Reproducibility Of Measurements Research Articles

Interscan reproducibility of computed tomography derived coronary plaque volume measurements using a semi-automated analysis software

Abstract Background Coronary computed tomography angiography (CCTA) enables detailed quantification and characterization of coronary atherosclerotic plaque, offering diagnostic and prognostic value. Despite the growing demand for accurate plaque analysis, studies on interscan reproducibility of automated plaque quantification are limited in number and size. Moreover, impact of clinical and technical factors on the reproducibility of plaque assessment tools are scarce. Purpose The objective of this study was to assess the interscan reproducibility of CCTA-derived plaque volume measurements and the implications of clinical and technical characteristics on interscan reproducibility. Methods A total of 101 patients with known coronary artery disease underwent two CCTA scans within hour interval using identical CT acquisition protocol. Coronary plaque volume measurements were quantified on a per-patient level using a contemporary semi-automated plaque analysis software. Results There was no statistically significant difference in median plaque volumes between the first and second scan. The direct correlation was excellent for volumes of non-calcified plaque (NCP), calcified plaque (CP), and total plaque (TP) across all analyses (Pearson’s coefficient 0.96 to 0.99), while moderate for low-density non-calcified plaque (LD-NCP) volumes (Pearson’s coefficient 0.77). Bland Altman analyses demonstrated high interscan agreement with narrow absolute and relative limits of agreement (LoA) across plaque subtypes, except for LD-NCP volumes (Table 1). Interscan reproducibility on CP volumes was affected by CT image quality with narrower LoA in scans with the highest image quality score (p = 0.003), or lowest image reconstructive iteration level (p <0.001). Limits of agreement were significantly narrower for NCP, CP, and TP volumes in lesions located in LAD compared to non-LAD lesions (p <0.001). However, no significant difference in LoA was present when comparing patients according to BMI (<27 and ≥27 kg/m2), heart rate (<65 and ≥65 beats per minute), or Agatston score (<193 and ≥193). Conclusions This comprehensive interscan reproducibility study revealed good agreement in the measurement of plaque subtypes. Adding new insight to existing literature, we have demonstrated that factors such as image quality, image reconstructive algorithms, and lesion location affect the reproducibility of plaque volume measurements. CT-derived plaque quantification using a semi-automated plaque analysis software holds potential for monitoring disease progression or regression in patients with CAD, provided high CCTA image quality.

Developing a Reproducible Radiomics Model for Diagnosis of Active Crohn's Disease on CT Enterography Across Annotation Variations and Acquisition Differences.

To systematically identify radiomics features on CT enterography (CTE) scans which can accurately diagnose active Crohn's disease across multiple sources of variation. Retrospective study of CTE scans curated between 2013 and 2015, comprising 164 subjects (65 male, 99 female; all patients were over the age of 18) with endoscopic confirmation for the presence or absence of active Crohn's disease. All patients had three distinct sets of scans available (full and reduced dose, where the latter had been reconstructed via two different methods), acquired on a single scanner at a single institution. Radiomics descriptors from annotated terminal ileum regions were individually and systematically evaluated for resilience to different imaging variations (changes in dose/reconstruction, batch effects, and simulated annotation differences) via multiple reproducibility measures. Multiple radiomics models (by accounting for each source of variation) were evaluated in terms of classifier area under the ROC curve (AUC) for identifying patients with active Crohn's disease, across separate discovery and hold-out validation cohorts. Radiomics descriptors selected based on resiliency to multiple sources of imaging variation yielded the highest overall classification performance in the discovery cohort (AUC = 0.79 ± 0.04) which also best generalized in hold-out validation (AUC = 0.81). Performance was maintained across multiple doses and reconstructions while also being significantly better (p < 0.001) than non-resilient descriptors or descriptors only resilient to a single source of variation. Radiomics features can accurately diagnose active Crohn's disease on CTE scans across multiple sources of imaging variation via systematic analysis of reproducibility measures. Clinical utility and translatability of radiomics features for diagnosis and characterization of Crohn's disease on CTE scans will be contingent on their reproducibility across multiple types and sources of imaging variation.

