UCLA Radiology
UCLA Thoracic Imaging
Publications
UCLA Thoracic Imaging Publication
November 2014

Cost-effectiveness of CT Screening in the National Lung Screening Trial.

Black WC, Gareen IF, Soneji SS, Sicks JD, Keeler EB, Aberle DR, Naeim A, Church TR, Silvestri GA, Gorelick J, Gatsonis C; National Lung Screening Trial Research Team.
BACKGROUND: The National Lung Screening Trial (NLST) showed that screening with low-dose computed tomography (CT) as compared with chest radiography reduced lung-cancer mortality. We examined the cost-effectiveness of screening with low-dose CT in the NLST. METHODS: We estimated mean life-years, quality-adjusted life-years (QALYs), costs per person, and incremental cost-effectiveness ratios (ICERs) for three alternative strategies: screening with low-dose CT, screening with radiography, and no screening. Estimations of life-years were based on the number of observed deaths that occurred during the trial and the projected survival of persons who were alive at the end of the trial. Quality adjustments were derived from a subgroup of participants who were selected to complete quality-of-life surveys. Costs were based on utilization rates and Medicare reimbursements. We also performed analyses of subgroups defined according to age, sex, smoking history, and risk of lung cancer and performed sensitivity analyses based on several assumptions.
November 2014

Toward Clinically Usable CAD for Lung Cancer Screening with Computed Tomography.

Brown MS, Lo P, Goldin JG, Barnoy E, Kim GH, McNitt-Gray MF, Aberle DR.
OBJECTIVES: The purpose of this study was to define clinically appropriate, computer-aided lung nodule detection (CAD) requirements and protocols based on recent screening trials. In the following paper, we describe a CAD evaluation methodology based on a publically available, annotated computed tomography (CT) image data set, and demonstrate the evaluation of a new CAD system with the functionality and performance required for adoption in clinical practice. METHODS: A new automated lung nodule detection and measurement system was developed that incorporates intensity thresholding, a Euclidean Distance Transformation, and segmentation based on watersheds. System performance was evaluated against the Lung Imaging Database Consortium (LIDC) CT reference data set.
November 2014

ACR Appropriateness Criteria® Rib Fractures.

Henry TS, Kirsch J, Kanne JP, Chung JH, Donnelly EF, Ginsburg ME, Heitkamp DE, Kazerooni EA, Ketai LH, McComb BL, Parker JA, Ravenel JG, Restrepo CS, Saleh AG, Shah RD, Steiner RM, Suh RD, Mohammed TL; Expert Panel on Thoracic Imaging:.
Rib fracture is the most common thoracic injury, present in 10% of all traumatic injuries and almost 40% of patients who sustain severe nonpenetrating trauma. Although rib fractures can produce significant morbidity, the diagnosis of associated complications (such as pneumothorax, hemothorax, pulmonary contusion, atelectasis, flail chest, cardiovascular injury, and injuries to solid and hollow abdominal organs) may have a more significant clinical impact. When isolated, rib fractures have a relatively low morbidity and mortality, and failure to detect isolated rib fractures does not necessarily alter patient management or outcome in uncomplicated cases. A standard posteroanterior chest radiograph should be the initial, and often the only, imaging test required in patients with suspected rib fracture after minor trauma. Detailed radiographs of the ribs rarely add additional information that would change treatment, and, although other imaging tests (eg, computed tomography, bone scan) have increased sensitivity for detection of rib fractures, there are little data to support their use. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review process include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
November 2014

PD-1 Blockade Induces Responses by Inhibiting Adaptive Immune Resistance.

Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, Grogan TR, Mateus C, Tomasic G, Glaspy JA, Emerson RO, Robins H, Pierce RH, Elashoff DA, Robert C, Ribas A.
Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types. One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8(+) T cells (termed adaptive immune resistance). Here we show that pre-existing CD8(+) T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analysed samples from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next-generation sequencing for T-cell antigen receptors (TCRs). In serially sampled tumours, patients responding to treatment showed proliferation of intratumoral CD8(+) T cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8-, PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8(+) T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance.
October 2014

Projected Outcomes Using Different Nodule Sizes to Define a Positive CT Lung Cancer Screening Examination.

