Nodule Enhancement and Metabolism

Perfusion and metabolism of malignant pulmonary nodules is qualitatively and quantitatively different from that of benign nodules. Contrast-enhanced CT can be used to differentiate between benign and malignant nodules because the intensity of enhancement is directly related to the vascularity of the nodule and therefore to the likelihood of malignancy [41-43]. This technique has recently been shown in a multi-institutional prospective trial to be useful for evaluation of nodules that are indeterminate in etiology after standard radiological evaluation [43]. Three-millimeter collimation images of the nodule are obtained before and after the intravenous administration of contrast (2 mL/sec; 300 mg iodine/mm; 420 mg iodine/kg). Serial 5-sec spiral acquisitions (3-mm collimation scans with 2-mm reconstruction intervals; 120 kVp, 280 mA, pitch of 1:1; standard reconstruction algorithm;

Figure 19 Benign pulmonary nodule. (A) Noncontrast computed tomography shows right lung nodule with attenuation value of 28 HU. (B) Contrast computed tomography shows no visual enhancement of nodule. Attenuation value measured 33 HU. The findings are consistent with a benign diagnosis. Note contrast in mediastinal vessels (arrow). (Courtesy of Tom Hartman, Mayo Clinic, Rochester, Minnesota.)

Figure 19 Benign pulmonary nodule. (A) Noncontrast computed tomography shows right lung nodule with attenuation value of 28 HU. (B) Contrast computed tomography shows no visual enhancement of nodule. Attenuation value measured 33 HU. The findings are consistent with a benign diagnosis. Note contrast in mediastinal vessels (arrow). (Courtesy of Tom Hartman, Mayo Clinic, Rochester, Minnesota.)

15-cm field of view) are performed at 1, 2, 3, and 4 min after the administration of contrast. Enhancement is determined by subtracting the precon-trast attenuation of the nodule from the maximal nodule attenuation after contrast administration. Typically, malignant nodules enhance more than 20 HU, while benign nodules enhance less than 15 HU [43] (Fig. 19). There are, however, several potential limitations to clinical application of this technique. Many nodules do not fulfill the selection criteria used in this study. For instance, nodules smaller than 5 mm in diameter and nodules that were not relatively spherical were excluded. Also, in some cases, it can be difficult to consistently reimage the nodule after contrast administration because of differences in the depth of inspiration. The technique does, however, have clinical utility: A nodule that enhances less than 15 HU is almost certainly benign (sensitivity 98%, specificity 58%, accuracy 77%) and can be managed conservatively with serial radiologic assessment. While the use of contrast-enhanced CT may reduce the number of benign nodules re sected, a significant proportion of benign nodules will enhance. Such nodules remain indeterminate in etiology and require additional radiologic evaluation, biopsy, or resection.

The use of CT nodule enhancement requires important attention to technical details. First, it is important to carefully follow the imaging protocol as outlined above. Second, with regard to obtaining region of interest (ROI) measurements, the circular or oval region of interest is centered on the image closest to the nodule equator and should comprise roughly 70% of the diameter of a nodule. All ROI measurements should be made on mediastinal window settings in order to to ensure that partial volume averaging is minimized. Careful inspection of the bronchovascular structures adjacent to the nodule will allow one to obtain ROI measurements at similar levels in the z axis of the nodule on serial scans. Third, this technique should only be performed on nodules that are relatively homogeneous in attenuation, without evidence of fat, calcification, cavitation, or necrosis. Finally, patients considered for this technique should be able to perform reproducible breath holds. In order to aid patients in performing reproducible breath holds, it is suggested to instruct them to ''take a small breath in and hold it'' (rather than a deep breath).