2D Echocardiographic aortic root dimensions and longitudinal analysis with artificial intelligence using an open dataset from a UK-wide collaborative

Abstract Background Surveillance of aortic dimensions requires reproducible measurements, and knowledge of the rate of progression in those with dilatation. Purpose To develop an open machine-learning method for measuring the aortic root and proximal ascending aorta on echocardiograms, validate it through a multi-expert panel from the Unity UK Echocardiography AI Collaborative, and applying the AI to derive the rate of progression in historical databases. Methods The neural network was trained on 1478 parasternal long-axis images. Each image was labelled with key points for the aortic annulus, sinus and sinotubular junction, and proximal ascending aorta dimensions. Labels accommodated inner-to-inner and leading-to-leading conventions. For validation, the end-diastolic and mid-systolic images were identified (accommodating different guidelines recommendations) from 100 studies, and 10 expert echocardiographers made the aortic measurements. The consensus of experts defined the reference standard, and the variation between individual experts defined the acceptable variation for the AI. The AI was then applied to 724 echocardiograms of 102 patients under surveillance spanning 12 years (ranging from 4 to 17 scans per patient) without intervention. Training data labels and networks are made freely available on our project website. Results The median absolute deviations between the AI and the expert consensus ranged from 0.06cm to 0.17cm across the 16 measurements. For the individual expert opinions this was from 0.08cm to 0.19cm. For 7/16 measurements, there was no statistically significant difference between the AI deviation and the individual-expert deviation. The AI’s confidence level was a useful indicator of the reliability of the AI measure. For the top 9 deciles of AI confidence level, the AI measurements had significantly smaller deviations than the individual experts. The rates of progression averaged across the three aortic measurements was 2.0 mm/decade (95% CI 1.0 to 3.0; p =0.007). Conclusion Expert consensus can be used to both define the reference standard and also the range of acceptable deviation from consensus. Overall, the AI performs similarly to experts and more importantly, provides an automated estimate of confidence. The validated AI is consistent over time, and when applied retrospectively to patients with dilated aortic roots, found the rate of progression was more rapid than in previously reported healthy patients. This approach could be applied generally in developing medical AI to not only make reproducible measurements but to automate large scale longitudinal studies with little input, and ultimately serves as a useful research and clinical tool.Figure: AI(red) vs Expert (blue)Table: AIDeviations from Consensus

Sizing of the aortic valve using virtual reality - next step towards personalized medicine?

Abstract Background High-quality imaging is integral throughout the transcatheter aortic valve implantation (TAVI) process, from patient selection and preprocedural planning to real-time guidance during the procedure and postprocedural follow-up. Multislice computed tomography (MSCT) is currently the gold standard. The next step in this area is the three-dimensional (3D) visualization of cardiac and extra-cardiac structures using virtual reality (VR). Purpose This study aimed to investigate the feasibility, accuracy, and reproducibility of VR for the visualization of the aortic valve, the surrounding structures, and its role in the planning of TAVI procedures. Methods Based on the preprocedural MSCT data of 60 patients who underwent TAVI at our heart center, measurements using 3mensio software were compared with 3D visualizations and measurements using VR software. Additionally, eight physicians evaluated the application of VR using a structured questionnaire to define its benefits and limitations. Results VR measurements correlated well with the 3mensio software measurements, and there were no significant differences between the two methods. The VR measurements were mentioned first: Annulus perimeter 77.4 ± 7.8 vs. 77.0 ± 8.1 (p=0.182), r = 0.929; Annulus diameter 24.6 ± 3.2 vs. 24.4 ± 2.6 (p=0.483), r = 0.868; LVOT diameter 23.5 ± 3.1 vs. 23.7 ± 2.8 (p=0.442), r = 0.785; SoV left 32.9 ± 4.1 vs. 32.7 ± 3.7 (p=0.331), r = 0.920; SoV right 30.8 ± 4.3 vs. 30.7 ± 3.7 (p=0.653), r = 0.909; noncoronary SoV 32.9 ± 3.6 vs. 32.6 ± 3.7 (p=0.209), r = 0.913; STJ 30.0 ± 3.6 vs. 29.7 ± 3.2 (p=0.175), rs = 0.882; Ascending aorta 34.5 ± 3.4 vs. 34.5 ± 3.1 (p=0.469), r = 0.921, RCA height 15.1 ± 3.2 vs. 15.4 ± 3.2 (p=0.179), rs = 0.910, LCA height 12.4 ± 2.7 vs. 12.3 ± 3.0 (p=0.252), rs = 0.924. Furthermore, users reported that VR simplified anatomical understanding (1.3 ± 0.5 vs. 1.9 ± 0.4, p = 0.046), and improved 3D comprehension (1.1 ± 0.4 vs. 2.3 ± 0.5, p = 0.023). Conclusion The use of VR in the planning of TAVI procedures enables precise and reproducible measurements. In addition, VR can help assess the often complex anatomy, which can increase the safety and efficiency of procedures. Further clinical studies are needed to evaluate the potential benefits of VR application in planning and performing other structural interventions.

