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Clinical Value and Study of Volume-based Perfusion with Lung Cancers at 64-slice CT

Author: DanFei
Tutor: ZengMengSu;ZhangZhiYong;GeZuo;HuJie;YangZuo
School: Fudan University
Course: Medical Imaging and Nuclear Medicine
Keywords: lung neoplasm solitary pulmonary nodule Tomography, X-ray computed perfusion temporal resolution radiation non-small cell lung cancer tumor size necrosis location pathological types solitary pulmonary nodule microvascular density angiogenesis functional imaging Diagnosis accuracy agreement agreement of observe reproducibility Rh-endostatin angiogenic treatment
CLC: R734.2
Type: PhD thesis
Year: 2009
Downloads: 110
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Abstract


Part oneFirst pass CT perfusion with lung cancers:usage of different temporal resolutionsPurpose:To find a good temporal resolution(TR) and reduce radiation dose in the CT perfusion(CTP) with lung cancers.Material and methods:Sixty patients with pathologically proved lung cancers were enrolled in a 30s dynamic first pass CTP (cine mode,TR of 0.5s).Parametric maps of one central slice for BF,BV,MTT and PS were calculated for TR datasets of 0.5,1,1.5,2,2.5,3 and 4s using GE’s Perfusion 3 software package.The analysis of covariance(AOCV) was used to judge whether the differences were found in values of BF,BV,MTT and PS with different TR datasets.In AOCV,the dependent variable was BF,BV,MTT and PS values, fixed factor was different groups of TR,and the covariate was the group of tumor size. Finally,each different TR datasets was compared with the reference dataset(TR of 0.5s) using Sidak test.Results:Statistically significant differences were found in means of values of BF and MTT with different TR datasets(P<0.001).No statistically significant differences were found in means of values of BV and PS with different TR datasets(P>0.05).Compared with TR dataset of 0.5s,no statistically significant differences were found in means of BF and MTT with TR datasets of 1s, 1.5s,2s(P>0.05),while statistically significant differences were found in means of BF and MTT with TR datasets of 2.5,3s,4s(P<0.05).Conclusions:When an axial scan with no table feed mode is used,it is recommended that TR of 1.5s should be taken and the radiation dose will be greatly reduced,and without a loss in quantitative accuracy in the CTP with lung cancers. Part twoVolume-based perfusion of NSCLC:evaluation of clinical and pathological factorsPurpose:To investigate the clinical and pathological factors which could be influence the deconvolution-based CT perfusion imaging with NSCLC at 64-slice CT.Material and methods:Ninety five patients with pathologically or cytologically proved NSCLC underwent the first pass CT volume-based perfusion(CTVP) examination at 64-slice CT(cine or axial scan mode with no table feed after intravenous injection of 50 ml contrast media followed by a saline flush of 30 ml at injection rate of 5 ml/s).BF,BV,MTT,and PS were determined with GE perfusion 3 software package.Pearson correlation coefficient was used to correlate the CTVP parameters with the tumor size.Student t statistics or Mann-Whitney nonparametric statistics were used to compare the differences of CTVP parameters between central and peripheral lung cancers.Student t statistics were applied to compare the differences of CTVP parameters between necrotic and no necrotic NSCLC,and between lung adenocarcinomas and squamous cell carcinomas.One-way ANOVA was employed to compare the differences of CTVP parameters among clinical stags,and among stages of lymph nodular metastases.Results:In 96 cases with NSCLC,BF and PS values were negatively,and MTT values were positively correlated with tumor size(r=-0.270,-0.329 and 0.379,respectively,and P<0.05 for all).In 43 patients of no necrotic NSCLC,BV values was positively correlated with tumor size (r=0.502,P<0.05).BF and PS values with central NSCLC were lower than these with peripheral NSCLC(P<0.05 for both),not MTT and BV values.BF、BV、PS values with no necrotic NSCLC were higher than these with necrotic NSCLC,not MTT values.BF and PS values with lung adenocarcinomas were higher than these of lung squamous cell carcinomas(P<0.05 for both),not MTT and PS values.No statistically differences were found among BF values with NSCLC of different clinical stages,and so did BV,MTT,and PS values(P>0.05 for all).No statistically differences were found among BF values with NSCLC of different stages of lymph nodular metastases, and so did BV,MTT,and PS values(P>0.05 for all).Conclusions:Tumor size, necrosis,tumor location and pathological types could influence the CTVP parameters with NSCLC,and should be addressed for clinical application in diagnosis of SPN and antiangiogenesis therapeutic monitoring. Part threeCT volume-based perfusion with SPNs:clinical evaluation Section one SPNs:CT volume-based perfusion differences in malignant and benign lesions and correlations with vascular parametersPurpose:To investigate the diagnostic value of SPNs with CTVP and the relationships between CTVP and microvascular density(MVD) and luminal vascular number(LVN) and luminal vascular