Ann Leung

All Publications

• Second Primary Lung Cancer Among Lung Cancer Survivors Who Never Smoked. JAMA network open Choi, E., Su, C. C., Wu, J. T., Aredo, J. V., Neal, J. W., Leung, A. N., Backhus, L. M., Lui, N. S., Le Marchand, L., Stram, D. O., Liang, S. Y., Cheng, I., Wakelee, H. A., Han, S. S. 2023; 6 (11): e2343278

  Abstract

  Lung cancer among never-smokers accounts for 25% of all lung cancers in the US; recent therapeutic advances have improved survival among patients with initial primary lung cancer (IPLC), who are now at high risk of developing second primary lung cancer (SPLC). As smoking rates continue to decline in the US, it is critical to examine more closely the epidemiology of lung cancer among patients who never smoked, including their risk for SPLC.To estimate and compare the cumulative SPLC incidence among lung cancer survivors who have never smoked vs those who have ever smoked.This population-based prospective cohort study used data from the Multiethnic Cohort Study (MEC), which enrolled participants between April 18, 1993, and December 31, 1996, with follow-up through July 1, 2017. Eligible individuals for this study were aged 45 to 75 years and had complete smoking data at baseline. These participants were followed up for IPLC and further SPLC development through the Surveillance, Epidemiology, and End Results registry. The data were analyzed from July 1, 2022, to January 31, 2023.Never-smoking vs ever-smoking exposure at MEC enrollment.The study had 2 primary outcomes: (1) 10-year cumulative incidence of IPLC in the entire study cohort and 10-year cumulative incidence of SPLC among patients with IPLC and (2) standardized incidence ratio (SIR) (calculated as the SPLC incidence divided by the IPLC incidence) by smoking history.Among 211 414 MEC participants, 7161 (3.96%) developed IPLC over 4 038 007 person-years, and 163 (2.28%) developed SPLC over 16 470 person-years. Of the participants with IPLC, the mean (SD) age at cohort enrollment was 63.6 (7.7) years, 4031 (56.3%) were male, and 3131 (43.7%) were female. The 10-year cumulative IPLC incidence was 2.40% (95% CI, 2.31%-2.49%) among ever-smokers, which was 7 times higher than never-smokers (0.34%; 95% CI, 0.30%-0.37%). However, the 10-year cumulative SPLC incidence following IPLC was as high among never-smokers (2.84%; 95% CI, 1.50%-4.18%) as ever-smokers (2.72%; 95% CI, 2.24%-3.20%), which led to a substantially higher SIR for never-smokers (14.50; 95% CI, 8.73-22.65) vs ever-smokers (3.50; 95% CI, 2.95-4.12).The findings indicate that SPLC risk among lung cancer survivors who never smoked is as high as among those with IPLC who ever-smoked, highlighting the need to identify risk factors for SPLC among patients who never smoked and to develop a targeted surveillance strategy.

  View details for DOI 10.1001/jamanetworkopen.2023.43278

  View details for PubMedID 37966839

• Risk Model-Based Lung Cancer Screening and Racial and Ethnic Disparities in the US. JAMA oncology Choi, E., Ding, V. Y., Luo, S. J., Ten Haaf, K., Wu, J. T., Aredo, J. V., Wilkens, L. R., Freedman, N. D., Backhus, L. M., Leung, A. N., Meza, R., Lui, N. S., Haiman, C. A., Park, S. L., Le Marchand, L., Neal, J. W., Cheng, I., Wakelee, H. A., Tammemägi, M. C., Han, S. S. 2023

  Abstract

  The revised 2021 US Preventive Services Task Force (USPSTF) guidelines for lung cancer screening have been shown to reduce disparities in screening eligibility and performance between African American and White individuals vs the 2013 guidelines. However, potential disparities across other racial and ethnic groups in the US remain unknown. Risk model-based screening may reduce racial and ethnic disparities and improve screening performance, but neither validation of key risk prediction models nor their screening performance has been examined by race and ethnicity.To validate and recalibrate the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012 (PLCOm2012) model-a well-established risk prediction model based on a predominantly White population-across races and ethnicities in the US and evaluate racial and ethnic disparities and screening performance through risk-based screening using PLCOm2012 vs the USPSTF 2021 criteria.In a population-based cohort design, the Multiethnic Cohort Study enrolled participants in 1993-1996, followed up through December 31, 2018. Data analysis was conducted from April 1, 2022, to May 19. 2023. A total of 105 261 adults with a smoking history were included.The 6-year lung cancer risk was calculated through recalibrated PLCOm2012 (ie, PLCOm2012-Update) and screening eligibility based on a 6-year risk threshold greater than or equal to 1.3%, yielding similar eligibility as the USPSTF 2021 guidelines.Predictive accuracy, screening eligibility-incidence (E-I) ratio (ie, ratio of the number of eligible to incident cases), and screening performance (sensitivity, specificity, and number needed to screen to detect 1 lung cancer).Of 105 261 participants (60 011 [57.0%] men; mean [SD] age, 59.8 [8.7] years), consisting of 19 258 (18.3%) African American, 27 227 (25.9%) Japanese American, 21 383 (20.3%) Latino, 8368 (7.9%) Native Hawaiian/Other Pacific Islander, and 29 025 (27.6%) White individuals, 1464 (1.4%) developed lung cancer within 6 years from enrollment. The PLCOm2012-Update showed good predictive accuracy across races and ethnicities (area under the curve, 0.72-0.82). The USPSTF 2021 criteria yielded a large disparity among African American individuals, whose E-I ratio was 53% lower vs White individuals (E-I ratio: 9.5 vs 20.3; P < .001). Under the risk-based screening (PLCOm2012-Update 6-year risk ≥1.3%), the disparity between African American and White individuals was substantially reduced (E-I ratio: 15.9 vs 18.4; P < .001), with minimal disparities observed in persons of other minoritized groups, including Japanese American, Latino, and Native Hawaiian/Other Pacific Islander. Risk-based screening yielded superior overall and race and ethnicity-specific performance to the USPSTF 2021 criteria, with higher overall sensitivity (67.2% vs 57.7%) and lower number needed to screen (26 vs 30) at similar specificity (76.6%).The findings of this cohort study suggest that risk-based lung cancer screening can reduce racial and ethnic disparities and improve screening performance across races and ethnicities vs the USPSTF 2021 criteria.

  View details for DOI 10.1001/jamaoncol.2023.4447

  View details for PubMedID 37883107

• Risk model-based management for second primary lung cancer among lung cancer survivors through a validated risk prediction model. Cancer Choi, E., Luo, S. J., Ding, V. Y., Wu, J. T., Kumar, A. V., Wampfler, J., Tammemägi, M. C., Wilkens, L. R., Aredo, J. V., Backhus, L. M., Neal, J. W., Leung, A. N., Freedman, N. D., Hung, R. J., Amos, C. I., Le Marchand, L., Cheng, I., Wakelee, H. A., Yang, P., Han, S. S. 2023

  Abstract

  Recent therapeutic advances and screening technologies have improved survival among patients with lung cancer, who are now at high risk of developing second primary lung cancer (SPLC). Recently, an SPLC risk-prediction model (called SPLC-RAT) was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. The predictive performance of SPLC-RAT was evaluated in a hospital-based cohort of lung cancer survivors.The authors analyzed data from 8448 ever-smoking patients diagnosed with initial primary lung cancer (IPLC) in 1997-2006 at Mayo Clinic, with each patient followed for SPLC through 2018. The predictive performance of SPLC-RAT and further explored the potential of improving SPLC detection through risk model-based surveillance using SPLC-RAT versus existing clinical surveillance guidelines.Of 8448 IPLC patients, 483 (5.7%) developed SPLC over 26,470 person-years. The application of SPLC-RAT showed high discrimination area under the receiver operating characteristics curve: 0.81). When the cohort was stratified by a 10-year risk threshold of ≥5.6% (i.e., 80th percentile from the SPLC-RAT development cohort), the observed SPLC incidence was significantly elevated in the high-risk versus low-risk subgroup (13.1% vs. 1.1%, p < 1 × 10-6 ). The risk-based surveillance through SPLC-RAT (≥5.6% threshold) outperformed the National Comprehensive Cancer Network guidelines with higher sensitivity (86.4% vs. 79.4%) and specificity (38.9% vs. 30.4%) and required 20% fewer computed tomography follow-ups needed to detect one SPLC (162 vs. 202).In a large, hospital-based cohort, the authors validated the predictive performance of SPLC-RAT in identifying high-risk survivors of SPLC and showed its potential to improve SPLC detection through risk-based surveillance.Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC). However, no evidence-based guidelines for SPLC surveillance are available for lung cancer survivors. Recently, an SPLC risk-prediction model was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. Using a large, real-world cohort of lung cancer survivors, we showed the high predictive accuracy and risk-stratification ability of the SPLC risk-prediction model. Furthermore, we demonstrated the potential to enhance efficiency in detecting SPLC using risk model-based surveillance strategies compared to the existing consensus-based clinical guidelines, including the National Comprehensive Cancer Network.

  View details for DOI 10.1002/cncr.35069

  View details for PubMedID 37877788

• Overall Survival Among Patients With De Novo Stage IV Metastatic and Distant Metastatic Recurrent Non-Small Cell Lung Cancer. JAMA network open Su, C. C., Wu, J. T., Choi, E., Myall, N. J., Neal, J. W., Kurian, A. W., Stehr, H., Wood, D., Henry, S. M., Backhus, L. M., Leung, A. N., Wakelee, H. A., Han, S. S. 2023; 6 (9): e2335813

  Abstract

  Despite recent breakthroughs in therapy, advanced lung cancer still poses a therapeutic challenge. The survival profile of patients with metastatic lung cancer remains poorly understood by metastatic disease type (ie, de novo stage IV vs distant recurrence).To evaluate the association of metastatic disease type on overall survival (OS) among patients with non-small cell lung cancer (NSCLC) and to identify potential mechanisms underlying any survival difference.Cohort study of a national US population based at a tertiary referral center in the San Francisco Bay Area using participant data from the National Lung Screening Trial (NLST) who were enrolled between 2002 and 2004 and followed up for up to 7 years as the primary cohort and patient data from Stanford Healthcare (SHC) for diagnoses between 2009 and 2019 and followed up for up to 13 years as the validation cohort. Participants from NLST with de novo metastatic or distant recurrent NSCLC diagnoses were included. Data were analyzed from January 2021 to March 2023.De novo stage IV vs distant recurrent metastatic disease.OS after diagnosis of metastatic disease.The NLST and SHC cohort consisted of 660 and 180 participants, respectively (411 men [62.3%] vs 109 men [60.6%], 602 White participants [91.2%] vs 111 White participants [61.7%], and mean [SD] age of 66.8 [5.5] vs 71.4 [7.9] years at metastasis, respectively). Patients with distant recurrence showed significantly better OS than patients with de novo metastasis (adjusted hazard ratio [aHR], 0.72; 95% CI, 0.60-0.87; P < .001) in NLST, which was replicated in SHC (aHR, 0.64; 95% CI, 0.43-0.96; P = .03). In SHC, patients with de novo metastasis more frequently progressed to the bone (63 patients with de novo metastasis [52.5%] vs 19 patients with distant recurrence [31.7%]) or pleura (40 patients with de novo metastasis [33.3%] vs 8 patients with distant recurrence [13.3%]) than patients with distant recurrence and were primarily detected through symptoms (102 patients [85.0%]) as compared with posttreatment surveillance (47 patients [78.3%]) in the latter. The main finding remained consistent after further adjusting for metastasis sites and detection methods.In this cohort study, patients with distant recurrent NSCLC had significantly better OS than those with de novo disease, and the latter group was associated with characteristics that may affect overall survival. This finding can help inform future clinical trial designs to ensure a balance for baseline patient characteristics.

  View details for DOI 10.1001/jamanetworkopen.2023.35813

  View details for PubMedID 37751203

• A hybrid modelling approach for abstracting CT imaging indications by integrating natural language processing from radiology reports with structured data from electronic health records. Khan, A., Wu, J., Choi, E., Graber-Naidich, A., Henry, S., Wakelee, H. A., Kurian, A. W., Liang, S., Leung, A., Langlotz, C., Backhus, L. M., Han, S. S. AMER ASSOC CANCER RESEARCH. 2023

  View details for Web of Science ID 001057852300077

• Chest Imaging. Seminars in respiratory and critical care medicine Remy-Jardin, M., Leung, A. N., Lynch, D. A. 2022; 43 (6): 763

  View details for DOI 10.1055/s-0042-1757884

  View details for PubMedID 36442472

• Utility of non-contrast-enhanced magnetic resonance imaging in predicting preoperative clinical stage and prognosis in patients with thymic epithelial tumor. Japanese journal of radiology Kuhara, A., Sumi, A., Chikasue, T., Kawaguchi, A., Tanoue, S., Nagata, S., Koganemaru, M., Abe, T., Kashihara, M., Mitsuoka, M., Ishii, H., Ohshima, K., Leung, A. N., Fujimoto, K. 2022

  Abstract

  PURPOSE: The purpose of this study was to find useful imaging features on non-contrast-enhanced magnetic resonance imaging (MRI) that can divide patients with thymic epithelial tumor (TET) into clinical stage I-II and III-IV groups under assumption that contrast media are contraindicated.MATERIALS AND METHODS: This retrospective study included 106 patients (median age, 60years; range, 27-82years; 62 women) with surgically resected TET who underwent MRI between August 1986 and July 2015. All cases were classified according to the 2015 WHO classification and staged using the eighth edition of the TNM system. Two radiologists independently evaluated 14 categories of MRI findings; the findings in patients with stage I-II were compared with those of patients with stage III-IV using a logistic regression model. Disease-specific survival associated with significant findings was calculated using the Kaplan-Meier method.RESULTS: Univariate analysis showed that stage III-IV patients were more likely to have tumors with an irregular contour, heterogeneity on T1WI, low-signal intensity on T2WI, irregular border with lung, findings of great vessel invasion (GVI) (hereafter, GVI sign), pericardial thickening/nodule, and lymphadenopathy (all, P<0.01). On multivariable analysis, only two findings, irregular border between tumor and lung (odds ratio [OR], 272.8; 95% CI 26.6-2794.1; P<0.001) and positive GVI sign (OR, 49.3; 95% CI 4.5-539.8; P=0.001) remained statistically significant. Patients with one or both features had significantly worse survival (log-rank test, P<0.001).CONCLUSION: For patients with TET who are unable to receive contrast for preoperative staging, the two image findings of an irregular border between tumor and lung and the positive GVI sign on non-contrast-enhanced MRI could be helpful in determining stage III-IV disease which is associated with a worse survival.

  View details for DOI 10.1007/s11604-022-01358-y

  View details for PubMedID 36374474

• Performance of a rule-based semi-automated method to optimize chart abstraction for surveillance imaging among patients treated for non-small cell lung cancer. BMC medical informatics and decision making Byrd, C., Ajawara, U., Laundry, R., Radin, J., Bhandari, P., Leung, A., Han, S., Asch, S. M., Zeliadt, S., Harris, A. H., Backhus, L. 2022; 22 (1): 148

  Abstract

  BACKGROUND: We aim to develop and test performance of a semi-automated method (computerized query combined with manual review) for chart abstraction in the identification and characterization of surveillance radiology imaging for post-treatment non-small cell lung cancer patients.METHODS: A gold standard dataset consisting of 3011 radiology reports from 361 lung cancer patients treated at the Veterans Health Administration from 2008 to 2016 was manually created by an abstractor coding image type, image indication, and image findings. Computerized queries using a text search tool were performed to code reports. The primary endpoint of query performance was evaluated by sensitivity, positive predictive value (PPV), and F1 score. The secondary endpoint of efficiency compared semi-automated abstraction time to manual abstraction time using a separate dataset and the Wilcoxon rank-sum test.RESULTS: Query for image type demonstrated the highest sensitivity of 85%, PPV 95%, and F1 score 0.90. Query for image indication demonstrated sensitivity 72%, PPV 70%, and F1 score 0.71. The image findings queries ranged from sensitivity 75-85%, PPV 23-25%, and F1 score 0.36-0.37. Semi-automated abstraction with our best performing query (image type) improved abstraction times by 68% per patient compared to manual abstraction alone (from median 21.5min (interquartile range 16.0) to 6.9min (interquartile range 9.5), p<0.005).CONCLUSIONS: Semi-automated abstraction using the best performing query of image type improved abstraction efficiency while preserving data accuracy. The computerized query acts as a pre-processing tool for manual abstraction by restricting effort to relevant images. Determining image indication and findings requires the addition of manual review for a semi-automatic abstraction approach in order to ensure data accuracy.

  View details for DOI 10.1186/s12911-022-01863-0

  View details for PubMedID 35659230

• COVID-19 Pandemic: The Road to Recovery. Radiology Leung, A. N. 2022: 220488

  View details for DOI 10.1148/radiol.220488

  View details for PubMedID 35348383

• NCCN Guidelines Insights: Lung Cancer Screening, Version 1.2022. Journal of the National Comprehensive Cancer Network : JNCCN Wood, D. E., Kazerooni, E. A., Aberle, D., Berman, A., Brown, L. M., Eapen, G. A., Ettinger, D. S., Ferguson, J. S., Hou, L., Kadaria, D., Klippenstein, D., Kumar, R., Lackner, R. P., Leard, L. E., Lennes, I. T., Leung, A. N., Mazzone, P., Merritt, R. E., Midthun, D. E., Onaitis, M., Pipavath, S., Pratt, C., Puri, V., Raz, D., Reddy, C., Reid, M. E., Sandler, K. L., Sands, J., Schabath, M. B., Studts, J. L., Tanoue, L., Tong, B. C., Travis, W. D., Wei, B., Westover, K., Yang, S. C., McCullough, B., Hughes, M. 2022; 20 (7): 754-764

  Abstract

  The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

  View details for DOI 10.6004/jnccn.2022.0036

  View details for PubMedID 35830884

• A Cost-Effectiveness Analysis of Lung Cancer Screening With Low-Dose Computed Tomography and a Diagnostic Biomarker. JNCI cancer spectrum Toumazis, I., Erdogan, S. A., Bastani, M., Leung, A., Plevritis, S. K. 2021; 5 (6): pkab081

  Abstract

  Background: The Lung Computed Tomography Screening Reporting and Data System (Lung-RADS) reduces the false-positive rate of lung cancer screening but introduces prolonged periods of uncertainty for indeterminate findings. We assess the cost-effectiveness of a screening program that assesses indeterminate findings earlier via a hypothetical diagnostic biomarker introduced in place of Lung-RADS 3 and 4A guidelines.Methods: We evaluated the performance of the US Preventive Services Task Force (USPSTF) recommendations on lung cancer screening with and without a hypothetical noninvasive diagnostic biomarker using a validated microsimulation model. The diagnostic biomarker assesses the malignancy of indeterminate nodules, replacing Lung-RADS 3 and 4A guidelines, and is characterized by a varying sensitivity profile that depends on nodules' size, specificity, and cost. We tested the robustness of our findings through univariate sensitivity analyses.Results: A lung cancer screening program per the USPSTF guidelines that incorporates a diagnostic biomarker with at least medium sensitivity profile and 90% specificity, that costs $250 or less, is cost-effective with an incremental cost-effectiveness ratio lower than $100 000 per quality-adjusted life year, and improves lung cancer-specific mortality reduction while requiring fewer screening exams than the USPSTF guidelines with Lung-RADS. A screening program with a biomarker costing $750 or more is not cost-effective. The health benefits accrued and costs associated with the screening program are sensitive to the disutility of indeterminate findings and specificity of the biomarker, respectively.Conclusions: Lung cancer screening that incorporates a diagnostic biomarker, in place of Lung-RADS 3 and 4A guidelines, could improve the cost-effectiveness of the screening program and warrants further investigation.

  View details for DOI 10.1093/jncics/pkab081

  View details for PubMedID 34738073

• Evaluation of Alternative Diagnostic Follow-up Intervals for Lung Reporting and Data System Criteria on the Effectiveness of Lung Cancer Screening. Journal of the American College of Radiology : JACR Bastani, M., Toumazis, I., Hedou', J., Leung, A., Plevritis, S. K. 2021

  Abstract

  PURPOSE: The ACR developed the Lung CT Screening Reporting and Data System (Lung-RADS) to standardize the diagnostic follow-up of suspicious screening findings. A retrospective analysis showed that Lung-RADS would have reduced the false-positive rate in the National Lung Screening Trial, but the optimal timing of follow-up examinations has not been established. In this study, we assess the effectiveness of alternative diagnostic follow-up intervals on lung cancer screening.METHODS: We used the Lung Cancer Outcome Simulator to estimate population-level outcomes of alternative diagnostic follow-up intervals for Lung-RADS categories 3 and 4A. The Lung Cancer Outcome Simulator is a microsimulation model developed within the Cancer Intervention and Surveillance Modeling Network Consortium to evaluate outcomes of national screening guidelines. Here, among the evaluated outcomes are percentage of mortality reduction, screens performed, lung cancer deaths averted, screen-detected cases, and average number of screens and follow-ups per death averted.RESULTS: The recommended 3-month follow-up interval for Lung-RADS category 4A is optimal. However, for Lung-RADS category 3, a 5-month, instead of the recommended 6-month, follow-up interval yielded higher mortality reduction (0.08% for men versus 0.05% for women), and higher number of deaths averted (36 versus 27), higher number of screen-detected cases (13 versus 7), and lower number of combined low-dose CTs and diagnostic follow-ups per death avoided (8 versus 5), per one million general population. Sensitivity analysis of nodule progression threshold verifies higher mortality reduction with 1-month earlier follow-up for Lung-RADS3.CONCLUSIONS: One month earlier diagnostic follow-ups for individuals with Lung-RADS category 3 nodules may result in higher mortality reduction and warrants further investigation.

  View details for DOI 10.1016/j.jacr.2021.08.001

  View details for PubMedID 34419477

• Development and Validation of a Risk Prediction Tool for Second Primary Lung Cancer. Journal of the National Cancer Institute Choi, E., Sanyal, N., Ding, V. Y., Gardner, R. M., Aredo, J. V., Lee, J., Wu, J. T., Hickey, T. P., Barrett, B., Riley, T. L., Wilkens, L. R., Leung, A. N., Le Marchand, L., Tammemagi, M. C., Hung, R. J., Amos, C. I., Freedman, N. D., Cheng, I., Wakelee, H. A., Han, S. S. 2021

  Abstract

  BACKGROUND: With advancing therapeutics, lung cancer (LC) survivors are rapidly increasing in number. While mounting evidence suggests LC survivors have high risk of second primary lung cancer (SPLC), there is no validated prediction tool available for clinical use to identify high-risk LC survivors for SPLC.METHODS: Using data from 6,325 ever-smokers in the Multiethnic Cohort (MEC) diagnosed with initial primary lung cancer (IPLC) in 1993-2017, we developed a prediction model for 10-year SPLC risk after IPLC diagnosis using cause-specific Cox regression. We evaluated the model's clinical utility using decision curve analysis and externally validated it using two population-based data, PLCO and NLST, that included 2,963 and 2,844 IPLC (101 and 93 SPLC cases), respectively.RESULTS: Over 14,063 person-years, 145 (2.3%) developed SPLC in MEC. Our prediction model demonstrated a high predictive accuracy (Brier score = 2.9, 95% confidence interval [CI] = 2.4-3.3) and discrimination (AUC = 81.9%, 95% CI=78.2%-85.5%) based on bootstrap validation in MEC. Stratification by the estimated risk quartiles showed that the observed SPLC incidence was statistically significantly higher in the 4th versus 1st quartile (9.5% versus 0.2%; P<.001). Decision curve analysis indicated that in a wide range of 10-year risk thresholds from 1% to 20%, the model yielded a larger net-benefit versus hypothetical all-screening or no-screening scenarios. External validation using PLCO and NLST showed an AUC of 78.8% (95% CI=74.6%-82.9%) and 72.7% (95% CI=67.7%-77.7%), respectively.CONCLUSIONS: We developed and validated a SPLC prediction model based on large population-based cohorts. The proposed prediction tool can help identify high-risk LC patients for SPLC and can be incorporated into clinical decision-making for SPLC surveillance and screening.

  View details for DOI 10.1093/jnci/djab138

  View details for PubMedID 34255071

• Managing Incidental Findings on Thoracic CT: Lung Findings. A White Paper of the ACR Incidental Findings Committee. Journal of the American College of Radiology : JACR Munden, R. F., Black, W. C., Hartman, T. E., MacMahon, H., Ko, J. P., Dyer, D. S., Naidich, D., Rossi, S. E., McAdams, H. P., Goodman, E. M., Brown, K., Kent, M., Carter, B. W., Chiles, C., Leung, A. N., Boiselle, P. M., Kazerooni, E. A., Berland, L. L., Pandharipande, P. V. 2021

  Abstract

  The ACR Incidental Findings Committee presents recommendations for managing incidentally detected lung findings on thoracic CT. The Chest Subcommittee is composed of thoracic radiologists who endorsed and developed the provided guidance. These recommendations represent a combination of current published evidence and expert opinion and were finalized by informal iterative consensus. The recommendations address commonly encountered incidental findings in the lungs and are not intended to be a comprehensive review of all pulmonary incidental findings. The goal is to improve the quality of care by providing guidance on management of incidentally detected thoracic findings.