Diagnostic value of aortic valve displacement by tissue tracking for identification of aortic valve stenosis severity

Abstract Background The assessment of aortic stenosis (AS) severity on transthoracic echocardiography (TTE) may be challenging, especially in normal flow, low gradient (NF LG) group with preserved ejection fraction (EF), where reclassification of AS severity after initial TTE was observed in 52% pts (1). Calcifications and fibrosis of valve leaflets result in increased stiffness and impaired mobility, which can be quantified by tissue tracking (TT). TT is an echocardiographic modality that displays longitudinal displacement of selected area by integrating tissue velocity over time. Purpose Assessment of the diagnostic value of aortic valve displacement (AVD) by TT as a test that may increase accuracy of AS severity diagnosis in TTE. Methods 205 pts (aged 71±10 yrs, men 43%) without more than mild aortic regurgitation, mitral or tricuspid valve disease, EF ≤55%, indexed stroke volume (SVI) ≤35 ml/m2, cardiac rhythm disturbances and poor acoustic window were selected out of 842 pts screened for AS in our institution between 2020 and 2023. Based on aortic valve area (AVA) value, moderate (n=51, AVA &amp;gt;1.0 cm2) or severe (n=154, AVA ≤1.0 cm2) AS was diagnosed. In severe AS group, 45 pts were classified as NF LG AS (mean gradient &amp;lt;40 mmHg). Additionally 30 pts (aged 68±10 yrs, men 46%) without abnormalities on TTE entered control group. During TTE in five- and three-chamber views, TT was applied and region of interest was adjusted to cover whole aortic valve (AV) during cardiac cycle. Single loop was analysed with Q-analysis software. The measurement in millimetres (mm) of positive wave representing displacement of AV was performed in both views by two independent echocardiographers (Figure 1). AVD was calculated by summing up results from both views. Receiver-operating characteristic curves for AVD in the whole study group and NF LG AS to diagnose severe AS were plotted. Results AVD was already significantly decreased in moderate AS compared with age- and sex-matched healthy controls, being 22.8±2.8 mm and 24.3±2.1 mm respectively (P=0.01). In pts with severe AS, AVD was further significantly reduced compared to moderate AS pts, being 19.3±3.2 mm (P&amp;lt;0.0001). In the whole study group, AVD with a cut-off point &amp;lt;19.6 mm provided 55.8% sensitivity but 96.1 % specificity to diagnose severe AS (Figure 2B). In pts with NF LG AS, AVD with a cut-off point &amp;lt;20.6 mm provided 71.4% sensitivity and a specificity of 79.6% (Figure 2A). Intraclass correlation coefficient of 0.87; 95% CI (0.84–0.89) indicated good interobserver reproducibility of AVD measurement. Conclusions Aortic valve displacement by tissue tracking in TTE is a valuable, new echocardiographic tool for identification of AS severity and may improve diagnostic accuracy of AS severity in NF LG AS.Figure 1Figure 2

Aortic integral distensibility based on the auto-segmented dynamic motion of the aortic wall

Abstract Background Aortic stiffness is important in cardiovascular diseases and predicting outcomes. Echocardiography is a widely used noninvasive imaging modality for assessing aortic stiffness, but its accuracy can be limited by the low spatial resolution of ultrasound-based images and the subjectivity of manual measurements of aortic dimensions. Automated segmentation analysis can provide a more accurate and objective measure. Objective An automated algorithm and software have been developed for segmenting the aortic wall. A new measurement technique called "Aortic Integral Distensibility (AID)" has been formulated using this framework. This method overcomes limitations of traditional method focusing solely on the two positions of Aortic Distensibility (AD). Method In this particular investigation, 112 participants were subjected to echocardiography in order to quantify the dynamics of the aortic wall. An automated algorithm was devised to delineate the aortic wall by utilizing an M-mode echocardiography scan. The statistical analysis encompassed the measurement of AD and AID before and after the age of 65 group. This analysis was conducted considering various risk factors, including age, gender, weight, BMI, smoking, and blood pressure. Additionally, clinical parameters, specifically AIx @75 (Augmentation Index) and Framingham Risk Score (FRS), were evaluated as well. Inter-rater reliability was conducted between the traditional AD and the newly implemented AID. Results The results indicate that the group under 65 had more distensibility than the group over 65, and AID measurements were slightly higher than AD measurements. SBP showed a strong correlation with AID, rather than AD. AIx @75 and FRS had a negative relationship with distensibility. In the 65 years or older group, there was a significant negative correlation observed between AIx @75 and AID (r = -0.4, p = 0.012). Furthermore, a strong correlation was also observed between FRS and AID (r = -0.53, p = 0.002). Bland-Altman analysis demonstrated that the automated methodology had better reproducibility and less variability in distensibility measurements than the manual methodology. Conclusion The study suggests that AID could be valuable for assessing aortic stiffness. AID could help clinicians diagnose and manage cardiovascular diseases more accurately. The automatic approach provides reliable measurements for aortic distensibility and strain, which has clinical implications.Schematic Chart of the Study Process

