Interstitial Lung Abnormalities at CT in the Korean National Lung Cancer Screening Program: Prevalence and Deep Learning-based Texture Analysis.

Background Interstitial lung abnormalities (ILAs) are associated with worse clinical outcomes, but ILA with lung cancer screening CT has not been quantitatively assessed. Purpose To determine the prevalence of ILA at CT examinations from the Korean National Lung Cancer Screening Program and define an optimal lung area threshold for ILA detection with CT with use of deep learning-based texture analysis. Materials and Methods This retrospective study included participants who underwent chest CT between April 2017 and December 2020 at two medical centers participating in the Korean National Lung Cancer Screening Program. CT findings were classified by three radiologists into three groups: no ILA, equivocal ILA, and ILA (fibrotic and nonfibrotic). Progression was evaluated between baseline and last follow-up CT scan. The extent of ILA was assessed visually and quantitatively with use of deep learning-based texture analysis. The Youden index was used to determine an optimal cutoff value for detecting ILA with use of texture analysis. Demographics and ILA subcategories were compared between participants with progressive and nonprogressive ILA. Results A total of 3118 participants were included in this study, and ILAs were observed with the CT scans of 120 individuals (4%). The median extent of ILA calculated by the quantitative system was 5.8% for the ILA group, 0.7% for the equivocal ILA group, and 0.1% for the no ILA group (P < .001). A 1.8% area threshold in a lung zone for quantitative detection of ILA showed 100% sensitivity and 99% specificity. Progression was observed in 48% of visually assessed fibrotic ILAs (15 of 31), and quantitative extent of ILA increased by 3.1% in subjects with progression. Conclusion ILAs were detected in 4% of the Korean lung cancer screening population. Deep learning-based texture analysis showed high sensitivity and specificity for detecting ILA with use of a 1.8% lung area cutoff value. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Egashira and Nishino in this issue.

Analysis of background echotexture on automated breast ultrasound using BI-RADS and modified classification: Association with clinical features and mammographic density.

PURPOSE: To analyze BE on ABUS using BI-RADS and a modified classification in association with mammographic density and clinical features. METHODS: Menopausal status, parity, and family history of breast cancer were collected for 496 women who underwent ABUS and mammography. Three radiologists independently reviewed all ABUS BE and mammographic density. Statistical analyses including kappa statistics (κ) for interobserver agreement, Fisher's exact test, and univariate and multivariate multinomial logistic regression were performed. RESULTS: BE distribution between the two classifications and between each classification and mammographic density were associated (P < 0.001). BI-RADS homogeneous-fibroglandular (76.8%) and modified heterogeneous BE (71.3%, 75.7%, and 87.5% of mild, moderate, and marked heterogeneous background echotexture, respectively) tended to be dense. BE was correlated between BI-RADS homogeneous-fat and modified homogeneous background (95.1%) and between BI-RADS homogeneous-fibroglandular or heterogeneous (90.6%) and modified heterogeneous (86.9%) (P < 0.001). In multinomial logistic regression, age < 50 years was independently associated with heterogeneous BE (OR, 8.89, P = 0.003, in BI-RADS; OR, 3.74; P = 0.020 in modified classification). CONCLUSION: BI-RADS homogeneous-fat and modified homogeneous BE on ABUS was likely to be mammographically fatty. However, BI-RADS homogeneous-fibroglandular or heterogeneous BE might be classified as any modified BE. Younger age was independently associated with heterogeneous BE.

Investigation of the putative role of antisense transcripts as regulators of sense transcripts by correlation analysis of sense-antisense pairs in colorectal cancers.

Antisense transcription occurs widely more expected than when it was first identified in bacteria in the 1980s. However, the functional relevance of antisense transcripts in transcription remains controversial. Here, we investigated the putative role of antisense transcripts in regulating their corresponding sense transcripts by analyzing changes in correlative relationships between sense-antisense pairs under tumor and normal conditions. A total of 3469 sense-antisense gene pairs (SAGPs) downloaded from BioMart mapped to a list of sense and antisense genes in RNA-seq data derived from 80 paired colorectal cancer (CRC) samples were analyzed. As a result, cancer-related genes were significantly enriched in the significantly correlated SAGPs (SCPs). Differentially expressed genes estimated between normal and tumor conditions were also significantly more enriched in SCPs than in non-SCPs. Interestingly, using differential correlation analysis, we found that tumor samples had a significantly larger density of genes with higher correlation coefficients than normal samples, as verified by various cancer transcriptomes from The Cancer Genome Atlas (TCGA). Moreover, we found that the magnitude of the correlation between SAGPs could distinguish poor prognostic CRCs from good prognostic CRCs, showing that correlation coefficients between the SAGPs of CRCs with a poor prognosis were significantly stronger than CRCs with a good prognosis. Consistent with this finding, the Cox proportion hazards model showed that the survival rates were significantly different between patients with high and low expression of genes in the SCPs. All these results strongly support the idea that antisense transcripts are important regulators of their corresponding sense transcripts.

