| Part I Dynamic Enhanced MSCT Study and Correlation with Vascular Endothelial Growth Factor and Microvessel DensityObjective To evaluate SPNs and involved vessels relationship, enhancement patterns and characteristics of dynamic enhancement at MSCT; and investigate the characteristics correlation with VEGF and MVD,blood supply of SPNs enhancement, and its clinic value in differential diagnosis of SPNs as well.Material and methods 50 patients verified by pathology and 1 by clinic with SPNs (diameter≤4cm) underwent MSCT dynamic enhanced scans (included preenhanced, dynamic enhanced scans). Whole lung was scanned at 15s after contrast injection; CT scans through SPNs were obtained at 45s, 75s, 135s, 195s and 255s after onset of injection. Preenhancment, peak enhancement, net enhancement, S/A ratio (the ratio of the net enhancement of SPN over aorta), SPN–involved vessels relationship, enhancement patterns, time-density curves of SPNs were assessed. Pearson correlation coefficient was used to correlate peak enhancement, net enhancement with extent of VEGF and MVD.Results 1. Of 51 SPNs, 28 (54.9%) were proved malignant, and 23(45.1%) benign. The diameters of SPNs were as follows: 1~2cm in 11 patients, 2~3cm in 20 patients, 3~4cm in 20 patients. The locations were as follows: 17 in right upper lobe, 2 in right middle lobe, 15 in right lower lobe, 10 in left upper lobe, and 7 in left lower lobe.2. Malignant nodules showed significantly higher peak enhancement(mean attenuation, 69.9HU) than that of benign nodules(mean attenuation,51.7HU)(P <0.001). Net enhancement of malignant nodules(mean attenuation, 32.9HU) was significantly higher than that of benign nodules(mean attenuation, 17.2HU) (P <0.001). S/A ratio of malignant nodules(mean ratio, 17.95%)was significantly higher than that of benign nodules(mean ratio,10.83%). Attenuation on preenhancement was not significantly different for malignant(mean attenuation, 37.0HU) and benign nodules(mean attenuation, 34.4HU)(P=0.179).Net enhancement of 20HU was used as a cutoff value in differentiation of malignant and benign nodules, sensitivity for malignant nodules was 96.43%(27 of 28 malignant nodules), specificity was 69.57% (16 of 23 benign nodules), positive predictive value was 79.41%(27 of 34 malignant readings), negative predictive value was 94.12%(16 of 17 benign readings), accuracy was 84.31%(43 of 51 nodules).3. Significant difference was revealed in enhancement patterns between benign and malignant nodules. Homogeneous or tendency to homogeneous enhancement in 22 of 28 malignant nodules(78.57%), heterogeneous in 4 (14.29%), peripheral in 1(3.57%), no enhancement in 1(3.57%). And no enhancement in 12 of 23 benign nodules(52.17%), homogeneous in 4 (17.39%), capsular in 3(13.04%), peripheral in 1(4.35%), heterogeneous in 3(13.04%).Significant difference was revealed in SPN-involved vessels relationship between benign and malignant nodules. Vessels contained within nodule in 23 of 28 malignant nodules(82.14%), compressed by nodule in 4(14.29%), not related in 1 (3.57%). Vessels contained within nodule in 4 of 23 benign nodules(17.39%), compressed by nodule in 12 (52.17%), not related in 7 (30.43%).In 27 cases of vessels contained within nodule, homogeneous enhancement was revealed in 20, heterogeneous in 5, peripheral in 1, no enhancement in 1. In 16 cases of vessels compressed by nodule, homogeneous enhancement was revealed in 6, heterogeneous in 1, peripheral in 1, no enhancement in 5, capsular in 3. In 8 cases of vessels not related to nodule, heterogeneous enhancement was revealed in 1, no enhancement in 7.4. The expression of MVD and VEGF was significantly different between benign and malignant nodules. VEGF correlated positively with peak enhancement and net enhancement (peak enhancement r=0.505,P=0.014; net enhancement r=0.565,P=0.005) . MVD correlated significantly positively with peak enhancem- ent and net enhancement (peak enhancement r=0.819,P<0.001; net enhancement r=0.845,P<0.001).Conclusion Net attenuation is one of important indices in differential diagnosis of benign and malignant nodules. With cutoff value as 20HU, it shows high sensitivity, accuracy, positive and negative predictive values in differential diagnosis of benign and malignant nodules. Correlation between SPN-involved vessels relationship and enhancement patterns indicates blood supply of SPNs enhancement. MSCT dynamic enhancement reflected the level of SPNs angiogenesis.Part II Demonstration of Signs in Solitary Pulmonary Nodules by MSCT Multi-planar Reformation and Volume Rending TechniqueObjective To compare the demonstration of signs in solitary pulmonary nodules by MPR and VRT, and to evaluate the potential role of these signs in the diagnosis of benign and malignant nodules.Material and methods 51 cases of SPNs(diameter≤4cm) confirmed by pathology and clinic underwent dynamic enhancement. MPR and VRT were applied to demonstrate the signs. Then evaluated the display of 5 signs(deep lobulation, spinous protuberance, pleural indentation, nodule notch due to pleural