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Lung cancer screening via annual low-dose computed tomography has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by a low-dose computed tomography. Changes in genome-wide cell-free DNA fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples and validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a 5-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths. Significance: Lung cancer screening has poor adoption. Our study describes the development and validation of a novel blood-based lung cancer screening test utilizing a highly affordable, low-coverage genome-wide sequencing platform to analyze cell-free DNA fragmentation patterns. The test could improve lung cancer screening rates leading to substantial public health benefits. See related commentary by Haber and Skates, p. 2025., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Accumulated knowledge on the outcomes related to size mismatch in lung transplantation derives from predicted total lung capacity equations rather than individualized measurements of donors and recipients. The increasing availability of computed tomography (CT) makes it possible to measure the lung volumes of donors and recipients before transplantation. We hypothesize that CT-derived lung volumes predict a need for surgical graft reduction and primary graft dysfunction., Methods: Donors from the local organ procurement organization and recipients from our hospital from 2012 to 2018 were included if their CT exams were available. The CT lung volumes and plethysmography total lung capacity were measured and compared with predicted total lung capacity using Bland Altman methods. We used logistic regression to predict the need for surgical graft reduction and ordinal logistic regression to stratify the risk for primary graft dysfunction., Results: A total of 315 transplant candidates with 575 CT scans and 379 donors with 379 CT scans were included. The CT lung volumes closely approximated plethysmography lung volumes and differed from the predicted total lung capacity in transplant candidates. In donors, CT lung volumes systematically underestimated predicted total lung capacity. Ninety-four donors and recipients were matched and transplanted locally. Larger donor and smaller recipient lung volumes estimated by CT predicted a need for surgical graft reduction and were associated with higher primary graft dysfunction grade., Conclusion: The CT lung volumes predicted the need for surgical graft reduction and primary graft dysfunction grade. Adding CT-derived lung volumes to the donor-recipient matching process may improve recipients' outcomes., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

As the COVID-19 pandemic impacts global populations, computed tomography (CT) lung imaging is being used in many countries to help manage patient care as well as to rapidly identify potentially useful quantitative COVID-19 CT imaging biomarkers. Quantitative COVID-19 CT imaging applications, typically based on computer vision modeling and artificial intelligence algorithms, include the potential for better methods to assess COVID-19 extent and severity, assist with differential diagnosis of COVID-19 versus other respiratory conditions, and predict disease trajectory. To help accelerate the development of robust quantitative imaging algorithms and tools, it is critical that CT imaging is obtained following best practices of the quantitative lung CT imaging community. Toward this end, the Radiological Society of North America's (RSNA) Quantitative Imaging Biomarkers Alliance (QIBA) CT Lung Density Profile Committee and CT Small Lung Nodule Profile Committee developed a set of best practices to guide clinical sites using quantitative imaging solutions and to accelerate the international development of quantitative CT algorithms for COVID-19. This guidance document provides quantitative CT lung imaging recommendations for COVID-19 CT imaging, including recommended CT image acquisition settings for contemporary CT scanners. Additional best practice guidance is provided on scientific publication reporting of quantitative CT imaging methods and the importance of contributing COVID-19 CT imaging datasets to open science research databases., (Copyright © 2021. Published by Elsevier Inc.)