Gierada DS, Pinsky P, Nath H, Chiles C, Duan F, Aberle DR.
BACKGROUND: Computed tomography (CT) screening for lung cancer has been associated with a high frequency of false positive results because of the high prevalence of indeterminate but usually benign small pulmonary nodules. The acceptability of reducing false-positive rates and diagnostic evaluations by increasing the nodule size threshold for a positive screen depends on the projected balance between benefits and risks. METHODS: We examined data from the National Lung Screening Trial (NLST) to estimate screening CT performance and outcomes for scans with nodules above the 4mm NLST threshold used to classify a CT screen as positive. Outcomes assessed included screening results, subsequent diagnostic tests performed, lung cancer histology and stage distribution, and lung cancer mortality. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the different nodule size thresholds. All statistical tests were two-sided.
September 2014

Toward Clinically Usable CAD for Lung Cancer Screening with Computed Tomography.

Brown MS, Lo P, Goldin JG, Barnoy E, Kim GH, McNitt-Gray MF, Aberle DR.
OBJECTIVES: The purpose of this study was to define clinically appropriate, computer-aided lung nodule detection (CAD) requirements and protocols based on recent screening trials. In the following paper, we describe a CAD evaluation methodology based on a publically available, annotated computed tomography (CT) image data set, and demonstrate the evaluation of a new CAD system with the functionality and performance required for adoption in clinical practice. METHODS: A new automated lung nodule detection and measurement system was developed that incorporates intensity thresholding, a Euclidean Distance Transformation, and segmentation based on watersheds. System performance was evaluated against the Lung Imaging Database Consortium (LIDC) CT reference data set.
September 2014

Current Readings: Percutaneous Ablation for Pulmonary Metastatic Disease.

Quirk MT, Pomykala KL, Suh RD.
Percutaneous image-guided ablation is a technique for maintaining local control of metastatic lung lesions that may, in selected patients, confer a survival benefit over no treatment or systemic therapy alone. Although the currently accepted treatment for oligometastatic pulmonary disease is surgical resection, the existing body of literature, including the recent investigations reviewed within this article, supports a role for percutaneous ablation as an important and relatively safe therapeutic option for nonsurgical and in carefully selected surgical patients, conferring survival benefits competitive with surgical metastasectomy. Continued clinical investigations are needed to further understand the nuances of thermal technologies and applications to treat lung primary and secondary pulmonary malignancy, directly compare available therapeutic options and further define the role of percutaneous image-guided ablation in the treatment of pulmonary metastatic disease.
August 2014

Interactive Lung Segmentation in Abnormal Human and Animal Chest CT Scans.

Kockelkorn TT, Schaefer-Prokop CM, Bozovic G, Muņoz-Barrutia A, van Rikxoort EM, Brown MS, de Jong PA, Viergever MA, van Ginneken B.
PURPOSE: Many medical image analysis systems require segmentation of the structures of interest as a first step. For scans with gross pathology, automatic segmentation methods may fail. The authors' aim is to develop a versatile, fast, and reliable interactive system to segment anatomical structures. In this study, this system was used for segmenting lungs in challenging thoracic computed tomography (CT) scans. METHODS: In volumetric thoracic CT scans, the chest is segmented and divided into 3D volumes of interest (VOIs), containing voxels with similar densities. These VOIs are automatically labeled as either lung tissue or nonlung tissue. The automatic labeling results can be corrected using an interactive or a supervised interactive approach. When using the supervised interactive system, the user is shown the classification results per slice, whereupon he/she can adjust incorrect labels. The system is retrained continuously, taking the corrections and approvals of the user into account. In this way, the system learns to make a better distinction between lung tissue and nonlung tissue. When using the interactive framework without supervised learning, the user corrects all incorrectly labeled VOIs manually. Both interactive segmentation tools were tested on 32 volumetric CT scans of pigs, mice and humans, containing pulmonary abnormalities.
May 2014

Diagnostic Performance Comparison of the Chartis System and High-Resolution Computerized Tomography Fissure Analysis for Planning Endoscopic Lung Volume Reduction.

Gompelmann D, Eberhardt R, Slebos DJ, Brown MS, Abtin F, Kim HJ, Holmes-Higgin D, Radhakrishnan S, Herth FJ, Goldin J.
BACKGROUND AND OBJECTIVE: Endobronchial valve (EBV) therapy is optimized in patients who demonstrate little or no collateral ventilation (CV). The accuracy of the Chartis System and visual assessment of high-resolution computerized tomography (HRCT) fissure completeness by a core radiology laboratory for classifying CV status was compared by evaluating the relationship of each method with target lobe volume reduction (TLVR) after EBV placement. METHODS: Retrospective HRCT fissure analysis of a study population who underwent catheter-based measurement of CV followed by complete occlusion of the targeted lobe by EBV. Accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the HRCT fissure analysis and the catheter-based measurement of CV for predicting TLVR was determined.
May 2014

ACR Appropriateness Criteria® Hemoptysis.