Feasibility, accuracy, and reproducibility of device sizing in virtual reality for percutaneous left atrial appendage closure - a single center study

Abstract Background Left atrial appendage closure (LAAC) is a safe and effective procedure for stroke prevention in patient with non-valvular atrial fibrillation. Procedural planning and device sizing remains challenging due to the highly complex and variable three-dimensional (3D) anatomy of the left atrial appendage (LAA). Virtual reality (VR) is a innovative, recent technology allowing a superior spatial orientation visualization of 3D imaging datasets. Purpose Therefore, we aimed to evaluate feasibility and accuracy of LAA measurements in VR for device sizing in patients planned for LAAC. Methods Twenty-one patients (79±7 years, 62% male) with non-valvular atrial fibrillation scheduled for LAAC were randomly included in our study. Preprocedural a multi-slice computed tomography (MSCT) was performed for device sizing in all patients. MSCT-based 3D models were established and visualized in VR using a dedicated software (VMersive, Warsaw, Poland). LAA dimensions (Ostium, landing zone (LZ), and depth) were assessed directly in the virtual environment. Conventional measurements of LAA ostium, landing zone (LZ) and depth using commercially available software were compared to measurements in VR. Results 3D reconstruction of MSCT datasets and visualization in VR were successfully performed automatically in all patients within a few seconds. MSCT and VR demonstrated good correlations for ostium minimum (r = 0.93), maximum (r = 0.8) and mean (r = 0.88, all p&amp;lt;0.001) diameters. Additionally, LZ minimum (r=0.84), maximum (r=0.86) and mean (r=0.9) diameters showed good correlation (all p&amp;lt;0.001). Moderate correlation was observed for depth measurements (r=0.76, p&amp;lt;0.001). Furthermore, intraclass correlation coefficients ranging from 0.88 to 0.98 denoted high inter- and intraobserver agreement. Conclusion Immersive VR allows highly feasible, accurate and reproducible measurements of the LAA dimensions directly in the virtual environment, hence enabling accurate device sizing for LAAC.

Evaluating the performance of automatic wave speed estimators of natural shear waves to assess myocardial stiffness

Abstract Introduction Cardiac Shear Wave Elastography is an emerging non-invasive technique using ultrafast echocardiographic imaging. Natural shear waves (SW) occur after mitral valve closure (MVC) and aortic valve closure (AVC), and their propagation velocities are directly related to myocardial stiffness. However, the current assessment of SW velocities lacks a gold standard method, and relies on manual measurements with their inherent variability. Purpose To explore new automated methods for shear wave velocity estimates, aiming to achieve greater accuracy, less variability, and high feasibility. Methods To visualize shear waves, anatomical M-modes were drawn (4±1 cm) along ventricular septum in parasternal long axis views (PLAX), acquired with high-frame-rate echocardiography (1055±159 Hz). M-modes were colour coded for tissue acceleration. SWs appear as tilted green bands after MVC &amp; AVC, the slope of which represents the SW propagation velocity. One hundred-twenty different slopes from healthy volunteers (n=67) and patients (n=53) were measured manually and with 9 different automatic methods. All automatic methods were initiated by indicating the approximate position of the shear wave in the M-mode with a mouse click of the user. Measurements were repeated three times to assess measurement reproducibility. (figure 1, A). In order to determine the influence of display settings, three different acceleration colour scales were tested (0.5, 1, 2 m/s²). (Figure 1, B). Failure of correctly identifying shear waves was counted to assess feasibility. Due to the lack of a gold standard, manual measurements of an experienced reader served as reference. Results Three of nine automatic methods: Radon Transformation (RT), Regression Segmentation Maximum value (RM), Regression Segmentation Weighted Maximum (RMW), revealed the least variability with repeated measurements (0.0±0.0 m/s for all) and colour scales (0.0±0.0, 0.1±0.2 and 0.1±0.2 m/s, resp.). Those three methods showed moderate to good agreement (r=0.66, ICC 0.77 [CI 0.64- 0.85]; r= 0.67, ICC 0.75 [CI 0.50 -0.86]; and r= 0.77, ICC 0.85 [CI 0.73-0.90], resp.) with manual measurements (r=0.96, ICC 0.98 [CI 0.97- 0.99] (figure 2). Conclusion RT, RM, and RMW showed a good reproducibility while RMW showed the best agreement with manual measurements. Our data suggest, that the RMW method could offer an objective alternative for SW velocity estimations. Further research is needed to explore their applicability in clinical scenarios.

