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PLENARY SESSION |
1 From the Department of Diagnostic Radiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905. From the Plenary Session, Friday Imaging Symposium: Algorithmic Controversies, at the 1999 RSNA scientific assembly. Received March 8, 2000; revision requested April 7 and received April 28; accepted April 28. Address correspondence to the author (e-mail: swensen.stephen@mayo.edu).
Index Terms: Lung, nodule, 60.281 • Lung neoplasms, CT, 60.12112, 60.12115, 60.12117 • Lung neoplasms, diagnosis, 60.30
Introduction
Evaluation of the solitary pulmonary nodule remains a significant and costly challenge in modern medicine. Approximately 50% of indeterminate lung nodules that undergo surgery for diagnosis are benign (1–4). Hospitalization for surgical removal of a nodule costs about $25,000 (5). A means short of biopsy by which diagnostic radiologists can help substantially reduce the percentage of benign nodules that undergo surgery for diagnosis is desirable.
Functional or dynamic imaging of lung nodules can be performed with many modalities. With computed tomography (CT), measurement of nodule growth and measurement of nodule enhancement could be considered examples of dynamic or functional imaging.
CT Measurement of Nodule Growth
Observation of nodule growth is an important and useful means of monitoring some selected lung nodules, particularly those that are smaller and those in patients at lower risk for malignancy (6,7). By using the volumetric data from spiral CT, it is possible to develop computer programs that allow nodule segmentation and three-dimensional rendering. These techniques should prove more accurate than manual two-dimensional measurement and should be useful in observing indeterminate lung nodules over periods of months. These computerized analysis techniques promise to be much more reproducible than manual two-dimensional methods and more sensitive to small changes in volume, which are not as readily detectable at analysis of serial two-dimensional images (6,7).
CT Measurement of Nodule Enhancement
CT measurement of nodule enhancement with iodinated contrast media is another example of dynamic or functional imaging. There are distinct differences in the vascularity and vasculature of benign and malignant modules (8–21) (Figs 1, 2). These differences may offer an opportunity to distinguish benign from malignant lung nodules by using radiologic imaging technology. Researchers have shown, with every modality at their disposal, that lung malignancies enhance more than benign lung nodules. This difference has been shown with angiography (10,13,14,17,22), contrast material–enhanced conventional tomography (23), 2-[fluorine-18]fluoro-2-deoxy-d-glucose positron emission tomography (24–27), gadolinium-enhanced magnetic resonance imaging (28,29), Doppler ultrasonography (30,31), and contrast-enhanced CT (32–34) (Figs 3, 4). Others have shown that differential nodule enhancement may help distinguish benign from malignant lesions in the breast (35,36), adrenal gland (37), and kidney (38). Are any of these techniques accurate enough in differentiation of benign from malignant lung nodules to be clinically useful?
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15 HU) at CT is strongly predictive of benignity (39). Seven centers participated in the study. Five hundred fifty indeterminate lung nodules were studied. Of these, 356 met all entrance criteria and were diagnosed as either benign or malignant nodules. On nonenhanced thin-section CT, the nodules were solid, 5–40 mm in diameter, relatively spherical, homogeneous, and without calcification or fat.
All patients were studied with 3-mm-collimation CT before and after intravenous injection of contrast material (injection rate, 2 mL/sec; iodine concentration, 300 mg/mL or 420 mg/kg). CT scans through the nodule were obtained 1, 2, 3, and 4 minutes after the onset of injection. The peak net nodule enhancement and time-attenuation curves were analyzed. An enhancement threshold of 15 HU defined a negative test result for malignancy.
The prevalence of malignancy was 48% (171 of 356 nodules). The median diameter of malignant nodules (17 mm) was significantly higher than that of benign nodules (13 mm) (P < .0001). The enhancement of malignant neoplasms (median, 38 HU; range, 14–165 HU) was significantly greater than that of granulomas and benign neoplasms (median, 10 HU; range, -20 to 96 HU) (P < .0001). With 15 HU as the threshold, the sensitivity was 98% (167 of 171 malignant nodules), specificity was 58%, and accuracy was 77% (39).
The results of this multicenter study corroborate the hypothesis that absence of significant lung nodule enhancement (15 HU) at CT is strongly predictive of benignity.
With spiral CT, it is now possible to perform both the lung nodule enhancement technique and an optimally contrast-enhanced CT examination of the chest and abdomen with the same injection of contrast material. Such a study is performed as follows: A spiral series of scans through the chest is obtained after a delay of 20 seconds from the onset of injection. Then, at 1 minute after the onset of injection, 3-mm-collimation spiral imaging through the nodule with a 1-mm reconstruction interval is performed for 5 seconds. Between the 1- and 2-minute scans of the nodule, spiral images are obtained through the lower chest and upper abdomen. This step allows scanning of the liver during optimal enhancement. Finally, spiral sections through the nodule are obtained at 2, 3, and 4 minutes. It is possible to perform this sequence without tube overheating. The vast majority of patients are able to tolerate the injection and breath-holding regimen.
We have found this method to be useful for optimizing CT evaluation of the chest and abdomen in patients with indeterminate nodules when there is a clinical suspicion of primary lung cancer. The combination of a contrast-enhanced CT study of the chest and abdomen with the lung nodule enhancement protocol does not add expense or substantial time (<5 minutes) to the complete examination.
The low false-negative rate of the CT nodule enhancement technique makes it potentially valuable in case management. A primary objective is to avoid misclassifying malignant lesions as benign. A nonenhancing lung nodule could be managed with radiologic surveillance alone (in a supportive clinical situation). Enhancing nodules, with the associated higher likelihood of malignancy, could be managed with biopsy or surgical removal. Because of the relatively low specificity, enhancing nodules may be appropriately managed with radiologic surveillance in a clinical situation in which the physician's clinical suspicion is extraordinarily low.
It may be most prudent to use the CT lung nodule enhancement technique for nodules with a diameter of 2.0 cm or less. Smaller nodules have a higher likelihood of benignity (40), are more difficult to sample successfully with transthoracic needle biopsy (41), and are less likely to contain substantial regions of necrosis, which could result in false-negative findings at CT enhancement studies (42).
Conclusions
Functional or dynamic imaging of lung nodules with CT may be clinically useful. Measurement of nodule growth with serial CT by using computerized segmentation and volume-rendering techniques looks promising. Stability of a nodule is strongly predictive of benignity. The CT lung nodule enhancement technique may be clinically useful in evaluation of indeterminate lung nodules. Absence of significant enhancement is strongly predictive of benignity.
References
3.0 cm) renal parenchymal tumor: detection, diagnosis, and controversies. Radiology 1991; 179:307-317.This article has been cited by other articles:
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  R. Yuan, P. M. Vos, and P. L. Cooperberg Computer-Aided Detection in Screening CT for Pulmonary Nodules. Am. J. Roentgenol., May 1, 2006; 186(5): 1280 - 1287. [Abstract] [Full Text] [PDF]
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 E. A. Hoffman and D. Chon Computed Tomography Studies of Lung Ventilation and Perfusion Proceedings of the ATS, December 1, 2005; 2(6): 492 - 498. [Abstract] [Full Text] [PDF]
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 J. P. Ko, H. Rusinek, E. L. Jacobs, J. S. Babb, M. Betke, G. McGuinness, and D. P. Naidich Small Pulmonary Nodules: Volume Measurement at Chest CT--Phantom Study Radiology, September 1, 2003; 228(3): 864 - 870. [Abstract] [Full Text] [PDF]
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