Ketai LH, Mohammed TL, Kirsch J, Kanne JP, Chung JH, Donnelly EF, Ginsburg ME, Heitkamp DE, Henry TS, Kazerooni EA, Lorenz JM, McComb BL, Ravenel JG, Saleh AG, Shah RD, Steiner RM, Suh RD; Expert Panel on Thoracic Imaging.
Although hemoptysis is often self-limited and benign in origin, it can be an indicator of serious disease including bronchiectasis, granulomatous infection, and malignancy. Hemoptysis severity can be graded on the basis of the quantity of expectorated blood: <30 mL of hemoptysis as minor, 30 to 300 mL as moderate to severe (major), and >300 to 400 mL in 24 hours as massive. Among patients with hemoptysis, chest radiographs are often abnormal and can guide evaluation. The overall risk for malignancy in patients with normal radiographs is low but may be as much as 5% to 10% in patients with >30 mL of hemoptysis and those who are above 40 years of age and have significant smoking history. A combination of negative computed tomography and bronchoscopy results predicts a very low likelihood of lung malignancy diagnosis over medium-term follow-up (2 to 3 y). Bronchial and nonbronchial systemic arteries are much more frequent sources of hemoptysis than pulmonary arteries. Major or massive hemoptysis can usually be stopped acutely by bronchial arterial embolization. Recurrences, however, are common and often require repeat embolization. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
May 2014

A Novel Fast Helical 4D-CT Acquisition Technique to Generate Low-Noise Sorting Artifact-Free Images at User-Selected Breathing Phases.

Thomas D, Lamb J, White B, Jani S, Gaudio S, Lee P, Ruan D, McNitt-Gray M, Low D.
PURPOSE: To develop a novel 4-dimensional computed tomography (4D-CT) technique that exploits standard fast helical acquisition, a simultaneous breathing surrogate measurement, deformable image registration, and a breathing motion model to remove sorting artifacts. METHODS AND MATERIALS: Ten patients were imaged under free-breathing conditions 25 successive times in alternating directions with a 64-slice CT scanner using a low-dose fast helical protocol. An abdominal bellows was used as a breathing surrogate. Deformable registration was used to register the first image (defined as the reference image) to the subsequent 24 segmented images. Voxel-specific motion model parameters were determined using a breathing motion model. The tissue locations predicted by the motion model in the 25 images were compared against the deformably registered tissue locations, allowing a model prediction error to be evaluated. A low-noise image was created by averaging the 25 images deformed to the first image geometry, reducing statistical image noise by a factor of 5. The motion model was used to deform the low-noise reference image to any user-selected breathing phase. A voxel-specific correction was applied to correct the Hounsfield units for lung parenchyma density as a function of lung air filling.
April 2014

ACR Appropriateness Criteria Blunt Chest Trauma.

Chung JH, Cox CW, Mohammed TL, Kirsch J, Brown K, Dyer DS, Ginsburg ME, Heitkamp DE, Kanne JP, Kazerooni EA, Ketai LH, Ravenel JG, Saleh AG, Shah RD, Steiner RM, Suh RD.
Imaging is paramount in the setting of blunt trauma and is now the standard of care at any trauma center. Although anteroposterior radiography has inherent limitations, the ability to acquire a radiograph in the trauma bay with little interruption in clinical survey, monitoring, and treatment, as well as radiography's accepted role in screening for traumatic aortic injury, supports the routine use of chest radiography. Chest CT or CT angiography is the gold-standard routine imaging modality for detecting thoracic injuries caused by blunt trauma. There is disagreement on whether routine chest CT is necessary in all patients with histories of blunt trauma. Ultimately, the frequency and timing of CT chest imaging should be site specific and should depend on the local resources of the trauma center as well as patient status. Ultrasound may be beneficial in the detection of pneumothorax, hemothorax, and pericardial hemorrhage; transesophageal echocardiography is a first-line imaging tool in the setting of suspected cardiac injury. In the blunt trauma setting, MRI and nuclear medicine likely play no role in the acute setting, although these modalities may be helpful as problem-solving tools after initial assessment. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
February 2014

The International Association Study Lung Cancer (IASLC) Strategic Screening Advisory Committee (SSAC) Response to the USPSTF Recommendations.

