Hester A. Gietema

A large-scale evaluation of automatic pulmonary nodule detection in chest CT using local image features and k-nearest-neighbour classification

A scheme for the automatic detection of nodules in thoracic computed tomography scans is presented and extensively evaluated. The algorithm uses the local image features of shape index and curvedness in order to detect candidate structures in the lung volume and applies two successive k-nearest-neighbour classifiers in the reduction of false-positives. The nodule detection system is trained and tested on three databases extracted from a large-scale experimental screening study. The databases are constructed in order to evaluate the algorithm on both randomly chosen screening data as well as data containing higher proportions of nodules requiring follow-up. The system results are extensively evaluated including performance measurements on specific nodule types and sizes within the databases and on lesions which later proved to be malignant. In a random selection of 813 scans from the screening study a sensitivity of 80% with an average 4.2 false-positives per scan is achieved. The detection results presented are a realistic measure of a CAD system performance in a low-dose screening study which includes a diverse array of nodules of many varying sizes, types and textures.

Quantifying the Extent of Emphysema: Factors Associated with Radiologists' Estimations and Quantitative Indices of Emphysema Severity Using the ECLIPSE Cohort

RATIONALE AND OBJECTIVES This study investigated what factors radiologists take into account when estimating emphysema severity and assessed quantitative computed tomography (CT) measurements of low attenuation areas. MATERIALS AND METHODS CT scans and spirometry were obtained on 1519 chronic obstructive pulmonary disease (COPD) subjects, 269 smoker controls, and 184 nonsmoker controls from the Evaluation of COPD Longitudinally to Indentify Surrogate Endpoints (ECLIPSE) study. CT scans were analyzed using the threshold technique (%<-950HU) and a low attenuation cluster analysis. Two radiologists scored emphysema severity (0 to 5 scale), described the predominant type and distribution of emphysema, and the presence of suspected small airways disease. RESULTS The percent low attenuation area (%LAA) and visual scores of emphysema severity correlated well (r = 0.77, P < .001). %LAA, low attenuation cluster analysis, and absence of radiologist described gas trapping, distribution, and predominant type of emphysema were predictors of visual scores of emphysema severity (all P < .001). CT scans scored as showing regions of gas trapping had smaller lesions for a similar %LAA than those without (P < .001). CONCLUSIONS Visual estimates of emphysema are not only determined by the extent of LAA, but also by lesion size, predominant type, and distribution of emphysema and presence/absence of areas of small airways disease. A computer analysis of low attenuation cluster size helps quantitative algorithms discriminate low attenuation areas from gas trapping, image noise, and emphysema.

Identification of chronic obstructive pulmonary disease in lung cancer screening computed tomographic scans.

CONTEXT Smoking is a major risk factor for both cancer and chronic obstructive pulmonary disease (COPD). Computed tomography (CT)-based lung cancer screening may provide an opportunity to detect additional individuals with COPD at an early stage. OBJECTIVE To determine whether low-dose lung cancer screening CT scans can be used to identify participants with COPD. DESIGN, SETTING, AND PATIENTS Single-center prospective cross-sectional study within an ongoing lung cancer screening trial. Prebronchodilator pulmonary function testing with inspiratory and expiratory CT on the same day was obtained from 1140 male participants between July 2007 and September 2008. Computed tomographic emphysema was defined as percentage of voxels less than -950 Hounsfield units (HU), and CT air trapping was defined as the expiratory:inspiratory ratio of mean lung density. Chronic obstructive pulmonary disease was defined as the ratio of forced expiratory volume in the first second to forced vital capacity (FEV(1)/FVC) of less than 70%. Logistic regression was used to develop a diagnostic prediction model for airflow limitation. MAIN OUTCOME MEASURES Diagnostic accuracy of COPD diagnosis using pulmonary function tests as the reference standard. RESULTS Four hundred thirty-seven participants (38%) had COPD according to lung function testing. A diagnostic model with CT emphysema, CT air trapping, body mass index, pack-years, and smoking status corrected for overoptimism (internal validation) yielded an area under the receiver operating characteristic curve of 0.83 (95% CI, 0.81-0.86). Using the point of optimal accuracy, the model identified 274 participants with COPD with 85 false-positives, a sensitivity of 63% (95% CI, 58%-67%), specificity of 88% (95% CI, 85%-90%), positive predictive value of 76% (95% CI, 72%-81%); and negative predictive value of 79% (95% CI, 76%-82%). The diagnostic model showed an area under the receiver operating characteristic curve of 0.87 (95% CI, 0.86-0.88) for participants with symptoms and 0.78 (95% CI, 0.76-0.80) for those without symptoms. CONCLUSION Among men who are current and former heavy smokers, low-dose inspiratory and expiratory CT scans obtained for lung cancer screening can identify participants with COPD, with a sensitivity of 63% and a specificity of 88%.

