The Importance of Routine Quality Control For Reproducible Pulmonary Measurements By in Vivo Micro-CT

Micro-Computed Tomography (CT) imaging provides densitometric and functional assessment of lung diseases in animal models, playing a key role either in understanding disease progression or in drug discovery studies.The generation of reliable and reproducible experimental data is strictly dependent on a system’s stability. Quality Controls (QC) are essential to monitor micro-CT performance but, although QC procedures are standardized and routinely employed in clinical practice, detailed guidelines for preclinical imaging are lacking. In this work, we propose a routine QC protocol for in vivo micro-CT, based on three commercial phantoms. To investigate the impact of a detected scanner drift on image post-processing, a retrospective analysis using twenty-two healthy mice was performed and lung density histograms used to compare the Area Under Curve (AUC), the skewness and the kurtosis before and after the drift. As expected, statistically significant differences were found for all the selected parameters [AUC: 532 ± 31 vs. 420 ± 38 (p < 0.001); skewness: 2.3 ± 0.1 vs. 2.5 ± 0.1 (p < 0.001) and kurtosis: 4.2 ± 0.3 vs. 5.1 ± 0.5 (p < 0.001)], confirming the importance of the designed QC procedure to obtain a reliable longitudinal quantification of disease progression and drug efficacy evaluation.

The Application Value of Spiral CT Lung Densitometry Software in the Diagnosis of Radiation-Induced Lung Injury

In order to study the application value of spiral CT lung density measurement software in the diagnosis of radioactive lung injury, the average CT values of lung apex, hilum, and diaphragm were measured by Pulmo automatic evaluation software of 16-slice spiral CT in 96 patients with different types of radiation lung injury diagnosed by conventional CT and 80 healthy subjects. The radiation lung injury on CT slices was classified, and the lung density was measured. In 96 patients with different types of radiation lung injury, 56 patients had different degrees of increase in average lung density, which was most obvious in the type of air insufficiency and chronic fibrosis. CT values of lung density in the ground glass stage and patch stage of acute radiation pneumonia had little influence due to the range and time of exposure. The lung density of 35 patients with radiation injury was measured in the normal range. There was a significant difference between normal lung density and abnormal lung density in different types of radiation lung injury (X2 = 56.718, P < 0.001 ). The mean lung density of 68 cases was normal and that of 12 cases was abnormal. There was a significant difference in lung density between the lung injury group and the normal group (X2 = 18.027, P < 0.001 ). Spiral CT lung density measurement can accurately evaluate the lung density values of different types of radiation lung injury and judge the correlation between lung density and different types of radiation lung injury. It is of great value to diagnose, locate, and master the radiation dose of different types of radiation lung injury.

A Preliminary Study on the Relationship Between High-resolution Computed Tomography and Lung Function in People at Risk of Developing Chronic Obstructive Pulmonary Disease

Background: There is high morbidity and mortality for patients with chronic obstructive pulmonary disease (COPD) in China. The aim of our study was to explore the differences in high-resolution computed tomography (HRCT) emphysema parameters, air trapping parameters, and lung density parameters between patients at high risk and low risk of developing COPD and evaluate their correlation with lung function indicators.Methods: In this retrospective, single-center cohort study, we enrolled outpatients from the Physical Examination Center and Respiratory Medicine of The First Affiliated Hospital of Wenzhou Medical University. The patients at risk of developing COPD were ≥40 years-old, had chronic cough or sputum production, and/or had exposure to risk factors for the disease and had not reached the diagnostic criteria. Patients were divided into a low-risk group and high-risk group according to FEV1/FVC≥80% and 80%>FEV1/FVC≥70%. The data on clinical characteristics, clinical symptom score, lung function, and HRCT were recorded.Results: 72 COPD high-risk patients and 86 COPD low-risk patients were enrolled in the study, and the air trapping index of the left, right, and bilateral lungs of the high-risk group were significantly higher than those of the low-risk group . Additionally, the mean lung density during expiration was significantly lower than that of the low-risk group. The emphysema index of left, right, and bilateral lungs was negatively correlated with FEV1/FVC (correlation coefficients were -0.33-0.22-0.26). There was a negative correlation between the air trapping index of left and right lungs and bilateral lungs and FEV1/FVC(correlation coefficients were -0.33-0.23-0.28, respectively), and the mean expiratory lung density of left and right lungs and bilateral lungs was positively correlated with FEV1/FVC (correlation coefficients were 0.31, 0.25, 0.29, respectively).Conclusions: The air trapping index and the mean expiratory lung density obtained by HRCT combined with post-processing technology can be used as a basis for distinguishing between people at high risk and low risk for developing COPD. Emphysema index, air trapping index, and mean expiratory lung density shows significantly negative correlation with FEV1/FVC, and this can be used to assess the pulmonary function status of people at risk of developing COPD.

