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ABSTRACT: Purpose:To characterize the variability in radiologists' interpretations of computed tomography (CT) studies in the National Lung Screening Trial (NLST) (including assessment of false-positive rates [FPRs] and sensitivity), to examine factors that contribute to variability, and to evaluate trade-offs between FPRs and sensitivity among different groups of radiologists.Materials and Methods:The HIPAA-compliant NLST was approved by the institutional review board at each screening center; all participants provided informed consent. NLST radiologists reported overall screening results, nodule-specific findings, and recommendations for diagnostic follow-up. A noncalcified nodule of 4 mm or larger constituted a positive screening result. The FPR was defined as the rate of positive screening examinations in participants without a cancer diagnosis within 1 year. Descriptive analyses and mixed-effects models were utilized. The average odds ratio (OR) for a false-positive result across all pairs of radiologists was used as a measure of variability.Results:One hundred twelve radiologists at 32 screening centers each interpreted 100 or more NLST CT studies, interpreting 72 160 of 75 126 total NLST CT studies in aggregate. The mean FPR for radiologists was 28.7% ± 13.7 (standard deviation), with a range of 3.8%-69.0%. The model yielded an average OR of 2.49 across all pairs of radiologists and an OR of 1.83 for pairs within the same screening center. Mean FPRs were similar for academic versus nonacademic centers (27.9% and 26.7%, respectively) and for centers inside (25.0%) versus outside (28.7%) the U.S. "histoplasmosis belt." Aggregate sensitivity was 96.5% for radiologists with FPRs higher than the median (27.1%), compared with 91.9% for those with FPRs lower than the median (P = .02).Conclusion:There was substantial variability in radiologists' FPRs. Higher FPRs were associated with modestly higher sensitivity.© RSNA, 2013.
Radiology 04/2013; · 5.73 Impact Factor
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ABSTRACT: ABSTRACT BACKGROUND: Partial volume averaging and tilt relative to the scan plane on transverse images limit the accuracy of CT airway wall thickness measurements, confounding assessment of the relationship between airway remodeling and clinical status in COPD. The purpose was to assess the effect of partial volume averaging and tilt corrections on airway wall thickness measurement accuracy and on relationships between airway wall thickening and clinical status in COPD. METHODS: Airway wall thickness measurements were obtained on transverse images from low dose CT examinations of 80 heavy smokers using the open-source program Airway Inspector. Measurements were corrected for partial volume averaging and tilt effects using an attenuation- and geometry-based algorithm, and compared with functional status. RESULTS: The algorithm reduced wall thickness measurements of smaller airways to a greater degree than larger airways, increasing the overall range. When restricted to analyses of airways with inner diameter smaller than 3.0 mm, for a theoretical airway of 2.0 mm inner diameter, the wall thickness decreased from 1.07 ± 0.07 mm to 0.29 ± 0.10 mm and square root of wall area decreased from 3.34 ± 0.15 mm to 1.58 ± 0.29 mm, comparable to histologic measurement studies. Corrected measurements had higher correlation with FEV1, differed more between BODE index scores, and explained a greater proportion of FEV1 variability in multivariate models. CONCLUSIONS: Correcting for partial volume averaging improves accuracy of airway wall thickness estimation, allowing direct measurement of the small airways to better define their role in COPD.
Chest 11/2012; · 5.25 Impact Factor
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Kyung Nyeo Jeon,
Jin Mo Goo,
Chang Hyun Lee,
Youkyung Lee,
Ji Yung Choo,
Nyoung Keun Lee,
Mi-Suk Shim,
In Sun Lee,
Kwang Gi Kim, David S Gierada,
Kyongtae T Bae
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ABSTRACT: The aim of this study was to evaluate whether a computer-aided diagnosis (CAD) system improves interobserver agreement in the interpretation of lung nodules at low-dose computed tomography (CT) screening for lung cancer.
Baseline low-dose screening CT examinations from 134 participants enrolled in the National Lung Screening Trial were reviewed by 7 chest radiologists. All participants consented to the use of their deidentified images for research purposes. Screening results were classified as positive when noncalcified nodules larger than 4 mm in diameter were present. Follow-up evaluation was recommended according to the nodule diameter: 4 mm or smaller, more than 4 to 8 mm, and larger than 8 mm. When multiple nodules were present, recommendations were based on the largest nodule. Readers initially assessed the nodule presence visually and measured the average nodule diameter manually. Revision of their decisions after reviewing the CAD marks and size measurement was allowed. Interobserver agreement evaluated using multirater κ statistics was compared between initial assessment and that with CAD.
