Functional Magnetic Resonance Imaging Of Prostate Cancer And The Relationships Between Imaging And Biological Characteristics

BackgroundsProstate cancer(PCa) is a biologically heterogeneous disease for which a variety of treatment options are available.To achieve more precise biological characterization of PCa is essential for developing individualized treatment programs and improving the efficacy.Autonomous proliferation of tumor will lead to hypoxic and high-acid micro-environment.The tumor enhances the endurance of the ability to survive the poor micro-environment and promote the angiogenesis by adjusting the relevant gene expression.Therefore,there may be a relatively dynamic balance among angiogenesis, cell proliferation and tissue micro-environment.With the development of imaging techniques,magnetic resonance(MR) with some functional imaging methods which can reflect the cell metabolism,water molecular diffusion,micro-architecture and the blood flow perfusion have been used to evaluate the angiogenesis in vivo.These functional MRI techniques provide new perspectives to evaluate the biological behavior of PCa,which is the information assurance of individualized treatment. Partâ… Correlative study of MRSI/DWI and angiogenesis,cell proliferation and HIF-lαof prostate cancer1.ObjectiveThe main objective of this part is to analyze the relationships between MRSI/DWI and angiogenesis,proliferation and HIF-1αof prostate cancer,as well as the significance of MRSI/DWI in assessing the biological behavior of prostate cancer. 2.Materials and methodsMRSI and DWI were performed using a 1.5 Tesla superconducting magnetic scanner(Siemens) equipped with a pelvic phased-array multi-coil.Healthy volunteers and patients with prostate cancer or benign prostate hyperplasia were included in this study.All data were transferred to Siemens Leonardo Workstation and regions of interest(ROI) of PCa,benign prostate hyperplasia(BPH),and peripheral zone(PZ) were drawn by a radiologist.The(Cho+Cr)/Cit ratios and ADC values were calculated.Cellularities of PCa were recorded based on hematoxylin and eosin staining.The microvessel density(MVD),vascular endothelial growth factor(VEGF), proliferating cell nuclear antigen(PCNA) and hypoxia inducible factor-1 alpha (HIF-1α) of PCa and BPH were detected by immunohistochemical techniques.The relationships among(Cho+Cr)/Cit ratio,ADC values,angiogenesis,proliferation and HIF-1αwere analyzed.3.Results3.1,The features of PCa and BPH on MRI/MRSI and DWIThe MR spectrum of prostate cancer was different from those of BPH and PZ. The average value of(Cho+Cr)/Cit ratio of PZ,BPH and PCa were 0.32±0.03, 0.55±0.04 and 4.19±0.25.The(Cho+Cr)/Cit ratios of prostate cancer were higher than those of PZ and BPH(P＜0.05).With the increasing of b value,the signal intensity of PZ,BPH and PCa changed differently fiom each others.The ADC values of PZ,BPH and PCa were 130.20±26.20×10^-5mm²/s,91.23±12.24×10^-5mm²/s and 52.11±10.19×10^-5mm²/s respectively.The ADC values of Pea were lower than those of BPH and PZ(P＜0.05).The higher(Cho+Cr)/Cit ratio of PCa corresponded to lower ADC values.The (Cho+Cr)/Cit ratio of PCa was correlated negatively with ADC values(P＜0.05).3.2.Comparative analysis of angiogenesis,proliferation and HIF-1αbetween PCa and BPHThe angiogenesis(VEGF,MVD),proliferation(PCNA,cellularity) and HIF-1αof PCa were higher than those of BPH(P＜0.05).The MVD,PCNA,cellularity, HIF-1αand stage of prostate cancer were correlated with each other positively (P＜0.05).The VEGF was correlated positively with MVD,PCNA,HIF-1α,Gleason grade and stage of prostate cancer were correlated with each other(P＜0.05).3.3.The relationships between MRSI,DWI and angiogenesis,proliferation and HIF-1αof PCa and BPHThe(Cho+Cr)/Cit ratios of PCa were correlated positively with VEGF,MVD, PCNA,cellularity,HIF-1α,Gleason grade and stage(P＜0.05).The ADC values of PCa were correlated negatively with cellularity,PCNA,HIF-1α,and MVD(P＜0.05). No relationships were observed among MRSI,DWI and the biological indexes of BPH(P＞0.05).Partâ…¡The Study of PWI,DTI and BOLD in Prostate1.ObjectiveThe objective of this part is to investigate the features and application value of PZ,BPH and prostate cancer in PWI,DTI and BOLD-fMRI.2.Materials and methodsThe clinic and pathologic information of 49 patients with histologically proven PCa were studied.The examination was performed in the supine position using 1.5T superconductive magnet Echo-speed scanner with intergrated endorectal surface coil and pelvic phased array multi-coil.Perfusion weighted imaging(PWI) was acquired using a modified single shot SE echo planar imaging(EPI) sequence.All