[Correlation of blood flow assessed by CT perfusion imaging and microvascular ultrastructure in non-small cell lung cancer: a preliminary study].

OBJECTIVE: To investigate the correlation between blood flow assessed by CT perfusion imaging and characteristics of microvascular ultrastructure in non-small cell lung cancer (NSCLC). METHODS: twenty-eight patients with non-small cell lung cancer proven surgically and pathologically underwent perfusion CT examination. The patients were divided into a hyper-perfusion group and a hypo-perfusion group by the median value of blood flow, and then the differences of microvascular ultrastructure in the two groups were analyzed. RESULTS: The median BF value of the 28 patients was 36.40 ml×100 g(-1)×min(-1). Take this median value as the boundary, the group with hypo-perfusion showed a significantly lower BF value than the group with hyper-perfusion [(30.84 ± 4.79) ml×100 g(-1)×min(-1) vs. (49.67 ± 10.89) ml×100 g(-1)×min(-1), t = -5.925, P < 0.001]. The group with lymph node metastasis showed a significantly lower BF value than the group without lymph node metastasis [(30.78 ± 5.24) ml×100 g(-1)×min(-1) vs. (50.73 ± 11.16) ml×100 g(-1)×min(-1), t = 3.490, P = 0.015]. The maturity of microvessels of the hyper-perfusion group was higher than that of the hypo-perfusion group. Under the electron microscope, the microvessels in the hypo-perfusion group showed a more narrow lumen, poorer integrity of basement membrane, a more close relationship between cancer cells and microvascular wall, and cancer cells were more easily seen in the microvascular lumen. CONCLUSION: The blood flow value of CT perfusion imaging may be related with the abnormal microvascular ultrastructure, and may be helpful to the prediction of metastasis risk in NSCLC.

[Correlation between computed tomographic vascular convergence sign and enhancement value in patients with pulmonary nodules].

OBJECTIVE: To explore the correlation between computed tomographic (CT) vascular convergence sign and enhancement value in patients with pulmonary nodules. METHODS: A total of 708 consecutive patients with pulmonary nodule received dual-source CT scan from January 2010 to January 2012. They were divided into vascular convergence sign group (including 4 subgroups) and non-vascular convergence sign group. Then the correlation between CT vascular convergence sign and enhancement values was analyzed. RESULTS: The enhancement values in vascular convergence sign group were significantly higher than those in non-vascular convergence sign group ((27.6 ± 10.5) vs (3.2 ± 2.8) HU, P = 0.000). The CT enhancement values in lesions tended to increase with the number of connecting blood vessels. However, no significant differences existed among the subgroups (P > 0.05). The accuracy of vascular convergence sign for detection of pulmonary malignant nodules was 84.9%, 70.6% and 60.3% according to the standards of CT enhancement values ≥ 15, 20, 25 HU respectively. The sensibility, specificity and accuracy of determining pulmonary malignant nodules were 97.2%, 68.8% and 93.7% according to the standard of vascular convergence sign. The accuracy of determining pulmonary nodules' CT enhancement values ≥ 15 HU was 88.1% according to the standard of vascular convergence sign. CONCLUSION: Vascular convergence sign may be used to indicate the enhancement of pulmonary nodules when CT enhancement images are not available.

Low tumor blood flow assessed with perfusion CT correlates with lymphatic involvement in patients with stage T1b non-small cell lung cancer.

BACKGROUND: To investigate the correlation of computed tomography (CT) perfusion parameters and lymphatic involvement in patients with stage T1b non-small cell lung cancer (NSCLC). METHODS: Forty-six patients (30 men and 16 women; age range, 36-73 years; mean age, 57 years), with stage T1b non-small cell lung cancer, underwent perfusion CT before surgery. The correlations between CT perfusion parameters (blood flow, blood volume, peak enhancement intensity), tumor angiogenesis (microvessel density and maturity of microvessels of surgical specimens) and lymphatic involvement were retrospectively investigated. Receiver operator curve (ROC) analysis was used to identify the parameter threshold at which tumors had or did not have lymph node metastasis, and the corresponding sensitivity and specificity were calculated. RESULTS: A significant tendency for tumors with low blood flow and high density of immature microvessels to show lymphatic involvement was found (all P < 0.001). High correlation (r =-0.769, P < 0.001) was observed between tumor blood flow and immature microvessels. The area under ROC curves (AUC) for blood flow to detect lymph node metastasis was 0.866 (95% confidence interval, 0.766-0.966). For blood flow, the sensitivity, specificity, and accuracy of predicting lymph node metastasis were 88.9, 64.3, and 73.9% respectively, if the cutoff point was set at 43.05 mL/100 g/minute. CONCLUSIONS: Blood flow may be useful to predict lymphatic involvement before surgery in stage T1b NSCLC.

Lymphatic microvessel density combined with CT used in the diagnosis of mediastinal and hilar lymph node metastasis of non-small cell lung cancer.

