Smoking-related emphysema is associated with idiopathic pulmonary fibrosis and rheumatoid lung.

BACKGROUND AND OBJECTIVE: A combined pulmonary fibrosis/emphysema syndrome has been proposed, but the basis for this syndrome is currently uncertain. The aim was to evaluate the prevalence of emphysema in idiopathic pulmonary fibrosis (IPF) and rheumatoid lung (rheumatoid arthritis-interstitial lung disease (RA-ILD)), and to compare the morphological features of lung fibrosis between smokers and non-smokers. METHODS: Using high-resolution computed tomography, the prevalence of emphysema and the pack-year smoking histories associated with emphysema were compared between current/ex-smokers with IPF (n = 186) or RA-ILD (n = 46), and non-chronic obstructive pulmonary disease (COPD) controls (n = 103) and COPD controls (n = 34). The coarseness of fibrosis was compared between smokers and non-smokers. RESULTS: Emphysema, present in 66/186 (35%) patients with IPF and 22/46 (48%) smokers with RA-ILD, was associated with lower pack-year smoking histories than in control groups (P < 0.05 for all comparisons). The presence of emphysema in IPF was positively linked to the pack-year smoking history (odds ratio 1.04, 95% confidence interval (CI) 1.02-1.06, P < 0.0005). In IPF, fibrosis was coarser in smokers than in non-smokers on univariate and multivariate analysis (P < 0.01 for all comparisons). In RA-ILD, fibrosis was coarser in patients with emphysema but did not differ significantly between smokers and non-smokers. CONCLUSIONS: In IPF and RA-ILD, a high prevalence of concurrent emphysema, in association with low pack-year smoking histories, and an association between coarser pulmonary fibrosis and a history of smoking in IPF together provide support for possible pathogenetic linkage to smoking in both diseases.

Non-specific interstitial pneumonia in cigarette smokers: a CT study.

The goal of this study was to seek indirect evidence that smoking is an aetiological factor in some patients with non-specific interstitial pneumonia (NSIP). Ten current and eight ex-smokers with NSIP were compared to controls including 137 current smokers with no known interstitial lung disease and 11 non-smokers with NSIP. Prevalence and extent of emphysema in 18 smokers with NSIP were compared with subjects meeting GOLD criteria for chronic obstructive pulmonary disease (COPD; group A; n = 34) and healthy smokers (normal FEV(1); group B; n = 103), respectively. Emphysema was present in 14/18 (77.8%) smokers with NSIP. Emphysema did not differ in prevalence between NSIP patients and group A controls (25/34, 73.5%), but was strikingly more prevalent in NSIP patients than in group B controls (18/103, 17.5%, P < 0.0005). On multiple logistic regression, the likelihood of emphysema increased when NSIP was present (OR = 18.8; 95% CI = 5.3-66.3; P < 0.0005) and with increasing age (OR = 1.04; 95% CI = 0.99-1.11; P = 0.08). Emphysema is as prevalent in smokers with NSIP as in smokers with COPD, and is strikingly more prevalent in these two groups than in healthy smoking controls. The association between NSIP and emphysema provides indirect support for a smoking pathogenesis hypothesis in some NSIP patients.

Idiopathic pulmonary fibrosis: outcome in relation to smoking status.

RATIONALE: The pathogenic importance of smoking status in idiopathic pulmonary fibrosis (IPF) is uncertain. In theory, increased oxidative stress in current and former smokers might promote disease progression. However, better survival has been reported for current smokers with IPF, although this might reflect less severe disease at presentation (a "healthy smoker effect"). OBJECTIVES: To determine whether smoking status is associated with survival differences in IPF. METHODS: A total of 249 patients with IPF were studied (current smokers, n = 20; former smokers, n = 166; never-smokers, n = 63). Survival was evaluated against smoking status, using proportional hazards analysis, adjusting for sex, age, disease severity (extent of the disease on high-resolution computed tomography, composite physiologic index [CPI], percentage predicted diffusing capacity for carbon monoxide in separate models), and the degree of honeycombing. MEASUREMENTS AND MAIN RESULTS: Current smokers had milder disease than did former smokers, with lower CPI scores (P < 0.0001), less extensive disease on high-resolution computed tomography (P < 0.005), and higher unadjusted survival (hazard ratio = 0.44; 95% confidence interval = 0.24, 0.80; P = 0.007). However, survival did not differ between current and former smokers (P = 0.39) after adjustment for CPI levels. By contrast, the increase in survival seen in nonsmokers than in former smokers (hazard ratio = 0.51; 95% confidence interval = 0.41, 0.83; P = 0.008) was amplified (P < 0.0005) by adjustment for CPI levels. CONCLUSIONS: In IPF, survival and severity-adjusted survival are higher in nonsmokers than in former smokers or the combined group of former and current smokers. By contrast, a better outcome in current smokers, compared with former smokers, reflects less severe disease at presentation and may represent a healthy smoker effect.

