Validation of a deep learning computer aided system for CT based lung nodule detection, classification, and growth rate estimation in a routine clinical population.

OBJECTIVE: In this study, we evaluated a commercially available computer assisted diagnosis system (CAD). The deep learning algorithm of the CAD was trained with a lung cancer screening cohort and developed for detection, classification, quantification, and growth of actionable pulmonary nodules on chest CT scans. Here, we evaluated the CAD in a retrospective cohort of a routine clinical population. MATERIALS AND METHODS: In total, a number of 337 scans of 314 different subjects with reported nodules of 3-30 mm in size were included into the evaluation. Two independent thoracic radiologists alternately reviewed scans with or without CAD assistance to detect, classify, segment, and register pulmonary nodules. A third, more experienced, radiologist served as an adjudicator. In addition, the cohort was analyzed by the CAD alone. The study cohort was divided into five different groups: 1) 178 CT studies without reported pulmonary nodules, 2) 95 studies with 1-10 pulmonary nodules, 23 studies from the same patients with 3) baseline and 4) follow-up studies, and 5) 18 CT studies with subsolid nodules. A reference standard for nodules was based on majority consensus with the third thoracic radiologist as required. Sensitivity, false positive (FP) rate and Dice inter-reader coefficient were calculated. RESULTS: After analysis of 470 pulmonary nodules, the sensitivity readings for radiologists without CAD and radiologist with CAD, were 71.9% (95% CI: 66.0%, 77.0%) and 80.3% (95% CI: 75.2%, 85.0%) (p < 0.01), with average FP rate of 0.11 and 0.16 per CT scan, respectively. Accuracy and kappa of CAD for classifying solid vs sub-solid nodules was 94.2% and 0.77, respectively. Average inter-reader Dice coefficient for nodule segmentation was 0.83 (95% CI: 0.39, 0.96) and 0.86 (95% CI: 0.51, 0.95) for CAD versus readers. Mean growth percentage discrepancy of readers and CAD alone was 1.30 (95% CI: 1.02, 2.21) and 1.35 (95% CI: 1.01, 4.99), respectively. CONCLUSION: The applied CAD significantly increased radiologist's detection of actionable nodules yet also minimally increasing the false positive rate. The CAD can automatically classify and quantify nodules and calculate nodule growth rate in a cohort of a routine clinical population. Results suggest this Deep Learning software has the potential to assist chest radiologists in the tasks of pulmonary nodule detection and management within their routine clinical practice.

Analysis of the interactions between small pulmonary nodules, clinical factors and the risk of malignancy in the chest following diagnosis of head and neck cancer.

BACKGROUND: This study aims to investigate radiological and clinical factors which predict malignancy in indeterminate pulmonary nodules in patients with head and neck cancer (HNC). METHODS: Prospective data were collected in 424 patients who were reviewed in the NHS Lothian HNC multidisciplinary meeting from May 2016 to May 2018. Staging and follow-up CT chest imaging were reviewed to identify and assess pulmonary nodules in all patients. RESULTS: About 61.8% of patients had at least one pulmonary nodule at staging CT. In total, 25 patients developed malignancy in the chest. Metastatic disease in the chest was significantly associated with unknown or negative p16 status (p < .0005). Pleural indentation and spiculation were associated with indeterminate nodules, subsequently being shown to represent metastatic disease (p > .0005 and p = .046, respectively). CONCLUSION: Negative or unknown p16 status was associated with an increased propensity to develop metastatic disease in the chest in patients with HNC.

Pulmonary embolism severity before and during the COVID-19 pandemic.