  View details for DOI 10.1016/j.jacr.2021.04.014

  View details for PubMedID 34246574

• Multi-institution consensus paper for acquisition of portable chest radiographs through glass barriers. Journal of applied clinical medical physics McKenney, S. E., Wait, J. M., Cooper, V. N., Johnson, A. M., Wang, J., Leung, A. N., Clements, J. 2021

  Abstract

  BACKGROUND: To conserve personal protective equipment (PPE) and reduce exposure to potentially infected COVID-19 patients, several Californian facilities independently implemented a method of acquiring portable chest radiographs through glass barriers that was originally developed by the University of Washington.METHODS: This work quantifies the transmission of radiation through a glass barrier using six radiographic systems at five facilities. Patient entrance air kerma (EAK) and effective dose were estimated both with and without the glass barrier. Beam penetrability and resulting exposure index (EI) and deviation index (DI) were measured and used to adjust the tube current-time product (mAs) for glass barriers. Because of beam hardening, the contrast-to-noise ratio (CNR) was measured with image quality phantoms to ensure diagnostic integrity. Finally, scatter surveys were performed to assess staff radiation exposure both inside and outside the exam room.RESULTS: The glass barriers attenuated a mean of 61% of the normal X-ray beams. When the mAs was increased to match EI values, there was no discernible degradation of image quality as determined by the CNR. This was corroborated with subjective assessments of image quality by chest radiologists. The glass-hardened beams acted as a filter for low energy X-rays, and some facilities observed slight changes in patient effective doses. There was scattering from both the phantoms and the glass barriers within the room.CONCLUSIONS: Glass barriers require an approximate 2.5 times increase in beam intensity, with all other technique factors held constant. Further refinements are necessary for increased source-to-image distance and beam quality in order to adequately match EI values. This does not result in a significant increase in the radiation dose delivered to the patient. The use of lead aprons, mobile shields, and increased distance from scattering sources should be employed where practicable in order to keep staff radiation doses as low as reasonably achievable.

  View details for DOI 10.1002/acm2.13330

  View details for PubMedID 34216091

• Head-to-head Comparison of Qualitative Radiologist Assessment With Automated Quantitative Computed Tomography Analysis for Bronchiolitis Obliterans Syndrome After Hematopoietic Cell Transplantation. Journal of thoracic imaging Sharifi, H., Guenther, Z. D., Leung, A. N., Johnston, L., Lai, Y. K., Hsu, J. L., Guo, H. H. 2021

  Abstract

  PURPOSE: Computed tomography (CT) findings of bronchiolitis obliterans syndrome (BOS) can be nonspecific and variable. This study aims to measure the incremental value of automated quantitative lung CT analysis to clinical CT interpretation. A head-to-head comparison of quantitative CT lung density analysis by parametric response mapping (PRM) with qualitative radiologist performance in BOS diagnosis was performed.MATERIALS AND METHODS: Inspiratory and end-expiratory CTs of 65 patients referred to a post-bone marrow transplant lung graft-versus-host-disease clinic were reviewed by 3 thoracic radiologists for the presence of mosaic attenuation, centrilobular opacities, airways dilation, and bronchial wall thickening. Radiologists' majority consensus diagnosis of BOS was compared with automated PRM air trapping quantification and to the gold-standard diagnosis of BOS as per National Institutes of Health (NIH) consensus criteria.RESULTS: Using a previously established threshold of 28% air trapping on PRM, the diagnostic performance for BOS was as follows: sensitivity 56% and specificity 94% (area under the receiver operator curve [AUC]=0.75). Radiologist review of inspiratory CT images alone resulted in a sensitivity of 80% and a specificity of 69% (AUC=0.74). When radiologists assessed both inspiratory and end-expiratory CT images in combination, the sensitivity was 92% and the specificity was 59% (AUC=0.75). The highest performance was observed when the quantitative PRM report was reviewed alongside inspiratory and end-expiratory CT images, with a sensitivity of 92% and a specificity of 73% (AUC=0.83).CONCLUSIONS: In the CT diagnosis of BOS, qualitative expert radiologist interpretation was noninferior to quantitative PRM. The highest level of diagnostic performance was achieved by the combination of quantitative PRM measurements with qualitative image feature assessments.

  View details for DOI 10.1097/RTI.0000000000000595

  View details for PubMedID 33999570

• Toxoplasmosis Among 38,751 Hematopoietic Stem Cell Transplant Recipients: A Systematic Review of Disease Prevalence and a Compilation of Imaging and Autopsy Findings. Transplantation Contopoulos-Ioannidis, D. G., Cho, S. M., Bertaina, A., Leung, A. N., Fischbein, N., Lanzman, B., Schwenk, H. T., Montoya, J. G. 2021

  Abstract

  BACKGROUND: Toxoplasmosis in hematopoietic stem cell transplant-recipients (HSCT) can be life threatening if not promptly diagnosed and treated.METHODS: We performed a systematic review (PubMed last search 03/29/2020) of toxoplasmosis among HSCT-recipients and calculated the toxoplasmosis prevalence across studies. We also created a compilation list of brain imaging, chest imaging and autopsy findings of toxoplasmosis among HSCT-recipients.RESULTS: We identified 46 eligible studies (47 datasets) with 399 toxoplasmosis cases among 38751 HSCT-recipients. There was large heterogeneity in the reported toxoplasmosis prevalence across studies, thus formal meta-analysis was not attempted. The median toxoplasmosis prevalence among 38751 HSCT-recipients was 2.14% (range 0-66.67%). Data on toxoplasmosis among at-risk R+HSCT-recipients were more limited (25 studies; 2404 R+HSCT-recipients [6.2% of all HSCT-recipients]) although the median number of R+HSCT-recipients was 56.79% across all HSCT-recipients. Median toxoplasmosis prevalence across studies among 2404 R+HSCT was 7.51% (range 0-80%) vs 0% (range 0-1.23%) among 7438 R-HSCT. There were limited data to allow meaningful analyses of toxoplasmosis prevalence according to prophylaxis-status of R+HSCT-recipients.CONCLUSION: Toxoplasmosis prevalence among HSCT-recipients is underestimated. The majority of studies report toxoplasmosis prevalence among all HSCT-recipients rather than only among the at-risk R+HSCT-recipients. In fact, the median toxoplasmosis prevalence among all R+/R- HSCT-recipients is 3.5-fold lower compared to the prevalence among only the at-risk R+HSCT-recipients and the median prevalence among R+HSCT-recipients is 7.51-fold higher than among R-HSCT-recipients. The imaging findings of toxoplasmosis among HSCT-recipients can be atypical. High-index of suspicion is needed in R+HSCT-recipients with fever, pneumonia or encephalitis.

  View details for DOI 10.1097/TP.0000000000003662

  View details for PubMedID 33654004

• Imaging of Pulmonary Hypertension in Adults: A Position Paper from the Fleischner Society. Radiology Remy-Jardin, M., Ryerson, C. J., Schiebler, M. L., Leung, A. N., Wild, J. M., Hoeper, M. M., Alderson, P. O., Goodman, L. R., Mayo, J., Haramati, L. B., Ohno, Y., Thistlethwaite, P., van Beek, E. J., Knight, S. L., Lynch, D. A., Rubin, G. D., Humbert, M. 2021: 203108

  Abstract

  Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mm Hg and classified into five different groups sharing similar pathophysiologic mechanisms, hemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: (a) Is noninvasive imaging capable of identifying PH? (b) What is the role of imaging in establishing the cause of PH? (c) How does imaging determine the severity and complications of PH? (d) How should imaging be used to assess chronic thromboembolic PH before treatment? (e) Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH. This article is a simultaneous joint publication in Radiology and European Respiratory Journal. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. © 2021 RSNA and the European Respiratory Society. Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2020203108

  View details for PubMedID 33399507

• Aorto-iliac/right leg arterial thrombosis necessitating limb amputation, pulmonary arterial, intracardiac, and ilio-caval venous thrombosis in a 40-year-old with COVID-19. Clinical imaging Madani, M. H., Leung, A. N., Becker, H. C., Chan, F. P., Fleischmann, D. n. 2021; 75: 1–4

  Abstract

  We describe a 40-year-old man with severe COVID-19 requiring mechanical ventilation who developed aorto-bi-iliac arterial, right lower extremity arterial, intracardiac, pulmonary arterial and ilio-caval venous thromboses and required right lower extremity amputation for acute limb ischemia. This unique case illustrates COVID-19-associated thrombotic complications occurring at multiple, different sites in the cardiovascular system of a single infected patient.

  View details for DOI 10.1016/j.clinimag.2020.12.036

  View details for PubMedID 33477081

• A risk-based framework for assessing real-time lung cancer screening eligibility that incorporates life expectancy and past screening findings. Cancer Toumazis, I., Alagoz, O., Leung, A., Plevritis, S. K. 2021

  Abstract

  Current lung cancer risk-based screening approaches use a single risk-threshold, disregard life-expectancy, and ignore past screening findings. We address these limitations with a comprehensive analytical framework, the individualized lung cancer screening decision (ENGAGE) tool that aims to optimize lung cancer screening for US ever-smokers under dynamic risk assessment by incorporating life expectancy and past screening findings over time.ENGAGE employs a partially observable Markov decision process framework that integrates published risk prediction and disease progression models, to dynamically assess the trade-off between the expected health benefits and harms associated with screening. ENGAGE evaluates lung cancer risk annually and provides real-time screening eligibility that maximizes the expected quality-adjusted life-years (QALYs) of ever-smokers. We compare ENGAGE against the 2013 U.S. Preventive Services Task Force (USPSTF) lung cancer screening guideline and single-threshold risk-based screening paradigms.Compared with the 2013 USPSTF guidelines, ENGAGE expands screening coverage among ever-smokers (ENGAGE: 78%, USPSTF: 61%), while reducing the number of screening examinations per person (ENGAGE:10.43, USPSTF:12.07, P < .001), yields higher effectiveness in terms of increased lung cancer-specific mortality reduction (ENGAGE: 19%, USPSTF: 15%, P < .001) and improves screening efficiency (ENGAGE: 696, USPSTF: 819 screens per death avoided, P < .001). When compared against a single-threshold risk-based screening strategy, ENGAGE increases QALY requiring 30% fewer screens per death avoided (ENGAGE: 696, single-threshold: 889, P < .001), and reduces false positives by 40%.ENGAGE provides a comprehensive framework for dynamic risk-based assessment of lung cancer screening eligibility by incorporating life expectancy and past screening findings that can serve to guide future policies on the effectiveness and efficiency of screening.A novel decision-analytical screening framework was developed for lung cancer, the individualized lung cancer screening decision (ENGAGE) tool to provide personalized screening schedules for ever-smokers. ENGAGE captures the dynamic nature of lung cancer risk and incorporates life expectancy into the screening decision-making process. ENGAGE integrates past screening findings and changes in smoking behavior of individuals and provides informed screening decisions that outperform existing screening guidelines and single-threshold risk-based screening approaches. A personalized lung cancer screening program facilitated by a tool such as ENGAGE could enhance the efficiency of lung cancer screening.

  View details for DOI 10.1002/cncr.33835

  View details for PubMedID 34383299

• Impact of Low-Dose CT Screening for Primary Lung Cancer on Subsequent Risk of Brain Metastasis. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Su, C. C., Wu, J. T., Neal, J. W., Popat, R. A., Kurian, A. W., Backhus, L. M., Nagpal, S., Leung, A. N., Wakelee, H. A., Han, S. S. 2021

  Abstract

  Brain metastasis (BM) is one of the most common metastases from primary lung cancer (PLC). Recently, the National Lung Screening Trial (NLST) demonstrated the efficacy of low-dose computed tomography (LDCT) screening on LC mortality reduction. However, it remains unknown if early detection of PLC through LDCT may be potentially beneficial in reducing the risk of subsequent metastases. Our study aimed to investigate the impact of LDCT screening for PLC on the risk of developing BM after PLC diagnosis.We used NLST data to identify 1,502 participants who were diagnosed with PLC in 2002-2009 and have follow-up data for BM. Cause-specific competing risk regression was applied to evaluate an association between BM risk and the mode of PLC detection-i.e., LDCT screen-detected versus non-LDCT screen-detected. Subgroup analyses were conducted in early-stage PLC patients and those who underwent surgery for PLC.Of 1502 participants, 41.4% had PLC detected through LDCT-screening versus 58.6% detected through other methods, e.g., chest X-Ray or incidental detection. Patients whose PLC was detected with LDCT-screening had a significantly lower 3-year incidence of BM (6.5%) versus those without (11.9%), with a cause-specific hazard ratio (HR) of 0.53 (p=0.001), adjusting for PLC stage, histology, diagnosis age and smoking status. This significant reduction in BM risk among PLCs detected through LDCT-screening persisted in subgroups of early-stage PLC participants (HR 0.47, p=0.002) and those who underwent surgery (HR 0.37, p=0.001).Early detection of PLC using LDCT-screening is associated with lower risk of BM after PLC diagnosis based on a large population-based study.

  View details for DOI 10.1016/j.jtho.2021.05.010

  View details for PubMedID 34091050

• Imaging of pulmonary hypertension in adults: a position paper from the Fleischner Society. The European respiratory journal Remy-Jardin, M., Ryerson, C. J., Schiebler, M. L., Leung, A. N., Wild, J. M., Hoeper, M. M., Alderson, P. O., Goodman, L. R., Mayo, J., Haramati, L. B., Ohno, Y., Thistlethwaite, P., van Beek, E. J., Knight, S. L., Lynch, D. A., Rubin, G. D., Humbert, M. 2021; 57 (1)

  Abstract

  Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mmHg and classified into five different groups sharing similar pathophysiologic mechanisms, haemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: a) Is noninvasive imaging capable of identifying PH? b) What is the role of imaging in establishing the cause of PH? c) How does imaging determine the severity and complications of PH? d) How should imaging be used to assess chronic thromboembolic PH before treatment? e) Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH.

  View details for DOI 10.1183/13993003.04455-2020

  View details for PubMedID 33402372

• Tobacco Smoking and Risk of Second Primary Lung Cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Aredo, J. V., Luo, S. J., Gardner, R. M., Sanyal, N. n., Choi, E. n., Hickey, T. P., Riley, T. L., Huang, W. Y., Kurian, A. W., Leung, A. N., Wilkens, L. R., Robbins, H. A., Riboli, E. n., Kaaks, R. n., Tjønneland, A. n., Vermeulen, R. C., Panico, S. n., Le Marchand, L. n., Amos, C. I., Hung, R. J., Freedman, N. D., Johansson, M. n., Cheng, I. n., Wakelee, H. A., Han, S. S. 2021

  Abstract

  Lung cancer survivors are at high risk of a second primary lung cancer (SPLC). However, SPLC risk factors have not been established and the impact of tobacco smoking remains controversial. We examined risk factors for SPLC across multiple epidemiologic cohorts and assessed the impact of smoking cessation on reducing SPLC risk.We analyzed data from 7,059 participants in the Multiethnic Cohort (MEC) diagnosed with an initial primary lung cancer (IPLC) between 1993 and 2017. Cause-specific proportional hazards models estimated SPLC risk. We conducted validation studies using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, N=3,423 IPLC cases) and European Prospective Investigation into Cancer and Nutrition (EPIC, N=4,731 IPLC cases) cohorts and pooled the SPLC risk estimates using random effects meta-analysis.Overall, 163 (2.3%) MEC cases developed a SPLC. Smoking pack-years (HR 1.18 per 10 pack-years; P<0.001) and smoking intensity (HR 1.30 per 10 cigarettes per day (CPD); P<0.001) were significantly associated with increased SPLC risk. Individuals who met the 2013 U.S. Preventive Services Task Force's (USPSTF) screening criteria at IPLC diagnosis also had an increased SPLC risk (HR 1.92; P<0.001). Validation studies with PLCO and EPIC showed consistent results. Meta-analysis yielded pooled HRs of 1.16 per 10 pack-years (Pmeta<0.001), 1.25 per 10 CPD (Pmeta<0.001), and 1.99 (Pmeta<0.001) for meeting the USPSTF criteria. In MEC, smoking cessation after IPLC diagnosis was associated with an 83% reduction in SPLC risk (HR 0.17; P<0.001).Tobacco smoking is a risk factor for SPLC. Smoking cessation after IPLC diagnosis may reduce the risk of SPLC. Additional strategies for SPLC surveillance and screening are warranted.

  View details for DOI 10.1016/j.jtho.2021.02.024

  View details for PubMedID 33722709

• A Shallow Convolutional Neural Network Predicts Prognosis of Lung Cancer Patients in Multi-Institutional CT-Image Data. Nature machine intelligence Mukherjee, P., Zhou, M., Lee, E., Schicht, A., Balagurunathan, Y., Napel, S., Gillies, R., Wong, S., Thieme, A., Leung, A., Gevaert, O. 2020; 2 (5): 274-282

  Abstract

  Lung cancer is the most common fatal malignancy in adults worldwide, and non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer diagnoses. Computed tomography (CT) is routinely used in clinical practice to determine lung cancer treatment and assess prognosis. Here, we developed LungNet, a shallow convolutional neural network for predicting outcomes of NSCLC patients. We trained and evaluated LungNet on four independent cohorts of NSCLC patients from four medical centers: Stanford Hospital (n = 129), H. Lee Moffitt Cancer Center and Research Institute (n = 185), MAASTRO Clinic (n = 311) and Charité - Universitätsmedizin (n=84). We show that outcomes from LungNet are predictive of overall survival in all four independent survival cohorts as measured by concordance indices of 0.62, 0.62, 0.62 and 0.58 on cohorts 1, 2, 3, and 4, respectively. Further, the survival model can be used, via transfer learning, for classifying benign vs malignant nodules on the Lung Image Database Consortium (n = 1010), with improved performance (AUC=0.85) versus training from scratch (AUC=0.82). LungNet can be used as a noninvasive predictor for prognosis in NSCLC patients and can facilitate interpretation of CT images for lung cancer stratification and prognostication.

  View details for DOI 10.1038/s42256-020-0173-6

  View details for PubMedID 33791593

  View details for PubMedCentralID PMC8008967

• The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society. Radiology Rubin, G. D., Haramati, L. B., Kanne, J. P., Schluger, N. W., Yim, J., Anderson, D. J., Altes, T., Desai, S. R., Goo, J. M., Inoue, Y., Luo, F., Prokop, M., Richeldi, L., Tomiyama, N., Leung, A. N., Ryerson, C. J., Sverzellati, N., Raoof, S., Volpi, A., Martin, I. B., Kong, C., Bush, A., Goldin, J., Humbert, M., Kauczor, H., Mazzone, P. J., Remy-Jardin, M., Schaefer-Prokop, C. M., Wells, A. U. 2020: 201365

  Abstract

  With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first three months of 2020, the COVID-19 pandemic has emerged as an unprecedented healthcare crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, healthcare delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and healthcare workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. While mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography (CXR) and computed tomography (CT) are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pre-test probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing COVID-19 patients across a spectrum of healthcare environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based upon the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of CXR and CT in the management of COVID-19.

  View details for DOI 10.1148/radiol.2020201365

  View details for PubMedID 32255413

• Integrating genomic features for non-invasive early lung cancer detection. Nature Chabon, J. J., Hamilton, E. G., Kurtz, D. M., Esfahani, M. S., Moding, E. J., Stehr, H., Schroers-Martin, J., Nabet, B. Y., Chen, B., Chaudhuri, A. A., Liu, C. L., Hui, A. B., Jin, M. C., Azad, T. D., Almanza, D., Jeon, Y. J., Nesselbush, M. C., Co Ting Keh, L., Bonilla, R. F., Yoo, C. H., Ko, R. B., Chen, E. L., Merriott, D. J., Massion, P. P., Mansfield, A. S., Jen, J., Ren, H. Z., Lin, S. H., Costantino, C. L., Burr, R., Tibshirani, R., Gambhir, S. S., Berry, G. J., Jensen, K. C., West, R. B., Neal, J. W., Wakelee, H. A., Loo, B. W., Kunder, C. A., Leung, A. N., Lui, N. S., Berry, M. F., Shrager, J. B., Nair, V. S., Haber, D. A., Sequist, L. V., Alizadeh, A. A., Diehn, M. 2020; 580 (7802): 245-251

  Abstract

  Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.

  View details for DOI 10.1038/s41586-020-2140-0

  View details for PubMedID 32269342

• Integrating genomic features for non-invasive early lung cancer detection NATURE Chabon, J. J., Hamilton, E. G., Kurtz, D. M., Esfahani, M. S., Moding, E. J., Stehr, H., Schroers-Martin, J., Nabet, B. Y., Chen, B., Chaudhuri, A. A., Liu, C., Hui, A. B., Jin, M. C., Azad, T. D., Almanza, D., Jeon, Y., Nesselbush, M. C., Keh, L., Bonilla, R. F., Yoo, C. H., Ko, R. B., Chen, E. L., Merriott, D. J., Massion, P. P., Mansfield, A. S., Jen, J., Ren, H. Z., Lin, S. H., Costantino, C. L., Burr, R., Tibshirani, R., Gambhir, S. S., Berry, G. J., Jensen, K. C., West, R. B., Neal, J. W., Wakelee, H. A., Loo, B. W., Kunder, C. A., Leung, A. N., Lui, N. S., Berry, M. F., Shrager, J. B., Nair, V. S., Haber, D. A., Sequist, L. V., Alizadeh, A. A., Diehn, M. 2020

  View details for DOI 10.1038/s41586-020-2140-0

  View details for Web of Science ID 000521531000011

• A shallow convolutional neural network predicts prognosis of lung cancer patients in multi-institutional computed tomography image datasets Nature Machine Intelligence Mukherjee, P., Zhou, M., Lee, E., Schicht, A., Balagurunathan, Y., Napel, S., Gillies, R., Wong, S., Thieme, A., Leung, A., Gevaert, O. 2020; 2 (5): 274–282

  View details for DOI 10.1038/s42256-020-0173-6

• The Role of Chest Imaging in Patient Management during the COVID-19 Pandemic: A Multinational Consensus Statement from the Fleischner Society. Chest Rubin, G. D., Ryerson, C. J., Haramati, L. B., Sverzellati, N. n., Kanne, J. P., Raoof, S. n., Schluger, N. W., Volpi, A. n., Yim, J. J., Martin, I. B., Anderson, D. J., Kong, C. n., Altes, T. n., Bush, A. n., Desai, S. R., Goldin, J. n., Goo, J. M., Humbert, M. n., Inoue, Y. n., Kauczor, H. U., Luo, F. n., Mazzone, P. J., Prokop, M. n., Remy-Jardin, M. n., Richeldi, L. n., Schaefer-Prokop, C. M., Tomiyama, N. n., Wells, A. U., Leung, A. N. 2020

  Abstract

  With more than 900,000 confirmed cases worldwide and nearly 50,000 deaths during the first three months of 2020, the COVID-19 pandemic has emerged as an unprecedented healthcare crisis. The spread of COVID-19 has been heterogeneous, resulting in some regions having sporadic transmission and relatively few hospitalized patients with COVID-19 and others having community transmission that has led to overwhelming numbers of severe cases. For these regions, healthcare delivery has been disrupted and compromised by critical resource constraints in diagnostic testing, hospital beds, ventilators, and healthcare workers who have fallen ill to the virus exacerbated by shortages of personal protective equipment. While mild cases mimic common upper respiratory viral infections, respiratory dysfunction becomes the principal source of morbidity and mortality as the disease advances. Thoracic imaging with chest radiography (CXR) and computed tomography (CT) are key tools for pulmonary disease diagnosis and management, but their role in the management of COVID-19 has not been considered within the multivariable context of the severity of respiratory disease, pre-test probability, risk factors for disease progression, and critical resource constraints. To address this deficit, a multidisciplinary panel comprised principally of radiologists and pulmonologists from 10 countries with experience managing COVID-19 patients across a spectrum of healthcare environments evaluated the utility of imaging within three scenarios representing varying risk factors, community conditions, and resource constraints. Fourteen key questions, corresponding to 11 decision points within the three scenarios and three additional clinical situations, were rated by the panel based upon the anticipated value of the information that thoracic imaging would be expected to provide. The results were aggregated, resulting in five main and three additional recommendations intended to guide medical practitioners in the use of CXR and CT in the management of COVID-19.

  View details for DOI 10.1016/j.chest.2020.04.003

  View details for PubMedID 32275978

• Traumatic Pneumothorax Presenting as a Subcutaneous "Airball". American journal of respiratory and critical care medicine Madhok, J. n., Madani, M. H., Leung, A. N., Mihm, F. n. 2020

  View details for DOI 10.1164/rccm.202006-2515IM

  View details for PubMedID 33197203

• Left Atrial Volume as a Biomarker of Atrial Fibrillation at Routine Chest CT: Deep Learning Approach. Radiology. Cardiothoracic imaging Bratt, A., Guenther, Z., Hahn, L. D., Kadoch, M., Adams, P. L., Leung, A. N., Guo, H. H. 2019; 1 (5): e190057

  Abstract

  To test the performance of a deep learning (DL) model in predicting atrial fibrillation (AF) at routine nongated chest CT.A retrospective derivation cohort (mean age, 64 years; 51% female) consisting of 500 consecutive patients who underwent routine chest CT served as the training set for a DL model that was used to measure left atrial volume. The model was then used to measure atrial size for a separate 500-patient validation cohort (mean age, 61 years; 46% female), in which the AF status was determined by performing a chart review. The performance of automated atrial size as a predictor of AF was evaluated by using a receiver operating characteristic analysis.There was good agreement between manual and model-generated segmentation maps by all measures of overlap and surface distance (mean Dice = 0.87, intersection over union = 0.77, Hausdorff distance = 4.36 mm, average symmetric surface distance = 0.96 mm), and agreement was slightly but significantly greater than that between human observers (mean Dice = 0.85 [automated] vs 0.84 [manual]; P = .004). Atrial volume was a good predictor of AF in the validation cohort (area under the receiver operating characteristic curve = 0.768) and was an independent predictor of AF, with an age-adjusted relative risk of 2.9.Left atrial volume is an independent predictor of the AF status as measured at routine nongated chest CT. Deep learning is a suitable tool for automated measurement.© RSNA, 2019See also the commentary by de Roos and Tao in this issue.