Lung diffusing capacity for nitric oxide and carbon monoxide in relation to morphological changes as assessed by computed tomography in patients with cystic fibrosis.

BACKGROUND: Due to large-scale destruction, changes in membrane diffusion (Dm) may occur in cystic fibrosis (CF), in correspondence to alterations observed by computed tomography (CT). Dm can be easily quantified via the diffusing capacity for nitric oxide (DLNO), as opposed to the conventional diffusing capacity for carbon monoxide (DLCO). We thus studied the relationship between DLNO as well as DLCO and a CF-specific CT score in patients with stable CF. METHODS: Simultaneous single-breath determinations of DLNO and DLCO were performed in 21 CF patients (mean +/- SD age 35 +/- 9 y, FEV1 66 +/- 28%pred). Patients also underwent spirometry and bodyplethysmography. CT scans were evaluated via the Brody score and rank correlations (rS) with z-scores of functional measures were computed. RESULTS: CT scores correlated best with DLNO (rS = -0.83; p < 0.001). Scores were also related to the volume-specific NO transfer coefficient (KNO; rS = -0.63; p < 0.01) and to DLCO (rS = -0.79; p < 0.001) but not KCO. Z-scores for DLNO were significantly lower than for DLCO (p < 0.001). Correlations with spirometric (e.g., FEV1, IVC) or bodyplethysmographic (e.g., SRaw, RV/TLC) indices were weaker than for DLNO or DLCO but most of them were also significant (p < 0.05 each). CONCLUSION: In this cross sectional study in patients with CF, DLNO and DLCO reflected CT-morphological alterations of the lung better than other measures. Thus the combined diffusing capacity for NO and CO may play a future role for the non-invasive, functional assessment of structural alterations of the lung in CF.

[Smoking-related interstitial lung diseases]. / Interstitielle Lungenerkrankungen bei Rauchern.

The most important smoking-related interstitial lung diseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis.

Acute pulmonary embolism on MDCT of the chest: prediction of cor pulmonale and short-term patient survival from morphologic embolus burden.

OBJECTIVE: To predict cor pulmonale and short-term outcome in patients with pulmonary embolism (PE), we retrospectively investigated three morphology-based MDCT systems for scoring pulmonary artery obstruction. MATERIALS AND METHODS: Eighty-nine consecutive patients (51 men and 38 women; age range, 23-83 years; median, 63.3 years) with an MDCT diagnosis of acute PE were included in the study. Sixty-four patients had a coexisting malignancy. PE severity was assessed by two masked observers using three percentage arterial obstruction indexes: two severity scores adapted from conventional angiography (excluding and including arterial branch obstruction grading: scores A and B, respectively) and a CT-derived severity score (index C). Echocardiographic reports were reviewed for elevation of right ventricular pressure. Obstruction index results were analyzed for correlation with pulmonary artery pressures and for prediction of cor pulmonale and 30-day survival. Statistical analysis included kappa, analysis of variance, linear correlation, chi-square, and logistic regression tests. RESULTS: Kappa values of 0.89, 0.82, and 0.78 were obtained for interobserver agreement on PE severity for indexes A, B, and C, respectively. PE severity was moderate but varied significantly between the scores (for index A: median, 25.0%; range, 6.3-100; for index B: median, 12.5%; range, 3.1-65.6; for index C: median, 7.1%; range, 0.65-65.8; p < 0.0001 [analysis of variance]). Index C correlated best with pulmonary artery pressures (r = 0.69; p < 0.0016) and the presence of cor pulmonale (p = 0.0051; odds ratio [OR], 1.20/percentage increase [95% confidence interval, 1.05-1.35]; for an index C cutoff of 21.3%: p = 0.0001; positive predictive value, 1; negative predictive value, 0.87). Eight patients died within 30 days after CT. The PE severity of indexes A and B was not associated with patient outcome (p > 0.05). With score C, PE severity was a significant predictor of early death (p = 0.018; OR, 1.03/percentage increase [95% confidence interval, 1.00-1.06]; for an index C cutoff of 21.3%: p = 0.018; overall OR, 6.77; positive predictive value, 0.24; negative predictive value, 0.96). CONCLUSION: Mastora score was a significant predictor of cor pulmonale and short-term outcome and may therefore allow therapy and risk stratification in patients with acute PE.