Radiologic-pathologic correlation of interstitial lung abnormalities and predictors for progression and survival.

OBJECTIVES: To evaluate radiologic and histologic correlations for interstitial lung abnormalities (ILAs) and to investigate radiologic or pathologic features contributing to disease progression and mortality. METHODS: From 268 patients who underwent surgical lung biopsy between January 2004 and April 2019, 45 patients with incidentally detected ILA and normal pulmonary function were retrospectively included. CT features were classified as subpleural fibrotic or non-fibrotic, and changes in ILA over at least 2 years of follow-up were evaluated. Histologic findings were categorized as definite, probable, indeterminate, or alternative diagnosis for usual interstitial pneumonia (UIP) patterns. Overall and progression-free survival were calculated using the Kaplan-Meier method, and the Cox proportional hazard method was used to examine predictors for ILA progression and survival. RESULTS: Among 36 subpleural fibrotic ILA subjects, 25 (69%) showed definite or probable UIP patterns, and 89% (8/9) of subpleural non-fibrotic ILA subjects showed an indeterminate or alternative diagnosis for UIP pattern on histopathology. On the radiologic-pathologic correlation, reticular opacity of fibrotic ILA was correlated with patchy involvement of fibrosis, and ground-glass attenuation of non-fibrotic ILA corresponded to diffuse interstitial thickening. The median progression time of ILA was 54 months, and fibrotic ILA increased the likelihood of progression (hazard ratio, 2.42; p = 0.017). The median survival time of ILA subjects was 123 months, and fibrotic ILA was associated with an increased risk of death (hazard ratio, 9.22; p = 0.025). CONCLUSIONS: Subpleural fibrotic ILAs are associated with pathologic UIP patterns, and it is important to recognize subpleural fibrotic ILA on CT to predict disease progression and mortality. KEY POINTS: • In total, 69% of subpleural fibrotic ILA showed definite or probable UIP patterns, while 11% of subpleural non-fibrotic ILA showed definite or probable UIP patterns. • Subpleural fibrotic ILA was associated with an increased rate of progression (hazard ratio, 2.42; p = 0.017), and the median progression-free time was 40 months. • Subpleural fibrotic ILA had an increased risk of death (hazard ratio, 9.22; p = 0.025), and the median survival time was 86 months.

Dynamic contrast-enhanced and diffusion-weighted MRI of invasive breast cancer for the prediction of sentinel lymph node status.

BACKGROUND: Although sentinel lymph node biopsy (SLNB) is the current standard for identifying lymph metastasis in breast cancer patients, there are complications of SLNB. PURPOSE: To evaluate preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) of invasive breast cancer for predicting sentinel lymph node metastasis. STUDY TYPE: Retrospective. POPULATION: In all, 309 patients who underwent clinically node-negative invasive breast cancer surgery FIELD STRENGTH/SEQUENCE: 3.0T, DCE-MRI, DWI. ASSESSMENT: We collected clinicopathologic variables (age, histologic and nuclear grade, extensive intraductal carcinoma component, lymphovascular invasion, and immunohistochemical profiles) and preoperative MRI features (tumor size, background parenchymal enhancement, internal enhancement, adjacent vessel sign, whole-breast vascularity, initial enhancement pattern, kinetic curve types, quantitative kinetic parameters, tumoral apparent diffusion coefficient [ADC], peritumoral maximal ADC, and peritumoral-tumoral ADC ratio). STATISTICAL TESTS: Multivariate logistic regressions were performed to determine independent variables associated with SLN metastasis, and the area under the receiver operating characteristic curve (AUC) was analyzed for those variables. RESULTS: 41 (13.3%) of the patients showed SLN metastasis. With MRI, tumor size (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.06-1.17), heterogeneous (OR, 5.33; 95% CI, 1.71-16.58), and rim (OR, 15.54; 95% CI, 2.12-113.72) enhancement and peritumoral-tumoral ADC ratio (OR, 72.79; 95% CI, 7.15-740.82) were independently associated with SLN metastasis. Clinicopathologic variables independently associated with SLN metastasis included age (OR, 0.96; 95% CI, 0.92-0.99) and CD31 (OR, 2.90; 95% CI, 1.04-8.92). The area under the curve (AUC) of MRI features (0.80; 95% CI, 0.73-0.87) was significantly higher than for clinicopathologic variables (0.68; 95% CI, 0.60-0.77; P = 0.048) and was barely below statistical significance for combined MRI features with clinicopathologic variables (0.84; 95% CI 0.78-0.90, P = 0.057). DATA CONCLUSION: Preoperative internal enhancement on DCE-MRI and peritumoral-tumoral ADC ratio on DWI might be useful for predicting SLN metastasis in patients with invasive breast cancer. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:615-626.