Signs and lines in lung ultrasound

Point-of-care ultrasound has become firmly established in acute and critical care settings, and is now increasingly being used as an important tool in the assessment of the lungs. In this article, we briefly describe the technique of lung ultrasound and the various lines and signs commonly encountered during sonography of the lung, namely the normally visualised A- and T-lines and the bat sign, sliding sign (power slide sign on colour Doppler), sea-shore sign, curtain sign, and the lung pulse. We have also described signs seen in various pathological conditions like B-lines seen in cases of increased lung density; the quad sign, sinusoid sign, thoracic spine sign, plankton sign and the jelly fish sign seen in pleural effusion; the stratosphere sign and the lung point sign seen in pneumothorax; the shred/fractal sign and tissue-like sign in consolidation, and the double lung point sign seen in transient tachypnoea of the newborn. With adequate and appropriate training, lung ultrasound can be effectively utilised as a pointof-care investigation.

Bronchoalveolar lavage affects thorax computed tomography of healthy and SARS-CoV-2 infected rhesus macaques (Macaca mulatta)

Medical imaging as method to assess the longitudinal process of a SARS-CoV-2 infection in non-human primates is commonly used in research settings. Bronchoalveolar lavage (BAL) is regularly used to determine the local virus production and immune effects of SARS-CoV-2 in the lower respiratory tract. However, the potential interference of those two diagnostic modalities is unknown in non-human primates. The current study investigated the effect and duration of BAL on computed tomography (CT) in both healthy and experimentally SARS-CoV-2-infected female rhesus macaques (Macaca mulatta). In addition, the effect of subsequent BALs was reviewed. Thorax CTs and BALs were obtained from four healthy animals and 11 experimentally SARS-CoV-2-infected animals. From all animals, CTs were obtained just before BAL, and 24 hours post-BAL. Additionally, from the healthy animals, CTs immediately after, and four hours post-BAL were obtained. Thorax CTs were evaluated for alterations in lung density, measured in Hounsfield units, and a visual semi-quantitative scoring system. An increase in the lung density was observed on the immediately post-BAL CT but resolved within 24 hours in the healthy animals. In the infected animals, a significant difference in both the lung density and CT score was still found 24 hours after BAL. Furthermore, the differences between time points in CT score were increased for the second BAL. These results indicate that the effect of BAL on infected lungs is not resolved within the first 24 hours. Therefore, it is important to acknowledge the interference between BAL and CT in rhesus macaques.

Quantitative CT lung densitometry for the diagnosis of bronchiolitis obliterans in children

Background: The purpose of this study was to evaluate the quantitative diagnostic performance of computed tomography (CT) densitometry in pediatric bronchiolitis obliterans (BO) patients. Methods: A retrospective chart review was performed on 109 children under age 18 who underwent 3D chest CT from March 2019 to March 2021. We measured the mean lung density (MLD) and calculated the difference of MLD (MLDD) in expiratory and inspiratory phase, the expiratory to inspiratory ratio of mean lung density (E/I MLD), and the relative volume percentage of lung density at 50 HU intervals (E600 to E950). We calculated the sensitivity, specificity, and diagnostic accuracy of lung density indices for the diagnosis of BO. Results: A total of 81 patients, 51 BO patients and 30 controls, were included in this study (mean age: 12.7 vs 11.4 years). Expiratory (EXP) MLD, MLDD, E/I MLD, and E900 were all statistically significantly worse in the BO group. Multivariate logistic regression analysis showed that MLDD (odds ratio [OR] = 0.98, p < .001), E/I MLD (OR = 1.39, p < .001), and E850 (OR = 1.54, p = 0.003) were significant densitometry parameters for BO diagnosis. In ROC analysis, E900 (cut-off 1.4%; AUC = 0.920), E/I MLD (cut-off 0.87; AUC = 0.887), and MLDD (cut-off 109 HU; AUC = 0.867) showed high accuracy in diagnosis of BO. Conclusion: The quantification of lung density with chest CT complements the diagnosis by providing additional indications of expiratory airflow limitation in pediatric BO patients.