  View details for DOI 10.1148/ryct.2019190057

  View details for PubMedID 33778529

  View details for PubMedCentralID PMC7977801

• Bone Marrow and Tumor Radiomics at 18F-FDG PET/CT: Impact on Outcome Prediction in Non-Small Cell Lung Cancer. Radiology Mattonen, S. A., Davidzon, G. A., Benson, J., Leung, A. N., Vasanawala, M., Horng, G., Shrager, J. B., Napel, S., Nair, V. S. 2019: 190357

  Abstract

  Background Primary tumor maximum standardized uptake value is a prognostic marker for non-small cell lung cancer. In the setting of malignancy, bone marrow activity from fluorine 18-fluorodeoxyglucose (FDG) PET may be informative for clinical risk stratification. Purpose To determine whether integrating FDG PET radiomic features of the primary tumor, tumor penumbra, and bone marrow identifies lung cancer disease-free survival more accurately than clinical features alone. Materials and Methods Patients were retrospectively analyzed from two distinct cohorts collected between 2008 and 2016. Each tumor, its surrounding penumbra, and bone marrow from the L3-L5 vertebral bodies was contoured on pretreatment FDG PET/CT images. There were 156 bone marrow and 512 tumor and penumbra radiomic features computed from the PET series. Randomized sparse Cox regression by least absolute shrinkage and selection operator identified features that predicted disease-free survival in the training cohort. Cox proportional hazards models were built and locked in the training cohort, then evaluated in an independent cohort for temporal validation. Results There were 227 patients analyzed; 136 for training (mean age, 69 years ± 9 [standard deviation]; 101 men) and 91 for temporal validation (mean age, 72 years ± 10; 91 men). The top clinical model included stage; adding tumor region features alone improved outcome prediction (log likelihood, -158 vs -152; P = .007). Adding bone marrow features continued to improve performance (log likelihood, -158 vs -145; P = .001). The top model integrated stage, two bone marrow texture features, one tumor with penumbra texture feature, and two penumbra texture features (concordance, 0.78; 95% confidence interval: 0.70, 0.85; P < .001). This fully integrated model was a predictor of poor outcome in the independent cohort (concordance, 0.72; 95% confidence interval: 0.64, 0.80; P < .001) and a binary score stratified patients into high and low risk of poor outcome (P < .001). Conclusion A model that includes pretreatment fluorine 18-fluorodeoxyglucose PET texture features from the primary tumor, tumor penumbra, and bone marrow predicts disease-free survival of patients with non-small cell lung cancer more accurately than clinical features alone. © RSNA, 2019 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2019190357

  View details for PubMedID 31526257

• Cost-Effectiveness Analysis of Lung Cancer Screening Accounting for the Effect of Indeterminate Findings JNCI CANCER SPECTRUM Toumazis, I., Tsai, E. B., Erdogan, S., Han, S. S., Wan, W., Leung, A., Plevritis, S. K. 2019; 3 (3)

  View details for DOI 10.1093/jncics/pkz035

  View details for Web of Science ID 000493383800010

• Cost-Effectiveness Analysis of Lung Cancer Screening Accounting for the Effect of Indeterminate Findings. JNCI cancer spectrum Toumazis, I., Tsai, E. B., Erdogan, S. A., Han, S. S., Wan, W., Leung, A., Plevritis, S. K. 2019; 3 (3): pkz035

  Abstract

  Numerous health policy organizations recommend lung cancer screening, but no consensus exists on the optimal policy. Moreover, the impact of the Lung CT screening reporting and data system guidelines to manage small pulmonary nodules of unknown significance (a.k.a. indeterminate nodules) on the cost-effectiveness of lung cancer screening is not well established.We assess the cost-effectiveness of 199 screening strategies that vary in terms of age and smoking eligibility criteria, using a microsimulation model. We simulate lung cancer-related events throughout the lifetime of US-representative current and former smokers. We conduct sensitivity analyses to test key model inputs and assumptions.The cost-effectiveness efficiency frontier consists of both annual and biennial screening strategies. Current guidelines are not on the frontier. Assuming 4% disutility associated with indeterminate findings, biennial screening for smokers aged 50-70 years with at least 40 pack-years and less than 10 years since smoking cessation is the cost-effective strategy using $100 000 willingness-to-pay threshold yielding the highest health benefit. Among all health utilities, the cost-effectiveness of screening is most sensitive to changes in the disutility of indeterminate findings. As the disutility of indeterminate findings decreases, screening eligibility criteria become less stringent and eventually annual screening for smokers aged 50-70 years with at least 30 pack-years and less than 10 years since smoking cessation is the cost-effective strategy yielding the highest health benefit.The disutility associated with indeterminate findings impacts the cost-effectiveness of lung cancer screening. Efforts to quantify and better understand the impact of indeterminate findings on the effectiveness and cost-effectiveness of lung cancer screening are warranted.

  View details for DOI 10.1093/jncics/pkz035

  View details for PubMedID 31942534

  View details for PubMedCentralID PMC6947892

• [18F] FDG Positron Emission Tomography (PET) Tumor and Penumbra Imaging Features Predict Recurrence in Non-Small Cell Lung Cancer TOMOGRAPHY Mattonen, S. A., Davidzon, G. A., Bakr, S., Echegaray, S., Leung, A. C., Vasanawala, M., Horng, G., Napel, S., Nair, V. S. 2019; 5 (1): 145–53

  View details for DOI 10.18383/j.tom.2018.00026

  View details for Web of Science ID 000460943000018

• [18F] FDG Positron Emission Tomography (PET) Tumor and Penumbra Imaging Features Predict Recurrence in Non-Small Cell Lung Cancer. Tomography (Ann Arbor, Mich.) Mattonen, S. A., Davidzon, G. A., Bakr, S., Echegaray, S., Leung, A. N., Vasanawala, M., Horng, G., Napel, S., Nair, V. S. 2019; 5 (1): 145–53

  Abstract

  We identified computational imaging features on 18F-fluorodeoxyglucose positron emission tomography (PET) that predict recurrence/progression in non-small cell lung cancer (NSCLC). We retrospectively identified 291 patients with NSCLC from 2 prospectively acquired cohorts (training, n = 145; validation, n = 146). We contoured the metabolic tumor volume (MTV) on all pretreatment PET images and added a 3-dimensional penumbra region that extended outward 1 cm from the tumor surface. We generated 512 radiomics features, selected 435 features based on robustness to contour variations, and then applied randomized sparse regression (LASSO) to identify features that predicted time to recurrence in the training cohort. We built Cox proportional hazards models in the training cohort and independently evaluated the models in the validation cohort. Two features including stage and a MTV plus penumbra texture feature were selected by LASSO. Both features were significant univariate predictors, with stage being the best predictor (hazard ratio [HR] = 2.15 [95% confidence interval (CI): 1.56-2.95], P < .001). However, adding the MTV plus penumbra texture feature to stage significantly improved prediction (P = .006). This multivariate model was a significant predictor of time to recurrence in the training cohort (concordance = 0.74 [95% CI: 0.66-0.81], P < .001) that was validated in a separate validation cohort (concordance = 0.74 [95% CI: 0.67-0.81], P < .001). A combined radiomics and clinical model improved NSCLC recurrence prediction. FDG PET radiomic features may be useful biomarkers for lung cancer prognosis and add clinical utility for risk stratification.

  View details for PubMedID 30854452

• Inter-observer agreement in identifying traction bronchiectasis on computed tomography: its improvement with the use of the additional criteria for chronic fibrosing interstitial pneumonia. Japanese journal of radiology Tominaga, J. n., Bankier, A. A., Lee, K. S., Leung, A. N., Remy-Jardin, M. n., Akira, M. n., Arakawa, H. n., Boiselle, P. M., Franquet, T. n., Fujimoto, K. n., Gevenois, P. A., Goo, J. M., Grenier, P. A., Hatabu, H. n., Ichikado, K. n., Im, J. G., Johkoh, T. n., Lee, K. N., Lynch, D. A., Noma, S. n., Song, J. W., Sakai, F. n., Sugiyama, Y. n. 2019

  Abstract

  To assess inter-observer variability in identifying traction bronchiectasis on computed tomography (CT) using additional criteria for chronic fibrosing interstitial pneumonia.Seven experts categorized CT image set representing 39 patients into three groups on the basis of the presence of traction bronchiectasis, using a three-point scale: 3-definitely/probably yes; 2-possibly yes; and 1-definitely/probably no. This scale served as a reference standard. The image set included cases of chronic fibrosing interstitial pneumonia, non-interstitial lung disease, and difficult-to-determine cases. Forty-eight observers similarly assessed the same image set, first according to the Fleischner Society definition, and second with additional criteria, in which traction bronchiectasis was observed exclusively in chronic fibrosing interstitial pneumonia. The agreement level between the reference standard and each observer's evaluation in each session was calculated using weighted kappa values which were compared between the two sessions using a paired t test.The mean weighted kappa value for all observers was significantly higher in the second reading session (mean 0.75) than in the first reading session (mean 0.62) (p < 0.001).Inter-observer agreement in identifying traction bronchiectasis improves when using the additional criteria which specify chronic fibrosing interstitial pneumonia as the underlying disease.

  View details for DOI 10.1007/s11604-019-00864-w

  View details for PubMedID 31522385

• Left Atrial Volume as a Biomarker of Atrial Fibrillation at Routine Chest CT: Deep Learning Approach Radiology: Cardiothoracic Imaging Bratt, A., Guenther, Z., Lewis, H., Kadoch, M., Adams, P. L., Leung, A. N., Guo, H. H. 2019; 1 (5): 1-7

  View details for DOI 10.1148/ryct.2019190057

• Emergent high fatality lung disease in systemic juvenile arthritis. Annals of the rheumatic diseases Saper, V. E., Chen, G. n., Deutsch, G. H., Guillerman, R. P., Birgmeier, J. n., Jagadeesh, K. n., Canna, S. n., Schulert, G. n., Deterding, R. n., Xu, J. n., Leung, A. N., Bouzoubaa, L. n., Abulaban, K. n., Baszis, K. n., Behrens, E. M., Birmingham, J. n., Casey, A. n., Cidon, M. n., Cron, R. Q., De, A. n., De Benedetti, F. n., Ferguson, I. n., Fishman, M. P., Goodman, S. I., Graham, T. B., Grom, A. A., Haines, K. n., Hazen, M. n., Henderson, L. A., Ho, A. n., Ibarra, M. n., Inman, C. J., Jerath, R. n., Khawaja, K. n., Kingsbury, D. J., Klein-Gitelman, M. n., Lai, K. n., Lapidus, S. n., Lin, C. n., Lin, J. n., Liptzin, D. R., Milojevic, D. n., Mombourquette, J. n., Onel, K. n., Ozen, S. n., Perez, M. n., Phillippi, K. n., Prahalad, S. n., Radhakrishna, S. n., Reinhardt, A. n., Riskalla, M. n., Rosenwasser, N. n., Roth, J. n., Schneider, R. n., Schonenberg-Meinema, D. n., Shenoi, S. n., Smith, J. A., Sönmez, H. E., Stoll, M. L., Towe, C. n., Vargas, S. O., Vehe, R. K., Young, L. R., Yang, J. n., Desai, T. n., Balise, R. n., Lu, Y. n., Tian, L. n., Bejerano, G. n., Davis, M. M., Khatri, P. n., Mellins, E. D. 2019

  Abstract

  To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

  View details for DOI 10.1136/annrheumdis-2019-216040

  View details for PubMedID 31562126

• An Analysis of Lung Cancer Screening Beliefs and Practice Patterns for Community Providers Compared to Academic Providers CANCER CONTROL Khairy, M., Duong, D. K., Shariff-Marco, S., Cheng, I., Jain, J., Balakrishnan, A., Liu, L., Gupta, A., Chandramouli, R., Hsing, A., Leung, A., Singh, B., Nair, V. S. 2018; 25 (1)

  View details for DOI 10.1177/1073274818806900

  View details for Web of Science ID 000449076800001

• A radiogenomic dataset of non-small cell lung cancer SCIENTIFIC DATA Bakr, S., Gevaert, O., Echegaray, S., Ayers, K., Zhou, M., Shafiq, M., Zheng, H., Benson, J., Zhang, W., Leung, A. C., Kadoch, M., Hoang, C. D., Shrager, J., Quon, A., Rubin, D. L., Plevritis, S. K., Napel, S. 2018; 5

  View details for DOI 10.1038/sdata.2018.202

  View details for Web of Science ID 000447363600001

• A radiogenomic dataset of non-small cell lung cancer. Scientific data Bakr, S., Gevaert, O., Echegaray, S., Ayers, K., Zhou, M., Shafiq, M., Zheng, H., Benson, J. A., Zhang, W., Leung, A. N., Kadoch, M., D Hoang, C., Shrager, J., Quon, A., Rubin, D. L., Plevritis, S. K., Napel, S. 2018; 5: 180202

  Abstract

  Medical image biomarkers of cancer promise improvements in patient care through advances in precision medicine. Compared to genomic biomarkers, image biomarkers provide the advantages of being non-invasive, and characterizing a heterogeneous tumor in its entirety, as opposed to limited tissue available via biopsy. We developed a unique radiogenomic dataset from a Non-Small Cell Lung Cancer (NSCLC) cohort of 211 subjects. The dataset comprises Computed Tomography (CT), Positron Emission Tomography (PET)/CT images, semantic annotations of the tumors as observed on the medical images using a controlled vocabulary, and segmentation maps of tumors in the CT scans. Imaging data are also paired with results of gene mutation analyses, gene expression microarrays and RNA sequencing data from samples of surgically excised tumor tissue, and clinical data, including survival outcomes. This dataset was created to facilitate the discovery of the underlying relationship between tumor molecular and medical image features, as well as the development and evaluation of prognostic medical image biomarkers.

  View details for PubMedID 30325352

• Invited Commentary on "Updated Fleischner Society Guidelines for Managing Incidental Pulmonary Nodules". Radiographics : a review publication of the Radiological Society of North America, Inc Leung, A. N. 2018; 38 (5): 1350–51

  View details for PubMedID 30207942

• Invited Commentary on "Updated Fleischner Society Guidelines for Managing Incidental Pulmonary Nodules" RADIOGRAPHICS Leung, A. N. 2018; 38 (5): 1350–51

  View details for DOI 10.1148/rg.2018180182

  View details for Web of Science ID 000444411200004

• Managing Incidental Findings on Thoracic CT: Mediastinal and Cardiovascular Findings. A White Paper of the ACR Incidental Findings Committee JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY Munden, R. F., Carter, B. W., Chiles, C., MacMahon, H., Black, W. C., Ko, J. P., McAdams, H., Rossi, S. E., Leung, A. N., Boiselle, P. M., Kent, M. S., Brown, K., Dyer, D. S., Hartman, T. E., Goodman, E. M., Naidich, D. P., Kazerooni, E. A., Berland, L. L., Pandharipande, P. V. 2018; 15 (8): 1087–96

  Abstract

  The ACR Incidental Findings Committee presents recommendations for managing incidentally detected mediastinal and cardiovascular findings found on CT. The Chest Subcommittee was composed of thoracic radiologists who developed the provided guidance. These recommendations represent a combination of current published evidence and expert opinion and were finalized by informal iterative consensus. The recommendations address the most commonly encountered mediastinal and cardiovascular incidental findings and are not intended to be a comprehensive review of all incidental findings associated with these compartments. Our goal is to improve the quality of care by providing guidance on how to manage incidentally detected thoracic findings.

  View details for PubMedID 29941240

• Computed Tomography Features associated With the Eighth Edition TNM Stage Classification for Thymic Epithelial Tumors JOURNAL OF THORACIC IMAGING Padda, S. K., Terrone, D., Tian, L., Khuong, A., Neal, J. W., Riess, J. W., Berry, M. F., Hoang, C. D., Burt, B. M., Leung, A. N., Schwartz, E. J., Shrager, J. B., Wakelee, H. A. 2018; 33 (3): 176–83

  Abstract

  The eighth edition of the TNM classification of malignant tumors for the first time includes an official staging system for thymic epithelial tumors (TETs) recognized by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). Staging is critical for the management of TETs, and determining stage accurately from imaging has the potential to improve clinical outcomes. We examine preoperative computed tomography (CT) characteristics of TETs associated with AJCC/UICC pathologic TNM stage.In this retrospective study, patients were included if they met all the following criteria: (1) diagnosis of TET, (2) had primary curative intent surgery performed at Stanford University, and (3) had available preoperative CT imaging for review. Tumor pathology was staged according to the eighth edition TNM classification. Fifteen CT scan features were examined from each patient case according to the International Thymic Malignancy Interest Group standard report terms in a blinded manner. A Lasso-regularized multivariate model was used to produce a weighted scoring system predictive of pathologic TNM stage.Examining the 54 patients included, the following CT characteristics were associated with higher pathologic TNM stage when using the following scoring system: elevated hemidiaphragm (score of 6), vascular endoluminal invasion (score of 6), pleural nodule (score of 2), lobulated contour (score of 2), and heterogeneous internal density (score of 1). Area under the receiver operating characteristic curve was 0.76.TETs with clearly invasive or metastatic features seen on CT are associated with having higher AJCC/UICC pathologic TNM stage, as expected. However, features of lobulated contour and heterogeneous internal density are also associated with higher stage disease. These findings need to be validated in an independent cohort.

  View details for PubMedID 29219888

• Lung Cancer Screening, Version 3.2018 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Wood, D. E., Kazerooni, E. A., Baum, S. L., Eapen, G. A., Ettinger, D. S., Hou, L., Jackman, D. M., Klippenstein, D., Kumar, R., Lackner, R. P., Leard, L. E., Lennes, I. T., Leung, A. C., Makani, S. S., Massion, P. P., Mazzone, P., Merritt, R. E., Meyers, B. F., Midthun, D. E., Pipavath, S., Pratt, C., Reddy, C., Reid, M. E., Rotter, A. J., Sachs, P. B., Schabath, M. B., Schiebler, M. L., Tong, B. C., Travis, W. D., Wei, B., Yang, S. C., Gregory, K. M., Hughes, M. 2018; 16 (4): 412–41

  Abstract

  Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. Early detection of lung cancer is an important opportunity for decreasing mortality. Data support using low-dose computed tomography (LDCT) of the chest to screen select patients who are at high risk for lung cancer. Lung screening is covered under the Affordable Care Act for individuals with high-risk factors. The Centers for Medicare & Medicaid Services (CMS) covers annual screening LDCT for appropriate Medicare beneficiaries at high risk for lung cancer if they also receive counseling and participate in shared decision-making before screening. The complete version of the NCCN Guidelines for Lung Cancer Screening provides recommendations for initial and subsequent LDCT screening and provides more detail about LDCT screening. This manuscript focuses on identifying patients at high risk for lung cancer who are candidates for LDCT of the chest and on evaluating initial screening findings.

  View details for DOI 10.6004/jnccn.2018.0020

  View details for Web of Science ID 000429534300011

  View details for PubMedID 29632061

• Presence of Even a Small Ground-Glass Component in Lung Adenocarcinoma Predicts Better Survival CLINICAL LUNG CANCER Berry, M. F., Gao, R., Kunder, C. A., Backhus, L., Khuong, A., Kadoch, M., Leung, A., Shrager, J. 2018; 19 (1): E47–E51

  Abstract

  While lepidic-predominant lung adenocarcinomas are known to have better outcomes than similarly sized solid tumors, the impact of smaller noninvasive foci within predominantly solid tumors is less clearly characterized. We tested the hypothesis that lung adenocarcinomas with even a small ground-glass opacity (GGO) component have a better prognosis than otherwise similar pure solid (PS) adenocarcinomas.The maximum total and solid-component diameters were determined by preoperative computed tomography in patients who underwent lobar or sublobar resection of clinical N0 adenocarcinomas without induction therapy between May 2003 and August 2013. Survival between patients with PS tumors (0% GGO) or tumors with a minor ground-glass (MGG) component (1%-25% GGO) was compared by Kaplan-Meier and Cox analyses.A total of 123 patients met the inclusion criteria, comprising 54 PS (44%) and 69 MGG (56%) whose mean ground-glass component was 18 ± 7%. The solid component tumor diameter was not significantly different between the groups (2.3 ± 1.2 cm vs. 2.5 ± 1.3 cm, P = .2). Upstaging to pN1-2 was more common for the PS group (13% [7/54] vs. 3% [2/69], P = .04), but the distribution of pathologic stage was not significantly different between the groups (PS 76% stage I [41/54] vs. MGG 80% stage I [55/69], P = .1). Having a MGG component was associated with markedly better survival in both univariate analysis (MGG 5-year overall survival 86.7% vs. PS 64.5%, P = .001) and multivariable survival analysis (hazard ratio, 0.30, P = .01).Patients with resected cN0 lung adenocarcinoma who have even a small GGO component have markedly better survival than patients with PS tumors, which may have implications for both treatment and surveillance strategies.

  View details for PubMedID 28743420

• An Analysis of Lung Cancer Screening Beliefs and Practice Patterns for Community Providers Compared to Academic Providers. Cancer control : journal of the Moffitt Cancer Center Khairy, M., Duong, D. K., Shariff-Marco, S., Cheng, I., Jain, J., Balakrishnan, A., Liu, L., Gupta, A., Chandramouli, R., Hsing, A., Leung, A., Singh, B., Nair, V. S. 2018; 25 (1): 1073274818806900

  Abstract

  Despite guidelines recommending annual low-dose computed tomography (LDCT) screening for lung cancer, uptake remains low due to the perceived complexity of initiating and maintaining a clinical program-problems that likely magnify in underserved populations. We conducted a survey of community providers at Federally Qualified Health Centers (FQHCs) in Santa Clara County, California, to evaluate provider-related factors that affect adherence. We then compared these findings to academic providers' (APs) LDCT screening knowledge, behaviors, and attitudes at an academic referral center in the same county. The 4 FQHCs enrolled care for 80 000 patients largely of minority descent and insured by Medi-Cal. Of the 75 FQHC providers (FQHCPs), 36 (48%) completed the survey. Of the 36 providers, 8 (22%) knew screening criteria. Fifteen (42%) FQHCPs discussed LDCT screening with patients. Compared to 36 APs, FQHCPs were more concerned about harms, false positives, discussion time, patient apathy, insurance coverage, and a lack of expertise for screening and follow-up. Yet, more FQHCPs thought screening was effective (27 [75%] of 36) compared to APs ( P = .0003). In conclusion, provider knowledge gaps are greater and barriers are different for community clinics caring for underserved populations compared to their academic counterparts, but practical and scalable solutions exist to enhance adoption.

  View details for PubMedID 30375235

• Non-Small Cell Lung Cancer Radiogenomics Map Identifies Relationships between Molecular and Imaging Phenotypes with Prognostic Implications. Radiology Zhou, M. n., Leung, A. n., Echegaray, S. n., Gentles, A. n., Shrager, J. B., Jensen, K. C., Berry, G. J., Plevritis, S. K., Rubin, D. L., Napel, S. n., Gevaert, O. n. 2018; 286 (1): 307–15

  Abstract

  Purpose To create a radiogenomic map linking computed tomographic (CT) image features and gene expression profiles generated by RNA sequencing for patients with non-small cell lung cancer (NSCLC). Materials and Methods A cohort of 113 patients with NSCLC diagnosed between April 2008 and September 2014 who had preoperative CT data and tumor tissue available was studied. For each tumor, a thoracic radiologist recorded 87 semantic image features, selected to reflect radiologic characteristics of nodule shape, margin, texture, tumor environment, and overall lung characteristics. Next, total RNA was extracted from the tissue and analyzed with RNA sequencing technology. Ten highly coexpressed gene clusters, termed metagenes, were identified, validated in publicly available gene-expression cohorts, and correlated with prognosis. Next, a radiogenomics map was built that linked semantic image features to metagenes by using the t statistic and the Spearman correlation metric with multiple testing correction. Results RNA sequencing analysis resulted in 10 metagenes that capture a variety of molecular pathways, including the epidermal growth factor (EGF) pathway. A radiogenomic map was created with 32 statistically significant correlations between semantic image features and metagenes. For example, nodule attenuation and margins are associated with the late cell-cycle genes, and a metagene that represents the EGF pathway was significantly correlated with the presence of ground-glass opacity and irregular nodules or nodules with poorly defined margins. Conclusion Radiogenomic analysis of NSCLC showed multiple associations between semantic image features and metagenes that represented canonical molecular pathways, and it can result in noninvasive identification of molecular properties of NSCLC. Online supplemental material is available for this article.

  View details for PubMedID 28727543

• Evaluating the impact of varied compliance to lung cancer screening recommendations using a microsimulation model CANCER CAUSES & CONTROL Han, S. S., Erdogan, S., Toumazis, I., Leung, A., Plevritis, S. K. 2017; 28 (9): 947–58

  Abstract

  The US preventive services task force (USPSTF) recently recommended that individuals aged 55-80 with heavy smoking history be annually screened by low-dose computed tomography (LDCT), thereby extending the stopping age from 74 to 80 compared to the national lung screening trial (NLST) entry criterion. This decision was made partly with model-based analyses from cancer intervention and surveillance modeling network (CISNET), which assumed perfect compliance to screening.As part of CISNET, we developed a microsimulation model for lung cancer (LC) screening and calibrated and validated it using data from NLST and the prostate, lung, colorectal, and ovarian cancer screening trial (PLCO), respectively. We evaluated population-level outcomes of the lifetime screening program recommended by the USPSTF by varying screening compliance levels.Validation using PLCO shows that our model reproduces observed PLCO outcomes, predicting 884 LC cases [Expected(E)/Observed(O) = 0.99; CI 0.92-1.06] and 563 LC deaths (E/O = 0.94 CI 0.87-1.03) in the screening arm that has an average compliance rate of 87.9% over four annual screening rounds. We predict that perfect compliance to the USPSTF recommendation saves 501 LC deaths per 100,000 persons in the 1950 U.S. birth cohort; however, assuming that compliance behaviors extrapolated and varied from PLCO reduces the number of LC deaths avoided to 258, 230, and 175 as the average compliance rate over 26 annual screening rounds changes from 100 to 46, 39, and 29%, respectively.The implementation of the USPSTF recommendation is expected to contribute to a reduction in LC deaths, but the magnitude of the reduction will likely be heavily influenced by screening compliance.

