Galectin-10 in serum extracellular vesicles reflects asthma pathophysiology.

BACKGROUND: Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes. OBJECTIVE: We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs). METHODS: We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps. RESULTS: We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo. CONCLUSION: Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.

Three-dimensional iodine mapping quantified by dual-energy CT for predicting programmed death-ligand 1 expression in invasive pulmonary adenocarcinoma.

We examined the association between texture features using three-dimensional (3D) io-dine density histogram on delayed phase of dual-energy CT (DECT) and expression of programmed death-ligand 1 (PD-L1) using immunostaining methods in non-small cell lung cancer. Consecutive 37 patients were scanned by DECT. Unenhanced and enhanced (3 min delay) images were obtained. 3D texture analysis was performed for each nodule to obtain 7 features (max, min, median, mean, standard deviation, skewness, and kurtosis) from iodine density mapping and extracellular volume (ECV). A pathologist evaluated a tumor proportion score (TPS, %) using PD-L1 immunostaining: PD-L1 high (TPS ≥ 50%) and low or negative expression (TPS < 50%). Associations between PD-L1 expression and each 8 parameter were evaluated using logistic regression analysis. The multivariate logistic regression analysis revealed that skewness and ECV were independent indicators associated with high PD-L1 expression (skewness: odds ratio [OR] 7.1 [95% CI 1.1, 45.6], p = 0.039; ECV: OR 6.6 [95% CI 1.1, 38.4], p = 0.037). In the receiver-operating characteristic analysis, the area under the curve of the combination of skewness and ECV was 0.83 (95% CI 0.67, 0.93) with sensitivity of 64% and specificity of 96%. Skewness from 3D iodine density histogram and ECV on dual energy CT were significant factors for predicting PD-L1 expression.

Assessment of pulmonary function in COPD patients using dynamic digital radiography: A novel approach utilizing lung signal intensity changes during forced breathing.

Objectives: To investigate the association of lung signal intensity changes during forced breathing using dynamic digital radiography (DDR) with pulmonary function and disease severity in patients with chronic obstructive pulmonary disease (COPD). Methods: This retrospective study included 46 healthy subjects and 33 COPD patients who underwent posteroanterior chest DDR examination. We collected raw signal intensity and gray-scale image data. The lung contour was extracted on the gray-scale images using our previously developed automated lung field tracking system and calculated the average of signal intensity values within the extracted lung contour on gray-scale images. Lung signal intensity changes were quantified as SImax/SImin, representing the maximum ratio of the average signal intensity in the inspiratory phase to that in the expiratory phase. We investigated the correlation between SImax/SImin and pulmonary function parameters, and differences in SImax/SImin by disease severity. Results: SImax/SImin showed the highest correlation with VC (rs = 0.54, P < 0.0001), followed by FEV1 (rs = 0.44, P < 0.0001), both of which are key indicators of COPD pathophysiology. In a multivariate linear regression analysis adjusted for confounding factors, SImax/SImin was significantly lower in the severe COPD group compared to the normal group (P = 0.0004) and mild COPD group (P=0.0022), suggesting its potential usefulness in assessing COPD severity. Conclusion: This study suggests that the signal intensity changes of lung fields during forced breathing using DDR reflect the pathophysiology of COPD and can be a useful index in assessing pulmonary function in COPD patients, potentially improving COPD diagnosis and management.

Photon-Counting Detector CT Radiological-Histological Correlation in Cadaveric Human Lung Nodules and Airways.

OBJECTIVES: The aim of this study was to compare the performances of photon-counting detector computed tomography (PCD-CT) and energy-integrating detector computed tomography (EID-CT) for visualizing nodules and airways in human cadaveric lungs. MATERIALS AND METHODS: Previously obtained 20 cadaveric lungs were scanned, and images were prospectively acquired by EID-CT and PCD-CT at a radiation dose with a noise level equivalent to the diagnostic reference level. PCD-CT was scanned with ultra-high-resolution mode. The EID-CT images were reconstructed with a 512 matrix, 0.6-mm thickness, and a 350-mm field of view (FOV). The PCD-CT images were reconstructed at 3 settings: PCD-512: same as EID-CT; PCD-1024-FOV350: 1024 matrix, 0.2-mm thickness, 350-mm FOV; and PCD-1024-FOV50: 1024 matrix, 0.2-mm thickness, 50-mm FOV. Two specimens per lung were examined after hematoxylin and eosin staining. The CT images were evaluated for nodules on a 5-point scale and for airways on a 4-point scale to compare the histology. The Wilcoxon signed rank test with Bonferroni correction was performed for statistical analyses. RESULTS: Sixty-seven nodules (1321 µm; interquartile range [IQR], 758-3105 µm) and 92 airways (851 µm; IQR, 514-1337 µm) were evaluated. For nodules and airways, scores decreased in order of PCD-1024-FOV50, PCD-1024-FOV350, PCD-512, and EID-CT. Significant differences were observed between series other than PCD-1024-FOV350 versus PCD-1024-FOV50 for nodules (PCD-1024-FOV350 vs PCD-1024-FOV50, P = 0.063; others P < 0.001) and between series other than EID-CT versus PCD-512 for airways (EID-CT vs PCD-512, P = 0.549; others P < 0.005). On PCD-1024-FOV50, the median size of barely detectable nodules was 604 µm (IQR, 469-756 µm) and that of barely detectable airways was 601 µm (IQR, 489-929 µm). On EID-CT, that of barely detectable nodules was 837 µm (IQR, 678-914 µm) and that of barely detectable airways was 1210 µm (IQR, 674-1435 µm). CONCLUSIONS: PCD-CT visualized small nodules and airways better than EID-CT and improved with high spatial resolution and potentially can detect submillimeter nodules and airways.