Introduction Renal cancer incidence has increased markedly in the United States in recent decades, largely due to incidentally detected tumours from computed tomography imaging. Here, we analyze the potential for low-dose computed tomography lung cancer screening to detect renal cancer. Methods The National Lung Screening Trial randomized subjects to three annual screens with either low-dose computed tomography or chest X-ray. Eligibility criteria included 30 + pack-years, current smoking or quit within 15 years, and age 55-74. Subjects were followed for seven years. Low-dose computed tomography screening forms collected information on lung cancer and non-lung cancer abnormalities, including abnormalities below the diaphragm. A reader study was performed on a sample of National Lung Screening Trial low-dose computed tomography images assessing presence of abnormalities below the diaphragms and abnormalities suspicious for renal cancer. Results There were 26,722 and 26,732 subjects enrolled in the low-dose computed tomography and chest X-ray arms, respectively, and there were 104 and 85 renal cancer cases diagnosed, respectively (relative risk = 1.22, 95% CI: 0.9-1.5). From 75,126 low-dose computed tomography screens, there were 46 renal cancer diagnoses within one year. Abnormalities below the diaphragm rates were 39.1% in screens with renal cancer versus 4.1% in screens without (P < 0.001). Cases with abnormalities below the diaphragms had shorter median time to diagnosis than those without (71 vs. 160 days, P = 0.004). In the reader study, 64% of renal cancer cases versus 13% of non-cases had abnormalities below the diaphragms; 55% of cases and 0.8% of non-cases had a finding suspicious for renal cancer (P < 0.001). Conclusion Low-dose computed tomography screens can potentially detect renal cancers. The benefits to harms tradeoff of incidental detection of renal tumours on low-dose computed tomography is unknown.

The NCCN Guidelines for Occult Primary tumors provide recommendations for the evaluation, workup, management, and follow-up of patients with occult primary tumors (cancers of unknown primary). These NCCN Guidelines Insights summarize major discussion points of the 2014 NCCN Occult Primary panel meeting. The panel discussed gene expression profiling (GEP) for the identification of the tissue of origin and concluded that, although GEP has a diagnostic benefit, a clinical benefit has not been demonstrated. The panel recommends against GEP as standard management, although 20% of the panel believes the diagnostic benefit of GEP warrants its routine use. In addition, the panel discussed testing for actionable mutations (eg, ALK) to help guide choice of therapy, but declined to add this recommendation., (Copyright © 2014 by the National Comprehensive Cancer Network.)

Occult primary tumors, or cancers of unknown primary (CUPs), are defined as histologically proven metastatic malignant tumors whose primary site cannot be identified during pretreatment evaluation. They have a wide variety of clinical presentations and a poor prognosis in most patients. Patients with occult primary tumors often present with general complaints, such as anorexia and weight loss. Clinical absence of primary tumor, early dissemination, aggressiveness, and unpredictability of metastatic pattern are characteristic of these tumors. Life expectancy is very short, with a median survival of 6 to 9 months. In most patients, occult primary tumors are refractory to systemic treatments, and chemotherapy is only palliative and does not significantly improve long-term survival. However, certain clinical presentations of these tumors are associated with a better prognosis. Special pathologic studies can identify subsets of patients with tumor types that are more responsive to chemotherapy. Treatment options should be individualized for this selected group of patients to achieve improved response and survival rates.

Background: To prospectively apply an automated, quantitative three-dimensional approach to imaging and airway analysis to assess airway remodeling in asthma patients., Methods: Using quantitative software (Pulmonary Workstation, version 0.139; VIDA Diagnostics; Iowa City, IA) that enables quantitative airway segment measurements of low-dose, thin-section (0.625 to 1.25 mm), multidetector-row CT (MDCT) scans, we compared airway wall thickness (WT) and wall area (WA) in 123 subjects participating in a prospective multicenter cohort study, the National Institutes of Health Severe Asthma Research Program (patients with severe asthma, n = 63; patients with mild-to-moderate asthma, n = 35); and healthy subjects, n = 25). A subset of these subjects underwent fiberoptic bronchoscopy and endobronchial biopsies (n = 32). WT and WA measurements were corrected for total airway diameter and area: WT and WA, respectively., Results: Subjects with severe asthma had a significantly greater WT% than patients with mild-to-moderate asthma and healthy subjects (17.2 +/- 1.5 vs 16.5 +/- 1.6 [p = 0.014] and 16.3 +/- 1.2 [p = 0.031], respectively) and a greater WA percentage (WA%) compared to patients with mild-to-moderate asthma and healthy subjects (56.6 +/- 2.9 vs 54.7 +/- 3.3 [p = 0.005] and 54.6 +/- 2.4 [p = 0.003], respectively). Both WT% and WA% were inversely correlated with baseline FEV(1) percent predicted (r = -0.39, p < 0.0001 and r = -0.40, p < 0.0001, respectively) and positively correlated with response to a bronchodilator (r = 0.28, p = 0.002 and r = 0.35, p < 0.0001, respectively). The airway epithelial thickness measure on the biopsy sample correlated with WT% (r = 0.47; p = 0.007) and WA% (r = 0.52; p = 0.003). In the same individual, there is considerable regional heterogeneity in airway WT., Conclusion: Patients with severe asthma have thicker airway walls as measured on MDCT scan than do patients with mild asthma or healthy subjects, which correlates with pathologic measures of remodeling and the degree of airflow obstruction. MDCT scanning may be a useful technique for assessing airway remodeling in asthma patients, but overlap among the groups limits the diagnostic value in individual subjects.

