Ultra-low-dose vs. standard-of-care-dose CT of the chest in patients with post-COVID-19 conditions-a prospective intra-patient multi-reader study.

OBJECTIVES: To conduct an intrapatient comparison of ultra-low-dose computed tomography (ULDCT) and standard-of-care-dose CT (SDCT) of the chest in terms of the diagnostic accuracy of ULDCT and intrareader agreement in patients with post-COVID conditions. METHODS: We prospectively included 153 consecutive patients with post-COVID-19 conditions. All participants received an SDCT and an additional ULDCT scan of the chest. SDCTs were performed with standard imaging parameters and ULDCTs at a fixed tube voltage of 100 kVp (with tin filtration), 50 ref. mAs (dose modulation active), and iterative reconstruction algorithm level 5 of 5. All CT scans were separately evaluated by four radiologists for the presence of lung changes and their consistency with post-COVID lung abnormalities. Radiation dose parameters and the sensitivity, specificity, and accuracy of ULDCT were calculated. RESULTS: Of the 153 included patients (mean age 47.4 ± 15.3 years; 48.4% women), 45 (29.4%) showed post-COVID lung abnormalities. In those 45 patients, the most frequently detected CT patterns were ground-glass opacities (100.0%), reticulations (43.5%), and parenchymal bands (37.0%). The accuracy, sensitivity, and specificity of ULDCT compared to SDCT for the detection of post-COVID lung abnormalities were 92.6, 87.2, and 94.9%, respectively. The median total dose length product (DLP) of ULDCTs was less than one-tenth of the radiation dose of our SDCTs (12.6 mGy*cm [9.9; 15.5] vs. 132.1 mGy*cm [103.9; 160.2]; p < 0.001). CONCLUSION: ULDCT of the chest offers high accuracy in the detection of post-COVID lung abnormalities compared to an SDCT scan at less than one-tenth the radiation dose, corresponding to only twice the dose of a standard chest radiograph in two views. CLINICAL RELEVANCE STATEMENT: Ultra-low-dose CT of the chest may provide a favorable, radiation-saving alternative to standard-dose CT in the long-term follow-up of the large patient cohort of post-COVID-19 patients.

Detection of Post-COVID-19 Lung Abnormalities: Photon-counting CT versus Same-Day Energy-integrating Detector CT.

Background Photon-counting detector (PCD) CT enables ultra-high-resolution lung imaging and may shed light on morphologic correlates of persistent symptoms after COVID-19. Purpose To compare PCD CT with energy-integrating detector (EID) CT for noninvasive assessment of post-COVID-19 lung abnormalities. Materials and Methods For this prospective study, adult participants with one or more COVID-19-related persisting symptoms (resting or exertional dyspnea, cough, fatigue) underwent same-day EID and PCD CT between April 2022 and June 2022. The 1.0-mm EID CT images and, subsequently, 1.0-, 0.4-, and 0.2-mm PCD CT images were reviewed for the presence of lung abnormalities. Subjective and objective EID and PCD CT image quality were evaluated using a five-point Likert scale (-2 to 2) and lung signal-to-noise ratios (SNRs). Results Twenty participants (mean age, 54 years ± 16 [SD]; 10 men) were included. EID CT showed post-COVID-19 lung abnormalities in 15 of 20 (75%) participants, with a median involvement of 10% of lung volume [IQR, 0%-45%] and 3.5 lobes [IQR, 0-5]. Ground-glass opacities and linear bands (10 of 20 participants [50%] for both) were the most frequent findings at EID CT. PCD CT revealed additional lung abnormalities in 10 of 20 (50%) participants, with the most common being bronchiectasis (10 of 20 [50%]). Subjective image quality was improved for 1.0-mm PCD versus 1.0-mm EID CT images (median, 1; IQR, 1-2; P < .001) and 0.4-mm versus 1.0-mm PCD CT images (median, 1; IQR, 1-1; P < .001) but not for 0.4-mm versus 0.2-mm PCD CT images (median, 0; IQR, 0-0.5; P = .26). PCD CT delivered higher lung SNR versus EID CT for 1.0-mm images (mean difference, 0.53 ± 0.96; P = .03) but lower SNR for 0.4-mm versus 1.0-mm images and 0.2-mm vs 0.4-mm images (-1.52 ± 0.68 [P < .001] and -1.15 ± 0.43 [P < .001], respectively). Conclusion Photon-counting detector CT outperformed energy-integrating detector CT in the visualization of subtle post-COVID-19 lung abnormalities and image quality. © RSNA, 2023 Supplemental material is available for this article.

