Small airway segmentation in thoracic computed tomography scans: a machine learning approach.

Small airway obstruction is a main cause for chronic obstructive pulmonary disease (COPD). We propose a novel method based on machine learning to extract the airway system from a thoracic computed tomography (CT) scan. The emphasis of the proposed method is on including the smallest airways that are still visible on CT. We used an optimized sampling procedure to extract airway and non-airway voxel samples from a large set of scans for which a semi-automatically constructed reference standard was available. We created a set of features which represent tubular and texture properties that are characteristic for small airway voxels. A random forest classifier was used to determine for each voxel if it belongs to the airway class. Our method was validated on a set of 20 clinical thoracic CT scans from the COPDGene study. Experiments show that our method is effective in extracting the full airway system and in detecting a large number of small airways that were missed by the semi-automatically constructed reference standard.

Epipericardial fat necrosis: an underdiagnosed condition.

OBJECTIVE: Epipericardial fat necrosis (EFN) is an uncommon benign and self-limited condition that leads patients to the emergency department (ED) owing to the onset of acute pleuritic chest pain. The aim of this study was to describe the cases of this disease in our institution and to illustrate the associated clinical and radiological findings. METHODS: We reviewed 3604 chest scans referred by the ED from November 2011 to July 2013. Patients diagnosed with epipericardial necrosis had their medical records and original tomography reports analysed. RESULTS: Chest pain was the primary complaint in 426 patients; 11 of them had definitive EFN findings characterized by a round soft-tissue attenuation lesion with a varying degree of strands. All patients presented with pleuritic chest pain on the same side as the lesion. Pericardial thickening, pleural effusion and mild atelectasis were the associated tomography findings. Cardiac enzyme and D-dimer tests performed during the episode were normal in all cases. 27% of the cases only were correctly diagnosed with EFN at the time of presentation. CONCLUSION: EFN is a benign inflammatory condition frequently overlooked in the ED by physicians and radiologists but is an important factor in the differential diagnosis of patients with acute chest pain. ADVANCES IN KNOWLEDGE: The article adds clinically and radiologically useful information about the condition and displays the importance of making the correct diagnosis to avoid unnecessary examinations.

Computed tomographic measures of airway morphology in smokers and never-smoking normals.

Bronchial wall area percent (WA% = 100 × wall area/total bronchial cross sectional area) is a standard computed tomographic (CT) measure of central airway morphology utilized in smokers with chronic obstructive pulmonary disease (COPD). Although it provides significant clinical correlations, the range of reported WA% is narrow. This suggests limited macroscopic change in response to smoking or that remodeling proportionally affects the airway wall and lumen dimensions such that their ratio is preserved. The objective of this study is to assess central airway wall area (WA), lumen area (Ai), and total bronchial area (Ao) from CT scans of 5,179 smokers and 92 never smoking normal subjects. In smokers, WA, Ai, and Ao were positively correlated with forced expiratory volume in 1 s (FEV1) expressed as a percent of predicted (FEV1%), and the WA% was negatively correlated with FEV1% (P < 0.0001 for all comparisons). Importantly, smokers with lower FEV1% tended to have airways of smaller cross-sectional area with lower WA. The increases in the WA% across GOLD stages of chronic obstructive pulmonary disease (COPD) can therefore not be due to increases in WA. The data suggest two possible origins for the WA% increases: 1) central airway remodeling resulting in overall reductions in airway caliber in excess of the decreased WA or 2) those with COPD had smaller native airways before they began smoking. In both cases, these observations provide an explanation for the limited range of values of WA% across stages of COPD.

Reference standard and statistical model for intersite and temporal comparisons of CT attenuation in a multicenter quantitative lung study.

