RATIONALE: The Scleroderma Lung Study II (SLS II) demonstrated significant improvements in pulmonary function and dyspnea at 24 months compared with baseline when patients with symptomatic scleroderma-related interstitial lung disease (SSc-ILD) were treated with either cyclophosphamide for 1 year (followed for another year on placebo) or mycophenolate mofetil for 2 years in a randomized, double-blind clinical trial. Physiologic and clinical outcomes of SLS II have been published previously. OBJECTIVES: The aim of the study was to assess changes from baseline in the extent of SSc-ILD on high-resolution computed tomography (HRCT) measured in the SLS II participants using quantitative image analysis after 2 years and to determine whether these HRCT changes were correlated with the changes in physiologic and clinical measures over the same time interval.

The diagnostic definition of indeterminate lung nodules as malignant or benign poses a major challenge for clinicians. We discovered a potential marker, the sodium-dependent glucose transporter 2 (SGLT2), whose activity identified metabolically active lung premalignancy and early-stage lung adenocarcinoma (LADC). We found that SGLT2 is expressed early in lung tumorigenesis and is found specifically in premalignant lesions and well-differentiated adenocarcinomas. SGLT2 activity could be detected in vivo by positron emission tomography (PET) with the tracer methyl 4-deoxy-4-[¹⁸F] fluoro-alpha-d-glucopyranoside (Me4FDG), which specifically detects SGLT activity. Using a combination of immunohistochemistry and Me4FDG PET, we identified high expression and functional activity of SGLT2 in lung premalignancy and early-stage/low-grade LADC. Furthermore, selective targeting of SGLT2 with FDA-approved small-molecule inhibitors, the gliflozins, greatly reduced tumor growth and prolonged survival in autochthonous mouse models and patient-derived xenografts of LADC. Targeting SGLT2 in lung tumors may intercept lung cancer progression at early stages of development by pairing Me4FDG PET imaging with therapy using SGLT2 inhibitors.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease (ILD). In this review, we describe the central role of high-resolution computed tomography (HRCT) in the diagnosis of IPF and discuss how communication between pulmonologists and radiologists might be improved to make the interpretation of HRCT scans more effective. Clinical information is important in the interpretation of HRCT scans, as the likelihood that specific radiologic features reflect IPF is not absolute, but dependent on the clinical context. In cases where the clinical context or HRCT pattern are inconclusive, multidisciplinary discussion (MDD) between a pulmonologist and radiologist (and, where relevant, a pathologist and rheumatologist) experienced in the differential diagnosis of ILD is necessary to establish a diagnosis. While it can be challenging to convene a face-to-face meeting, MDD can be conducted virtually or by telephone to enable each specialty group to contribute. To make the MDD most effective, it is important that relevant clinical information (for example, on the patient's clinical history, exposures and the results of serological tests) is shared with all parties in advance. A common lexicon to describe HRCT features observed in ILD can also help improve the effectiveness of MDD. A working diagnosis may be made in patients who do not fulfill all the diagnostic criteria for any specific type of ILD, but this diagnosis should be reviewed at regular intervals, with repeat of clinical, radiological, and laboratory assessments as appropriate, as new information pertinent to the patient's diagnosis may become available.

The prevalence of idiopathic pulmonary fibrosis (IPF) is increasing worldwide and there has been increased interest in developing efficacious drug therapies for this terminal disease (1). Currently, there is debate as to what is the most valid endpoint to be used in clinical trials, although the current consensus is that using a 10% decline in FVC as the primary measure of outcome in IPF is indicative of clinically significant disease progression (2, 3). In addition, the unpredictable and variable rate of decline of patients with diagnosed IPF makes it very challenging to select patients for a given drug trial and to compare results across different study populations. Characterization of indicators suggesting a poor prognosis at baseline in IPF is essential to guide optimal management and in drug trial settings, to allow for cohort enrichment to identify patients who are likely to experience increased clinical events, thereby reducing sample sizes and reducing the prohibitive costs...

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.

PURPOSE: Stereotactic body radiation therapy (SBRT) and heat-based ablation (HBA) are both potentially safe and effective treatments for primary and metastatic lung tumors. Both are suboptimal for centrally located tumors, with SBRT having a higher risk of significant toxicity and HBA having lower efficacy. This study evaluates the safety and efficacy of combination SBRT-HBA to determine whether combined treatment can result in superior outcomes to each treatment alone. METHODS AND MATERIALS: Patients with 1 or 2 primary or metastatic lung tumors ≤ 5 cm in size were enrolled in a prospective phase 2 trial and treated with SBRT in 3 fractions followed by HBA. Tumors < 1 cm from the central bronchial tree received a total of 36 Gy, and tumors 1 to 2 cm away received 42 Gy. HBA was delivered within 10 days after SBRT. The primary endpoints were local control, toxicity, and degree of decline in lung function. The secondary endpoints were progression-free survival and overall survival.