Fetal MRI radiomics: non-invasive and reproducible quantification of human lung maturity.

OBJECTIVES: To assess the reproducibility of radiomics features extracted from the developing lung in repeated in-vivo fetal MRI acquisitions. METHODS: In-vivo MRI (1.5 Tesla) scans of 30 fetuses, each including two axial and one coronal T2-weighted sequences of the whole lung with all other acquisition parameters kept constant, were retrospectively identified. Manual segmentation of the lungs was performed using ITK-Snap. One hundred radiomics features were extracted from fetal lung MRI data using Pyradiomics, resulting in 90 datasets. Intra-class correlation coefficients (ICC) of radiomics features were calculated between baseline and repeat axial acquisitions and between baseline axial and coronal acquisitions. RESULTS: MRI data of 30 fetuses (12 [40%] females, 18 [60%] males) at a median gestational age of 24 + 5 gestational weeks plus days (GW) (interquartile range [IQR] 3 + 3 GW, range 21 + 1 to 32 + 6 GW) were included. Median ICC of radiomics features between baseline and repeat axial MR acquisitions was 0.92 (IQR 0.13, range 0.33 to 1), with 60 features exhibiting excellent (ICC > 0.9), 27 good (> 0.75-0.9), twelve moderate (0.5-0.75), and one poor (ICC < 0.5) reproducibility. Median ICC of radiomics features between baseline axial and coronal MR acquisitions was 0.79 (IQR 0.15, range 0.2 to 1), with 20 features exhibiting excellent, 47 good, 29 moderate, and four poor reproducibility. CONCLUSION: Standardized in-vivo fetal MRI allows reproducible extraction of lung radiomics features. In the future, radiomics analysis may improve diagnostic and prognostic yield of fetal MRI in normal and pathologic lung development. KEY POINTS: • Non-invasive fetal MRI acquired using a standardized protocol allows reproducible extraction of radiomics features from the developing lung for objective tissue characterization. • Alteration of imaging plane between fetal MRI acquisitions has a negative impact on lung radiomics feature reproducibility. • Fetal MRI radiomics features reflecting the microstructure and shape of the fetal lung could complement observed-to-expected lung volume in the prediction of postnatal outcome and optimal treatment of fetuses with abnormal lung development in the future.

Impact of a content-based image retrieval system on the interpretation of chest CTs of patients with diffuse parenchymal lung disease.

OBJECTIVES: Content-based image retrieval systems (CBIRS) are a new and potentially impactful tool for radiological reporting, but their clinical evaluation is largely missing. This study aimed at assessing the effect of CBIRS on the interpretation of chest CT scans from patients with suspected diffuse parenchymal lung disease (DPLD). MATERIALS AND METHODS: A total of 108 retrospectively included chest CT scans with 22 unique, clinically and/or histopathologically verified diagnoses were read by eight radiologists (four residents, four attending, median years reading chest CT scans 2.1± 0.7 and 12 ± 1.8, respectively). The radiologists read and provided the suspected diagnosis at a certified radiological workstation to simulate clinical routine. Half of the readings were done without CBIRS and half with the additional support of the CBIRS. The CBIRS retrieved the most likely of 19 lung-specific patterns from a large database of 6542 thin-section CT scans and provided relevant information (e.g., a list of potential differential diagnoses). RESULTS: Reading time decreased by 31.3% (p < 0.001) despite the radiologists searching for additional information more frequently when the CBIRS was available (154 [72%] vs. 95 [43%], p < 0.001). There was a trend towards higher overall diagnostic accuracy (42.2% vs 34.7%, p = 0.083) when the CBIRS was available. CONCLUSION: The use of the CBIRS had a beneficial impact on the reading time of chest CT scans in cases with DPLD. In addition, both resident and attending radiologists were more likely to consult informational resources if they had access to the CBIRS. Further studies are needed to confirm the observed trend towards increased diagnostic accuracy with the use of a CBIRS in practice. KEY POINTS: • A content-based image retrieval system for supporting the diagnostic process of reading chest CT scans can decrease reading time by 31.3% (p < 0.001). • The decrease in reading time was present despite frequent usage of the content-based image retrieval system. • Additionally, a trend towards higher diagnostic accuracy was observed when using the content-based image retrieval system (42.2% vs 34.7%, p = 0.083).

Ultrahigh-Resolution Photon-Counting Detector CT of the Lungs: Association of Reconstruction Kernel and Slice Thickness With Image Quality.

