Deep learning-based prognostication in idiopathic pulmonary fibrosis using chest radiographs.

OBJECTIVES: To develop and validate a deep learning-based prognostic model in patients with idiopathic pulmonary fibrosis (IPF) using chest radiographs. METHODS: To develop a deep learning-based prognostic model using chest radiographs (DLPM), the patients diagnosed with IPF during 2011-2021 were retrospectively collected and were divided into training (n = 1007), validation (n = 117), and internal test (n = 187) datasets. Up to 10 consecutive radiographs were included for each patient. For external testing, three cohorts from independent institutions were collected (n = 152, 141, and 207). The discrimination performance of DLPM was evaluated using areas under the time-dependent receiver operating characteristic curves (TD-AUCs) for 3-year survival and compared with that of forced vital capacity (FVC). Multivariable Cox regression was performed to investigate whether the DLPM was an independent prognostic factor from FVC. We devised a modified gender-age-physiology (GAP) index (GAP-CR), by replacing DLCO with DLPM. RESULTS: DLPM showed similar-to-higher performance at predicting 3-year survival than FVC in three external test cohorts (TD-AUC: 0.83 [95% CI: 0.76-0.90] vs. 0.68 [0.59-0.77], p < 0.001; 0.76 [0.68-0.85] vs. 0.70 [0.60-0.80], p = 0.21; 0.79 [0.72-0.86] vs. 0.76 [0.69-0.83], p = 0.41). DLPM worked as an independent prognostic factor from FVC in all three cohorts (ps < 0.001). The GAP-CR index showed a higher 3-year TD-AUC than the original GAP index in two of the three external test cohorts (TD-AUC: 0.85 [0.80-0.91] vs. 0.79 [0.72-0.86], p = 0.02; 0.72 [0.64-0.80] vs. 0.69 [0.61-0.78], p = 0.56; 0.76 [0.69-0.83] vs. 0.68 [0.60-0.76], p = 0.01). CONCLUSIONS: A deep learning model successfully predicted survival in patients with IPF from chest radiographs, comparable to and independent of FVC. CLINICAL RELEVANCE STATEMENT: Deep learning-based prognostication from chest radiographs offers comparable-to-higher prognostic performance than forced vital capacity. KEY POINTS: • A deep learning-based prognostic model for idiopathic pulmonary fibrosis was developed using 6063 radiographs. • The prognostic performance of the model was comparable-to-higher than forced vital capacity, and was independent from FVC in all three external test cohorts. • A modified gender-age-physiology index replacing diffusing capacity for carbon monoxide with the deep learning model showed higher performance than the original index in two external test cohorts.

External validation of deep learning-based automated detection algorithm for chest radiograph: practical issues in outpatient clinic.

BACKGROUND: There have been no reports on diagnostic performance of deep learning-based automated detection (DLAD) for thoracic diseases in real-world outpatient clinic. PURPOSE: To validate DLAD for use at an outpatient clinic and analyze the interpretation time for chest radiographs. MATERIAL AND METHODS: This is a retrospective single-center study. From 18 January 2021 to 18 February 2021, 205 chest radiographs with DLAD and paired chest CT from 205 individuals (107 men and 98 women; mean ± SD age: 63 ± 8 years) from an outpatient clinic were analyzed for external validation and observer performance. Two radiologists independently reviewed the chest radiographs by referring to the paired chest CT and made reference standards. Two pulmonologists and two thoracic radiologists participated in observer performance tests, and the total amount of time taken during the test was measured. RESULTS: The performance of DLAD (area under the receiver operating characteristic curve [AUC] = 0.920) was significantly higher than that of pulmonologists (AUC = 0.756) and radiologists (AUC = 0.782) without assistance of DLAD. With help of DLAD, the AUCs were significantly higher for both groups (pulmonologists AUC = 0.853; radiologists AUC = 0.854). A greater than 50% decrease in mean interpretation time was observed in the pulmonologist group with assistance of DLAD compared to mean reading time without aid of DLAD (from 67 s per case to 30 s per case). No significant difference was observed in the radiologist group (from 61 s per case to 61 s per case). CONCLUSION: DLAD demonstrated good performance in interpreting chest radiographs of patients at an outpatient clinic, and was especially helpful for pulmonologists in improving performance.

