Peripheral pulmonary nodules: relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression

Abstract

Background: The aim of this study is to investigate the relationship between 16-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF (vascular endothelial growth factor) expression in patients with benign and malignant pulmonary nodules, and differential diagnosis between benign and malignant pulmonary nodules.

Methods: Sixty-four patients with benign and malignant pulmonary nodules underwent 16-slice spiral CT perfusion imaging. The CT perfusion imaging was analyzed for TDC (time density curve), perfusion parametric maps, and the respective perfusion parameters. Immunohistochemical findings of MVD (microvessel density) measurement and VEGF expression was evaluated.

Results: The shape of the TDC of peripheral lung cancer was similar to those of inflammatory nodule. PH (peak height), PHpm/PHa (peak height ratio of pulmonary nodule to aorta), BF (blood flow), BV (blood volume) value of peripheral lung cancer and inflammatory nodule were not statistically significant (all P > 0.05). Both showed significantly higher PH, PHpm/PHa, BF, BV value than those of benign nodule (all P < 0.05). Peripheral lung cancer showed significantly higher PS (permeability surface) value than that of inflammatory nodule and benign nodule (all P < 0.05). BV, BF, PS, MTT, PH, PHpm/PHa, and MVD among three groups of peripheral lung cancers were not significantly (all P > 0.05). In the case of adenocarcinoma, BV, BF, PS, PHpm/PHa, and MVD between poorly and well differentiation and between poorly and moderately differentiation were statistically significant (all P < 0.05). The peripheral lung cancers with VEGF positive expression showed significantly higher PH, PHpm/PHa, BF, BV, PS, and MVD value than those of the peripheral lung cancer with VEGF negative expression, and than those of benign nodule with VEGF positive expression (all P < 0.05). When investigating VEGF negative expression, it is found that PH, PHpm/PHa, and MVD of inflammatory nodule were significantly higher than those of peripheral lung cancer, PS of inflammatory nodule were significantly lower than that of peripheral lung cancer (all P < 0.05). PH, PHpm/PHa, BF, and BV of benign nodule were significantly lower than those of inflammatory nodule (all P < 0.05), rather than PS and MTT (mean transit time) (all P > 0.05). PH, PHpm/PHa, BV, and PS of benign nodule were significantly lower than those of peripheral lung cancer (all P < 0.05). In the case of VEGF positive expression, MVD was positively correlated with PH, PHpm/PHa, BF, BV, and PS of peripheral lung cancer and PS of benign nodule (all P < 0.05).

Conclusion: Multi-slice spiral CT perfusion imaging closely correlated with tumor angiogenesis and reflected MVD measurement and VEGF expression. It provided not only a non-invasive method of quantitative assessment for blood flow patterns of peripheral pulmonary nodules but also an applicable diagnostic method for peripheral pulmonary nodules.

Figure 1

Time density curve of peripheral lung cancer, inflammatory nodule, and benign nodule.

Figure 2

(A-H) Poorly differentiated adenocarcinoma found in the apicoposterior segment of superior lobe of the left lung of a 56 year-old male. (A) Time density curve. (B-F) (original image, BF, BV, MTT, PS) typeI parametric maps, PS value is higher (30.883). (G) CD34 staining shows many immature tumor microvessels (× 200). (H) VEGF expression is strong positive (× 400).

Figure 3

(A-H) Well differentiated squamous cell carcinoma found in the posterior basal segment of inferior lobe of the right lung of a 61-year-old male. (A) Time density curve. (B-F) (original image, BF, BV, MTT, PS) TypeII parametric maps, PS value is higher (27.051). (G) CD34 staining shows many immature tumor microvessels (× 200). (H) VEGF expression is strong positive (× 400).

Figure 4

(A-H) Inflammatory nodule found in segmentum basale anterius of inferior lobe of the right lung of a 46-year-old male. (A) Time density curve. (B-F) (original image, BF, BV, MTT, PS) TypeIII parametric maps, PS value was lower (5.63). (G) CD34 staining shows many expanded mature microvessels (× 200). (H) VEGF expression is negative (× 400).

Figure 5

(A-H) Tuberculoma found in apical segment of superior lobe of the right lung of a 39-year-old female. (A) Time density curve. (B-F) (original image, BF, BV, MTT, PS) typeI parametric maps, PS value was lower (6.81). (G) CD34 staining shows a few of more mature microvessels (× 200). (H) VEGF expression is negative (× 400).

Figure 6

(A-H) Hamartoma found in apicoposterior segment of superior of the left lung of a 54-year-old male. (A) Time density curve. (B-F) (original image, BF, BV, MTT, PS) type I parametric maps, PS value was moderate (12.029). (G) CD34 staining shows a few of more mature microvessels (× 200). (H) VEGF expression is negative (× 400).