Positron emission tomography (PET) imaging is an alternative to contrast-enhanced CT. Metabolism of glucose is typically increased in malignant nodules compared to benign nodules. PET, using the D-glucose analog 18F-labeled 2-deoxy-D-glucose (FDG), can be used to image this increase in glucose metabolism, allowing differentiation of malignant from benign nodules (Fig. 20) [44-48]. Sensitivity, specificity, and accuracy for detection of malignancy in nodules 10 mm or greater in diameter is 96, 88, and 94%, respectively, with FDG PET imaging [44,47-53]. Because the probability of malignancy is high when a nodule has increased FDG uptake, these nodules should be either biopsied or resected. When FDG uptake by a nodule 10 mm or greater in diameter is low, it will almost certainly be benign. False-negative results are uncommon, but can occur with some carcinoid tumors and bronchi-oloalveolar cell carcinomas (Fig. 21) [54,55]. Limitations in spatial resolution can also result in false-negative studies when lesions smaller than 10 mm in diameter are evaluated [56]. The use of FDG PET as a single test has, however, been reported to be a better predictor of malignancy than standard clinical and morphologic criteria used in Bayesian analysis [51]. In an attempt to detect the small percentage of malignant nodules falsely designated benign after FDG PET imaging, serial radiological assessment for 2 years is performed on all nodules with low FDG uptake that are not biopsied or resected. Although the high specificity of PET imaging for benign lesions can substantially reduce the number of benign nodules resected, benign neoplasms and nodules due to

Lung Fluoro

Figure 20 Non-small-cell lung cancer manifesting as hypermetabolic nodule on [18F] fluorodeoxyglucose (FDG) positron emission tomographic scan. (A) Computed tomography shows small nodule in right upper lobe (arrow). Note marked emphysema-tous lung disease. (B) Axial positron emission tomographic image with [18F] fluoro-deoxyglucose shows increased FDG uptake within nodule (arrow) when compared to mediastinum. The findings are suggestive of malignancy and resection revealed lung cancer. M, mediastinum; V, vertebral body.

Figure 20 Non-small-cell lung cancer manifesting as hypermetabolic nodule on [18F] fluorodeoxyglucose (FDG) positron emission tomographic scan. (A) Computed tomography shows small nodule in right upper lobe (arrow). Note marked emphysema-tous lung disease. (B) Axial positron emission tomographic image with [18F] fluoro-deoxyglucose shows increased FDG uptake within nodule (arrow) when compared to mediastinum. The findings are suggestive of malignancy and resection revealed lung cancer. M, mediastinum; V, vertebral body.

Lung Fluoro

Figure 21 Bronchioloalveolar cell cancer manifesting as hypometabolic nodule on [18F] fluorodeoxyglucose (FDG) positron emission tomographic scan. (A) Computed tomography shows a poorly marginated right upper lobe nodule containing small focal lucencies. Appearance is suspicious for bronchioloalveolar cell cancer. (B) Axial positron emission tomographic image with [18F] fluorodeoxyglucose shows minimal FDG uptake within nodule (arrow) when compared to mediastinum. Findings are suggestive of benignity. Transthoracic needle aspiration biopsy was performed because of CT appearance and revealed bronchioloalveolar cell cancer. M, mediastinum; *, trachea. (From Ref. 65.)

Figure 21 Bronchioloalveolar cell cancer manifesting as hypometabolic nodule on [18F] fluorodeoxyglucose (FDG) positron emission tomographic scan. (A) Computed tomography shows a poorly marginated right upper lobe nodule containing small focal lucencies. Appearance is suspicious for bronchioloalveolar cell cancer. (B) Axial positron emission tomographic image with [18F] fluorodeoxyglucose shows minimal FDG uptake within nodule (arrow) when compared to mediastinum. Findings are suggestive of benignity. Transthoracic needle aspiration biopsy was performed because of CT appearance and revealed bronchioloalveolar cell cancer. M, mediastinum; *, trachea. (From Ref. 65.)

infection and inflammation (tuberculosis, histoplasmosis, rheumatoid arthritis, etc.) can result in false-positive diagnoses (Fig. 22).

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