Semiquantitative Measure Research Articles

18F-FDG PET/CT in the diagnosis of infective endocarditis

Abstract Background Increased uptake of 18F-fluorodeoxyglucose (FDG) by positron-emission tomography/computed tomography (PET/CT) is one of the diagnostic criteria for prosthetic valve endocarditis (PVE). However, there is limited data on the diagnostic value of FDG PET/CT in diagnosing native valve endocarditis (NVE) and semi-quantitative parameters of FDG uptake. Purpose The objective of this retrospective study was to evaluate the accuracy of FDG PET/CT and additional value of semi-quantitative measures of FDG uptake in the detection of NVE and PVE. Methods All patients who had undergone FDG PET/CT due to suspected infective endocarditis (IE) at a single tertiary referral center between 2010 and 2020 were identified. Additional patients who underwent FDG PET/CT for detecting an infection focus were included as controls. Clinical reports were evaluated and images were analyzed for maximal standardized uptake value (SUVmax) and target to background ratio (TBR = SUVmax normalized to mean blood pool SUV) around valves. The scan was defined positive based on either clinical reading or previously proposed cut-off values for SUVmax and TBR (>4.2 and >2.1, respectively). The final diagnosis of IE was defined based on all available information in electronic medical records. Results The study cohort included 16 patients with suspected NVE (median age 58 years, 88% male), 24 patients with suspected PVE (median age 72 years, 92% male) and 37 patients who underwent FDG PET/CT for detecting an infectious focus (8 with a prosthetic valve). The final diagnosis was definite IE in 25 (14 PVE), possible IE in 7 (6 PVE), and no IE in 45 (12 with a prosthetic valve). Overall, clinical reading of FDG PET/CT identified 17 (sensitivity 68%) of definite IE with a specificity of 91% and accuracy of 83%. Compared with NVE, the sensitivity of FDG PET/CT was higher in the detection of PVE (46% vs. 86%) whereas specificity was lower (97% vs. 75%) resulting in small difference in accuracy (84% vs. 81%). In PVE, SUVmax had higher sensitivity (93%) than clinical reading, resulting in the same accuracy (81%) despite lower specificity (67%). A combination of either positive clinical reading or positive SUVmax identified all patients with PVE (sensitivity 100%). In NVE, TBR had higher sensitivity (64%) than clinical reading, but accuracy (66%) and specificity (67%) were significantly lower. Conclusions FDG PET/CT shows high sensitivity in the detection of PVE and high specificity in the detection of NVE in a real-world clinical cohort. Semi-quantitative parameters of FDG uptake can improve sensitivity of detecting PVE maintaining diagnostic accuracy. However, in NVE semi-quantitative parameters were associated with a prominent reduction in specificity.

Association of quantitative histopathology measurements with antemortem medial temporal lobe cortical thickness in the Alzheimer’s disease continuum

The medial temporal lobe (MTL) is a hotspot for neuropathology, and measurements of MTL atrophy are often used as a biomarker for cognitive decline associated with neurodegenerative disease. Due to the aggregation of multiple proteinopathies in this region, the specific relationship of MTL atrophy to distinct neuropathologies is not well understood. Here, we develop two quantitative algorithms using deep learning to measure phosphorylated tau (p-tau) and TDP-43 (pTDP-43) pathology, which are both known to accumulate in the MTL and are associated with MTL neurodegeneration. We focus on these pathologies in the context of Alzheimer’s disease (AD) and limbic predominant age-related TDP-43 encephalopathy (LATE) and apply our deep learning algorithms to distinct histology sections, on which MTL subregions were digitally annotated. We demonstrate that both quantitative pathology measures show high agreement with expert visual ratings of pathology and discriminate well between pathology stages. In 140 cases with antemortem MR imaging, we compare the association of semi-quantitative and quantitative postmortem measures of these pathologies in the hippocampus with in vivo structural measures of the MTL and its subregions. We find widespread associations of p-tau pathology with MTL subregional structural measures, whereas pTDP-43 pathology had more limited associations with the hippocampus and entorhinal cortex. Quantitative measurements of p-tau pathology resulted in a significantly better model of antemortem structural measures than semi-quantitative ratings and showed strong associations with cortical thickness and volume. By providing a more granular measure of pathology, the quantitative p-tau measures also showed a significant negative association with structure in a severe AD subgroup where semi-quantitative ratings displayed a ceiling effect. Our findings demonstrate the advantages of using quantitative neuropathology to understand the relationship of pathology to structure, particularly for p-tau, and motivate the use of quantitative pathology measurements in future studies.

