) and clinical chemistry analyzer concentrations were made. Portable blood glucose meter and FGMS readings were compared to that of the clinical chemistry analyzer. Analytical and clinical accuracy were assessed using ISO 15197:2013 criteria, including Parkes error grid analysis.ResultsThe proportions of readings in the low BG range (BG <100 mg/dL) for which the test method measurement was within ±15 mg/dL of the reference BG for the PBGM and FGMS were 81.7% (161/197) and 39.1% (72/184), respectively. The proportions of readings for the PBGM and FGMS, which were not likely to affect clinical outcome according to Parkes error grid analysis, were 97.9% (233/238) and 80.1% (177/221), respectively.Conclusions and Clinical ImportanceIn this model, there was limited agreement between the FGMS and reference standard BG measurements. The FGMS (measuring IG concentrations) was compared to peripheral BG concentrations, not brain‐tissue glucose concentrations, and failed to reliably detect hypoglycemia.

Mass balance method for SI-traceable purity assignment of synthetic oxytocin

Oxytocin is not only a significant peptide drug for enhancing uterine contractions, but also an emerging biomarker and therapeutic target of mental disorders in clinical practice. There is a pressing need for the standardization of oxytocin assays because of its low pharmaceutical quality and large variations among measurement approaches. International System of Units (SI)-traceable analytical methods and well-characterized pure reference materials are urgently needed to set up standard reference measurement systems in laboratory medicine, ensuring the accuracy and comparability of test results. Herein, the purity assignment of a synthetic oxytocin containing a disulfide linkage was established based on a mass balance method, which had never been performed for a cross-linked peptide. An in-house validated liquid chromatography-high-resolution tandem mass spectrometry method was developed for the determination of structurally-related impurities in the study material. Twenty-one structurally-related impurities including deamidations, oxidations, and amino acid insertions, etc. ranging from 0.05 mg g-1 to 15.65 mg g-1 were identified and quantified by applying a hierarchy calibration concept. This study subsequently discusses a fit for purpose assessment for non-peptide related impurities including water, non-volatile counterions, inorganic elements, and volatile organic compounds that were determined using coulometric Karl Fischer titration, ion chromatography, inductively coupled plasma mass spectrometry, and headspace gas chromatography-mass spectrometry, respectively. The resulting assigned value (796.5 mg g-1) is determined to be traceable to SI associated with a small measurement uncertainty of 6.5 mg g-1 (k = 2). The method developed in this study has been verified through an international key comparison jointly coordinated by the Bureau International des Poids et Mesures and the National Institute of Metrology.

Automated Quality-Controlled Cardiovascular Magnetic Resonance Pericardial Fat Quantification Using a Convolutional Neural Network in the UK Biobank.

Background: Pericardial adipose tissue (PAT) may represent a novel risk marker for cardiovascular disease. However, absence of rapid radiation-free PAT quantification methods has precluded its examination in large cohorts.Objectives: We developed a fully automated quality-controlled tool for cardiovascular magnetic resonance (CMR) PAT quantification in the UK Biobank (UKB).Methods: Image analysis comprised contouring an en-bloc PAT area on four-chamber cine images. We created a ground truth manual analysis dataset randomly split into training and test sets. We built a neural network for automated segmentation using a Multi-residual U-net architecture with incorporation of permanently active dropout layers to facilitate quality control of the model's output using Monte Carlo sampling. We developed an in-built quality control feature, which presents predicted Dice scores. We evaluated model performance against the test set (n = 87), the whole UKB Imaging cohort (n = 45,519), and an external dataset (n = 103). In an independent dataset, we compared automated CMR and cardiac computed tomography (CCT) PAT quantification. Finally, we tested association of CMR PAT with diabetes in the UKB (n = 42,928).Results: Agreement between automated and manual segmentations in the test set was almost identical to inter-observer variability (mean Dice score = 0.8). The quality control method predicted individual Dice scores with Pearson r = 0.75. Model performance remained high in the whole UKB Imaging cohort and in the external dataset, with medium–good quality segmentation in 94.3% (mean Dice score = 0.77) and 94.4% (mean Dice score = 0.78), respectively. There was high correlation between CMR and CCT PAT measures (Pearson r = 0.72, p-value 5.3 ×10−18). Larger CMR PAT area was associated with significantly greater odds of diabetes independent of age, sex, and body mass index.Conclusions: We present a novel fully automated method for CMR PAT quantification with good model performance on independent and external datasets, high correlation with reference standard CCT PAT measurement, and expected clinical associations with diabetes.

Step length estimation with wearable sensors using a switched-gain nonlinear observer

This paper focuses on step length estimation using inertial measurement sensors. Accurate step length estimation has a number of useful health applications, including its use in characterizing the postural instability of Parkinson’s disease patients. Three different sensor configurations are studied using sensors on the shank and/or thigh of a human subject. The estimation problem has several challenges due to unknown measurement bias, misalignment of the sensors on the body and the desire to use a minimum number of sensors. A nonlinear estimation problem is formulated that aims to estimate shank angle, thigh angle, bias parameters of the inertial sensors and step lengths. A nonlinear observer is designed using Lyapunov analysis and requires solving an LMI to find a stabilizing observer gain. It turns out that global stability over the entire operating region can only be obtained by using switched gains, one gain for each piecewise monotonic region of the nonlinear output function. Experimental results are presented on the performance of the nonlinear observer and compared with gold standard reference measurements from an infrared camera capture system. An innovative technique that utilizes three sensors is shown to provide a step length accuracy nearly equal to that of the four-sensor configuration.