  View details for PubMedID 28702814

  View details for PubMedCentralID PMC5880208

• Prediction of EGFR and KRAS mutation in non-small cell lung cancer using quantitative 18F FDG-PET/CT metrics. Oncotarget Minamimoto, R., Jamali, M., Gevaert, O., Echegaray, S., Khuong, A., Hoang, C. D., Shrager, J. B., Plevritis, S. K., Rubin, D. L., Leung, A. N., Napel, S., Quon, A. 2017; 8 (32): 52792-52801

  Abstract

  This study investigated the relationship between epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in non-small-cell lung cancer (NSCLC) and quantitative FDG-PET/CT parameters including tumor heterogeneity. 131 patients with NSCLC underwent staging FDG-PET/CT followed by tumor resection and histopathological analysis that included testing for the EGFR and KRAS gene mutations. Patient and lesion characteristics, including smoking habits and FDG uptake parameters, were correlated to each gene mutation. Never-smoker (P < 0.001) or low pack-year smoking history (p = 0.002) and female gender (p = 0.047) were predictive factors for the presence of the EGFR mutations. Being a current or former smoker was a predictive factor for the KRAS mutations (p = 0.018). The maximum standardized uptake value (SUVmax) of FDG uptake in lung lesions was a predictive factor of the EGFR mutations (p = 0.029), while metabolic tumor volume and total lesion glycolysis were not predictive. Amongst several tumor heterogeneity metrics included in our analysis, inverse coefficient of variation (1/COV) was a predictive factor (p < 0.02) of EGFR mutations status, independent of metabolic tumor diameter. Multivariate analysis showed that being a never-smoker was the most significant factor (p < 0.001) for the EGFR mutations in lung cancer overall. The tumor heterogeneity metric 1/COV and SUVmax were both predictive for the EGFR mutations in NSCLC in a univariate analysis. Overall, smoking status was the most significant factor for the presence of the EGFR and KRAS mutations in lung cancer.

  View details for DOI 10.18632/oncotarget.17782

  View details for PubMedID 28881771

  View details for PubMedCentralID PMC5581070

• Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017 RADIOLOGY MacMahon, H., Naidich, D. P., Goo, J., Lee, K., Leung, A. C., Mayo, J. R., Mehta, A. C., Ohno, Y., Powell, C. A., Prokop, M., Rubin, G. D., Schaefer-Prokop, C. M., Travis, W. D., Van Schil, P. E., Bankier, A. A. 2017; 284 (1): 228–43

  Abstract

  The Fleischner Society Guidelines for management of solid nodules were published in 2005, and separate guidelines for subsolid nodules were issued in 2013. Since then, new information has become available; therefore, the guidelines have been revised to reflect current thinking on nodule management. The revised guidelines incorporate several substantive changes that reflect current thinking on the management of small nodules. The minimum threshold size for routine follow-up has been increased, and recommended follow-up intervals are now given as a range rather than as a precise time period to give radiologists, clinicians, and patients greater discretion to accommodate individual risk factors and preferences. The guidelines for solid and subsolid nodules have been combined in one simplified table, and specific recommendations have been included for multiple nodules. These guidelines represent the consensus of the Fleischner Society, and as such, they incorporate the opinions of a multidisciplinary international group of thoracic radiologists, pulmonologists, surgeons, pathologists, and other specialists. Changes from the previous guidelines issued by the Fleischner Society are based on new data and accumulated experience. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 13, 2017.

  View details for PubMedID 28240562

• Patient and primary care provider attitudes and adherence towards lung cancer screening at an academic medical center. Preventive medicine reports Duong, D. K., Shariff-Marco, S., Cheng, I., Naemi, H., Moy, L. M., Haile, R., Singh, B., Leung, A., Hsing, A., Nair, V. S. 2017; 6: 17-22

  Abstract

  Low dose CT (LDCT) for lung cancer screening is an evidence-based, guideline recommended, and Medicare approved test but uptake requires further study. We therefore conducted patient and provider surveys to elucidate factors associated with utilization. Patients referred for LDCT at an academic medical center were questioned about their attitudes, knowledge, and beliefs on lung cancer screening. Adherent patients were defined as those who met screening eligibility criteria and completed a LDCT. Referring primary care providers within this same medical system were surveyed in parallel about their practice patterns, attitudes, knowledge and beliefs about screening. Eighty patients responded (36%), 48 of whom were adherent. Among responders, non-Hispanic patients (p = 0.04) were more adherent. Adherent respondents believed that CT technology is accurate and early detection is useful, and they trusted their providers. A majority of non-adherent patients (79%) self-reported an intention to obtain a LDCT in the future. Of 36 of 87 (41%) responding providers, only 31% knew the correct lung cancer screening eligibility criteria, which led to a 37% inappropriate referral rate from 2013 to 2015. Yet, 75% had initiated lung cancer screening discussions, 64% thought screening was at least moderately effective, and 82% were interested in learning more of the 33 providers responding to these questions. Overall, patients were motivated and providers engaged to screen for lung cancer by LDCT. Non-adherent patient "procrastinators" were motivated to undergo screening in the future. Additional follow through on non-adherence may enhance screening uptake, and raising awareness for screening eligibility through provider education may reduce inappropriate referrals.

  View details for DOI 10.1016/j.pmedr.2017.01.012

  View details for PubMedID 28210538

  View details for PubMedCentralID PMC5304233

• Prediction of EGFR and KRAS mutation in non-small cell lung cancer using quantitative 18F FDG-PET/CT metrics. Oncotarget Minamimoto, R., Jamali, M., Gevaert, O., Echegaray, S., Khuong, A., Hoang, C. D., Shrager, J. B., Plevritis, S. K., Rubin, D. L., Leung, A. N., Napel, S., Quon, A. 2017

  Abstract

  This study investigated the relationship between epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in non-small-cell lung cancer (NSCLC) and quantitative FDG-PET/CT parameters including tumor heterogeneity. 131 patients with NSCLC underwent staging FDG-PET/CT followed by tumor resection and histopathological analysis that included testing for the EGFR and KRAS gene mutations. Patient and lesion characteristics, including smoking habits and FDG uptake parameters, were correlated to each gene mutation. Never-smoker (P < 0.001) or low pack-year smoking history (p = 0.002) and female gender (p = 0.047) were predictive factors for the presence of the EGFR mutations. Being a current or former smoker was a predictive factor for the KRAS mutations (p = 0.018). The maximum standardized uptake value (SUVmax) of FDG uptake in lung lesions was a predictive factor of the EGFR mutations (p = 0.029), while metabolic tumor volume and total lesion glycolysis were not predictive. Amongst several tumor heterogeneity metrics included in our analysis, inverse coefficient of variation (1/COV) was a predictive factor (p < 0.02) of EGFR mutations status, independent of metabolic tumor diameter. Multivariate analysis showed that being a never-smoker was the most significant factor (p < 0.001) for the EGFR mutations in lung cancer overall. The tumor heterogeneity metric 1/COV and SUVmax were both predictive for the EGFR mutations in NSCLC in a univariate analysis. Overall, smoking status was the most significant factor for the presence of the EGFR and KRAS mutations in lung cancer.

  View details for DOI 10.18632/oncotarget.17782

  View details for PubMedID 28538213

• Left Atrium Maximal Axial Cross-Sectional Area is a Specific Computed Tomographic Imaging Biomarker of World Health Organization Group 2 Pulmonary Hypertension. Journal of thoracic imaging Jivraj, K., Bedayat, A., Sung, Y. K., Zamanian, R. T., Haddad, F., Leung, A. N., Rosenberg, J., Guo, H. H. 2017; 32 (2): 121-126

  Abstract

  Left heart disease is associated with left atrial enlargement and is a common cause of pulmonary hypertension (PH). We investigated the relationship between left atrium maximal axial cross-sectional area (LA-MACSA), as measured on chest computed tomography (CT), and PH due to left heart disease (World Health Organization group 2) in patients with right heart catheterization-proven PH.A total of 165 patients with PH who had undergone right heart catheterization with pulmonary artery pressure and pulmonary capillary wedge pressure (PCWP) measurements and nongated chest CTs were included. LA-MACSA, LA anterior-posterior, and LA transverse measurements were independently obtained using the hand-drawn region-of-interest and distance measurement tools on standard PACS by 2 blinded cardiothoracic radiologists. Nonparametric statistical analyses and receiver operating characteristic curve were performed.Forty-three patients had group 2 PH (PCWP>15 mm Hg), and 122 had nongroup 2 PH (PCWP≤15 mm Hg). Median LA-MACSA was significantly different between the group 2 PH and nongroup 2 PH patients (2312 vs. 1762 mm, P<0.001). Interobserver concordance correlation for LA-MACSA was high at 0.91 (P<0.001). At a threshold of 2400 mm, LA-MACSA demonstrated 93% specificity for classifying group 2 PH (area under the curve, 0.73; P<0.001).LA-MACSA is a readily obtainable and reproducible measurement of left atrial enlargement on CT and can distinguish between group 2 and nongroup 2 PH with high specificity.

  View details for DOI 10.1097/RTI.0000000000000252

  View details for PubMedID 28009778

• Thoracic Imaging Features of Legionnaire's Disease INFECTIOUS DISEASE CLINICS OF NORTH AMERICA Mittal, S., Singh, A. P., Gold, M., Leung, A. N., Haramati, L. B., Katz, D. S. 2017; 31 (1): 43-+

  Abstract

  Imaging examinations are often performed in patients with Legionnaires' disease. The literature to date has documented that the imaging findings in this disorder are relatively nonspecific, and it is therefore difficult to prospectively differentiate legionella pneumonia from other forms of pneumonia, and from other noninfectious thoracic processes. Through a review of clinical cases and the literature, our objective is for the reader to gain a better understanding of the spectrum of radiographic manifestations of Legionnaires' disease.

  View details for PubMedID 28159175

• Predictive radiogenomics modeling of EGFR mutation status in lung cancer SCIENTIFIC REPORTS Gevaert, O., Echegaray, S., Khuong, A., Hoang, C. D., Shrager, J. B., Jensen, K. C., Berry, G. J., Guo, H. H., Lau, C., Plevritis, S. K., Rubin, D. L., Napel, S., Leung, A. N. 2017; 7

  Abstract

  Molecular analysis of the mutation status for EGFR and KRAS are now routine in the management of non-small cell lung cancer. Radiogenomics, the linking of medical images with the genomic properties of human tumors, provides exciting opportunities for non-invasive diagnostics and prognostics. We investigated whether EGFR and KRAS mutation status can be predicted using imaging data. To accomplish this, we studied 186 cases of NSCLC with preoperative thin-slice CT scans. A thoracic radiologist annotated 89 semantic image features of each patient's tumor. Next, we built a decision tree to predict the presence of EGFR and KRAS mutations. We found a statistically significant model for predicting EGFR but not for KRAS mutations. The test set area under the ROC curve for predicting EGFR mutation status was 0.89. The final decision tree used four variables: emphysema, airway abnormality, the percentage of ground glass component and the type of tumor margin. The presence of either of the first two features predicts a wild type status for EGFR while the presence of any ground glass component indicates EGFR mutations. These results show the potential of quantitative imaging to predict molecular properties in a non-invasive manner, as CT imaging is more readily available than biopsies.

  View details for DOI 10.1038/srep41674

  View details for PubMedID 28139704

• Radiomics and its emerging role in lung cancer research, imaging biomarkers and clinical management: State of the art Lee, G., Lee, H., Park, H., Schiebler, M. L., van Beek, E. R., Ohno, Y., Seo, J., Leung, A. ELSEVIER IRELAND LTD. 2017: 297–307

  Abstract

  With the development of functional imaging modalities we now have the ability to study the microenvironment of lung cancer and its genomic instability. Radiomics is defined as the use of automated or semi-automated post-processing and analysis of large amounts of quantitative imaging features that can be derived from medical images. The automated generation of these analytical features helps to quantify a number of variables in the imaging assessment of lung malignancy. These imaging features include: tumor spatial complexity, elucidation of the tumor genomic heterogeneity and composition, subregional identification in terms of tumor viability or aggressiveness, and response to chemotherapy and/or radiation. Therefore, a radiomic approach can help to reveal unique information about tumor behavior. Currently available radiomic features can be divided into four major classes: (a) morphological, (b) statistical, (c) regional, and (d) model-based. Each category yields quantitative parameters that reflect specific aspects of a tumor. The major challenge is to integrate radiomic data with clinical, pathological, and genomic information to decode the different types of tissue biology. There are many currently available radiomic studies on lung cancer for which there is a need to summarize the current state of the art.

  View details for PubMedID 27638103

• A Rapid Segmentation-Insensitive "Digital Biopsy" Method for Radiomic Feature Extraction: Method and Pilot Study Using CT Images of Non-Small Cell Lung Cancer. Tomography : a journal for imaging research Echegaray, S., Nair, V., Kadoch, M., Leung, A., Rubin, D., Gevaert, O., Napel, S. 2016; 2 (4): 283-294

  Abstract

  Quantitative imaging approaches compute features within images' regions of interest. Segmentation is rarely completely automatic, requiring time-consuming editing by experts. We propose a new paradigm, called "digital biopsy," that allows for the collection of intensity- and texture-based features from these regions at least 1 order of magnitude faster than the current manual or semiautomated methods. A radiologist reviewed automated segmentations of lung nodules from 100 preoperative volume computed tomography scans of patients with non-small cell lung cancer, and manually adjusted the nodule boundaries in each section, to be used as a reference standard, requiring up to 45 minutes per nodule. We also asked a different expert to generate a digital biopsy for each patient using a paintbrush tool to paint a contiguous region of each tumor over multiple cross-sections, a procedure that required an average of <3 minutes per nodule. We simulated additional digital biopsies using morphological procedures. Finally, we compared the features extracted from these digital biopsies with our reference standard using intraclass correlation coefficient (ICC) to characterize robustness. Comparing the reference standard segmentations to our digital biopsies, we found that 84/94 features had an ICC >0.7; comparing erosions and dilations, using a sphere of 1.5-mm radius, of our digital biopsies to the reference standard segmentations resulted in 41/94 and 53/94 features, respectively, with ICCs >0.7. We conclude that many intensity- and texture-based features remain consistent between the reference standard and our method while substantially reducing the amount of operator time required.

  View details for DOI 10.18383/j.tom.2016.00163

  View details for PubMedID 28612050

  View details for PubMedCentralID PMC5466872

• Adaptation of Mycobacterium tuberculosis to Impaired Host Immunity in HIV-Infected Patients JOURNAL OF INFECTIOUS DISEASES Walter, N. D., de Jong, B. C., Garcia, B. J., Dolganov, G. M., Worodria, W., Byanyima, P., Musisi, E., Huang, L., Chan, E. D., Van, T. T., Antonio, M., Ayorinde, A., Kato-Maeda, M., Nahid, P., Leung, A. M., Yen, A., Fingerlin, T. E., Kechris, K., Strong, M., Voskuil, M. I., Davis, J. L., Schoolnik, G. K. 2016; 214 (8): 1205-1211

  Abstract

  It is unknown whether immunosuppression influences the physiologic state of Mycobacterium tuberculosis in vivo. We evaluated the impact of host immunity by comparing M. tuberculosis and human gene transcription in sputum between human immunodeficiency virus (HIV)-infected and uninfected patients with tuberculosis.We collected sputum specimens before treatment from Gambians and Ugandans with pulmonary tuberculosis, revealed by positive results of acid-fast bacillus smears. We quantified expression of 2179 M. tuberculosis genes and 234 human immune genes via quantitative reverse transcription-polymerase chain reaction. We summarized genes from key functional categories with significantly increased or decreased expression.A total of 24 of 65 patients with tuberculosis were HIV infected. M. tuberculosis DosR regulon genes were less highly expressed among HIV-infected patients with tuberculosis than among HIV-uninfected patients with tuberculosis (Gambia, P < .0001; Uganda, P = .037). In profiling of human genes from the same sputa, HIV-infected patients had 3.4-fold lower expression of IFNG (P = .005), 4.9-fold higher expression of ARG1 (P = .0006), and 3.4-fold higher expression of IL10 (P = .0002) than in HIV-uninfected patients with tuberculosis.M. tuberculosis in HIV-infected patients had lower expression of the DosR regulon, a critical metabolic and immunomodulatory switch induced by NO, carbon monoxide, and hypoxia. Our human data suggest that decreased DosR expression may result from alternative pathway activation of macrophages, with consequent decreased NO expression and/or by poor granuloma formation with consequent decreased hypoxic stress.

  View details for DOI 10.1093/infdis/jiw364

  View details for PubMedID 27534685

• A Rapid Segmentation-Insensitive 'Digital Biopsy' Method for Radiomic Feature Extraction; Method and Pilot Study Using CT Images of Non-Small Cell Lung Cancer Tomography Echegaray, S., Nair, V., Kadoch, M., Leung, A., Rubin, D., Gevaert, O., Napel Sandy , et al 2016; 2 (4): 283–94

  Abstract

  Quantitative imaging approaches compute features within images' regions of interest. Segmentation is rarely completely automatic, requiring time-consuming editing by experts. We propose a new paradigm, called "digital biopsy," that allows for the collection of intensity- and texture-based features from these regions at least 1 order of magnitude faster than the current manual or semiautomated methods. A radiologist reviewed automated segmentations of lung nodules from 100 preoperative volume computed tomography scans of patients with non-small cell lung cancer, and manually adjusted the nodule boundaries in each section, to be used as a reference standard, requiring up to 45 minutes per nodule. We also asked a different expert to generate a digital biopsy for each patient using a paintbrush tool to paint a contiguous region of each tumor over multiple cross-sections, a procedure that required an average of <3 minutes per nodule. We simulated additional digital biopsies using morphological procedures. Finally, we compared the features extracted from these digital biopsies with our reference standard using intraclass correlation coefficient (ICC) to characterize robustness. Comparing the reference standard segmentations to our digital biopsies, we found that 84/94 features had an ICC >0.7; comparing erosions and dilations, using a sphere of 1.5-mm radius, of our digital biopsies to the reference standard segmentations resulted in 41/94 and 53/94 features, respectively, with ICCs >0.7. We conclude that many intensity- and texture-based features remain consistent between the reference standard and our method while substantially reducing the amount of operator time required.

  View details for DOI 10.18383/j.tom.2016.00163

  View details for PubMedCentralID PMC5466872

• Diameter of Solid Tumor Component Alone Should be Used to Establish T Stage in Lung Adenocarcinoma. Annals of surgical oncology Burt, B. M., Leung, A. N., Yanagawa, M., Chen, W., Groth, S. S., Hoang, C. D., Nair, V. S., Shrager, J. B. 2015; 22: 1318-1323

  Abstract

  The computed tomographic (CT) appearance of so-called ground glass components within lung adenocarcinomas correlate with noninvasive tumor histology, and solid radiographic components correlate with invasive histology. We hypothesized that T stage might be more accurately applied by considering the solid component nodule diameter rather than total nodule diameter.We identified 74 patients with a solitary lung adenocarcinoma who underwent resection without receiving neoadjuvant therapy. Maximum total diameter and solid diameter of the nodules were measured on CT scans performed within 3 months of surgery. Cox proportional hazard modeling and Kaplan-Meier analyses were performed to determine whether total nodule diameter or solid component diameter was more predictive of overall survival.Thirty-three patients (45 %) had a solid nodule and 41 patients (55 %) had a part-solid nodule. Most patients were white (59 %) and female (69 %), and 42 % had never smoked. Seventy-four percent underwent lobectomy and 23 % sublobar resection. Sixty-six percent had pathologic stage I disease, 22 % stage II, and 12 % stage IIIA. Mean ± SD total and solid nodule diameters were 32.1 ± 17.5 and 24.8 ± 18.0 mm, respectively (p = 0.01). Among patients with part-solid nodules, multivariate modeling incorporating significant univariate predictors of survival (age, gender, procedure, N descriptor) revealed that maximum solid diameter was associated with overall survival (hazard ratio 1.4, p = 0.01), while maximum total diameter was not.In a largely non-Asian cohort undergoing resection for adenocarcinoma, radiographic diameter of the solid component of a part-solid lesion on CT predicts overall survival better than total lesion diameter. These data provide further evidence to support altering the T descriptor for lung adenocarcinoma for part-solid nodules.

  View details for DOI 10.1245/s10434-015-4780-0

  View details for PubMedID 26228108

• Diameter of Solid Tumor Component Alone Should be Used to Establish T Stage in Lung Adenocarcinoma ANNALS OF SURGICAL ONCOLOGY Burt, B. M., Leung, A. N., Yanagawa, M., Chen, W., Groth, S. S., Hoang, C. D., Nair, V. S., Shrager, J. B. 2015; 22: S1318-S1323

  Abstract

  The computed tomographic (CT) appearance of so-called ground glass components within lung adenocarcinomas correlate with noninvasive tumor histology, and solid radiographic components correlate with invasive histology. We hypothesized that T stage might be more accurately applied by considering the solid component nodule diameter rather than total nodule diameter.We identified 74 patients with a solitary lung adenocarcinoma who underwent resection without receiving neoadjuvant therapy. Maximum total diameter and solid diameter of the nodules were measured on CT scans performed within 3 months of surgery. Cox proportional hazard modeling and Kaplan-Meier analyses were performed to determine whether total nodule diameter or solid component diameter was more predictive of overall survival.Thirty-three patients (45 %) had a solid nodule and 41 patients (55 %) had a part-solid nodule. Most patients were white (59 %) and female (69 %), and 42 % had never smoked. Seventy-four percent underwent lobectomy and 23 % sublobar resection. Sixty-six percent had pathologic stage I disease, 22 % stage II, and 12 % stage IIIA. Mean ± SD total and solid nodule diameters were 32.1 ± 17.5 and 24.8 ± 18.0 mm, respectively (p = 0.01). Among patients with part-solid nodules, multivariate modeling incorporating significant univariate predictors of survival (age, gender, procedure, N descriptor) revealed that maximum solid diameter was associated with overall survival (hazard ratio 1.4, p = 0.01), while maximum total diameter was not.In a largely non-Asian cohort undergoing resection for adenocarcinoma, radiographic diameter of the solid component of a part-solid lesion on CT predicts overall survival better than total lesion diameter. These data provide further evidence to support altering the T descriptor for lung adenocarcinoma for part-solid nodules.

  View details for DOI 10.1245/s10434-015-4780-0

  View details for Web of Science ID 000367288100136

• Computed Tomography (CT) Characteristics Associated with the Proposed IASLC/ITMIG TNM Pathologic Staging System for Thymoma Padda, S. K., Terrone, D., Khuong, A., Tian, L., Neal, J. W., Riess, J. W., Berry, M., Leung, A. N., Schwartz, E. J., Shrager, J. B., Wakelee, H. A. ELSEVIER SCIENCE INC. 2015: S196

  View details for Web of Science ID 000370365100273

• Predicting adenocarcinoma recurrence using computational texture models of nodule components in lung CT (vol 42, pg 2054, 2015) MEDICAL PHYSICS Depeursinge, A., Yanagawa, M., Leung, A. N., Rubin, D. L. 2015; 42 (5): 2653

  View details for PubMedID 25979058

• Automated classification of usual interstitial pneumonia using regional volumetric texture analysis in high-resolution computed tomography. Investigative radiology Depeursinge, A., Chin, A. S., Leung, A. N., Terrone, D., Bristow, M., Rosen, G., Rubin, D. L. 2015; 50 (4): 261-267

  Abstract

  We propose a novel computational approach for the automated classification of classic versus atypical usual interstitial pneumonia (UIP).Thirty-three patients with UIP were enrolled in this study. They were classified as classic versus atypical UIP by a consensus of 2 thoracic radiologists with more than 15 years of experience using the American Thoracic Society evidence-based guidelines for computed tomography diagnosis of UIP. Two cardiothoracic fellows with 1 year of subspecialty training provided independent readings. The system is based on regional characterization of the morphological tissue properties of lung using volumetric texture analysis of multiple-detector computed tomography images. A simple digital atlas with 36 lung subregions is used to locate texture properties, from which the responses of multidirectional Riesz wavelets are obtained. Machine learning is used to aggregate and to map the regional texture attributes to a simple score that can be used to stratify patients with UIP into classic and atypical subtypes.We compared the predictions on the basis of regional volumetric texture analysis with the ground truth established by expert consensus. The area under the receiver operating characteristic curve of the proposed score was estimated to be 0.81 using a leave-one-patient-out cross-validation, with high specificity for classic UIP. The performance of our automated method was found to be similar to that of the 2 fellows and to the agreement between experienced chest radiologists reported in the literature. However, the errors of our method and the fellows occurred on different cases, which suggests that combining human and computerized evaluations may be synergistic.Our results are encouraging and suggest that an automated system may be useful in routine clinical practice as a diagnostic aid for identifying patients with complex lung disease such as classic UIP, obviating the need for invasive surgical lung biopsy and its associated risks.

