The Differentiai Diagnostic Value Of¹⁸F-FDG PET-CT Double Phase Imaging Tombination With Diagnosis CT Scan For Solitary Pulmonary Nodules

BackgroundWith the availability of low-dose spiral CT scan of the lung, the little solitary pulmonary nodules that was difficult to detect on conventional chest radiographs has increasingly been detected. It is difficult to be differential diagnosis for radiology doctor. For nonselected populations, a newly presenting SPNs on chest radilgraphy has a20-40%likelihood of being malignant. In two thirds of cases, both CT and chest X-rays are unable to differentiate between benign and malignant lesions on the basis of calcifications or density features alone. Therefore, early diagnosis of malignant lesions is mandatory to promptly intiate appropriate treatment. In the past decade,18F-FDG PET and18F-FDG PET-CT has been proven value in metabolic characterization of SPNs, and avoid the unessential surgery.However, fluorodeoxyglucose (FDG) is not a cancer-specific agent, and false positive findings in benign diseases have been reported in active inflammation or infection, tuberculoma, lung benign neoplasm (including pulmonary sclerosing haemangiomas), because some cells such as neutrophil and macrophages show increased FDG accumulation[19], but the mechanism of enhanced uptake of FDG in PSH is still unknown.The CT of the integrate PET-CT is the multidetector, and it is important in the diagnosis value. Now, more and more doctor believe the CT in the integrate PET-CT can help them to avoid the false-positive and false-negative. Howere, to our knowledge, few studys has reported18F-FDG PET-CT double stage imaging combined with lesion-diagnosis contrast CT scan findings in SPNs and18F-FDG PET-CT double stage imaging combined with HRCT finding in GGNs.This study paid main attention to the differential diagnostic value of double-phase imaging and diagnosis CT in SPNs. The two parts below were included:1)The differential diagnostic value of18F-FDG PET-CT double stage imaging combination with HRCT for solitary pulmonary ground-glass nodules (including pure ground-glass nodules and mixed ground-glass nodules).2) The differential diagnostic value of18F-FDG PET-CT double stage imaging combination with lesion-diagnosis contrast CT scan for solitary pulmonary solid nodules.The innovation of the study as the follows:1)△T/Nmax was the first time to use for the diagnosis of ground-glass nodules in18F-FDG PET-CT imaging.2) The way of double-time point18F-FDG PET-CT combinate with multi-phase contrast-enhanced neoplasm-diagnosis CT scan was the first time used to diagnosis of the solid solitary pulmonary nodules.3) The morphology of uptake in18F-FDG was used to diagnosis the solitary pulmonary nodules at the first time. PART IThe differential diagnostic value of18F-FDG PET-CT double stage imaging combination with HRCT for solitary pulmonary ground-glass nodulesObjective:Compared the18F-FDG PET-CT double stage imaging and HRCT features of the ground-glass nodules with the pathology, to study the statistical analysis of the malignant ground-glass nodules.Methods:This was a prospective study.63patients who were referred for18F-FDG PET-CT to determine the SPNs in July2010to February2013including51malignancy nodules (22males and29females, the mean age was55.9±16.7years),12benign nodules (7males and5females, the mean age was51.3±10.4years). Including38pGGNs (28of malignant nodules,10of benign nodules),25mGGNs (23of malignant nodules,2of benign nodules). With the consent of patients, HRCT was sacned after the delay time at the same day. The diagnosis of PET-CT only and PET-CT combination with HRCT was made by two doctors individually who had a knowledge with unuclear medicine and radiology. When they had the different idea, they should decide after discussion.To measure the SUVmax of the double-time point, compulate RI, compulate the diagnosis criterion of different SUVmax and RI for the GGNs, compulate Youden index, and select the best dignosis criterion. To compulate the SUVmax of different pathology type, and examine the statistical significance of the t-test.Results:1. The clinical value of double time-point18F-FDG PET-CT for GGNs(1) The clinical value of double time-point18F-FDG PET-CT for pGGNsThe sensitivity and specificity and accuray and Youden index of early imaging in pGGNs were75.0%and90%and78.9%and0.650; of SUVmax≥1.5and SUVmax≥2.0and SUVmax≥2.5in