Extra domain A-containing fibronectin expression in Spin90-deficient fibroblasts mediates cancer-stroma interaction and promotes breast cancer progression.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment play major roles in supporting cancer progression. A previous report showed that SPIN90 downregulation is correlated with CAF activation and that SPIN90-deficient CAFs promote breast cancer progression. However, the mechanisms that mediate cancer-stroma interaction and how such interactions regulate cancer progression are not well understood. Here, we show that extra domain A (EDA)-containing fibronectin (FN), FN(+)EDA, produced by mouse embryonic fibroblasts (MEFs) derived from Spin90-knockout (KO) mice increases their own myofibroblast differentiation, which facilitates breast cancer progression. Increased FN(+)EDA in Spin90-KO MEFs promoted fibril formation in the extracellular matrix (ECM) and specifically interacted with integrin α4ß1 as the mediating receptor. Moreover, FN(+)EDA expression by Spin90-KO MEFs increased proliferation, migration, and invasion of breast cancer cells. Irigenin, a specific inhibitor of the interaction between integrin α4ß1 and FN(+)EDA, significantly blocked the effects of FN(+)EDA, such as fibril formation by Spin90-KO MEFs and proliferation, migration, and invasion of breast cancer cells. In orthotopic breast cancer mouse models, irigenin injection remarkably reduced tumor growth and lung metastases. It was supported by that FN(+)EDA in assembled fibrils was accumulated in cancer stroma of human breast cancer patients in which SPIN90 expression was downregulated. Our data suggest that SPIN90 downregulation increases FN(+)EDA and promotes ECM stiffening in breast cancer stroma through an assembly of long FN(+)EDA-rich fibrils; moreover, engagement of the Integrin α4ß1 receptor facilitates breast cancer progression. Inhibitory effects of irigenin on tumor growth and metastasis suggest the potential of this agent as an anticancer therapeutic.

Risk of pleural recurrence after percutaneous transthoracic needle biopsy in stage I non-small-cell lung cancer.

OBJECTIVES: To determine whether percutaneous transthoracic needle biopsy (PTNB) increased the risk of pleural recurrence in stage I non-small-cell lung cancer (NSCLC). METHODS: In this retrospective study, we reviewed 830 consecutive patients with stage I NSCLC who underwent curative resection between 2004 and 2010. Cox regression analyses with propensity score matching were performed to identify risk factors for pleural recurrence. RESULTS: Of 830 patients, 540 (65.1%) underwent PTNB before surgery, while 290 (34.9%) underwent preoperative bronchoscopic biopsy or intraoperative wedge resection for a pathological diagnosis. Concomitant pleural recurrence occurred in 42 patients (5.1% [95% CI, 3.8-6.8]; 34 [6.3%] PTNB patients and eight [2.8%] non-PTNB patients) and isolated pleural recurrence took place in 26 patients (3.1% [95% CI, 2.1-4.6]; 20 [3.7%] PTNB patients and 6 [2.1%] non-PTNB patients). On multivariate analysis after matching, only visceral pleural invasion was associated with concomitant pleural recurrence (hazard ratio [HR]=3.367; 95% CI, 1.262-8.986; p=0.015) and isolated pleural recurrence (HR=3.216; 95% CI, 1.037-9.978; p=0.043), while PTNB was associated with neither concomitant nor isolated pleural recurrence (p=0.605 and p=0.963, respectively). Among 540 patients undergoing PTNB, the transfissural approach did not have a significant association with pleural recurrence (p=0.539 and p=0.313, respectively); instead, visceral pleural invasion and microscopic lymphatic invasion were significantly associated with concomitant pleural recurrence, and microscopic lymphatic invasion was associated with isolated pleural recurrence (p<0.05). CONCLUSION: PTNB did not significantly increase the risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion was responsible for pleural recurrence. KEY POINTS: • PTNB did not significantly increase the risk of pleural recurrence in stage I NSCLC, whereas visceral pleural invasion was responsible for pleural recurrence. • The transfissural approach in PTNB did not increase the risk of pleural recurrence. • PTNB can be performed for the confirmatory diagnosis of peripheral stage I lung cancer without concern for the risk of pleural recurrence.

Pulmonary subsolid nodules: value of semi-automatic measurement in diagnostic accuracy, diagnostic reproducibility and nodule classification agreement.