  View details for DOI 10.1097/RLI.0000000000000127

  View details for PubMedID 25551822

  View details for PubMedCentralID PMC4355184

• Predicting adenocarcinoma recurrence using computational texture models of nodule components in lung CT MEDICAL PHYSICS Depeursinge, A., Yanagawa, M., Leung, A. N., Rubin, D. L. 2015; 42 (4): 2054-2063

  Abstract

  To investigate the importance of presurgical computed tomography (CT) intensity and texture information from ground-glass opacities (GGO) and solid nodule components for the prediction of adenocarcinoma recurrence.For this study, 101 patients with surgically resected stage I adenocarcinoma were selected. During the follow-up period, 17 patients had disease recurrence with six associated cancer-related deaths. GGO and solid tumor components were delineated on presurgical CT scans by a radiologist. Computational texture models of GGO and solid regions were built using linear combinations of steerable Riesz wavelets learned with linear support vector machines (SVMs). Unlike other traditional texture attributes, the proposed texture models are designed to encode local image scales and directions that are specific to GGO and solid tissue. The responses of the locally steered models were used as texture attributes and compared to the responses of unaligned Riesz wavelets. The texture attributes were combined with CT intensities to predict tumor recurrence and patient hazard according to disease-free survival (DFS) time. Two families of predictive models were compared: LASSO and SVMs, and their survival counterparts: Cox-LASSO and survival SVMs.The best-performing predictive model of patient hazard was associated with a concordance index (C-index) of 0.81 ± 0.02 and was based on the combination of the steered models and CT intensities with survival SVMs. The same feature group and the LASSO model yielded the highest area under the receiver operating characteristic curve (AUC) of 0.8 ± 0.01 for predicting tumor recurrence, although no statistically significant difference was found when compared to using intensity features solely. For all models, the performance was found to be significantly higher when image attributes were based on the solid components solely versus using the entire tumors (p < 3.08 × 10(-5)).This study constitutes a novel perspective on how to interpret imaging information from CT examinations by suggesting that most of the information related to adenocarcinoma aggressiveness is related to the intensity and morphological properties of solid components of the tumor. The prediction of adenocarcinoma relapse was found to have low specificity but very high sensitivity. Our results could be useful in clinical practice to identify patients for which no recurrence is expected with a very high confidence using a presurgical CT scan only. It also provided an accurate estimation of the risk of recurrence after a given duration t from surgical resection (i.e., C-index = 0.81 ± 0.02).

  View details for DOI 10.1118/1.4916088

  View details for Web of Science ID 000352273200059

  View details for PubMedID 25832095

  View details for PubMedCentralID PMC4385100

• Lung Cancer Screening, Version 1.2015 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Wood, D. E., Kazerooni, E., Baum, S. L., Dransfield, M. T., Eapen, G. A., Ettinger, D. S., Hou, L., Jackman, D. M., Klippenstein, D., Kumar, R., Lackner, R. P., Leard, L. E., Leung, A. N., Makani, S. S., Massion, P. P., Meyers, B. F., Otterson, G. A., Peairs, K., Pipavath, S., Pratt-Pozo, C., Reddy, C., Reid, M. E., Rotter, A. J., Sachs, P. B., Schabath, M. B., Sequist, L. V., Tong, B. C., Travis, W. D., Yang, S. C., Gregory, K. M., Hughes, M. 2015; 13 (1): 23-34

  Abstract

  The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide recommendations for selecting individuals for lung cancer screening, and for evaluation and follow-up of nodules found during screening, and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights focus on the major updates to the 2015 NCCN Guidelines for Lung Cancer Screening, which include a revision to the recommendation from category 2B to 2A for one of the high-risk groups eligible for lung cancer screening. For low-dose CT of the lung, the recommended slice width was revised in the table on "Low-Dose Computed Tomography Acquisition, Storage, Interpretation, and Nodule Reporting."

  View details for Web of Science ID 000347793200007

  View details for PubMedID 25583767

• OPTIMIZED STEERABLE WAVELETS FOR TEXTURE ANALYSIS OF LUNG TISSUE IN 3-D CT: CLASSIFICATION OF USUAL INTERSTITIAL PNEUMONIA Depeursinge, A., Pad, P., Chin, A. S., Leung, A. N., Rubin, D. L., Mueller, H., Unser, M., IEEE IEEE. 2015: 403–6

  View details for Web of Science ID 000380546000096

• Lung Volume Reduction After Stereotactic Ablative Radiation Therapy of Lung Tumors: Potential Application to Emphysema INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Binkley, M. S., Shrager, J. B., Leung, A. N., Popat, R., Trakul, N., Atwood, T. F., Chaudhuri, A., Maxim, P. G., Diehn, M., Loo, B. W. 2014; 90 (1): 216-223

  Abstract

  Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema.We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ≥6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABR and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, α/β = 3).27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ≥3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, -0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, -3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ≥60 Gy (r(2)=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r(2)=0.47, P<.0001).We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across multiple clinical parameters. These data serve to inform our ongoing prospective trial of stereotactic ablative volume reduction (SAVR) for severe emphysema in poor candidates for LVRS.

  View details for DOI 10.1016/j.ijrobp.2014.05.025

  View details for Web of Science ID 000341456500029

• COMPUTED TOMOGRAPHY (CT) CHARACTERISTICS ASSOCIATED WITH MASAOKA-KOGA PATHOLOGIC STAGE IN THYMOMA Padda, S., Terrone, D., Khuong, A., Tian, L., Neal, J. W., Riess, J. W., Hoang, C. D., Burt, B. M., Leung, A. N., Shrager, J. B., Wakelee, H. A. LIPPINCOTT WILLIAMS & WILKINS. 2014: S222

  View details for Web of Science ID 000344627500014

• Lung volume reduction after stereotactic ablative radiation therapy of lung tumors: potential application to emphysema. International journal of radiation oncology, biology, physics Binkley, M. S., Shrager, J. B., Leung, A. N., Popat, R., Trakul, N., Atwood, T. F., Chaudhuri, A., Maxim, P. G., Diehn, M., Loo, B. W. 2014; 90 (1): 216-223

  Abstract

  Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema.We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ≥6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABR and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, α/β = 3).27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ≥3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, -0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, -3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ≥60 Gy (r(2)=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r(2)=0.47, P<.0001).We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across multiple clinical parameters. These data serve to inform our ongoing prospective trial of stereotactic ablative volume reduction (SAVR) for severe emphysema in poor candidates for LVRS.

  View details for DOI 10.1016/j.ijrobp.2014.05.025

  View details for PubMedID 25015205

• ACR-STR practice parameter for the performance and reporting of lung cancer screening thoracic computed tomography (CT): 2014 (Resolution 4). Journal of thoracic imaging Kazerooni, E. A., Austin, J. H., Black, W. C., Dyer, D. S., Hazelton, T. R., Leung, A. N., McNitt-Gray, M. F., Munden, R. F., Pipavath, S. 2014; 29 (5): 310-316

  View details for DOI 10.1097/RTI.0000000000000097

  View details for PubMedID 24992501

• Professionalism in radiology. Journal of thoracic imaging Leung, A. N. 2014; 29 (5): 284-288

  Abstract

  Professionalism has been described as the "basis of medicine's contract with society." This article reviews the foundational principles of medical professionalism and, more specifically, defines the nature and scope of radiologists' responsibilities to patients. In the face of ongoing changes in the environment of medical practice, maintenance of professionalism is an adaptive challenge that will require successful practitioners to be open to and actively engaged in continuous learning and self-improvement. Imaging 3.0 is a change process developed by the American College of Radiology to help radiologists redefine and reprioritize their professional activities as the discipline transitions from a volume-based to value-based specialty.

  View details for DOI 10.1097/RTI.0000000000000100

  View details for PubMedID 25160596

• Prognostic importance of volumetric measurements in stage I lung adenocarcinoma. Radiology Yanagawa, M., Tanaka, Y., Leung, A. N., Morii, E., Kusumoto, M., Watanabe, S., Watanabe, H., Inoue, M., Okumura, M., Gyobu, T., Ueda, K., Honda, O., Sumikawa, H., Johkoh, T., Tomiyama, N. 2014; 272 (2): 557-567

  Abstract

  Purpose To perform volumetric analysis of stage I lung adenocarcinomas by using an automated computer program and to determine value of volumetric computed tomographic (CT) measurements associated with prognostic factors and outcome. Materials and Methods Consecutive patients (n = 145) with stage I lung adenocarcinoma who underwent surgery after preoperative chest CT were enrolled. By using volumetric automated computer-assisted analytic program, nodules were classified into three subgroups: pure ground glass, part solid, or solid. Total tumor volume, solid tumor volume, and percentage of solid volume of each cancer were calculated after eliminating vessel components. One radiologist measured the longest diameter of the solid tumor component and of total tumor with their ratio, which was defined as solid proportion. The value of these quantitative data by examining associations with pathologic prognostic factors and outcome measures (disease-free survival and overall survival) were analyzed with logistic regression and Cox proportional hazards regression models, respectively. Significant parameters identified at univariate analysis were included in the multiple analyses. Results All 22 recurrences occurred in patients with nodules classified as part solid or solid. Multiple logistic regression analysis revealed that percentage of solid volume of 63% or greater was an independent indicator associated with pleural invasion (P = .01). Multiple Cox proportional hazards regression analysis revealed that percentage of solid volume of 63% or greater was a significant indicator of lower disease-free survival (hazard ratio, 18.45 [95% confidence interval: 4.34, 78.49]; P < .001). Both solid tumor volume of 1.5 cm(3) or greater and percentage of solid volume of 63% or greater were significant indicators of decreased overall survival (hazard ratio, 5.92 and 9.60, respectively [95% confidence interval: 1.17, 30.33 and 1.17, 78.91, respectively]; P = .034 and .036, respectively). Conclusion Two volumetric measurements (solid volume, ≥1.5 cm(3); percentage of solid volume, ≥63%) were found to be independent indicators associated with increased likelihood of recurrence and/or death in patients with stage I adenocarcinoma. © RSNA, 2014.

  View details for DOI 10.1148/radiol.14131903

  View details for PubMedID 24708191

• Ultra-low-dose CT of the Lung: Effect of Iterative Reconstruction Techniques on Image Quality. Academic radiology Yanagawa, M., Gyobu, T., Leung, A. N., Kawai, M., Kawata, Y., Sumikawa, H., Honda, O., Tomiyama, N. 2014; 21 (6): 695-703

  Abstract

  To compare quality of ultra-low-dose thin-section computed tomography (CT) images of the lung reconstructed using model-based iterative reconstruction (MBIR) and adaptive statistical iterative reconstruction (ASIR) to filtered back projection (FBP) and to determine the minimum tube current-time product on MBIR images by comparing to standard-dose FBP images.Ten cadaveric lungs were scanned using 120 kVp and four different tube current-time products (8, 16, 32, and 80 mAs). Thin-section images were reconstructed using MBIR, three ASIR blends (30%, 60%, and 90%), and FBP. Using the 8-mAs data, side-to-side comparison of the four iterative reconstruction image sets to FBP was performed by two independent observers who evaluated normal and abnormal findings, subjective image noise, streak artifact, and overall image quality. Image noise was also measured quantitatively. Subsequently, 8-, 16-, and 32-mAs MBIR images were compared to standard-dose FBP images. Comparisons of image sets were analyzed using the Wilcoxon signed rank test with Bonferroni correction.At 8 mAs, MBIR images were significantly better (P < .005) than other reconstruction techniques except in evaluation of interlobular septal thickening. Each set of low-dose MBIR images had significantly lower (P < .001) subjective and objective noise and streak artifacts than standard-dose FBP images. Conspicuity and visibility of normal and abnormal findings were not significantly different between 16-mAs MBIR and 80-mAs FBP images except in identification of intralobular reticular opacities.MBIR imaging shows higher overall quality with lower noise and streak artifacts than ASIR or FBP imaging, resulting in nearly 80% dose reduction without any degradations of overall image quality.

  View details for DOI 10.1016/j.acra.2014.01.023

  View details for PubMedID 24713541

• CT patterns of fungal pulmonary infections of the lung: Comparison of standard-dose and simulated low-dose CT (vol 81, pg 2860, 2012) EUROPEAN JOURNAL OF RADIOLOGY Christe, A., Lin, M. C., Yen, A. C., Hallett, R. L., Roychoudhury, K., Schmitzberger, F., Fleischmann, D., Leung, A. N., Rubin, G. D., Vock, P., Roos, J. E. 2013; 82 (11): 2067

  View details for DOI 10.1016/j.ejrad.2013.07.021

  View details for Web of Science ID 000325484600053

• CT patterns of fungal pulmonary infections of the lung: Comparison of standard-dose and simulated low-dose CT EUROPEAN JOURNAL OF RADIOLOGY Christe, A., Lin, M. C., Yen, A. C., Hallett, R. L., Roychoudhury, K., Schmitzberger, F., Fleischmann, D., Leung, A. N., Rubin, G. D., Vock, P., Roos, J. E. 2012; 81 (10): 2860-2866

  Abstract

  To assess the effect of radiation dose reduction on the appearance and visual quantification of specific CT patterns of fungal infection in immuno-compromised patients.Raw data of thoracic CT scans (64 × 0.75 mm, 120 kVp, 300 reference mAs) from 41 consecutive patients with clinical suspicion of pulmonary fungal infection were collected. In 32 patients fungal infection could be proven (median age of 55.5 years, range 35-83). A total of 267 cuboids showing CT patterns of fungal infection and 27 cubes having no disease were reconstructed at the original and 6 simulated tube currents of 100, 40, 30, 20, 10, and 5 reference mAs. Eight specific fungal CT patterns were analyzed by three radiologists: 76 ground glass opacities, 42 ground glass nodules, 51 mixed, part solid, part ground glass nodules, 36 solid nodules, 5 lobulated nodules, 6 spiculated nodules, 14 cavitary nodules, and 37 foci of air-space disease. The standard of reference was a consensus subjective interpretation by experts whom were not readers in the study.The mean sensitivity and standard deviation for detecting pathological cuboids/disease using standard dose CT was 0.91 ± 0.07. Decreasing dose did not affect sensitivity significantly until the lowest dose level of 5 mAs (0.87 ± 0.10, p=0.012). Nodular pattern discrimination was impaired below the dose level of 30 reference mAs: specificity for fungal 'mixed nodules' decreased significantly at 20, 10 and 5 reference mAs (p<0.05). At lower dose levels, classification drifted from 'solid' to 'mixed nodule', although no lesion was missed.Our simulation data suggest that tube current levels can be reduced from 300 to 30 reference mAs without impairing the diagnostic information of specific CT patterns of pulmonary fungal infections.

  View details for DOI 10.1016/j.ejrad.2011.06.059

  View details for Web of Science ID 000308079700067

  View details for PubMedID 21835569

• Expert Opinion What are the Greatest Challenges and/or Barriers to Applying Evidence-based Medicine in the Daily Practice of Cardiopulmonary Radiology? JOURNAL OF THORACIC IMAGING Boiselle, P. M., Collins, J., Dodd, J. D., Herold, C. J., Leung, A. N. 2012; 27 (5): 271

  View details for DOI 10.1097/RTI.0b013e31825d3131

  View details for Web of Science ID 000308219900009

  View details for PubMedID 22914119

• Non-Small Cell Lung Cancer: Identifying Prognostic Imaging Biomarkers by Leveraging Public Gene Expression Microarray Data-Methods and Preliminary Results RADIOLOGY Gevaert, O., Xu, J., Hoang, C. D., Leung, A. N., Xu, Y., Quon, A., Rubin, D. L., Napel, S., Plevritis, S. K. 2012; 264 (2): 387-396

  Abstract

  To identify prognostic imaging biomarkers in non-small cell lung cancer (NSCLC) by means of a radiogenomics strategy that integrates gene expression and medical images in patients for whom survival outcomes are not available by leveraging survival data in public gene expression data sets.A radiogenomics strategy for associating image features with clusters of coexpressed genes (metagenes) was defined. First, a radiogenomics correlation map is created for a pairwise association between image features and metagenes. Next, predictive models of metagenes are built in terms of image features by using sparse linear regression. Similarly, predictive models of image features are built in terms of metagenes. Finally, the prognostic significance of the predicted image features are evaluated in a public gene expression data set with survival outcomes. This radiogenomics strategy was applied to a cohort of 26 patients with NSCLC for whom gene expression and 180 image features from computed tomography (CT) and positron emission tomography (PET)/CT were available.There were 243 statistically significant pairwise correlations between image features and metagenes of NSCLC. Metagenes were predicted in terms of image features with an accuracy of 59%-83%. One hundred fourteen of 180 CT image features and the PET standardized uptake value were predicted in terms of metagenes with an accuracy of 65%-86%. When the predicted image features were mapped to a public gene expression data set with survival outcomes, tumor size, edge shape, and sharpness ranked highest for prognostic significance.This radiogenomics strategy for identifying imaging biomarkers may enable a more rapid evaluation of novel imaging modalities, thereby accelerating their translation to personalized medicine.

  View details for DOI 10.1148/radiol.12111607

  View details for PubMedID 22723499

• Lung Cancer Screening JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Wood, D. E., Eapen, G. A., Ettinger, D. S., Hou, L., Jackman, D., Kazerooni, E., Klippenstein, D., Lackner, R. P., Leard, L., Leung, A. N., Massion, P. P., Meyers, B. F., Munden, R. F., Otterson, G. A., Peairs, K., Pipavath, S., Pratt-Pozo, C., Reddy, C., Reid, M. E., Rotter, A. J., Schabath, M. B., Sequist, L. V., Tong, B. C., Travis, W. D., Unger, M., Yang, S. C. 2012; 10 (2): 240-265

  View details for Web of Science ID 000300067400008

  View details for PubMedID 22308518

• American Thoracic Society Documents: An Official American Thoracic Society/Society of Thoracic Radiology Clinical Practice Guideline-Evaluation of Suspected Pulmonary Embolism in Pregnancy RADIOLOGY Leung, A. N., Bull, T. M., Jaeschke, R., Lockwood, C. J., Boiselle, P. M., Hurwitz, L. M., James, A. H., McCullough, L. B., Menda, Y., Paidas, M. J., Royal, H. D., Tapson, V. F., Winer-Muram, H. T., Chervenak, F. A., Cody, D. D., McNitt-Gray, M. F., Stave, C. D., Tuttle, B. D., ATS STR Comm Pulm Embolism Pregnan 2012; 262 (2): 635-646

  Abstract

  Pulmonary embolism (PE) is a leading cause of maternal mortality in the developed world. Along with appropriate prophylaxis and therapy, prevention of death from PE in pregnancy requires a high index of clinical suspicion followed by a timely and accurate diagnostic approach.To provide guidance on this important health issue, a multidisciplinary panel of major medical stakeholders was convened to develop evidence-based guidelines for evaluation of suspected pulmonary embolism in pregnancy using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. In formulation of the recommended diagnostic algorithm, the important outcomes were defined to be diagnostic accuracy and diagnostic yield; the panel placed a high value on minimizing cumulative radiation dose when determining the recommended sequence of tests.Overall, the quality of the underlying evidence for all recommendations was rated as very low or low with some of the evidence considered for recommendations extrapolated from studies of the general population. Despite the low quality evidence, strong recommendations were made for three specific scenarios: performance of chest radiography (CXR) as the first radiation-associated procedure; use of lung scintigraphy as the preferred test in the setting of a normal CXR; and performance of computed-tomographic pulmonary angiography (CTPA) rather than digital subtraction angiography (DSA) in a pregnant woman with a nondiagnostic ventilation-perfusion (V/Q) result.The recommendations presented in this guideline are based upon the currently available evidence; availability of new clinical research data and development and dissemination of new technologies will necessitate a revision and update.

  View details for DOI 10.1148/radiol.11114045

  View details for Web of Science ID 000300300200031

  View details for PubMedID 22282185

• An Official American Thoracic Society/Society of Thoracic Radiology Clinical Practice Guideline: Evaluation of Suspected Pulmonary Embolism In Pregnancy AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Leung, A. N., Bull, T. M., Jaeschke, R., Lockwood, C. J., Boiselle, P. M., Hurwitz, L. M., James, A. H., McCullough, L. B., Menda, Y., Paidas, M. J., Royal, H. D., Tapson, V. F., Winer-Muram, H. T., Chervenak, F. A., Cody, D. D., McNitt-Gray, M. F., Stave, C. D., Tuttle, B. D., ATS-STR Comm Pulm Embolism Pregnan 2011; 184 (10): 1200-1208

  Abstract

  Pulmonary embolism (PE) is a leading cause of maternal mortality in the developed world. Along with appropriate prophylaxis and therapy, prevention of death from PE in pregnancy requires a high index of clinical suspicion followed by a timely and accurate diagnostic approach.To provide guidance on this important health issue, a multidisciplinary panel of major medical stakeholders was convened to develop evidence-based guidelines for evaluation of suspected pulmonary embolism in pregnancy using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system. In formulation of the recommended diagnostic algorithm, the important outcomes were defined to be diagnostic accuracy and diagnostic yield; the panel placed a high value on minimizing cumulative radiation dose when determining the recommended sequence of tests.Overall, the quality of the underlying evidence for all recommendations was rated as very low or low, with some of the evidence considered for recommendations extrapolated from studies of the general population. Despite the low-quality evidence, strong recommendations were made for three specific scenarios: performance of chest radiography (CXR) as the first radiation-associated procedure; use of lung scintigraphy as the preferred test in the setting of a normal CXR; and performance of computed-tomographic pulmonary angiography (CTPA) rather than digital subtraction angiography (DSA) in a pregnant woman with a nondiagnostic ventilation-perfusion (V/Q) result.The recommendations presented in this guideline are based upon the currently available evidence; availability of new clinical research data and development and dissemination of new technologies will necessitate a revision and update.

  View details for DOI 10.1164/rccm.201108-1575ST

  View details for Web of Science ID 000297015600021

  View details for PubMedID 22086989

• Integrating medical images and transcriptomic data in non-small cell lung cancer Gevaert, O., Xu, J., Hoang, C., Leung, A., Quon, A., Rubin, D., Napel, S., Plevritis, S. AMER ASSOC CANCER RESEARCH. 2011

  View details for DOI 10.1158/1538-7445.AM2011-4148

  View details for Web of Science ID 000209701405023

• Case 166: Metastatic Left Pulmonary Artery Sarcoma RADIOLOGY Mittra, E. S., Iagaru, A. H., Leung, A. N. 2011; 258 (2): 645-648

  View details for DOI 10.1148/radiol.10082169

  View details for Web of Science ID 000286653700037

  View details for PubMedID 21273527

• Yield of diagnostic procedures for invasive fungal infections in neutropenic febrile patients with chest computed tomography abnormalities MYCOSES Ho, D. Y., Lin, M., Schaenman, J., Rosso, F., Leung, A. N., Coutre, S. E., Sista, R. R., Montoya, J. G. 2011; 54 (1): 59-70

  Abstract

  Haematological patients with neutropenic fever are frequently evaluated with chest computed tomography (CT) to rule out invasive fungal infections (IFI). We retrospectively analysed data from 100 consecutive patients with neutropenic fever and abnormal chest CT from 1998 to 2005 to evaluate their chest CT findings and the yield of diagnostic approaches employed. For their initial CTs, 79% had nodular opacities, with 24.1% associated with the halo sign. Other common CT abnormalities included pleural effusions (48%), ground glass opacities (37%) and consolidation (31%). The CT findings led to a change in antifungal therapy in 54% of the patients. Fifty-six patients received diagnostic procedures, including 46 bronchoscopies, 25 lung biopsies and seven sinus biopsies, with a diagnostic yield for IFI of 12.8%, 35.0% and 83.3%, respectively. In conclusion, chest CT plays an important role in the evaluation of haematological patients with febrile neutropenia and often leads to a change in antimicrobial therapy. Pulmonary nodules are the most common radiological abnormality. Sinus or lung biopsies have a high-diagnostic yield for IFI as compared to bronchoscopy. Patients with IFI may not have sinus/chest symptoms, and thus, clinicians should have a low threshold for performing sinus/chest imaging, and if indicated and safe, a biopsy of the abnormal areas.

  View details for DOI 10.1111/j.1439-0507.2009.01760.x

  View details for PubMedID 19793207

• Epoprostenol-associated pneumonitis: diagnostic use of a T-cell proliferation assay. journal of heart and lung transplantation Kudelko, K. T., Nadeau, K., Leung, A. N., Liu, J., Haddad, F., Zamanian, R. T., de Jesus Perez, V. 2010; 29 (9): 1071-1075

  Abstract

  We describe a case of severe drug-induced interstitial pneumonitis in a woman with idiopathic pulmonary arterial hypertension receiving epoprostenol confirmed by a drug T-cell proliferation assay. Proliferation assays were completed in our patient and in a healthy control. Isolated T cells were incubated with CD3-depleted peripheral blood mononuclear cells and then stimulated to proliferate with (3)H-thymidine in the presence of epoprostenol, other prostanoid analogs, and controls. A significant (p < 0.001) T-cell proliferation response occurred in our patient in the presence of epoprostenol alone. There was a trend towards an increased T-cell response to treprostinil but this was statistically insignificant. There was no significant T-cell response to the diluent alone, normal saline, iloprost, or alprostadil. There was no significant proliferation to any drug in the healthy control. Hence, a drug T-cell proliferation assay confirmed that epoprostenol can rarely incite a profound inflammatory response in the pulmonary interstitium.

  View details for DOI 10.1016/j.healun.2010.04.023

  View details for PubMedID 20627625

  View details for PubMedCentralID PMC2926193

• Epoprostenol-associated pneumonitis: Diagnostic use of a T-cell proliferation assay JOURNAL OF HEART AND LUNG TRANSPLANTATION Kudelko, K. T., Nadeau, K., Leung, A. N., Liu, J., Haddad, F., Zamanian, R. T., Perez, V. D. 2010; 29 (9): 1071-1075

  Abstract

  We describe a case of severe drug-induced interstitial pneumonitis in a woman with idiopathic pulmonary arterial hypertension receiving epoprostenol confirmed by a drug T-cell proliferation assay. Proliferation assays were completed in our patient and in a healthy control. Isolated T cells were incubated with CD3-depleted peripheral blood mononuclear cells and then stimulated to proliferate with (3)H-thymidine in the presence of epoprostenol, other prostanoid analogs, and controls. A significant (p < 0.001) T-cell proliferation response occurred in our patient in the presence of epoprostenol alone. There was a trend towards an increased T-cell response to treprostinil but this was statistically insignificant. There was no significant T-cell response to the diluent alone, normal saline, iloprost, or alprostadil. There was no significant proliferation to any drug in the healthy control. Hence, a drug T-cell proliferation assay confirmed that epoprostenol can rarely incite a profound inflammatory response in the pulmonary interstitium.

