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CT Scan Screening for Lung Cancer: Risk Factors for Nodules and Malignancy in a High-Risk Urban Cohort

Greenberg, Alissa K; Lu, Feng; Goldberg, Judith D; Eylers, Ellen; Tsay, Jun-Chieh; Yie, Ting-An; Naidich, David; McGuinness, Georgeann; Pass, Harvey; Tchou-Wong, Kam-Meng; Addrizzo-Harris, Doreen; Chachoua, Abraham; Crawford, Bernard; Rom, William N
BACKGROUND: Low-dose computed tomography (CT) for lung cancer screening can reduce lung cancer mortality. The National Lung Screening Trial reported a 20% reduction in lung cancer mortality in high-risk smokers. However, CT scanning is extremely sensitive and detects non-calcified nodules (NCNs) in 24-50% of subjects, suggesting an unacceptably high false-positive rate. We hypothesized that by reviewing demographic, clinical and nodule characteristics, we could identify risk factors associated with the presence of nodules on screening CT, and with the probability that a NCN was malignant. METHODS: We performed a longitudinal lung cancer biomarker discovery trial (NYU LCBC) that included low-dose CT-screening of high-risk individuals over 50 years of age, with more than 20 pack-year smoking histories, living in an urban setting, and with a potential for asbestos exposure. We used case-control studies to identify risk factors associated with the presence of nodules (n = 625) versus no nodules (n = 557), and lung cancer patients (n = 30) versus benign nodules (n = 128). RESULTS: The NYU LCBC followed 1182 study subjects prospectively over a 10-year period. We found 52% to have NCNs >4 mm on their baseline screen. Most of the nodules were stable, and 9.7% of solid and 26.2% of sub-solid nodules resolved. We diagnosed 30 lung cancers, 26 stage I. Three patients had synchronous primary lung cancers or multifocal disease. Thus, there were 33 lung cancers: 10 incident, and 23 prevalent. A sub-group of the prevalent group were stable for a prolonged period prior to diagnosis. These were all stage I at diagnosis and 12/13 were adenocarcinomas. CONCLUSIONS: NCNs are common among CT-screened high-risk subjects and can often be managed conservatively. Risk factors for malignancy included increasing age, size and number of nodules, reduced FEV1 and FVC, and increased pack-years smoking. A sub-group of screen-detected cancers are slow-growing and may contribute to over-diagnosis and lead-time biases.
PMCID:3388074
PMID: 22768300
ISSN: 1932-6203
CID: 171565

Reversed halo sign after radiofrequency ablation of a lung nodule

Mango, Victoria L; Naidich, David P; Godoy, Myrna C B
We report a case of the 'reversed halo sign' 6 weeks after radiofrequency ablation (RFA) of a lung neoplasm in an 80-year-old man. The 'reversed halo sign,' first described on computed tomography in cryptogenic organizing pneumonia, has later been described as being associated with a wide range of pulmonary pathologies, including paracoccidiodomycosis, tuberculosis, lymphomatoid granulomatosis, Wegener granulomatosis, invasive pulmonary fungal infections, and sarcoidosis. Although a number of computed tomography findings have been reported after RFA of both primary lung tumors and pulmonary metastases, this case demonstrates that the reversed halo sign may also occur after RFA
PMID: 21307780
ISSN: 1536-0237
CID: 139469

Lung pathologic findings in a local residential and working community exposed to world trade center dust, gas, and fumes

Caplan-Shaw, Caralee E; Yee, Herman; Rogers, Linda; Abraham, Jerrold L; Parsia, Sam S; Naidich, David P; Borczuk, Alain; Moreira, Andre; Shiau, Maria C; Ko, Jane P; Brusca-Augello, Geraldine; Berger, Kenneth I; Goldring, Roberta M; Reibman, Joan
OBJECTIVE: : To describe pathologic findings in symptomatic World Trade Center-exposed local workers, residents, and cleanup workers enrolled in a treatment program. METHODS: : Twelve patients underwent surgical lung biopsy for suspected interstitial lung disease (group 1, n = 6) or abnormal pulmonary function tests (group 2, n = 6). High-resolution computed axial tomography and pathologic findings were coded. Scanning electron microscopy with energy-dispersive x-ray spectroscopy was performed. RESULTS: : High-resolution computed axial tomography showed reticular findings (group 1) or normal or airway-related findings (group 2). Pulmonary function tests were predominantly restrictive. Interstitial fibrosis, emphysematous change, and small airway abnormalities were seen. All cases had opaque and birefringent particles within macrophages, and examined particles contained silica, aluminum silicates, titanium dioxide, talc, and metals. CONCLUSIONS: : In symptomatic World Trade Center-exposed individuals, pathologic findings suggest a common exposure resulting in alveolar loss and a diverse response to injury
PMID: 21860325
ISSN: 1536-5948
CID: 137445