Nested PCR effective to detect low viral loads of SARS-CoV-2 in animal samples

SARS-CoV-2 emerged from an animal source and was then transmitted to humans, causing the COVID-19 pandemic. Since a wide range of animals are susceptible to SARS-CoV-2 infection, the zoonotic potential of SARS-CoV-2 increases with every new animal infected. The molecular gold standard assay for SARS-CoV-2 detection is real-time RT-PCR, where the Ct obtained is proportional to the amount of nucleic acid and can be a semi-quantitative measure of the viral load. However, since the use of real-time RT-PCR assays in animal samples is low due to the high costs, the use of validated nested PCR assays will help to monitor large-scale animal samplings, by reducing the costs of detection. In the present study, 140 samples from dogs and cats (15 SARS-CoV-2-positive samples with Ct values from 27 to 33, and 125 negative samples), previously analyzed by real-time RT-PCR, were analyzed by nested PCR. To increase the number of positive samples to determine the sensitivity of the assay, 40 human samples obtained during COVID-19 diagnosis in 2020 were included. The specificity of the primers was analyzed against samples positive to canine coronavirus (CCV) and feline infectious peritonitis virus (FIPV). To calculate the limit of detection (LoD) of the nested PCR, the viral load was estimated extrapolating the Ct value obtained by real-time RT-PCR. The Ct values obtained were considered as semi-quantitative and were able to distinguish between high, moderate and low viral loads. The Kappa value or “agreement” between assays and reliability of the nested PCR were also determined. Eleven of the animal samples analyzed by nested PCR targeting the N gene were detected as positive, while 129 were detected as negative to the virus, with Ct values ranging between17 and 31.5. All the samples from humans analyzed by nested PCR were positive. These results indicate that the assay has a sensitivity of near 95 % and a specificity of 100 %. No unspecific reactions analyzed by nested PCR were observed with the samples positive to CCV and FIPV. The samples detected as positive to SARS-CoV-2 by nested PCR were those that presented a Ct between17 and 31.5. The LoD of the nested PCR was estimated close to 50 copies/µL of viral load, corresponding with a Ct of 31.5. The Kappa value between assays was excellent (k = 0.829). The results obtained demonstrate that nested PCR is useful to detect SARS-CoV-2 low viral loads at a lower cost than with real-time RT-PCR.

Quantitative indicators for environmental and social sustainability performance assessment of the supply chain

AbstractIn the era of globalization, supply chains are becoming less transparent, facing pressing sustainability challenges such as the inappropriate use of natural resources, poor working conditions, and environmental degradation. This paper addresses these issues by presenting a pioneering sustainability assessment framework aimed at increasing transparency and accountability in global supply chains. Emerging from a systematic literature review and insights from the Global Reporting Initiative (GRI), the framework comprises 91 robust performance indicators: 36 environmental and 55 social. These indicators, a mix of quantitative and semi-quantitative measures, provide a comprehensive tool for assessing the sustainability performance of supply chain actors across a range of sectors. The framework not only facilitates companies in measuring their own and their suppliers’ sustainability performance but also enhances their capacity to effectively communicate their environmental and social progress to stakeholders. Additionally, it is designed to seamlessly integrate with Industry 4.0 technologies, enabling more dynamic assessments.

Prevalence of SARS-CoV-2 antibodies and associated factors in the adult population of Belgium: a general population cohort study between March 2021 and April 2022

BackgroundThis study assessed seroprevalence trends of SARS-CoV-2 antibodies in the Belgian adult population between March 2021 and April 2022, and explored factors associated with seropositivity and seroreversion among the vaccinated and unvaccinated population.MethodsA prospective longitudinal surveillance study was conducted within a random sample of the general population (18 + years) in Belgium, selected from the national register through a multistage sampling design. Participants provided a saliva sample and completed a survey questionnaire on three occasions: at baseline and in two follow-up waves. Outcome variables included (1) seropositivity, defined as the presence of SARS-CoV-2 antibodies, assessed with a semi-quantitative measure of anti-RBD (Receptor Binding Domain) IgG ELISA and (2) seroreversion, defined as passing from a positive to a negative antibody test between two measurements. Trends in SARS-CoV-2 antibody prevalence were assessed using binary logistic regression with contrasts applying post-stratification. Potential determinants of seropositivity were assessed through multilevel logistic regressions.ResultsIn total 6,178 valid observations were obtained from 2,768 individuals. SARS-CoV-2 antibody prevalence increased from 25.1% in the beginning of the study period to 92.3% at the end. Among the vaccinated population, factors significantly associated with higher seropositivity rates were being younger, having a bachelor diploma, living with others, having had a vaccine in the last 3 months and having received a nucleic-acid vaccine or a combination. Lower seropositivity rates were observed among vaccinated people with a neurological disease and transplant patients. Factors significantly associated with higher seropositivity rates among the unvaccinated population were having non-O blood type and being non-smoker. Among vaccinated people, the seroreversion rate was much lower (0.3%) in those who had received their latest vaccine in the last 3 months compared to those who had received their latest vaccine more than 3 months ago (2.7%) (OR 0.13; 95%CI 0.04–0.42).ConclusionsThe rapid increase in antibody seropositivity in the general adult population in Belgium during the study period was driven by the vaccination campaign which ran at full speed during this period. Among vaccinated people, seropositivity varied in function of the time since last vaccine, the type of vaccine, sociodemographic features and health status.