Quantitative Computed Tomography in COPD: Possibilities and Limitations

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by chronic airflow limitation. Unraveling of this heterogeneity is challenging but important, because it might enable more accurate diagnosis and treatment. Because spirometry cannot distinguish between the different contributing pathways of airflow limitation, and visual scoring is time-consuming and prone to observer variability, other techniques are sought to start this phenotyping process. Quantitative computed tomography (CT) is a promising technique, because current CT technology is able to quantify emphysema, air trapping, and large airway wall dimensions. This review focuses on CT quantification techniques of COPD disease components and their current status and role in phenotyping COPD.

Pulmonary Perifissural Nodules on CT Scans: Rapid Growth Is Not a Predictor of Malignancy

PURPOSE To assess the prevalence, natural course, and malignancy rate of perifissural nodules (PFNs) in smokers participating in a lung cancer screening trial. MATERIALS AND METHODS As part of the ethics-committee approved Dutch-Belgian Randomised Lung Cancer Multi-Slice Screening Trial (NELSON), computed tomography (CT) was used to screen 2994 current or former heavy smokers, aged 50-74 years, for lung cancer. CT was repeated after 1 and 3 years, with additional follow-up CT scans if necessary. All baseline CT scans were screened for nodules. Nodule volume was determined with automated volumetric analysis. Homogeneous solid nodules, attached to a fissure with a lentiform or triangular shape, were classified as PFNs. Nodules were considered benign if they did not grow during the total follow-up period or were proved to be benign in a follow-up by a pulmonologist. Prevalence, growth, and malignancy rate of PFNs were assessed. RESULTS At baseline screening, 4026 nodules were detected in 1729 participants, and 19.7% (794 of 4026) of the nodules were classified as PFNs. The mean size of the PFNs was 4.4 mm (range: 2.8-10.6 mm) and the mean volume was 43 mm3 (range: 13-405 mm3). None of the PFNs were found to be malignant during follow-up. Between baseline and the first follow-up CT scan, 15.5% (123 of 794) were found to have grown, and 8.3% (66 of 794) had a volume doubling time of less than 400 days. One PFN was resected and proved to be a lymph node. CONCLUSION PFNs are frequently found at CT scans for lung cancer. They can show growth rates in the range of malignant nodules, but none of the PFNs in the present study turned out to be malignant. Recognition of PFNs can reduce the number of follow-up examinations required for the workup of suspicious nodules.

The relationship between lung function impairment and quantitative computed tomography in chronic obstructive pulmonary disease.