BACKGROUND AND AIMS: Lymphatic microvessel density (LMVD) has been demonstrated to correlate with tumor metastasis. The purpose of this study is to determine whether the criteria combining LMVD with computed tomography (CT) could improve the diagnostic accuracy of lymph node (LN) metastasis in non-small cell lung cancer (NSCLC). METHODS: Ninety four patients with NSCLC who had chest CT scans preoperatively and LMVD tested by immunohistochemistry postoperatively were randomized into two groups: the training set (n = 66) and the test set (n = 28). Cut-off point of LMVD was selected to separate the LN metastasis-predictive positive and negative groups. On the basis of LMVD levels, chest CTs of the training set were re-analyzed and hypothetical criteria for LN metastasis diagnosis were established. Diagnostic characteristics for LN metastasis were tested by using the combined criteria in the test set as compared to those of CT alone. RESULTS: There was a significantly positive correlation between LMVD and LN metastasis (p <0.01). For sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV), accuracy was 67, 81, 75, 81 and 79% for the combined criteria, respectively. Diagnostic efficacy of the combined criteria was significantly higher than that of CT only (p <0.05). CONCLUSIONS: Diagnosis of LN metastasis using a combination of LMVD and CT is superior to the CT-only diagnosis. In future clinical trials, it is necessary to evaluate the efficacy of adjuvant therapy for the selection of patients according to the combined criteria.

[Relationship between multi-slice spiral CT pulmonary perfusion imaging and the expression of EphB4 and ephrinB2 in non-small cell lung cancer].

OBJECTIVE: To investigate the role of the expression of ephrinB2 and EphB4 in non-small cell lung cancer (NSCLC), and their relationship with multi-slice spiral CT pulmonary perfusion imaging. METHODS: Thirty-one nodules with pathologically proven NSCLC underwent CT perfusion scan. The perfusion parameters including blood flow (BF), blood volume (BV), peak enhancement image (PEI) were collected. The expression of ephrinB2 and EphB4 in tumor cells and interstitial vasculature were detected by immunohistochemistry. Correlation analysis and trend test were used to assess the relationship between ephrinB2/EphB4 expression and clinicopathological features, and between ephrinB2/EphB4 expression and perfusion parameters. RESULTS: Positive expression of ephrinB2 and EphB4 in the NSCLC group was 83.9% and 71.0%, respectively, significantly higher than that in the internal control group (P < 0.01). The expression of ephrinB2 and EphB4 was consistently in tumor parenchyma but differently in tumor vessels. The expressions of ephrinB2 and EphB4 were positively correlated with lymphatic metastasis (P < 0.05). The expression of EphB4 was negatively correlated with blood flow (BF) and blood volume (BV), respectively (P < 0.05). There was a significant positive correlation between ephrinB2 expression and BF (r = 0.516, P = 0.003), and a positive correlation between ephrinB2 expression and BV (r = 0.448, P = 0.013). The expressions of ephrinB2 and EphB4 were not correlated with PEI (P > 0.05). The values of BF and BV in the high and moderate EphB4 expression groups were significantly decreased compared with that in the negative group (P < 0.01). The value of BF in the high ephrinB2 expression group was significantly increased compared with that in the moderately positive group and negative group (P < 0.01). The value of BV in the high ephrinB2 expression group was significantly increased compared with that in the negative group (P < 0.01). CONCLUSION: The CT pulmonary perfusion imaging reflects the density difference of blood vessels with functional lumen, and such difference also depends on the quantity and quality of vasculature with functional lumen.

[Evaluating the short-term effect of gefitinib in advanced lung adenocarcinoma with positive EGFR-mutant by dual source volume perfusion CT].

OBJECTIVE: To investigate tumor vascularity by dual source volume perfusion computed tomography (VPCT) in advanced lung adenocarcinoma with positive EGFR-mutant and determine whether any of the VPCT parameters would predict the tumor response to gefitinib. METHODS: Twelve patients (5 males and 7 females, Median age: 53 years, range: 36 - 69 years) with advanced lung adenocarcinoma received VPCT scan. All patients with positive EGFR-mutant were confirmed by pathological biopsy. After a 6-week therapy of gefitinib, VPCT was repeated and the short-term effect evaluated by the RECIST criteria. The VPCT parameters (blood volume, blood flow and permeability surface) of 12 patients were compared with their differentiation grade and short-term effect. RESULTS: Short-term effects were poor in those cases in whom BF increased after a 6-week of targeted therapy (P = 0.030). BF and PS at pre-therapy were negatively correlated with differentiation grade (r = -0.603, -0.694, P = 0.038, 0.012). There was a negative correlation between the rate of BF decline and differentiation grade (r = -0.686, P = 0.029); a negative correlation existed between the trend of BF and RECIST criteria (r = -0.707, P = 0.010). But there was no significant correlation with differentiation grade (P = 0.059). If the BF decline was considered effective, the dual source VPCT could predict the effect of RECIST criteria. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of VPCT was 100%, 66.7%, 83.3%, 75% and 100% respectively. CONCLUSION: Dual source VPCT of advanced lung adenocarcinoma can assess effectively tumor vascularity and perfusion changes after the therapy of gefitinib. It is important in evaluating the response of targeted therapy in lung cancer.

Role of immature microvessels in assessing the relationship between CT perfusion characteristics and differentiation grade in lung cancer.