[15O]H2O myocardial perfusion positron emission tomography: Added value of relative stress perfusion deficit in the prediction of significant coronary artery stenosis in a mixedpopulation

BackgroundIt remains unknown whether estimation of the relative stress perfusion deficit offers added value in the prediction of significant coronary artery stenosis in myocardial perfusion imaging with [15O]H2O positron emission tomography (PET) in a population with high prevalence of established cardiac disease. MethodsDuring eight months, we consecutively included all patients undergoing [15O]H2O PET and subsequent invasive coronary angiography (ICA). Significant stenosis was defined from ICA as fractional flow reserve ≤.8 or coronary artery narrowing of ≥70%. We calculated absolute and relative total perfusion deficits (aTPD and rTPD, respectively) as semiquantitative measures of the extent and severity of reduced stress perfusion. A multivariate logistic regression analysis was performed to test the adjusted associations (odds ratio (OR) with 95% CI) with significant coronary artery stenosis. ResultsOf 800 patients undergoing [15O]H2O PET, 144 underwent ICA, where 142 patients had aTPD of ≥3% and 79 (55%) of these had at least one significant stenosis. In an adjusted analysis, rTPD (OR10% increase = 2.12 (1.44-3.12), P < .001), previous coronary artery bypass grafting (CABG) (OR = .11 (.03-.36), P < .001) and reduced left ventricular ejection fraction (LVEF) (OR = .25 (.08-.84), P = .02) were independently associated with significant stenosis, whereas the association with aTPD (OR10% increase = 1.14 (.98-1.32), P = .08) was modest. ConclusionsIn the presence of an absolute perfusion deficit (aTPD of ≥3%), rTPD may improve the prediction of significant stenosis in a heterogeneous population of patients examined with [15O]H2O PET. Furthermore, previous CABG and reduced LVEF are associated with nonstenotic perfusion deficiencies, suggesting caution when interpreting myocardial perfusion imaging in such patients.

Exploring the nigrostriatal and digestive interplays in Parkinson's disease using dynamic total-body [11C]CFT PET/CT.

Dynamic total-body imaging enables new perspectives to investigate the potential relationship between the central and peripheral regions. Employing uEXPLORER dynamic [11C]CFT PET/CT imaging with voxel-wise simplified reference tissue model (SRTM) kinetic modeling and semi-quantitative measures, we explored how the correlation pattern between nigrostriatal and digestive regions differed between the healthy participants as controls (HC) and patients with Parkinson's disease (PD). Eleven participants (six HCs and five PDs) underwent 75-min dynamic [11C]CFT scans on a total-body PET/CT scanner (uEXPLORER, United Imaging Healthcare) were retrospectively enrolled. Time activity curves for four nigrostriatal nuclei (caudate, putamen, pallidum, and substantia nigra) and three digestive organs (pancreas, stomach, and duodenum) were obtained. Total-body parametric images of relative transporter rate constant (R1) and distribution volume ratio (DVR) were generated using the SRTM with occipital lobe as the reference tissue and a linear regression with spatial-constraint algorithm. Standardized uptake value ratio (SUVR) at early (1-3min, SUVREP) and late (60-75min, SUVRLP) phases were calculated as the semi-quantitative substitutes for R1 and DVR, respectively. Significant differences in estimates between the HC and PD groups were identified in DVR and SUVRLP of putamen (DVR: 4.82 ± 1.58 vs. 2.58 ± 0.53; SUVRLP: 4.65 ± 1.36 vs. 2.84 ± 0.67; for HC and PD, respectively, both p < 0.05) and SUVREP of stomach (1.12 ± 0.27 vs. 2.27 ± 0.65 for HC and PD, respectively; p < 0.01). In the HC group, negative correlations were observed between stomach and substantia nigra in both the R1 and SUVREP values (r=-0.83, p < 0.05 for R1; r=-0.94, p < 0.01 for SUVREP). Positive correlations were identified between pancreas and putamen in both DVR and SUVRLP values (r = 0.94, p < 0.01 for DVR; r = 1.00, p < 0.001 for SUVRLP). By contrast, in the PD group, no correlations were found between the aforementioned target nigrostriatal and digestive areas. The parametric images of R1 and DVR generated from the SRTM model, along with SUVREP and SUVRLP, were proposed to quantify dynamic total-body [11C]CFT PET/CT in HC and PD groups. The distinction in correlation patterns of nigrostriatal and digestive regions between HC and PD groups identified by R1 and DVR, or SUVRs, may provide new insights into the disease mechanism.

