Lung imaging patterns in connective tissue disease-associated interstitial lung disease impact prognosis and immunosuppression response.

OBJECTIVES: Interstitial lung disease (ILD) in connective tissue diseases (CTD) have highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality and immunosuppression response. METHODS: Patients with CTD-ILD had high-resolution chest computed tomography (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern (usual interstitial pneumonia [UIP]; non-specific interstitial pneumonia [NSIP]; organizing pneumonia [OP]; fibrotic hypersensitivity pneumonitis [fHP]; and other). Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment. RESULTS: Of 645 CTD-ILD patients, the frequent CTDs were systemic sclerosis (n = 215), rheumatoid arthritis (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with UIP, FVC decline was slower for NSIP (1.1%/year, 95%CI 0.2, 1.9) and OP (3.5%/year, 95%CI 2.0, 4.9), and mortality was lower for NSIP (HR 0.65, 95%CI 0.45, 0.93) and OP (HR 0.18, 95%CI 0.05, 0.57), but higher in fHP (HR 1.58, 95%CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95%CI 1.4, 2.8), with no change for UIP or fHP. CONCLUSION: Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.

Canadian Association of Radiologists Thoracic Imaging Referral Guideline.

The Canadian Association of Radiologists (CAR) Thoracic Expert Panel consists of radiologists, respirologists, emergency and family physicians, a patient advisor, and an epidemiologist/guideline methodologist. After developing a list of 24 clinical/diagnostic scenarios, a rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for one or more of these clinical/diagnostic scenarios. Recommendations from 30 guidelines and contextualization criteria in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) for guidelines framework were used to develop 48 recommendation statements across the 24 scenarios. This guideline presents the methods of development and the referral recommendations for screening/asymptomatic individuals, non-specific chest pain, hospital admission for non-thoracic conditions, long-term care admission, routine pre-operative imaging, post-interventional chest procedure, upper respiratory tract infection, acute exacerbation of asthma, acute exacerbation of chronic obstructive pulmonary disease, suspect pneumonia, pneumonia follow-up, immunosuppressed patient with respiratory symptoms/febrile neutropenia, chronic cough, suspected pneumothorax (non-traumatic), clinically suspected pleural effusion, hemoptysis, chronic dyspnea of non-cardiovascular origin, suspected interstitial lung disease, incidental lung nodule, suspected mediastinal lesion, suspected mediastinal lymphadenopathy, and elevated diaphragm on chest radiograph.

Integration and Application of Radiologic Patterns From Clinical Practice Guidelines on Idiopathic Pulmonary Fibrosis and Fibrotic Hypersensitivity Pneumonitis.

BACKGROUND: Clinical practice guidelines separately describe radiologic patterns of usual interstitial pneumonia (UIP) and fibrotic hypersensitivity pneumonitis (fHP), without direction on whether or how to apply these approaches concurrently within a single patient. RESEARCH QUESTION: How can we integrate guideline-defined radiologic patterns to diagnose interstitial lung disease (ILD) and what are the pitfalls associated with described patterns that require reassessment in future guidelines? STUDY DESIGN AND METHODS: Patients from the Canadian Registry for Pulmonary Fibrosis underwent detailed reevaluation in standardized multidisciplinary discussion. CT scan features were quantified by chest radiologists masked to clinical data, and guideline-defined patterns were assigned. Clinical data then were provided to the radiologist and an ILD clinician, who jointly determined the leading diagnosis. RESULTS: Clinical-radiologic diagnosis in 1,593 patients was idiopathic pulmonary fibrosis (IPF) in 26%, fHP in 12%, connective tissue disease-associated ILD (CTD-ILD) in 34%, idiopathic pneumonia with autoimmune features in 12%, and unclassifiable ILD in 10%. Typical and probable UIP patterns corresponded to a diagnosis of IPF in 66% and 57% of patients, respectively. Typical fHP pattern corresponded to an fHP clinical diagnosis in 65% of patients, whereas compatible fHP was nonspecific and associated with CTD-ILD or IPAF in 48% of patients. No pattern ruled out CTD-ILD. Gas trapping affecting > 5% of lung parenchyma on expiratory imaging was an important feature broadly separating compatible and typical fHP from other patterns (sensitivity, 0.77; specificity, 0.91). INTERPRETATION: An integrated approach to guideline-defined UIP and fHP patterns is feasible and supports > 5% gas trapping as an important branch point. Typical or probable UIP and typical fHP patterns have moderate predictive values for a corresponding diagnosis of IPF and fHP, although occasionally confounded by CTD-ILD; compatible fHP is nonspecific.