area(LVA) and luminal vascular perimeter (LVP).Material and methods:Sixty-five patients with proved SPNs were enrolled in a dynamic first pass CTVP.BF,BV,MTT,and PS were determined by GE Perfusion 3 software package.Thirty-eight patients were underwent immunohistochemical staining with CD34 andα-smooth muscle action(SMA).When MVDs were counted, any CD34 highlighted single endothelial cell or cell cluster that was clearly separate from adjacent tissue elements was counted as a single countable microvessel.For LVN,LVA,and LVP,only SMA highlighted with a discernible lumen could be defined as a luminal/mature vessel,and measured by imaging analysis software.The statics was undergone by two parts.In the first part,the means of four perfusion parameters between malignant and benign nodules were compared.Then,ROC curve for perfusion parameters between malignant and benign nodules were used,and the diagnostic accuracy were compared through the areas under ROC curves,and the integral cut-off were taken.Finally,according to the sensitivities and specificities of different perfusion parameters,the combined tests were done.In the second part, perfusion and vascular parameters between malignant and benign nodules were compared,which were 38 nodules underwent immunohistochemical staining.Pearson or Spearman correlation coefficients were used to investigate relationships between perfusion and vascular parameters.Results:BF,BV and PS values of malignant nodules were higher than those of benign nodules.Statistically significant differences were found between BF and BV and PS values of malignant nodules with those of benign nodules,respectively(P<0.001 for all),not MTT values.BF,BV and PS values could be used to judge whether a SPN was benign or malignant,the AUCRoc were 0.844 and 0.854 and 0.831,respectively(P<0.001 for all).No statistically significant differences were found in the diagnostic accuracy with three ROC curves. When BF=50 ml/min/100g was used,the sensitivity was 93%,the specificity was 59%.When BV=3 ml/100g was used,the sensitivity was 86%,the specificity was 68%.When PS=10 ml/min/100g was used,the sensitivity was 86%,the specificity was 77%.The combined specificity of the serial test combined BF with PS value and combined BV with PS value were all 82%.In those patients having SPNs stained with CD34 and SMA,statistically significant differences were found in BF,BV,PS,LVA, LVP,LVN of malignant nodules and those of benign nodules,respectively(P<0.05 for all);not MTT values and MVD,respectively.BV value were positively correlated with MVD(r=0.483,P<0.05),but not the values of BF and MTT and PS,respectively. Significant correlations were observed between BF value and LVA and LVP and LVN(r=0.547 and r=0.507 and r=0.404,respectively,P<0.05 for all).Significant correlations were observed between BV value and LVA and LVP(r=0.714 and r=0.504,respectively,P<0.05 for both),but had not LVN.Significant correlations were observed between PS value and LVA and LVP and LVN(r=0.507 and r=0.541 and r=0.473,respectively,P<0.05 for all),Significant correlations were not observed between MTT value and LVA and LVP and LVN,respectively.Conclusions:CTVP could be used to the diagnose of SPNs.CTVP could reflect luminal/mature vessels more,and had better correlations between luminal vascular parameters than MVD. CTVP should take the place of MVD as a non-invasive method to investigate the state ofangiogenesis or vessel reflections.Section two SPNs:diagnostic accuracy and agreement with CT volume-based perfusion and routine thorax CTPurpose:To investigate whether CT volume-based perfusion(CTVP) combined with routine thorax CT examination could improve the accuracy and agreement for the diagnosis of SPNs by radiologists.Material and methods:Sixty-five patients with pathological and clinical proved SPNs were enrolled in a dynamic first-pass CTVP study.As a part of the study,routine thorax CT examination including non-enhanced and enhanced scan in delayed phase were involved.Perfusion images were preceded by GE Perfusion 3 software package.Two junior and two senior radiologists made a diagnosis by means of those routine thorax CT datasets(method A) blandly.After a month,they made a diagnosis based on CTVP and routine thorax CT datasets(method B) blandly.ROC curves were used to analyses every doctor’s diagnosis made by method A and B.ROC curves before and after CTVP used were compared in every doctor.ROC curves for method A and B with different doctor were compared, respectively.Intra-class correlation coefficients(ICC) were used to investigate the agreements for diagnosis made by four radiologists before and after CTVP used, respectively.Results:With method A,the AUCROC in two junior and two senior radiologists were 0.748,0.765,0.894 and 0.901,respectively.With method B,those were 0.967,0.950,0.978 and 0.967,respectively.By AUCROC analysis,with method A,no significant statistical differences were found in accuracy of junior or senior radiologists,while significant statistical differences were found in accuracy between junior and senior radiologists(P<0.05 for all).After CTVP datasets were used,no significant statistical differences