Multirater κ values for the positivity of the screening results and follow-up recommendations were improved from moderate (κ = 0.53-0.54) at initial assessment to good (κ = 0.66-0.67) after reviewing CAD results. The average percentage of agreement between reader pairs on the positivity of screening results and follow-up recommendations per case was also increased from 77% and 72% at initial assessment to 84% and 80% with CAD, respectively.
Computer-aided diagnosis may improve the reader agreement on the positivity of screening results and follow-up recommendations in the assessment of low-dose screening CT.
Investigative radiology 06/2012; 47(8):457-61. · 4.85 Impact Factor
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ABSTRACT: To measure reader variability related to the evaluation of screening chest radiographs (CXRs) for findings of primary lung cancer.
From the National Lung Screening Trial (NLST), 100 cases were randomly selected from baseline CXR examinations for retrospective interpretation by 9 NLST radiologists; images with noncalcified lung nodules (NCNs) or other abnormalities suspicious for lung cancer as determined by the original NLST reader were oversampled. Agreement on the presence of pulmonary nodules and abnormalities suspicious for cancer and recommendations for follow-up were assessed by the multirater κ statistic.
The multirater κ statistic for interreader agreement on the presence of at least 1 NCN was 0.38. Rates at which readers reported the presence of at least 1 NCN ranged from 32% to 63% (mean, 41%); among 16 subjects with NCN and a cancer diagnosis within 1 year of the CXR examination, an average of 87% (range, 81% to 94%) of cases were classified as suspicious for cancer across all readers. The multirater κ for agreement on follow-up recommendations was 0.34; pairwise κ values ranged from 0.15 to 0.64 (mean, 0.36). For all subjects, readers recommended a follow-up procedure classified as high level (computed tomography, fluorodeoxyglucose-positron emission tomography, or biopsy) 42% of the time on average (range, 30% to 67%); this increased to 84% (range, 52% to 100%) when readers reported an NCN and 88% (range, 82% to 94%) for subjects with cancer.
Reader agreement for screening CXR interpretation and follow-up recommendations is fair overall but is high for malignant lesions.
Journal of thoracic imaging 05/2012; 27(4):249-54. · 1.42 Impact Factor
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ABSTRACT: To determine whether quantitative computed tomographic (CT) measurements of emphysema and airway dimensions are associated with lung cancer risk in a screening population.
Institutional review board approval and informed consent for the use of deidentified images were obtained. In this retrospective study, CT scans were analyzed from 279 participants in the CT screening arm of the National Lung Screening Trial who were diagnosed with lung cancer and 279 participants who were not diagnosed with lung cancer after a median follow-up period of 6.6 years. Quantitative CT measurements of emphysema and right upper lobe apical segmental and subsegmental airway dimensions, and multiple patient history-related variables, were compared between the two groups. Significant variables were tested in multivariate models for association with lung cancer by using multiple logistic regression.
The emphysema index of percentage upper lung volume less than -950 HU had the strongest association with lung cancer (mean, 10.7% [standard deviation, 13.5] in patients vs 7.2% [standard deviation, 10.4] in control subjects; P < .001), but the relationship was weak (R(2) = 0.015, P < .001, c = 0.57). No CT measures of emphysema had an association with lung cancer independent of the patient medical history variables. Airway dimensions were not associated with lung cancer.
Quantitative CT measurements of emphysema but not airway dimensions were only weakly associated with lung cancer, demonstrating no potential practical value for clinical risk stratification.
Radiology 09/2011; 261(3):950-9. · 5.73 Impact Factor
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ABSTRACT: To quantitatively characterize early emphysematous changes in the lung microstructure of current and former smokers with noninvasive helium 3 ((3)He) lung morphometry and to compare these results with the clinical standards, pulmonary function testing (PFT) and low-dose computed tomography (CT).
This study was approved by the local institutional review board, and all subjects provided informed consent. Thirty current and former smokers, each with a minimum 30-pack-year smoking history and mild or no abnormalities at PFT, underwent (3)He lung morphometry. This technique is based on diffusion MR imaging with hyperpolarized (3)He gas and yields quantitative localized in vivo measurements of acinar airway geometric parameters, such as airway radii, alveolar depth, and number of alveoli per unit lung volume. These measurements enable calculation of standard morphometric characteristics, such as mean linear intercept and surface-to-volume ratio.