Sybil: A Validated Deep Learning Model to Predict Future Lung Cancer Risk From a Single Low-Dose Chest Computed Tomography.

PURPOSE: Low-dose computed tomography (LDCT) for lung cancer screening is effective, although most eligible people are not being screened. Tools that provide personalized future cancer risk assessment could focus approaches toward those most likely to benefit. We hypothesized that a deep learning model assessing the entire volumetric LDCT data could be built to predict individual risk without requiring additional demographic or clinical data. METHODS: We developed a model called Sybil using LDCTs from the National Lung Screening Trial (NLST). Sybil requires only one LDCT and does not require clinical data or radiologist annotations; it can run in real time in the background on a radiology reading station. Sybil was validated on three independent data sets: a heldout set of 6,282 LDCTs from NLST participants, 8,821 LDCTs from Massachusetts General Hospital (MGH), and 12,280 LDCTs from Chang Gung Memorial Hospital (CGMH, which included people with a range of smoking history including nonsmokers). RESULTS: Sybil achieved area under the receiver-operator curves for lung cancer prediction at 1 year of 0.92 (95% CI, 0.88 to 0.95) on NLST, 0.86 (95% CI, 0.82 to 0.90) on MGH, and 0.94 (95% CI, 0.91 to 1.00) on CGMH external validation sets. Concordance indices over 6 years were 0.75 (95% CI, 0.72 to 0.78), 0.81 (95% CI, 0.77 to 0.85), and 0.80 (95% CI, 0.75 to 0.86) for NLST, MGH, and CGMH, respectively. CONCLUSION: Sybil can accurately predict an individual's future lung cancer risk from a single LDCT scan to further enable personalized screening. Future study is required to understand Sybil's clinical applications. Our model and annotations are publicly available.[Media: see text].

Utility of Noncancerous Chest CT Features for Predicting Overall Survival and Noncancer Death in Patients With Stage I Lung Cancer Treated With Stereotactic Body Radiotherapy.

BACKGROUND. Noncancerous imaging markers can be readily derived from pre-treatment diagnostic and radiotherapy planning chest CT examinations. OBJECTIVE. The purpose of this article was to explore the ability of noncancerous features on chest CT to predict overall survival (OS) and noncancer-related death in patients with stage I lung cancer treated with stereotactic body radiation therapy (SBRT). METHODS. This retrospective study included 282 patients (168 female, 114 male; median age, 75 years) with stage I lung cancer treated with SBRT between January 2009 and June 2017. Pretreatment chest CT was used to quantify coronary artery calcium (CAC) score, pulmonary artery (PA)-to-aorta ratio, emphysema, and body composition in terms of the cross-sectional area and attenuation of skeletal muscle and subcutaneous adipose tissue at the T5, T8, and T10 vertebral levels. Associations of clinical and imaging features with OS were quantified using a multivariable Cox proportional hazards (PH) model. Penalized multivariable Cox PH models to predict OS were constructed using clinical features only and using both clinical and imaging features. The models' discriminatory ability was assessed by constructing time-varying ROC curves and computing AUC at prespecified times. RESULTS. After a median OS of 60.8 months (95% CI, 55.8-68.0), 148 (52.5%) patients had died, including 83 (56.1%) with noncancer deaths. Higher CAC score (11-399: hazard ratio [HR], 1.83 [95% CI, 1.15-2.91], p = .01; ≥ 400: HR, 1.63 [95% CI, 1.01-2.63], p = .04), higher PA-to-aorta ratio (HR, 1.33 [95% CI, 1.16-1.52], p < .001, per 0.1-unit increase), and lower thoracic skeletal muscle index (HR, 0.88 [95% CI, 0.79-0.98], p = .02, per 10-cm2/m2 increase) were independently associated with shorter OS. Discriminatory ability for 5-year OS was greater for the model including clinical and imaging features than for the model including clinical features only (AUC, 0.75 [95% CI, 0.68-0.83] vs 0.61 [95% CI, 0.53-0.70]; p < .01). The model's most important clinical or imaging feature according to mean standardized regression coefficients was the PA-to-aorta ratio. CONCLUSION. In patients undergoing SBRT for stage I lung cancer, higher CAC score, higher PA-to-aorta ratio, and lower thoracic skeletal muscle index independently predicted worse OS. CLINICAL IMPACT. Noncancerous imaging features on chest CT performed before SBRT improve survival prediction compared with clinical features alone.