PURPOSE: The purpose of this study was to detect and analyze anomalies between a large number of computed tomography (CT) scanners, tracked over time, utilized to collect human pulmonary CT data for a national multicenter study: chronic obstructive pulmonary disease genetic epidemiology study (COPDGene). METHODS: A custom designed CT reference standard "Test Object" has been developed to evaluate the relevant differences in CT attenuation between CT scanners in COPDGene. The materials used in the Test Object to assess CT scanner accuracy and precision included lung equivalent foam (-856 HU), internal air (-1000 HU), water (0 HU), and acrylic (120 HU). Nineteen examples of the Test Object were manufactured. Initially, all Test Objects were scanned on the same CT scanner before the Test Objects were sent to the 20 specific sites and 42 individual CT scanners that were used in the study. The Test Objects were scanned over 17 months while the COPDGene study continued to recruit subjects. A mixed linear effect statistical analysis of the CT scans on the 19 Test Objects was performed. The statistical model reflected influence of reconstruction kernels, tube current, individual Test Objects, CT scanner models, and temporal consistency on CT attenuation. RESULTS: Depending on the Test Object material, there were significant differences between reconstruction kernels, tube current, individual Test Objects, CT scanner models, and temporal consistency. The two Test Object materials of most interest were lung equivalent foam and internal air. With lung equivalent foam, there were significant (p < 0.05) differences between the Siemens B31 (-856.6, ±0.82; mean ± SE) and the GE Standard (-856.6 ± 0.83) reconstruction kernel relative to the Siemens B35 reference standard (-852.5 ± 1.4). Comparing lung equivalent foam attenuation there were also significant differences between CT scanner models (p < 0.01), tube current (p < 0.005), and in temporal consistency (p < 0.005) at individual sites. However, there were no significant effects measurable using different examples of the Test Objects at the various sites compared to the reference scans of the 19 Test Objects. For internal air, significant (p < 0.005) differences were found between all reconstruction kernels (Siemens B31, GE Standard, and Phillips B) compared to the reference standard. There were significant differences between CT models (p < 0.005), and tube current (p < 0.005). There were no significant effects measurable using different examples of the Test Objects at the various sites compared to the reference scans of the 19 Test Objects. Differences, across scanners, between external air and internal air measures in this simple (relative to the in vivo lung) test object varied by as much as 15 HU. CONCLUSIONS: The authors conclude that the Test Object designed for this study was able to detect significant effects regarding individual CT scanners that altered the CT attenuation measurements relevant to the study that are used to determine lung density. Through an understanding of individual scanners, the Test Object analysis can be used to detect anomalies in an individual CT scanner and to statistically model out scanner differences and individual scanner changes over time in a large multicenter trial.

Red blood cell fatty acids are associated with depression in a case-control study of adolescents.

INTRODUCTION: Epidemiological studies suggest that reduced intakes and/or blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with increased risk for depression in adults, but data on adolescents are scarce. The objective of this study was to determine whether red blood cell (RBC) levels of EPA+DHA (the omega-3 index) and/or the overall RBC fatty acid profile differ between depressed adolescents (cases) and non-depressed adolescents (controls). PATIENTS AND METHODS: We measured the RBC fatty acid composition of cases admitted to the hospital for depression (n=150) and compared it to that of controls (n=161). RESULTS: Cases and controls had similar ages, gender proportions, and body mass index (BMI) distributions, but there was a significant difference in racial/ethnic composition due to differences in recruitment sites. The unadjusted odds ratio for case status was 0.72 (95% CI; 0.55-0.95) for a 1% absolute increase in the omega-3 index. A multivariable logistic regression model was used to determine which fatty acids were useful in classifying cases and controls; BMI, age, gender, and race/ethnicity were forced into the model. Seven fatty acids were selected (DHA, myristic, stearic, oleic, trans linoleic, trans palmitoleic, and alpha-linolenic acids) to optimize the model fit to the data. In the adjusted model, the odds ratio was 0.67 (95% CI; 0.49-0.93) for a 1 SD increase in DHA. Adding the seven fatty acid profile to the basic model increased the area under the ROC curve by 12.6% (7.5%-17.6%). DISCUSSION AND CONCLUSION: These findings support the hypothesis that adolescent depression is associated with a perturbed RBC fatty acid pattern which includes a reduced omega-3 index. Intervention studies with EPA and DHA should be conducted in this vulnerable population for which few, safe therapeutic options currently exist.