BACKGROUND. Prior work has shown improved image quality for photon-counting detector (PCD) CT of the lungs compared with energy-integrating detector CT. A paucity of the literature has compared PCD CT of the lungs using different reconstruction parameters. OBJECTIVE. The purpose of this study is to the compare the image quality of ultra-high-resolution (UHR) PCD CT image sets of the lungs that were reconstructed using different kernels and slice thicknesses. METHODS. This retrospective study included 29 patients (17 women and 12 men; median age, 56 years) who underwent noncontrast chest CT from February 15, 2022, to March 15, 2022, by use of a commercially available PCD CT scanner. All acquisitions used UHR mode (1024 × 1024 matrix). Nine image sets were reconstructed for all combinations of three sharp kernels (BI56, BI60, and BI64) and three slice thicknesses (0.2, 0.4, and 1.0 mm). Three radiologists independently reviewed reconstructions for measures of visualization of pulmonary anatomic structures and pathologies; reader assessments were pooled. Reconstructions were compared with the clinical reference reconstruction (obtained using the BI64 kernel and a 1.0-mm slice thickness [BI641.0-mm]). RESULTS. The median difference in the number of bronchial divisions identified versus the clinical reference reconstruction was higher for reconstructions with BI640.4-mm (0.5), BI600.4-mm (0.3), BI640.2-mm (0.5), and BI600.2-mm (0.2) (all p < .05). The median bronchial wall sharpness versus the clinical reference reconstruction was higher for reconstructions with BI640.4-mm (0.3) and BI640.2-mm (0.3) and was lower for BI561.0-mm (-0.7) and BI560.4-mm (-0.3) (all p < .05). Median pulmonary fissure sharpness versus the clinical reference reconstruction was higher for reconstructions with BI640.4-mm (0.3), BI600.4-mm (0.3), BI560.4-mm (0.5), BI640.2-mm (0.5), BI600.2-mm (0.5), and BI560.2-mm (0.3) (all p < .05). Median pulmonary vessel sharpness versus the clinical reference reconstruction was lower for reconstructions with BI561.0-mm (-0.3), BI600.4-mm (-0.3), BI560.4-mm (-0.7), BI640.2-mm (-0.7), BI600.2-mm (-0.7), and BI560.2-mm (-0.7). Median lung nodule conspicuity versus the clinical reference reconstruction was lower for reconstructions with BI561.0-mm (-0.3) and BI560.4-mm (-0.3) (both p < .05). Median conspicuity of all other pathologies versus the clinical reference reconstruction was lower for reconstructions with BI561.0 mm (-0.3), BI560.4-mm (-0.3), BI640.2-mm (-0.3), BI600.2-mm (-0.3), and BI560.2-mm (-0.3). Other comparisons among reconstructions were not significant (all p > .05). CONCLUSION. Only the reconstruction using BI640.4-mm yielded improved bronchial division identification and bronchial wall and pulmonary fissure sharpness without a loss in pulmonary vessel sharpness or conspicuity of nodules or other pathologies. CLINICAL IMPACT. The findings of this study may guide protocol optimization for UHR PCD CT of the lungs.

[Chest radiography findings in diffuse parenchymal lung diseases]. / Röntgenbefunde bei diffusen parenchymatösen Lungenerkrankungen.

CLINICAL ISSUE: Diffuse parenchymal lung diseases include a heterogeneous group of diseases of the lung parenchyma, the alveolar spaces, the vessels and the airways, which can be triggered by various pathomechanisms, such as inflammation and fibrotic changes. Since the therapeutic approaches and prognoses differ significantly between the diseases, the correct diagnosis is of fundamental importance. In routine clinical practice, next to the patients' history, the clinical presentation, the laboratory findings and the bronchoscopy, imaging plays a central role in establishing a diagnosis. PRACTICAL RECOMMENDATIONS: The diagnosis of diffuse parenchymal lung diseases is an enormous challenge for clinicians, radiologists as well as pathologists and should therefore preferably be carried out in a multidisciplinary setting. Since patients often present with unspecific, respiratory symptoms, chest radiographs are the first imaging method used. Many patterns of diffuse parenchymal lung diseases (e.g., ground-glass opacities and consolidations), their distribution (e.g., cranial-caudal) and the presence of additional findings (e.g., mediastinal lymphadenopathy) are often already detectable on chest X­rays. However, the imaging reference standard and thus, an integral part of the assessment of diffuse parenchymal lung disease, is the chest HR-CT. In some cases, the pattern of the HR-CT is pathognomonic, in others it is unspecific for a disease, so that further diagnostic steps are necessary.