of the data were transferred to GE Advanced Workstation 4.2.In order to eliminate the variation of individuals,the indexes of obturator internus were used as internal references.The indexes of PWI were calculated by Functool 2 which included signal intensity-time curve(SI-TC),relative negative enhancement integral(rNEI),mean time to enhance (rMTE),time to minimum(rTTM),maximum slope of decrease(rMSD) and blood flow(rBF).DTI and BOLD were performed using a 1.5 Tesla superconducting magnetic scanner(Siemens) equipped with a pelvic phased-array multi-coil.Healthy volunteers and patients with prostate cancer or benign prostate hyperplasia were included in this study.BOLD data were acquired during 5×2minute episodes alternating between air and carbogen(95%O₂/5%CO₂) breathing.All data were transferred to Siemens Leonardo Workstation and different regions of interest(ROI) of PCa,BPH,and PZ were drawn by a radiologist.Using the DTI card,the FA,mean ADC values,el,e2 and e3 of DTI were calculated and the corresponding index maps were produced.The SI-TC and percentage of signal increase were recorded.3.Results3.1.Perfusion Weighted Imaging MR(PWI) of PZ,BPH and PCaThe SI-TC of PCa showed rapid and steep inverted peak after the injection of contrast.The signal intensity increased quickly after the firs-pass of contrast with the signal intensity lower than that of before contrast's arrival.The rNEI of PZ,BPH and PCa were 1.37±0.88,3.22±2.07 and 6.44±4.29.The rNEI,rTTM and rMSD of prostate cancer were higher than those of BPH and PZ(P＜0.05),while the MTE and TTM of prostate cancer were shorter than those of normal PZ and BPH(P＜0.05). Positive correlation was found between rNEI and Gleason grade,TNM and PSA level (P＜0.05).There was a negative correlation between rTTM and Gleason grade,TNM of prostate cancer(r=-0.46;-0.51,P＜0.05).3.2.Diffusion Tensor Imaging MR(DTI) of PZ,BPH and PCaThe tractional anisotropy(FA) of PZ,BPH and PCa were 0.16±0.03,0.23±0.04 and 0.46±0.02.The FA of prostate cancer were higher than those of BPH and PZ (P＜0.05).The ADC values,e1,e2 and e3 of PZ,BPH and PCa were different from each others(P＜0.05).Obvious differences among e1,e2 and e3 were observed (P＜0.05).3.3.Blood oxygen level-dependent(BOLD) MR of PZ,BPH and PCaThe SI-TC showed obvious enhancement during carbogen breathing.The signal intensity returned to baseline during the following period of normal air breathing.A repeated but less sharp signal changes were observed during the second period of carbogen breathing.The increasing rate of SI PZ,BPH and PCa were 7.80±0.06, 12.00±0.13 and 5.00±0.03,respectively.The increasing rate of SI of normal central gland was higher than that of peripheral zone(P＜0.05).The increasing rate of SI of BPH were higher than those of PZ and PCa(P＜0.05).4.Conclusion(1).The ROIs of PZ,BPH and PCa have the different characteristics respectively on MRSI and DWI.The(Cho+Cr)/Cit ratios of PCa were correlated positively with VEGF,MVD,PCNA,cellularity,Gleason grade and stage.The ADC values of PCa were correlated negatively with cellularity,PCNA and MVD.Therefore,¹H-MRSI and DWI are helpful to predict the variables of angiogenesis,proliferation and microenvironment of prostate cancer.(2).The correlation among angiogenesis, proliferation and microenvironment demonstrate that there is a dynamic balance between the biological features of prostate cancer.This dynamic balance is crucial to the development of prostate cancer.(3).PWI can reflect the difference in microcirculation between PCa and benign tissues.Combined with conventional MRI, PWI is helpful to detect lesions.According to the correlation between indexes of PWI and clinicopathological results of prostate cancer,PWI can be used to evaluate the biological features.(4).The FA,ADC,e1,e2 and e3 acquired from DTI can used to evaluate the three-dimensional architecture of PZ,BPH and PCa.The DTI and DTT have the potential to evaluate the micro-structural changes of prostatic diseases. (5).BOLD-fMRI during carbogen breathing is feasible.Its signal changes can be distinguished clearly between prostate cancer and contrlateral normat prostate tissue, which contributes to the diagnosis of early prostate cancer.According to the BOLD-fMRI,the function and maturity of micro-vascular may be evaluated.(6)Every functional MR technique is provided with their own advantages.Multiple functional magnetic resonance technologies can reflect the molecular level changes from different prospectives and assess the individualized biological characteristics of prostate cancer non-invasively.So,combining multi-methods together may offer more information for clinical diagnosis and therapy.