Field JK, Aberle DR, Altorki N, Baldwin DR, Dresler C, Duffy SW, Goldstraw P, Hirsch FR, Pedersen JH, de Koning HJ, Mulshine JL, Sullivan DC, Tsao MS, Travis WD; International Association for the Study of Lung Cancer Strategic Screening Advisory Committee.
The International Association for the Study of Lung Cancer (IASLC) Strategic Screening Advisory Committee (SSAC) has prepared the following response to the United States Preventive Services Task Force (USPSTF) draft recommendatio on computed tomography (CT) screening with associated systemic review. The Cancer Care Ontario Programme in Evidence-Based Care (CCOP) has also undertaken a similar systemic review. The IASLC SSAC was set up during the World Lung Cancer Conference 2011.
February 2014

Overdiagnosis in Low-dose Computed Tomography Screening for Lung Cancer.

Patz EF Jr, Pinsky P, Gatsonis C, Sicks JD, Kramer BS, Tammemägi MC, Chiles C, Black WC, Aberle DR; NLST Overdiagnosis Manuscript Writing Team.
IMPORTANCE Screening for lung cancer has the potential to reduce mortality, but in addition to detecting aggressive tumors, screening will also detect indolent tumors that otherwise may not cause clinical symptoms. These overdiagnosis cases represent an important potential harm of screening because they incur additional cost, anxiety, and morbidity associated with cancer treatment. OBJECTIVE To estimate overdiagnosis in the National Lung Screening Trial (NLST). DESIGN, SETTING, AND PARTICIPANTS We used data from the NLST, a randomized trial comparing screening using low-dose computed tomography (LDCT) vs chest radiography (CXR) among 53,452 persons at high risk for lung cancer observed for 6.4 years, to estimate the excess number of lung cancers in the LDCT arm of the NLST compared with the CXR arm. MAIN OUTCOMES AND MEASURES We calculated 2 measures of overdiagnosis: the probability that a lung cancer detected by screening with LDCT is an overdiagnosis (PS), defined as the excess lung cancers detected by LDCT divided by all lung cancers detected by screening in the LDCT arm; and the number of cases that were considered overdiagnosis relative to the number of persons needed to screen to prevent 1 death from lung cancer.
February 2014

Changes in Right Heart Haemodynamics and Echocardiographic Function in an Advanced Phenotype of Pulmonary Hypertension and Right Heart Dysfunction Associated with Pulmonary Fibrosis.

Saggar R, Khanna D, Vaidya A, Derhovanessian A, Maranian P, Duffy E, Belperio JA, Weigt SS, Dua S, Shapiro SS, Goldin JG, Abtin F, Lynch JP 3rd, Ross DJ, Forfia PR, Saggar R.
BACKGROUND: Pulmonary hypertension (PH)-targeted therapy in the setting of pulmonary fibrosis (PF) is controversial; the main clinical concern is worsening of systemic hypoxaemia. We sought to determine the effects of gentle initiation and chronic administration of parenteral treprostinil on right heart function in patients with PF associated with an advanced PH phenotype. METHODS: Open-label, prospective analysis of patients with PF-PH referred for lung transplantation (LT). Advanced PH was defined as mean pulmonary artery pressure (mPAP) ≥35 mm Hg. We compared haemodynamics, Doppler echocardiography (DE), oxygenation, dyspnoea and quality of life indices, and 6 min walk distance (6MWD) before and 12 weeks after parenteral treprostinil.
February 2014

Target Lobe Volume Reduction and COPD Outcome Measures After Endobronchial Valve Therapy.

Valipour A, Herth FJ, Burghuber OC, Criner G, Vergnon JM, Goldin J, Sciurba F, Ernst A; VENT study group.
Endobronchial valve (EBV) therapy may be associated with improvements in chronic obstructive pulmonary disease-related outcomes and may therefore be linked to improvements in the body mass index, airflow obstruction, dyspnoea, exercise capacity (BODE) index. Data from 416 patients with advanced emphysema and hyperinflation across Europe and USA, who were randomised to EBV (n=284) or conservative therapy (n=132) were analysed. Quantitative image analysis was used to compare the volume of the targeted lobe at baseline and at 6 months to determine target lobe volume reduction (TLVR). 44% of patients receiving EBV therapy (versus 24.7% of controls) had clinically significant improvements in the BODE index (p<0.001). BODE index was significantly reduced by mean±sd 1.4±1.8, 0.2±1.3 and 0.1±1.3 points in patients with TLVR >50%, 20%-50% and <20%, respectively (intergroup differences p<0.001), but increased by 0.3±1.2 points in controls. Changes in BODE were predicted by baseline BODE and correlated significantly with lobar exclusion and lung volumes at 6 months. A greater proportion of patients in the treatment group than in the control group achieved a clinically meaningful improvement in BODE index; however, the likelihood of benefit was less than half in both groups. Patients in whom TLVR was obtained had greater improvements in clinical outcomes.