Reproducibility of Thermography for Measuring Skin Temperature of Upper Limbs in Breast Cancer Survivors

Background/Objectives: Breast cancer-related lymphedema (BCRL) is a chronic condition that has early diagnosis as a critical component for proper treatment. Thermography, a non-invasive imaging method, is considered a promising complementary tool for the diagnosis and monitoring of BCRL, especially in subclinical stages. The present study aimed to evaluate the intra- and inter-examiner reproducibility of thermography for measuring the skin temperature of the upper limbs (UL) of women with and without BCRL. Methods: This study, conducted with women who underwent a unilateral mastectomy, assessed BCRL using indirect volumetry. Maximum, minimum, and mean skin temperatures were measured in five regions of interest (ROI) of each UL (C1, C2, C3, C4, and Cup) in four different postures. Reproducibility measures were assessed using an intraclass correlation coefficient, 95% confidence interval, and coefficient of variation. Results: The sample comprised 30 women; 14 were diagnosed with BCRL. A total of 120 thermograms were recorded in different postures, and 3600 ROI were analyzed in the UL with and without BRCL. The intraclass correlation coefficient of the analyses indicated intra- and inter-examiner reproducibility from good to excellent (0.82 to 1.00) for all skin temperatures evaluated (maximum, minimum, and mean). The coefficient of variation for all measures was below 10%, indicating low variability. Conclusions: Our findings demonstrate that thermography shows good-to-excellent reproducibility across multiple postures and regions of interest, reinforcing its potential as a non-invasive and reliable method for assessing lymphedema in breast cancer survivors. This study establishes a foundation for incorporating thermography into clinical practice for early BCRL detection, particularly in subclinical stages, thus improving patient management and outcomes.

Automated, Reproducible, and Reconfigurable Human Head Phantom for Experimental Testing of Microwave Systems for Stroke Classification

ABSTRACTMicrowave systems for prehospital stroke classification are currently being developed. In the future, these systems should enable rapid recognition of the type of stroke, shorten the time to start treatment, and thus significantly improve the prognosis of patients. In this study, we realized a realistic and reconfigurable 3D human head phantom for the development, testing, and validation of these newly developed diagnostic methods. The phantom enables automated and reproducible measurements for different positions of the stroke model. The stroke model itself is also interchangeable, so measurements can be made for different types, sizes, and shapes of strokes. Furthermore, an extensive series of measurements was performed at a frequency of 1 GHz, and an SVM classification algorithm was deployed, which successfully identified ischemic stroke in 80% of the corresponding measured data. If similar classification accuracy could be achieved in patients, it would lead to a dramatic reduction in the consequences of strokes.

Non-Targeted Metabolomics Reveal Apomorphine’s Therapeutic Effects and Lysophospholipid Alterations in Steatohepatitis

Metabolic dysfunction-associated steatohepatitis (MASH), characterized by progressive inflammation and fibrosis, evolves from metabolic dysfunction-associated steatotic liver disease and significantly heightens the risk of cirrhosis and hepatocellular carcinoma. Understanding metabolic pathways that influence MASH progression is crucial for developing targeted therapies. Non-targeted metabolomics offer a comprehensive view of metabolic alterations, enabling identification of novel biomarkers and pathways without preconceived ideas. Conversely, targeted metabolomics deliver precise and reproducible measurements, focusing on predefined metabolites to accurately quantify established pathways. This study utilized hepatocyte-specific PTEN knockout mice as a model to explore metabolic shifts associated with MASH. By integrating non-targeted metabolomics and targeted metabolomics, we analyzed liver samples from three groups: normal, pathological (MASH-affected), and MASH-affected, but treated with apomorphine, an antioxidant and recently reported ferroptosis inhibitor with potential therapeutic effects. Metabolic profiling identified lysophospholipids (LPLs) as significantly altered metabolites, with elevated levels in the MASH model and a notable reduction after apomorphine treatment. This suggests that LPLs are central to the etiology of MASH and may serve as targets for therapeutic intervention. Our findings underscore the effectiveness of apomorphine in modulating disease-specific metabolic disruptions, offering insights into its potential as a treatment for human MASH.

The Critical Shoulder Angle as a Highly Specific Predictor of a Full-Thickness Rotator Cuff Tear: A Case-Control Study.