LI-RADS v2014 categorization of hepatocellular carcinoma: Intraindividual comparison between gadopentetate dimeglumine-enhanced MRI and gadoxetic acid-enhanced MRI.

OBJECTIVES: To use Liver Imaging Reporting and Data System (LI-RADS) categorization and features of hepatocellular carcinomas (HCCs) to intraindividually compare gadopentetate dimeglumine-enhanced magnetic resonance imaging (Gd-DTPA-MRI) and gadoxetic acid-enhanced MRI (Gd-EOB-MRI), before and after applying modified major features. METHODS: Of 77 HCCs in 64 patients analysed, 17 HCCs were confirmed histopathologically and 46 patients had cirrhosis. Gd-EOB-MRI and Gd-DTPA-MRI were evaluated for the presence of major and ancillary features by two radiologists. LI-RADS categorization was done for Gd-DTPA-MRI (LI-RADS-DTPA) and for Gd-EOB-MRI before and after applying modified major features (hepatobiliary phase [HBP] hypointensity as an additional major feature, LI-RADS-EOBm1; HBP hypointense rim as capsule appearance, LI-RADS-EOBm2; and transitional phase [TP] hypointensity as washout appearance, LI-RADS-EOBm3). Sensitivities of LR-5 categorization for the diagnosis of HCC were compared. RESULTS: Washout (p=0.012) and capsule appearance (p<0.001) were less frequently observed on Gd-EOB-MRI. Sensitivity for LR-5 categorization was significantly higher with LI-RADS-DTPA compared with LI-RADS-EOB (p=0.001) and LI-RADS-EOBm2 (p=0.004), while sensitivity for LR-5 categorization with LI-RADS-EOBm1 (p=0.210) and LI-RADS-EOBm3 (p=0.727) was comparable. CONCLUSION: Modifying LI-RADS for use with Gd-EOB-MRI, such as applying HBP hypointensity as an additional major feature or using TP hypointensity as washout appearance, can improve the sensitivity for the detection of HCC. KEY POINTS: • Adding HBP hypointensity as additional major feature improved sensitivity of LR-5 categorization. • Adding TP hypointensity as modified washout appearance improved sensitivity of LR-5 categorization. • Sensitivities for LR-5 classification were comparable between LI-RADS-DTPA, LI-RADS-EOBm1, and LI-RADS-EOBm3.

Comparison of Diagnostic Performance between Classic and Modified Abbreviated Breast MRI and the MRI Features Affecting Their Diagnostic Performance.

Abbreviated breast magnetic resonance imaging (AB-MRI) has emerged as a supplementary screening tool, though protocols have not been standardized. The purpose of this study was to compare the diagnostic performance of modified and classic AB-MRI and determine MRI features affecting their diagnostic performance. Classic AB-MRI included one pre- and two post-contrast T1-weighted imaging (T1WI) scans, while modified AB-MRI included a delayed post-contrast axial T1WI scan and an axial T2-weighted interpolated scan obtained between the second and third post-contrast T1WI scans. Four radiologists (two specialists and two non-specialists) independently categorized the lesions. The MRI features investigated were lesion size, lesion type, and background parenchymal enhancement (BPE). The Wilcoxon rank-sum test, Fisher's exact test, and bootstrap-based test were used for statistical analysis. The average area under the curve (AUC) for modified AB-MRI was significantly greater than that for classic AB-MRI (0.76 vs. 0.70, p = 0.010) in all reader evaluations, with a similar trend in specialist evaluations (0.83 vs. 0.76, p = 0.004). Modified AB-MRI demonstrated increased AUCs and better diagnostic performance than classic AB-MRI, especially for lesion size > 10 mm (p = 0.018) and mass lesion type (p = 0.014) in specialist evaluations and lesion size > 10 mm (p = 0.003) and mild (p = 0.026) or moderate BPE (p = 0.010) in non-specialist evaluations.