indentation, the positive bronchus sign) by MPR combined with VRT. Counted the detection rate and frequency of 7 signs(deep lobulation, spinous protuberance, pleural indentation, nodule notch due to pleural indentation, vacuole sign, the positive bronchus sign, speculation) in malignant nodules and analyzed the difference in displaying 7 signs in benign and malignant SPNs.Results 1. On MPR images, the occurrence of signs(deep lobulation, spinous protuberance, pleural indentation, nodule notch due to pleural indentation, the positive bronchus sign) was higher than that on CT axial images. The amount was 1.65~3.75 times than that of CT axial scans. On MPR images, the occurrence of SPNs with 5 signs was higher than that on CT axial images, the difference was significant.2. The occurrence of signs in malignant nodules was as follows: deep lobulation(75%), the positive bronchus sign(75%), pleural indentation(67.9%), spinous protuberance(57.1%), nodule notch due to pleural indentation(53.6%), speculation(53.6%) , vacuole sign (21.4%). The occurrence of signs in benign nodules was as follows: the positive bronchus sign(30.4%), spinous protuberance(26.1%), pleural indentation(17.4%), speculation(17.4%), vacuole sign(13.0%), deep lobulation(13.0%), nodule notch due to pleural indentation(0). The potential role of 7 signs detection in malignant nodules was as follows: nodule notch due to pleural indentation, deep lobulation, pleural indentation, speculation, the positive bronchus sign, spinous protuberance, vacuole sign. Signs of deep lobulation, nodule notch due to pleural indentation, pleural indentation, speculation, spinous protuberance, the positive bronchus sign showed significant difference in detection of malignant and benign nodules, except vacuole sign. Signs occurred in malignant nodules more than in benign nodules. No sign of nodule notch due to pleural indentation was detected in benign nodules. 15 cases with notch due to pleural indentation of 19 malignant nodules with pleural indentation were revealed(78.95%). 3. On SPN-bronchus relationship types, type I occurred more in malignant than in benign nodules, significant difference was found (P=0.001); occurrence of type II,III,IV,V showed no significant difference between malignant and benign nodules.Conclusion MPR combined with VRT in thin-slice MSCT scans, significantly improves detection rate of signs in SPNs. Deep lobulation, nodule notch due to pleural indentation accurately demonstrate the malignacy. According to references and our study, more than 2 above signs indicate malignancy.Part III Assessment of Malignancy or Benign of SPNs with Morphology, Dynamic Enhancement and Combination Method by Receiver Operating Characteristive CurveObjective To compare the assessment of malignancy or benign of SPNs with morphology, dynamic enhancement and combination method by receiver operating characteristive curve(ROC). Material and methods 28 malignant and 23 benign nodules underwent preenhanced and dynamic enhanced MSCT scans, imaging technique was the same as part one and postprocessing as part two. Those complete clinical and pathological materials were collected. Preenhancement, dynamic enhancement and combination method were evaluated by 3 physicans, the results were analyzed by ROC.Results 1. Suspected and definite malignancy were united as malignancy, suspected and definite benign were united as benign. The mean sensitivity of preenhancement, dynamic enhancement and combination method was 61.90%,61.90%,83.33%, respectively. The mean specificity was 60.87%,68.11%,82.61%, the mean accuracy 61.44%,64.72%,83.00%. Preenhancement combined with dynamic enhancement greatly improved the sensitivity, specificity and accuracy.2. Area under ROC in preenhancement (mean, Az=0.703) showed no significant difference (P<0.05)with that in dynamic enhancement (mean, Az=0.751), concerning on assessment of malignancy and benign. Area under ROC in combination method (mean, Az=0.919) was larger than that in both preenhancemen(tmean, Az=0.703)and dynamic enhancement(mean, Az=0.751). Area under ROC in combination method reviewed by every physician had significant difference with that in preenhancement(P<0.05).Area under ROC in combination method reviewed by physician1 had significant difference with that in dynamic enhancement. Area under ROC in combination method reviewed by physician2,3 had no significant difference with that in dynamic enhancement(physician2, P=0.0836; physician3,P=0.0702).3. Area under ROC among every physician in preenhancement or dynamic enhancement or combination method showed no significant difference(P>0.1).Conclusion Morphology and dynamic enhancement have not obvious difference in assessment of malignancy and benign. But combination method greatly improves the assessment and accuracy. Therefore, preenhancement combined with dynamic enhancement provides more details on morphology and blood perfusion in SPNs, has higher detection rate than preenhancement or dynamic enhancement.
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