AbstractObjectivesTo determine the relationship between lung function impairment and quantitative computed tomography (CT) measurements of air trapping and emphysema in a population of current and former heavy smokers with and without airflow limitation.MethodsIn 248 subjects (50 normal smokers; 50 mild obstruction; 50 moderate obstruction; 50 severe obstruction; 48 very severe obstruction) CT emphysema and CT air trapping were quantified on paired inspiratory and end-expiratory CT examinations using several available quantification methods. CT measurements were related to lung function (FEV1, FEV1/FVC, RV/TLC, Kco) by univariate and multivariate linear regression analysis.ResultsQuantitative CT measurements of emphysema and air trapping were strongly correlated to airflow limitation (univariate r-squared up to 0.72, p < 0.001). In multivariate analysis, the combination of CT emphysema and CT air trapping explained 68-83% of the variability in airflow limitation in subjects covering the total range of airflow limitation (p < 0.001).ConclusionsThe combination of quantitative CT air trapping and emphysema measurements is strongly associated with lung function impairment in current and former heavy smokers with a wide range of airflow limitation.Key Points• CT helps to automatically assess lung disease in heavy smokers • CT quantitatively measures emphysema and small airways disease in heavy smokers • CT air trapping and CT emphysema are associated with lung function impairment

Towards a close computed tomography monitoring approach for screen detected subsolid pulmonary nodules

Pulmonary subsolid nodules (SSNs) have a high likelihood of malignancy, but are often indolent. A conservative treatment approach may therefore be suitable. The aim of the current study was to evaluate whether close follow-up of SSNs with computed tomography may be a safe approach. The study population consisted of participants of the Dutch-Belgian lung cancer screening trial (Nederlands Leuvens Longkanker Screenings Onderzoek; NELSON). All SSNs detected during the trial were included in this analysis. Retrospectively, all persistent SSNs and SSNs that were resected after first detection were segmented using dedicated software, and maximum diameter, volume and mass were measured. Mass doubling time (MDT) was calculated. In total 7135 volunteers were included in the current analysis. 264 (3.3%) SSNs in 234 participants were detected during the trial. 147 (63%) of these SSNs in 126 participants disappeared at follow-up, leaving 117 persistent or directly resected SSNs in 108 (1.5%) participants available for analysis. The median follow-up time was 95 months (range 20–110 months). 33 (28%) SSNs were resected and 28 of those were (pre-) invasive. None of the non-resected SSNs progressed into a clinically relevant malignancy. Persistent SSNs rarely developed into clinically manifest malignancies unexpectedly. Close follow-up with computed tomography may be a safe option to monitor changes. Persistent subsolid pulmonary nodules may be safely monitored with follow-up computed tomography http://ow.ly/CqWN1

Toward automatic regional analysis of pulmonary function using inspiration and expiration thoracic CT

PURPOSE To analyze pulmonary function using a fully automatic technique which processes pairs of thoracic CT scans acquired at breath-hold inspiration and expiration, respectively. The following research objectives are identified to: (a) describe and systematically analyze the processing pipeline and its results; (b) verify that the quantitative, regional ventilation measurements acquired through CT are meaningful for pulmonary function analysis; (c) identify the most effective of the calculated measurements in predicting pulmonary function; and (d) demonstrate the potential of the system to deliver clinically important information not available through conventional spirometry. METHODS A pipeline of automatic segmentation and registration techniques is presented and demonstrated on a database of 216 subjects well distributed over the various stages of COPD (chronic obstructive pulmonary disorder). Lungs, fissures, airways, lobes, and vessels are automatically segmented in both scans and the expiration scan is registered with the inspiration scan using a fully automatic nonrigid registration algorithm. Segmentations and registrations are examined and scored by expert observers to analyze the accuracy of the automatic methods. Quantitative measures representing ventilation are computed at every image voxel and analyzed to provide information about pulmonary function, both globally and on a regional basis. These CT derived measurements are correlated with results from spirometry tests and used as features in a kNN classifier to assign COPD global initiative for obstructive lung disease (GOLD) stage. RESULTS The steps of anatomical segmentation (of lungs, lobes, and vessels) and registration in the workflow were shown to perform very well on an individual basis. All CT-derived measures were found to have good correlation with spirometry results, with several having correlation coefficients, r, in the range of 0.85-0.90. The best performing kNN classifier succeeded in classifying 67% of subjects into the correct COPD GOLD stage, with a further 29% assigned to a class neighboring the correct one. CONCLUSIONS Pulmonary function information can be obtained from thoracic CT scans using the automatic pipeline described in this work. This preliminary demonstration of the system already highlights a number of points of clinical importance such as the fact that an inspiration scan alone is not optimal for predicting pulmonary function. It also permits measurement of ventilation on a per lobe basis which reveals, for example, that the condition of the lower lobes contributes most to the pulmonary function of the subject. It is expected that this type of regional analysis will be instrumental in advancing the understanding of multiple pulmonary diseases in the future.