EMPHYSEMA QUANTIFICATION IN A MULTI-SCANNER HRCT COHORT USING LOCAL INTENSITY DISTRIBUTIONS.

This article investigates the suitability of local intensity distributions to analyze six emphysema classes in 342 CT scans obtained from 16 sites hosting scanners by 3 vendors and a total of 9 specific models in subjects with Chronic Obstructive Pulmonary Disease (COPD). We propose using kernel density estimation to deal with the inherent sparsity of local intensity histograms obtained from scarcely populated regions of interest. We validate our approach by leave-one-subject-out classification experiments and full-lung analyses. We compare our results with recently published LBP texture-based methodology. We demonstrate the efficacy of using intensity information alone in multi-scanner cohorts, which is a simpler, more intuitive approach.

A computer-aided diagnosis system for quantitative scoring of extent of lung fibrosis in scleroderma patients.

OBJECTIVES: To evaluate an improved quantitative lung fibrosis score based on a computer-aided diagnosis (CAD) system that classifies CT pixels with the visual semi-quantitative pulmonary fibrosis score in patients with scleroderma-related interstitial lung disease (SSc-ILD). METHODS: High-resolution, thin-section CT images were obtained and analysed on 129 subjects with SSc-ILD (36 men, 93 women; mean age 48.8±12.1 years) who underwent baseline CT in the prone position at full inspiration. The CAD system segmented each lung of each patient into 3 zones. A quantitative lung fibrosis (QLF) score was established via 5 steps: 1) images were denoised; 2) images were grid sampled; 3) the characteristics of grid intensities were converted into texture features; 4) texture features classified pixels as fibrotic or non-fibrotic, with fibrosis defined by a reticular pattern with architectural distortion; and 5) fibrotic pixels were reported as percentages. Quantitative scores were obtained from 709 zones with complete data and then compared with ordinal scores from two independent expert radiologists. ROC curve analyses were used to measure performance. RESULTS: When the two radiologists agreed that fibrosis affected more than 1% or 25% of a zone or zones, the areas under the ROC curves for QLF score were 0.86 and 0.96, respectively. CONCLUSIONS: Our technique exhibited good accuracy for detecting fibrosis at a threshold of both 1% (i.e. presence or absence of pulmonary fibrosis) and a clinically meaningful threshold of 25% extent of fibrosis in patients with SSc-ILD.

Bronchiolitis obliterans syndrome in popcorn production plant workers.

Following sentinel case recognition, an excess of fixed airways obstruction was found among current workers in a microwave popcorn plant associated with butter flavouring exposures. In order to characterise the clinical presentation of sentinel cases, the medical records of sentinel cases were reviewed, interviews conducted and serial spirometric testing performed. Cases worked in microwave popcorn production, and five of the nine cases had mixed flavourings. Most had never smoked or smoked minimally. Cases showed onset of cough, shortness of breath and wheezing 5 months to 9 yrs after starting work at the popcorn plant. Initial forced expiratory volume in one second ranged 14.0-66.8% of the predicted value. Eight high-resolution computed tomography scans showed marked bronchial wall thickening and mosaic attenuation with air trapping. Open lung biopsy results were consistent with, or diagnostic of, constrictive bronchiolitis in two of three cases. Five cases are on lung transplantation waiting lists. After leaving employment, nearly all cases experienced stabilisation of their lung function within 2 yrs. Astute clinicians can help identify new causes of airways obstruction by alerting public health authorities to unexplained disease cases occurring in groups of workers.

Ten year follow up of ulcerative colitis patients with and without low grade dysplasia.