Cystic fibrosis in the 21st century: what every radiologist should know.

Cystic Fibrosis (CF) is the most common lethal genetic disorder in Caucasian populations, affecting roughly 70,000 individuals worldwide. This autosomal recessive disorder causes a wide spectrum of multisystemic manifestations, most of which are either directly or indirectly related to defective epithelial chloride secretion. The current median life expectancy is 44 years; however, a significant proportion of the CF population now live into the 5th decade and beyond due to advances in treatment. As life expectancy of CF patients increases, there is a newly emerging adult CF population with unique radiological manifestations spanning multiple organ systems, which often require follow-up imaging. The goal of this article is to review the multiple systemic manifestations and complications of CF on different imaging modalities and explore the appropriate radiological follow up recommended.

Comparison of Percutaneous Image-Guided Microwave Ablation and Cryoablation for Sarcoma Lung Metastases: A 10-Year Experience.

BACKGROUND. To our knowledge, outcomes between percutaneous microwave ablation (MWA) and cryoablation of sarcoma lung metastases have not been compared. OBJECTIVE. The purpose of this study was to compare technical success, complications, local tumor control, and overall survival (OS) after MWA versus cryoablation of sarcoma lung metastases. METHODS. This retrospective cohort study included 27 patients (16 women, 11 men; median age, 64 years; Eastern Cooperative Oncology Group performance score, 0-2) who, from 2009 to 2021, underwent 39 percutaneous CT-guided ablation sessions (21 MWA and 18 cryoablation sessions; one to four sessions per patient) to treat 65 sarcoma lung metastases (median number of tumors per patient, one [range, one to 12]; median tumor diameter, 11.0 mm [range, 5-33 mm]; 25% of tumors were nonperipheral). We compared complications according to ablation modality by use of generalized estimating equations. We evaluated ablation modality, tumor size, and location (peripheral vs nonperipheral) in relation to local tumor progression by use of proportional Cox hazard models, with death as the competing risk. We estimated OS using the Kaplan-Meier method. RESULTS. Primary technical success was 97% for both modalities. Median follow-up was 23 months (range, one to 102 months; interquartile range, 12-44 months). A total of seven of 61 tumors (11%) showed local progression. Estimated 1-year and 2-year local control rates were, for tumors 1 cm or smaller, 97% and 95% after MWA versus 99% and 98% after cryoablation, and for tumors larger than 1 cm, 74% and 62% after MWA versus 86% and 79% after cryoablation. Tumor size of 1 cm or smaller was associated with a decreased cumulative incidence of local progression (p = .048); ablation modality and tumor location were not associated with progression (p = .86 and p = .54, respectively). Complications (Common Terminology Criteria for Adverse Events [CTCAE] grade, ≤ 3) occurred in 17 of 39 sessions (44%), prompting chest tube placement in nine (23%). There were no CTCAE grade 4 or 5 complications. OS at 1, 2, and 3 years was 100%, 89%, and 82%, respectively. CONCLUSION. High primary technical success, local control, and OS support the use of MWA and cryoablation for treating sarcoma lung metastases. Ablation modality and tumor location did not affect local progression. The rate of local tumor progression was low, especially for small tumors. No life-threatening complications occurred. CLINICAL IMPACT. Percutaneous MWA and cryoablation are both suited for the treatment of sarcoma lung metastases, especially for tumors 1 cm or smaller, whether peripheral or nonperipheral. Complications, if they occur, are not life-threatening.

Image-Guided Percutaneous Lung Needle Biopsy: How we do it.