Abstract TP246: Circadian Variability of the Clot Burden Score in Acute Anterior Circulation Ischemic Stroke

Background/Purpose: Fibrinolytic activity in blood plasma displays a circadian rhythm with a drop in the morning hours that may predispose to acute thrombotic events. The Clot Burden Score (CBS) is a semiquantitative measure on CT angiography (CTA) of thrombus extent in proximal anterior circulation strokes that has been correlated with functional outcome. Higher clot burden has also been shown to have lower recanalization rates with intravenous thrombolytics. We aimed to investigate whether CBS is a parameter that displays circadian variability. Methods: We performed a retrospective analysis on consecutive stroke patients presenting &lt;24 hours from symptom onset or last known well (LKW) with an occlusion in the anterior circulation confirmed on CTA. CBS was scored on a 10-point negative ordinal scale with 2-points subtracted for occlusion of the supraclinoid ICA, proximal M1, or distal M1, and 1-point subtracted for occlusion of the infraclinoid ICA, A1, or either M2 branches. No points were subtracted for occlusion distal to A1 or M2. Subjects were grouped into four 6-hour intervals, MORNING: 6:00-11:59, DAY: 12:00-17:59, EVENING: 18:00-23:59, and NIGHT: 0:00-5:59, based on the time of onset/LKW. CBS values were compared between groups using the Kruskal-Wallis test with pairwise comparisons. Results: 240 subjects were included with median age of 75 (IQR 65-84), NIHSS score of 17 (IQR 10-24), and time from onset/LKW to CTA of 5 hours (IQR 2-11). 73 subjects had onset during the MORNING, 56 during the DAY, 86 during the EVENING, and 25 during the NIGHT. The median CBS from MORNING time onset was 6 (IQR 5-9), compared to 7 (IQR 6-9) from the DAY, 7.5 (IQR 6-9) from the EVENING, and 7 (IQR 5-8.5) from the NIGHT. CBS was significantly lower in the MORNING compared to the EVENING, p=0.037. CBS was not significantly different between all other pairwise comparisons, p&gt;0.107. Conclusion: CBS as a measure of thrombus extent in proximal anterior circulation strokes on CTA appears to show circadian variability, with lower scores (higher clot burden) during MORNING onset (6:00-11:59) than the EVENING (18:00-23:59). This may have implications for future studies of chronotherapeutic protocols.

Abstract TP133: Clot Burden Score Correlates Best With Hypoperfusion Volume and Predicts Final Infarct ASPECTS&lt;=3 in Anterior Circulation Ischemic Strokes

Purpose: Clot Burden Score (CBS) is a semiquantitative measure of thrombus extent on CTA for proximal anterior circulation strokes whose relationship with perfusion metrics has not been fully explored. CBS has potential added value during stroke triage if perfusion imaging is not available or suboptimal. We aimed to investigate if CBS is (1) correlated to perfusion estimates of infarct core volume, hypoperfusion volume, or collateral status, and (2) a predictor of final infarct extent without reperfusion therapy. Methods: Retrospective analysis included consecutive patients (1) arriving &lt;24 hours from onset, (2) with occlusion in the intracranial ICA, M1, M2, or A1 or combination, (3) with concurrent CTP, and (4) had followup CT or DWI during hospitalization. CBS is a 10-point negative ordinal scale: 2-points subtracted for occlusion of supraclinoid ICA, proximal M1, or distal M1, and 1-point subtracted for occlusion of infraclinoid ICA, A1, or M2. Correlation of CBS with perfusion metrics was evaluated using Spearman's rank test. Final infarct ASPECTS were scored for those without thrombolysis or thrombectomy. Multivariate logistic regression was used to identify predictors of final ASPECTS&lt;=3 (approximating &gt;=100mL). ROC analysis was evaluated to assess performance and optimal thresholds. Results: 222 patients included with median (IQR) age of 75 (65-84) and NIHSS of 18 (11-24). Median CBS was 7 (6-9) and best correlated to Tmax&gt;6s r=-0.579 (hypoperfusion volume), followed by HIR r=-0.401 (collateral status) and rCBF&lt;30% r=-0.306 (core volume), all p&lt;0.001. 71 (32.0%) untreated patients also had median CBS of 7 (6-9). CBS and Tmax&gt;6s had the strongest correlation to final ASPECTS in this subgroup, r=0.637 and r=-0.686 (both p&lt;0.001). 22 of these (30.1%) had final ASPECTS&lt;=3. Multivariate logistic regression including CBS, Tmax&gt;6s, HIR, baseline ASPECTS, and NIHSS showed only CBS as independent predictor of final ASPECTS&lt;=3 (p&lt;0.001). ROC AUC for CBS was 0.902 [95% CI: 0.819-0.985] with optimal threshold of &lt;=6 for sensitivity 86.4% and specificity 81.6%. Conclusion: CBS as a measure of thrombus extent correlates best with baseline hypoperfusion volume on CTP and independently predicts very large final infarcts (ASPECTS&lt;=3) without treatment.