Risk assessment of acute pulmonary embolism utilizing coronary artery calcifications in patients that have undergone CT pulmonary angiography and transthoracic echocardiography.

OBJECTIVE: To evaluate the relation of coronary artery calcifications (CAC) on non-ECG-gated CT pulmonary angiography (CTPA) with short-term mortality in patients with acute pulmonary embolism (PE). METHODS: We retrospectively included all in-patients between May 2007 and December 2014 with an ICD-9 code for acute PE and CTPA and transthoracic echocardiography available. CAC was qualitatively graded as absent, mild, moderate, or severe. Relations of CAC with overall and PE-related 30-day mortality were assessed using logistic regression analyses. The independence of those relations was assessed using a nested approach, first adjusting for age and gender, then for RV strain, peak troponin T, and cardiovascular risk factors for an overall model. RESULTS: Four hundred seventy-nine patients were included (63 ± 16 years, 52.8% women, 47.2% men). In total, 253 (52.8%) had CAC-mild: 143 (29.9%); moderate: 89 (18.6%); severe: 21 (4.4%). Overall mortality was 8.8% (n = 42) with higher mortality with any CAC (12.6% vs. 4.4% without; odds ratio [OR] 3.1 [95%CI 2.1-14.5]; p = 0.002). Mortality with severe (19.0%; OR 5.1 [95%CI 1.4-17.9]; p = 0.011), moderate (11.2%; OR 2.7 [95%CI 1.1-6.8]; p = 0.031), and mild CAC (12.6%; OR 3.1 [95%CI 1.4-6.9]; p = 0.006) was higher than without. OR adjusted for age and gender was 2.7 (95%CI 1.0-7.1; p = 0.050) and 2.6 (95%CI 0.9-7.1; p = 0.069) for the overall model. PE-related mortality was 4.0% (n = 19) with higher mortality with any CAC (5.9% vs. 1.8% without; OR 3.5 [95%CI 1.1-10.7]; p = 0.028). PE-related mortality with severe CAC was 9.5% (OR 5.8 [95%CI 1.0-34.0]; p = 0.049), with moderate CAC 6.7% (OR 4.0 [95%CI 1.1-14.6]; p = 0.033), and with mild 4.9% (OR 2.9 [95%CI 0.8-9.9]; p = 0.099). OR adjusted for age and gender was 4.2 (95%CI 0.9-20.7; p = 0.074) and 3.4 (95%CI 0.7-17.4; p = 0.141) for the overall model. Patients with sub-massive PE showed similar results. CONCLUSION: CAC is frequent in acute PE patients and associated with short-term mortality. Visual assessment of CAC may serve as an easy, readily available tool for early risk stratification in those patients. KEY POINTS: • Coronary artery calcification assessed on computed tomography pulmonary angiography is frequent in patients with acute pulmonary embolism. • Coronary artery calcification assessed on computed tomography pulmonary angiography is associated with 30-day overall and PE-related mortality in patients with acute pulmonary embolism. • Coronary artery calcification assessed on computed tomography pulmonary angiography may serve as an additional, easy readily available tool for early risk stratification in those patients.

[Morphological and functional sequelae after COVID-19 pneumonia]. / Morphologische und funktionelle Folgen nach COVID-19-Pneumonie.

BACKGROUND: Following coronavirus disease 2019 (COVID-19), a proportion of patients report prolonged or worsening symptoms and impairments. These symptoms are increasingly referred to as "long COVID" syndrome. They may be associated with radiological changes on computed tomography (CT) and pulmonary function impairment. OBJECTIVES: To discuss the role of long-term assessment of COVID-19 patients to determine which patients may benefit from follow-up. MATERIALS AND METHODS: This article presents the current results of clinical, radiological, and pulmonary function follow-up tests after COVID-19 pneumonia. RESULTS: Chronic fatigue and dyspnea are the most common persistent symptoms after COVID-19. Patients also present impaired exercise capacity. On CT, ground-glass opacities and parenchymal bands are the most common residual changes after COVID-19 pneumonia, histologically corresponding to organizing pneumonia. A proportion of patients who had severe COVID-19 pneumonia may show fibrotic-like changes during follow-up. Patients with severe acute infection may present with a restrictive syndrome with lower diffusing capacity for carbon monoxide (DLCO) and total lung capacity (TLC) values. Overall, significant and continuous improvement in all symptoms as well as radiomorphological and functional changes were observed over time. CONCLUSIONS: Patients with persistent symptoms after COVID-19 should be evaluated and treated in specialized post-COVID-19 clinics in a multidisciplinary manner.