Dual-energy MDCT: Comparison of pulmonary artery enhancement on dedicated CT pulmonary angiography, routine and low contrast volume studies

Godoy, Myrna C B; Heller, Samantha L; Naidich, David P; Assadourian, Bernard; Leidecker, Christianne; Schmidt, Bernhard; Vlahos, Ioannis
PURPOSE: The aim of this study was (a) to compare arterial enhancement in simultaneously acquired high- and low-kilovoltage images; and (b) to determine whether low tube-voltage imaging would permit PE evaluation on routine chest CT studies or CTPA studies performed with a low volume of contrast media. MATERIALS AND METHODS: We compared 20 CTPA studies (CTPA group), 20 routine thoracic CT studies (RT group) and 10 CTPA studies performed with reduced volume of contrast media (RC group). HU values were measured in all groups at 80kVp and 140kVp images in multiple pulmonary arterial segments bilaterally. The diagnostic quality of the central and peripheral vascular enhancement and the image noise were evaluated at both energies using a five-point scale. RESULTS: For all patients, the mean CT attenuation values were greater at 80kVp than 140kVp images (p<0.001). At 80kVp, CTPA group attenuation values were greater than RT group (p=0.03) with a similar trend at 140kVp (p=0.08). At both 140kVp and 80kVp, CTPA group attenuation values were greater than RC group (p=0.02 and p=0.03, respectively). Qualitative analysis showed that at 140kVp CTPA studies had better global image quality scores than RT (p=0.003) and RC (p=0.001) groups. However, at 80kVp, there was no significant difference of global image quality between CTPA and the other groups (p=0.4 and p=0.5, respectively). Although measurable image noise was greater at 80kVp than 140kVp (p<0.001), qualitative analysis revealed lower image noise at 80kVp images. CONCLUSION: DECT at 80kVp increases arterial enhancement in both CTPA and routine studies. For routine studies this results in central and peripheral enhancement quality equivalent to that of CTPA studies. Low tube-voltage imaging allows marked contrast volume reduction for CTPA. In selected cases, satisfactory lower radiation dose CT might be achievable using lower kVp imaging alone
PMID: 20149952
ISSN: 1872-7727
CID: 136990

Expert opinion: role of percutaneous biopsy of part-solid nodules in the IASLC/ATS/ERS international multidisciplinary classification of lung adenocarcinoma [Editorial]

Franks, Teri J; Galvin, Jeffrey R; Jett, James R; Naidich, David P; Boiselle, Phillip M
PMID: 21778873
ISSN: 0883-5993
CID: 470662

Imaging of incidental findings on thoracic computed tomography

Alpert, Jeffrey B; Naidich, David P
With continued improvement of high-resolution multidetector computed tomography imaging, there is an increasing number of unsuspected thoracic findings. Although many of these findings are of little clinical significance, other findings such as small incidental lung nodules require additional imaging to exclude more worrisome causes, often resulting in greater exposure to ionizing radiation, increased cost, and patient anxiety. Although greater uniformity among radiologists regarding likely benign findings may help reduce unnecessary imaging studies, the lack of clear follow-up guidelines for many findings suggests that further investigation is needed in some areas
PMID: 21333778
ISSN: 1557-8275
CID: 124103

Bronchoscopic fibered confocal fluorescence microscopy image characteristics and pathologic correlations