The critical shoulder angle (CSA) has become an important topic of study in patients with rotator cuff tears (RCTs). However, there are conflicting data on whether the CSA can differentiate between patients with normal shoulder pathology and full-thickness RCTs on shoulder radiographs. The purpose of this study was to define the relationship between full-thickness RCTs and the CSA. It was hypothesized that patients with full-thickness RCTs would have an increased CSA compared with matched controls. Cross-sectional study; Level of evidence, 3. This retrospective case-control study identified patients with magnetic resonance imaging scans showing full-thickness RCTs between 2009 and 2019. A 1 to 1 propensity score match was performed to identify a control group with normal rotator cuffs while controlling for baseline participant characteristics-including age, sex, body mass index, and tobacco use. A total cohort of 532 was identified, with 266 cases and 266 controls. Two independent observers measured CSAs on true anteroposterior shoulder radiographs. There was no difference in baseline participant characteristics between the RCT and the non-RCT groups (P > .05). The mean CSA for the entire cohort was 33.6°± 4.2°. The CSA did not significantly vary by sex (P = .088) or tobacco usage (P = .16). The mean CSA for the RCT case group, 36.2°± 3.3°, was significantly different from the mean CSA for the control group, 30.9°± 3.3° (P < .0001). The receiver operating characteristic curve analysis produced an area under the curve of 0.88 (P < .0001). At CSAs ≥35°, there was a 67.7% sensitivity and 89.4% specificity for having a full-thickness RCT. Last, each degree of increase in the CSA increased the risk of having an associated RCT by 1.7 times (OR, 1.7 [95% CI, 1.551-1.852]; P < .0001). Patients with RCTs had significantly higher CSAs compared with matched controls. Increased CSA was an independent risk factor for RCTs, with an odds ratio of 1.7 per degree. The CSA is an accurate test (area under the curve, 0.88) with good sensitivity (67.7%) and specificity (89.4%) at values ≥35°. The CSA is a simple, reproducible measurement that can assist in clinical decision-making regarding full-thickness RCTs.

Repeatability and Reproducibility of pseudo-Continuous Arterial Spin Labeling Measured Brain Perfusion in Healthy Volunteers and Glioblastoma Patients.

Arterial spin labeled (ASL) MRI has gained recognition as a quantitative perfusion imaging method for managing patients with brain tumors. Limited studies have so far investigated the reproducibility of ASL-derived perfusion in patients with brain tumors. This study aims to evaluate intrasession repeatability and intersession reproducibility of perfusion measurements using 3D pseudo-continuous ASL (pCASL) with Cartesian TSE (TSE-CASPR) in healthy volunteers (HV) and glioblastoma (GBM) patients at 3 Tesla and compare against 3D pCASL with GRASE. This prospective study (NCT03922984) was approved by the institutional review board and written informed consent was obtained from all subjects. HV underwent repeated pCASL evaluations 2-4 weeks apart between November 2021 and October 2022. GBM patients were recruited for longitudinal MRI from September 2019 to February 2023. Intrasession repeatability (HV and GBM) and intersession reproducibility (HV only) of pCASL were assessed using linear regression, Bland-Altman analyses, intraclass correlation coefficient (ICC) with 95% confidence interval (CI), and within-subject coefficients of variation (wsCV). Twenty HV (9 men, age: 25.1±1.7 years, range 23-30 years) and 21 GBM patients (15 men; age: 59.8±14.3 years, range 28-81 years) were enrolled. Within imaging session, 3D pCASL measured perfusion with TSE-CASPR and GRASE respectively achieved high R2 values (0.88-0.95; 0.93-0.96), minimal biases (-0.46 to 0.81; -0.08 to 0.35 mL/100g/min), high ICC [95% CI] (0.96-0.98 [0.94-0.98]; 0.96-0.98 [0.92-0.99]), and low wsCV (6.64%-9.07%; 5.20%-8.16%) in HV (N=20) and GBM patients (N=21). Across imaging session, 3D pCASL in HV (N=20) achieved high R2 values (0.71; 0.82), minimal biases (-1.2; -0.90 mL/100g/min), high ICC [95% CI] values (0.85 [0.81-0.89]; 0.90 [0.87-0.93]), and low wsCV values (13.82%; 9.98%). Our study demonstrated excellent intrasession repeatability of 3D pCASL measured cerebral perfusion in HV and GBM patients and good to excellent intersession reproducibility in HV. 3D pCASL with GRASE performed slightly better than 3D pCASL with TSE-CASPR in HV; however, in GBM patients, 3D pCASL with TSE-CASPR showed better performance in tumor regions with nearly twofold higher SNR. ASL measured perfusion could serve as a non-contrast quantitative imaging biomarker to facilitate the management of GBM patients. ASL = arterial spin labeling; pCASL = pseudo-continuous arterial spin labeling; GBM = glioblastoma; CBF = cerebral blood flow; CASPR = Cartesian acquisition with spiral profile reordering; GRASE = gradient and spin echo; NAGM = normal-appearing gray matter.