Diagnostic Accuracy of Magnetic Resonance Imaging Features and Tumor-to-Nipple Distance for the Nipple-Areolar Complex Involvement of Breast Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis evaluated the accuracy of preoperative breast magnetic resonance imaging (MRI) features and tumor-to-nipple distance (TND) for diagnosing occult nipple-areolar complex (NAC) involvement in breast cancer. MATERIALS AND METHODS: The MEDLINE, Embase, and Cochrane databases were searched for articles published until March 20, 2022, excluding studies of patients with clinically evident NAC involvement or those treated with neoadjuvant chemotherapy. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Two reviewers independently evaluated studies that reported the diagnostic performance of MRI imaging features such as continuity to the NAC, unilateral NAC enhancement, non-mass enhancement (NME) type, mass size (> 20 mm), and TND. Summary estimates of the sensitivity and specificity curves and the summary receiver operating characteristic (SROC) curve of the MRI features for NAC involvement were calculated using random-effects models. We also calculated the TND cutoffs required to achieve predetermined specificity values. RESULTS: Fifteen studies (n = 4002 breast lesions) were analyzed. The pooled sensitivity and specificity (with 95% confidence intervals) for NAC involvement diagnosis were 71% (58-81) and 94% (91-96), respectively, for continuity to the NAC; 58% (45-70) and 97% (95-99), respectively, for unilateral NAC enhancement; 55% (46-64) and 83% (75-88), respectively, for NME type; and 88% (68-96) and 58% (40-75), respectively, for mass size (> 20 mm). TND had an area under the SROC curve of 0.799 for NAC involvement. A TND of 11.5 mm achieved a predetermined specificity of 85% with a sensitivity of 64%, and a TND of 12.3 mm yielded a predetermined specificity of 83% with a sensitivity of 65%. CONCLUSION: Continuity to the NAC and unilateral NAC enhancement may help predict occult NAC involvement in breast cancer. To achieve the desired diagnostic performance with TND, a suitable cutoff value should be considered.

Development of a Breast Cancer Risk Prediction Model Incorporating Polygenic Risk Scores and Nongenetic Risk Factors for Korean Women.

BACKGROUND: To develop a breast cancer prediction model for Korean women using published polygenic risk scores (PRS) combined with nongenetic risk factors (NGRF). METHODS: Thirteen PRS models generated from single or multiple combinations of the Asian and European PRSs were evaluated among 20,434 Korean women. The AUC and increase in OR per SD were compared for each PRS. The PRSs with the highest predictive power were combined with NGRFs; then, an integrated prediction model was established using the Individualized Coherent Absolute Risk Estimation (iCARE) tool. The absolute breast cancer risk was stratified for 18,142 women with available follow-up data. RESULTS: PRS38_ASN+PRS190_EB, a combination of Asian and European PRSs, had the highest AUC (0.621) among PRSs, with an OR per SD increase of 1.45 (95% confidence interval: 1.31-1.61). Compared with the average risk group (35%-65%), women in the top 5% had a 2.5-fold higher risk of breast cancer. Incorporating NGRFs yielded a modest increase in the AUC of women ages >50 years. For PRS38_ASN+PRS190_EB+NGRF, the average absolute risk was 5.06%. The lifetime absolute risk at age 80 years for women in the top 5% was 9.93%, whereas that of women in the lowest 5% was 2.22%. Women at higher risks were more sensitive to NGRF incorporation. CONCLUSIONS: Combined Asian and European PRSs were predictive of breast cancer in Korean women. Our findings support the use of these models for personalized screening and prevention of breast cancer. IMPACT: Our study provides insights into genetic susceptibility and NGRFs for predicting breast cancer in Korean women.

The Value of the Illness-Death Model for Predicting Outcomes in Patients with Non-Small Cell Lung Cancer.