Computer-aided Detection of Lung Cancer on Chest Radiographs: Effect on Observer Performance

PURPOSE To assess how computer-aided detection (CAD) affects reader performance in detecting early lung cancer on chest radiographs. MATERIALS AND METHODS In this ethics committee-approved study, 46 individuals with 49 computed tomographically (CT)-detected and histologically proved lung cancers and 65 patients without nodules at CT were retrospectively included. All subjects participated in a lung cancer screening trial. Chest radiographs were obtained within 2 months after screening CT. Four radiology residents and two experienced radiologists were asked to identify and localize potential cancers on the chest radiographs, first without and subsequently with the use of CAD software. A figure of merit was calculated by using free-response receiver operating characteristic analysis. RESULTS Tumor diameter ranged from 5.1 to 50.7 mm (median, 11.8 mm). Fifty-one percent (22 of 49) of lesions were subtle and detected by two or fewer readers. Stand-alone CAD sensitivity was 61%, with an average of 2.4 false-positive annotations per chest radiograph. Average sensitivity was 63% for radiologists at 0.23 false-positive annotations per chest radiograph and 49% for residents at 0.45 false-positive annotations per chest radiograph. Figure of merit did not change significantly for any of the observers after using CAD. CAD marked between five and 16 cancers that were initially missed by the readers. These correctly CAD-depicted lesions were rejected by radiologists in 92% of cases and by residents in 77% of cases. CONCLUSION The sensitivity of CAD in identifying lung cancers depicted with CT screening was similar to that of experienced radiologists. However, CAD did not improve cancer detection because, especially for subtle lesions, observers were unable to sufficiently differentiate true-positive from false-positive annotations.

Distribution of emphysema in heavy smokers: Impact on pulmonary function

PURPOSE To investigate impact of distribution of computed tomography (CT) emphysema on severity of airflow limitation and gas exchange impairment in current and former heavy smokers participating in a lung cancer screening trial. MATERIALS AND METHODS In total 875 current and former heavy smokers underwent baseline low-dose CT (30 mAs) in our center and spirometry and diffusion capacity testing on the same day as part of the Dutch-Belgian Lung Cancer Screening Trial (NELSON). Emphysema was quantified for 872 subjects as the number of voxels with an apparent lowered X-ray attenuation coefficient. Voxels attenuated <-950 HU were categorized as representing severe emphysema (ES950), while voxels attenuated between -910 HU and -950 HU represented moderate emphysema (ES910). Impact of distribution on severity of pulmonary function impairment was investigated with logistic regression, adjusted for total amount of emphysema. RESULTS For ES910 an apical distribution was associated with more airflow obstruction and gas exchange impairment than a basal distribution (both p<0.01). The FEV(1)/FVC ratio was 1.6% (95% CI 0.42% to 2.8%) lower for apical predominance than for basal predominance, for Tlco/V(A) the difference was 0.12% (95% CI 0.076-0.15%). Distribution of ES950 had no impact on FEV(1)/FVC ratio, while an apical distribution was associated with a 0.076% (95% CI 0.038-0.11%) lower Tlco/V(A) (p<0.001). CONCLUSION In a heavy smoking population, an apical distribution is associated with more severe gas exchange impairment than a basal distribution; for moderate emphysema it is also associated with a lower FEV(1)/FVC ratio. However, differences are small, and likely clinically irrelevant.