OBJECTIVES: Early in the coronavirus 2019 (COVID-19) pandemic, a high frequency of pulmonary embolism was identified. This audit aims to assess the frequency and severity of pulmonary embolism in 2020 compared to 2019. METHODS: In this retrospective audit, we compared computed tomography pulmonary angiography (CTPA) frequency and pulmonary embolism severity in April and May 2020, compared to 2019. Pulmonary embolism severity was assessed with the Modified Miller score and the presence of right heart strain was assessed. Demographic information and 30-day mortality was identified from electronic health records. RESULTS: In April 2020, there was a 17% reduction in the number of CTPA performed and an increase in the proportion identifying pulmonary embolism (26%, n = 68/265 vs 15%, n = 47/320, p < 0.001), compared to April 2019. Patients with pulmonary embolism in 2020 had more comorbidities (p = 0.026), but similar age and sex compared to 2019. There was no difference in pulmonary embolism severity in 2020 compared to 2019, but there was an increased frequency of right heart strain in May 2020 (29 vs 12%, p = 0.029). Amongst 18 patients with COVID-19 and pulmonary embolism, there was a larger proportion of males and an increased 30 day mortality (28% vs 6%, p = 0.008). CONCLUSION: During the COVID-19 pandemic, there was a reduction in the number of CTPA scans performed and an increase in the frequency of CTPA scans positive for pulmonary embolism. Patients with both COVID-19 and pulmonary embolism had an increased risk of 30-day mortality compared to those without COVID-19. ADVANCES IN KNOWLEDGE: During the COVID-19 pandemic, the number of CTPA performed decreased and the proportion of positive CTPA increased. Patients with both pulmonary embolism and COVID-19 had worse outcomes compared to those with pulmonary embolism alone.

Can dynamic imaging, using 18F-FDG PET/CT and CT perfusion differentiate between benign and malignant pulmonary nodules?

BACKGROUND: The aim of the study was to derive and compare metabolic parameters relating to benign and malignant pulmonary nodules using dynamic 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) PET/CT, and nodule perfusion parameters derived through perfusion computed tomography (CT). PATIENTS AND METHODS: Twenty patients with 21 pulmonary nodules incidentally detected on CT underwent a dynamic 18F-FDG PET/CT and a perfusion CT. The maximum standardized uptake value (SUVmax) was measured on conventional 18F-FDG PET/CT images. The influx constant (Ki ) was calculated from the dynamic 18F-FDG PET/CT data using Patlak model. Arterial flow (AF) using the maximum slope model and blood volume (BV) using the Patlak plot method for each nodule were calculated from the perfusion CT data. All nodules were characterized as malignant or benign based on histopathology or 2 year follow up CT. All parameters were statistically compared between the two groups using the nonparametric Mann-Whitney test. RESULTS: Twelve malignant and 9 benign lung nodules were analysed (median size 20.1 mm, 9-29 mm) in 21 patients (male/female = 11/9; mean age ± SD: 65.3 ± 7.4; age range: 50-76 years). The average SUVmax values ± SD of the benign and malignant nodules were 2.2 ± 1.7 vs. 7.0 ± 4.5, respectively (p = 0.0148). Average Ki values in benign and malignant nodules were 0.0057 ± 0.0071 and 0.0230 ± 0.0155 min-1, respectively (p = 0.0311). Average BV for the benign and malignant nodules were 11.6857 ± 6.7347 and 28.3400 ± 15.9672 ml/100 ml, respectively (p = 0.0250). Average AF for the benign and malignant nodules were 74.4571 ± 89.0321 and 89.200 ± 49.8883 ml/100g/min, respectively (p = 0.1613). CONCLUSIONS: Dynamic 18F-FDG PET/CT and perfusion CT derived blood volume had similar capability to differentiate benign from malignant lung nodules.

Coronary Artery Calcification on Thoracic Computed Tomography Is an Independent Predictor of Mortality in Patients With Bronchiectasis.