The Growth Rate of Subsolid Lung Adenocarcinoma Nodules at Chest CT.

Background Confirming that subsolid adenocarcinomas show exponential growth is important because it would justify using volume doubling time to assess their growth. Purpose To test whether the growth of lung adenocarcinomas manifesting as subsolid nodules at chest CT is accurately represented by an exponential model. Materials and Methods Patients with lung adenocarcinomas manifesting as subsolid nodules surgically resected between January 2005 and May 2018, with three or more longitudinal CT examinations before resection, were retrospectively included. Overall volume (for all nodules) and solid component volume (for part-solid nodules) were measured over time. A linear mixed-effects model was used to identify the growth pattern (linear, exponential, quadratic, or power law) that best represented growth. The interactions between nodule growth and clinical, CT morphologic, and pathologic parameters were studied. Results Sixty-nine patients (mean age, 70 years ± 9 [standard deviation]; 48 women) with 74 lung adenocarcinomas were evaluated. Overall growth and solid component growth were better represented by an exponential model (adjusted R2 = 0.89 and 0.95, respectively) than by a quadratic model (r2 = 0.88 and 0.93, respectively), a linear model (r2 = 0.87 and 0.92, respectively), or a power law model (r2 = 0.82 and 0.93, respectively). Faster overall volume growth was associated with a history of lung cancer (P < .001), a baseline nodule volume less than 500 mm3 (P = .03), and histologic findings of invasive adenocarcinoma (P < .001). The median volume doubling time of noninvasive adenocarcinoma was significantly longer than that of invasive adenocarcinoma (939 days [interquartile range, 588-1563 days] vs 678 days [interquartile range, 392-916 days], respectively; P = .01). Conclusion The overall volume growth of adenocarcinomas manifesting as subsolid nodules at chest CT was best represented by an exponential model compared with the other tested models. This justifies the use of volume doubling time for the growth assessment of these nodules. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kuriyama and Yanagawa in this issue.

Right ventricular strain in patients with pulmonary embolism and syncope.

Patients with acute pulmonary embolism (PE) can present with various clinical manifestations including syncope. The mechanism of syncope in PE is not fully elucidated and data of right ventricular (RV) function in patients has been limited. We retrospectively identified 477 consecutive patients hospitalized with acute PE diagnosed with a computed tomogram (CT) who also had a transthoracic echocardiogram (TTE) 24 h prior to or 48 h after diagnosis. Parameters of RV strain on CT, TTE, electrocardiogram (ECG), and clinical characteristics and adverse outcomes were collected. Patients with all three studies available for assessment were included (n = 369) and those with syncope (n = 34) were compared to patients without syncope (n = 335). Patients with syncope were more likely to demonstrate RV strain on all three modes of assessment compared to those without syncope [17 (50%) vs. 67 (20%); p = 0.001], and those patients were more likely to receive advanced therapies [9 (53%) vs. 15 (22%); p = 0.02]. PE-related mortality was highest among those presenting with high-risk PE and syncope (36%, OR 20.1, 95% CI 5.3-81.1; p < 0.001) and was low in patients with syncope without criteria for high-risk PE (3%, OR 1.2, 95% CI 0.2-10.0; p < 0.001). In conclusion, acute PE patients with syncope are more likely to demonstrate multimodality evidence of RV strain and to receive advanced therapies. Syncope was only associated with increased PE-related mortality in patients presenting with a high-risk PE. Syncope alone without evidence of RV strain is associated with low short-term adverse events and is similar to those without syncope.

Mitral annular plane systolic excursion and tricuspid annular plane systolic excursion for risk stratification of acute pulmonary embolism.