Correlation Between Lung Density Changes Under Different Dose Gradients and Radiation Pneumonitis—Based on an Analysis of Computed Tomography Scans During Esophageal Cancer Radiotherapy

PurposeTo assess the relationship between different doses of radiation and lung density changes and to determine the ability of this correlation to identify esophageal cancer (EC) patients who develop radiation pneumonitis (RP) and the occurrence time of RP.MethodsA planning computed tomography (CT) scan and a re-planning CT scan were retrospectively collected under institutional review board approval for each of 103 thoracic segment EC patients who underwent radiotherapy (RT). The isodose curve was established on the planning CT with an interval of 5 Gy, which was used as the standard for dividing different gradient doses. Planning CT and re-planning CT scans were matched and the mean lung CT value (HU) between different doses gradients was automatically obtained by the software system. The density change value (ΔHU) was the difference of CT value between each dose gradient before and after treatment. The correlation between ΔHU and the corresponding dose was calculated, as well as the regression coefficients. Additionally the correlation between ΔHU and the occurrence and time of RP (&lt; 4 weeks, 4–12 weeks, &gt; 12 weeks) was calculated.ResultsThe radiation dose and ΔHU was positively correlated, but the correlation coefficient and regression coefficient were lower, 0.261 (P &lt;0.001) and 0.127 (P &lt;0.001), respectively. With the increase of radiation dose gradient, ΔHU in RP≥2 group was higher than that in RP&lt;2 group, and there was significant difference between two groups in ΔHU20-25, ΔHU25-30, ΔHU30-35, ΔHU35-40, ΔHU40-45, ΔHU45-50 (p&lt;0.05). The occurrence time of RP was negatively correlated with the degree of ΔHU (P&lt;0.05), with a high correlation coefficient (Y = week actual value −0.521, P &lt; 0.001) (Y = week grade value −0.381, P = 0.004) and regression coefficient (Y = week actual value −0.503, P&lt;0.001) (Y = week rating value −0.401, P=0.002).ConclusionsA relationship between radiation dose and lung density changes was observed. For most dose intervals, there was an increase of ΔHU with an increased radiation dose, although low correlation coefficient. ΔHU were obvious after irradiation with dose ≥20 Gy which was closely related to the occurrence of RP. For patients with RP, the more obvious ΔHU, the earlier the occurrence of RP, there was a significant negative correlation between them.

Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COPD

Background Soluble receptor for advanced glycation end products (sRAGE) is a proposed emphysema and airflow obstruction biomarker; however, previous publications have shown inconsistent associations and only one study has investigate the association between sRAGE and emphysema. No cohorts have examined the association between sRAGE and progressive decline of lung function. There have also been no evaluation of assay compatibility, receiver operating characteristics, and little examination of the effect of genetic variability in non-white population. This manuscript addresses these deficiencies and introduces novel data from Pittsburgh COPD SCCOR and as well as novel work on airflow obstruction. A meta-analysis is used to quantify sRAGE associations with clinical phenotypes. Methods sRAGE was measured in four independent longitudinal cohorts on different analytic assays: COPDGene (n = 1443); SPIROMICS (n = 1623); ECLIPSE (n = 2349); Pittsburgh COPD SCCOR (n = 399). We constructed adjusted linear mixed models to determine associations of sRAGE with baseline and follow up forced expiratory volume at one second (FEV1) and emphysema by quantitative high-resolution CT lung density at the 15th percentile (adjusted for total lung capacity). Results Lower plasma or serum sRAGE values were associated with a COPD diagnosis (P < 0.001), reduced FEV1 (P < 0.001), and emphysema severity (P < 0.001). In an inverse-variance weighted meta-analysis, one SD lower log10-transformed sRAGE was associated with 105 ± 22 mL lower FEV1 and 4.14 ± 0.55 g/L lower adjusted lung density. After adjusting for covariates, lower sRAGE at baseline was associated with greater FEV1 decline and emphysema progression only in the ECLIPSE cohort. Non-Hispanic white subjects carrying the rs2070600 minor allele (A) and non-Hispanic African Americans carrying the rs2071288 minor allele (A) had lower sRAGE measurements compare to those with the major allele, but their emphysema-sRAGE regression slopes were similar. Conclusions Lower blood sRAGE is associated with more severe airflow obstruction and emphysema, but associations with progression are inconsistent in the cohorts analyzed. In these cohorts, genotype influenced sRAGE measurements and strengthened variance modelling. Thus, genotype should be included in sRAGE evaluations.