Solitary pulmonary nodules: comparison of multi-slice computed tomography perfusion study with vascular endothelial growth factor and microvessel density

Abstract

Background: The solitary pulmonary nodule (SPN) is one of the most common findings on chest radiographs. The objectives of clinical practice are to differentiate malignant nodules from benign nodules in the least invasive way and to make a specific diagnosis. This study was aimed to evaluate the correlation between perfusion imaging features and microvessel density (MVD) and vascular endothelial growth factors (VEGF) in SPNs using multi-slice computed tomography (MSCT); and to provide the theoretical basis for SPN blood flow pattern and blood flow quantitative features. Also, the study called for the discussion of the method's clinical application value in the differential diagnosis of benign and malignant SPNs.

Methods: Sixty-eight patients with SPN underwent multi-location dynamic contrast enhanced (nonionic contrast material was administrated via the antecubital vein at a rate of 4 ml/s) MSCT. Precontrast and postcontrast attenuations on every scan was studied. Perfusion, peak height, and the ratio of the peak height of the SPN to that of the aorta were analyzed. Perfusion was calculated using the maximum gradient of the time-density curves (TDC) and the peak height of the aorta. The quantitative parameters (perfusion, peak height, ratio of peak height of the SPN to that of the aorta) of the blood flow pattern were compared with MVD and the VEGF expression of immunohistochemistry.

Results: The perfusion peak heights of malignant ((96.15 +/- 11.55) HU) and inflammatory ((101.15 +/- 8.41) HU) SPNs were significantly higher than those of benign ((47.24 +/- 9.15) HU) SPNs (P < 0.05, P < 0.05). Ratios of SPN-to-aorta of malignant and inflammatory SPNs were significantly higher than those of benign SPNs (P < 0.05, P < 0.05). No significant differences were found between the peak height and SPN-to-aorta ratio of malignant SPNs and inflammatory SPNs (P > 0.05, P > 0.05). The precontrast densities of inflammatory SPNs were lower than those of malignant SPNs (P < 0.05). Perfusion values of malignant and inflammatory SPNs were significantly higher than those of the benign SPNs (P < 0.05, P < 0.05). The VEGF positive expressions appeared in 32 patients with malignant SPNs and 2 patients with benign SPNs, and the average value of the MVD was higher in patients with malignant SPNs (36.88 +/- 6.76) than in patients with either benign (4.51 +/- 0.60) or inflammatory (26.11 +/- 5.43) SPNs (P < 0.05, P < 0.05). There were statistically significant correlations between the CT perfusion feature and the MVD. The highest correlation was between the peak height of SPN and the MVD (r = 0.657, P < 0.05).

Conclusions: Tumor microvessel density and VEGF expression facilitate the exploration of the pathophysiological basis of CT perfusion in SPNs. Multi-slice CT perfusion has shown strong positive correlations with angiogenesis in SPNs.