OBJECTIVES: We hypothesized that semi-automatic diameter measurements would improve the accuracy and reproducibility in discriminating preinvasive lesions and minimally invasive adenocarcinomas from invasive pulmonary adenocarcinomas appearing as subsolid nodules (SSNs) and increase the reproducibility in classifying SSNs. METHODS: Two readers independently performed semi-automatic and manual measurements of the diameters of 102 SSNs and their solid portions. Diagnostic performance in predicting invasive adenocarcinoma based on diameters was tested using logistic regression analysis with subsequent receiver operating characteristic curves. Inter- and intrareader reproducibilities of diagnosis and SSN classification according to Fleischner's guidelines were investigated for each measurement method using Cohen's κ statistics. RESULTS: Semi-automatic effective diameter measurements were superior to manual average diameters for the diagnosis of invasive adenocarcinoma (AUC, 0.905-0.923 for semi-automatic measurement and 0.833-0.864 for manual measurement; p<0.05). Reproducibility of diagnosis between the readers also improved with semi-automatic measurement (κ=0.924 for semi-automatic measurement and 0.690 for manual measurement, p=0.012). Inter-reader SSN classification reproducibility was significantly higher with semi-automatic measurement (κ=0.861 for semi-automatic measurement and 0.683 for manual measurement, p=0.022). CONCLUSIONS: Semi-automatic effective diameter measurement offers an opportunity to improve diagnostic accuracy and reproducibility as well as the classification reproducibility of SSNs. KEY POINTS: • Semi-automatic effective diameter measurement improves the diagnostic accuracy for pulmonary subsolid nodules. • Semi-automatic measurement increases the inter-reader agreement on the diagnosis for subsolid nodules. • Semi-automatic measurement augments the inter-reader reproducibility for the classification of subsolid nodules.

Predictive CT Features of Visceral Pleural Invasion by T1-Sized Peripheral Pulmonary Adenocarcinomas Manifesting as Subsolid Nodules.

OBJECTIVE: The objective of our study was to determine whether visceral pleural invasion (VPI) of T1-sized peripheral pulmonary adenocarcinomas manifesting as subsolid nodules (SSNs) abutting the pleural surface or associated with pleural tags can be predicted. MATERIALS AND METHODS: Our study population consisted of 188 T1-sized peripheral pulmonary adenocarcinomas that appeared as SSNs (24 pure ground-glass nodules [GGNs] and 164 part-solid nodules) and underwent surgical resection between January 2007 and December 2013. Logistic regression analysis was performed to identify significant factors in predicting VPI. RESULTS: VPI occurred in 36 of 188 adenocarcinomas (19.1%). There were no cases of VPI in patients with pure GGNs. In part-solid nodules, there were significant differences regarding the presence of pleural contact, presence of pleural thickening, presence of solid portion abutting the pleura, nodule size, solid portion size, solid proportion, interface length, and length of the solid portion contacting the pleura (p < 0.05). Multivariate analysis revealed pleural contact (p < 0.001), pleural thickening (p = 0.003), solid proportion greater than 50% (p = 0.002), and nodule size greater than 20 mm (p = 0.015) as significant independent predictive features for VPI with adjusted odds ratios of 8.300, 3.966, 4.636, and 2.993, respectively. CONCLUSION: In part-solid nodules, the CT features of pleural contact, pleural thickening, solid proportion greater than 50%, and nodule size greater than 20 mm were shown to be significant indicators of VPI by T1-sized peripheral adenocarcinomas.

Prediction of microvascular invasion of hepatocellular carcinoma using gadoxetic acid-enhanced MR and (18)F-FDG PET/CT.

PURPOSE: To identify the gadoxetic acid-enhanced MR and the (18)F-fludeoxyglucose (FDG) PET/CT findings associated with microvascular invasion (MVI) of hepatocellular carcinoma (HCC) in patients who are undergoing liver transplantation (LT). METHODS: Fifty-one patients with 78 HCCs underwent LT. Preoperative MRI and (18)F-FDG PET/CT findings were retrospectively analyzed and the association of the imaging findings with MVI was assessed. RESULTS: Univariate analysis revealed that hypointensity seen on T1WI (OR = 4.329, p = 0.011), peritumoral enhancement (OR = 7.000, p = 0.008), inhomogeneity on arterial phase (OR = 4.321, p = 0.011), delayed phase (OR = 4.519, p = 0.009) or hepatobiliary phase (OR = 3.564, p = 0.032), and the large tumor size (>5 cm) (OR = 12.091, p = 0.001) showed statistically significant associations with MVI. The ratio of tumor maximum standardized uptake value (SUV) to normal liver mean SUV (TSUVmax/LSUVmean) (2.05 ± 1.43 vs. 1.08 ± 0.37) revealed significantly higher value in the MVI-positive group. Multivariate analysis revealed that peritumoral enhancement and a TSUVmax/LSUVmean of 1.2 or greater had a statistically significant association with MVI, with odds ratios of 10.648 (p = 0.016) and 14.218 (p = 0.001), respectively. CONCLUSIONS: Preoperative imaging findings such as peritumoral enhancement seen on gadoxetic acid-enhanced MR and a TSUVmax/LSUVmean of 1.2 or more on (18)F-FDG PET/CT, may suggest the presence of MVI in HCC patients.