Diagnostic value of [ 68 Ga]Ga-Pentixafor PET/CT in malignant melanoma: a pilot study.

To evaluate the diagnostic value of [ 68 Ga] Ga-Pentixafor in malignant melanoma patients. In this prospective study, patients with histology-proven melanoma were included and underwent [ 18 F]fluoro-D-glucose ([ 18 F]FDG) and [ 68 Ga] Ga-Pentixafor PET/computed tomography (CT) within a week. Suspicious lesions were interpreted as benign vs. malignant, and the corresponding semi-quantitative PET/CT parameters were recorded and compared. Twelve consecutive melanoma patients (mean age: 60 ± 6) were included. Two patients were referred for initial staging, two for detecting recurrence and eight for evaluating the extent of metastases. Overall, [ 18 F]FDG PET/CT showed 236 tumoral lesions, including two primary tumors, two recurrent lesions, 29 locoregional metastases and 203 distant metastases. In [ 68 Ga]Ga-Pentixafor PET/CT, 101 tumoral lesions were detected, including two primary tumors, one recurrence, 16 locoregional metastases and 82 distant metastases. Notably, a documented brain metastasis was only visualized on [ 68 Ga]Ga-Pentixafor PET/CT images. Compared with [ 18 F]FDG, [ 68 Ga]Ga-Pentixafor PET/CT provided a 42% detection rate. Regarding semi-quantitative measures, the intensity of uptake and tumor-to-background ratios were significantly lower on [ 68 Ga]Ga-Pentixafor PET/CT [average maximum standard uptake value (SUV max ) of 2.72 ± 1.33 vs. 11.41 ± 14.79; P value <0.001 and 1.17 ± 0.53 vs. 5.32 ± 7.34; P value <0.001, respectively]. When comparing [ 68 Ga]Ga-Pentixafor PET/CT with [ 18 F]FDG PET/CT, not only did [ 68 Ga]Ga-Pentixafor PET/CT detect fewer lesions, but the intensity of uptake and the TBRs were also lower on [ 68 Ga]Ga-Pentixafor PET/CT. Thus, our results may indicate a limited potential of this novel tracer in cutaneous melanoma patients compared to [ 18 F]FDG PET/CT. Given the lower TBRs, applying this radiotracer in radioligand therapies is also questionable.

Trends in Melanoma Patient Survival Based on Tumor Depth and Anatomic Location

Skin cancer is the most common cancer. Melanoma composes less than 4% of total cases but is the cause of most skin cancer deaths. However, in the United States, melanoma has the fifth highest rate of incidence of all cancers with an average 93.5% 5-year survival rate. However, when melanoma spreads either to regional lymph nodes or to distant organs, the prognosis drops significantly, so there is a critical need to identify patients at risk for tumor spread. The objective of this research project is to determine the correlation between tumor depth and anatomic location with metastasis outcomes. We identified a cohort of 923 Stage 1 &amp; 2 patients (those without lymph node metastases) from the Indiana University Simon Cancer Center Registry with an average follow up of 4 years (Std. dev = 3.2). We retrieved the clinicopathologic descriptions of their melanomas using a database from the IU Pathology department. Patients were stratified by tumor stage, location, and depth of invasion, and survival rates were analyzed Cox proportional hazard models and log-rank tests. Kaplan-Meier plots were generated with the survminer package. The results of the study indicate that there is no difference in metastasis for patients with similar levels of tumor invasion but different anatomic locations. Unexpectedly, multivariate cox regression showed that mitotic count was a stronger predictor of metastasis than tumor invasion. These results indicate that there is a need for bioinformatic tools to more accurately quantify semi-quantitative measures of tumor morphology. This would allow for rigorous research and higher precisions prognostic tools.

Comparison of tracer kinetic models for 68Ga-PSMA-11 PET in intermediate-risk primary prostate cancer patients

Background68Ga-PSMA-11 positron emission tomography enables the detection of primary, recurrent, and metastatic prostate cancer. Regional radiopharmaceutical uptake is generally evaluated in static images and quantified as standard uptake values (SUVs) for clinical decision-making. However, analysis of dynamic images characterizing both tracer uptake and pharmacokinetics may offer added insights into the underlying tissue pathophysiology. This study was undertaken to evaluate the suitability of various kinetic models for 68Ga-PSMA-11 PET analysis. Twenty-three lesions in 18 patients were included in a retrospective kinetic evaluation of 55-min dynamic 68Ga-PSMA-11 pre-prostatectomy PET scans from patients with biopsy-demonstrated intermediate- to high-risk prostate cancer. Three kinetic models—a reversible one-tissue compartment model, an irreversible two-tissue compartment model, and a reversible two-tissue compartment model, were evaluated for their goodness of fit to lesion and normal reference prostate time-activity curves. Kinetic parameters obtained through graphical analysis and tracer kinetic modeling techniques were compared for reference prostate tissue and lesion regions of interest.ResultsSupported by goodness of fit and information loss criteria, the irreversible two-tissue compartment model optimally fit the time-activity curves. Lesions exhibited significant differences in kinetic rate constants (K1, k2, k3, Ki) and semiquantitative measures (SUV and %ID/kg) when compared with reference prostatic tissue. The two-tissue irreversible tracer kinetic model was consistently appropriate across prostatic zones.ConclusionsAn irreversible tracer kinetic model is appropriate for dynamic analysis of 68Ga-PSMA-11 PET images. Kinetic parameters estimated by Patlak graphical analysis or full compartmental analysis can distinguish tumor from normal prostate tissue.