early imaging in pGGNs, the specificity were100%for the all criterion, the sensitivity were32.1%and17.9%and14.3%individually, the accuracy were50%and39.5%and36.8%individually, the Youden index were0.321and0.179and0.143. The Youden index of SUVmax≥0.8was0.450, the sensitivity and specificity and accuracy were75.0%and70.0%and78.9%individually. The Youden index of SUVmax≥1.0was higher and it has higher specificity, and the sensitivity was good, so we think the criterion of SUVmax^1.0could be used to clinical diagnosis.The sensitivity and specificity and accuray of RI≥5%were50%and90%and60.5%, the Youden index was0.4. The sensitivity of RI≥10%and RI≥15%and RI≥20%were35.7%and28.6%and17.9%individually, the specificity were all100%, the accuracy were52.7%and47.4%and39.5%, the Youden index were0.357and0.286and0.179. The sensitivity and specificity and accuracy and Youden index of RI≥2.5%were60.7%and70.0%and61.2%and0.307. The criterion of RI≥5%had the higher clinical value from the the statistical analysis.The sensitivity and specificity and accuray of AT/N max≥5%were71.4%and90.0%and76.3%, the Youden index was0.614. The specificity of AT/N and△T/N max≥15%and△T/N max≥20%were all100%, the sensitivity were53.6%and42.9%and39.3%, the accuracy were65.8%and57.9%and55.3%, the Youden index were0.536and0.429and0.393. The sensitivity and specificity and accuray and Youden index of△T/N max≥2.5%were75.0%and60.0%and71.7%and0.350individually. The Youden index of s△T/N max≥5%was the highest, and was the higher specificity, and this criterion had the higher clinical value.(2) The clinical value of double time-point18F-FDG PET-CT for mGGNsThe sensitivity and specificity and accuracy and Youden index of SUVmax≥2.5were60.9%and100%and64%and0.609. The specificity of SUVmax≥0.8and SUVmax≥1.0and SUVmax≥1.5were0%for all, the sensitivity were100%and100%and87%, the accuracy were92%and92%and80%, the Youden index were0and0and-0.130. The sensitivity and specificity and accuracy of SUVmax≥2.0were69.6%and50%and68%, the Youden index was0.196. The Youden index of SUVmax≥2.5was the highest, and it has better specificity, but the sensitivity and accuracy were low. The sensitivity and accuracy ofSUVmax≥0.8and SUVmax≥1.0were higher, but the specificity was bad.The sensitivity and specificity and accuracy and Youden index of RI≥5%were65.2%and0%and60%and-0.348. The sensitivity of RI≥10%and and RI≥2O%were43.5%and17.4%and13.0%, the specificity were100%for all, the accuracy were48.0%and24.0%and20.0%individually, the Youden index were0.435and0.174and0.130. The Youden index of RI≥2.5%was negative value. The Youden index of RI≥10%was higher, but the sensitivity and accuracy were low. The clinical value of RI was no helpful for diagnosis.The specificity of△T/N max≥2.5%and△T/N max≥5%and△T/N max≥10%and△T/N max≥15%were0%for all, the sensitivity were78.3%and73.9%and60.9%and52.2%, the accuracy were72.0%and68.0%and56.0%and48.0%, the Youden index were-0.217and-0.216and-0.391and-0.478. The sensitivity and specificity and accuracy and Youden index of△T/N max≥:20%were43.5%and50%and44%and-0.065. The Youden index of△T/N max were all negative value, so it was no helpful for the diagnosis of mGGNs.2. The clinical value of HRCT for GGNsThe sensitivity and specificity and accuracy of HRCT for pGGNs were88.5%and45.5%and73.7%, the Youden index was0.340.The sensitivity and specificity and accuracy of HRCT for mGGNs were100%and0%and92.2%, the Youden index was0.3. The clinical value of double time-point imaging combination with HRCT for GGNs(1) The sensitivity and accuracy and Youden index of SUVmax≥1.0of early imaging18F-FDG PET-CT combination with HRCT and△T/N max≥5%combination with HRCT of pGGNs were increased, and the specificity was invariability. The statistical outcome showed the two ways had better clinical value.