Noninvasive (3)He lung morphometry was used to detect alterations in acinar structure in smokers with normal PFT findings. When compared with smokers with the largest forced expiratory volume in 1 second (FEV(1)) to forced vital capacity (FVC) ratio, those with chronic obstructive pulmonary disease had significantly reduced alveolar depth (0.07 mm vs 0.13 mm) and enlarged acinar ducts (0.36 mm vs 0.3 mm). The mean alveolar geometry measurements in the healthiest subjects were in excellent quantitative agreement with literature values obtained by using invasive techniques (acinar duct radius, 0.3 mm; alveolar depth, 0.14 mm at 1 L above functional residual capacity). (3)He lung morphometry depicted greater abnormalities than did PFT and CT. No adverse events were associated with inhalation of (3)He gas.
(3)He lung morphometry yields valuable noninvasive insight into early emphysematous changes in alveolar geometry with increased sensitivity compared with conventional techniques.
Radiology 09/2011; 260(3):866-74. · 5.73 Impact Factor
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ABSTRACT: To mathematically model the relationship between CT measurements of emphysema obtained from images reconstructed using different section thicknesses and kernels and to evaluate the accuracy of the models for converting measurements to those of a reference reconstruction.
CT raw data from the lung cancer screening examinations of 138 heavy smokers were reconstructed at 15 different combinations of section thickness and kernel. An emphysema index was quantified as the percentage of the lung with attenuation below -950 HU (EI950). Linear, quadratic, and power functions were used to model the relationship between EI950 values obtained with a reference 1 mm, medium smooth kernel reconstruction and values from each of the other 14 reconstructions. Preferred models were selected using the corrected Akaike information criterion (AICc), coefficients of determination (R2), and residuals (conversion errors), and cross-validated by a jackknife approach using the leave-one-out method.
The preferred models were power functions, with model R2 values ranging from 0.949 to 0.998. The errors in converting EI950 measurements from other reconstructions to the 1 mm, medium smooth kernel reconstruction in leave-one-out testing were less than 3.0 index percentage points for all reconstructions, and less than 1.0 index percentage point for five reconstructions. Conversion errors were related in part to image noise, emphysema distribution, and attenuation histogram parameters. Conversion inaccuracy related to increased kernel sharpness tended to be reduced by increased section thickness.
Image reconstruction-related differences in quantitative emphysema measurements were successfully modeled using power functions.
Medical Physics 08/2011; 38(8):4894-902. · 2.83 Impact Factor
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ABSTRACT: Imaging of the lungs in patients with asthma has evolved dramatically over the last decade with sophisticated techniques, such as computed tomography, magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography. New insights into current and future modalities for imaging in asthmatic patients and their application are discussed to potentially shed a clearer picture of the underlying pathophysiology of asthma, especially severe asthma, and the proposed clinical utility of imaging in patients with this common disease.
The Journal of allergy and clinical immunology 05/2011; 128(3):467-78. · 9.17 Impact Factor
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ABSTRACT: To measure reader agreement in determining whether lung nodules detected at baseline screening computed tomography (CT) had changed at subsequent screening examinations and to evaluate the variability in recommendations for further follow-up.
All subjects were enrolled in the National Lung Screening Trial (NLST), and each participant consented to the use of their de-identified images for research purposes. The authors randomly selected 100 cases of nodules measuring at least 4.0 mm at 1-year screening CT that were considered by the original screening CT reader to be present on baseline CT scans; nodules considered by the original reader to have changed were oversampled. Selected images from each case showing the entire nodule at both examinations were preloaded on a picture archiving and communication system workstation. Nine radiologists served as readers, and they evaluated whether the nodule was present at baseline and recorded the bidimensional measurements and nodule characteristics at each examination, presence or absence of change, results of screening CT, and follow-up recommendations (high-level follow-up, low-level follow-up, no follow-up).
On the basis of reviews during case selection, five nodules seen at follow-up were judged not to have been present at baseline; for 19 of the remaining 95 cases, at least one reader judged the nodule not to have been present at baseline. For the 76 nodules that were unanimously considered to have been present at baseline, 21%-47% (mean ± standard deviation, 30% ± 9) were judged to have grown. The κ values were similar for growth (κ = 0.55) and a positive screening result (κ = 0.51) and were lower for a change in margins and attenuation (κ = 0.27-0.31). The κ value in the recommendation of high- versus low-level follow-up was high (κ = 0.66).