Radiologic Progression of Interstitial Lung Abnormalities following Surgical Resection in Patients with Lung Cancer.

In this study, we aimed to assess the prevalence of interstitial lung abnormalities (ILAs) and investigate the rates and risk factors associated with radiologic ILA progression among patients with lung cancer following surgical resection. Patients who underwent surgical resection for lung cancer at our institution from January 2015 to December 2020 were retrospectively evaluated and grouped according to their ILA status as having no ILAs, equivocal ILAs, or ILAs. Progression was determined by simultaneously reviewing the baseline and corresponding follow-up computed tomography (CT) scans. Among 346 patients (median age: 67 (interquartile range: 60-74) years, 204 (59.0%) men), 22 (6.4%) had equivocal ILAs, and 33 (9.5%) had ILAs detected upon baseline CT. Notably, six patients (6/291; 2.1%) without ILAs upon baseline CT later developed ILAs, and 50% (11/22) of those with equivocal ILAs exhibited progression. Furthermore, 75.8% (25/33) of patients with ILAs upon baseline CT exhibited ILA progression (76.9% and 71.4% with fibrotic and non-fibrotic ILAs, respectively). Multivariate analysis revealed that ILA status was a significant risk factor for ILA progression. ILAs and equivocal ILAs were associated with radiologic ILA progression after surgical resection in patients with lung cancer. Hence, early ILA detection can significantly affect clinical outcomes.

Primary pulmonary synovial sarcoma with delayed diagnosis in a 69-year-old man: A case report.

RATIONALE: Primary pulmonary synovial sarcoma is a rare malignant pulmonary tumor accompanied by calcifications in approximately 15% of cases. These calcifications usually have a fine, stippled appearance; coarse shapes have seldom been reported. Moreover, the presence of coarse calcifications often suggests benign tumors, which vastly differ in treatment. We present a rare case of primary pulmonary sarcoma with coarse intratumoral calcifications, the diagnosis of which was delayed because of its radiologic appearance. PATIENT CONCERNS: A computed tomography (CT) scan of a 69-year-old man with right upper quadrant (RUQ) pain revealed an incidental mass at the base of the right lower lobe, the margin of which was not well described with respect to the liver, and intratumoral coarse calcification was noted. Initially, the lesion was believed to be hepatic, and magnetic resonance imaging (MRI) was performed. Based on its imaging features, the mass was thought to be a pulmonary lesion, and a preliminary diagnosis of a benign lesion, such as a hamartoma or granuloma, was made. Four months after the initial CT scan, the patient's RUQ pain had aggravated; however, no change in the mass was observed on follow-up CT. DIAGNOSIS: The final diagnosis was primary pulmonary sarcoma, proven by surgical biopsy. INTERVENTIONS: Wedge resection of the right lower lobe was performed, and the patient received adjuvant chemotherapy. OUTCOMES: The patient's RUQ pain improved, and no recurrence or metastasis has been reported to date. LESSONS: This case describes a rare presentation of a primary pulmonary synovial sarcoma with coarse intratumoral calcifications and the MRI features of the lesion. Intratumoral coarse calcifications often suggest benign lesions, such as hamartomas or post-inflammatory granulomas; however, as malignant lesions cannot be completely excluded, other radiologic and clinical features should be considered carefully. Focal areas of enhancement and eccentric calcification distribution might suggest malignant lesions such as primary pulmonary synovial sarcoma. Furthermore, despite not being used routinely, MRI scans might be helpful because advanced MRI techniques, such as diffusion-weighted imaging, can help distinguish malignant lesions from benign lesions. If the clinical course of a patient suggests malignancy, a more aggressive biopsy strategy should be considered.