Repeatability and reproducibility of artificial intelligence-acquired fetal brain measurements (SonoCNS) in the second and third trimesters of pregnancy

Artificial Intelligence (AI)-based algorithms are increasingly entering clinical practice, aiding in the assessment of fetal anatomy and biometry. One such tool for evaluating the fetal head and central nervous system structures is SonoCNS™, which delineates appropriate planes for measuring head circumference (HC), biparietal diameter (BPD), occipitofrontal diameter (OFD), transcerebellar diameter (TCD), width of the posterior horn of the lateral ventricle (Vp), and cisterna magna (CM) based on a 3D volume acquired at the level of the fetal head’s thalamic plane. This study aimed to evaluate the intra- and interobserver variability of measurements obtained using this software. The study included 381 patients, 270 in their second trimester of pregnancy (70%) and 111 in the third trimester. Each patient underwent manual biometric measurements of the aforementioned structures and twice using the SonoCNS software. We calculated the intraobserver variability between the manual measurements and the average of the automated measurements, as well as the interobserver variability for automated measurements. We also compared the median examination time for manual and automated measurements. The interclass correlation coefficients (ICC) for interobserver and intraobserver variability for parameters BPD, HC, and OFD ranged from good to excellent reproducibility in the general population and subgroups (> 0.75). CM and Vp measurements, both in the general population and subgroups, fell into the category of moderate (0.5–0.75) and poor reproducibility (< 0.5). TCD measurements showed moderate (> 0.5) to good reproducibility (0.75–0.9), and OFD showed good and excellent reproducibility. The assessment of the biometry of fetal head structures using SonoCNS took an average of 63 s compared to 14 s for manual measurement (p < 0.001). The SonoCNS™ software is characterized by good to excellent reproducibility and repeatability in the measurement of fetal skull biometry (BPD, HC, and OFD), with poorer performance in measurements of intracranial structures (CM, Vp, TCD). Apart from biometric parameters, the software is useful in clinical practice for delineating appropriate planes from the acquired volume of the fetal head and shortening examination time.

Evaluation and real-world experience of a neutralization susceptibility screening assay for broadly neutralizing anti-HIV-1 antibodies.

Development of a screening assay for the clinical use of broadly neutralizing antibodies (bnAbs) is a priority for HIV therapy and cure initiatives. We assessed the PhenoSense Monoclonal Antibody (mAb) Assay (Labcorp-Monogram Biosciences) which is CLIA-validated and has been used prospectively and retrospectively in multiple recent bnAb clinical trials. When performed on pre-ART plasma and on-ART longitudinal PBMC samples sourced from a recent clinical trial, the PhenoSense mAb Assay produced robust reproducibility, concordance across sample types, and expected ranges in the susceptibility measures of bnAbs in clinical development. PhenoSense mAb applied retrospectively to baseline samples from three recent studies correlated with published laboratory-based study evaluations, but baseline bnAb susceptibility was not consistently predictive of durable virus suppression. Assessment of the feasibility of the assay in four recent clinical studies provides estimates of assay success rate and processing time. The PhenoSense mAb Assay provides reproducible bnAb susceptibility measurements across relevant sample types yet was not consistently predictive of virus suppression. Logistical and operational assay requirements can impact timely clinical trial conduct. These results inform bnAb studies in development.

Dimensional assessment on baseline MRI of soft-tissue sarcomas: longest diameter, sum and product of diameters, and volume-which is the best measurement method to predict patients' outcomes?

The longest diameter (LD) is a strong prognostic factor for patients with soft-tissue sarcoma (STS). Other dimensional assessments, such as the sum of diameters (SoD), product of diameters (PoD), and volume (3D-COG - proposed by the Children Oncology Group), can be rapidly performed; however, their prognostic values have never been compared to LD. Our goal was to investigate their performance in improving patients' prognostication for STS of the lower limbs. All consecutive adults managed with curative intent at our sarcoma reference center for a newly diagnosed STS of the lower limbs between 2000 and 2017, with pre-treatment MRI, were included in this retrospective study. Multivariable Cox regression models were trained to predict metastasis-free survival (MFS) in a Training cohort of 66.7% patients based on LD, PoD, SoD, or 3D-COG (and systematically including age, histologic grade, histotype, radiotherapy, chemotherapy, and surgical margins as covariables). The models were then compared on a validation cohort of 33.3% patients using concordance indices (c-index). The same approach was applied for overall survival (OS) and local relapse-free survival (LFS). Measurement reproducibility among three readers was evaluated with an intraclass correlation coefficient (ICC). 382 patients were included in the survival modeling (72/253 [28.5%] metastatic relapses in Training and 36/129 [27.9%] metastatic relapses in Validation). Higher dimensions were associated with lower MFS (multivariable hazard ratio [HR] = 2.44 and P = 0.0018 for LD; HR = 1.88 and P = 0.0009 for PoD, HR = 1.52 and P = 0.0041 for SoD; and HR = 1.08 and P = 0.0195 for 3D-COG). Higher c-indices were obtained with PoD model in Training (c-index = 0.772) and Validation (c-index = 0.688), but they were not significantly higher thanthose obtained with LD model. None of the measurements was associated with LFS or OS. All measurements demonstrated excellent ICC (> 0.95). Regarding its simplicity and good performance, LD appeared as the best metric to incorporate in prognostic models and nomograms for MFS.