The Lung Screening Study (LSS) was a pilot study designed to assess the feasibility of conducting a large scale randomized controlled trial (RCT) of low radiation dose spiral computed tomography (LDCT) versus chest X-ray (CXR) for lung cancer screening. Baseline results of LSS have been previously reported. Here, we report on the findings at the year one screen and on the final results of the LSS study. A total of 1660 subjects were randomized to the LDCT arm and 1658 to the CXR arm. Compliance with screening declined from 96% at baseline to 86% at year one in the LDCT arm and declined from 93% at baseline to 80% at year one in the CXR arm. Positivity rates for the year one screen were 25.8% for LDCT and 8.7% for CXR. Cancer yield was significantly less at year one for LDCT, 0.57%, than at baseline, 1.9%; cancer yield for CXR increased from 0.45% at baseline to 0.68% at year one. Forty lung cancers in the LDCT arm and 20 in the CXR arm were diagnosed over the study period. Stage I cancers comprised 48% of cases in the LDCT arm and 40% in the CXR arm. A total of 16 stage III-IV cancers were observed in the LDCT arm versus nine in the CXR arm. The LSS has established the feasibility of a RCT comparing annual spiral CT to chest X-ray for lung cancer screening.

Purpose: To evaluate the repeatability of quantitative computed tomographic (CT) indexes of emphysema and the effect of spirometric gating of lung volume during CT in candidates for lung volume reduction surgery (LVRS)., Materials and Methods: Initial and same-day repeat routine inspiratory spiral chest CT studies were performed in 29 LVRS candidates (group 1, routine study vs repeat study). In a separate cohort of 29 LVRS candidates, spiral chest CT studies were performed both without and with spirometric gating by using a spirometer to trigger scanning at 90% of vital capacity (group 2, spirometric gating study). In each study, Pearson and intraclass correlation coefficients were calculated to determine the agreement between multiple pairs of whole-lung quantitative CT indexes of emphysema, and mean values were compared with two-tailed paired t tests., Results: Pearson and intraclass correlation coefficients were high for all quantitative CT indexes (all > or = 0.92). No significant differences were found between mean values of quantitative CT indexes in group 1. Variation in quantitative CT results was small but more prominent in group 2 than in group 1. The variation in quantitative CT results was primarily related to differences in lung volume (r(2) as great as 0.83)., Conclusion: Repeatability of quantitative CT test results in LVRS candidates is high and unlikely to improve by using spirometric gating.