Diagnostic Accuracy and Complication of Computed Tomography (CT)-Guided Percutaneous Transthoracic Lung Biopsy in Patients 80 Years and Older.

This research evaluated the diagnostic accuracy and complication rate of computed tomography (CT)-guided percutaneous transthoracic lung biopsy (PTNB) in patients 80 years and older. The study sought to identify risk factors for diagnostic failures or complications of PTNBs. We examined 247 CT-guided PTNBs performed from January 2017 through December 2020, noting patient demographics, lesion or procedure types, pathology reports, and other procedure-related complications. Study groups were divided into two: one with patients aged 80 years and older (Group 1) and the other with patients aged 60 to 80 years (Group 2). The research first determined each groups' diagnostic accuracy, sensitivity, specificity, diagnostic failure rate, and complication rate and then evaluated the risk factors for diagnostic failures and complications. The diagnostic accuracy, sensitivity, specificity, and diagnostic failure rates were 95.6%, 94.9%, 100%, and 18.9%, respectively, in Group 1. The overall and major complication rates in Group 1 were 29.6% and 3.7%, respectively. Lesion size was the only risk factor for diagnostic failure (adjusted odds ratio [OR], 0.46; 95% confidence interval [CI], 0.24-0.90). There was no significant risk factor for complications in Group 1. CT-guided PTNBs in patients 80 years and older indicate comparable diagnostic accuracy and complication rates.

Learning Curve of C-Arm Cone-beam Computed Tomography Virtual Navigation-Guided Percutaneous Transthoracic Needle Biopsy.

OBJECTIVE: To evaluate the learning curve for C-arm cone-beam computed tomography (CBCT) virtual navigation-guided percutaneous transthoracic needle biopsy (PTNB) and to determine the amount of experience needed to develop appropriate skills for this procedure using cumulative summation (CUSUM). MATERIALS AND METHODS: We retrospectively reviewed 2042 CBCT virtual navigation-guided PTNBs performed by 7 novice operators between March 2011 and December 2014. Learning curves for CBCT virtual navigation-guided PTNB with respect to its diagnostic performance and the occurrence of biopsy-related pneumothorax were analyzed using standard and risk-adjusted CUSUM (RA-CUSUM). Acceptable failure rates were determined as 0.06 for diagnostic failure and 0.25 for PTNB-related pneumothorax. RESULTS: Standard CUSUM indicated that 6 of the 7 operators achieved an acceptable diagnostic failure rate after a median of 105 PTNB procedures (95% confidence interval [CI], 14-240), and 6 of the operators achieved acceptable pneumothorax occurrence rate after a median of 79 PTNB procedures (95% CI, 27-155). RA-CUSUM showed that 93 (95% CI, 39-142) and 80 (95% CI, 38-127) PTNB procedures were required to achieve acceptable diagnostic performance and pneumothorax occurrence, respectively. CONCLUSION: The novice operators' skills in performing CBCT virtual navigation-guided PTNBs improved with increasing experience over a wide range of learning periods.

Distinguishing between Thymic Epithelial Tumors and Benign Cysts via Computed Tomography.

OBJECTIVE: To investigate whether computed tomography (CT) and fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) may be applied to distinguish thymic epithelial tumors (TETs) from benign cysts in the anterior mediastinum. MATERIALS AND METHODS: We included 262 consecutive patients with pathologically proven TETs and benign cysts 5 cm or smaller who underwent preoperative CT scans. In addition to conventional morphological and ancillary CT findings, the relationship between the lesion and the adjacent mediastinal pleura was evaluated qualitatively and quantitatively. Mean lesion attenuation was measured on CT images. The maximum standardized uptake value (SUVmax) was obtained with FDG-PET scans in 40 patients. CT predictors for TETs were identified with multivariate logistic regression analysis. For validation, we assessed the diagnostic accuracy and inter-observer agreement between four radiologists in a size-matched set of 24 cysts and 24 TETs using a receiver operating characteristic curve before and after being informed of the study findings. RESULTS: The multivariate analysis showed that post-contrast attenuation of 60 Hounsfield unit or higher (odds ratio [OR], 12.734; 95% confidence interval [CI], 2.506-64.705; p = 0.002) and the presence of protrusion from the mediastinal pleura (OR, 9.855; 95% CI, 1.749-55.535; p = 0.009) were the strongest CT predictors for TETs. SUVmax was significantly higher in TETs than in cysts (5.3 ± 2.4 vs. 1.1 ± 0.3; p < 0.001). After being informed of the study findings, the readers' area under the curve improved from 0.872-0.955 to 0.949-0.999 (p = 0.066-0.149). Inter-observer kappa values for protrusion were 0.630-0.941. CONCLUSION: Post-contrast CT attenuation, protrusion from the mediastinal pleura, and SUVmax were useful imaging features for distinguishing TETs from cysts in the anterior mediastinum.