Reader agreement on nodule growth and screening result was moderate to substantial. Agreement on follow-up recommendations was lower.
Radiology 02/2011; 259(1):263-70. · 5.73 Impact Factor
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Jeffrey J Atkinson,
Barbara A Lutey,
Yoko Suzuki,
Holly M Toennies,
Diane G Kelley,
Dale K Kobayashi,
Whitney G Ijem,
Gaetan Deslee,
Carla H Moore,
M Eileen Jacobs,
Susan H Conradi, David S Gierada,
Richard A Pierce,
Tomoko Betsuyaku,
Robert M Senior
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ABSTRACT: Matrix metalloprotease (MMP)-9 is an elastolytic endopeptidase produced by activated macrophages that may be involved in the development of human pulmonary emphysema and could be inhibited with existing compounds. Mouse models have demonstrated that excess MMP-9 production can result in permanent alveolar destruction.
To determine if MMP-9 causes cigarette smoke-induced emphysema using MMP-9 knockout mice and human samples.
Mouse lungs were analyzed for inflammation and airspace enlargement using a mainstream smoke-exposure model. Human macrophage mRNA was isolated from subjects with emphysema by laser capture microdissection. Human blood monocyte mRNA was isolated from subjects with greater than 30 pack-year smoking history. Human gene expression was determined by quantitative polymerase chain reaction and compared with emphysema severity determined by automated computed tomography analysis. Plasma Clara cell secretory protein and surfactant protein-D were quantified to measure ongoing lung injury.
Mice deficient in MMP-9 develop the same degree of cigarette smoke-induced inflammation and airspace enlargement as strain-matched controls. Macrophages are the predominant source of MMP-9 production in human emphysema specimens and similar quantities of macrophage MMP-9 mRNA is present in areas of lung with and without emphysema. Circulating monocytes produce more MMP-9 in individuals with advanced emphysema severity despite no correlation of MMP-9 with markers of ongoing lung damage.
These results suggest that MMP-9 in humans who smoke is similar to smoke-exposed mice, where MMP-9 is present in emphysematous lung but not correlated with the emphysema. To the degree that the mechanisms of emphysema in humans who smoke resemble the mouse model, these data suggest specific inhibition of MMP-9 is unlikely to be an effective therapy for cigarette smoke-induced emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT 00757120).
American Journal of Respiratory and Critical Care Medicine 11/2010; 183(7):876-84. · 11.08 Impact Factor
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ABSTRACT: Airway wall dimensions can be determined in vivo using transverse computed tomographic (CT) images, but the measurement of airway phantoms shows that the wall thickness is consistently overestimated for small airways. This phantom study was performed to derive and test corrections to the measurements on the basis of consideration of partial volume averaging and tilt effects.
A lung phantom with six polycarbonate tubes embedded in foam was scanned, and the cross-sectional dimensions of the tubes were determined using the full width at half maximum, zero crossing, and phase congruency edge detection methods. Equations were derived using the reported wall intensity to correct for partial volume averaging. Corrections for the overestimation of the wall thickness due to the tilt of the tube with respect to the CT z-axis were also derived.
All three methods (full width at half maximum, zero crossing, and phase congruency) overestimated the wall thickness of the small polycarbonate tubes. It was verified that two sources of error were partial volume averaging and tilt that was introduced when the phantom was positioned with tube axes at an angle to the CT z-axis. The corrections were applied to the measured tube wall dimensions and substantially reduced the deviation of the CT measurements from the true values.
Correcting for partial volume effects and airway tilt greatly increases the accuracy of simulated airway wall measurements in transverse CT images.
Academic radiology 10/2010; 17(12):1525-34. · 2.09 Impact Factor
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David S Gierada,
Jason C Woods,
Richard E Jacob,
Andrew J Bierhals,
Cliff K Choong,
Seth T Bartel,
Yulin V Chang,
Nitin A Das,
Cheng Hong,
Barbara A Lutey,
Jon H Ritter,
Thomas K Pilgram,
Joel D Cooper,
G Alexander Patterson,
Richard J Battafarano,
Bryan F Meyers,
Dmitriy A Yablonskiy,
Mark S Conradi
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ABSTRACT: To evaluate the use of inflation-fixed lung tissue for emphysema quantification with computed tomography (CT) and He magnetic resonance (MR) diffusion imaging.