PURPOSE: The illness-death model (IDM) is a comprehensive approach to evaluate the relationship between relapse and death. This study aimed to illustrate the value of the IDM for identifying risk factors and evaluating predictive probabilities for relapse and death in patients with non-small cell lung cancer (NSCLC) in comparison with the disease-free survival (DFS) model. MATERIALS AND METHODS: We retrospectively analyzed 612 NSCLC patients who underwent a curative operation. Using the IDM, the risk factors and predictive probabilities for relapse, death without relapse, and death after relapse were simultaneously evaluated and compared to those obtained from a DFS model. RESULTS: The IDM provided more detailed risk factors according to the patient's disease course, including relapse, death without relapse, and death after relapse, in patients with resected lung cancer. In the IDM, history of malignancy (other than lung cancer) was related to relapse and smoking history was associated with death without relapse; both were indistinguishable in the DFS model. In addition, the IDM was able to evaluate the predictive probability and risk factors for death after relapse; this information could not be obtained from the DFS model. CONCLUSION: Compared to the DFS model, we found that the IDM provides more comprehensive information on transitions between states and disease stages and provides deeper insights with respect to understanding the disease process among lung cancer patients.

Prognosis and recurrence patterns in patients with early stage lung cancer: a multi-state model approach.

Background: We aimed to assess whether recurrence patterns affect survival and to use a multi-state model to predict the prognosis of early stage non-small cell lung cancer in patients who underwent surgical resection. Methods: Patients with early stage non-small cell lung cancer who underwent surgical resection at two tertiary medical centers between 2010 and 2015 were retrospectively analyzed. A multi-state model was employed with one initial state (surgery), two intermediate states (locoregional recurrence, distant metastasis), and one absorbing state (death), comprising five transitions: surgery to locoregional recurrence, surgery to distant metastasis, surgery to death without recurrence, locoregional recurrence to death, and distant metastasis to death. Cox proportional hazards models stratified for these transitions were performed with the risk factors; transition probabilities for each patient were predicted. Results: A total of 949 patients were identified [median age: 67 years, male: 614 (64.6%)]. Recurrence occurred in 194 (20.4%) patients (locoregional recurrence: 7.3%, distant metastasis: 13.1%). Hazard ratios for distant metastasis after surgery were higher for older age (hazard ratio: 1.03, 95% confidence interval: 1.01-1.06) and adenocarcinoma (hazard ratio: 1.67, 95% confidence interval: 1.06-2.61). Lower lobe location exhibited a higher hazard ratio for death after surgery without recurrence (hazard ratio: 1.59, 95% confidence interval: 1.00-2.53). Stage IIB lung cancer showed a higher probability of transition to distant metastasis after surgery than other stages. Cumulative transition hazards rapidly increased in both recurrence patterns until approximately two years after surgery (locoregional recurrence: 0.052; distant metastasis: 0.104). Patients with distant metastasis were more likely to die within 5 years of surgery than those with locoregional recurrence (6.8% and 2.6%, respectively). Conclusions: With the multi-state model, risk factors and post-relapse survival probabilities differed between locoregional recurrence and distant metastasis. These findings may enable clinicians to establish personalized follow-up strategies for patients undergoing curative resection for early stage non-small cell lung cancer.

Generation-based study of airway remodeling in smokers with normal-looking CT with normalization to control inter-subject variability.

PURPOSE: With the help of quantitative computed tomography (QCT), it is possible to identify smoking-associated airway remodeling. However, there is currently little information on whether QCT-based airway metrics are sensitive to early airway wall remodeling in subclinical phases of smoking-associated airway disease. This study aimed to evaluate a predictive model that normalized airway parameters and investigate structural airway alterations in smokers with normal-looking CT using the normalization scheme. METHODS: In this retrospective analysis, 222 non-smokers (male 97, female 125) and 69 smokers (male 66, female 3) from January 2014 to December 2016 were included, and airway parameters were quantitatively analyzed. To control inter-subject variability, multiple linear regressions of tracheal wall thickness (WT), diameter (D), and luminal area (LA) were performed, adjusted for age, sex, and height. Using this normalization scheme, airway parameters with matched generation were compared between smokers and non-smokers. RESULTS: Using the normalization scheme, it was possible to assess generation-based structural alterations of the airways in subclinical smokers. Smokers showed diffuse luminal narrowing of airways for most generations (P < 0.05, except 3rd generation), no change in wall thickness of the proximal bronchi (1st-3rd generation), and a thinning of distal airways (P <0.05, ≥4th generation). CONCLUSION: QCT assessment for subclinical smokers can help identify minimal structural changes in airways induced by smoking.

A genome-wide association study of quantitative computed tomographic emphysema in Korean populations.

Emphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema severity and characterize the potential function of the associated loci in Korean population. We performed a genome-wide association study (GWAS) on quantitative emphysema in subjects with or without COPD from two Korean COPD cohorts. We investigated the functional consequences of the loci using epigenetic annotation and gene expression data. We also compared our GWAS results with an epigenome-wide association study and previous differential gene expression analysis. In total, 548 subjects (476 [86.9%] male) including 514 COPD patients were evaluated. We identified one genome-wide significant SNP (P < 5.0 × 10-8), rs117084279, near PIBF1. We identified an additional 57 SNPs (P < 5.0 × 10-6) associated with emphysema in all subjects, and 106 SNPs (P < 5.0 × 10-6) in COPD patients. Of these candidate SNPs, 2 (rs12459249, rs11667314) near CYP2A6 were expression quantitative trait loci in lung tissue and a SNP (rs11214944) near NNMT was an expression quantitative trait locus in whole blood. Of note, rs11214944 was in linkage disequilibrium with variants in enhancer histone marks in lung tissue. Several genes near additional SNPs were identified in our previous EWAS study with nominal level of significance. We identified a novel SNP associated with quantitative emphysema on CT. Including the novel SNP, several candidate SNPs in our study may provide clues to the genetic etiology of emphysema in Asian populations. Further research and validation of the loci will help determine the genetic factors for the development of emphysema.

Deep Learning for the Classification of Small (≤2 cm) Pulmonary Nodules on CT Imaging: A Preliminary Study.

RATIONALE AND OBJECTIVES: We aimed to present a deep learning-based malignancy prediction model (CT-lungNET) that is simpler and faster to use in the diagnosis of small (≤2 cm) pulmonary nodules on nonenhanced chest CT and to preliminarily evaluate its performance and usefulness for human reviewers. MATERIALS AND METHODS: A total of 173 whole nonenhanced chest CT images containing 208 pulmonary nodules (94 malignant and 11 benign nodules) ranging in size from 5 mm to 20 mm were collected. Pathologically confirmed nodules or nodules that remained unchanged for more than 1 year were included, and 30 benign and 30 malignant nodules were randomly assigned into the test set. We designed CT-lungNET to include three convolutional layers followed by two fully-connected layers and compared its diagnostic performance and processing time with those of AlexNET by using the area under the receiver operating curve (AUROC). An observer performance test was conducted involving eight human reviewers of four different groups (medical students, physicians, radiologic residents, and thoracic radiologists) at test 1 and test 2, referring to the CT-lungNET's malignancy prediction rate with pairwise comparison receiver operating curve analysis. RESULTS: CT-lungNET showed an improved AUROC (0.85; 95% confidence interval: 0.74-0.93), compared to that of the AlexNET (0.82; 95% confidence interval: 0.71-0.91). The processing speed per one image slice for CT-lungNET was about 10 times faster than that for AlexNET (0.90 vs. 8.79 seconds). During the observer performance test, the classification performance of nonradiologists was increased with the aid of CTlungNET, (mean AUC improvement: 0.13; range: 0.03-0.19) but not significantly so in the radiologists group (mean AUC improvement: 0.02; range: -0.02 to 0.07). CONCLUSION: CT-lungNET was able to provide better classification results with a significantly shorter amount of processing time as compared to AlexNET in the diagnosis of small pulmonary nodules on nonenhanced chest CT. In this preliminary observer performance test, CT-lungNET may have a role acting as a second reviewer for less experienced reviewers, resulting in enhanced performance in the diagnosis of early lung cancer.

Epigenome-Wide Association Analysis of Differentially Methylated Signals in Blood Samples of Patients with Non-Small-Cell Lung Cancer.

Lung cancer is a common form of cancer and the leading cause of cancer-related deaths worldwide. Early diagnosis using noninvasive biomarkers may play an important role in increasing the survival rate of patients with lung cancer. Biomarkers of DNA methylation in blood samples may improve the early diagnosis of lung cancer. Here, we used peripheral blood samples obtained from 150 patients diagnosed with non-small-cell lung cancer (NSCLC) and 150 healthy controls. The latter were selected by frequency matching with the 150 patients with NSCLC, based on age, sex, and smoking status. Genome-wide methylation profiles were obtained using a MethylationEPIC BeadChip Kit, which covers the 850k bp cytosine-phosphate-guanine site. This analysis showed two significant differentially methylated changes (cg12169243 [DPH6] and cg25429010 [IMP3]) associated with NSCLC in current smokers, six changes (cg09245319, cg17183999 [USP7], cg06366994 [CPE], cg24992236 [MEG9], cg22144719, and cg22448179 [epidermal growth factor receptor]) associated with epidermal growth factor receptor mutation in patients with adenocarcinoma, and four changes (cg25021476 [RSL24D1], cg04989085 [FAM113B], cg20905681 [CKAP4], and cg26379694) associated with advanced-stage NSCLC compared with stage I NSCLC. The validation of these DNA methylation changes and further research on the related genes may help develop easily accessible biomarkers for the early diagnosis or prognosis of NSCLC.