The Potential Role of Grid-Like Software in Bedside Chest Radiography in Improving Image Quality and Dose Reduction: An Observer Preference Study.

Objective: To compare the observer preference of image quality and radiation dose between non-grid, grid-like, and grid images. Materials and Methods: Each of the 38 patients underwent bedside chest radiography with and without a grid. A grid-like image was generated from a non-grid image using SimGrid software (Samsung Electronics Co. Ltd.) employing deep-learning-based scatter correction technology. Two readers recorded the preference for 10 anatomic landmarks and the overall appearance on a five-point scale for a pair of non-grid and grid-like images, and a pair of grid-like and grid images, respectively, which were randomly presented. The dose area product (DAP) was also recorded. Wilcoxon's rank sum test was used to assess the significance of preference. Results: Both readers preferred grid-like images to non-grid images significantly (p < 0.001); with a significant difference in terms of the preference for grid images to grid-like images (p = 0.317, 0.034, respectively). In terms of anatomic landmarks, both readers preferred grid-like images to non-grid images (p < 0.05). No significant differences existed between grid-like and grid images except for the preference for grid images in proximal airways by two readers, and in retrocardiac lung and thoracic spine by one reader. The median DAP were 1.48 (range, 1.37-2.17) dGy*cm2 in grid images and 1.22 (range, 1.11-1.78) dGy*cm2 in grid-like images with a significant difference (p < 0.001). Conclusion: The SimGrid software significantly improved the image quality of non-grid images to a level comparable to that of grid images with a relatively lower level of radiation exposure.

Application of Deconvolution Algorithm of Point Spread Function in Improving Image Quality: An Observer Preference Study on Chest Radiography.

Objective: To evaluate the preference of observers for image quality of chest radiography using the deconvolution algorithm of point spread function (PSF) (TRUVIEW ART algorithm, DRTECH Corp.) compared with that of original chest radiography for visualization of anatomic regions of the chest. Materials and Methods: Prospectively enrolled 50 pairs of posteroanterior chest radiographs collected with standard protocol and with additional TRUVIEW ART algorithm were compared by four chest radiologists. This algorithm corrects scattered signals generated by a scintillator. Readers independently evaluated the visibility of 10 anatomical regions and overall image quality with a 5-point scale of preference. The significance of the differences in reader's preference was tested with a Wilcoxon's signed rank test. Results: All four readers preferred the images applied with the algorithm to those without algorithm for all 10 anatomical regions (mean, 3.6; range, 3.2-4.0; p < 0.001) and for the overall image quality (mean, 3.8; range, 3.3-4.0; p < 0.001). The most preferred anatomical regions were the azygoesophageal recess, thoracic spine, and unobscured lung. Conclusion: The visibility of chest anatomical structures applied with the deconvolution algorithm of PSF was superior to the original chest radiography.

Erratum: Application of Deconvolution Algorithm of Point Spread Function in Improving Image Quality: An Observer Preference Study on Chest Radiography.

[This corrects the article on p. 147 in vol. 19, PMID: 29354011.].

Monitoring tumor response to the vascular disrupting agent CKD-516 in a rabbit VX2 intramuscular tumor model using PET/MRI: Simultaneous evaluation of vascular and metabolic parameters.