OBJECTIVE: Renal cell carcinoma (RCC) has a propensity to metastasize to the chest, with the lungs being the most common distant metastatic site. The histologic subtype of RCC has implications for prognosis. CONCLUSION: Significant advances have been made in the management of metastatic RCC, both in systemic and locoregional therapies. The aim of this article is to review appearances of intrathoracic metastases from RCC and to discuss treatment considerations.

PURPOSE: To determine size of ablation zone and pulmonary hemorrhage in double-freeze (DF) vs modified triple-freeze (mTF) cryoablation protocols with different probe sizes in porcine lung. MATERIALS AND METHODS: In 10 healthy adult pigs, 20 pulmonary cryoablations were performed using either a 2.4-mm or a 1.7-mm probe. Either conventional DF or mTF protocol was used. Serial noncontrast CT scans were performed during ablations. Ablation iceball and hemorrhage volumes were measured and compared between protocols and probe sizes.

Purpose To determine feasibility and safety of biopsy and repeat biopsy for assessment of programmed cell death ligand-1 (PD-L1) status. Materials and Methods This retrospective analysis reviewed 101 patients who underwent transthoracic core needle biopsy for the KEYNOTE-001 (MK-3475) clinical trial of pembrolizumab, an antiprogrammed cell death-1 therapy for non-small cell lung cancer, from May 2012 to September 2014. Sixty-one male patients (mean age, 66.1 years; range 36-83 years) and 40 female patients (mean age, 66.8 years; age range, 36-90 years) were included. Data collected included population characteristics, treatment history, target location, size, and depth from pleura. Adequacy of the tissue sample for diagnostic testing and rates of biopsy-related complications were assessed. Statistical analysis was performed by using univariate and multivariate generalized linear models to determine significant risk factors for biopsy complications. Results A total of 110 intrathoracic biopsies were performed, and 101 (91.8%) were performed as repeat biopsies subsequent to a previous percutaneous or bronchoscopic biopsy or previous surgical biopsy or resection. More than 84.5% (93 of 110) of biopsies were performed in patients who had undergone previous local or systemic therapy. Specimens were adequate for evaluation of PD-L1 expression in 96.4% of biopsies. Procedure-related complications occurred in 28 biopsies (25.4%); pneumothorax was most common (22.7%). Overall mean number of core needle biopsy samples obtained was 7.9 samples. Conclusion Image-guided transthoracic core needle biopsy is an effective method for obtaining tissue for PD-L1 expression analysis.

PURPOSE: To study the variability in volume change estimates of pulmonary nodules due to segmentation approaches used across several algorithms and to evaluate these effects on the ability to predict nodule malignancy. METHODS: We obtained 100 patient image datasets from the National Lung Screening Trial (NLST) that had a nodule detected on each of two consecutive low dose computed tomography (LDCT) scans, with an equal proportion of malignant and benign cases (50 malignant, 50 benign). Information about the nodule location for the cases was provided by a screen capture with a bounding box and its axial location was indicated. Five participating quantitative imaging network (QIN) institutions performed nodule segmentation using their preferred semi-automated algorithms with no manual correction; teams were allowed to provide additional manually corrected segmentations (analyzed separately). The teams were asked to provide segmentation masks for each nodule at both time points. From these masks, the volume was estimated for the nodule at each time point; the change in volume (absolute and percent change) across time points was estimated as well. We used the concordance correlation coefficient (CCC) to compare the similarity of computed nodule volumes (absolute and percent change) across algorithms. We used Logistic regression model on the change in volume (absolute change and percent change) of the nodules to predict the malignancy status, the area under the receiver operating characteristic curve (AUROC) and confidence intervals were reported. Because the size of nodules was expected to have a substantial effect on segmentation variability, analysis of change in volumes was stratified by lesion size, where lesions were grouped into those with a longest diameter of <8 mm and those with longest diameter ≥ 8 mm.

This Review provides an updated approach to the diagnosis of idiopathic pulmonary fibrosis (IPF), based on a systematic search of the medical literature and the expert opinion of members of the Fleischner Society. A checklist is provided for the clinical evaluation of patients with suspected usual interstitial pneumonia (UIP). The role of CT is expanded to permit diagnosis of IPF without surgical lung biopsy in select cases when CT shows a probable UIP pattern. Additional investigations, including surgical lung biopsy, should be considered in patients with either clinical or CT findings that are indeterminate for IPF. A multidisciplinary approach is particularly important when deciding to perform additional diagnostic assessments, integrating biopsy results with clinical and CT features, and establishing a working diagnosis of IPF if lung tissue is not available. A working diagnosis of IPF should be reviewed at regular intervals since the diagnosis might change. Criteria are presented to establish confident and working diagnoses of IPF.