PURPOSE: Coronary artery calcification (CAC) on thoracic computed tomography (CT) can identify patients at risk of coronary artery disease (CAD) mortality. However, the overlap between bronchiectasis and CAC severity for predicting subsequent outcomes is unknown. MATERIALS AND METHODS: CT images from 362 patients (mean age 66±14 y, 38% male) with known bronchiectasis were assessed. Bronchiectasis severity was assessed using the Bronchiectasis Severity Index (0 to 4, mild; 5 to 8, moderate; and ≥9, severe). CAC was assessed with a visual ordinal score (0, none; 1, mild; 2, moderate; 3, severe) in each of the left main stem, left anterior descending, left circumflex, and right coronary arteries. Vessel CAC scores were summed and categorized as none (0), mild (1 to 3), moderate (4 to 8), and severe (9 to 12). RESULTS: Patients with severe bronchiectasis were older (P<0.001), but were not more likely to have a history of CAD, hypertension, or smoking. CAC was present in 196 (54%). Over a mean of 6±2 years, 59 (16%) patients died. Patients with moderate or severe CAC were 5 times more likely to die than patients without CAC (hazard ratio: 5.49, 95% confidence interval: 2.82-10.70, P<0.001). Patients with severe bronchiectasis were 10 times more likely to die than patients with mild bronchiectasis (hazard ratio: 10.11, 95% confidence interval: 4.22-24.27, P<0.001). CAC and bronchiectasis severity were independent predictors of mortality, but age, sex, smoking, and history of CAD or cerebrovascular disease were not. CONCLUSIONS: CAC is common in patients with bronchiectasis, and both CAC and bronchiectasis severity are independent predictors of mortality.

Predicting outcomes in rheumatoid arthritis related interstitial lung disease.

The aim of this study was to compare radiology-based prediction models in rheumatoid arthritis-related interstitial lung disease (RAILD) to identify patients with a progressive fibrosis phenotype.RAILD patients had computed tomography (CT) scans scored visually and using CALIPER and forced vital capacity (FVC) measurements. Outcomes were evaluated using three techniques, as follows. 1) Scleroderma system evaluating visual interstitial lung disease extent and FVC values; 2) Fleischner Society idiopathic pulmonary fibrosis (IPF) diagnostic guidelines applied to RAILD; and 3) CALIPER scores of vessel-related structures (VRS). Outcomes were compared to IPF patients.On univariable Cox analysis, all three staging systems strongly predicted outcome (scleroderma system hazard ratio (HR) 3.78, p=9×10-5; Fleischner system HR 1.98, p=2×10-3; and 4.4% VRS threshold HR 3.10, p=4×10-4). When the scleroderma and Fleischner systems were combined, termed the progressive fibrotic system (C-statistic 0.71), they identified a patient subset (n=36) with a progressive fibrotic phenotype and similar 4-year survival to IPF. On multivariable analysis, with adjustment for patient age, sex and smoking status, when analysed alongside the progressive fibrotic system, the VRS threshold of 4.4% independently predicted outcome (model C-statistic 0.77).The combination of two visual CT-based staging systems identified 23% of an RAILD cohort with an IPF-like progressive fibrotic phenotype. The addition of a computer-derived VRS threshold further improved outcome prediction and model fit, beyond that encompassed by RAILD measures of disease severity and extent.

Nebulisation of synthetic lamellar lipids mitigates radiation-induced lung injury in a large animal model.

Methods to protect against radiation-induced lung injury (RILI) will facilitate the development of more effective radio-therapeutic protocols for lung cancer and may provide the means to protect the wider population in the event of a deliberate or accidental nuclear or radiological event. We hypothesised that supplementing lipid membranes through nebulization of synthetic lamellar lipids would mitigate RILI. Following pre-treatment with either nebulised lamellar lipids or saline, anaesthetised sheep were prescribed fractionated radiotherapy (30 Gray (Gy) total dose in five 6 Gy fractions at 3-4 days intervals) to a defined unilateral lung volume. Gross pathology in radio-exposed lung 37 days after the first radiation treatment was consistent between treatment groups and consisted of deep red congestion evident on the pleural surface and firmness on palpation. Consistent histopathological features in radio-exposed lung were subpleural, periarteriolar and peribronchial intra-alveolar oedema, alveolar fibrosis, interstitial pneumonia and type II pneumocyte hyperplasia. The synthetic lamellar lipids abrogated radiation-induced alveolar fibrosis and reduced alpha-smooth muscle actin (ASMA) expression in radio-exposed lung compared to saline treated sheep. Administration of synthetic lamellar lipids was also associated with an increased number of cells expressing dendritic cell-lysosomal associated membrane protein throughout the lung.

Gray Scale Ultrasound, Color Doppler Ultrasound, and Contrast-Enhanced Ultrasound in Renal Parenchymal Diseases.