Prediction of solid and micropapillary components in lung invasive adenocarcinoma: radiomics analysis from high-spatial-resolution CT data with 1024 matrix.

PURPOSE: To predict solid and micropapillary components in lung invasive adenocarcinoma using radiomic analyses based on high-spatial-resolution CT (HSR-CT). MATERIALS AND METHODS: For this retrospective study, 64 patients with lung invasive adenocarcinoma were enrolled. All patients were scanned by HSR-CT with 1024 matrix. A pathologist evaluated subtypes (lepidic, acinar, solid, micropapillary, or others). Total 61 radiomic features in the CT images were calculated using our modified texture analysis software, then filtered and minimized by least absolute shrinkage and selection operator (LASSO) regression to select optimal radiomic features for predicting solid and micropapillary components in lung invasive adenocarcinoma. Final data were obtained by repeating tenfold cross-validation 10 times. Two independent radiologists visually predicted solid or micropapillary components on each image of the 64 nodules with and without using the radiomics results. The quantitative values were analyzed with logistic regression models. The receiver operating characteristic curves were generated to predict of solid and micropapillary components. P values < 0.05 were considered significant. RESULTS: Two features (Coefficient Variation and Entropy) were independent indicators associated with solid and micropapillary components (odds ratio, 30.5 and 11.4; 95% confidence interval, 5.1-180.5 and 1.9-66.6; and P = 0.0002 and 0.0071, respectively). The area under the curve for predicting solid and micropapillary components was 0.902 (95% confidence interval, 0.802 to 0.962). The radiomics results significantly improved the accuracy and specificity of the prediction of the two radiologists. CONCLUSION: Two texture features (Coefficient Variation and Entropy) were significant indicators to predict solid and micropapillary components in lung invasive adenocarcinoma.

Dual-source photon-counting computed tomography for coronary in-stent observation: influence of heart rate and virtual monoenergetic image.

To investigate the effect of heart rate and virtual monoenergetic image (VMI) on coronary stent imaging in dual-source photon-counting detector computed tomography (PCD-CT). A dynamic cardiac phantom was used to vary the heart rate at 50 beats per minute (bpm), 70 bpm, and 90 bpm. Five types of stents (4.0 mm, 3.5 mm, 3.0 mm, 2.75 mm, and 2.5 mm diameter) were scanned at three different locations and reconstructed VMI at 70 keV. In addition, 50% stenosis was assessed for 3.0 mm and 4.0 mm stents. To assess in-stent stenosis, 40 keV, 70 keV, and 100 keV images were compared. Measurable lumen and contrast to noise ratio (CNR) from lumen to stenosis were evaluated quantitatively. A-4-point scale was used for the qualitative image quality of in-stent stenosis. The measurable lumen had no significant differences among heart rates in patent stents (p = 0.55). In-stent stenosis, the residual lumen was significantly larger in 40 keV [27.5% (20.8-32.3%)] than in 70 keV [11.5% (10.0-23.0%), p < 0.05] and 100 keV [0% (0-5.2%), p < 0.05]. The CNR was higher in 40 keV [12.5 (7.5-18.2)] than in 70 keV [5.3 (2.9-7.7), p < 0.05] and 100 keV [1.3 (0.5-2.7), p < 0.05]. The image quality was better in 40 keV (3.4 ± 0.7) than in 70 keV [(2.6 ± 0.8), p < 0.05] and 100 keV [(1.3 ± 0.4), p < 0.05]. Dual-source PCD-CT maintains a measurable lumen even at high heart rates. Adjusting the VMI can be helpful in visualizing the in-stent stenosis.

Association between interstitial lung abnormality and mortality in patients with esophageal cancer.

PURPOSE: To investigate the relationship between interstitial lung abnormalities (ILAs) and mortality in patients with esophageal cancer and the cause of mortality. MATERIALS AND METHODS: This retrospective study investigated patients with esophageal cancer from January 2011 to December 2015. ILAs were visually scored on baseline CT using a 3-point scale (0 = non-ILA, 1 = indeterminate for ILA, and 2 = ILA). ILAs were classified into subcategories of non-subpleural, subpleural non-fibrotic, and subpleural fibrotic. Five-year overall survival (OS) was compared between patients with and without ILAs using the multivariable Cox proportional hazards model. Subgroup analyses were performed based on cancer stage and ILA subcategories. The prevalences of treatment complications and death due to esophageal cancer and pneumonia/respiratory failure were analyzed using Fisher's exact test. RESULTS: A total of 478 patients with esophageal cancer (age, 66.8 years ± 8.6 [standard deviation]; 64 women) were evaluated in this study. Among them, 267 patients showed no ILAs, 125 patients were indeterminate for ILAs, and 86 patients showed ILAs. ILAs were a significant factor for shorter OS (hazard ratio [HR] = 1.68, 95% confidence interval [CI] 1.10-2.55, P = 0.016) in the multivariable Cox proportional hazards model adjusting for age, sex, smoking history, clinical stage, and histology. On subgroup analysis using patients with clinical stage IVB, the presence of ILAs was a significant factor (HR = 3.78, 95% CI 1.67-8.54, P = 0.001). Subpleural fibrotic ILAs were significantly associated with shorter OS (HR = 2.22, 95% CI 1.25-3.93, P = 0.006). There was no significant difference in treatment complications. Patients with ILAs showed a higher prevalence of death due to pneumonia/respiratory failure than those without ILAs (non-ILA, 2/95 [2%]; ILA, 5/39 [13%]; P = 0.022). The prevalence of death due to esophageal cancer was similar in patients with and without ILA (non-ILA, 82/95 [86%]; ILA 32/39 [82%]; P = 0.596). CONCLUSION: ILAs were significantly associated with shorter survival in patients with esophageal cancer.