INTRODUCTION: Risk stratification for acute pulmonary embolism (PE) incorporates metrics of right ventricle (RV) function. Significant RV dysfunction influences left ventricular (LV) function, though LV function metrics are not utilized for stratifying outcomes in patients with PE. Mitral annular plane systolic excursion (MAPSE) is a linear echocardiographic (TTE) measure that evaluates longitudinal LV function and may aid in risk stratification for acute PE. METHODS: Using a single-center database of patients with PE from 2007 to 2014, MAPSE was calculated for all TTE's available with sufficient quality (n = 362). A MAPSE of ≥11 mm was used as a normal reference. Thirty-day adverse outcomes were defined as administration of vasopressor, fibrinolytic therapy, open embolectomy, or 30-day PE-related mortality. Odds ratios (OR) and adjusted OR (AOR) were calculated using logistic regression analysis. Tricuspid annular plane systolic excursion (TAPSE) measurements were incorporated to determine the additive benefit of MAPSE. RESULTS: Compared with the reference MAPSE ≥ 11 mm and LVEF > 50%, patients with MAPSE < 11 mm and an LVEF > 50% had worse outcomes (AOR 2.94 [95% CI: 1.08-7.98], P = 0.035). Among patients with LVEF > 50%, the presence of both a MAPSE < 11 mm and TAPSE < 16 mm was associated with greater odds of adverse outcomes compared with isolated depressed TAPSE (AOR 10.75 [95% CI: 3.06-37.8], P < 0.01 vs AOR 1.68 [95% CI: 0.18-15.6], P = 0.65). CONCLUSION: A depressed MAPSE, in patients with preserved LVEF, is associated with worse outcomes in patients with acute PE. The addition of MAPSE to TAPSE appears to have a greater prognostic value than either alone and may further aid in risk stratification, but for confirmation further prospective data are needed.

[Radiological manifestations of pulmonary diseases in COVID-19]. / Radiologische Manifestationen von Lungenerkrankungen bei COVID-19.

CLINICAL ISSUE: Since its emergence in late 2019, the disease caused by the novel coronavirus, termed COVID-19, has been declared a pandemic by the World Health Organization. Reference standard for the diagnosis of COVID-19 is a positive reverse transcription polymerase chain reaction (RT-PCR) test. While the RT-PCR shows a high specificity, its sensitivity depends on the duration of symptoms, viral load, quality of the sample, and the assay used. STANDARD RADIOLOGICAL METHODS: Chest radiography and computed tomography (CT) of the chest are the imaging modalities primarily used for assessment of the lung manifestations, extent, and complications of COVID-19 pneumonia. PERFORMANCE: Sensitivity and specificity of chest radiography is low. While sensitivity of CT for detecting COVID-19 pneumonia is high-averaging around 90%-its specificity is low-between 25 and 33%. PRACTICAL RECOMMENDATIONS: Indications for imaging in patients with suspected or diagnosed COVID-19 infection should be carefully considered to minimize the risk of infection for medical personnel and other patients. Imaging, particularly CT, can assess disease extent, complications, and differential diagnoses. COVID-19 pneumonia typically presents with bilateral, subpleural areas of ground glass opacifications with or without consolidations. During the course of the disease features resembling organizing pneumonia can occur. Follow-up examinations after recovery from COVID-19 pneumonia should focus on fibrotic changes of the lung parenchyma.

Software-based risk stratification of pulmonary adenocarcinomas manifesting as pure ground glass nodules on computed tomography.

OBJECTIVES: To assess the performance of the "Computer-Aided Nodule Assessment and Risk Yield" (CANARY) software in the differentiation and risk assessment of histological subtypes of lung adenocarcinomas manifesting as pure ground glass nodules on computed tomography (CT). METHODS: 64 surgically resected and histologically proven adenocarcinomas manifesting as pure ground-glass nodules on CT were assessed using CANARY software, which classifies voxel-densities into three risk components (low, intermediate, and high risk). Differences in risk components between histological adenocarcinoma subtypes were analysed. To determine the optimal threshold reflecting the presence of an invasive focus, sensitivity, specificity, negative predictive value, and positive predictive value were calculated. RESULTS: 28/64 (44%) were adenocarcinomas in situ (AIS); 26/64 (41%) were minimally invasive adenocarcinomas (MIA); and 10/64 (16%) were invasive ACs (IAC). The software showed significant differences in risk components between histological subtypes (P<0.001-0.003). A relative volume of 45% or less of low-risk components was associated with histological invasiveness (specificity 100%, positive predictive value 100%). CONCLUSIONS: CANARY-based risk assessment of ACs manifesting as pure ground glass nodules on CT allows the differentiation of their histological subtypes. A threshold of 45% of low-risk components reflects invasiveness in these groups. KEY POINTS: • CANARY-based risk assessment allows the differentiation of their histological subtypes. • 45% or less of low-risk component reflects histological invasiveness. • CANARY has potential role in suspected adenocarcinomas manifesting as pure ground-glass nodules.

Harms of off-label erythropoiesis-stimulating agents for critically ill people.