Ultrasound (US), which may be combination of gray scale and spectral Doppler US, color and power Doppler US, with or without microbubble contrast agents, is usually the first imaging modality to be used in renal parenchymal diseases. The most typical appearance of diffuse renal parenchymal diseases on gray scale US is an increased renal cortical echogenicity and increased or reduced corticomedullary differentiation. Spectral Doppler analysis of intrarenal flows may reveal an increase in intrarenal resistive index value greater than 0.70 in native kidneys, and greater than 0.8 in renal transplants. Gray scale US and spectral Doppler US do not exhibit high specificity and sensitivity because different renal parenchymal diseases often display the same US appearance, whereas the same renal parenchymal disease may present different appearances on US according to disease stage. Consequently, correlation of the US pattern with patient's history and clinical background is essential for a correct characterization.

Validation of an imaging based cardiovascular risk score in a Scottish population.

OBJECTIVES: A radiological risk score that determines 5-year cardiovascular disease (CVD) risk using routine care CT and patient information readily available to radiologists was previously developed. External validation in a Scottish population was performed to assess the applicability and validity of the risk score in other populations. METHODS: 2915 subjects aged ≥40 years who underwent routine clinical chest CT scanning for non-cardiovascular diagnostic indications were followed up until first diagnosis of, or death from, CVD. Using a case-cohort approach, all cases and a random sample of 20% of the participant's CT examinations were visually graded for cardiovascular calcifications and cardiac diameter was measured. The radiological risk score was determined using imaging findings, age, gender, and CT indication. RESULTS: Performance on 5-year CVD risk prediction was assessed. 384 events occurred in 2124 subjects during a mean follow-up of 4.25 years (0-6.4 years). The risk score demonstrated reasonable performance in the studied population. Calibration showed good agreement between actual and 5-year predicted risk of CVD. The c-statistic was 0.71 (95%CI:0.67-0.75). CONCLUSIONS: The radiological CVD risk score performed adequately in the Scottish population offering a potential novel strategy for identifying patients at high risk for developing cardiovascular disease using routine care CT data.

Analysis of the incidence and factors predictive of outcome in patients with head and neck cancer with pulmonary nodules.

BACKGROUND: The management of pulmonary nodules is challenging; unfortunately, little is known about the incidence and significance of pulmonary nodules in patients with head and neck cancer. METHODS: A review was conducted of 400 consecutive patients with head and neck cancer. Imaging was reviewed to identify the incidence of nodules and patient, tumor, and radiological factors associated with the risk of malignancy. RESULTS: Nodules were found in 58% of patients, with a malignant rate of 6%. Age was the only predictor of having a nodule and advanced-stage III + IV was a predictor of malignancy (P = .023; odds ratio [OR] 10.64; confidence interval 1.33-84.98). CONCLUSION: Patients presenting with head and neck cancer have a higher incidence of pulmonary nodules and a higher risk of malignancy. In contrast to the British Thoracic Society (BTS) guidelines, which use size to guide the need for serial scans, we would recommend follow-up imaging in all patients with head and neck cancer with nodules, irrespective of size.

Ectopic fat accumulation in patients with COPD: an ECLIPSE substudy.

BACKGROUND: Obesity is increasingly associated with COPD, but little is known about the prevalence of ectopic fat accumulation in COPD and whether this can possibly be associated with poor clinical outcomes and comorbidities. The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) substudy tested the hypothesis that COPD is associated with increased ectopic fat accumulation and that this would be associated with COPD-related outcomes and comorbidities. METHODS: Computed tomography (CT) images of the thorax obtained in ECLIPSE were used to quantify ectopic fat accumulation at L2-L3 (eg, cross-sectional area [CSA] of visceral adipose tissue [VAT] and muscle tissue [MT] attenuation, a reflection of muscle fat infiltration) and CSA of MT. A dose-response relationship between CSA of VAT, MT attenuation and CSA of MT and COPD-related outcomes (6-minute walking distance [6MWD], exacerbation rate, quality of life, and forced expiratory volume in 1 second [FEV1] decline) was addressed with the Cochran-Armitage trend test. Regression models were used to investigate possible relationships between CT body composition indices and comorbidities. RESULTS: From the entire ECLIPSE cohort, we identified 585 subjects with valid CT images at L2-L3 to assess body composition. CSA of VAT was increased (P<0.0001) and MT attenuation was reduced (indicating more muscle fat accumulation) in patients with COPD (P<0.002). Progressively increasing CSA of VAT was not associated with adverse clinical outcomes. The probability of exhibiting low 6MWD and accelerated FEV1 decline increased with progressively decreasing MT attenuation and CSA of MT. In COPD, the probability of having diabetes (P=0.024) and gastroesophageal reflux (P=0.0048) at baseline increased in parallel with VAT accumulation, while the predicted MT attenuation increased the probability of cardiovascular comorbidities (P=0.042). Body composition parameters did not correlate with coronary artery scores or with survival. CONCLUSION: Ectopic fat accumulation is increased in COPD, and this was associated with relevant clinical outcomes and comorbidities.