(2) The sensitivity and specificity and accuracy and Youden index of SUVmax≥2.5of early imaging18F-FDG PET-CT combination with HRCT for mGGNs were100%and50%and92%and0.50. The sensitivity and specificity and accuracy and Youden index of RI≥10%imaging combination with HRCT for mGGNs were91.3%and50%and88%and0.413. The two ways could increase the accuracy and sensitivity, but the specificity decreased.4. The statistical analysis of the malignant ground-glass nodules and the difference of SUVmax in the different pathologic typings38pGGNs were confirmed by histopathology and follow up, the diameter≤ 3.0cm,2of AAH (average value of SUVmax was0.08±0.06),5of bronchioloalveolar carcinoma (average value of SUVmax was1.65±0.62),13of well-differentiated adenocarcinoma (average value of SUVmax was1.15±0.6),8of moderately differentiated adenocarcinoma (average value of SUVmax was1.89±1.14),10of inflammatory nodules (only one uptake of18F-FDG). The average value of SUVmax in malignant nodules has no significant.25were mGGNs (24were confirmed with pathology,1was confirmed follow up), including7of well-differentiated adenocarcinoma (average value of SUVmax was2.7±0.88),9of moderately differentiated adenocarcinoma (average value of SUVmax was4.60±2.77),2of poor differentiated adenocarcinoma (average value of SUVmax was3.60±0.99),5of bronchioloalveolar carcinoma (average value of SUVmax was2.30±1.24),1of PSH (SUVmax was2.5),1of inflammatory nodule (SUVmax was1.8). The average value of SUVmax in malignant nodules has no significant.Conclusion:Double time-point18F-FDG PET-CT imaging combination with HRCT in the diagnosis of GGNs appears to be better accuracy and sensitivity.SUVmax≥1.0and AT/N max≥5%in the diagnosis of pGGNs appears to be better efficiency.SUVmax≥2.5in the diagnosis of mGGNs appears to be better efficiency. Although the specificity of RI≥10%was better, the sensitivity and accuracy were poor.The lobulation and speculation and pleural indentation sign in pGGNs and the air bronchogram and the vascular convergence sign in mGGNs of HRCT were helpful for the diagnosis.The malignant ground-glass nodules and the difference of SUVmax in the different pathologic typings has no significance. PART IIThe differential diagnostic value of18F-FDG PET-CT double stage imaging combination with diagnosis CT for solitary pulmonary solid nodulesObjectiveTo study the diagnosis value of F-FDG PET-CT double stage imaging combination with diagnosis CT of solitary pulmonary nodules.MethodsThis was a prospective study.47patients who were referred for18F-FDG PET-CT to determine the SPNs in July2010to February2013.including33malignancy nodules (18males and15females, the mean age was59.3±18.9years),14benign nodules (8males and6females, the mean age was50.7±13.8years). With the consent of patients, multi-phase contrast-enhanced neoplasm-diagnosis CT scan was performed after the delay time at the same day.Two doctors analysis the following individually:the shape of18F-FDG uptake, SUVmax, RI, the shape of CT contrast, the time of peak enhancement, the washout time of peak enhancement. The net enhancement value were split into five groups:no enhanemence (net enhancement value<15Hu), low enhancemence (15Hu≤net enhancement value≤25Hu), moderate enhancemence (net enhancement value was25-45Hu), high enhancemence (net enhancement value was46-59Hu), special high enhancemence (net enhancement≥60Hu). The characteristics of CT enhancemence were split into three groups:(1) low-high enhancemence, the plateau,(2) no or low ring enhancemence,(3) low-special high enhancemence and the peak decreased. We think (1) as malignant,(2) or (3) as benign.The uptake of18F-FDG were split into four groups:(1) sharp high uptake of18F-FDG (SUVmax≥8),(2) high uptake of18F-FDG (2.5≤SUVmax<8),(3) moderate uptake of18F-FDG (1.5≤SUVmax<2.5),(4) no or low uptake of18F-FDG (SUVmax<1.5).The form of uptake of18F-FDG were split into three groups:nodules (clear margin and sharp high uptake of F-FDG), ring uptake in margin (no uptake of18F-FDG in center), patchy (unclear edage, high or moderate uptake of18F-FDG). Malignant criterion was nodule or pathy or ring with high or sharp high uptake of18F-FDG. Benign criterion was pathy or ring with moderate or no or low uptake of18F-FDG.PET-CT combination with multi-phase contrast-enhanced neoplasm-diagnosis CT scan:if the nodule had both malignant criterion, we thought it as manlignant; if the nodule had both benign criterion, we thought it as benign; if the nodule had one malignant criterion, we thought it over and decided through consultation.Statistical analysis:The statistical software SPSS13.0was used. All dates were analyzed for significance by using the X2test, value of P<0.05were accepted as significance.Results(1) The clinical value of multi-phase contrast-enhanced neoplasm-diagnosis CT scan for solid SPNs24malignant SPNs with low to high enhancemence and plateau,6malignant SPNs with low to moderate enhancemence and peak decreased,3malignant SPNs with no enhancemence.2benign SPNs with low to high enhancemence and plateau,7benign SPNs with no or ring enhancemence,5benign SPNs with moderate to high enhancemence and peak decreased. The sensitivity and specificity and accuracy and Youden index were72.7%and85.7%and76.6%and0.584.