BACKGROUND: Anaemia is a common problem experienced by critically-ill people. Treatment with erythropoiesis-stimulating agents (ESAs) has been used as a pharmacologic strategy when the blunted response of endogenous erythropoietin has been reported in critically-ill people. The use of ESAs becomes more important where adverse clinical outcomes of transfusing blood products is a limitation. However, this indication for ESAs is not licensed by regulatory authorities and is called off-label use. Recent studies concern the harm of ESAs in a critical care setting. OBJECTIVES: To focus on harms in assessing the effects of erythropoiesis-stimulating agents (ESAs), alone or in combination, compared with placebo, no treatment or a different active treatment regimen when administered off-label to critically-ill people. SEARCH METHODS: We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO via OvidSP, CINAHL, all evidence-based medicine (EBM) reviews including IPA and SCI-Expanded, Conference Proceedings Citation Index- Science, BIOSIS Previews and TOXLINE up to February 2017. We also searched trials registries, checked reference lists of relevant studies and tracked their citations by using SciVerse Scopus. SELECTION CRITERIA: We considered randomized controlled trials (RCTs) and controlled observational studies, which compared scheduled systemic administration of ESAs versus other effective interventions, placebo or no treatment in critically-ill people. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and evaluated the eligibility of retrieved records, extracted data and assessed the risks of bias and quality of the included studies. We resolved differences in opinion by consensus or by involving a third review author. We assessed the evidence using GRADE and created a 'Summary of findings' table. We used fixed-effect or random-effects models, depending on the heterogeneity between studies. We fitted three-level hierarchical Bayesian models to calculate overall treatment effect estimates. MAIN RESULTS: Of the 27,865 records identified, 39 clinical trials and 14 observational studies, including a total of 945,240 participants, were eligible for inclusion. Five studies are awaiting classification. Overall, we found 114 adverse events in 33 studies (30 RCTs and three observational studies), and mortality was reported in 41 studies (32 RCTs and nine observational studies). Most studies were at low to moderate risk of bias for harms outcomes. However, overall harm assessment and reporting were of moderate to low quality in the RCTs, and of low quality in the observational studies. We downgraded the GRADE quality of evidence for venous thromboembolism and mortality to very low and low, respectively, because of risk of bias, high inconsistency, imprecision and limitations of study design.It is unclear whether there is an increase in the risk of any adverse events (Bayesian risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.21; 3099 participants; 9 studies; low-quality evidence) or venous thromboembolism (Bayesian RR 1.04, 95% CI 0.70 to 1.41; 18,917 participants; 18 studies; very low-quality evidence).There was a decreased risk of mortality with off-label use of ESAs in critically-ill people (Bayesian RR 0.76, 95% CI 0.61 to 0.92; 930,470 participants; 34 studies; low-quality evidence). AUTHORS' CONCLUSIONS: Low quality of evidence suggests that off-label use of ESAs may reduce mortality in a critical care setting. There was a lack of high-quality evidence about the harm of ESAs in critically-ill people. The information for biosimilar ESAs is less conclusive. Most studies neither evaluated ESAs' harm as a primary outcome nor predefined adverse events. Any further studies of ESA should address the quality of evaluating, recording and reporting of adverse events.

Normal spectrum of pulmonary parametric response map to differentiate lung collapsibility: distribution of densitometric classifications in healthy adult volunteers.

OBJECTIVES: Pulmonary parametric response map (PRM) was proposed for quantitative densitometric phenotypization of chronic obstructive pulmonary disease. However, little is known about this technique in healthy subjects. The purpose of this study was to describe the normal spectrum of densitometric classification of pulmonary PRM in a group of healthy adults. METHODS: 15 healthy volunteers underwent spirometrically monitored chest CT at total lung capacity (TLC) and functional residual capacity (FRC). The paired CT scans were analyzed by PRM for voxel-by-voxel characterization of lung parenchyma according to 4 densitometric classifications: normal lung (TLC ≥ -950 HU, FRC ≥ -856 HU); expiratory low attenuation area (LAA) (TLC ≥ -950 HU, FRC < -856 HU); dual LAA (TLC<-950 HU, FRC < -856 HU); uncharacterized (TLC < -950 HU, FRC ≥ -856 HU). RESULTS: PRM spectrum was 78 % ± 10 % normal lung, 20 % ± 8 % expiratory LAA, and 1 % ± 1 % dual LAA. PRM was similar between genders, there was moderate correlation between dual LAA and spirometrically assessed TLC (R = 0.531; p = 0.042), and between expiratory LAA and VolExp/Insp ratio (R = -0.572; p = 0.026). CONCLUSIONS: PRM reflects the predominance of normal lung parenchyma in a group of healthy volunteers. However, PRM also confirms the presence of physiological expiratory LAA seemingly related to air trapping and a minimal amount of dual LAA likely reflecting emphysema. KEY POINTS: • Co-registration of inspiratory and expiratory computed tomography allows dual-phase densitometry. • Dual-phase co-registered densitometry reflects heterogeneous regional changes in lung function. • Quantification of lung in healthy subjects is needed to set reference values. • Expiratory low attenuation areas <30 % could be considered within normal range.