Hyperpolarized (3)He gas MRI was used to form maps of the effective diffusivity of gas in human lungs. Images of diffusion as well as spin density are presented from a study of 11 healthy volunteers and 5 patients with severe emphysema. The effective rate of diffusion, D(e), of the gas is reduced by the alveolar walls; tissue destruction in emphysema is hypothesized to result in larger D(e). Indeed, the mean value of D(e) in the emphysematous lungs is found here to be about 2.5 times that of healthy lungs, although still smaller than the unrestricted diffusivity of (3)He in free air. Histograms of D(e) values across coronal slices are presented. The results are discussed in terms of spatial variations, variations among individuals, healthy and diseased, and variations due to changes in lung volume. Magn Reson Med 44:174-179, 2000., (Copyright 2000 Wiley-Liss, Inc.)

We applied the rapid imaging capability of echo planar MR pulse sequences and hyperpolarized (3)He ventilation imaging to observe the dynamic distribution of gas in the lungs during breathing. Findings in five normal volunteers (age 19-53 years) and four patients with severe smoking-related emphysema (age 56-71 years) were compared. All studies were performed on a 1.5 T whole body scanner using a 30 cm Helmholtz surface coil and 0.5 l of 20-40% polarized (3)He mixed with 1-2 l nitrogen. Our echo planar imaging pulse sequence allowed acquisition of each image in 0.04 s, with a pixel size of 7 mm(2) (TR = 40.5 ms, TE = 12.1 ms, flip angle = 22 degrees, echo train length = 32, matrix = 32 x 64, field of view = 225 x 450 mm, slice thickness = 10 mm). Imaging was performed in the transaxial plane repeatedly at 3, 10 or 20 evenly spaced levels, immediately before and during breathing of the gas mixture. In normal subjects during the first breath, (3)He appeared throughout each slice first in the mid lungs, then in the lower lungs, then in the upper lungs, with slightly greater signal in the dependent posterior regions. In patients with emphysema, sequential filling of different lung regions was seen during the first breath, with delayed filling of other regions observed during rebreathing and room air washout. We conclude that subsecond dynamic (3)He MR ventilation imaging can reveal normal and abnormal ventilation phenomena not seen with conventional scintigraphic methods, and offers another approach to the study of ventilation physiology and pathophysiology., (Copyright 2000 John Wiley & Sons, Ltd.)

Objectives: We used whole-lung quantitative CT analysis (QCT)-an objective method of evaluating emphysema severity and distribution based on measurement of lung density-to determine whether subjective selection criteria for lung volume reduction surgery are applied consistently and to model the patient selection process, and assessed the relationship of the model to postoperative outcome., Design: Logistic regression analysis using QCT indexes of emphysema and preoperative physiologic test results as the independent variables, and the decision to operate as the dependent variable., Setting: University hospital., Patients: Seventy patients selected for bilateral lung volume reduction surgery and 32 otherwise operable patients excluded from surgery based on subjective assessment of emphysema morphology on chest radiography, CT, and perfusion scintigraphy., Intervention: Bilateral lung volume reduction surgery in the selected group., Measurements and Results: Emphysema in patients selected for surgery was more severe overall and in the upper lungs by multiple QCT indexes (p < 0.01, unpaired two-tailed t test). Physiologic abnormalities were slightly more severe in selected patients (p < 0.05, unpaired two-tailed t test). The range of many QCT and physiologic values overlapped considerably between the selected and excluded groups. The percent severe emphysema (<- 960 Hounsfield units [HU]), upper/lower lung emphysema ratio (- 900 HU threshold), and residual volume were the key variables in the model predicting selection decisions (model r(2) = 0.48; p < 0.0001). The model correctly predicted selection decisions in 87% of all cases, 91% of the selected group, and 78% of the excluded group. Surgical patients with a higher model-derived probability of selection had greater postoperative improvement in FEV(1) and 6-min walk distance., Conclusions: Radiologic selection criteria are applied consistently to the majority of patients. QCT features are strongly associated with selection decisions, are related to outcome, and may help improve consistency and confidence in patient selection.