  View details for DOI 10.1016/j.healun.2010.04.023

  View details for Web of Science ID 000281494800016

  View details for PubMedCentralID PMC2926193

• Computer-aided detection (CAD) of lung nodules in CT scans: radiologist performance and reading time with incremental CAD assistance EUROPEAN RADIOLOGY Roos, J. E., Paik, D., Olsen, D., Liu, E. G., Chow, L. C., Leung, A. N., Mindelzun, R., Choudhury, K. R., Naidich, D. P., Napel, S., Rubin, G. D. 2010; 20 (3): 549-557

  Abstract

  The diagnostic performance of radiologists using incremental CAD assistance for lung nodule detection on CT and their temporal variation in performance during CAD evaluation was assessed.CAD was applied to 20 chest multidetector-row computed tomography (MDCT) scans containing 190 non-calcified > or =3-mm nodules. After free search, three radiologists independently evaluated a maximum of up to 50 CAD detections/patient. Multiple free-response ROC curves were generated for free search and successive CAD evaluation, by incrementally adding CAD detections one at a time to the radiologists' performance.The sensitivity for free search was 53% (range, 44%-59%) at 1.15 false positives (FP)/patient and increased with CAD to 69% (range, 59-82%) at 1.45 FP/patient. CAD evaluation initially resulted in a sharp rise in sensitivity of 14% with a minimal increase in FP over a time period of 100 s, followed by flattening of the sensitivity increase to only 2%. This transition resulted from a greater prevalence of true positive (TP) versus FP detections at early CAD evaluation and not by a temporal change in readers' performance. The time spent for TP (9.5 s +/- 4.5 s) and false negative (FN) (8.4 s +/- 6.7 s) detections was similar; FP decisions took two- to three-times longer (14.4 s +/- 8.7 s) than true negative (TN) decisions (4.7 s +/- 1.3 s).When CAD output is ordered by CAD score, an initial period of rapid performance improvement slows significantly over time because of non-uniformity in the distribution of TP CAD output and not to a changing reader performance over time.

  View details for DOI 10.1007/s00330-009-1596-y

  View details for Web of Science ID 000274544800005

  View details for PubMedID 19760237

• Best Cases from the AFIP Fatal 2009 Influenza A (H1N1) Infection, Complicated by Acute Respiratory Distress Syndrome and Pulmonary Interstitial Emphysema RADIOGRAPHICS Guo, H. H., Sweeney, R. T., Regula, D., Leung, A. N. 2010; 30 (2): 327-333

  View details for DOI 10.1148/rg.302095213

  View details for Web of Science ID 000275622400003

  View details for PubMedID 20068001

• Cystic Fibrosis HRCT Scores Correlate Strongly With Pseudomonas Infection PEDIATRIC PULMONOLOGY Robinson, T. E., Leung, A. N., Chen, X., Moss, R. B., Emond, M. J. 2009; 44 (11): 1107-1117

  Abstract

  In order to establish a valid surrogate outcome measure, it must be shown that the outcome measure (chest HRCT scores in cystic fibrosis [CF] patients) demonstrates strong statistical association with established endpoints of disease, such as Pseudomonas aeruginosa (Pa) airway acquisition, acute exacerbations, or mortality.We estimated and tested the association between Pa infection status (Pa+ vs. Pa-) and baseline chest HRCT scores in 25 children with mild-to-moderate CF lung disease. For comparison, we estimated the association between Pa status and pulmonary function tests (PFTs), chest X-rays (CXR) scores, and BMI. Pa acquisition was determined from respiratory culture results and systematic review of clinic notes.All subjects had respiratory cultures performed prior to or at baseline with a median of 19 months of retrospective culture observation (SD = 15.7 months, range: 0-52.5 months). The difference between age-adjusted mean total HRCT score for Pa+ versus Pa- was highly significant (P < 0.00001) with a near-perfect separation between scores in Pa+ versus Pa- patients. Similar results were found for several HRCT sub-scores. Among PFTs, only residual volume-to-total lung capacity (RV/TLC) had a significant difference between group means (P = 0.03), but the overlap between groups in RV/TLC measurements was large.CF HRCT scores correlate highly with Pa acquisition, a clinically meaningful measure of progressing CF lung disease. HRCT scores are highly sensitive at predicting Pa acquisition status, while most PFT measures, chest radiograph (CXR) scores, and body mass index are not. These results provide further evidence that HRCT is appropriate for use in patient care and as an outcome measure in clinical trials.

  View details for DOI 10.1002/ppul.21107

  View details for Web of Science ID 000271602200009

  View details for PubMedID 19824046

• Discordance rates between preliminary and final radiology reports on cross-sectional imaging studies at a level 1 trauma center ACADEMIC RADIOLOGY Stevens, K. J., Griffiths, K. L., Rosenberg, J., Mahadevan, S., Zatz, L. M., Leung, A. N. 2008; 15 (10): 1217-1226

  Abstract

  The goal was to determine discordance rates between preliminary radiology reports provided by on-call radiology house staff and final reports from attending radiologists on cross-sectional imaging studies requested by emergency department staff after hours.A triplicate carbon copy reporting form was developed to provide permanent records of preliminary radiology reports and to facilitate communication of discrepant results to the emergency department. Data were collected over 21 weeks to determine the number of discordant readings. Patients' medical records were reviewed to show whether discrepancies were significant or insignificant and to assess their impact on subsequent management and patient outcome.The emergency department requested 2830 cross-sectional imaging studies after hours and 2311 (82%) had a copy of the triplicate form stored in radiology archives. Discrepancies between the preliminary and final report were recorded in 47 (2.0%), with 37 (1.6%) considered significant: 14 patients needed no change, 13 needed a minor change, and 10 needed a major change in subsequent management. Ten (0.43%) of the discordant scans were considered insignificant. A random sample of 104 (20%) of the 519 scans without a paper triplicate form was examined. Seventy-one (68%) did have a scanned copy of the triplicate form in the electronic record, with a discrepancy recorded in 3 (4.2%), which was not statistically different from the main cohort (P = .18).Our study suggests a high level of concordance between preliminary reports from on-call radiology house staff and final reports by attending subspecialty radiologists on cross-sectional imaging studies requested by the emergency department.

  View details for DOI 10.1016/j.acra.2008.03.017

  View details for PubMedID 18790392

• Primary interpretation of thoracic MDCT images using coronal reformations AMERICAN JOURNAL OF ROENTGENOLOGY Kwan, S. W., Partik, B. L., Zinck, S. E., Chan, F. P., Kee, S. T., Leung, A. N., Voracek, M., Rubin, G. D. 2005; 185 (6): 1500-1508

  Abstract

  The objective of this study was to evaluate the accuracy and efficiency of primary interpretation of thoracic MDCT using coronal reformations as compared with transverse images.Fifty patients (18 females, 32 males; age range, 15-93 years; mean age, 63.6 years) underwent 4-MDCT of the chest (detector width, 1 mm; beam pitch, 1.5). Contrast material was administered in 20 of the 50 patients. Coronal and transverse sections were reformatted into 5-mm-thick sections at 3.5-mm intervals. All available image and clinical data consensually reviewed by two thoracic radiologists served as the reference standard. Subsequently, three other thoracic radiologists independently evaluated reformatted coronal and transverse images at two separate review sessions. Each image set was assessed in 58 categories for abnormalities of the lungs, mediastinum, pleura, chest wall, diaphragm, abdomen, and skeleton. Interpretation times and number of images assessed were recorded. Sensitivity, specificity, and interobserver concordance were calculated. Differences in mean sensitivities and specificities were evaluated with Wilcoxon's signed rank test.The most common findings identified were pulmonary nodules (n = 73, transverse images; n = 72, coronal images) and emphysema (n = 45, transverse; n = 40, coronal). The mean detection sensitivity of all lesions was significantly (p = 0.001) lower on coronal (44% +/- 26% [SD]) than on transverse (51% +/- 22%) images, whereas the mean detection specificity was significantly (p = 0.005) higher (96% +/- 5% vs 95% +/- 6%, respectively). Reporting findings for significantly (p < 0.001) fewer coronal images (mean, 63.0 +/- 4.6 images) than transverse images (mean, 91.9 +/- 8.8 images) took significantly (p = 0.025) longer (mean, 263 +/- 56 sec vs 238 +/- 45 sec, respectively).Primary interpretation of thoracic MDCT is less sensitive and more time-consuming using 5-mm-thick coronal reformations as compared with transverse images.

  View details for DOI 10.2214/AJR.04.1335

  View details for Web of Science ID 000233510600019

  View details for PubMedID 16304004

• Recurrent lymphoma of the lung - Computed tomography appearance JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Hwang, G. L., Leung, A. N., Zinck, S. E., Berry, G. J. 2005; 29 (2): 228-230

  Abstract

  To describe the computed tomography findings of recurrent lymphoma involving the lung.Computed tomography scans of 15 patients with biopsy-proven recurrent lymphoma involving the lung were reviewed. Group mean age of enrolled patients was 38 years (range: 14-68 years). Pathologic specimens were obtained by thoracoscopic or open wedge biopsy (n = 8), transbronchial biopsy (n = 5), and fine needle aspiration (n = 2).Nodules, the most common manifestation, were present in all patients; nodules were greater than 10 in number in 12 (80%) of 15 cases and predominantly 6-10 mm in size in 8 cases (53%). Nodular distribution was bilateral and multilobar except in 2 patients, in whom a solitary pulmonary nodule was found. Lymphadenopathy was the second most common finding; it was seen in 13 (87%) of 15 cases and involved an average of 5 nodal stations.Recurrent lymphoma in the lung most commonly manifests as multiple pulmonary nodules that are typically bilateral and multilobar in distribution.

  View details for Web of Science ID 000228030400014

  View details for PubMedID 15772542

• Pulmonary nodules on multi-detector row CT scans: Performance comparison of radiologists and computer-aided detection RADIOLOGY Rubin, G. D., Lyo, J. K., Paik, D. S., Sherbondy, A. J., Chow, L. C., Leung, A. N., Mindelzun, R., Schraedley-Desmond, P. K., Zinck, S. E., Naidich, D. P., Napel, S. 2005; 234 (1): 274-283

  Abstract

  To compare the performance of radiologists and of a computer-aided detection (CAD) algorithm for pulmonary nodule detection on thin-section thoracic computed tomographic (CT) scans.The study was approved by the institutional review board. The requirement of informed consent was waived. Twenty outpatients (age range, 15-91 years; mean, 64 years) were examined with chest CT (multi-detector row scanner, four detector rows, 1.25-mm section thickness, and 0.6-mm interval) for pulmonary nodules. Three radiologists independently analyzed CT scans, recorded the locus of each nodule candidate, and assigned each a confidence score. A CAD algorithm with parameters chosen by using cross validation was applied to the 20 scans. The reference standard was established by two experienced thoracic radiologists in consensus, with blind review of all nodule candidates and free search for additional nodules at a dedicated workstation for three-dimensional image analysis. True-positive (TP) and false-positive (FP) results and confidence levels were used to generate free-response receiver operating characteristic (ROC) plots. Double-reading performance was determined on the basis of TP detections by either reader.The 20 scans showed 195 noncalcified nodules with a diameter of 3 mm or more (reference reading). Area under the alternative free-response ROC curve was 0.54, 0.48, 0.55, and 0.36 for CAD and readers 1-3, respectively. Differences between reader 3 and CAD and between readers 2 and 3 were significant (P < .05); those between CAD and readers 1 and 2 were not significant. Mean sensitivity for individual readings was 50% (range, 41%-60%); double reading resulted in increase to 63% (range, 56%-67%). With CAD used at a threshold allowing only three FP detections per CT scan, mean sensitivity was increased to 76% (range, 73%-78%). CAD complemented individual readers by detecting additional nodules more effectively than did a second reader; CAD-reader weighted kappa values were significantly lower than reader-reader weighted kappa values (Wilcoxon rank sum test, P < .05).With CAD used at a level allowing only three FP detections per CT scan, sensitivity was substantially higher than with conventional double reading.

  View details for DOI 10.1148/radiol.2341040589

  View details for Web of Science ID 000225864800038

  View details for PubMedID 15537839

• Chronic expanding hematoma: Mystery or misnomer? Reply AMERICAN JOURNAL OF ROENTGENOLOGY Hwang, G. L., Moffat, S. D., Mitchell, J. D., Leung, A. N. 2004; 183 (1): 244-244

  View details for Web of Science ID 000222163900048

• Case 63: hepatopulmonary syndrome. Radiology Leung, A. N. 2003; 229 (1): 64-67

  View details for PubMedID 14519870

• Invasive aspergillosis in the setting of cardiac transplantation 37th Annual Meeting of the Infectious-Diseases-Society-of-America Montoya, J. G., Chaparro, S. V., Celis, D., Cortes, J. A., Leung, A. N., Robbins, R. C., Stevens, D. A. UNIV CHICAGO PRESS. 2003: S281–S292

  Abstract

  Among patients undergoing heart transplantation, Aspergillus is the opportunistic pathogen with the highest attributable mortality. The median time of onset from transplantation for invasive pulmonary aspergillosis (IPA) was 46 days, but the median time to first positive culture result was 104 days among patients with Aspergillus colonization but no invasive disease. Most patients with IPA presented with fever and cough within the first 90 days of transplantation and with single or multiple pulmonary nodules. None of the heart transplant recipients with either IPA or invasive extrapulmonary aspergillosis (IEPA) had associated neutropenia. Human leukocyte antigen A1 locus was found significantly more frequently among patients colonized with Aspergillus than among patients with IPA (P<.006) or IEPA (P<.001). Even in the absence of neutropenia, IPA should be suspected for heart transplant recipients who have fever and respiratory symptoms within the first 3 months of transplantation, have a positive result of culture of respiratory secretions, and have abnormal radiological findings (particularly nodules).

  View details for PubMedID 12975755

• Composite spirometric-computed tomography outcome measure in early cystic fibrosis lung disease AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Robinson, T. E., Leung, A. N., Northway, W. H., Blankenberg, F. G., Chan, F. P., Bloch, D. A., Holmes, T. H., Moss, R. B. 2003; 168 (5): 588-593

  Abstract

  With the advent of therapies aimed at young patients with cystic fibrosis, who have mildly reduced pulmonary function, the need for improved outcome measures that discriminate treatment effects has become important. Pulmonary function measurements or chest high-resolution computed tomography (HRCT) scores have been separately used to assess interventions. We evaluated these modalities separately and together during a treatment study to develop a more sensitive outcome measure. In a 1-year trial, 25 children randomized either to daily Pulmozyme or to normal saline aerosol were evaluated at randomization and at 3 and 12 months. Outcome variables were pulmonary function test (PFT) results, a global HRCT score, and a composite score incorporating PFTs and HRCT scoring. Regression analyses with generalized estimating equations permitted estimation of the difference in treatment effect between groups over time for each outcome. The largest difference in treatment effects observed at 12 months, measured by the percentage change from baseline, were with the composite total and maximal CT/PFT scores (35.4 and 30.4%), compared with mean forced expiratory flow during the middle half of the FVC (FEF25-75%) (13.0%) and total and maximal global HRCT scores (6.2%, 7.2%). The composite total and maximal CT/PFT scores were the most sensitive outcome measures for discriminating a treatment effect in children with cystic fibrosis with normal or mildly reduced pulmonary function during a 1-year trial of Pulmozyme.

  View details for DOI 10.1164/rccm.200209-1093OC

  View details for PubMedID 12746252

• Chronic expanding hematoma of the thorax AMERICAN JOURNAL OF ROENTGENOLOGY Hwang, G. L., Moffatt, S. D., Mitchell, J. D., Leung, A. N. 2003; 180 (4): 1182-1183

  View details for Web of Science ID 000181745500064

  View details for PubMedID 12646486

• Videofluoroscopy of swallowing abnormalities in 22 symptomatic patients after cardiovascular surgery. AMERICAN JOURNAL OF ROENTGENOLOGY Partik, B. L., Scharitzer, M., Schueller, G., Voracek, M., Schima, W., Schober, E., Mueller, M. R., Leung, A. N., Denk, D. M., Pokieser, P. 2003; 180 (4): 987-992

  Abstract

  The aim of this study was to evaluate the types of swallowing abnormalities that occur in symptomatic patients who have undergone cardiovascular surgery.From 1994 to 2001, 22 patients (17 males and five females; age range, 4-89 years; mean age, 64 years) who had swallowing abnormalities after cardiovascular surgery were referred for a videofluoroscopic swallowing study. Each study was analyzed for functional abnormalities of the tongue, soft palate, epiglottis, hyoid and larynx, pharynx, upper esophageal sphincter, and esophagus. Also, the performance of transesophageal echocardiography, long-term intubation, or both was noted.Swallowing abnormalities were present in 18 patients (81.8%) (range, one to eight functional abnormalities; mean, 3.9 functional abnormalities). The distribution of abnormalities across the functional units statistically significantly deviated (chi(2) = 14.4; df = 6; p = 0.025) from uniform distribution, with abnormalities most commonly involving the hyoid and larynx (13 patients [59.1%]) and the pharynx (10 patients [45.5%]). Aspiration was found in 13 patients (59.1%) (predeglutitive, n = 1; intradeglutitive, n = 4; postdeglutitive, n = 3; and mixed, n = 5). In the 14 patients (63.6%) who underwent transesophageal echocardiography, long-term intubation, or both, we frequently found incomplete tilting of the epiglottis, pharyngeal weakness, and postdeglutitive aspiration.Most patients with swallowing problems after cardiovascular surgery present with multiple abnormalities that most commonly affect the hyoid and larynx and the pharynx and result predominantly in intra- or postdeglutitive aspiration. The performance of transesophageal echocardiography and long-term intubation may influence the types of swallowing abnormalities.

  View details for Web of Science ID 000181745500018

  View details for PubMedID 12646442

• Using a dedicated lung-marker system for localization of pulmonary nodules before thoracoscopic surgery AMERICAN JOURNAL OF ROENTGENOLOGY Partik, B. L., Leung, A. N., Muller, M. R., Breitenseher, M., Eckersberger, F., Dekan, G., Helbich, T. H., Metz, V. 2003; 180 (3): 805-809

  Abstract

  Our aim was to evaluate the effectiveness of a commercially available dedicated lung-marker system for localization of pulmonary nodules before video-assisted thoracoscopic surgery.Guidewires were positioned under CT fluoroscopy guidance in 16 patients (11 men, five women; age range, 39-79 years; mean age, 60.4 years). We measured the size of the targeted nodule, its distance to the closest pleural surface, the angle between the introducer needle and the chest wall, and the time for performance of the procedure in each patient. Note was made of any complications after guidewire placement.In the 16 patients, the average nodule size was 6.7 mm (range, 3-12 mm), the average distance to the pleural surface was 10.6 mm (range, 3-22 mm), and the average pleural puncture angle was 59 degrees (range, 25-78 degrees). The marking procedure was completed within an average of 9.5 min (range, 7-15 min). Small pneumothoraces occurred in five (31.3%) of 16 patients. In 15 (93.8%) of 16 patients, thoracoscopic resection of the targeted nodule was successful; in one patient with dyspnea (6.3%), inaccurate localization resulting in an open thoracotomy occurred because an intervening fissure was not visualized. Dislodgement of the guidewire into the pleural space occurred in one patient (6.3%).The dedicated lung-marker system is a fast and effective method for localization of pulmonary nodules before thoracoscopic resection.

  View details for Web of Science ID 000181153400042

  View details for PubMedID 12591700

• Fast tomosynthesis for lung cancer detection using the SBDX geometry Medical Imaging 2003 Conference Fahrig, R., Pineda, A. R., Solomon, E. G., Leung, A. N., Pejc, N. J. SPIE-INT SOC OPTICAL ENGINEERING. 2003: 371–378

  View details for Web of Science ID 000184199600036

• Bronchogenic carcinoma after lung transplantation: Frequency, clinical characteristics, and imaging findings RADIOLOGY Collins, J., Kazerooni, E. A., Lacomis, J., McAdams, H. P., Leung, A. N., Shiau, M., Semenkovich, J., Love, R. B. 2002; 224 (1): 131-138

  Abstract

  To determine the frequency, clinical characteristics, and radiologic findings of bronchogenic carcinoma in patients surviving more than 1 month after lung transplantation.The study population was composed of 2,168 consecutive patients at seven lung transplantation centers who survived longer than 1 month after lung transplantation. Medical records, chest radiographs, and computed tomographic (CT) scans obtained at the time of diagnosis and prior images when available were reviewed for various items of information and imaging features.Twenty-four (1%) of the 2,168 patients, all with single-lung transplants, developed cancer in the native lung. Eighteen patients had emphysema, and six had pulmonary fibrosis. The frequencies of cancer in patients with emphysema and fibrosis were 2% (18 of 859 patients) and 4% (six of 147 patients), respectively. Twelve (50%) of their 24 cancers were detected at chest radiography. Fourteen (58%) patients had clinical symptoms. Twenty-one (88%) of the 24 patients had one (n = 11) or more (n = 10) nodules, and nine (38%) had one (n = 8) or more (n = 1) masses visible on CT scans. Nodules and masses were visible on 12 (50%) and seven (29%) of 24 chest radiographs, respectively. Eleven (48%) of 23 cancers for which prior chest radiographs were available were seen retrospectively on prior chest radiographs.Bronchogenic carcinoma develops in the native lung of transplant recipients with emphysema and pulmonary fibrosis with frequencies of 2% and 4%, respectively. The carcinomas most commonly manifest as a pulmonary nodule or mass on chest radiographs, with more nodules seen on CT scans.

  View details for DOI 10.1148/radiol.2241011189

  View details for Web of Science ID 000176454700019

  View details for PubMedID 12091672

• Short echo time MR spectroscopic imaging of the lung parenchyma JOURNAL OF MAGNETIC RESONANCE IMAGING Gold, G. E., Pauly, J. M., Leung, A. N., Block, W. F., Meyer, C. H., Sze, R., Macovski, A., Stark, P. 2002; 15 (6): 679-684

  Abstract

  To perform short echo time MR spectroscopic imaging of the lung parenchyma on normal volunteers.A short echo time projection-reconstruction spectroscopic imaging sequence was implemented on a commercial 1.5T whole body MRI scanner. Images and spectra of the lung parenchyma were obtained from five normal volunteers. Breath-held spectroscopic imaging was also performed.Spectroscopic imaging of short-T2* species allows visualization of different anatomic structures based upon their frequency shifts. A characteristic peak from the parenchyma was seen at three ppm from water frequency.Short echo time MR spectroscopic imaging of the lung parenchyma was demonstrated in normal volunteers. This method may improve proton imaging of the lungs and add specificity to the diagnosis of pulmonary disease.

  View details for DOI 10.1002/jmri.10113

  View details for Web of Science ID 000175918300008

  View details for PubMedID 12112518

• Pulmonary cryptococcosis: CT and pathologic findings JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Zinck, S. E., Leung, A. N., Frost, M., Berry, G. J., Muller, N. L. 2002; 26 (3): 330-334

  Abstract

  The purpose of this work was to describe the CT and pathologic findings of pulmonary cryptococcosis.CT scans of 11 patients (7 immunocompromised, 4 immunocompetent) with proven pulmonary cryptococcosis were analyzed for number, morphologic characteristics, and distribution of parenchymal abnormalities as well for presence of lymphadenopathy and pleural effusion. Pathology of lung specimens obtained by open biopsy or resection (n = 5) and transbronchial biopsy (n = 1) was reviewed by one dedicated pulmonary pathologist.Pulmonary nodules, either solitary or multiple, were the most common CT finding, present in 10 of 11 patients (91%); associated findings included masses (n = 4), CT halo sign (n = 3), and consolidation (n = 2). On histologic examination, focal areas of ground-glass attenuation surrounding or adjacent to nodules were found to represent airspace collections of macrophages and proteinaceous fluid.Pulmonary cryptococcosis should be considered in the differential diagnosis of solitary or multiple pulmonary nodules (with or without associated CT halo sign), particularly in immunocompromised patients.

  View details for DOI 10.1097/01.RCT.0000014445.78.502.F9

  View details for Web of Science ID 000175799800002

  View details for PubMedID 12016357

• CT of noninfectious granulomatous lung disease RADIOLOGIC CLINICS OF NORTH AMERICA Zinck, S. E., Schwartz, E., Berry, G. J., Leung, A. N. 2001; 39 (6): 1189-?

  Abstract

  Noninfectious granulomatous diseases of the lung consist of a diverse group of disorders that logically can be subdivided into those with and without associated vasculitis. This article reviews the epidemiologic, clinical, pathologic, and radiologic features of sarcoidosis, hypersensitivity pneumonitis, berylliosis, and the five entities traditionally classified as pulmonary angiitis and granulomatosis.