Flat panel detector-based volumetric CT: prototype evaluation with volumetry of small artificial nodules in a pulmonary phantom.

PURPOSE: To evaluate amorphous silicone-based flat panel detector volumetric CT (VCT) in volumetric assessment of small nodules in a pulmonary phantom, and to perform comparative experiments with 4-row multislice CT (MSCT). MATERIALS AND METHODS: Seventy synthetic nodules (volume range (VR): 0.99-185.77 mm; estimated diameter range (ED): 1.4-7.8 mm) were scanned in spherical shape and after iso-volumetric deformation with VCT and MSCT using 0.63 mm (MSCT I) and 1.25 mm (MSCT II) collimations. Measured volumes and percent measurement errors (PME) were compared between the 3 CT modes before and after nodule deformation. For each measurement pair before and after deformation, the post-deformation relative volumetric inaccuracy (RIA) was determined. Volume, PME, and RIA differences were tested using Wilcoxon and Friedman methods. RESULTS: The volumes of the smallest nodules (VR = 0.99-2.83 mm, ED = 1.4-1.9 mm) were computable only from VCT scans. In VCT, measured volumes and PMEs before and after deformation differed significantly less compared with MSCT (VCT: P = 0.06 and 0.56, respectively; MSCT I: P = 0.0012 and 0.006, respectively; and MSCT II: P < 0.0001 for measured volumes and PMEs). In VCT PMEs of 5.51-32.21 mm nodules (ED = 2.4-4.1 mm) before and after deformation were significantly below MSCT (VCT averages = 1.43-1.91% and 1.98-3.48%, for spherical and deformed nodules, respectively; MSCT I averages = 9.97-26.1% and 12.16-38.10%, respectively; MSCT II averages = 17.79-46.18 and 18.14-54.66%, respectively, P < 0.0001) and RIAs in VCT were significantly below MSCT (VCT: 0.50-2.62%, MSCT I: 3.35-15.97%, and MSCT II: 4.29-18.46%; P = 0.0001-0.0039). CONCLUSION: VCT volumetry is highly accurate in volumetry of smallest nodules with estimated diameters of 1.4-4.1 mm.

The challenge of the solitary pulmonary nodule: diagnostic assessment with multislice spiral CT.

The advent of fast multiscale computed tomography (MSCT) technology has sparked new interest in the noninvasive assessment of the solitary pulmonary nodule (SPN). Fast scanning within a single breath-hold period, simultaneous acquisition of multiple thin slices with subsequent morphologic characterization of the nodule, determination of perfusion patterns as well as growth rates has led to unprecedented improvements in this emerging field. This article reviews the capabilities of MSCT in the diagnostic assessment of the SPN.

The use of flat panel volumetric computed tomography (fpVCT) in osteoporosis research.