Excess long-term mortality in outpatient deep venous thrombosis patients managed in an ambulatory care setting.

BACKGROUND: Deep venous thrombosis (DVT) is increasingly being managed in the outpatient setting, particularly patients deemed low-risk at presentation. The long-term outcomes of these patients remain unclear. AIM: To determine the long-term outcomes of patients with DVT and those with raised D-dimer without DVT managed exclusively by an ambulatory care pathway. DESIGN: Retrospective cohort analysis. METHODS: 828 consecutive patients assessed at the Ambulatory Care Clinic of a tertiary care university hospital between 1 January and 31 December 2008 for potential lower limb DVT were analysed. Primary and secondary outcome was all-cause mortality and new diagnosis of cancer, respectively. Median follow-up was 6.4 years. RESULTS: The final cohort comprised 131 patients with DVT, 396 with raised D-dimer without DVT and 165 with normal D-dimer without DVT. Long-term survival was 72.5% for DVT, 75.3% for elevated D-dimer without thrombosis and 93.3% for those with normal D-dimer ( P < 0.0001). The risk of death with DVT remained significant after adjusting for age, gender, previous cancer, recent surgery and previous thromboembolism (HR 2.17, 95% CI [1.07, 4.38]). Cancer accounted for 44.4 and 37.8% of deaths within the first and second groups, respectively. 50% of cancers in the former group were diagnosed during follow-up vs. 95.1% in the latter. CONCLUSION: The 5-year survival of patients with DVT managed via ambulatory care was worse than expected. An algorithm is urgently needed to identify predictors of adverse outcomes for both these patients as well as those with raised D-dimer without thrombosis.

Management of pulmonary nodules in head and neck cancer patients - Our experience and interpretation of the British Thoracic Society Guidelines.

BACKGROUND: and purpose of the study: The frequency of lung nodules in the head and neck cancer population is unknown, currently the only guidance available recommends following local policy. The aim of this study was to determine the incidence of pulmonary nodules in our head and neck cancer group and interpret the recently updated British Thoracic Society (BTS) Lung Nodule Guidelines in a head and neck cancer setting. METHODS: 100 patients were diagnosed with head and neck cancer between July 2013-March 2014, clinico-pathological, demographic and radiological data was extracted from the electronic records. Images with lung findings were re-reviewed by a single consultant radiologist for patients with lung pathology on the initial staging CT report. RESULTS: Twenty patients (20%) had discreet pulmonary findings on CT. Eleven (11%) had lung nodules, 6 (6%) had lesions suspicious for metastasis and 3 (3%) had co-incidental bronchogenic primary cancers. These patients were re-imaged between 6 and 18 months and in 1 patient the previously identified 7 mm nodule had progressed to 16 mm at 1 year. There was no set follow up imaging protocol used. CONCLUSION: The MDT in NHS Lothian has reviewed the BTS guidance and now has a local policy for the management of lung nodules in head and neck cancer patients. Lung Nodules in the head and neck cancer population are common >10%. Higher risk patients with larger nodules should be risk assessed with validated assessment tools. PET-CT has a place in the assessment of lung nodules when risk of malignancy is high.

Dynamic (4D) CT perfusion offers simultaneous functional and anatomical insights into pulmonary embolism resolution.