OBJECTIVES: To determine whether the CKD-516 produces a significant change in vascular and metabolic parameters in PET/MRI. MATERIALS AND METHODS: With institutional Animal Care and Use Committee approval, 18 VX2 carcinoma tumors implanted in bilateral back muscles of 9 rabbits were evaluated. Serial PET/MRI were performed before, 4 hours after and 1-week after vascular disrupting agent, CKD-516 at a dose of 0.7 mg/kg (treated group, n = 10) or saline (control group, n = 8) administration. PET/MRI-derived parameters and their interval changes were compared between the treated and control group by using the linear mixed model. Each parameter within each group was also compared by using the linear mixed model. RESULTS: Changes of the volume transfer coefficient (Ktrans) and the initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) in the treated group were significantly larger compared with those in the control group at 4-hour follow-up (mean, -39.91% vs. -6.04%, P = 0.018; and -49.71% vs. +6.23%, P = 0.013). Change of metabolic tumor volume (MTV) in the treated group was significantly smaller compared with that in the control group at 1-week follow-up (mean, +118.34% vs. +208.87%, P = 0.044). Serial measurements in the treated group revealed that Ktrans and iAUC decreased at 4-hour follow-up (P < 0.001) and partially recovered at 1-week follow-up (P = 0.001 and 0.024, respectively). MTV increased at a 4-hour follow-up (P = 0.038) and further increased at a 1-week follow-up (P < 0.001), while total lesion glycolysis (TLG) did not show a significant difference between the time points. SUVmax and SUVmean did not show significant interval changes between time points (P > 0.05). CONCLUSIONS: PET/MRI is able to monitor the changes of vascular and metabolic parameters at different time points simultaneously, and confirmed that vascular changes precede the metabolic changes by VDA, CKD-516.

Improving the prediction of lung adenocarcinoma invasive component on CT: Value of a vessel removal algorithm during software segmentation of subsolid nodules.

PURPOSE: To evaluate the value of a vessel removal algorithm in segmentation of subsolid nodules by comparing the software solid component measurement on CT, before and after vessel removal, with the measurement of the invasive component on pathology in lung adenocarcinomas manifesting as subsolid nodules. MATERIALS AND METHODS: Between January 2014 and June 2015, 73 subsolid nodules with an invasive component of ≤10 mm on pathology were selected for analyses. For each nodule, semi-automated segmentation was performed by 2 radiologists and 3-dimensional (D) longest, axial longest and effective diameters of solid component were obtained from software, before and after using a vessel removal tool. These measurements were compared with the invasive component diameter on pathology using the paired t-test and Pearson's correlation test. RESULTS: Sixty-eight successfully segmented subsolid nodules were included. The mean maximal diameter of the invasive component on pathology was 4.6 mm (range, 0-10 mm). The correlation between software and pathology measurements was significant (p < 0.01) and the correlation after vessel removal (r = 0.49-0.54) was better than before vessel removal (r = 0.27-0.41). The mean measurement difference between solid component on CT and invasive tumor on pathology was significantly larger before vessel removal than after vessel removal in all measurements. The smallest mean measurement difference was obtained with 3D longest diameter of solid component after vessel removal in both readers (-0.26 mm to 0.10 mm), with no significant difference from pathology (p = 0.53-0.83). CONCLUSION: By adding a vessel removal algorithm in software segmentation of subsolid nodules, the prediction of invasive component in lung adenocarcinomas can be improved.

Bronchovascular injury associated with clinically significant hemoptysis after CT-guided core biopsy of the lung: Radiologic and histopathologic analysis.

OBJECTIVE: To evaluate bronchovascular injuries as the causative occurrence for clinically significant hemoptysis after percutaneous transthoracic needle biopsy (PTNB). MATERIALS AND METHODS: We included 111 consecutive patients who experienced hemoptysis after cone beam CT (CBCT)-guided PTNB from January 2014 through January 2017. Clinically significant hemoptysis was defined as hemoptysis causing hemodynamic instability or oxygen desaturation greater than 10% of baseline. The lesion characteristics were evaluated on CT images. The penetration of bronchovascular structures along the trajectory of the introducer needle and potential penetration at the firing of the biopsy gun were assessed on CBCT images. The cutting injury of bronchovascular structures was histopathologically assessed in biopsy specimens. The associated factors for clinically significant hemoptysis were assessed using logistic regression analyses. RESULTS: Seventeen patients (15.3%; 95%CI, 9.7%-23.2%) had clinically significant hemoptysis. On univariate analysis, the open bronchus sign (P = .004), nodule consistency (P = .012), potential penetration of a pulmonary vessel or bronchus 1 mm or larger at firing (P = .008 and P = .038, respectively), and a cutting injury of a pulmonary vessel 1 mm or larger (P = .007) or a bronchial structure (P = .041) were associated with clinically significant hemoptysis. Multivariate analysis found the following significant associated factors: potential penetration of a pulmonary vessel 1 mm or larger at firing (OR, 3.874; 95%CI, 1.072-13.997; P = .039) and cutting injury of a pulmonary vessel 1 mm or larger (OR, 6.920; 95%CI, 1.728-27.711; P = .006) or a bronchial structure (OR 4.604; 95%CI, 1.194-17.755; P = .027). CONCLUSION: Potential penetration and cutting injury of bronchovascular structures 1mm or larger at firing were independently associated with clinically significant hemoptysis after PTNB.