(2) The clinical value of double time-point18F-FDG PET-CT for solid SPNsThe sensitivity and specificity and accuracy and Youden index of SUVmax≥2.0of early imaging were100%and7.1%and72.3%and0.071. The Youden index of SUVmax≥3.5was higher, but the sensitivity and specificity were low.The Youden index of RI≥5%was0.214, and the sensitivity and accuracy were100%and72.3%, but the specificity was21.4%and it was low. The Youden index of RI≥10%and RI≥15%and RI≥20%and RI≥25%were negative value, and this showed this way has limited clinical value.(3) The clinical value of double time-point18F-FDG PET-CT combination with multi-phase contrast-enhanced neoplasm-diagnosis CT scan for solid SPNsSUVmax≥3.5and RI≥5%combination with multi-phase contrast-enhanced neoplasm-diagnosis CT scan individually, it can decrease the specificity to92.9%and95.7%, the accuracy to97.9%and95.7%, the Youden index to0.929and0.857. Double time-point18F-FDG PET-CT combination with multi-phase contrast-enhanced neoplasm-diagnosis CT scan appears to be better efficiency for solid SPNs.(4) The pathologic typings of solid SPNs compare with double time-point18F-FDG PET-CT combination with multi-phase contrast-enhanced neoplasm-diagnosis CT scanIn the32malignant SPNs, the shape of18F-FDG was pathy or nodular or ringlike. Of24malignant SPNs showed low to special high enhancemence and plateau, of5malignant SPNs showed low to moderate enhancemence and the peak decreased, of3malignant SPNs showed no enhancemence.In7tuberculoma lesions, the shape of I8F-FDG was ringlike or pathy,3of no enhancement,3of ringlike enhancement,1of the peak enhancement fall.In1spherical puenmonia, the shape of18F-FDG was nodular, the peak enhancement fall after Ⅳ contrast material20"-80". In1suppurative inflammation, the the shape of18F-FDG was nodular, the peak enhancement fall after Ⅳ contrast material20".In5PSH, the shape of18F-FDG was pathy,2of low enhancement and plateau,3of the peak enhancement fall.4PSH showed perotumor vessel sign,1PSH showed tail sign,3PSH showed air trapping sign.ConclusionSUVmax≥3.5of early imaging and RI≥5%combination with multi-phase contrast-enhanced neoplasm-diagnosis CT scan individually, it can decrease the specificity and the accuracy. Double time-point F-FDG PET-CT combination with multi-phase contrast-enhanced neoplasm-diagnosis CT scan appears to be better efficiency for solid SPNs.If the SPNs appeared low to high enhancemence and plateau in multi-phase contrast-enhanced neoplasm-diagnosis CT scan, it could cut down the false negative result of18F-FDG PET-CT.If the SPNs appeared no or ringlike enhancemence in multi-phase contrast-enhanced neoplasm-diagnosis CT scan, it could cut down the positive false result of18F-FDG PET-CT.If the SPNs appeared low to high enhancemence and the peak fall in multi-phase contrast-enhanced neoplasm-diagnosis CT scan, especially appeared perotumor vessel sign, tail sign, air trapping sign, the diagnosis of PSH should be made. PART IIIThe diagnostic value of18F-FDG PET-CT for different sizes pulmonary solitary nodulesObjectiveThe goal of our study was to investigate the correlation between the size of pulmonary nodules (include pGGNs, mGGNs, solid SPNs) and the SUVmax for malignant and benign nodules.MethodsThis was a prospective study.63patients who were referred for F-FDG PET-CT to determine the SPNs in July2010to February2013.including51malignancy nodules (22males and29females, the mean age was55.9±16.7years),12benign nodules (7males and5females, the mean age was51.3±10.4years); including38pGGNs (28of malignant nodules,10of benign nodules), including25mGGNs (23of malignant nodules,2of benign nodules).148patients who were referred for18F-FDG PET-CT to determine the SPNs in July2010to February2013including94malignancy nodules (50males and44females, the mean age was56.3±23.9years),54benign nodules (36males and18females, the mean age was49.3±35.1years).With the consent of patients, HRCT was performed after the delay time at the same day.According to the size on pulmonary window, all the nodules were divided into three groups:D1≤1cm,lcm<D2≤2.0cm,2cm<D3≤3.0cm.Malignant criterion of pGGNs were SUVmax≥1.0,△T/Nmax≥5%; malignant criterion of mGGNs were