The World Health Organization (WHO) increasingly recognizes the need and utility for quality diagnostic tests. Historically, imaging has played a key role for diagnosis and treatment plans for global health infectious diseases, like tuberculosis and human immunovirus (HIV) and acquired immunodeficiency syndrome. However, according to the WHO, there is a global rise in noncommunicable diseases, such as cancer and cardiovascular diseases, for which imaging has been an integral part of care in areas of high access to health care for decades [1]. In analysis of WHO member states, a wide gap is shown between nations that have imaging and related treatment services and those that have minimal to no access [2]. This background supports the increasing trend for radiology to be part of global health initiatives and underscores the dire need for medical imaging services in areas that currently lack access and human capacity [3]...

OBJECTIVE: A recently proposed "5DCT" protocol uses deformable registration of free-breathing fast-helical CT scans to generate a breathing motion model. In order to allow accurate registration, free-breathing images are required to be free of doubling-artefacts, which arise when tissue motion is greater than scan speed. METHODS: Using a unique set of digital phantoms based on patient data and verified with a motion phantom, this work identifies the minimum scanner parameters required to successfully generate free-breathing artefact-free fast-helical scans. A motion phantom and 5 patients were imaged 25 times under free-breathing conditions in alternating directions with a 64-slice CT scanner employing a low-dose fast-helical protocol. A series of high temporal resolution (0.1 s) 5DCT scan data sets was generated in each case. A simulated CT scanner was used to "image" each free-breathing data set. Various CT scanner detector widths and rotation times were simulated, and verified using the motion phantom results. Motion-induced artefacts were quantified in patient images using structural similarity maps to determine the similarity between axial slices.

A clinical validation of the bone scan lesion area (BSLA) as a quantitative imaging biomarker was performed in metastatic castration-resistant prostate cancer (mCRPC). BSLA was computed from whole-body bone scintigraphy at baseline and week 12 posttreatment in a cohort of 198 mCRPC subjects (127 treated and 71 placebo) from a clinical trial involving a different drug from the initial biomarker development. BSLA computation involved automated image normalization, lesion segmentation, and summation of the total area of segmented lesions on bone scan AP and PA views as a measure of tumor burden. As a predictive biomarker, treated subjects with baseline BSLA [Formula: see text] had longer survival than those with higher BSLA ([Formula: see text] and [Formula: see text]). As a surrogate outcome biomarker, subjects were categorized as progressive disease (PD) if the BSLA increased by a prespecified 30% or more from baseline to week 12 and non-PD otherwise. Overall survival rates between PD and non-PD groups were statistically different ([Formula: see text] and [Formula: see text]). Subjects without PD at week 12 had longer survival than subjects with PD: median 398 days versus 280 days. BSLA has now been demonstrated to be an early surrogate outcome for overall survival in different prostate cancer drug treatments.

OBJECTIVE: It is crucial for clinicians to stay up to date on current literature in order to apply recent evidence to clinical decision making. Automatic summarization systems can help clinicians quickly view an aggregated summary of literature on a topic. Casama, a representation and summarization system based on "contextualized semantic maps," captures the findings of biomedical studies as well as the contexts associated with patient population and study design. This paper presents a user-oriented evaluation of Casama in comparison to a context-free representation, SemRep. MATERIALS AND METHODS: The effectiveness of the representation was evaluated by presenting users with manually annotated Casama and SemRep summaries of ten articles on driver mutations in cancer. Automatic annotations were evaluated on a collection of articles on EGFR mutation in lung cancer. Seven users completed a questionnaire rating the summarization quality for various topics and applications.

PURPOSE: CT Perfusion (CTP) is a widely used clinical imaging modality. However, CTP typically involves the use of substantial radiation dose (CTDI_vol ≥~200 mGy). The purpose of this study is to present a low-dose CTP technique using a projection view-sharing reconstruction algorithm originally developed for dynamic MRI - "K-space Weighted Image Contrast" (KWIC). METHODS: The KWIC reconstruction is based on an angle-bisection scheme. In KWIC, a Fourier transform was performed along each projection to form a "k-space"-like CT data space, based on the central-slice theorem. As a projection view-sharing technique, KWIC preserves the spatiotemporal resolution of undersampled CTP data by progressively increasing the number of projection views shared for more distant regions of "k-space". KWIC reconstruction was evaluated on a digital FORBILD head phantom with numerically simulated time-varying objects. The numerically simulated scans were undersampled using the angle-bisection scheme to achieve 50%, 25%, and 12.5% of the original dose (288, 144, and 72 projections, respectively). The area-under-the-curve (AUC), time-to-peak (TTP), and full width half maximum (FWHM) were measured in KWIC recons and compared to fully sampled filtered back projection (FBP) reconstructions. KWIC reconstruction and dose reduction was also implemented for three clinical CTP cases (45 s, 1156 projections per turn, 1 s/turn, CTDI_vol 217 mGy). Quantitative perfusion metrics were computed and compared between KWIC reconstructed CTP data and those of standard FBP reconstruction.

BACKGROUND: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma. METHODS: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score.