RATIONALE AND OBJECTIVES: Improvements in imaging technology have led to the increased use of computed tomography (CT). For example, micro-CT and quantitative CT (QCT) are now often used in osteoporosis research, in which micro-CT is able to analyze small bones or bone samples with high spatial resolution. In contrast, QCT is able to investigate large samples with low spatial resolution. The aim of this study was to test the usefulness of flat-panel volumetric CT (fpVCT) in a rat model of osteopenia. MATERIAL AND METHODS: Twenty-two 3-month-old rats underwent ovariectomy and were either left untreated or supplemented with estradiol for 15 weeks. After sacrificing, the rats' second lumbar vertebral body bone mineral density (BMD) was analyzed using fpVCT and ashing. The results were compared to those of a microstructural analysis of the first lumbar vertebrae and a biomechanical evaluation of the fourth lumbar vertebrae. RESULTS: BMD measurements using both fpVCT (0.39 vs 0.35 mg/cm(3)) and ashing (0.52 vs 0.48 mg/cm(3)) demonstrated a significant improvement after estradiol supplementation. The correlation coefficient of the two methods was 0.858. After estradiol supplementation, the bone microstructural and bone biomechanical parameters were improved, compared to no treatment. The correlations of both the microstructural and the biomechanical evaluations were closer for BMD measured using fpVCT (r = 0.482-0.769) than on the basis of ashing (r = 0.345-0.573). FpVCT was not able to display the trabecular microstructure of the rat lumbar vertebrae. CONCLUSION: The use of fpVCT demonstrated a close relationship between morphologic and biomechanical evaluations in a rat model of osteopenia. Because of its different proportions, fpVCT might be able to bridge the gap between micro-CT and QCT in analyzing larger animals.

Computer-assisted detection of pulmonary embolism: performance evaluation in consensus with experienced and inexperienced chest radiologists.

The value of a computer-aided detection tool (CAD) as second reader in combination with experienced and inexperienced radiologists for the diagnosis of acute pulmonary embolism (PE) was assessed prospectively. Computed tomographic angiography (CTA) scans (64 x 0.6 mm collimation; 61.4 mm/rot table feed) of 56 patients (31 women, 34-89 years, mean = 66 years) with suspected PE were analysed by two experienced (R1, R2) and two inexperienced (R3, R4) radiologists for the presence and distribution of emboli using a five-point confidence rating, and by CAD. Informed consent was obtained from all patients. Results were compared with an independent reference standard. Inter-observer agreement was calculated by kappa, confidence assessed by ROC analysis. A total of 1,116 emboli [within mediastinal (n = 72), lobar (n = 133), segmental (n = 465) and subsegmental arteries (n = 455)] were included. CAD detected 343 emboli (sensitivity = 30.74%, correct-positive rate = 6.13/patient; false-positive rate = 4.1/patient). Inter-observer agreement was good (R1, R2: kappa = 0.84, 95% CI = 0.81-0.87; R3, R4: kappa = 0.79, 95% CI = 0.76-0.81). Extended inter-observer agreement was higher in mediastinal and lobar than in segmental and subsegmental arteries (kappa = 0.84-0.86 and kappa = 0.51-0.58 for mediastinal/lobar and segmental/subsegmental arteries, respectively P < 0.05). Agreement between experienced and inexperienced readers was improved by CAD (kappa = 0.60-0.62 and kappa = 0.69-0.72 before and after CAD consensus, respectively P < 0.05). The experienced outperformed the inexperienced readers (Az = 0.95, 0.93, 0.89 and 0.86 for R1-4, respectively, P < 0.05). CAD significantly improved overall performances of readers 3 and 4 (Az = 0.86 for R3, R4 and Az = 0.89 for R3, R4 with CAD, P < 0.05), by enhancing sensitivities in segmental/subsegmental arteries. CAD improved experienced readers' sensitivities in segmental/subsegmental arteries (sens. = 0.93 and 0.90 for R1, R2 before and 0.97 and 0.94 for R1, R2 after CAD consensus, P < 0.05), without significant improvement of their overall performances (P > 0.05). Particularly inexperienced readers benefit from consensus with CAD data, greatly improving detection of segmental and subsegmental emboli. This system is advocated as a second reader.

Computer-aided detection and automated CT volumetry of pulmonary nodules.

With use of multislice computed tomography (MSCT), small pulmonary nodules are being detected in vast numbers, constituting the majority of all noncalcified lung nodules. Although the prevalence of lung cancers among such lesions in lung cancer screening populations is low, their isolation may contribute to increased patient survival. Computer-aided diagnosis (CAD) has emerged as a diverse set of diagnostic tools to handle the large number of images in MSCT datasets and most importantly, includes automated detection and volumetry of pulmonary nodules. Current CAD systems can significantly enhance experienced radiologists' performance and outweigh human limitations in identifying small lesions and manually measuring their diameters, augment observer consistency in the interpretation of such examinations and may thus help to detect significantly higher rates of early malignomas and give more precise estimates on chemotherapy response than can radiologists alone. In this review, we give an overview of current CAD in lung nodule detection and volumetry and discuss their relative merits and limitations.