SUVmax≥2.5, RI≥10%; malignant criterion of solid SPNs were SUVmax≥3.5, RI≥5%.Statistical analysis:The statistical software SPSS13.0was used. All dates were analyzed for significance by using the X2test, value of P<0.05were accepted as significance.Results1. The diagnostic value of18F-FDG PET-CT for different sizes pGGNsThe cases of D1and D2and D3were8cases (6of benign,2of malignant),26cases (4of benign,22of malignant),4cases (all of malignant). Malignant criterion of pGGNs were SUVmax≥1.0:the sensitivity and specificity and accuracy of D1were0%,0%,75%; the sensitivity and specificity and accuracy of D2were77.3%,50%,73.1%; the sensitivity and specificity and accuracy of D3were100%,0%,100%; Youden index of the three group were-1,0.273,0. The false negative rate of D1was100%, and the false negative rate of pGGNs decreased with the diameter increasing.Malignant criterion of pGGNs were△T/Nmax≥5%:the sensitivity and specificity and accuracy of D1were0%,0%,75%; the sensitivityand specificity and accuracy of D2were77.3%,75%,76.9%; the sensitivityand specificity and accuracy of D3were75%,0%,75%; Youden index of the three group were-1,0.523,-0.25. The false negative rate of D1was100%, and the false negative rate of pGGNs decreased with the diameter increasing.Three groups of malignant pGGNs in SUVmax were0.4±0.14,1.36±0.74,2.26±0.96. The groups D1and D2of benign pGGNs in SUVmax were0.58±0.17,0.92±0.43. The groups of pGGNs in SUVmax was no significant.2. The diagnostic value of18F-FDG PET-CT for different sizes mGGNsThe cases of D1and D2and D3were2cases (all of malignant),11cases (1of benign,10of malignant),12cases (1of benign,11of malignant)Malignant criterion of mGGNs were SUVmax≥2.5:the sensitivity and specificity and accuracy of D1were50%,0%,50%; the sensitivity and specificity and accuracy of D2were50%,100%,54.5%; the sensitivity and specificity and accuracy of D3were72.7%,100%,75%; Youden index of the three group were-1.5,0.5,0.272. The false negative rate of D1and D2were50%, and the false negative rate of D3was27.3%.Malignant criterion of mGGNs were RI≥10%: the sensitivity and specificity and accuracy of D1were0%,0%,0%; the sensitivityand specificity and accuracy of D2were50%,100%,54.5%; the sensitivity and specificity and accuracy of D3were45.5%,100%,50%; Youden index of the three group were-1,0.5,-0.455. The false negative rate of D1was100%, and the false negative rate of D2and D3were50%,54.5%.Three groups of malignant mGGNs in SUVmax were2.54±1.65,3.05±2.12,3.74+2.31. The three groups in SUVmax was no significant.3. The diagnostic value of18F-FDG PET-CT for different sizes solid SPNsThe cases of D1and D2and D3were8cases (4of benign,4of malignant),69 cases (26of benign,43of malignant),71cases (24of benign,47of malignant)Malignant criterion of solid SPNs were SUVmax≥3.5:the sensitivity and specificity and accuracy of D1were24%,75%,50%; the sensitivity and specificity and accuracy of D2were67.4%,73.1%,69.6%; the sensitivity and specificity and accuracy of D3were80.1%,50%,70.4%; Youden index of the three group were0,0.405,0.301. The false positive rate of D1and D2and D3were75%,32.6%,19.1%. The false positive rate of increased with the diameter increasing, but the false negative decreased.Malignant criterion of solid SPNs were RI^5%:the sensitivity and specificity and accuracy of D1were50%,50%,50%; the sensitivityand specificity and accuracy of D2were79.1%,46.2%,66.7%; the sensitivity and specificity and accuracy of D3were91.5%,37.5%,72.3%; Youden index of the three group were0,0.253,0.290. The false positive rate of the three groups were50%,53.8%,62.5%., and the negative rate were50%,20.9%,8.5%. With the diameter increasing, the false negative decreased.Three groups of malignant solid SPNs in SUVmax were1.88+1.55,4.84+2.75,6.64+3.35. Three groups of benign solid SPNs in SUVmax were2.13+1.20,3.51+2.54,4.13+2.31. The groups of D3in SUVmax was significant.Conclusion1. SUVmax≥1.0and△T/Nmax≥5%in D2group of pGGNs had best diagnostic efficiency. The false negative rate was100%, and with the diameter increasing the false negative rate decreased.2. SUVmax≥2.5in D3group of mGGNs had best diagnostic efficiency.3. SUVmax≥3.5in D2and D3group of solid SPNs had better diagnostic efficiency, had better sensitivity and specificity in D3. The false positive rate increased with the diameter increasing, but the false negative rate decreased. The groups of D3in SUVmax was significant.