were found in accuracy of every radiologist.While method B were compared to method A,significant statistical differences were found in accuracy of every radiologists,respectively(P<0.001 for all).With method A,ICC for four radiologists were 0.612.After CTVP datasets were used,the ICC was increased to 0.854.Conclusions:Compared to routine thorax CT used singly,usage of the datasets of CTVP and routine thorax CT could improve the accuracy and agreement for radiologists’ diagnosis of SPNs.Diagnosis of SPNs with CTVP plus routine thorax CT should be addressed in clinical application. Part fourLung cancer CT volume-based perfusion:evaluation of combining endostar with chemotherapySection one NSCLC perfusion at 64-Slice CT:reproducibility of volume-based quantitative measurementPurpose:To know the reproducibility of volume-based quantitative measurement of NSCLC perfusion using 64-slice CT.Materials and methods:Sixty patients with pathological-proved NSCLC were enrolled in this dynamic first pass volume-based CT perfusion study(8×5 mm collimation),and 14 patients of them were underwent the second scan within 24h.Those 60 patients were divided into≤3cm and>3cm groups according to the longest diameters,and each group had 30 patients.Fourteen patients who were underwent twice CTVP scans were also classified to≤3cm and>3cm groups according to the same standard,and each group had 7 patients. Using GE perfusion 3 software package,two independent radiologists determined the values of BF、BV、MTT and PS.A radiologist determined the perfusion of 14 patients who underwent twice scans.Intraclass correlation coefficient(ICC) and Bland-Altman statistics were used to evaluate the agreement of observer and the reproducibility of CTVP imaging.Results:In NSCLC(≤3 cm),the agreements of observer with CTVP parameters were good(ICC>0.75 for all).In the group,with BF, BV,and MTT values,the values of ICC and RC for the agreement of intra-observer were higher than those for the inter-observer.In NSCLC(>3 cm),the agreements of intra-observer with CTVP parameters were good(ICC>0.75 for all).In that group, with BF and BV values,the agreements of inter-observer were good(ICC>0.75 for both),while with MTT and PS values,which were moderate or bad(ICC<0.75 for both).Also in all perfusion parameters of that group,the values of ICC and RC for the agreement of intra-observer were higher than those for the inter-observer,except ICC with BF value.In both two groups of NSCLC,the reproducibility with BF,BV,and PS values were good(ICC>0.75 for all).For NSCLC(≤3 cm),RC values with BF, BV,MTT and PS values were 56%,45%,114%,and 78%,respectively,and the 95% change intervals of RC were -39~53%,-29~62%,-83~145%,and -57~98%, respectively.For NSCLC(>3 cm),those values were 46%,30%,59%,and 33%, respectively,and the 95%change intervals of RC were- 48~45%,-33~26%,-54~64%, and -18~48%.Conclusions:There is greater inter- than intraobserver agreement for CTVP measurements of NSCLC,generally.There is greater reproducibility of tumor size>3cm than tumor size≤3cm.BF and BV could be addressed for reliable clinical application in antiangiogenesis therapeutic monitoring with NSCLC patients.Section two Usage of CT volume-based perfusion for combining endostar with chemotherapy in NSCLC patients:initial experiencePurpose:The aim of this study was to know whether CT volume-based perfusion (CTVP) could early display the therapeutic activity for combing Rh-endostatin (endostar) with chemotherapy in advanced NSCLC patients.Materials and methods: Fifteen patients with initial treated advanced NSCLC were divided into two groups. Nine patients in the trial group were treated with endostar plus chemotherapy,and 6 patients in the control group were treated with single chemotherapy.Patients in two groups were all underwent 30s first pass CTVP(Cine mode,8×5 mm slice thickness) before and after treatment of first cycle.A radiologist used GE perfusion 3 software to get tumor BF,BV,MTT,and PS.The sums of longest diameters of the appointed target lesions in the transversal plane for response evaluation criteria in solid tumors (RECIST) were also calculated.Wilcoxon nonparametric statistic was used to compare BF,BV,MTT,PS,and sum of longest diameters between two groups.Fish’s exact test was employed to compare the ratio of CTVP difference of first cycle to baseline between two groups.Results:In the trial group,BF values after first cycle were higher than the baseline(P=0.038),not other CTVP parameters and the sum of longest diameters.In the control group,the sum of longest diameters after treatments were smaller than baseline(P=0.028),not all perfusion parameters.The ratio of CTVP difference of first cycle to baseline in the trial group was higher than these in the control group(P=0.047).Conclusions:In the treatment of combing endostar with chemotherapy in advanced NSCLC patients,tumor perfusion would be increase early. CTVP is feasible in showing changes ofperfusion induced by antiangiogenic therapy.

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CLC: > Medicine, health > Oncology > Respiratory system tumors > Lung tumors
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