Mass Balance Method for Si-Traceable Purity Assignment of Synthetic Oxytocin

Oxytocin is not only a significant peptide drug for enhancing uterine contractions, but also an emerging biomarker and therapeutic target of mental disorders in clinical practice. There is a pressing need for the standardization of OXT assays because of its low pharmaceutical quality and large variations among measurement approaches. SI-traceable analytical methods and well-characterized pure reference materials are urgently needed to set up standard reference measurement systems in laboratory medicine, ensuring the accuracy and comparability of test results during the manufacture, clinical diagnosis and treatment. Herein, the purity assignment of a synthetic oxytocin containing a disulfide linkage was established based on a mass balance method, which had never been performed for a cross-linked peptide. An in-house validated liquid chromatography-high-resolution tandem mass spectrometry method was developed for the determination of structurally-related impurities in the study material. 21 structurally-related impurities including deamidations, oxidations, and amino acid insertions, etc. ranging from 0.05 mg g-1 to 15.65 mg g-1 were identified and quantified by applying a hierarchy calibration concept. This study subsequently discusses a fit for purpose assessment for non-peptide related impurities including water, non-volatile counterions, inorganic elements, and volatile organic compounds that were determined using coulometric Karl Fischer titration, ion chromatography, inductively coupled plasma mass spectrometry, and headspace gas chromatography-mass spectrometry, respectively. The resulting assigned value (796.5 mg g-1) is determined to be traceable to SI units associated with a small measurement uncertainty of 6.5 mg g-1 (k= 2). The method developed in this study has been verified through an international key comparison jointly coordinated by the Bureau International des Poids et Mesures and the National Institute of Metrology.

Correlation and Agreement of Yttrium-90 Positron Emission Tomography/Computed Tomography with Ex Vivo Radioembolization Microsphere Deposition in the Rabbit VX2 Liver Tumor Model

PurposeTo demonstrate a stronger correlation and agreement of yttrium-90 (90Y) positron emission tomography (PET)/computed tomography (CT) measurements with explant liver tumor dosing compared with the standard model (SM) for radioembolization. Materials and MethodsHepatic VX2 tumors were implanted into New Zealand white rabbits, with growth confirmed by 7 T magnetic resonance imaging. Seventeen VX2 rabbits provided 33 analyzed tumors. Treatment volumes were calculated from manually drawn volumes of interest (VOI) with three-dimensional surface renderings. Radioembolization was performed with glass 90Y microspheres. PET/CT imaging was completed with scatter and attenuation correction. Three-dimensional ellipsoid VOI were drawn to encompass tumors on fused images. Tumors and livers were then explanted for inductively coupled plasma (ICP)-optical emission spectroscopy (OES) analysis of microsphere content. 90Y PET/CT and SM measurements were compared with reference standard ICP-OES measurements of tumor dosing with Pearson correlation and Bland-Altman analyses for agreement testing with and without adjustment for tumor necrosis. ResultsThe median infused activity was 33.3 MBq (range, 5.9–152.9). Tumor dose was significantly correlated with 90Y PET/CT measurements (r = 0.903, P < .001) and SM estimates (r = 0.607, P < .001). Bland-Altman analyses showed that the SM tended to underestimate the tumor dosing by a mean of −8.5 Gy (CI, −26.3–9.3), and the degree of underestimation increased to a mean of −18.3 Gy (CI, −38.5–1.9) after the adjustment for tumor necrosis. Conclusions90Y PET/CT estimates were strongly correlated and had better agreement with reference measurements of tumor dosing than SM estimates.

Computer-aided quantification of non-contrast 3D black blood MRI as an efficient alternative to reference standard manual CT angiography measurements of abdominal aortic aneurysms