Automated CT volumetry of pulmonary metastases: the effect of a reduced growth threshold and target lesion number on the reliability of therapy response assessment using RECIST criteria.

The purpose of this study was to evaluate the reproducibility of CT-volumetric tumour response assessment of pulmonary metastasis using variable volume change thresholds (VCT) and target lesions with response evaluation criteria in solid tumours (RECIST). Fifty consecutive patients with pulmonary metastases undergoing follow-up multislice CT under chemotherapy were assessed for response to chemotherapy with modifications to RECIST: (1) decreasing the percentual VCT for diagnosis of tumour response (range = 70%-20%), (2) reducing the number of target lesions (range = 1-5). Continuous and categorical observer agreements were tested by Bland and Altman and extended (kappa(e)) or non-weighted kappa (kappa) and correlated with percentual VCT to predict observer agreement. A total of 202 metastases were evaluated (average volume = 522.4 mm(3) +/- 902.4 mm(3)). General agreement on treatment response was very high (kappa(e) = 0.93-1), but was reduced with VCT < 35% (kappa(e) < 0.95). Kappa correlation with VCT values was strong (r=0.94-0.96; p< or =0.0002). Average confidence decreased significantly at VCT < 45% (p < 0.01) and agreement on stable disease at VCT < 35% (kappa(e) < 0.95; p < 0.01). Reduction of target lesions (n < 3; VCT = 35%) resulted in decreased reader confidence (for n = 1: kappa = 0.49; p < 0.05). Agreement for evaluation of treatment response was robust using VCT > or =35% and > or =3 metastases. This may translate into shortening of follow-up intervals or enable for response assessment with tumours displaying minimal volume change.

Pulmonary embolism at multi-detector row CT of chest: one-year survival of treated and untreated patients.

PURPOSE: To retrospectively assess outcome in patients with clinically unsuspected pulmonary embolism (PE) at chest multi-detector row computed tomography (CT). MATERIALS AND METHODS: Institutional review board approval and informed consent were not required. PE was assessed in consecutive CT scans in 1966 patients (mean age, 60 years; range, 15-96 years; male-female ratio, 1.79) and graded with severity score. Studies with true-positive and false-negative radiologic diagnoses were determined. Coexisting morbidity, anticoagulant therapy (ACT), complications, and 1-year outcome were reviewed. Statistical evaluation included Mann-Whitney U test, chi(2) test, Poisson regression, and Kaplan-Meier statistics. RESULTS: Scans were PE positive in 117 patients. Clinical data review was complete in 96 patients; 63 of 96 patients had malignancy; in 58, PE was not suspected. In 38 of these 58 patients, radiology report findings were false-negative (mean severity score, 20.21 +/- 17.88 [standard deviation] and 9.55 +/- 7.12 for those with true-positive and false-negative findings, respectively; P = .012). Forty-nine patients received therapeutic ACT; 21, prophylactic ACT; and 26, no treatment. PE severity was higher in patients with therapeutic ACT versus those without (P < .001). Bleeding complications were more frequent with therapeutic ACT (two early deaths, five major nonfatal hemorrhages) than without (one minor hemorrhage; P = .037). There were eight early deaths (therapeutic ACT, seven; without ACT, one; P = .037). Positive predictors of early death included severity score >28, use of systemic thrombolytic therapy, occurrence of major hemorrhage, and new-onset cardiac or renal failure (P = .001-.043). Negative predictors were report with false-negative findings and no therapeutic ACT (P = .007-.037). Predictors of late death (n = 25) were older age, malignancy, and renal failure (P = .001-.043). CONCLUSION: Clinically unsuspected PE may remain undetected at routine chest CT; these patients have favorable short-term outcome without therapeutic ACT.

Inadequacy of manual measurements compared to automated CT volumetry in assessment of treatment response of pulmonary metastases using RECIST criteria.