A comparison of visual assessment and semi-quantification for the diagnostic and prognostic use of [18F]flortaucipir PET in a memory clinic cohort

Purpose[18F]Flortaucipir PET is a powerful diagnostic and prognostic tool for Alzheimer’s disease (AD). Tau status definition is mainly based in the literature on semi-quantitative measures while in clinical settings visual assessment is usually preferred. We compared visual assessment with established semi-quantitative measures to classify subjects and predict the risk of cognitive decline in a memory clinic population.MethodsWe included 245 individuals from the Geneva Memory Clinic who underwent [18F]flortaucipir PET. Amyloid status was available for 207 individuals and clinical follow-up for 135. All scans were blindly evaluated by three independent raters who visually classified the scans according to Braak stages.Standardized uptake value ratio (SUVR) values were obtained from a global meta-ROI to define tau positivity, and the Simplified Temporo-Occipital Classification (STOC) was applied to obtain semi-quantitatively tau stages. The agreement between measures was tested using Cohen’s kappa (k). ROC analysis and linear mixed-effects models were applied to test the diagnostic and prognostic values of tau status and stages obtained with the visual and semi-quantitative approaches.ResultsWe found good inter-rater reliability in the visual interpretation of tau Braak stages, independently from the rater’s expertise (k>0.68, p<0.01). A good agreement was equally found between visual and SUVR-based classifications for tau status (k=0.67, p<0.01). All tau-assessment modalities significantly discriminated amyloid-positive MCI and demented subjects from others (AUC>0.80) and amyloid-positive from negative subjects (AUC>0.85). Linear mixed-effect models showed that tau-positive individuals presented a significantly faster cognitive decline than the tau-negative group (p<0.01), independently from the classification method.ConclusionOur results show that visual assessment is reliable for defining tau status and stages in a memory clinic population. The high inter-rater reliability, the substantial agreement, and the similar diagnostic and prognostic performance of visual rating and semi-quantitative methods demonstrate that [18F]flortaucipir PET can be robustly assessed visually in clinical practice.

Goal Attainment Scaling for Depression: Validation of the Japanese GAS-D Tool in Patients with Major Depressive Disorder.

Goal attainment scaling (GAS) has been proposed as a person-centric, semi-quantitative measure that assimilates achievement of individually set goals into a single standardized "goal attainment score" that can be compared at the population level. We aimed to examine the reliability and validity of the Japanese version of the GAS for depression (GAS-D) tool in assessing goal attainment in people living with major depressive disorder (MDD). This was a prespecified analysis of a prospective, 24-week, multicenter, observational cohort study of employed Japanese outpatients with MDD initiating treatment with vortioxetine according to the Japanese label (JRCT1031210200). Participants were assessed using the Japanese version of the GAS-D and other clinical rating scales at baseline and Weeks 8, 12 and 24. Goal attainment was significantly associated with symptom severity as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS) scale, confirming convergent validity. In particular, GAS-D scores were significantly related to MADRS total score at Weeks 12 and 24, indicating that improvements in overall symptom severity with vortioxetine treatment were likely to be reflected in the achievement of individualized treatment goals. With an intraclass correlation coefficient of 0.67 (95% CI 0.45-0.82), the GAS-D also showed moderate test-retest reliability between Weeks 8 and 12 while proving independent of demographic characteristics. The results of this open-label study support the use of the GAS-D as a valid and sensitive outcome measure in the assessment of treatment response in MDD.