Imaging of Large Airways Disorders.

OBJECTIVE: Recent technical advances, including the routine use of CT thin sections and techniques such as 2D minimum-intensity-projection and 3D volume images, have increased our ability to detect large airways diseases. Furthermore, dedicated CT protocols allow the evaluation of dynamic airway dysfunction. CONCLUSION: With diseases of the large airways more commonly seen in daily practice, it is important that radiologists be familiar with the appearances, differential diagnosis, and clinical implications of these entities.

Contrast Agent Dynamics Determine Radiomics Profiles in Oncologic Imaging.

BACKGROUND: The reproducibility of radiomics features extracted from CT and MRI examinations depends on several physiological and technical factors. The aim was to evaluate the impact of contrast agent timing on the stability of radiomics features using dynamic contrast-enhanced perfusion CT (dceCT) or MRI (dceMRI) in prostate and lung cancers. METHODS: Radiomics features were extracted from dceCT or dceMRI images in patients with biopsy-proven peripheral prostate cancer (pzPC) or biopsy-proven non-small cell lung cancer (NSCLC), respectively. Features that showed significant differences between contrast phases were identified using linear mixed models. An L2-penalized logistic regression classifier was used to predict class labels for pzPC and unaffected prostate regions-of-interest (ROIs). RESULTS: Nine pzPC and 28 NSCLC patients, who were imaged with dceCT and/or dceMRI, were included in this study. After normalizing for individual enhancement patterns by defining seven individual phases based on a reference vessel, 19, 467 and 128 out of 1204 CT features showed significant temporal dynamics in healthy prostate parenchyma, prostate tumors and lung tumors, respectively. CT radiomics-based classification accuracy of healthy and tumor ROIs was highly dependent on contrast agent phase. For dceMRI, 899 and 1027 out of 1118 features were significantly dependent on time after contrast agent injection for prostate and lung tumors. CONCLUSIONS: CT and MRI radiomics features in both prostate and lung tumors are significantly affected by interindividual differences in contrast agent dynamics.

Metabolic tumor volume and sites of organ involvement predict outcome in NSCLC immune-checkpoint inhibitor therapy.

PURPOSE: The purpose of this study was to assess the ability of pretreatment PET parameters and peripheral blood biomarkers to predict progression-free survival (PFS) and overall survival (OS) in NSCLC patients treated with ICIT. METHODS: We prospectively included 87 patients in this study who underwent pre-treatment [18F]-FDG PET/CT. Organ-specific and total metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured using a semiautomatic software. Sites of organ involvement (SOI) were assessed by PET/CT. The log-rank test and Cox-regression analysis were used to assess associations between clinical, laboratory, and imaging parameters with PFS and OS. Time dependent ROC were calculated and model performance was evaluated in terms of its clinical utility. RESULTS: MTV increased with the number of SOI and was correlated with neutrophil and lymphocyte cell count (Spearman's rho = 0.27 or 0.32; p =.02 or 0.003; respectively). Even after adjustment for known risk factors, such as PD-1 expression and neutrophil cell count, the MTV and the number of SOI were independent risk factors for progression (per 100 cm3; adjusted hazard ratio [aHR]: 1.13; 95% confidence interval [95%CI]: 1.01-1.28; p =.04; single SOI vs. ≥ 4 SOI: aHR: 2.26, 95%CI: 1.04-4.94; p =.04). MTV and the number of SOI were independent risk factors for overall survival (per 100 cm3 aHR: 1.11, 95%CI: 1.01-1.23; p =.03; single SOI vs. ≥ 4 SOI: aHR: 4.54, 95%CI: 1.64-12.58; p =.04). The combination of MTV and the number of SOI improved the risk stratification for PFS and OS (log-rank test p <.001; C-index: 0.64 and 0.67). CONCLUSION: The MTV and the number of SOI are simple imaging markers that provide complementary information to facilitate risk stratification in NSCLC patients scheduled for ICIT.