Rapid repetitive MRI of hyperpolarized (HP) gases using echo-planar imaging (EPI) has been theoretically investigated and experimentally demonstrated for (3)He in human lung. A quantitative treatment of signal attenuation and magnetization consumption for the unique circumstance of a rapidly diffusing nonrenewable magnetization source has been performed. Rapid (compared to the human respiratory cycle) and repetitive imaging of the lung gas space with EPI and a single delivered bolus of HP-(3)He is feasible using low flip angles, provided the voxels are not too small. A coarse-grid (32 x 64) EPI pulse sequence has been developed and implemented to image the lungs of healthy volunteers during rebreathing of a HP-(3)He/N(2) gas mixture. A set of three 10-mm axial slices was imaged every 0.12 sec for the 36 sec duration of rebreathing, yielding a real-time visualization of ventilation. Despite some mild artifacts, the images are of good quality and show changes in gas density related to respiratory physiology. Magn Reson Med 42:507-514, 1999., (Copyright 1999 Wiley-Liss, Inc.)

Purpose: To investigate the use of gadolinium as a computed tomographic (CT) contrast agent., Materials and Methods: In vitro attenuation measurements of multiple dilutions of gadodiamide and ioversol were compared. In three pigs, 50-mL boluses of undiluted gadodiamide were injected intravenously at 2 mL/sec, and repeated single-level scans were obtained through the lung bases, liver, and kidneys. The doses of 0.8-1.0 mmol of gadolinium per kilogram of body weight were approximately three times the highest doses currently used in patients. Enhancement was determined from attenuation measurements in the aorta, pulmonary arteries, liver, and kidneys., Results: In vitro, the attenuation of undiluted gadodiamide (3,069 HU) was equivalent to that of ioversol diluted to 106 mg of iodine per milliliter and at equimolar concentrations was 50% greater than that of ioversol. The magnitude of and time to peak enhancement were 141 HU and 27 seconds (n = 3) for the aorta; 168 HU and 21 seconds (n = 3) for the pulmonary arteries; 23 HU and 65 seconds (n = 2) for the liver; and 63 HU and 32 seconds (n = 1) for the kidneys. Time-attenuation curves revealed a useful duration of enhancement of 20-30 seconds for the aorta and pulmonary arteries., Conclusion: Gadolinium produces good vascular enhancement, adequate renal enhancement, and suboptimal hepatic enhancement. Further study is needed to determine the safety of the gadolinium dose required to produce similar enhancement in patients.

The diaphragm performs most of the physiologic work of inspiration, and forms an anatomic barrier between the thoracic and abdominal cavities. Disorders of the diaphragm can be related to impairment of either of these functions, and most have radiologic manifestations. Both intrathoracic and intra-abdominal disease processes can alter the normal radiologic appearance of the diaphragm. Abnormalities are usually first detected on chest radiographs, often incidentally in asymptomatic patients, and many require further characterization by other imaging studies for definitive diagnosis. Fluoroscopy, CT, and MR imaging are frequently the most useful additional studies, whereas ultrasonography, barium contrast studies, and liver-spleen scintigraphy are occasionally helpful. Selection of the most appropriate radiologic technique in a given clinical situation can greatly facilitate the diagnosis of diaphragm abnormalities.

Objective: This study was performed to assess the accuracy of determining lung volume in patients with emphysema using MR imaging and then to investigate changes in thoracic dimensions after lung volume reduction surgery., Subjects and Methods: Fast gradient-echo breath-hold MR imaging through the entire thorax at full inspiration and expiration was performed in 21 patients with severe emphysema and was performed again in nine of the patients who underwent surgery. Lung volumes were determined using a semiautomated computerized method of delineating the lungs and summing cross-sectional areas. These summed areas were compared with volumes measured on plethysmography and CT. Postoperative changes in thoracic structure were determined by measuring anteroposterior and transverse lung dimensions and lung height before and after surgery., Results: The correlation coefficients and SEM for determining inspiratory lung volume were MR imaging versus plethysmography, r = .77, SEM = -12% (volume measured as less on MR imaging); CT versus plethysmography, r = .86, SEM = -13% (volume measured as less on CT); and MR imaging versus CT, r = .87, SEM = 4% (volume measured as greater on MR imaging). The correlation coefficients and SEM for determining expiratory volume on MR imaging versus plethysmography were r = .77, SEM = 6% (volume measured as greater on MR imaging). After surgery, decreases were found in all thoracic dimensions, and such decreases were greatest at expiration., Conclusion: MR measurements of lung volume are comparable with those of CT and differ from those of plethysmography. Changes in thoracic dimensions after lung volume reduction surgery are consistent with improved respiratory mechanics.