Image-guided lung needle biopsy allows for minimally invasive diagnosis of lung pathology. In the setting of suspected malignancy, the biopsy not only confirms the diagnosis but also allows for molecular profiling, a requisite for tailored systemic therapy. Needle biopsy can also characterize non-neoplastic entities such as infections not responding to treatment and other inflammatory processes. A successful and safe lung needle biopsy starts with lesion and patient selection and careful pre-procedural evaluation. Here we review the indications and contraindications, diagnostic alternatives, approach planning and sequential procedural steps with the goal of maximizing both yield and patient safety. We discuss technical tips for preventing complications such as pleural anesthesia, the saline seal, the blood patch, the banana bend, hydro dissection, and the rapid needle out/patient rollover maneuver. We also review how to manage complications, avoid non-diagnostic biopsies, and provide recommendations for post-procedural observation and imaging follow-up.

Active Versus Passive Thaw After Percutaneous Cryoablation of Pulmonary Tumors: Effect on Incidence, Grade, and Onset of Hemoptysis.

BACKGROUND. Hemoptysis is common after percutaneous image-guided cryoablation of pulmonary tumors. OBJECTIVE. The purpose of our study was to evaluate the effect of a final active thaw on the incidence, grade, and onset of hemoptysis after percutaneous cryoablation of pulmonary tumors. METHODS. This retrospective cohort study included 60 consecutive CT-guided cryoablation sessions targeting 95 pulmonary tumors in 47 patients from March 2017 to September 2020. The final thaw of a triple-freeze protocol was active (electrical, helium-free) in 27 of 60 sessions (45%, active group) and passive in 33 of 60 sessions (55%, passive group). The incidence, onset, and management of hemoptysis were recorded using prospectively collected data. Hemoptysis, pneumothorax, and hemothorax within 30 days after ablation were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The volume of immediate posttreatment changes on CT was quantified using semiautomated segmentation. Outcomes were compared between groups using generalized estimating equation models. A parsimonious multivariable model for hemoptysis incidence was developed using purposeful selection of predefined covariates followed by bootstrap resampling. Local tumor control was compared between groups using the Kaplan-Meier method and log-rank testing. RESULTS. Hemoptysis occurred after 26 of 60 (43%) sessions and was self-limited (CTCAE grade 1) in 22 of 26 (85%) sessions. The incidence of hemoptysis was lower in the active group than in the passive group (19% vs 64%, respectively; p = .002). The odds of hemoptysis adjusted for immediate posttreatment changes were 92% lower in the active group (odds ratio [OR], 0.08 [95% CI, 0.02-0.37]; p = .004). The odds of hemoptysis greater than grade 1 were 79% lower in the active group (OR, 0.21 [95% CI, 0.07-0.64]; p = .006). In the active group, the onset of hemoptysis was significantly delayed (OR, 0.75 [95% CI, 0.61-0.91]; p = .005). Pneumothorax (p = .60), hemothorax (p = .84), and local tumor control (p = .77) did not differ between groups. CONCLUSION. Active thaw after the final freeze reduces the incidence and grade of hemoptysis and delays the onset of hemoptysis after percutaneous cryoablation of pulmonary tumors without adversely affecting other procedural complications and local tumor control. CLINICAL IMPACT. Active thaw after the final freeze improves the safety profile of triple-freeze cryoablation of pulmonary tumors by reducing the incidence and grade of hemoptysis and by delaying the onset of hemoptysis beyond the immediate recovery period.

Imaging of the Middle and Visceral Mediastinum.

The visceral mediastinum contains important vascular and non-vascular structures including the heart, great vessels, lymph nodes, and portions of the esophagus and trachea. Multiple imaging modalities, including chest radiography, computed tomography, MR imaging, and nuclear medicine studies, can be used to detect, diagnose, and characterize masses in this compartment. Lymphadenopathy is the most common process involving the visceral mediastinum and can be seen with a wide variety of diseases. Less commonly seen entities include foregut duplication cysts, neoplasms and other lesions arising from the trachea and esophagus, paragangliomas as well as other mesenchymal tumors.

Effectiveness and Safety of Sclerotherapy for Treatment of Low-Flow Vascular Malformations of the Oropharyngeal Region.