The added value of lung perfusion scintigraphy semiquantitative measures in post-COVID patients with persistent dyspnea without pulmonary embolism

ABSTRACT Background Persistent dyspnea is frequent in post-COVID patients, even in the absence of pulmonary embolism (PE). In this scenario, the role of lung perfusion scintigraphy is unclear. The present study correlated scintigraphy-based semiquantitative perfusion parameters with chest high-resolution computed tomography (hrCT) volumetric indexes and clinical data in post-COVID patients with persistent dyspnea. Research design and methods Sixty patients (30 post-COVID and 30 not previously affected by COVID-19) with persistent dyspnea submitted to lung perfusion scintigraphy and hrCT were retrospectively recruited. Perfusion rates of the pulmonary fields and hrCT-based normalized inflated, emphysematous, infiltrated, collapsed, and vascular lung volumes were calculated. Inflammatory and coagulation biomarkers were collected. PE at imaging was an exclusion criterion. Results Compared to controls, reduced perfusion rates of the lower pulmonary fields and higher perfusion rates of the middle ones were observed in post-COVID patients, while hrCT findings were superimposable between the two groups. Perfusion rates of lower pulmonary fields were significantly associated only with abnormal lung volumes at hrCT. Conclusions In post-COVID dyspnea without PE, lung perfusion scintigraphy may reveal a pulmonary involvement not detectable by hrCT. Post-COVID patients may show decreased perfusion rates of lower pulmonary fields in the presence of normal vascular density and markers of inflammation/coagulation.

Assessment of Contact Allergens in "Hypoallergenic" Athletic Shoes by Mass Spectrometry.

Background: Identification of athletic shoes for patients with contact allergy is difficult. Company reports of allergen content are often incorrect. Objectives: To determine whether chemical analysis of 4 athletic shoes, previously reported to be free of the most common contact allergens, contain quantifiable allergen levels. Methods: Samples from the uppers and insoles of 4 shoes believed to be free of common allergens were assessed by mass spectrometry. A total of 4 rubber accelerators and 2 adhesives were directly quantified and additional 7 rubber accelerators were assessed using semiquantitative measures. Results: Aside from carbamates (assayed as 59 ppm zinc in insoles) in SeaVee's Sixty-Six sneakers, para-tertiarybutylphenol formaldehyde resin (PTBFR) (assayed as 7.6 ppm paratertiary butylphenol or 4-tertiary butylphenol [4TBP] in uppers) in Allbirds Tree Runners and rosin (assayed as 628 ppm sodium abietate in uppers) and carbamates (24 ppm zinc in uppers) in Saucony Jazz sneakers, these shoes had low levels of all allergens assayed in this study. Tom's Carlo sneakers contained rosin (127 ppm sodium abietate in insoles), PTBFR (6.5 ppm 4TBP in uppers), and carbamates (112 ppm sodium abietate in insoles) but had low levels of all other assayed allergens. Conclusions: Although identifying allergen-free shoes is challenging, the results of this analysis will help patch testing physicians recommend athletic shoes to patients with specific allergies.

Can lung semi-quantitative measurements and mediastinal adipose tissue volume predict prognosis in patients with idiopathic pulmonary fibrosis (IPF)? A CT-based preliminary study.

The aim of this study was to assess the potential of subcutaneous adipose tissue volume, mediastinal adipose tissue volume, lung density, and lung volume (as measured on high-resolution computed tomography) to predict disease progression in patients with idiopathic pulmonary fibrosis (IPF). Additionally, the study aimed to evaluate the changes in these semiquantitative measures over time. The HRCT images of 57 patients diagnosed with IPF were retrospectively screened. Subcutaneous adipose tissue volume, mediastinal adipose tissue volume, and mean lung density and volume were measured at the time of diagnosis and at the 12th month. The ability of these parameters to predict progression was evaluated using the univariate and multivariate Cox regression analyses. Low mediastinal adipose tissue volume at diagnosis had a 0.991-fold effect [odds ratio (OR)= 0.991, 95% confidence interval (CI)= 0.984-0.997, p< 0.001] on progression. Low mediastinal adipose tissue volume at diagnosis had a 0.993-fold effect [odds ratio (OR)= 0.993, 95% confidence interval (CI)= 0.975-1.011, p< 0.001] and progression development at the 12th month had a 6.5-fold effect [odds ratio (OR)= 6.516, 95% confidence interval (CI)= 1.594-26.639, p< 0.009] on mortality. This study indicate that the prognosis was better in those with a large mediastinal adipose tissue volume among the patients with IPF.

Zircon and apatite fingerprints on the magma fertility for the Jurassic igneous rocks in the southern Lhasa subterrane, Tibet