Long-Term Reproducibility of BMD-Measurements with Clinical QCT Using Simultaneous and Asynchronous Calibration Methods and Different Measurement and Reconstruction Protocols.

Osteoporosis is underdiagnosed and undertreated. To improve timely fracture risk assessment optimized densitometry methods are required such as opportunistic spinal quantitative computed tomography (QCT). However, it is unclear how to best calibrate these scans and correct for potential scanner drift of QCT when used for monitoring bone mineral density (BMD) changes. We compared gold standard simultaneous calibration with asynchronous calibration methods, assessing mid-term (12weeks) and long-term (1.5years) reproducibility of BMD measurements. Cortical and trabecular compartments of the European Spine Phantom were studied with ten different protocols including low dose and high resolution (HR)-modes. Based on weekly phantom data, we compared simultaneous calibration to asynchronous single (termed global) or monthly calibration. The accuracy was better for trabecular measurements than for cortical measurements for all calibration methods. Reproducibility was excellent for all methods and slightly better for asynchronous than for simultaneous calibration both for trabecular and cortical bone. For HR protocols, reproducibility was better than for low dose measurements. In trabecular compartments averaged HR-BMD remained stable for global (- 0.1%/year, ns) but not for simultaneous calibration (- 1.5%/year, p < 0.001). No significant drifts could be detected for averaged low dose BMD (- 0.9 to + 0.8%/year) for either calibration method. Our data suggest that with regard to precision and accuracy measurements with asynchronous calibration are suitable for vertebral BMD assessment (no contrast agents) in clinical practice. Regular (e.g., monthly) stability tests using a calibration phantom could assure long term stability of at least 1year.

Enhancing low-level tritium detection in environmental waters: assessing the Hidex ULLA liquid scintillation counter

Tritium (³H) is a vital tracer in isotope hydrology and environmental studies, necessitating accurate and precise low-level detection methods. This study evaluated the performance of the new Hidex ULLA Liquid Scintillation Counter for ultra-low-level tritium assays in environmental water samples. The optimization of instrumental parameters enabled accurate and reproducible 3H measurements. Test samples (10–132 TU) were analyzed in triplicate, including 3H-free water and NIST traceable standards. The results demonstrated excellent accuracy and reproducibility, as evidenced by Zeta scores and linearity across these tritium concentrations. The system's stability over extended measurement time periods ensured reliable performance for routine ultra-low level 3H analysis. The optimization of key parameters such as coincidence time and region of interest (ROI) achieved the highest figure of merit (FoM) by using a 25 ns coincidence time and the DigPb open mode for optimal spectral fittings. Detection limits (DL) based on ISO11929 recommendations were significantly improved but highlighted the need for sample enrichment for most low-level environmental applications, with LSC counting times preferably exceeding 1000 min. Overall, the Hidex ULLA Liquid Scintillation Counter proved to be a robust and reliable instrument suitable for ultra-low-level tritium detection in environmental water samples.

Pancreatic ultrasound: An update of measurements, reference values, and variations of the pancreas.

Reliable and reproducible measurement methods have been established, and reference values are used in almost all scientific disciplines. Knowledge of reference values is crucial to distinguish physiological from pathological processes and, therefore, subsequently, for the clinical management of patients. Image storage and documentation of measurements and normal findings should be part of quality assurance in imaging. This paper aims to review the published literature and provide current knowledge of sonographic measurements and reference values of the pancreas. Moreover, the role of clinical influencing factors such as age, gender, constitution, and ethnicity is also analyzed.

In Situ Raman Spectroscopy as a Valuable Tool for Monitoring Crystallization Kinetics in Molecular Glasses

The performance of in situ Raman microscopy (IRM) in monitoring the crystallization kinetics of amorphous drugs (griseofulvin and indomethacin) was evaluated using a comparison with the data obtained via differential scanning calorimetry (DSC). IRM was found to accurately and sensitively detect the initial stages of the crystal growth processes, including the rapid glass–crystal surface growth or recrystallization between polymorphic phases, with the reliable localized identification of the particular polymorphs being the main advantage of IRM over DSC. However, from the quantitative point of view, the reproducibility of the IRM measurements was found to be potentially significantly hindered due to inaccurate temperature recording and calibration, variability in the Raman spectra corresponding to the fully amorphous and crystalline phases, and an overly limited number of spectra possible to collect during acceptable experimental timescales because of the applied heating rates. Since theoretical simulations showed that, from the kinetics point of view, the constant density of collected data points per kinetic effect results in the smallest distortions, only the employment of the fast Raman mapping functions could advance the performance of IRM above that of calorimetric measurements.