Hypovascular hypointense nodules in hepatobiliary phase without T2 hyperintensity: long-term outcomes and added value of DWI in predicting hypervascular transformation.

PURPOSE: To evaluate outcomes and risk factors associated with hypervascularization in hypovascular, hepatobiliary phase (HBP) hypointense nodules (HHNs) without T2 hyperintensity on gadoxetic acid-enhanced magnetic resonance (MR) images in chronic liver disease patients. MATERIALS AND METHODS: 222 HHNs were analyzed. Multivariate analysis with a Cox proportional hazard regression model was used. RESULTS: 41 nodules became hypervascular hepatocellular carcinoma (HCC). History of HCC, hyperintensity on T1WI or DWI, and higher growth rate were risk factors for hypervascularization (P < .05). CONCLUSION: History of HCC, hyperintensity on T1WI or DWI, and higher growth rate were associated with nodular progression to hypervascular HCC.

Evaluation of an automated breast volume scanner according to the fifth edition of BI-RADS for breast ultrasound compared with hand-held ultrasound.

OBJECTIVES: To investigate the automated breast volume scanner (ABVS) in comparison with hand-held ultrasound (HHUS) according to the fifth edition of BI-RADS ultrasound. MATERIAL AND METHODS: A total of 831 lesions in 786 patients who underwent both HHUS and ABVS were included. Three radiologists independently evaluated the sonographic features of each lesion according to the fifth BI-RADS edition. The kappa coefficient (κ) was calculated for each BI-RADS descriptor and final assessment category. The accuracy of malignancy prediction and diagnostic performance of the BI-RADS descriptors were assessed using multivariate logistic regression and area under the receiver operator characteristic curve (AUC), respectively. RESULTS: ABVS and HHUS showed moderate to good interobserver agreement (κ = 0.53-0.67 and 0.55-0.70, respectively) except in associated features (κ = 0.31 and 0.36, respectively) for BI-RADS lexicons. Irregular shape, a non-circumscribed margin, and posterior features (combined or shadowing) were independently associated with malignancy in both ABVS and HHUS. Calcification presence on ABVS (odds ratio [OR], 95% confidence interval [CI]: 2.09, 1.11-3.94) and non-parallel orientation on HHUS (OR, 95% CI: 2.04, 1.10-3.78) were independently associated with malignancy. There were no significant differences between ABVS and HHUS in sensitivity (84.2% vs. 84.2%), specificity (80.5% vs. 83.9%), or AUC (0.88 vs. 0.90). CONCLUSIONS: According to the fifth BI-RADS edition, ABVS is not statistically significantly different from HHUS with regard to interobserver variability and diagnostic performance.

Polymorphisms of miR-146a, miR-149, miR-196a2, and miR-499 are associated with osteoporotic vertebral compression fractures in Korean postmenopausal women.

Genetic factors have been shown to be a small but significant predictor for osteoporosis and osteoporotic fracture risk. We performed a case-control association study to determine the association between miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms and osteoporotic vertebral compression fracture (OVCF) susceptibility. In total, 286 unrelated postmenopausal Korean women (57 with OVCFs, 55 with non-OVCFs, and 174 healthy controls) were recruited. All subjects underwent dual energy X-ray absorptiometry to determine BMD at the lumbar spine and femoral neck. We focused on four single nucleotide polymorphisms (SNPs) of pre-miRNA sequences including miR-146aC>G (rs2910164), miR-149T>C (rs2292832), miR-196a2T>C (rs11614913), and miR-499A>G (rs3746444). Genotype frequencies of these four SNPs were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. The TT genotype of miR-149aT>C was less frequent in subjects with OVCFs, suggesting a protective effect against OVCF risk (Odds ratio [OR], 0.435; 95% confidence interval [CI], 0.22-0.85, p = 0.014), whereas the miR-146aCG/ miR-196a2TC combined genotype was more frequent in OVCF patients (OR, 5.163; 95%CI, 1.057-25.21, p = 0.043), suggesting an increase in OVCF risk. Additionally, combinations of miR-146a, -149, -196a2, and -449 showed a significant association with increased prevalence of OVCFs in postmenopausal women. In particular, the miR-146aG/-149T/-196a2C/-449G allele combination was significantly associated with an increased risk of OVCF (OR, 35.01; 95% CI, 1.919-638.6, p = 0.001). Our findings suggest that the TT genotype of miR-149aT>C may contribute to decreased susceptibility to OVCF in Korean postmenopausal women. Conversely, the miR-146aCG/ miR-196a2TC combined genotype and the miR-146aG/-149T/-196a2C/-449G allele combination may contribute to increased susceptibility to OVCF. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:244-253, 2018.