Fourteen subjects representing a range of chronic obstructive pulmonary disease severity who underwent complete or lobar lung resection were studied. Computed tomographic measurements of lung attenuation and MR measurements of the hyperpolarized 3He apparent diffusion coefficient (ADC) in resected specimens fixed in inflation with heated formalin vapor were compared with measurements obtained before fixation.
The mean (SD) CT emphysema indices were 56% (17%) before and 58% (19%) after fixation (P = 0.77; R = 0.76). Index differences correlated with differences in lung volume (R = 0.47). The mean (SD) 3He ADCs were 0.40 (0.15) cm/s before and 0.39 (0.14) cm/s after fixation (P = 0.03, R = 0.98). The CT emphysema index and the 3He ADC were correlated before (R = 0.89) and after fixation (R = 0.79).
Concordance of CT and 3He MR imaging measurements in unfixed and inflation-fixed lungs supports the use of inflation-fixed lungs for quantitative imaging studies in emphysema.
Journal of computer assisted tomography 08/2010; 34(5):773-9. · 1.38 Impact Factor
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ABSTRACT: The purpose of this study was to assess the accuracy of emphysema measurements obtained from systematic samples of evenly spaced CT images compared with measurements obtained from the entire scan.
Evenly spaced transverse sections from the CT studies of 136 heavy smokers who underwent screening for lung cancer in the National Lung Screening Trial and of 112 subjects who underwent imaging before lung volume reduction surgery were sampled retrospectively. The samples were acquired both by selection of specific numbers of evenly spaced images and by selection of images at specific distance intervals. The percentage of lung pixels with attenuation below specific thresholds was used as an emphysema index. The image sample error was determined as the difference in emphysema index between the image samples and the entire scan.
The largest absolute image sample errors in the National Lung Screening Trial cohort with image sample sizes of five, 10, and 20 were 2.2, 0.8, and 0.5 index percentage points, respectively, at 1-mm section thickness (-960 HU threshold), and 2.6, 1.1, and 0.5 index percentage points at 5-mm section thickness (-930 HU threshold). The largest errors in the lung volume reduction surgery cohort for image sample sizes of five and 10 were 5.6 and 2.3 index percentage points at 8- to 10-mm section thickness (-900 HU threshold). Image sample errors were equivalent for the two sampling methods.
Systematic sampling resulted in very small errors in emphysema quantification and may be useful for decreasing radiation exposure in clinical research studies of emphysema.
American Journal of Roentgenology 03/2010; 194(3):585-91. · 2.78 Impact Factor
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David S Gierada
Journal of Magnetic Resonance Imaging 02/2010; 31(3):768. · 2.70 Impact Factor
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Gaetan Deslee,
Tracy L Adair-Kirk,
Tomoko Betsuyaku,
Jason C Woods,
Carla H Moore, David S Gierada,
Susan H Conradi,
Jeffrey J Atkinson,
Holly M Toennies,
John T Battaile,
Dale K Kobayashi,
G Alexander Patterson,
Michael J Holtzman,
Richard A Pierce
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ABSTRACT: Oxidative stress is widely proposed as a pathogenic mechanism for chronic obstructive pulmonary disease (COPD), but the molecular pathway connecting oxidative damage to tissue destruction remains to be fully defined. We suggest that reactive oxygen species (ROS) oxidatively damage nucleic acids, and this effect requires multiple repair mechanisms, particularly base excision pathway components 8-oxoguanine-DNA glycosylase (OGG1), endonuclease III homologue 1 (NTH1), and single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1), as well as the nucleic acid-binding protein, Y-box binding protein 1 (YB1). This study was therefore designed to define the levels of nucleic-acid oxidation and expression of genes involved in the repair of COPD and in corresponding models of this disease. We found significant oxidation of nucleic acids localized to alveolar lung fibroblasts, increased levels of OGG1 mRNA expression, and decreased concentrations of NTH1, SMUG1, and YB1 mRNA in lung samples from subjects with very severe COPD compared with little or no COPD. Mice exposed to cigarette smoke exhibited a time-dependent accumulation of nucleic-acid oxidation in alveolar fibroblasts, which was associated with an increase in OGG1 and YB1 mRNA concentrations. Similarly, human lung fibroblasts exposed to cigarette smoke extract exhibited ROS-dependent nucleic-acid oxidation. The short interfering RNA (siRNA)-dependent knockdown of OGG1 and YB1 expression increased nucleic-acid oxidation at the basal state and after exposure to cigarette smoke. Together, our results demonstrate ROS-dependent, cigarette smoke-induced nucleic-acid oxidation in alveolar fibroblasts, which may play a role in the pathogenesis of emphysema.