BACKGROUND AND AIMS: Low grade dysplasia (LGD) is believed to predispose to colorectal cancer (CRC), and proctocolectomy has been advocated when this is identified. Between 1978 and 1990, 160 patients with longstanding extensive ulcerative colitis (UC) were recruited for annual colonoscopic surveillance and 40 developed LGD at some stage. We report the outcome of this cohort 10 years after the original study ended. METHODS: Retrospective cohort study and histopathological review of the original diagnoses of LGD. The outcome of 158/160 (98.8%) patients was established in 2000. RESULTS: Of the 128 patients still alive and with an intact colon at the end of 1990, two were not traceable, 29 had LGD, and 97 had no dysplasia (controls). After 10 years, high grade dysplasia (HGD) or CRC developed in 3/29 LGD (10%) and in 4/97 controls (4.0%). Kaplan-Meier analysis from 1991 to death or colectomy did not show a statistically significant difference between the two groups (log rank test p=0.63). Histopathological review demonstrated the unreliability of LGD diagnosis. Agreement between pathologists was uniformly poor: kappa <0.4 for all comparisons. CONCLUSION: LGD diagnosis is not sufficiently reliable to justify prophylactic colectomy. Conservative management of established LGD cases should not be ruled out.

Interferon-gamma for delayed pulmonary toxicity syndrome resistant to steroids.

Delayed pulmonary toxicity syndrome, characterized by interstitial pneumonia and pulmonary fibrosis, is common following high-dose bischloroethylnitrosourea (BCNU) (carmustine, [1,3-bis (2-chloroethyl)-1-nitrosourea]) containing chemotherapeutic regimens. Depending upon the treatment protocol, it may develop in over 70% of patients. Early and aggressive corticosteroid treatment leads to improvement in the majority of patients. However, up to 8% of affected patients may fail to respond to corticosteroids and develop progressive respiratory failure leading to death. No alternatives to corticosteroids have thus far been shown useful. We report the symptomatic and physiological improvement of a patient with severe steroid-resistant delayed pulmonary toxicity syndrome, following treatment with interferon-gamma.

High-resolution CT features of severe asthma and bronchiolitis obliterans.

AIM: To evaluate the high-resolution CT findings of severe asthma (SA) and bronchiolitis obliterans (BO) and determine whether any reliable discriminating HRCT features exist. MATERIALS AND METHODS: HRCT examinations of the chest of 30 patients with SA and 14 patients with BO were analysed. Images were scored for the presence and extent of 21 CT findings. RESULTS: The most consistent HRCT features in SA were bronchial wall thickening in 30 (100%), expiratory air trapping in 19 of 22 examinations with expiratory images (87%), inspiratory decreased attenuation in 18 (60%), and bronchial luminal narrowing in 12 (40%). The most consistent HRCT features in BO were expiratory air trapping in 10 of 10 examinations with expiratory images (100%), bronchial wall thickening in 13 (93%), inspiratory decreased attenuation in 11 (79%), ground glass opacity in seven (50%), and mosaic pattern of attenuation in seven (50%). Decreased attenuation was more extensive in BO than in SA on both inspiratory and expiratory images. The mosaic pattern of attenuation was present in seven (50%) BO patients but in only one (3%) SA patients (P=0.0006). CONCLUSIONS: Mosaic pattern of attenuation, when present, is highly suggestive of BO, but SA and BO may be indistinguishable.

High-resolution CT of idiopathic interstitial pneumonias.

Important recent changes have occurred in our understanding of the IIPs. IPF (characterized histologically as UIP) is recognized as a progressive disease with a relatively poor prognosis, and with a characteristic CT appearance. The radiologist must be able to distinguish between UIP and the other IIPs. Complications of IPF include accelerated progression, lung cancer, and secondary infection. NSIP has a better prognosis than IPF, and has ground-glass attenuation as its salient CT feature. COP (formerly known as BOOP) is included as an IIP because its clinical, physiologic, and imaging features overlap with those of the other IIPs. It is characterized on CT by consolidation and ground-glass attenuation. AIP is the idiopathic form of ARDS. LIP and DIP are less common IIPs, both characterized by ground-glass attenuation.

Hypoxemia explained 36 years later.