Filner, Joshua J; Bonura, Eric J; Lau, Stephanie T; Abounasr, Khader K; Naidich, David; Morice, Rodolfo C; Eapen, George A; Jimenez, Carlos A; Casal, Roberto F; Ost, David
BACKGROUND: Fibered confocal fluorescence microscopy (FCFM) is a new imaging modality in bronchoscopy. The purpose of this study was to assess FCFM reliability, interpretation, and to make image-pathologic correlations. METHODS: Twenty-six patients underwent FCFM. A validation set was used to determine image characteristics and interobserver reliability. Each patient underwent bronchoscopy using a standardized protocol. The images were evaluated by 4 observers based on brightness, fiber thickness, and alveolar cellularity. Image characteristics showing good interobserver agreement were tested to see if they were related to smoking status. Subsequently, 18 consecutive patients underwent FCFM and biopsy to correlate images with pathology. The blinded reviewers were asked to distinguish between controls and patients with pathologically proven disease. RESULTS: Interobserver agreement for image brightness, as measured by intraclass correlation coefficients (ICCs), ranged from 0.48 to 0.92 (P<0.001) and varied by location. ICCs for image brightness were high, ranging from 0.53 to 0.99 (P<0.001). Agreement for fiber thickness was poor for respiratory bronchioles (ICC 0.12, P<0.05) and fair for alveoli (ICC range, 0.37 to 0.42, P<0.001). The intraobserver (ICC range, 0.69 to 0.91, P<0.001) and intrapatient (ICC 0.65 to 0.84, P<0.001) reliability were excellent. Computer image interpretation showed excellent agreement with humans (ICC 0.62 to 0.99, P<0.001). Smoking was inversely associated with respiratory bronchiole brightness (P<0.001). In FCFM-pathologic correlation, FCFM could distinguish normal from diseased tissue; however, specific diseases could not be distinguished from other diseases. CONCLUSION: FCFM shows a high degree of image reliability and can detect changes in the respiratory bronchioles because of smoking and other diseases, but whether it can discriminate among diseases requires additional study.
PMID: 23169014
ISSN: 1948-8270
CID: 184982

A dynamic method for automated lung nodule morphology characterization [Meeting Abstract]

Stember J.; Naidich D.; Ko J.; Rusinek H.
Purpose: Many potential lung cancers start out as small pulmonary nodules showing up as incidental findings on chest radiograph or computed tomography (CT) scans. Diagnosis is confirmed via biopsy, usually involving broncoscopy or CT-guided biopsy. However, these are invasive procedures that expose patients to additional risks. An alternative mode of tumor detection lies in administering successive chest CT scans. This has the advantage of avoiding those risks associated with biopsy. Overall, there is growing evidence for the effectiveness of low-dose CT for lung cancer screening. Morphology is an important indicator of malignant potential for lung nodules detected at CT. Automated methods for morphology assessment have previously been described for breast cancer visualized on mammography [1]. The most common measure of nodule shape is area-to-perimeter-length ratio (APR), low APR values being associated with spiculated or lobulated shape. APR is a static measure and thus highly susceptible to alterations by random noise and artifacts in image acquisition. We introduce and analyze the self-overlap (SO) method as a dynamic automated morphological detection scheme. SO measures the rate of change of nodule masks as a function of the radius of the blurring kernel. In other words, SO measures the degree to which a nodule's shape changes or stays intact upon successive pixel averaging that blurs the original image. Irregularities at the surface mean that a significant number of high-attenuation pixels (representing solid nodular tissue) are surrounded by low-attenuation pixels (representing air). Averaging each pixel with its neighboring pixels thus serves to trim back lobulations and spiculations from a nodule image. Hence, comparedto smooth nodules, lobulated and spiculated nodules are subject to more of this trimming upon successive averaging, so that their shape changes more, resulting in lower SO values. Due to its dynamical nature, we hypothesized that SO is more resilient to random image noise than APR. Methods: In experiment 1 we compare our algorithm with APR for nodules simulated using a spherical harmonic model (degree = 0-7) rasterized and contaminated with random noise. In experiment 2 we compare the new measure with a consensus of two expert morphology ratings of 119 nodules from clinical CT exams. Results: Experiment 1 shows that both methods display the desired trend in that APR and SO both decrease with increasing spherical harmonic degree-meaning more lobulations. As such both methods serve as measures of surface smoothness. However, SO displays significantly greater robustness to CT image noise; for both methods, we calculate variability as standard deviation over mean. We find that APR's variability in the face of random noise is on the order of ten times that of SO. This finding suggests that SO is much more robust than APR to the effects of random noise. Using a logistic regression model, in experiment 2 we achieved 89.9% agreement with the consensus assessment of two expert radiologists, versus 87.4% for APR. Conclusion: Simulation nodules show that both our dynamic method (SO) and a representative static method (APR) for automated lung nodule surface morphology determination yield clear trends as functions of surface smoothness. Hence both methods can, with proper fitting and cutoff selection, yield faithful predictions that have over 80% agreement with expert assessment. However, when the simulation nodules are subjected to random noise, SO yields much more consistent and reproducible results than APR. Overall, we conclude that our method, due to its robustness to the random noise and CT artifacts that can plague nodule images, is well suited for clinical application
EMBASE:70493006
ISSN: 1861-6410
CID: 136629