The products of long-lasting magmatism (ca. 170 Myr) related to the northward subduction of the Neo-Tethys Ocean are preserved in the southern Lhasa subterrane (SLT). However, only a few large porphyry Cu–Au deposits related to these igneous rocks have been discovered in the Xiongcun ore concentration area. Here, we present zircon and apatite data on Jurassic fertile suites (FS), barren suites (BS), and recently proposed prospecting target suites (PTS) in the SLT, intending to present a case study of the regional-scale porphyry metallogenic potential. The zircon geochemical data with Rayleigh fractionation modeling show that the zircon geochemical characteristics of the FS and PTS were affected by high proportions of amphibole and titanite crystallization, whereas the zircon geochemistry of the BS displays the effects of plagioclase fractionation or mixing with the least evolved melts. The zircon Ce4+/Ce3+ and Eu/Eu* values cannot be used to trace the oxygen fugacity of the magma due to prior or simultaneous mineral crystallization. However, the zircon Ce/Ce* and Ce/Nd ratios may be used as semiquantitative measures of the magma redox conditions. This result is similar to that calculated by the new magmatic oxybarometer using trace elements in zircon, showing that the FS (ΔFMQ = 1.21 ± 0.42) and PTS (ΔFMQ = 1.29 ± 0.51) have higher oxygen fugacity levels than the BS (ΔFMQ = 0.40 ± 0.88). The melt S contents estimated from magmatic apatites are lower in the FS and PTS than in the BS, which is attributed to prior anhydrite crystallization under high oxygen fugacity and low temperature conditions. The higher Cl in the melt of the FS (average 0.098 wt%) than in the melts of the PTS (average 0.045 wt%) and BS (average 0.04 wt%) shows that elevated Cl contents in melts are likely important for forming porphyry Cu–Au deposits. The combined geochemical characteristics of zircon and apatite suggest that a high oxygen fugacity (ΔFMQ > 1.2), prior or concurrent anhydrite crystallization, and high zircon Eu/Eu* (>0.6), Ce4+/Ce3+, and (Yb/Dy)N values can be used to refine potential porphyry Cu–Au targets on a regional scale in the SLT. High melt Cl contents and apatite MnO and Pb contents can effectively indicate fertile suites at the deposit scale.

Quantitatively Measured Infrapatellar Fat Pad Signal Intensity Alteration is Associated with Joint Effusion-synovitis in Knee Osteoarthritis.

The objective of this study is to investigate whether quantitatively measured infrapatellar fat pad (IPFP) signal intensity alteration is associated with joint effusion-synovitis in people with knee osteoarthritis (OA) over two years. Among 255 knee OA patients, IPFP signal intensity alteration represented by four measurement parameters [standard deviation of IPFP signal intensity (IPFP sDev), upper quartile value of IPFP high signal intensity region (IPFP UQ (H)), ratio of IPFP high signal intensity region volume to whole IPFP volume (IPFP percentage (H)), and clustering factor of IPFP high signal intensity (IPFP clustering factor (H))] was measured quantitatively at baseline and two-year follow-up using magnetic resonance imaging (MRI). Effusion-synovitis of the suprapatellar pouch and other cavities were measured both quantitatively and semi-quantitatively as effusion-synovitis volume and effusion-synovitis score at baseline and two-year follow-up using MRI. Mixed effects models assessed the associations between IPFP signal intensity alteration and effusion-synovitis over two years. In multivariable analyses, all four parameters of IPFP signal intensity alteration were positively associated with total effusion-synovitis volume and effusion-synovitis volumes of the suprapatellar pouch and of other cavities over two years (all P＜0.05). They were also associated with the semi-quantitative measure of effusion-synovitis except for IPFP percentage (H) with effusion-synovitis in other cavities. Quantitatively measured IPFP signal intensity alteration is positively associated with joint effusion-synovitis in people with knee OA, suggesting that IPFP signal intensity alteration may contribute to effusion-synovitis and a coexistent pattern of these two imaging biomarkers could exist in knee OA patients.

Clinical utility of somatostatin receptor positron emission tomography imaging biomarkers for characterization of meningioma among incidental central nervous system lesions.

Somatostatin receptor (SSTR) PET imaging is utilized with increasing frequency in the clinical management of neuroendocrine tumors. Incidental PET-avid CNS lesions are commonly noted and presumed to be meningiomas. However, SSTR PET lacks specificity for meningioma identification. This study aimed to clarify the role of SSTR-based imaging in the classification of incidental CNS lesions based on current clinical practice. Patients who underwent both Ga-68-DOTATATE PET and brain MRI and had an incidental CNS lesion identified with a radiographic prediction of meningioma via one (discordant prediction) or both (concordant prediction) imaging modalities were retrospectively analyzed. Imaging indication, semiquantitative measures, and clinical history were recorded. Among 48 patients with a CNS lesion identified on both imaging modalities, most scans were performed for a history of neuroendocrine tumor (64.6%). Cases with concordant lesion-type prediction of meningioma between imaging modalities ( N = 24) displayed a significantly higher SUV max (median 7.9 vs. 4.0; P = 0.008) and Krenning score (median 3.0 vs. 2.0; P = 0.005) on Ga-68-DOTATATE PET compared with cases with a discordant prediction of meningioma ( N = 24). In cases with lower SUV max values, Ga-68-DOTATATE was more likely to discordantly predict meningioma without agreement by the corresponding MRI. Prior cranial radiation or use of somatostatin mimetics did not affect quantitative radiographic measures, and MRI-based tumor size was similar across groups. Lesions with increased avidity may be more confidently predicted as meningioma in Ga-68-DOTATATE PET scans, whereas there is more discrepancy in prediction among low SUV cases.