Open Bronchus Sign on CT: A Risk Factor for Hemoptysis after Percutaneous Transthoracic Biopsy.

Objective: We hypothesized that open bronchi within target pulmonary lesions are associated with percutaneous transthoracic needle biopsy (PTNB)-related hemoptysis. We sought to analyze and compare patient characteristics and target features as well as biopsy-related factors between patients with and without PTNB-related hemoptysis. Materials and Methods: We retrospectively analyzed 1484 patients (870 males and 614 females; median age, 66 years) who had undergone 1569 cone-beam CT (CBCT)-guided PTNBs. Patient characteristics (sex, age, and pathologic diagnosis), nodule features (nodule type, size, location, and presence of an open bronchus in target nodules), and biopsy-related factors (biopsy needle size, pleura-to-target distance, blood test results, open bronchus unavoidability [OBU] index, etc.) were investigated. OBU index, which was assessed using the pre-procedural CBCT, was a subjective scoring system for the probability of needle penetration into the open bronchus. Univariate analysis and subsequent multivariate logistic regression analysis were conducted to reveal the independent risk factors for PTNB-related hemoptysis. For a subgroup of nodules with open bronchi, a trend analysis between the occurrence of hemoptysis and the OBU index was performed. Results: The independent risk factors for hemoptysis were sex (female; odds ratio [OR], 1.918; p < 0.001), nodule size (OR, 0.837; p < 0.001), open bronchus (OR, 2.101; p < 0.001), and pleura-to-target distance (OR, 1.135; p = 0.003). For the target nodules with open bronchi, a significant trend between hemoptysis and OBU index (p < 0.001) was observed. Conclusion: An open bronchus in a biopsy target is an independent predictor of hemoptysis, and careful imaging review may potentially reduce PTNB-related hemoptysis.

Validation of prediction models for risk stratification of incidentally detected pulmonary subsolid nodules: a retrospective cohort study in a Korean tertiary medical centre.

OBJECTIVES: To validate the performances of two prediction models (Brock and Lee models) for the differentiation of minimally invasive adenocarcinoma (MIA) and invasive pulmonary adenocarcinoma (IPA) from preinvasive lesions among subsolid nodules (SSNs). DESIGN: A retrospective cohort study. SETTING: A tertiary university hospital in South Korea. PARTICIPANTS: 410 patients with 410 incidentally detected SSNs who underwent surgical resection for the pulmonary adenocarcinoma spectrum between 2011 and 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: Using clinical and radiological variables, the predicted probability of MIA/IPA was calculated from pre-existing logistic models (Brock and Lee models). Areas under the receiver operating characteristic curve (AUCs) were calculated and compared between models. Performance metrics including sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were also obtained. RESULTS: For pure ground-glass nodules (n=101), the AUC of the Brock model in differentiating MIA/IPA (59/101) from preinvasive lesions (42/101) was 0.671. Sensitivity, specificity, accuracy, PPV and NPV based on the optimal cut-off value were 64.4%, 64.3%, 64.4%, 71.7% and 56.3%, respectively. Sensitivity, specificity, accuracy, PPV and NPV according to the Lee criteria were 76.3%, 42.9%, 62.4%, 65.2% and 56.3%, respectively. AUC was not obtained for the Lee model as a single cut-off of nodule size (≥10 mm) was suggested by this model for the assessment of pure ground-glass nodules. For part-solid nodules (n=309; 26 preinvasive lesions and 283 MIA/IPAs), the AUC was 0.746 for the Brock model and 0.771 for the Lee model (p=0.574). Sensitivity, specificity, accuracy, PPV and NPV were 82.3%, 53.8%, 79.9%, 95.1% and 21.9%, respectively, for the Brock model and 77.0%, 69.2%, 76.4%, 96.5% and 21.7%, respectively, for the Lee model. CONCLUSIONS: The performance of prediction models for the incidentally detected SSNs in differentiating MIA/IPA from preinvasive lesions might be suboptimal. Thus, an alternative risk calculation model is required for the incidentally detected SSNs.