American Journal of Respiratory Cell and Molecular Biology 12/2009; 43(5):576-84. · 5.13 Impact Factor
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David S Gierada,
Andrew J Bierhals,
Cliff K Choong,
Seth T Bartel,
Jon H Ritter,
Nitin A Das,
Cheng Hong,
Thomas K Pilgram,
Kyongtae T Bae,
Bruce R Whiting,
Jason C Woods,
James C Hogg,
Barbara A Lutey,
Richard J Battafarano,
Joel D Cooper,
Bryan F Meyers,
G Alexander Patterson
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ABSTRACT: Computed tomography (CT) section thickness and reconstruction kernel each influence CT measurements of emphysema. This study was performed to assess whether their effects are related to the magnitude of the measurement.
Low-radiation-dose multidetector CT was performed in 21 subjects representing a wide range of emphysema severity. Images were reconstructed using 20 different combinations of section thickness and reconstruction kernel. Emphysema index values were determined as the percentage of lung pixels having attenuation lower than multiple thresholds ranging from -960 HU to -890 HU. The index values obtained from the different thickness-kernel combinations were compared by repeated measures analysis of variance and Bland-Altman plots of mean versus difference in all subjects, and correlated with quantitative histology (mean linear intercept, Lm) in a subset of resected lung specimens.
The effects of section thickness and reconstruction kernel on the emphysema index were significant (P < .001) and diminished as the index attenuation threshold was raised. The changes in index values from changing the thickness-kernel combination were largest for subjects with intermediate index values (10%-30%), and became progressively smaller for those with lower and higher index values. This pattern was consistent regardless of the thickness-kernel combinations compared and the HU threshold used. Correlations between the emphysema index values obtained with each thickness-kernel combination and Lm ranged from r = 0.55-0.68 (P = .007-.03).
The effects of CT section thickness and kernel on emphysema index values varied systematically with the magnitude of the emphysema index. All reconstruction techniques provided significant correlations with quantitative histology.
Academic radiology 11/2009; 17(2):146-56. · 2.09 Impact Factor
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David S Gierada,
Jason C Woods,
Andrew J Bierhals,
Seth T Bartel,
Jon H Ritter,
Cliff K Choong,
Nitin A Das,
Cheng Hong,
Thomas K Pilgram,
Yulin V Chang,
Richard E Jacob,
James C Hogg,
Richard J Battafarano,
Joel D Cooper,
Bryan F Meyers,
G Alexander Patterson,
Dmitriy A Yablonskiy,
Mark S Conradi
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ABSTRACT: To characterize the effect of diffusion time on short-range hyperpolarized (3)He magnetic resonance imaging (MRI) diffusion measurements across a wide range of emphysema severity.
(3)He diffusion MRI was performed on 19 lungs or lobes resected from 18 subjects with varying degrees of emphysema using three diffusion times (1.6 msec, 5 msec, and 10 msec) at constant b value. Emphysema severity was quantified as the mean apparent diffusion coefficient (ADC) and as the percentage of pixels with ADC higher than multiple thresholds from 0.30-0.55 cm(2)/sec (ADC index). Quantitative histology (mean linear intercept) was obtained in 10 of the lung specimens from 10 of the subjects.
The mean ADCs with diffusion times of 1.6, 5.0, and 10.0 msec were 0.46, 0.40, and 0.37 cm(2)/sec, respectively (P < 0.0001, analysis of variance [ANOVA]). There was no relationship between the ADC magnitude and the effect of diffusion time on ADC values. The mean linear intercept correlated with ADC (r = 0.91-0.94, P < 0.001) and ADC index (r = 0.78-0.92, P < 0.01) at all diffusion times.
Decreases in ADC with longer diffusion time were unrelated to emphysema severity. The strong correlations between the ADC at all diffusion times tested and quantitative histology demonstrate that ADC is a robust measure of emphysema.
Journal of Magnetic Resonance Imaging 10/2009; 30(4):801-8. · 2.70 Impact Factor
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ABSTRACT: The purpose of this study was to describe the effect of implementing an imaging quality assurance program on CT image quality in the Lung Screening Study component of the National Lung Screening Trial.