For patients with emphysema, imaging studies have been useful for diagnostic purposes and for preoperative patient selection for surgical intervention, such as bullectomy, lung transplantation, and LVRS. Chest radiography is useful in evaluating hyperinflation. Inspiratory and expiratory films are used to estimate diaphragmatic excursion and air-trapping. CT scan is used to evaluate the anatomy and distribution of emphysema throughout the lungs, providing information clinically unobtainable by other means. Both imaging techniques are useful for detecting other disease processes. Radionuclide lung scanning also provides an estimate of target areas, volume occupying but nonfunctioning lung. Cohort studies utilizing these imaging techniques have demonstrated associations between preoperative characteristics and postoperative outcome. The imaging studies, especially the chest radiograph, have also played an important role in postoperative management. Many other imaging options are available, such as HRCT scan, quantitative CT scan, and single photon emission CT scan. Other techniques, such as MR imaging, may play a future role as well.

Objective: This study describes the atypical presentation of atelectasis as a pseudomass in patients with severe bullous emphysema., Materials and Methods: The radiologic studies and clinical records of 11 patients with severe bullous emphysema and mass-like opacities representing atelectatic lung were reviewed. The diagnosis was proven by surgery in nine patients and by follow-up imaging in two patients., Results: Pseudomasses were found primarily in the upper lobes and the right middle lobe (n = 10). Common features included an oblong, lenticular, or triangular shape (n = 8); a sharp interface with aerated lung (n = 9); hyperexpansion of the hemithorax containing the pseudomass (n = 8); a central location abutting the mediastinum (n = 8); and adjacent emphysema (n = 11). CT revealed subsegmental atelectasis in other lobes adjacent to the bullous lung in six patients. In three patients, the pseudomasses were associated with persistent distention of large bullae following spontaneous pneumothoraces. Reexpansion of pseudomasses occurred in seven of the eight patients who underwent resection of bullous lung., Conclusion: These pseudomasses most likely result from compression of the lung by adjacent large bullae. The diagnosis should be suspected when central, sharply marginated, mass-like opacities that are oblong, lenticular, or triangular are bordered by severe bullous emphysema.

Lung volume reduction surgery (LVRS), which involves the bilateral wedge resection of 20% to 30% of the most diseased lung through a median sternotomy, is emerging as a promising treatment option for select patients with severe, debilitating emphysema. This article details our observations and preliminary investigations related to the imaging evaluation of patients including selection criteria, postoperative findings, and structural changes in the thorax after surgery. Routine preoperative evaluation includes inspiratory and expiratory chest radiographs, computed tomography (CT) examination, and nuclear medicine lung scan. Investigational studies include quantitative CT to assess disease severity and dynamic magnetic resonance imaging to study respiratory movements. Postoperative improvement in FEV1, oxygenation, and exercise tolerance correlate with the degree of heterogeneity, hyperinflation, lung compression, upper lobe severity, and percentage of retained mildly diseased lung shown on preoperative imaging studies. Postoperative radiographic monitoring is important for detection of complications. Postoperative follow-up examinations show reduced thoracic distention, improved coordination of respiratory movement, and increased diaphragm curvature and excursion, supporting the hypothesis of improved respiratory mechanics as a major contributing factor to the success of LVRS.