The Clinical Applications Of CT Perfusion Imaging In Glioma And Correlative Studies With Experimental Histopathology Of Glioma Angiogenesis

Part I: Correlative Studies of CT and CT Perfusion Imaging with histopathology in rat brain C6 gliomaObjective To observe manifestations of CT and CT perfusion imaging in rat brain C6 glioma, Correlative studies were performed between the manifestations of CT and CT perfusion imaging with histopathology. Methods Rat C6 glioma cells were cultured in vitro and harvested, counted, resuspended in serum-free medium for intracerebral injection. About 10~6 cells were injected into the caudate nucleus of rat brain under guiding of stereotaxic apparatus to establish a rat brain glioma model. CT and CT perfusion imaging were conducted after 12-18 days implantation in rat brain C6 glioma. After CT examination, all tumor-bearing rat were perfusion-fixed with 4% paraformaldehyde. The glioma-containing samples were sliced at a coronal plane and stained with hematoxylin and eosin (HE). The manifestations of CT and CBV (cerebral blood volume) imaging were compared with pathologic and immunohistochemical appearances. Results C6 rat brain glioma was solid tumor, all rat brain C6 gliomas presented as low density on CT and demonstrated obvious homogeneous or annular enhancement after the administration of contrast medium. CT perfusion imaging showed that the rCBV (regional cerebral blood volume) value increased in C6 glioma. Histopathologic analysis revealed that all the tumor growed invasively, and as the volume of tumor increase, massive necrosis developed in the central of tumor. There were a lot of neovascular and blood antrum in the tumor, the dilated vascular could be seen around tumor. It was highly significant (P<0.01) that the high VEGF expression part in the tumors had a high rCBV value. Conclusion Rat brain C6 glioma was a very stable and ideal animal model for experimental glioma studies. CT can provide its pathomorphologic information precisely and CT perfusion imaging can provide the changes of angiogenesis activity in vivo. Part II: Correlative Studies of early histopathologic changes of rat brain C6 glioma to antiangiogenic treatment with CT Perfusion imagingObjective To observe the therapeutic effect of antiangiogenesis on rat brain C6 glioma and to study the practical value of CT perfusion in evaluating the early response of the tumor to the treatment. Methods 20 cases of rat brain C6 glioma were divided into treatment group and control group at random. At the 14 days after tumor implantation, the endostatin was administered continuously at a dose of 10mg/kg/d/for 7 days. Conventional CT scan was performed to calculate the volume of tumor; CT perfusion was performed to measure the cerebral blood volume (CBV) of tumor before and 48 hours after the treatment, and microvessel density (MVD) in rats C6 glioma were detected with immunohistochemistry technique. Results The volumes of glioma in the treatment group and control group all increased continuously, but the volume of glioma in the treatment group was significantly smaller than that in control group after treatment. The tumor volume was 246.3 ± 46.6 mm~3 in endostatin treated group which was lower than that in control group 356.2 ± 78.3 mm~3(p<0.01). The rCBV value in treatment group was 38.462± 1.96ml/100g and the MVD was 15.61±6.58 , which were lower than those in control group with statistical significance(p<0.01). Conclusion Endostatin could inhibit the angiogenesis of the rat C6 glioma. CT perfusion is an effective method to observe the early response and to predict the efficacy of tumor to antiangiogenic treatment. Part III: Correlation of CT Perfusion Imaging with VEGF Expression in human gliomasObjective To obtain rCBV (relative cerebral blood volume) value by using multi-slice helical CT perfusion imaging, to evaluate the correlation between rCBV value and VEGF (vascular endothelial growth factor) expression in human gliomas. Methods Multi-slice helical CT perfusion imaging was performed after routine scanning in 24 patients with brain glioma, including 8 cases of low-grade glioma 10 cases of anaplastic astrocytoma and 6 cases of glioblastoma. The rCBV values were calculated and the VEGF expressions in tumors were determined by immunohistochemistry method. The correlation of CT perfusion imaging with the pathologic grade and VEGF expression was analyzed. Results The rCBV value in low-grade glioma, anaplastic astrocytoma and glioblastoma were 4.524 ± 0.4628, 6.672 ± 0.8462, 9.849± 1.2636:and the ALD values of VEGF expression in different grade glioma groups were 0.3177 ± 0.0768, 0.4693 + 0.0956, 0.6368 ±0.1072 respectively. Statistically significant difference in rCBV existed between different groups. The rCBV value was closely correlated with VEGF expression in glioma. Conclusion The VEGF expression of glioma has a positive correlation with rCBV value in CT perfusion imaging. CT perfusion imaging can be used in the assessment of angiogenesis activity of brain glioma. Part IV: MSCT perfusion imaging in preoperative grading of brain gliomasObjective To evaluate MSCT perfusion imaging in the preoperative assessment of histological grade in brain gliomas. Methods Multi-slice helical CT perfusion imaging was performed in 24 patients with astrocytic tumours, the scanning images were processed in adw 4.0 workstation, CBF (cerebral blood flow),CBV (cerebral blood volume),MTT (mean transit time), and PS (Permeability Surface) values were calculated and perfusion maps were analyzed. Results The CBF values in low grade astrocytoma, anaplastic astrocytoma and Glioblastoma group were 34.868± 13.285, 68.325 ± 18.268, 106.315±28.269 ml/min/100g respectively. The CBV values were 2.733 ± 0.8274, 4.755 ± 0.4367, 6.654 ± 0.5249 ml/100g respectively. The MTT values were 3.98 ± 1.68, 4.06 ± 2.06. 4.03 ± 1.85 min respectively. The PS Values were 3.668 ± 0.5237, 8.3524 ± 0.8975,14.7452 ± 0.328 ml/min/100g respectively. Statistically significant difference in CBF,CBV and PS value existed between each group. There is no statistically significant difference in MTT value between each group. Conclusion MSCT perfusion imaging and the parameters CBF,CBV&PS are useful in preoperative estimating the histological grade of astrocytic tumours.