PURPOSE: To evaluate the efficacy and safety of sclerotherapy with sodium tetradecyl sulfate (STS) and bleomycin for treatment of venous malformations (VMs) of the oropharyngeal region. MATERIALS AND METHODS: A retrospective study of 33 patients with 46 VMs of the buccal and pharyngolaryngeal cavity associated with impairment of eating, respiration, or elocution was performed. Individual lesions were divided based on their anterior or posterior location, using the base of the tongue as an anatomic landmark. Lesion size was estimated with the use of orthogonal measurements on magnetic resonance or ultrasound images before and after treatment to assess radiologic response. Sclerotherapy sessions were performed under ultrasound, fluoroscopic, and, if needed, endoscopic guidance. Clinical response was assessed with the use of the Manchester Orofacial Pain Disability Scale. Methods for airway management were also compiled. RESULTS: Following sclerotherapy, average VM diameter was reduced by 31.4% (P < .0001) on a per-patient basis and by 30.8% (P < .0001) on a per-lesion basis. The Manchester score improved by an average of 37.0% (P = .013). Four patients reported a worsening of symptoms, and 11 patients experienced symptomatic recurrence. Complications include pneumonia (5 patients) and urgent placement of a post-procedure tracheostomy (4 patients). Patients with posterior malformations experienced more complications (emergency tracheostomies in 4 and pneumonias in 4). CONCLUSIONS: Sclerotherapy using STS is an efficient treatment for venous malformations of the buccal and pharyngolaryngeal cavity but can lead to significant complication for posterior lesions. Careful assessment of the airway is needed before treatment, and prophylactic tracheotomy should be considered in patients with posterior lesions.

Spreading of multiple Listeria monocytogenes abscesses via central nervous system fiber tracts: case report.

Animal studies have shown that Listeria monocytogenes can probably access the brain through a peripheral intraneural route, and it has been suggested that a similar process may occur in humans. However, thus far, its spreading through the central nervous system (CNS) has not been completely elucidated. The authors present a case of multiple L. monocytogenes cerebral abscesses characterized by a pattern of distribution that suggested spread along white matter fiber tracts and reviewed the literature to identify other cases for analysis. They elected to include only those cases with 3 or more cerebral abscesses to make sure that the distribution was not random, but rather followed a pattern. In addition, they included those cases with abscesses in both the brainstem and the cerebral hemispheres, but excluded cases in which abscesses were located solely in the brainstem. Of 77 cases of L. monocytogenes CNS abscesses found in the literature, 17 involved multiple abscesses. Of those, 6 were excluded for lack of imaging and 3 because they involved only the brainstem. Of the 8 remaining cases from the literature, one was a case of bilateral abscesses that did not follow a fiber tract; another was also bilateral, but with lesions appearing to follow fiber tracts on one side; and in the remaining 6, to which the authors added their own case for a total of 7, all the abscesses were located exclusively in the same hemisphere and distributed along white matter fiber tracts. The findings suggest that after entering the CNS, L. monocytogenes travels within the axons, resulting in a characteristic pattern of distribution of multiple abscesses along the white matter fiber tracts in the brain. This report is the first description suggesting intraaxonal CNS spread of L. monocytogenes infection in humans following its entry into the brain. This distinct pattern is clearly seen on imaging and its recognition may be valuable in the diagnosis of listeriosis. This finding may allow for earlier diagnosis, which may improve outcome.

Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo.

TDP-43 has been found in inclusion bodies of multiple neurological disorders, including amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's disease and Alzheimer's disease. Mutations in the TDP-43 encoding gene, TARDBP, have been subsequently reported in sporadic and familial ALS patients. In order to investigate the pathogenic nature of these mutants, the effects of three consistently reported TARDBP mutations (A315T, G348C and A382T) were tested in cell lines, primary cultured motor neurons and living zebrafish embryos. Each of the three mutants and wild-type (WT) human TDP-43 localized to nuclei when expressed in COS1 and Neuro2A cells by transient transfection. However, when expressed in motor neurons from dissociated spinal cord cultures these mutant TARDBP alleles, but less so for WT TARDBP, were neurotoxic, concomitant with perinuclear localization and aggregation of TDP-43. Finally, overexpression of mutant, but less so of WT, human TARDBP caused a motor phenotype in zebrafish (Danio rerio) embryos consisting of shorter motor neuronal axons, premature and excessive branching as well as swimming deficits. Interestingly, knock-down of zebrafisfh tardbp led to a similar phenotype, which was rescued by co-expressing WT but not mutant human TARDBP. Together these approaches showed that TARDBP mutations cause motor neuron defects and toxicity, suggesting that both a toxic gain of function as well as a novel loss of function may be involved in the molecular mechanism by which mutant TDP-43 contributes to disease pathogenesis.