  View details for Web of Science ID 000172023200008

  View details for PubMedID 11699668

• Cellulose granulomatosis presenting as centrilobular nodules: CT and histologic findings AMERICAN JOURNAL OF ROENTGENOLOGY Bendeck, S. E., Leung, A. N., Berry, G. J., Daniel, D., Ruoss, S. J. 2001; 177 (5): 1151-1153

  View details for Web of Science ID 000171732700034

  View details for PubMedID 11641191

• Spirometer-triggered high-resolution computed tomography and pulmonary function measurements during an acute exacerbation in patients with cystic fibrosis JOURNAL OF PEDIATRICS Robinson, T. E., Leung, A. N., Northway, W. H., Blankenberg, F. G., Bloch, D. A., Oehlert, J. W., Al-Dabbagh, H., Hubli, S., Moss, R. B. 2001; 138 (4): 553-559

  Abstract

  To evaluate a high-resolution computed tomography (HRCT) scoring system, clinical parameters, and pulmonary function measurements in patients with cystic fibrosis (CF) before and after therapy for a pulmonary exacerbation.Patients (n = 17) were evaluated by spirometer-triggered HRCT imaging, clinical parameters, and pulmonary function tests (PFTs) before and after treatment. HRCT scans were reviewed by 3 radiologists using a modified Bhalla scoring system.Bronchiectasis, bronchial wall thickening, and air trapping were identified in all subjects on initial evaluation. The initial total HRCT score correlated significantly with the Brasfield score (r = -.91, P <.001) and several PFT measures. After treatment, there were improvements in the acute change clinical score (ACCS) (P <.001), most pulmonary function measurements, and total HRCT score (P <.05). Bronchiectasis, bronchial wall thickening, and air trapping did not significantly change. Mucus plugging subcomponent HRCT score, slow vital capacity (SVC), forced expiratory volume in 1 second (FEV(1)), and forced vital capacity (FVC) (percent predicted) and reversible and total HRCT scores were most sensitive to change by effect size analysis.Improvements occurred with treatment in total and reversible HRCT scores, PFTs, and ACCS. Total and reversible HRCT scores and percent predicted SVC, FEV1, and FVC were the most sensitive to change. The greatest change was seen in the mucus plugging subcomponent HRCT score.

  View details for PubMedID 11295720

• Paclitaxel-induced hypersensitivity pneumonitis: radiographic and CT findings. AJR. American journal of roentgenology Wong, P., Leung, A. N., Berry, G. J., Atkins, K. A., Montoya, J. G., Ruoss, S. J., Stockdale, F. E. 2001; 176 (3): 718-720

  View details for PubMedID 11222212

• Case report - Paclitaxel-induced hypersensitivity pneumonitis: Radiographic and CT findings AMERICAN JOURNAL OF ROENTGENOLOGY Wong, P., Leung, A. N., Berry, G. J., Atkins, K. A., Montoya, J. G., Ruoss, S. J., Stockdale, F. E. 2001; 176 (3): 718-720

  View details for Web of Science ID 000167118800027

• Digital storage phosphor chest radiography: An ROC study of the effect of 2K versus 4K matrix size on observer performance RADIOLOGY Miro, S. P., Leung, A. N., Rubin, G. D., Choi, Y. H., Kee, S. T., Mindelzun, R. E., Stark, P., Wexler, L., Plevritis, S. K., Betts, B. J. 2001; 218 (2): 527-532

  Abstract

  To compare observer performance in the detection of abnormalities on 1,760 x 2,140 matrix (2K) and 3,520 x 4,280 matrix (4K) digital storage phosphor chest radiographs.One hundred sixty patients who underwent dedicated computed tomography (CT) of the thorax were prospectively recruited into the study. Posteroanterior and lateral computed radiographs of the chest were acquired in each patient and printed in 2K and 4K formats. Six radiologists independently analyzed the hard-copy images and scored the presence of parenchymal (opacities 2 cm, and subtle interstitial), mediastinal, and pleural abnormalities on a five-point confidence scale. With CT as the reference standard, observer performance tests were carried out by using receiver operating characteristic (ROC) analysis.Analysis of averaged observer performance showed 2K and 4K images were equally effective in detection of all three groups of abnormalities. In the detection of the three subtypes of parenchymal abnormalities, there were no significant differences in averaged performance between the 2K and 4K formats (area below ROC curve [A(z)] values: opacities 2 cm, 0.86 +/-.025 and 0.85 +/- 0.030; subtle interstitial abnormalities, 0.73 +/- 0.041 and 0.72 +/- 0.041). Averaged performance in detection of mediastinal and pleural abnormalities was equivalent (A(z) values: mediastinal, 0.70 +/- 0.046 and 0.73 +/- 0.033; pleural, 0.85 +/- 0.032 and 0.86 +/- 0.033).Observer performance in detection of parenchymal, mediastinal, and pleural abnormalities was not significantly different on 2K and 4K storage phosphor chest radiographs.

  View details for Web of Science ID 000166728200033

  View details for PubMedID 11161174

• A model for faculty mentoring in academic radiology ACADEMIC RADIOLOGY Illes, J., Glover, G. H., Wexler, L., Leung, A. N., Glazer, G. M. 2000; 7 (9): 717-724

  Abstract

  The purpose of this report is to describe the development and implementation of a faculty mentoring program in radiology designed to promote the career development of junior faculty and enhance communication in the department.The mentoring program was implemented in five stages: organizational readiness, participant recruitment, mentor matching and orientation, implementation, and evaluation. Evaluations were based on Likert scale ratings and qualitative feedback. A retrospective analysis was also conducted of the annual performance reviews of junior faculty in the areas of research, teaching, patient care, and overall performance.An average of 83% (19 of 23) of the junior faculty participated in the pilot phase of the mentoring program. During five rounds of testing, the median rating (1 indicates not important; 10, extremely important) from responding junior faculty was 10 for overall value of individual mentoring meetings; the median rating for the mentors responding was 8.75. Research and academic development were identified as the areas of greatest importance to the faculty. Research and patient care were most improved as assessed by faculty peers during performance reviews. The schedule of semiannual formal mentoring meetings was reported to be optimal.The program was implemented to the satisfaction of junior faculty and mentors, and longitudinal performance suggests positive effects. Issues to be contended with include confidentiality and the time needed for mentoring beyond already saturated schedules. Overall, the authors propose that mentoring programs can be an asset to academic radiology departments and a key factor in maintaining their vitality.

  View details for Web of Science ID 000089143200007

  View details for PubMedID 10987334

• A curriculum in chest radiology for diagnostic radiology residency, with goals and objectives ACADEMIC RADIOLOGY Kazerooni, E. A., Collins, J., Reddy, G. P., Nath, H. P., Batra, P. V., Boxt, L. M., Duerinckx, A. J., Erasmus, J. J., Fishman, J. E., Leung, A. N., Tarver, R. D., Wexler, L., Winer-Muram, H. T. 2000; 7 (9): 730-743

  View details for Web of Science ID 000089143200010

  View details for PubMedID 10987336

• Aorta and iliac arteries: Single versus multiple detector-row helical CT angiography RADIOLOGY Rubin, G. D., Shiau, M. C., Leung, A. N., Kee, S. T., Logan, L. J., Sofilos, M. C. 2000; 215 (3): 670-676

  Abstract

  To compare single- versus four-channel helical computed tomographic (CT) aortography.Forty-eight patients with aortic aneurysm or dissection underwent four- and one-channel CT angiography. Scan pairs covered the thoracic inlet to the diaphragm (n = 10) and supraceliac abdominal aorta (n = 19) or thoracic inlet (n = 19) to the femoral arterial bifurcations. For four-channel CT, nominal section thickness and pitch were 2.5 mm and 6.0, respectively, and for one-channel CT, 3.0 mm and 2.0 to the infrarenal aorta and 5.0 mm and 2.0 to the femoral arteries. Effective section thickness, scanning duration, scanning coverage, dose of iodinated contrast material, and mean aortoiliac attenuation were compared. Data were summarized as speed (coverage/duration), scanning efficiency (speed/section thickness), and contrast efficiency (mean aortic attenuation/dose of contrast material).At four- versus one-channel CT, CT angiography was 2.6 times faster, scanning efficiency was 4.1 times greater, contrast efficiency was 2.5 times greater, dose of contrast material was reduced (mean, 57%; 97 vs 232 mL) without a significant change in aortic enhancement, and sections were thinner (mean, 40%; 3.2 vs 5.3 mm) despite a 59% shorter scanning duration (22 vs 56 seconds).Substantially reduced doses of contrast medium, shorter scanning durations, and narrower effective sections result with four- versus one-channel CT aortography. No advantages of one-channel CT aortography were demonstrated.

  View details for Web of Science ID 000087247000009

  View details for PubMedID 10831682

• Bronchocentric granulomatosis: Computed tomographic findings in five patients CLINICAL RADIOLOGY Ward, S., Heyneman, L. E., Flint, J. D., Leung, A. N., Kazerooni, E. A., Muller, N. L. 2000; 55 (4): 296-300

  Abstract

  The aim of this study was to assess the CT manifestations of bronchocentric granulomatosis.The CT results of five patients with bronchocentric granulomatosis were retrospectively analysed. The patients ranged from 20 to 72 years of age and included three men and two women. The diagnosis of bronchocentric granulomatosis was made at lobectomy (n = 2), open lung biopsy (n = 2), and transbronchial biopsy (n = 1). Only one of the five patients had asthma.The main findings consisted of a spiculated mass lesion (n = 3) or lobar consolidation with associated mild volume loss (n = 2). One of the two patients with consolidation had extensive mucoid impaction. The abnormalities involved predominantly an upper lobe in four patients and a lower lobe in one patient. In the four resected specimens, the macroscopic pathological appearance was consolidation (n = 2) and mass lesion (n = 2). Microscopically, the typical histology of airway-centred necrotizing granulomata was present in all cases. Aspergillus hyphae were identified in two cases. Nocardia sp. was cultured from the biopsy specimen in one case.The CT manifestations of bronchocentric granulomatosis consist of a focal mass or lobar consolidation with atelectasis. These reflect the presence of granuloma formation with or without associated bronchial obstruction.

  View details for Web of Science ID 000089135100008

  View details for PubMedID 10767190

• Primary bronchogenic carcinoma after heart or lung transplantation: Radiologic and clinical findings JOURNAL OF THORACIC IMAGING Choi, Y. H., Leung, A. N., Miro, S., Poirier, C., Hunt, S., Theodore, J. 2000; 15 (1): 36-40

  Abstract

  Chronic immunosuppression in organ transplant recipients predisposes to the development of malignant disease. The authors describe their 29-year institutional experience of bronchogenic carcinoma developing after heart and lung transplantation. Seven cases of bronchogenic carcinoma were diagnosed in 1,119 heart and lung transplant recipients. Computed tomography scans and radiographs at time of diagnosis, as well as prior radiographs available in six patients were retrospectively analyzed by two radiologists in consensus. The seven cases involved six heart and one lung transplant recipients. Six patients were smokers with a mean smoking history of 66 pack-years. Mean time interval from transplantation to cancer detection was 25 months. Radiologic findings consisted of a solitary pulmonary nodule (n = 3), mass with satellite nodules (n = 1), and obstructive pneumonitis (n = 1). In the sixth patient, the cancer was not radiographically visible because of obscuration by adjacent fibrosis. On review, radiographic abnormalities were present a mean of 12 months prior to diagnosis in 66% of patients. In the heart or lung transplant population, bronchogenic carcinoma develops in recipients with extensive smoking histories. It presents radiographically as a nodule, mass, or obstructive pneumonitis, and is usually visible on radiographs before the time of diagnosis.

  View details for Web of Science ID 000084709000008

  View details for PubMedID 10634661

• Computed tomographic angiography: Historical perspective and new state-of-the-art using multi detector-row helical computed tomography Workshop on Multiple Perspectives in Magnetic Resonance Imaging Contrast Rubin, G. D., Shiau, M. C., Schmidt, A. J., Fleischmann, D., Logan, L., Leung, A. N., Jeffrey, R. B., Napel, S. LIPPINCOTT WILLIAMS & WILKINS. 1999: S83–S90

  Abstract

  Since its clinical introduction in 1991, volumetric computed tomography scanning using spiral or helical scanners has resulted in a revolution for diagnostic imaging. In addition to new applications for computed tomography, such as computed tomographic angiography and the assessment of patients with renal colic, many routine applications such as the detection of lung and liver lesions have substantially improved. Helical computed tomographic technology has improved over the past eight years with faster gantry rotation, more powerful X-ray tubes, and improved interpolation algorithms, but the greatest advance has been the recent introduction of multi detector-row computed tomography scanners. These scanners provide similar scan quality at a speed gain of 3-6 times greater than single detector-row computed tomography scanners. This has a profound impact on the performance of computed tomography angiography, resulting in greater anatomic coverage, lower iodinated contrast doses, and higher spatial resolution scans than single detector-row systems.

  View details for Web of Science ID 000084391500012

  View details for PubMedID 10608402

• Accuracy of CT in the diagnosis of allergic bronchopulmonary aspergillosis in asthmatic patients AMERICAN JOURNAL OF ROENTGENOLOGY Ward, S., Heyneman, L., Lee, M. J., Leung, A. N., Hansell, D. M., Muller, N. L. 1999; 173 (4): 937-942

  Abstract

  The purpose of this study was to assess the accuracy of high-resolution CT in the diagnosis of allergic bronchopulmonary aspergillosis in asthmatic patients.The high-resolution CT scans of 44 asthmatic patients with allergic bronchopulmonary aspergillosis and 38 asthmatic patients without allergic bronchopulmonary aspergillosis were analyzed retrospectively and randomly by two independent observers for these features: bronchial wall thickening, bronchiectasis, centrilobular nodules, mucoid impaction, mosaic perfusion, atelectasis, and consolidation. Each observer made a final diagnosis with a stated degree of confidence. The results are expressed as the average number of observations by the two observers.Findings seen more commonly in patients with allergic bronchopulmonary aspergillosis than in patients with asthma alone included bronchiectasis, centrilobular nodules, and mucoid impaction (p < .01, chi-square test). Bronchiectasis was present in 42 (95%) of 44 patients with allergic bronchopulmonary aspergillosis, centrilobular nodules in 41 (93%), and mucoid impaction in 29.5 (67%) (average of two observers). In the asthmatic control group, bronchiectasis was detected in 11 (29%) of 38 patients, centrilobular nodules in 10.5 (28%), and mucoid impaction in 4%. Bronchiectasis was seen in 184 (70%) of 264 lobes of patients with allergic bronchopulmonary aspergillosis compared with 19.5 (9%) of 228 lobes in asthmatic controls (p < .001, chi-square test).In asthmatic patients, bronchiectasis affecting three or more lobes, centrilobular nodules, and mucoid impaction are findings on high-resolution CT that are highly suggestive of allergic bronchopulmonary aspergillosis.

  View details for Web of Science ID 000082714900015

  View details for PubMedID 10511153

• Radiology of pneumonia CLINICS IN CHEST MEDICINE Katz, D. S., Leung, A. N. 1999; 20 (3): 549-?

  Abstract

  Chest radiography is the imaging technique of choice in evaluating patients with suspected pneumonia because of its low radiation dose, low cost, and wide accessibility. In daily practice, radiographs are used to confirm the clinical diagnosis of pneumonia, characterize the extent and severity of disease, search for complications such as empyema, monitor the response to therapy, and examine for possible alternative or additional diagnoses. Although CT scan has no defined role in the routine assessment of patients with either community-acquired or nosocomial pneumonias, its advantages of superior contrast resolution and cross-sectional display can often be helpful in the analysis of complex cases, particularly when radiographic evidence of associated central obstruction, cavitation, lymphadenopathy, or empyema is equivocal. In the immunocompromised patient population, high-resolution CT has been shown to be more sensitive than plain film radiography in the early detection of pulmonary infections.

  View details for Web of Science ID 000083128300008

  View details for PubMedID 10516903

• Radiologic findings: Pulmonary infections after bone marrow transplantation JOURNAL OF THORACIC IMAGING Choi, Y. H., Leung, A. N. 1999; 14 (3): 201-206

  Abstract

  Pulmonary infections are a significant source of morbidity and mortality in the bone marrow transplant population. This pictorial essay reviews the typical time period and imaging findings associated with common pulmonary pathogens that affect bone marrow transplant recipients.

  View details for Web of Science ID 000081198700007

  View details for PubMedID 10404506

• Standardized high-resolution CT of the lung using a spirometer-triggered electron beam CT scanner AMERICAN JOURNAL OF ROENTGENOLOGY Robinson, T. E., Leung, A. N., Moss, R. B., Blankenberg, F. G., Al-Dabbagh, H., Northway, W. H. 1999; 172 (6): 1636-1638

  View details for Web of Science ID 000080427900034

  View details for PubMedID 10350305

• Assessment of pulmonary lesions with F-18-fluorodeoxyglucose positron imaging using coincidence mode gamma cameras JOURNAL OF NUCLEAR MEDICINE Weber, W., Young, C., Abdel-Dayem, H. M., Sfakianakis, G., Weir, G. J., Swaney, C. M., Gates, M., Stokkel, M. P., Parker, A., Hines, H., Khanvali, B., Liebig, J. R., Leung, A. N., Sollitto, R., Caputo, G., WAGNER, H. N. 1999; 40 (4): 574-578

  Abstract

  Accurate assessment of lung carcinoma remains a significant clinical problem, often leading to surgical procedures without curative potential. PET with 18F-fluorodeoxyglucose (FDG) has shown promise in differentiating benign from malignant lesions and in staging the extent of disease, resulting in improved treatment at a significant cost savings. This multicenter prospective study used dual-detector coincidence imaging with FDG to categorize pulmonary lesions as benign or malignant. The goal of this study was to determine the sensitivity and specificity of dual-detector coincidence imaging of FDG in patients with pulmonary lesions who were scheduled to have a diagnostic procedure for histopathologic confirmation.A total of 96 patients with pulmonary lesions with a lesion size ranging from 1 to 7 cm with a mean of 3.44 cm based on their chest radiograph or CT scan were studied using FDG scans with a dual-detector coincidence detection system. An additional 24 patients were entered as control subjects. The studies of 120 subjects were interpreted in random order by three physicians experienced in the use of FDG in patients with lung cancer. Surgical pathology was used as the standard for identifying malignant lesions.There was 94% agreement between the readers in the independent interpretation of the FDG studies. In the 96 patients with pulmonary lesions, FDG studies were 97% sensitive and 80% specific in identifying proven malignant lesions.The results of this prospective study provide evidence that dual-detector coincidence imaging with FDG provides an accurate, sensitive and specific means of diagnosing malignancy in patients with pulmonary lesions.

  View details for Web of Science ID 000079521800016

  View details for PubMedID 10210215

• Spirometer-triggered high resolution computed tomography (HRCT) of the chest, clinical score, and pulmonary function measurements in cystic fibrosis (CF) patients before and after treatment for a pulmonary exacerbation Robinson, T. E., Leung, A. N., Moss, R. B., Blankenberg, F. G., Bloch, D. A., Oehlert, J. W., Al-Dabbagh, H., Hubli, S., Northway, W. H. INT PEDIATRIC RESEARCH FOUNDATION, INC. 1999: 355A

  View details for DOI 10.1203/00006450-199904020-02108

  View details for Web of Science ID 000079476702092

• Pulmonary infections after bone marrow transplantation: Clinical and radiographic findings RADIOLOGY Leung, A. N., Gosselin, M. V., Napper, C. H., Braun, S. G., Hu, W. W., Wong, R. M., Gasman, J. 1999; 210 (3): 699-710

  Abstract

  To assess the clinical and radiographic findings of pulmonary infections diagnosed by using invasive means.Fifty-nine episodes of pulmonary infection were diagnosed in 52 (7.2%) of a consecutive series of 725 adult bone marrow transplant recipients. Causative organisms, time of diagnoses, radiographic patterns, and mortality rates were reviewed.Cytomegalovirus and Aspergillus species were the two most common pathogens, accounting for 22 and 17 episodes, respectively. During the first 30 days after bone marrow transplantation, fungi caused the majority (nine [82%] of 11 episodes) of pulmonary infections; from days 31 to 100, viruses predominated (21 [62%] of 34 episodes). Recipients of allogeneic transplants had a higher probability of developing Cytomegalovirus pneumonitis than did the recipients of autologous and syngeneic transplants (P < .001). Radiographic findings of Cytomegalovirus pneumonia consisted of parenchymal opacification (90%) and innumerable nodules smaller than 5 mm (29%); in two patients, radiographs were normal. Nodules, masses, or nodules and masses, present in nine (69%) of the 13 patients with Aspergillus infection, were the most common radiographic findings in invasive aspergillosis. Bone marrow transplant recipients with a documented pulmonary infection were found to have a lower event-free survival than recipients without infection (P < .001).Opportunistic pathogens account for the majority of pulmonary infections requiring invasive diagnosis and tend to manifest at predictable times in the course of events following recovery from bone marrow transplantation. Cytomegalovirus, the most common pathogen, causes a spectrum of radiographic findings that includes normal findings. Occurrence of a pulmonary infection is associated with an increased mortality rate.

  View details for Web of Science ID 000078796500018

  View details for PubMedID 10207470

• Pulmonary tuberculosis: The essentials RADIOLOGY Leung, A. N. 1999; 210 (2): 307-322

  View details for Web of Science ID 000078277900003

  View details for PubMedID 10207408

• Lung transplantation for lymphangioleiomyomatosis: Role of imaging in the assessment of complications related to the underlying disease RADIOLOGY Collins, J., Muller, N. L., Kazerooni, E. A., McAdams, H. P., Leung, A. N., Love, R. B. 1999; 210 (2): 325-332

  Abstract

  To identify the complications and imaging findings related to lymphangioleiomyomatosis (LAM) after lung transplantation.The authors retrospectively reviewed the clinical histories and imaging studies of 13 patients from five major medical centers who underwent unilateral (n = 8) or bilateral (n = 5) lung transplantation for LAM between 1991 and 1997. Complications related to LAM, both before and after transplantation, were recorded.The following LAM-related complications were found during and after transplantation: excessive pleural adhesions (n = 4), native lung pneumothorax (n = 3), chylous effusion (n = 1), chylous ascites (n = 3), complications from renal angiomyolipomas (n = 4), and recurrent LAM (n = 1). Diagnosis could be made or suggested with computed tomography (CT) in all cases. Four patients (31%) died; one patient died of complications of LAM.Patients who have undergone lung transplantation for LAM have increased morbidity and mortality due to complications related to their underlying disease. These LAM-related complications can be diagnosed or suggested with CT.

  View details for Web of Science ID 000078277900005

  View details for PubMedID 10207410

• Chronic pulmonary coccidioidomycosis: computed tomographic and pathologic findings in 18 patients CANADIAN ASSOCIATION OF RADIOLOGISTS JOURNAL-JOURNAL DE L ASSOCIATION CANADIENNE DES RADIOLOGISTES Kim, K. I., Leung, A. N., Flint, J. D., Muller, N. L. 1998; 49 (6): 401-407

  Abstract

  To review the computed tomographic (CT) findings in pathologically proven chronic pulmonary coccidioidomycosis.The study included 19 pulmonary lesions caused by mycologically and pathologically proven chronic coccidioidomycosis in 18 immunocompetent patients (aged 22 to 75 years, mean 57 years) who had a chest CT scan. Thirteen patients were Canadians who had travelled to an endemic area, and 5 were inhabitants of an endemic area in southern California and Arizona. The CT findings were assessed to determine the type, size, margin, internal architecture and location of parenchymal abnormalities.The CT findings included solitary nodules of 1.0 to 2.0 cm (mean 1.7 cm) in diameter in 17 patients, a focal area of ground-glass attenuation in 1 patient, and focal consolidation in 1 patient. Ten of the nodules had homogeneous attenuation on CT, 2 had central areas of low attenuation, 2 showed cavitation, 2 had foci of calcifications and 1 had bubble lucency. The nodules were located peripherally (in 14 patients) and centrally (in 3 patients). The predominant histologic finding in these nodules was a necrotizing granuloma. Three nodules were surrounded by halos of ground-glass attenuation, which were shown on histologic examination to represent granulomatous inflammation (in 2 cases) and pulmonary hemorrhage due to a pulmonary artery-bronchial fistula (in 1 case). Two nodules had adjacent consolidation, which was due to granulomatous inflammation surrounding a necrotizing granuloma.Necrotizing granulomas in chronic coccidioidomycosis appear as a well-defined nodule on CT, while granulomatous inflammation may appear as areas of ground-glass attenuation or consolidation.

  View details for Web of Science ID 000077752200007

  View details for PubMedID 9879269

• Thoracic spiral CT: Influence of subsecond gantry rotation on image quality RADIOLOGY Rubin, G. D., Leung, A. N., Robertson, V. J., Stark, P. 1998; 208 (3): 771-776

  Abstract

  To determine if the lower milliampere second setting and shorter acquisition time of subsecond spiral computed tomography (CT) affects the image quality of thoracic CT scans.In 92 consecutive outpatients referred for thoracic CT, spiral CT (120 kV, 292 mA) was performed with 1-second (n = 45) or 0.75-second (n = 47) scanning time. An equal percentage of patients (70%) in each group received intravenous contrast medium. At six mediastinal and six lung zones, degradation due to motion and noise, respectively, were graded independently on a four-point scale by three blinded radiologists. Statistically significant differences were determine with a two-tailed test.Mediastinal image quality was significantly better on 0.75-second scans than on 1-seconds scans (P < .001). Regions with the greatest improvement in image quality were around the aortic root, cardiac ventricles, and aortic arch. Lung image quality was also better on 0.75-second scans than on 1-second scans (P = .04). On 0.75- and 1-second scans, respectively, motion-related artifacts were found to degrade image quality 6.2 and 8.7 times more than noise-related artifacts in the mediastinum and 2.6 and 3.9 times more in the lungs.Subsecond spiral CT is associated with improved clarity and diminished motion artifacts on mediastinal and pulmonary images when compared with 1-second spiral CT.