OBJECTIVE: Resolution and long-term functional effects of pulmonary emboli are unpredictable. This study was carried out to assess persisting vascular bed perfusion abnormalities and resolution of arterial thrombus in patients with recent pulmonary embolism (PE). METHODS AND MATERIALS: 26 Patients were prospectively evaluated by dynamic (4D) contrast enhanced CT perfusion dynamic pulmonary CT perfusion. Intermittent volume imaging was performed every 1.5-1.7s during breath-hold and perfusion values were calculated by maximum-slope technique. Thrombus load (modified Miller score; MMS) and ventricular diameter were determined. Perfusion maps were visually scored and correlated with residual endoluminal filling defects. RESULTS: The mean initial thrombus load was 13.1±4.6 MMS (3-16), and 1.2±2.1 MMS (0-8) at follow up. From the 24 CTPs with diagnostic quality perfusion studies, normal perfusion was observed in 7 (29%), and mildly-severely abnormal in 17 (71%). In 15 patients with no residual thrombus on follow up CTPA, normal perfusion was observed in 6, and abnormal perfusion in 9. Perfusion was abnormal in all patients with residual thrombus on follow up CTPA. Pulmonary perfusion changes were classified as reduced (n=4), delayed (systemic circulation pattern; n=5), and absent (no-flow; n=5). The right ventricle was dilated in 12/25 (48%) at presentation, and normal in all 26 follow up scans. Weak correlation was found between initial ventricular dilatation and perfusion abnormality at follow up (r=0.15). CONCLUSIONS: Most patients had substantial perfusion abnormality at 3-6 months post PE. Abnormal perfusion patterns were frequently observed in patients and in regions with no corresponding evidence of residual thrombus on CTPA. Some defects exhibit delayed, presumed systemic, enhancement (which we have termed 'stunned' lung). CT perfusion provides combined anatomical and functional information about PE resolution.

Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD.

Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality.pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic-femoral pulse wave velocity.pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=-0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05).In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD.

T1 characteristics of interstitial pulmonary fibrosis on 3T MRI-a predictor of early interstitial change?

BACKGROUND: Computed tomography (CT) is routinely used for diagnosis and characterisation of idiopathic pulmonary fibrosis (IPF). The technique however has limited sensitivity in detection and monitoring of early fibrotic changes. The aim of this study was to evaluate T1 characteristics in the radiologically diseased lung parenchyma in IPF patient compared to apparently normal parenchyma in both interstitial lung disease (ILD) patients and healthy volunteers and to investigate the feasibility of the technique in prediction of early fibrotic lung changes that may not be visible on CT. METHODS: Ten patients with IPF underwent high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) on the same day of attendance. 3T MRI was repeated in seven patients with IPF to test the reproducibility of results. The control group included healthy volunteers (n=10). A modified look-locker inversion-recovery (MOLLI) sequence (124×192 acquisition matrix; 8 mm slice) was performed during a 15-20 s breathhold in a single slice. The position of MR slice was pre-selected where there was CT evidence of normal and fibrotic lung. MOLLI imaging was performed prior to the contrast administration, and at 15, 25, 30 and 35 min post Gadolinium. The imaging data were then processed with a curve-fitting technique to estimate T1 values. T1 values of the apparent fibrotic and normal lung in IPF patients and normal lung were compared. RESULTS: Fibrotic lung had a higher pre-contrast T1 than either morphologically normal lung in ILD patients or control lung (P=0.02) in healthy volunteers (1309±123, 1069±71, and 1011±172 ms, respectively). Morphologically normal lung T1 and control lung T1 were not significantly different pre-contrast, however, at 10 min after administration of Gadolinium, control lung had a significantly shorter T1 than either fibrotic or morphologically normal lung (494±34, 670±63, and 619±41 ms, respectively; P=0.001). T1 for fibrotic lung continued to decrease until 20 min after contrast agent administration (P≤0.0001), whereas morphologically normal lung T1 did not significantly change after 10 min (P>0.3). This indicates delayed uptake of contrast agent in the fibrotic lung compared with morphologically normal lung. CONCLUSIONS: T1 mapping of patients with IPF at 3T is feasible and demonstrates a significant difference between fibrotic lung tissue and morphologically normal lung tissue both before Gadolinium administration and at 10 min delayed post-contrast images. The technique is able to evaluate early fibrosis in patients with apparently morphologically normal lung.