The National Lung Screening Trial is a multicenter study in which 53,457 subjects at increased risk of lung cancer were randomized to undergo three annual chest CT or radiographic screenings for lung cancer to determine the relative effect of use of the two screening tests on lung cancer mortality. Of the 26,724 subjects randomized to the CT screening arm of the National Lung Screening Trial, the Lung Screening Study randomized 17,309 through 10 screening centers. The others were randomized through the American College of Radiology Imaging Network. Quality assurance procedures were implemented that included centralized review of a random sample of 1,504 Lung Screening Study CT examinations. Quality defect rates were tabulated.
Quality defect rates ranged from 0% (section reconstruction interval) to 7.1% (reconstructed field of view), and most errors were sporadic. However, a recurrently high effective tube current-time product setting at one center, excessive streak artifact at one center, and excessive section thickness at one center were detected and corrected through the quality assurance process. Field-of-view and scan length errors were less frequent over the second half of the screening period (p < 0.01 for both parameters, two-tailed, paired Student's t test). Error rates varied among the screening centers and reviewers for most parameters evaluated.
Our experience suggested that centralized monitoring of image quality is helpful for reducing quality defects in multicenter trials.
American Journal of Roentgenology 09/2009; 193(2):419-24. · 2.78 Impact Factor
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ABSTRACT: The structure and integrity of pulmonary acinar airways and their changes in different diseases are of great importance and interest to a broad range of physiologists and clinicians. The introduction of hyperpolarized gases has opened a door to in vivo studies of lungs with MRI. In this study we demonstrate that MRI-based measurements of hyperpolarized (3)He diffusivity in human lungs yield quantitative information on the value and spatial distribution of lung parenchyma surface-to-volume ratio, number of alveoli per unit lung volume, mean linear intercept, and acinar airway radii-parameters that have been used by lung physiologists for decades and are accepted as gold standards for quantifying emphysema. We validated our MRI-based method in six human lung specimens with different levels of emphysema against direct unbiased stereological measurements. We demonstrate for the first time MRI images of these lung microgeometric parameters in healthy lungs and lungs with different levels of emphysema (mild, moderate, and severe). Our data suggest that decreases in lung surface area per volume at the initial stages of emphysema are due to dramatic decreases in the depth of the alveolar sleeves covering the alveolar ducts and sacs, implying dramatic decreases in the lung's gas exchange capacity. Our novel methods are sufficiently sensitive to allow early detection and diagnosis of emphysema, providing an opportunity to improve patient treatment outcomes, and have the potential to provide safe and noninvasive in vivo biomarkers for monitoring drug efficacy in clinical trials.
Journal of Applied Physiology 09/2009; 107(4):1258-65. · 3.75 Impact Factor
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ABSTRACT: To quantify regional gas trapping in the lung by using computed tomographic (CT)-determined specific gas volume and hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging in a porcine model of airway obstruction.
Four porcine lungs were removed after sacrifice for unrelated cardiac experiments, for which animal studies approval was obtained. Dynamic expiratory thin-section CT and (3)He MR imaging were performed during passive deflation from total lung capacity after obstructions were created with inverted one-way endobronchial exit valves in segmental or lobar bronchi to produce identifiable regions of trapped gas. Changes in specific gas volume were assessed from CT data for defined regions of interest within and outside of obstructed segments and for entire lobes. Helium 3 data were analyzed according to the corresponding regional signal reduction during expiration, compared with the total magnetic moment at each time point.
In 4.5 seconds of free collapse, volume decreased by 6% +/- 2 (standard error) and 53% +/- 3, respectively, in trapped-gas lobes and in unobstructed regions (P < .0001). Specific gas volume changed by 6% +/- 2 in areas of trapped gas and decreased by 56% +/- 3 in unobstructed regions, from 3.4 mL/g +/- 0.2 to 1.5 mL/g +/- 0.1 (P < .0001). The (3)He signal intensity decreased by 25% +/- 6 and 71% +/- 3, respectively, in trapped-gas and normal regions (P = .0008). In unobstructed regions, the percentage decreases in specific gas volume and (3)He signal intensity were not statistically different from one another (P = .89).
The results obtained from the model of gas trapping demonstrate that CT-determined specific gas volume and (3)He MR imaging can help identify and quantify the extent of regional trapped gas in explanted porcine lungs.
Radiology 08/2009; 253(2):380-9. · 5.73 Impact Factor