Dynamic contrast-enhanced breast magnetic resonance imaging for the prediction of early and late recurrences in breast cancer.

The aim of the study was to evaluate dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) features for the prediction of early and late recurrences in patients with breast cancer.Of 1030 breast cancer patients who underwent surgery at our hospital from January 2007 to July 2011, 83 recurrent breast cancer patients were enrolled in this study. We compared MRI features (background parenchymal enhancement [BPE], internal enhancement, adjacent vessel sign, whole-breast vascularity, initial enhancement pattern, kinetic curve types, and quantitative kinetic parameters) and clinico-pathologic variables (age, stage, histologic grade, nuclear grade, existence of lymphovascular invasion and extensive intraductal carcinoma component, and immunohistochemical profiles) between patients with early (≤2.5 years after surgery) and late recurrence (>2.5 years after surgery). Cox proportional hazard regression analysis was performed to evaluate independent risk factors for early and late recurrence.On breast MRI, prominent ipsilateral whole-breast vascularity was independently associated with early recurrence (hazard ratio [HR], 2.86; 95% confidence intervals [CI], 1.39-5.88) and moderate or marked BPE (HR, 2.08; 95% CI, 1.04-4.18) and rim enhancement (HR, 2.14; 95% CI, 1.00-4.59) were independently associated with late recurrence. Clinico-pathologic variables independently associated with early recurrence included negative estrogen receptor (HR, 0.53; 95% CI, 0.29-0.96), whereas T2 stage (HR, 2.08; 95% CI, 1.04-4.16) and nuclear grade III (HR, 2.54; 95% CI, 1.29-4.98) were associated with late recurrence.In DCE-MRI, prominent ipsilateral whole-breast vascularity, moderate or marked BPE, and rim enhancement could be useful for predicting recurrence timing in patients with breast cancer.

Differentiating Smoking-Related Interstitial Fibrosis (SRIF) from Usual Interstitial Pneumonia (UIP) with Emphysema Using CT Features Based on Pathologically Proven Cases.

OBJECTIVE: To differentiate smoking-related interstitial fibrosis (SRIF) from usual interstitial pneumonia (UIP) with emphysema on CT in combined pulmonary fibrosis and emphysema (CPFE) patients. MATERIALS AND METHODS: This study was approved by the institutional review board and informed consent was waived. We included 65 patients who underwent lung biopsy under the suspicion of UIP pattern on HRCT, and after radiologic-pathologic correlation, they were divided into three groups: UIP without emphysema (n = 30), UIP with emphysema (n = 26), and SRIF (n = 9). The quantitative extent of emphysema in the entire lung was visually assessed and fibrotic patterns were qualitatively analyzed based on six characteristics (asymmetry, juxta-subpleural sparing, emphysema beside the honeycombing area, absence of ground grass attenuation/reticulation in honeycombing area, inhomogeneous honeycombing, and absence of honeycombing in the upper lobes). Kaplan-Meier analysis was used for survival analysis, and logistic regression with a receiver operating characteristic curve was used to predict the possibility of SRIF. RESULTS: In qualitative analysis of fibrotic patterns, SRIF tended to exhibit more than three of six fibrotic features, whereas UIP with emphysema demonstrated about two of these characteristics (p = 0.035). In addition, SRIF had a higher extent of emphysema than UIP with emphysema when they have same amount of fibrosis (p = 0.014). In patients with SRIF, 5-year survival rate was 85.7%, while it was 40.7% in UIP with emphysema patients (p = 0.035). CONCLUSION: Fibrotic CT patterns and survival rate differed between SRIF and UIP with emphysema among CPFE patients, which explains the variable prognosis of CPFE.