Lung ultrasonography as a direct measure of evolving respiratory dysfunction and disease severity in patients with acute pancreatitis.

BACKGROUND: The value of lung ultrasonography in the diagnosis of respiratory dysfunction and severity stratification in patients with acute pancreatitis (AP) was investigated. METHODS: Over a 3-month period, 41 patients (median age: 59.1 years; 21 males) presenting with a diagnosis of potential AP were prospectively recruited. Each participant underwent lung ultrasonography and the number of comet tails was linked with contemporaneous clinical data. Group comparisons, areas under the curve (AUC) and respective measures of diagnostic accuracy were investigated. RESULTS: A greater number of comet tails were evident in patients with respiratory dysfunction (P = 0.021), those with severe disease (P < 0.001) and when contemporaneous and maximum CRP exceeded 100 mg/L (P = 0.048 and P = 0.003 respectively). Receiver-operator characteristic plot area under the curve (AUC) was greater when examining upper lung quadrants, using respiratory dysfunction and AP severity as variables of interest (AUC = 0.783, 95% C.I.: 0.544-0.962, and AUC = 0.996, 95% C.I.: 0.982-1.000, respectively). Examining all lung quadrants except for the lower lateral resulted in greater AUCs for contemporaneous and maximum CRP (AUC = 0.708, 95% C.I.: 0.510-0.883, and AUC = 0.800, 95% C.I.: 0.640-0.929). DISCUSSION: Ultrasonography of non-dependent lung parenchyma can reliably detect evolving respiratory dysfunction in AP. This simple bedside technique shows promise as an adjunct to severity stratification.

Association Between Interstitial Lung Abnormalities and All-Cause Mortality.

IMPORTANCE: Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated. OBJECTIVE: To investigate whether interstitial lung abnormalities are associated with increased mortality. DESIGN, SETTING, AND POPULATION: Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006). EXPOSURES: Interstitial lung abnormality status as determined by chest CT evaluation. MAIN OUTCOMES AND MEASURES: All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort. RESULTS: Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.5]; P = .03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P < .001), COPDGene (HR, 1.8 [95% CI, 1.1 to 2.8]; P = .01), and ECLIPSE (HR, 1.4 [95% CI, 1.1 to 2.0]; P = .02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis. CONCLUSIONS AND RELEVANCE: In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.

Lung ultrasonography as a direct measure of evolving respiratory dysfunction and disease severity in patients with acute pancreatitis.

BACKGROUND: The value of lung ultrasonography in the diagnosis of respiratory dysfunction and severity stratification in patients with acute pancreatitis (AP) was investigated. METHODS: Over a 3-month period, 41 patients (median age: 59.1 years; 21 males) presenting with a diagnosis of potential AP were prospectively recruited. Each participant underwent lung ultrasonography, and the number of comet tails present on scans was linked with contemporaneous clinical data. Group comparisons, areas under the curve (AUC) and respective measures of diagnostic accuracy were investigated. RESULTS: A greater number of comet tails were evident in patients with respiratory dysfunction (P = 0.013), those with severe disease (P = 0.001) and when contemporaneous and maximum in-patient C-reactive protein (CRP) exceeded 150 mg/l (P = 0.018 and P = 0.049, respectively). Receiver-operator characteristic plot area under the curve (AUC) was greater when examining upper lung quadrants, using respiratory dysfunction and AP severity as variables of interest (AUC = 0.803, 95% CI: 0.583-1.000, and AUC = 0.996, 95% CI: 0.983-1.000, respectively). Examining all lung quadrants resulted in greater AUCs for contemporaneous and maximum CRP (AUC = 0.764, 95% CI: 0.555-0.972, and AUC = 0.704, 95% CI: 0.510-0.898). DISCUSSION: Ultrasonography of non-dependent lung parenchyma can reliably detect evolving respiratory dysfunction in AP. This simple bedside technique shows promise as an adjunct to severity stratification.