A 37-year-old man who had an atrial septal defect (ASD) corrected as an infant was found to be hypoxemic with a 22% shunt. An MRI scan revealed that the patient's inferior vena cava drained into his left rather than his right atrium, a previously undetected complication of his ASD repair 36 years before.

Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema.

Emphysema due to cigarette smoking is characterized by a loss of alveolar structures. We hypothesize that the disappearance of alveoli involves apoptosis of septal endothelial cells and a decreased expression of lung vascular endothelial growth factor (VEGF) and its receptor 2 (VEGF R2). By terminal transferase dUTP nick end labeling (TUNEL) in combination with immunohistochemistry, we found that the number of TUNEL+ septal epithelial and endothelial cells/lung tissue nucleic acid (microg) was increased in the alveolar septa of emphysema lungs (14.2 +/- 2.0/microg, n = 6) when compared with normal lungs (6.8 +/- 1.3/microg, n = 7) (p < 0.01) and with primary pulmonary hypertensive lungs (2.3 +/- 0.8/microg, n = 5) (p < 0.001). The cell death events were not significantly different between healthy nonsmoker (7.4 +/- 1.9/microg) and smoker (5.7 +/- 0.7/microg) control subjects. The TUNEL results were confirmed by single-stranded DNA and active caspase-3 immunohistochemistry, and by DNA ligation assay. Emphysema lungs (n = 12) had increased levels of oligonucleosomal-length DNA fragmentation when compared with normal lungs (n = 11). VEGF, VEGF R2 protein, and mRNA expression were significantly reduced in emphysema. We propose that epithelial and endothelial alveolar septal death due to a decrease of endothelial cell maintenance factors may be part of the pathogenesis of emphysema.

Cell proliferation in type C gastritis affecting the intact stomach.

AIMS: Type C gastritis caused by bile reflux has a characteristic appearance, similar to that seen in other forms of chemical gastritis, such as those associated with NSAIDs or alcohol. An increase in mucosal cell proliferation increases the likelihood of a neoplastic clone of epithelial cells emerging, particularly where there is chronic epithelial injury associated with bile reflux. It has been shown previously that type C gastritis is associated with increased cell proliferation in the postsurgical stomach. The aim of this study was to determine cell proliferation in type C gastritis caused by bile reflux affecting the intact stomach. METHODS: Specimens from 15 patients with a histological diagnosis of type C gastritis on antral biopsy were obtained from the pathology archives between 1994 and 1997. A control group of nine normal antral biopsies was also selected and all underwent MIB-1 immunostaining. The gastric glands were divided into three zones (zone 1, gastric pit; zone 2, isthmus; and zone 3, gland base) and the numbers of positively staining nuclei for 500 epithelial cell nuclei were counted in each zone to determine the percentage labelling index (LI%). RESULTS: Cell proliferation was significantly higher in all three zones of the gastric glands with type C gastritis compared with controls as follows: zone 1, median LI% in type C gastritis 64.7 (range, 7.8-99.2), controls 4.7 (range, 2.0-11.3); zone 2, median LI% in type C gastritis 94.7 (range, 28.8-98.7), controls 40.2 (range, 23.1-70.3); and zone 3, median LI% in type C gastritis 20.0 (range, 1.3-96.0), controls 2.6 (range, 0.9-8.7). CONCLUSIONS: Bile reflux is thought to act as a promoter of gastric carcinogenesis in the postsurgical stomach. The same may be true in the intact stomach.

Lymphomatoid granulomatosis: radiologic features and pathologic correlations.

OBJECTIVE: The purpose of this paper is to define the radiologic features of lymphomatoid granulomatosis and correlate them with histopathologic features. CONCLUSION: Lymphomatoid granulomatosis shows characteristic CT features such as peribronchovascular distribution of nodules, coarse irregular opacities, small thin-walled cysts, and conglomerating small nodules. Large masses and occlusion of large vessels also occur. Histopathologic examination shows the nodules are caused by intravascular and perivascular infiltration by atypical lymphoid cells.