  View details for Web of Science ID 000075488200033

  View details for PubMedID 9722858

• Epstein-Barr-virus-associated lymphoproliferative disease of the lung: CT and histologic findings 83rd Annual Meeting of the Radiological-Society-of-North-America Collins, J., Muller, N. L., Leung, A. N., McGuinness, G., Mergo, P. J., Flint, J. D., Warner, T. F., Poirier, C., Theodore, J., Zander, D., Yee, H. T. RADIOLOGICAL SOC NORTH AMERICA. 1998: 749–59

  Abstract

  To assess the computed tomographic (CT) and histologic findings of intrathoracic lymphoproliferative disease (LPD) associated with the Epstein-Barr virus (EBV).The authors retrospectively reviewed the CT scans of the chest and the pathologic specimens obtained in 24 patients with histologically proved intrathoracic LPD and with positive serologic findings or immunohistochemical staining for EBV. Five patients had acquired immunodeficiency syndrome (AIDS); one had common variable immune deficiency; and 18 were receiving immunosuppressive therapy for heart, lung, or heart-lung (n =15) or bone marrow (n = 2) transplantation and vasculitis (n = 1).Final diagnoses included malignant lymphoma (n = 15), polyclonal LPD (n = 8), and hyperplasia of bronchus-associated lymphoid tissue (n = 1). CT findings included multiple nodules (n = 21), lymphadenopathy (n = 9), areas of groundglass opacification (n = 8), septal thickening (n = 7), consolidation (n = 5), pleural effusion (n = 4), and solitary endobronchial lesion (n = 2). The nodules were 2-4 cm in diameter, involved mainly the middle and lower lung zones, and frequently had a predominantly peribronchovascular (n = 15) or subpleural (n = 14) distribution.EBV-associated LPD may range from benign lymphoid hyperplasia to high-grade lymphoma. The most common CT manifestation consists of multiple nodules, frequently in a predominantly peribronchovascular or subpleural distribution.

  View details for Web of Science ID 000075488200031

  View details for PubMedID 9722856

• Unsuspected pulmonary embolism: Prospective detection on routine helical CT scans RADIOLOGY Gosselin, M. V., Rubin, G. D., Leung, A. N., Huang, J., Rizk, N. W. 1998; 208 (1): 209-215

  Abstract

  To determine the prevalence of unsuspected pulmonary embolism (PE) on routine thoracic helical computed tomographic (CT) scans and to quantify the improvement in PE detection by using a cine-paging mode on a workstation instead of hard-copy review.Seven hundred eighty-five patients referred for routine contrast medium-enhanced thoracic CT within 9 months were prospectively recruited. Helical CT was performed. Studies were prospectively interpreted by four radiologists. Two radiologists performed routine, undirected, hard-copy consensus review for official interpretation; two of three thoracic radiologists independently performed a dedicated workstation-based search for PE. The presence of PE involving the main, lobar, or segmental pulmonary arteries was assigned a score of 1-5 (1 = definitely negative, 5 = definitely positive) by each independent reviewer. Patients with a score of 4 or 5 underwent lower-extremity ultrasound, ventilation-perfusion scintigraphy, or both, followed by pulmonary CT angiography if the findings were still equivocal.Twelve (1.5%) of the 785 patients had unsuspected PE, with an inpatient prevalence of 5% (eight of 160) and an outpatient prevalence of 0.6% (four of 625). Of the 12 patients with unsuspected PE, 10 (83%) had cancer. Of the 81 inpatients with cancer, seven (9%) had unsuspected PE. A dedicated workstation-based search resulted in detection of PE in three more patients (25%) than did hard-copy interpretation.The prevalence of unsuspected PE was highest among inpatients with cancer. A directed, workstation-based search can improve the PE detection rate over that with hard-copy review.

  View details for Web of Science ID 000074296300033

  View details for PubMedID 9646815

• Primary malignant pulmonary hemangiopericytoma CLINICAL IMAGING Katz, D. S., Lane, M. J., Leung, A. N., Marcus, F. S., Sakata, M. K. 1998; 22 (3): 192-195

  Abstract

  A primary malignant pulmonary hemangiopericytoma was diagnosed in a 45-year-old woman who complained of 10 months of cough and exertional dyspnea. One year after resection of the mass, a metastatic lesion was removed from the contralateral lung. The literature on this unusual pulmonary lesion is reviewed.

  View details for Web of Science ID 000072936200005

  View details for PubMedID 9559231

• Sarcoidosis activity: Correlation of HRCT findings with those of Ga-67 scanning, bronchoalveolar lavage, and serum angiotensin-converting enzyme assay JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Leung, A. N., Brauner, M. W., Caillat-Vigneron, N., Valeyre, D., Grenier, P. 1998; 22 (2): 229-234

  Abstract

  The objective of this study was to correlate the findings of sarcoidosis on high resolution CT (HRCT) with indexes of disease activity as measured with 67Ga scan, bronchoalveolar lavage (BAL), and serum angiotensin-converting enzyme (SACE) assay.Twenty-nine patients with proven sarcoidosis underwent HRCT scan, 67Ga scan, BAL, and SACE assay within a 1 month period. The extent of parenchymal involvement by nodules, consolidation, ground-glass attenuation, and linear opacities was quantified to the nearest 10% of surface area affected on the CT examination. Whole-lung gallium uptake was quantified and the percentage of BAL-recovered lymphocytes (BAL-%LC) and SACE levels obtained by chart review. CT scores of disease extent were correlated with measured indexes of activity using the Spearman rank correlation coefficient.The mean extent of nodules, consolidation, ground-glass attenuation, and linear opacities on HRCT images was 15.1 +/- 16.6, 1.6 +/- 4.0, 17.5 +/- 25.4, and 7.6 +/- 9.6%, respectively. The extent of nodules and consolidation correlated with the intensity of lung gallium uptake (r = 0.46, p < 0.02), BAL-%LC (r = 0.50, p < 0.01), and SACE levels (r = 0.38, p < 0.05). No significant correlation was found between extent of ground-glass attenuation or linear opacities with any indexes of disease activity.On HRCT scan, nodules and consolidation in sarcoidosis reflect disease activity as measured by 67Ga scan, BAL, and SACE assay.

  View details for DOI 10.1097/00004728-199803000-00013

  View details for Web of Science ID 000072592200012

  View details for PubMedID 9530385

• Bronchiolitis obliterans after lung transplantation - Detection using expiratory HRCT CHEST Leung, A. N., Fisher, K., Valentine, V., Girgis, R. E., Berry, G. J., Robbins, R. C., Theodore, J. 1998; 113 (2): 365-370

  Abstract

  The objective of this study was to determine if air trapping, as detected on expiratory high-resolution CT (HRCT), is useful as an indicator of bronchiolitis obliterans (BO) in lung transplant recipients. MATERIALS andCorresponding inspiratory and expiratory HRCT images at five different levels and spirometry were obtained in 21 lung transplant recipients. Eleven patients had BO proved by transbronchial biopsy specimens; the remaining 10 patients had no pathologic or functional evidence of airways disease. Two "blinded" observers assessed the inspiratory images for the presence of bronchiectasis and mosaic pattern of lung attenuation, and the expiratory images for presence and extent of air trapping. Statistical comparison of the frequency of HRCT findings between patients with and without BO was performed using Fisher's Exact Test.On inspiratory images, bronchiectasis and mosaic pattern of lung attenuation were present in 4 (36%) and 7 (64%) of 11 patients with BO, and 2 (20%) and 1 (10%) of 10 patients without BO (p>0.05 and p<0.05), respectively. The sensitivity, specificity, and accuracy of bronchiectasis and mosaic pattern for BO were 36%, 80%, and 57%, and 64%, 90%, and 70%, respectively. On expiratory images, air trapping was found in 10 of 11 (91%) patients with BO compared to 2 of 10 (20%) patients without BO (p<0.002). Air trapping was found to have a sensitivity of 91%, specificity of 80%, and accuracy of 86% for BO. Air trapping was identified in one patient with BO who had normal results of baseline spirometric function tests.Air trapping, as detected on expiratory HRCT, was the most sensitive and accurate radiologic indicator of BO in the lung transplant population.

  View details for Web of Science ID 000072002900022

  View details for PubMedID 9498953

• Clinics in diagnostic imaging (27). Sarcoidosis. Singapore medical journal Leung, A. N. 1997; 38 (7): 302-304

  Abstract

  A 44-year-old Caucasian man presented with third-degree heart block. Chest radiograph and high-resolution computed tomography (HRCT) of the thorax showed mediastinal and bilateral hilar lymphadenopathy associated with a diffuse, bilateral micronodular pattern. The HRCT findings and differential diagnosis of sarcoidosis are reviewed.

  View details for PubMedID 9339099

• Simulated dose reduction in conventional chest CT: Validation study RADIOLOGY Mayo, Whittall, K. P., Leung, A. N., Hartman, T. E., Park, C. S., Primack, S. L., Chambers, G. K., Limkeman, M. K., Toth, T. L., Fox, S. H. 1997; 202 (2): 453–57

  Abstract

  To validate a technique of computer-simulated dose reduction for conventional chest computed tomography (CT).In 27 patients, CT scans were obtained at 200, 100, and 40 mAs at two levels. The raw data from the 200-mAs scan were modified on a computer workstation to simulate the increased noise present on 100- and 40-mAs scans. Real and simulated 100- and 40-mAs images were independently assessed in random order for overall image quality and radiologic findings by four subspecialty-trained chest radiologists who were blinded to the technique. The four observers were given paired real and simulated images. They were asked to identify the real image and note any difference in diagnostic quality.No difference was seen in overall image quality or radiologic findings between real and simulated images (P > .05). In the paired comparison, 433 of 864 (50.1%) real images were correctly identified.Computer modification of 200-mAs raw scan data to simulate 100- and 40-mAs noise levels produces reconstructed images indistinguishable from real 100- and 40-mAs scans. This technique provides realistic reduced-dose images without patient radiation exposure and with identical image registration and motion artifact.

  View details for DOI 10.1148/radiology.202.2.9015073

  View details for Web of Science ID A1997WD82200029

  View details for PubMedID 9015073

• Spiral CT of the thorax in daily practice: Optimization of technique JOURNAL OF THORACIC IMAGING Leung, A. N. 1997; 12 (1): 2-10

  Abstract

  Effective utilization of spiral computed tomography (CT) technology in imaging of the thorax requires an understanding of technical parameters that affect image and scan quality. This article discusses how operator-controlled scan parameters can be optimized to achieve diagnostic and cost-effective examinations appropriate for daily clinical practice.

  View details for Web of Science ID A1997WA70200002

  View details for PubMedID 8989754

• MRI of pulmonary embolism using Gd-DTPA-polyethylene glycol polymer enhanced 3D fast gradient echo technique in a canine model MAGNETIC RESONANCE IMAGING Li, K. C., Pelc, L. R., NAPEL, S. A., Goris, M. L., Lin, D. T., SONG, C. K., Leung, A. N., Rubin, G. D., HOLLETT, M. D., Harris, D. P. 1997; 15 (5): 543-550

  Abstract

  This study was to evaluate the accuracy of MR angiography (MRA) using a Gd-DTPA-polyethylene glycol polymer (Gd-DTPA-PEG) with a 3D fast gradient echo (3D fgre) technique in diagnosing pulmonary embolism in a canine model. Pulmonary emboli were created in six mongrel dogs (20-30 kg) by injecting tantalum oxide-doped autologous blood clots into the femoral veins via cutdowns. MRI was performed with a 1.5 T GE Signa imager using a 3D fgre sequence (11.9/2.3/15 degrees) following intravenous injection of 0.06 mmol Gd/kg of Gd-DTPA-PEG. The dogs were euthanized and spiral CT of the lungs were then obtained on the deceased dogs. The MRI images were reviewed independently and receiver-operating-characteristic (ROC) curves were used for statistical analysis using spiral CT results as the gold standard. The pulmonary emboli were well visualized on spiral CT. Out of 108 pulmonary segments in the six dogs, 24 contained emboli >2 mm and 27 contained emboli < or = 2 mm. With unblinded review, MRI detected 79% of emboli >2 mm and only 48% of emboli < or = 2 mm. The blinded review results were significantly worse. Gd-DTPA-PEG enhanced 3D fgre MRI is potentially able to demonstrate pulmonary embolism with fairly high degree of accuracy, but specialized training for the interpretations will be required.

  View details for Web of Science ID A1997XM76800004

  View details for PubMedID 9253998

• Radiologic manifestations of lymphoma in the thorax AMERICAN JOURNAL OF ROENTGENOLOGY Au, V., Leung, A. N. 1997; 168 (1): 93-98

  View details for Web of Science ID A1997VZ55500019

  View details for PubMedID 8976927

• Optimization of thoracic spiral CT: Effects of iodinated contrast medium concentration RADIOLOGY Rubin, G. D., Lane, M. J., Bloch, D. A., Leung, A. N., Stark, P. 1996; 201 (3): 785-791

  Abstract

  To determine the effect of varying iodine concentration on arterial enhancement and perivenous artifact during thoracic spiral computed tomographic (CT) scanning.One hundred thirty-eight outpatients received 15.0 g (n = 76) or 22.5 g (n = 62) of iodine (300 mg/mL iodine) while undergoing thoracic spiral CT. Patients received either undiluted contrast medium, 1:1 normal saline dilution, or 3:1 normal saline dilution. Contrast medium was injected at a flow rate determined to deliver the entire iodine dose within 40 seconds. Attenuation was measured within arteries and veins. Three blinded thoracic radiologists independently graded perivenous artifact and arterial enhancement.Perivenous artifacts were statistically significantly reduced with successive iodine dilution (P < .002). Arterial enhancement was statistically significantly better with 15.0 g of iodine diluted 1:1 when compared with the same iodine dose undiluted or diluted 3:1 (P < .01). Arterial enhancement achieved with 15.0 g of iodine diluted 1:1 was not statistically significantly lower than that achieved with 22.5 g of iodine diluted 1:1 (P > .31); however, venous artifact was greater with 22.5 g of iodine (P < .004).Reduced iodine concentration appears to diminish perivenous artifact and to result in improved arterial enhancement during thoracic spiral CT.

  View details for Web of Science ID A1996VU50000033

  View details for PubMedID 8939232

• Volumetric, analysis of volumetric data: Achieving a paradigm shift RADIOLOGY Rubin, G. D., Napel, S., Leung, A. N. 1996; 200 (2): 312-317

  View details for Web of Science ID A1996UY07800003

  View details for PubMedID 8685316

• Effects of lobar atelectasis on the distribution of pleural effusion and pneumothorax JOURNAL OF THORACIC IMAGING Stark, P., Leung, A. 1996; 11 (2): 145-149

  Abstract

  Atelectasis is known to change the retractility of the involved part of the lung and the pleural pressure adjacent to it. Consequently, pleural effusions or pneumothoraxes will change their distribution and preferentially migrate toward the site of atelectasis. This alteration will often result in an atypical distribution of pleural liquid or gas. The radiological implications of this phenomenon are discussed herein.

  View details for Web of Science ID A1996UP14200004

  View details for PubMedID 8820023

• Pulmonary tuberculosis: Comparison of CT findings in HIV-seropositive and HIV-seronegative patients RADIOLOGY Leung, A. N., Brauner, M. W., Gamsu, G., MlikaCabanne, N., BenRomdhane, H., Carette, M. F., Grenier, P. 1996; 198 (3): 687–91

  Abstract

  To determine the differences in the computed tomographic (CT) appearance of pulmonary tuberculosis (TB) between patients with and patients without human immunodeficiency virus (HIV) infection.CT scans and chest radiographs of 42 HIV-seropositive and 42 HIV-seronegative patients with pulmonary TB were reviewed. CD4 T-lymphocyte counts, measured in 40 seropositive patients, were at least 200 cells per microliter in 10 patients and were less that 200 cells per microliter in 30.Seropositive patients had a higher prevalence of lymphadenopathy at chest radiography (P< .05). The seropositive patients had a lower prevalence of consolidation (P< .05), cavitation (P< .01), and postprimary pattern (P< .05) at CT. HIV-seropositive patients had a higher frequency of miliary (P< .01) and extrapulmonary disease (P< .001). Similar features of pulmonary TB were observed in seropositive patients with mild and severe immunosuppression.HIV-seropositive patients had a lower prevalence of localized parenchymal disease and a higher prevalence of disseminated disease at CT.

  View details for DOI 10.1148/radiology.198.3.8628855

  View details for Web of Science ID A1996TW21200013

  View details for PubMedID 8628855

• Radiographic appearance of central venous catheters AMERICAN JOURNAL OF ROENTGENOLOGY Fisher, K. L., Leung, A. N. 1996; 166 (2): 329-337

  Abstract

  Central venous catheters (CVCs) are defined as venous access devices whose tips terminate in the superior or inferior vena cava, regardless of insertion site. CVCs allo reliable, painless, and repeated entry into the venous system and are commonly used for the administration of IV therapy, parenteral nutrition, and blood products as well as for the periodic blood sampling, hemodynamic monitoring, and hemodialysis. Catheter composition and design vary and depend on the duration of intended use and specific functions required. The purpose of this essay is to illustrate commonly used catheters, discuss factors governing catheter selection, and review important catheter-related complications.

  View details for Web of Science ID A1996TR34300018

  View details for PubMedID 8553941

• Abnormalities of the airways and lung parenchyma in asthmatics: CT observations in 50 patients and inter- and intraobserver variability EUROPEAN RADIOLOGY Grenier, P., MoureyGerosa, Benali, K., Brauner, M. W., Leung, A. N., Lenoir, S., Cordeau, M. P., Mazoyer, B. 1996; 6 (2): 199-206

  Abstract

  The purpose of the study was to evaluate the CT abnormalities of airways and lung parenchyma in asthmatic patients and to assess inter- and intraobserver variability for these abnormalities. The CT scans of 50 asthmatic patients and 10 healthy volunteers were assessed independently by four independent chest radiologists who were masked with respect to the clinical information. Bronchiectasis involving mostly subsegmental and distal bronchi was noted in 28.5% of the asthmatic subjects and none of the non-asthmatics. Bronchial wall thickening, small centrilobular opacities and decreased lung attenuation were observed in 82%, 21% and 31% of asthmatic patients respectively, compared with 7%, 5% and 7% of healthy subjects. The intra- and inter-observer agreements for these four CT abnormalities were measured by the kappa statistic and ranged from 0.60 to 0.79 and from 0.40 to 0.64, respectively. It is concluded that asthmatic patients may exhibit bronchial wall thickening, bronchiectasis and morphological abnormalities suggestive of distal airways disease that can be assessed on CT scans with a clinically acceptable observer variability.

  View details for Web of Science ID A1996UE80500015

  View details for PubMedID 8797980

• VOLUMETRIC APPLICATIONS FOR SPIRAL CT IN THE THORAX Conference on Physiology and Function from Multidimensional Images Rubin, G. D., Napel, S., Leung, A. SPIE - INT SOC OPTICAL ENGINEERING. 1994: 353–360

  View details for Web of Science ID A1994BA56T00032

• INTRATHORACIC PEDIATRIC TUBERCULOSIS - A REPORT OF 202 CASES TUBERCLE AND LUNG DISEASE PINEDA, P. R., Leung, A., Muller, N. L., Allen, E. A., Black, W. A., FitzGerald, J. M. 1993; 74 (4): 261-266

  Abstract

  Until recently paediatric tuberculosis rates were in decline in developed countries, but more recently there has been a significant change in these trends. Tuberculosis in British Columbia (BC) is centralized and all paediatric cases diagnosed between 1979 and 1988 were reviewed. There were 252 notifications during the study period but 50 cases were excluded (31 extrapulmonary cases, 11 with missing records and 8 because of incorrect diagnoses). There were 109 (54%) female patients. The age range was 4 months-15 years (6.4 +/- 4.1 years). 52% were 5 years old or less. 75 (37.1%) were aboriginal Canadians, 61 (30.2%) were Asian, 50 (24.8%) were Caucasian and 16 (8%) were included in miscellaneous or unknown groups. Primary pulmonary disease occurred in 197 (97.5%); the remaining 5 had post-primary disease. A history of close contact was elicited in 158 children (78.2%). All but 8 (4%) had a positive PPD response to 5TU. 40% of children had symptoms, the most frequent being cough (51%) and fever (28.4%). Mycobacteriology was carried out in 169 (83.7%) children. Bacteriologic confirmation was achieved in 45 patients (22.2%). Chest X-rays were reviewed in 186 cases. Lymphadenopathy occurred in 93.5%, with hilar (34%) and combined hilar-paratracheal (26%) being the commonest findings. The majority of patients were treated with isoniazid and rifampin, with a minority receiving streptomycin or pyrazinamide in the initial intensive phase. 14 (6.9%) children had adverse reactions to their drugs but these were rapidly reversed with the withdrawal of the responsible drug. Response to therapy was excellent and there were no deaths.

  View details for Web of Science ID A1993LT95700007

  View details for PubMedID 8219178

• PARENCHYMAL OPACIFICATION IN CHRONIC INFILTRATIVE LUNG-DISEASES - CT-PATHOLOGICAL CORRELATION RADIOLOGY Leung, A. N., MILLER, R. R., Muller, N. L. 1993; 188 (1): 209-214

  Abstract

  To correlate areas of parenchymal opacification on thin-section computed tomographic (CT) scans with histologic findings in patients with chronic infiltrative lung disease, the CT and histologic findings were evaluated in 29 patients with 11 such diseases. Open-lung biopsy was performed after CT. The area of predominant involvement was classified as air space, interstitium, or a mixture of both. A pathologic score of disease activity was assigned, and the extent of fibrosis was assessed whenever fibrosis was present. Parenchymal opacification on CT scans corresponded to abnormalities that affected mainly the air spaces in three patients (10%), the interstitium in 13 patients (45%), or both to a similar degree in 13 patients (45%). In 25 of 29 patients (86%), parenchymal opacification was associated with potentially treatable or reversible disease. Abnormalities considered irreversible were seen in three patients with end-stage fibrosis and one patient with talcosis. Parenchymal opacification on thin-section CT scans is a nonspecific finding in diseases that affect the air spaces, interstitium, or both but usually indicates potentially treatable or reversible disease.

  View details for Web of Science ID A1993LH28400040

  View details for PubMedID 8511299

• PRIMARY TUBERCULOSIS IN CHILDHOOD - RADIOGRAPHIC MANIFESTATIONS RADIOLOGY Leung, A. N., Muller, N. L., PINEDA, P. R., FitzGerald, J. M. 1992; 182 (1): 87-91

  Abstract

  The aim of the study was to review the radiologic features of primary tuberculosis in childhood and to determine whether differences in patterns of disease occur among age and ethnic groups. Chest radiographs of 191 children with pediatric primary tuberculosis were reviewed by two observers. Lymphadenopathy, present in 92% of cases, was the most common abnormality identified on the initial chest radiograph and typically involved the hilar and paratracheal regions. Parenchymal abnormalities, identified in 70% of cases, occurred more commonly in the right lung (P less than .001). Children 0-3 years of age had a higher prevalence of lymphadenopathy (P less than .01) and a lower prevalence of parenchymal abnormalities (P less than .001) than older children. A lower prevalence of lymphadenopathy was found in whites than in nonwhites (P less than .02). The radiologic abnormalities often progressed in the initial follow-up. Lymphadenopathy, with or without concomitant parenchymal abnormality, is the radiologic hallmark of primary tuberculosis in childhood. However, distinct age-related and racial differences in presenting patterns of disease exist and should be recognized.

  View details for Web of Science ID A1992GW05400019

  View details for PubMedID 1727316

• CHRONIC DIFFUSE INFILTRATIVE LUNG-DISEASE - COMPARISON OF DIAGNOSTIC-ACCURACY OF HIGH-RESOLUTION AND CONVENTIONAL CT AMERICAN JOURNAL OF ROENTGENOLOGY Leung, A. N., Staples, C. A., Muller, N. L. 1991; 157 (4): 693-696

  Abstract

  We compared the accuracies of high-resolution CT (HRCT) and conventional CT in determining the specific diagnoses in 75 consecutive patients with chronic diffuse infiltrative lung disease. Without knowledge of clinical or pathologic data, two reviewers independently assessed three separate sets of CT scans in random order: three HRCT scans, three 10-mm collimation CT scans obtained at the same levels as the HRCT scans, and a complete conventional CT scan. The HRCT scans were obtained at the level of the aortic arch, tracheal carina, and 1 cm above the right hemidiaphragm by using 1.5-mm collimation and a high spatial resolution algorithm. Observers gave the most likely diagnosis along with their degree of diagnostic confidence. The correct diagnosis, irrespective of confidence level, was reached with 71% of the HRCT scans and with 72% of both the corresponding 10-mm and complete conventional CT scans. Confidence level 1 (definite) was reached with 49% of HRCT scans, 31% of corresponding 10-mm scans, and 43% of complete conventional CT examinations; the correct diagnosis was made in 92%, 96%, and 94% of those examinations, respectively. In none of the patients were findings on the limited HRCT scan normal when findings on the conventional CT scan were abnormal. We conclude that in most patients with chronic infiltrative lung disease a specific diagnosis can be made by obtaining a limited number of HRCT scans.

  View details for Web of Science ID A1991GF74300003

  View details for PubMedID 1892019

• CT IN DIFFERENTIAL-DIAGNOSIS OF DIFFUSE PLEURAL DISEASE AMERICAN JOURNAL OF ROENTGENOLOGY Leung, A. N., Muller, N. L., MILLER, R. R. 1990; 154 (3): 487-492

  Abstract

  The CT features of benign and malignant pleural diseases have been described. However, the accuracy of these features in the differential diagnosis of diffuse pleural disease has not been assessed before. Without knowledge of clinical or pathologic data, we reviewed the CT findings in 74 consecutive patients with proved diffuse pleural disease (39 malignant and 35 benign). The patients included 53 men and 21 women 23-78 years old. Features that were helpful in distinguishing malignant from benign pleural disease were (1) circumferential pleural thickening, (2) nodular pleural thickening, (3) parietal pleural thickening greater than 1 cm, and (4) mediastinal pleural involvement. The specificities of these findings were 100%, 94%, 94%, and 88%, respectively. The sensitivities were 41%, 51%, 36%, and 56%, respectively. Twenty-eight of 39 malignant cases (sensitivity, 72%; specificity, 83%) were identified correctly by the presence of one or more of these criteria. Malignant mesothelioma (n = 11) could not be reliably differentiated from pleural metastases (n = 24). We conclude that CT is helpful in the differential diagnosis of diffuse pleural disease, particularly in differentiation of malignant from benign conditions.

  View details for Web of Science ID A1990CN84800006

  View details for PubMedID 2106209