BackgroundNon-contrast 3D black blood MRI is a promising tool for abdominal aortic aneurysm (AAA) surveillance, permitting accurate aneurysm diameter measurements needed for patient management. PurposeTo evaluate whether automated AAA volume and diameter measurements obtained from computer-aided segmentation of non-contrast 3D black blood MRI are accurate, and whether they can supplant reference standard manual measurements from contrast-enhanced CT angiography (CTA). Materials and MethodsThirty AAA patients (mean age, 71.9 ± 7.9 years) were recruited between 2014 and 2017. Participants underwent both non-contrast black blood MRI and CTA within 3 months of each other. Semi-automatic (computer-aided) MRI and CTA segmentations utilizing deformable registration methods were compared against manual segmentations of the same modality using the Dice similarity coefficient (DSC). AAA lumen and total aneurysm volumes and AAA maximum diameter, quantified automatically from these segmentations, were compared against manual measurements using Pearson correlation and Bland-Altman analyses. Finally, automated measurements from non-contrast 3D black blood MRI were evaluated against manual CTA measurements using the Wilcoxon test, Pearson correlation and Bland-Altman analyses. ResultsSemi-automatic segmentations had excellent agreement with manual segmentations (lumen DSC: 0.91 ± 0.03 and 0.94 ± 0.03; total aneurysm DSC: 0.92 ± 0.02 and 0.94 ± 0.03, for black blood MRI and CTA, respectively). Automated volume and maximum diameter measurements also had excellent correlation to their manual counterparts for both black blood MRI (volume: r = 0.99, P < 0.001; diameter: r = 0.97, P < 0.001) and CTA (volume: r = 0.99, P < 0.001; diameter: r = 0.97, P < 0.001). Compared to manual CTA measurements, bias and limits of agreement (LOA) for automated MRI measurements (lumen volume: 1.49, [−4.19 7.17] cm3; outer wall volume: −2.46, [−14.05 9.13] cm3; maximal diameter: 0.08, [−6.51 6.67] mm) were largely equivalent to those of manual MRI measurements, particularly for maximum AAA diameter (lumen volume: 0.73, [−6.47 7.93] cm3; outer wall volume: 0.98, [−10.54 12.5] cm3; maximal diameter: 0.08, [−3.67 3.83] mm). ConclusionSemi-automatic segmentation of non-contrast 3D black blood MRI efficiently provides reproducible morphologic AAA assessment yielding accurate AAA diameters and volumes with no clinically relevant differences compared to either automatic or manual measurements based on CTA.

Prospective correction of patient-specific respiratory motion in myocardial T1 and T2 mapping.

Respiratory motion in cardiovascular MRI presents a challenging problem with many potential solutions. Current approaches require breath-holds, apply retrospective image registration, or significantly increase scan time by respiratory gating. Myocardial T1 and T2 mapping techniques are particularly sensitive to motion as they require multiple source images to be accurately aligned prior to the estimation of tissue relaxation. We propose a patient-specific prospective motion correction (PROCO) strategy that corrects respiratory motion on the fly with the goal of reducing the spatial variation of myocardial parametric mapping techniques. A rapid, patient-specific training scan was performed to characterize respiration-induced motion of the heart relative to a diaphragmatic navigator, and a parametric mapping pulse sequence utilized the resulting motion model to prospectively update the scan plane in real-time. Midventricular short-axis T1 and T2 maps were acquired under breath-hold or free-breathing conditions with and without PROCO in 7 healthy volunteers and 3 patients. T1 and T2 were measured in 6 segments and compared to reference standard breath-hold measurements using Bland-Altman analysis. PROCO significantly reduced the spatial variation of parametric maps acquired during free-breathing, producing limits of agreement of -47.16 to 30.98 ms (T1 ) and -1.35 to 4.02 ms (T2 ), compared to -67.77 to 74.34 ms (T1 ) and -2.21 to 5.62 ms (T2 ) for free-breathing acquisition without PROCO. Patient-specific respiratory PROCO method significantly reduced the spatial variation of myocardial T1 and T2 mapping, while allowing for 100% efficient free-breathing acquisitions.

Rapid, Single-View Speckle-Tracking-Based Method for Examining Left Ventricular Systolic and Diastolic Function in Point of Care Ultrasound.

A rapid, reliable quantitative assessment of left ventricular systolic and diastolic function is important for patient treatment in urgent and dynamic settings. Quantification of annular velocities based on a single 2-dimensional image loop, rather than on Doppler velocities, could be useful in point-of-care or focused cardiac ultrasound. We hypothesized that novel speckle-tracking-based mitral annular velocities would correlate with reference standard tissue Doppler imaging (TDI) velocities in a focused cardiac ultrasound-esque setting. Two echocardiographers each performed transthoracic echocardiographic measurements before and after induction of anesthesia in supine patients undergoing cardiac surgery. Speckle-tracking echocardiography (STE)-based systolic (S'STE ) and diastolic (E'STE and A'STE ) velocities were compared to TDI and global longitudinal strain/strain rate. We also compared mitral annular displacement by speckle tracking with M-mode imaging. Twenty-five patients were included and examined in both preinduction and postinduction states. Speckle-tracking-based velocities correlated with TDI measurements in both states (S', r = 0.73 and 0.76; E', r = 0.87 and 0.65; and A', r = 0.65 and 0.73), showing a mean bias of 25% to 30% of the reference standard measurement. The correlation of S'STE with strain and the strain rate (S-wave) and E'STE with the strain rate (E-wave) was good in awake, spontaneously breathing patients but was less strong in the ventilated state. Similarly, displacement by speckle tracking correlated with M-mode measurements in both states (r = 0.91 and 0.84). Measurements required medians of 31 and 34 seconds; reproducibility was acceptable for S'STE and E'STE . Speckle-tracking-based mitral annular velocities and displacement correlate well with conventional measures as well as with deformation imaging. They may be clinically useful in rapidly assessing both systolic and diastolic function from a single 2-dimensional image loop.