BACKGROUND AND AIMS: We undertook this study to investigate the association between CT perfusion characteristics and differentiation grade in lung cancer, as well as the pathological basis of this association. METHODS: Seventy three patients received CT perfusion scan and pathological biopsy, and 30 of them were available for comparison. In these 30 patients, the region detected with pathological biopsy was consistent with the region of interest of CT perfusion. We compared the CT perfusion parameters [blood volume (BV), blood flow (BF), and peak enhancement intensity (PEI)] of these patients with their differentiation grade of lung cancer and microvessel count, which includes microvessel density (MVD) and maturity. RESULTS: The lower the grade of differentiation of the nodules, the more drastically perfusion parameters decreased. BF was best correlated with differentiation grade (r = -0.845, p = 0.000), compared to BV and PEI (r = -0.674, -0.438, p = 0.000, 0.015, respectively). Poorly differentiated lung cancer showed significantly higher density of immature microvessels than that of highly differentiated lung cancer (p = 0.001). There was a correlation between the differentiation grade and the density of immature microvessels (r = 0.669, p = 0.000), but there was no significant correlation with MVD and the density of mature microvessel (r = 0.345, 0.269, p = 0.062, 0.150, respectively). The density of immature microvessels still increased with declining BF value in the nodules when the grade of differentiation of lung cancer was under control (r = -0.748, p = 0.000). CONCLUSIONS: CT perfusion characteristics are helpful to differentiate lung cancer differentiation, pathologically basing on the density of immature microvessels rather than MVD.

[Significance and mechanism of MSCT perfusion scan on differentiation of NSCLC].

OBJECTIVE: To determine the significance of MSCT perfusion scan on differentiation of NSCLC and to investigate its possible mechanisms. METHODS: Forty four NSCLC patients underwent CT perfusion scan by MSCT. Among them, 22 cases were selected to detected the two-dimensional tumor microvascular architecture phenotype (2D-TMAP), the relationships between CT perfusion parameters (BF, BV, PEI, TIP), and the differentiation of NSCLC were analysed by using the correlation analysis and trend test. Spearman correlation analysis was used to study the relationships between CT perfusion parameters, differentiation, and 2D-TMAP. RESULTS: The total BF, BV and PEI decreased with decreasing differentiation of NSCLC (P<0.05). The total PEI showed a positive correlation with the total MVD (P<0.05). There were negative correlations between the surrounding area BF, the total BF, BV, and PEI, the uncomplete lumen of the surrounding area MVD, and expression of PCNA, respectively (P<0.05). There were positive correlations between degree of differentiation and the uncomplete lumen of the surrounding area MVD (P<0.05). It was the same as degree of differentiation and expression of PCNA, VEGF, respectively. There were positive correlations between the uncomplete lumen of the surrounding area MVD and expression of VEGF, ephrinB2, EphB4, and PCNA, respectively (P<0.05). CONCLUSION: Perfusion parameters reflect the difference of density of vassels with mature functional lumen. Careful evaluation of the differences of blood flow pattern in pulmonary space-occupying lesions by MSCT perfusion scan can be used to identify the degree of NSCLC differentiation.

[Mesh structure of two-dimensional tumor microvascular architecture phenotype heterogeneity in non-small cell lung cancer].

OBJECTIVE: To investigate the structural characteristics and clinical significance of two-dimensional tumor microvascular architecture phenotype (2D-TMAP) in non-small cell lung cancer (NSCLC). METHODS: Thirty surgical specimens of NSCLC were collected. The sections of the tumor tissues corresponding to the slice of CT perfusion imaging were selected to construct the 2D-TMAP expression. Spearman correlation analysis was used to examine the relation between the 2D-TMAP expression and the clinicopathological features of NSCLC. RESULTS: A heterogeneity was noted in the 2D-TMAP expression of NSCLC. The microvascular density (MVD) in the area surrounding the tumor was higher than that in the central area, but the difference was not statistically significant. The density of the microvessels without intact lumen was significantly greater in the surrounding area than in the central area (P=0.030). The total MVD was not correlated to tumor differentiation (r=0.042, P=0.831). The density of the microvessels without intact lumen in the surrounding area was positively correlated to degree of tumor differentiation and lymph node metastasis (r=0.528 and 0.533, P=0.041 and 0.028, respectively), and also to the expressions of vascular endothelial growth factor (VEGF), ephrinB2, EphB4, and proliferating cell nuclear antigen (PCNA) (r=0.504, 0.549, 0.549, and 0.370; P=0.005, 0.002, 0.002, and 0.048, respectively). The degree of tumor differentiation was positively correlated to PCNA and VEGF expression (r=0.604 and 0.370, P=0.001 and 0.048, respectively), but inversely to the integrity of microvascular basement membrane (r=-0.531, P=0.033). CONCLUSION: The 2D-TMAP suggests the overall state of the micro-environment for tumor growth. The 2D-TMAP of NSCLC regulates angiogenesis and tumor cell proliferation through a mesh-like structure, and better understanding of the characteristics and possible mechanism of 2D-TMAP expression can be of great clinical importance.