The purpose of this study was to compare relative values of manual unidimensional measurements (MD) and automated volumetry (AV) for longitudinal treatment response assessment in patients with pulmonary metastases. Fifty consecutive patients with pulmonary metastases and repeat chest multidetector-row CT (median interval=2 months) were independently assessed by two radiologists for treatment response using Response Evaluation Criteria In Solid Tumours (RECIST). Statistics included relative measurement errors (RME), intra-/interobserver correlations, limits of agreement (95% LoA), and kappa. A total of 202 metastases (median volume=182.22 mm(3); range=3.16-5,195.13 mm(3)) were evaluated. RMEs were significantly higher for MD than for AV (intraobserver RME=2.34-3.73% and 0.15-0.22% for MD and AV respectively; P<0.05. Interobserver RME=3.53-3.76% and 0.22-0.29% for MD and AV respectively; P<0.05). Overall correlation was significantly better for AV than for MD (P<0.05). Intraobserver 95% LoAs were -1.85 to 1.75 mm for MD and -11.28 to 9.84 mm(3) for AV. The interobserver 95% LoA were -1.46 to 1.92 mm for MD and -11.17 to 9.33 mm(3) for AV. There was total intra-/interobserver agreement on response using AV (kappa=1). MD intra- and interobserver agreements were 0.73-0.84 and 0.77-0.80 respectively. Of the 200 MD response ratings, 28 (14/50 patients) were discordant. Agreement using MD dropped significantly from total remission to progressive disease (P<0.05). We therefore conclude that AV allows for better reproducibility of response evaluation in pulmonary metastases and should be preferred to MD in these patients.

Imaging of macrophage-related lung diseases.

Macrophage-related pulmonary diseases are a heterogeneous group of disorders characterized by macrophage accumulation, activation or dysfunction. These conditions include smoking-related interstitial lung diseases, metabolic disorders such as Niemann-Pick or Gaucher disease, and rare primary lung tumors. High-resolution computed tomography abnormalities include pulmonary ground-glass opacification secondary to infiltration by macrophages, centrilobular nodules or interlobular septal thickening reflecting peribronchiolar or septal macrophage accumulation, respectively, emphysema caused by macrophage dysfunction, and honeycombing following macrophage-related lung matrix remodeling.

Computer-assisted detection of pulmonary nodules: evaluation of diagnostic performance using an expert knowledge-based detection system with variable reconstruction slice thickness settings.

The purpose of this study was to evaluate the performance of a computer-assisted diagnostic (CAD) tool using various reconstruction slice thicknesses (RST). Image data of 20 patients undergoing multislice CT for pulmonary metastasis were reconstructed at 4.0, 2.0 and 0.75 mm RST and assessed by two blinded radiologists (R1 and R2) and CAD. Data were compared against an independent reference standard. Nodule subgroups (diameter >10, 4-10, <4 mm) were assessed separately. Statistical methods were the ROC analysis and Mann-Whitney U test. CAD was outperformed by readers at 4.0 mm (Az = 0.18, 0.62 and 0.69 for CAD, R1 and R2, respectively; P<0.05), comparable at 2.0 mm (Az = 0.57, 0.70 and 0.69 for CAD, R1 and R2, respectively), and superior using 0.75 mm RST (Az = 0.80, 0.70 and 0.70 and sensitivity = 0.74, 0.53 and 0.53 for CAD, R1 and R2, respectively; P<0.05). Reader performances were significantly enhanced by CAD (Az = 0.93 and 0.95 for R1 + CAD and R2 + CAD, respectively, P<0.05). The CAD advantage was best for nodules <10 mm (detection rates = 93.3, 89.9, 47.9 and 47.9% for R1 + CAD, R2 + CAD, R1 and R2, respectively). CAD using 0.75 mm RST outperformed radiologists in nodules below 10 mm in diameter and should be used to replace a second radiologist. CAD is not recommended for 4.0 mm RST.

Computer-assisted detection of pulmonary nodules: performance evaluation of an expert knowledge-based detection system in consensus reading with experienced and inexperienced chest radiologists.