Magnetic resonance imaging of mixed ground glass nodules [Meeting Abstract]

Koo C.W.; Chen Q.C.; Sigmund E.E.; Mcgorty K.; Mason D.M.; Naidich D.P.
Purpose: To evaluate mixed ground glass nodules (GGNs) utilizing 3 Tesla (T) MRI and 32-channel torso-array-coil and to correlate non-echo planar diffusion weighted imaging (DWI) and T2<sup>*</sup> measurements with pathologic findings. Materials and Methods: Twelve patients with 13 GGNs >1cm in diameter detected on computed tomography were prospectively recruited for this Institutional Review Board approved study. T1-weighted 2D gradient echo (GRE), T2-weighted 2D turbo spin echo with fat saturation, T2<sup>*</sup>-weighted multiple GRE, and diffusion weighted single shot twice-refocused spin echo axial images of the GGNs were acquired at end inspiration without intravenous contrast. Apparent diffusion coefficient (ADC) and T2<sup>*</sup> values were determined and correlated to pathology. Results: All GGNs were visualized with the T2-weighted 2D TSE sequence providing the best morphologic delineation. Pathology was available for 9 of 13 lesions. ADC ranged from 1.19 to 1.78 mum<sup>2</sup>/ms (mean 1.45+/-0.19) and T2<sup>*</sup> ranged from 6.78 to 27.81 mum<sup>2</sup>/ms (median 16.13, mean 16.68+/- 7.19) for the 7 malignant lesions. ADC was 1.59 and 1.42 and T2<sup>*</sup> was 6.78 and 20.24 for the 2 malignant lesions with positive epidermal growth factor receptors. ADC ranged from 0.9 to 1.47 mum<sup>2</sup>/ms (mean 1.18 +/-0.4) and T2<sup>*</sup> ranged from 6.87 to 10.93 (mean 8.9 +/-2.87) for the 2 benign lesions. Conclusion: 3T MRI with a 32-channel torso-array-coil provides a radiation free means of GGN evaluation. The T2-weighted 2D TSE with fat saturation sequence yields the best lesion visibility. DWI and T2<sup>*</sup> measurements may provide quantitative measures for distinguishing malignant from benign nodules
EMBASE:70506013
ISSN: 0883-5993
CID: 136977

Dual-energy computed tomography imaging of the aorta

Vlahos, Ioannis; Godoy, Myrna C B; Naidich, David P
There are 2 inseparable and complimentary technical advantages of dual-energy computed tomography (CT) imaging of the thoracic aorta. One advantage stems from the simultaneous availability of low and high peak kilovoltage (kVp) spectra data and, in particular, the benefits conferred by the improved conspicuity of iodinated contrast media at lower kVp CT imaging. This, in turn, permits improved aortic visualization or, alternatively, reduction in the volume or rate of contrast administration. Image noise at low kilovoltage does not appear to be a significant issue, with the backup availability of simultaneously acquired high kVp images a distinct advantage over single, low kVp imaging techniques. The second advantage of dual-energy CT imaging stems from the potential to calculate material-specific images derived mathematically from the simultaneous availability of attenuation measurements at 2 distinct energies. These material-specific data sets include virtual noncontrast images, virtual contrast, or 'bone-subtracted' angiographic-like images. These techniques may confer significant advantages in the evaluation of patients with aortic disease, improving interpretation and reducing reconstruction time, while potentially reducing the need for, and associated radiation burden of, precontrast or postcontrast multiphasic imaging
PMID: 21042067
ISSN: 1536-0237
CID: 114185