The Feasibility Study Of Using BOLD FMRI With Non-hemodynamic Response Function Analysis Method To Detect The Oxygenation Changes Within Rats Subcutanous C6Glioma

Part I Animal Model Establishment and Pathological Observation ofrats bearing C6subcutanous gliomaObjectives: Compare the tumor formation rate and growth rule of the C6subcutanousglioma models established by C6cell suspension inoculation and tumor mass inoculationmethods respectively,and select the optimal method for the second part of the experiment.Methods:21Wistar rats were divided into two groups including C6cell suspensioninoculation group and tumor mass inoculation group to establish the tumor models. Theformation rate, latent period, diameters and relative volume of the tumor were observedand recorded regularly. Compare the differences of the formation rate,latent period and themaximum diameter and the relative volume of the tumor between the two groups atdifferent time points after inoculation,and analysis the growth tendency of the tumor.Compare the differences of the formation rate and latent period between the two groups.All of tumors were perform HE staining with the tumor paraffin section and observe thepathological features by microscope.Results:1. The tumor formation rate of the cell suspension inoculation group was100%, and the latency was8.45±0.69(d), while another group was60%and9.83±1.72(d).2. The maximum diameter of the tumors estabilished by cell suspension inoculation weremuch bigger than the ones built by tumor mass inoculation during14days to20days afterinoculation.Similarly, there were significant statistically differences about ralative volumeof tumors between the two groups during16days to20days after inoculation.3. The maximum diameter of tumor was increasing linealy,and the relative volume seem to beexponential trend.4. HE staining showed that the pathological feature of C6subcutaneousgliomas were correspondence with the ones in the brain.Conclusion: The establishment methods of rat C6subcutaneous glioma model wererelatively simple. Comparing with tumor mass inoculation,the model established by cellsuspension method is a kind of ideal model characterized by higher tumor formation rate,faster growth rate and more stable.Part II Using BOLD fMRI to evaluate the relationship betweenoxygenation changes after Carbogen inhalation and angiogenesis withinrats subcutanous C6gliomaObjectives: To discuss the feasibility and value of using BOLD fMRI with non-HRFanalyzed post-processing algorithm to detect the oxygenation changes after carbogeninhalation inside the rat C6glioma model.Methods:1.20male Wistar rats were used to establish the the rat C6subcutanousglioma model by cell suspension inoculation.2. The tumor-bearing rats were performedMRI scan by1.5T Achieva Dual type superconducting magnetic resonance imagingsystem and Micro-47microscopic coil."oxy-localization map" and "oxy-amplitude map"were generated by non-HRF analyzed post-processing algorithm based on functionalimaging data.3. ROIs (ROImax, ROInon-max and ROInone) were defined according tothe processed image. And the parameters (T value, PSC, ΔSI) were extracted or calculatedfrom each ROIs drawn on image data as well as the MVN values counted on thehistopathological sections according to the site of these ROIs.4. Compare the mean Tvalue, PSC, ΔSI measured from each ROIs, and make a correlation analysis among T value,PSC, ΔSI and MVN extracted from ROImax and ROInone-max.Results:1. The tumor formation rate was100%.2. The"oxy-localization map" and "oxy-amplitude map"can overlay with any anatomic image. the former can reflect theregions of reoxygenation, but the latter reflect the amplitude of oxgenation changes.3. Themean BOLD signal measured in ROImax and most of the ROInon-max (57/60) whichlocated on the tumor parenchyma increased obviously as soon as Carbogen inhalation, thenflatten out when reached a certain level.While the mean BOLD signal measured inROInone and ROInon-max (3/60) which located on the necrosis displayed no variationtendency after Carbogen inhalation.4. The measurements obtained in ROInone, includingT value, PSC and ΔSI were reduced significantly in comparing with ones got fromROImax and ROInon-max (P <0.01). Correlation analysis showed that in ROImax, onlyPSC were positive correlated with MVN (Pearson r=0.59, P=0.01). And In ROInon-max,the significant positive correlation was not only been detected between PSC and MVN(Spearman r=0.55, P=0.00), but also between ΔSI and MVN (Spearman r=0.37, P=0.00).Conclusion: BOLD fMRI combined with non-HRF post-processing method can beused to evaluate tumor oxygenation changes. The postprocessing image could overlay withany anatomic image,contributing to the combination of morphology and function, as wellas implementation"visualization"of biological information. And the oxy-amplitude map hasmore important clinical significance comparing with oxy-localization map.