To evaluate the performance of experienced versus inexperienced radiologists in comparison and in consensus with an interactive computer-aided detection (CAD) system for detection of pulmonary nodules. Eighteen consecutive patients (mean age: 62.2 years; range 29-83 years) prospectively underwent routine 16-row multislice computed tomography (MSCT). Four blinded radiologists (experienced: readers 1, 2; inexperienced: readers 3, 4) assessed image data against CAD for pulmonary nodules. Thereafter, consensus readings of readers 1+3, reader 1+CAD and reader 3+CAD were performed. Data were compared against an independent gold standard. Statistical tests used to calculate interobserver agreement, reader performance and nodule size were Kappa, ROC and Mann-Whitney U. CAD and experienced readers outperformed inexperienced readers (Az=0.72, 0.71, 0.73, 0.49 and 0.50 for CAD, readers 1-4, respectively; P<0.05). Performance of reader 1+CAD was superior to single reader and reader 1+3 performances (Az=0.93, 0.72 for reader 1+CAD and reader 1+3 consensus, respectively, P<0.05). Reader 3+CAD did not perform superiorly to experienced readers or CAD (Az=0.79 for reader 3+CAD; P>0.05). Consensus of reader 1+CAD significantly outperformed all other readings, demonstrating a benefit in using CAD as an inexperienced reader replacement. It is questionable whether inexperienced readers can be regarded as adequate for interpretation of pulmonary nodules in consensus with CAD, replacing an experienced radiologist.

Soft copy versus hard copy reading in digital mammography.

The objective of this study was to compare soft copy reading at a mammography work station with hard copy reading of full-field digital mammographic images. Mammograms of 60 patients ( n = 29 malignant, n = 31 benign) performed with full-field digital mammography (Senographe 2000D, GE, Buc, France) were evaluated. Reading was performed based on hard copy prints (Scopix, Agfa, Leverkusen, Germany) and on 2 k x 2.5 k high-resolution monitors (Sun Ultra 60, Sun Microsystems, Palo Alto, California, USA). Four readers with different levels of experience in mammography categorized the mammograms according to the BI-RADS classification. The comparative study was performed by four readers, and at least 2 months elapsed between the reading sessions. Postprocessing, of course, was available only at the work station (windowing and leveling, zooming, inversion). Sensitivity, specificity, and positive predictive value were evaluated. Diagnostic accuracy of the evaluation was determined. Sensitivity for malignant lesions in hard copy versus soft copy reading was 97% vs 90%, 97% vs 97%, 93% vs 97%, and 76% vs 76% for the four readers, respectively. Specificity was 52% vs 68%, 58% vs 74%, 65% vs 48%, and 61% vs 68%. Accuracy for the classification of malignant lesions according to the BI-RADS categories showed no difference between hard copy and soft copy reading. Soft copy reading is possible with the available system and enables radiologists to use the advantages of a digital system.

Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice.

BACKGROUND & AIMS: Proteases play key roles in the pathogenesis of tumor growth and invasion. This study assesses the expression of cathepsin B in dysplastic adenomatous polyps. METHODS: Aged Apc(Min/+) mice served as an experimental model for familial adenomatous polyposis. The 4 experimental groups consisted of (a) animals injected with a novel activatable, cathepsin B sensing near infrared fluorescence (NIRF) imaging probe; (b) animals injected with a nonspecific NIRF; (c) uninjected control animals; and (d) non-APC(Min/+) mice injected with the cathepsin B probe. Lesions were analyzed by immunohistochemistry, Western blotting, reverse transcription-polymerase chain reaction, and optical imaging. RESULTS: Cathepsin B was consistently overexpressed in adenomatous polyps. When mice were injected intravenously with the cathepsin reporter probe, intestinal adenomas became highly fluorescent indicative of high cathepsin B enzyme activity. Even microscopic adenomas were readily detectable by fluorescence, but not light, imaging. The smallest lesion detectable measured 50 microm in diameter. Adenomas in the indocyanine green and/or noninjected group were only barely detectable above the background. CONCLUSIONS: The current experimental study shows that cathepsin B is up-regulated in a mouse model of adenomatous polyposis. Cathepsin B activity can be used as a biomarker to readily identify such lesions, particularly when contrasted against normal adjacent mucosa. This detection technology can be adapted to endoscopy or tomographic optical imaging methods for screening of suspicious lesions and potentially for molecular profiling in vivo.