| Objective Malignant glioma is a common malignant intracranial tumor, its prognosis is poor. With the emergence of temozolomide, surgery, oral for temozolomide joint of radiation treatment become the standard of malignant glioma therapy, this treatment protocol can significantly improve survival of patients with malignant glioma. Even after active treatment, most patients with malignant glioma have to undergo the process of tumor recurrence. At the same time, the treatment protocol increased the risk of radiation necrosis of the normal brain tissue. Conventional contrast-enhanced magnetic resonance imaging can not distinguish between glioma recurrence and radiation necrosis accurately. And the treatment and prognosis of the two lesions are entirely different. So it is very important to distinguish them accurately. This study explored the methods for establishing the model of intracranial C6 glioma and the cerebral radiation necrosis in rats. We obtained multiple sequences MRI of the intracranial C6 glioma and the cerebral radiation necrosis in rats by 7T small animal MRI equipment and got the data of imaging by the image-analysis software. Then we found out the sequences of MRI that have significant differences of the two kinds of lesions through the ststistical analysis. Synthetically considered the difference of sequences and their clinical significance, we set a method to accurate identification of glioma and cerebral radiation necrosis. Used the method to the patients of suspicious glioma recurrence after surgery and radiation treatment, and verified the diagnostic accuracy of it to distinguish the glioma recurrence from radiation necrosis and its value in clinical application.Materials and Methods A 10 ul volume of 1 x 108 / ml C6 glioma cell suspension was injected into the right caudate nucleus of adult wistar rats via stereotactic method by micro injection pump. The growth of intracranial C6 glioma was observed by magnetic resonance imaging scan. The brain tissue of rats was irradiated by Varian linac with a total dose 40 Gy. The irradiated area is 1 x 1 cm2 of the left cerebral hemisphere of rats and the progress of cerebral radiation necrosis was observed by magnetic resonance imaging scan. The brain MR imaging of rat models of intracranial C6 glioma and cerebral radiation necrosis were obtained by Bruker 7T small animal MRI equipment. These MR images included CE-T1 WI, T2 WI, DTI, MRS and PWI. After obtained these MR imaging datum by matched analysis software of SIEMENS, we conducted the statistical analysis between the two kinds of rat models. And we got a diagnosis equation flow diagram based on MRS and PWI data to different between glioma and radiation necrosis. Then we retrospective analyzed 20 patients with suspected recurrent glioma. They were initially diagnosed of glioblastoma by pathology after surgery and accepted radiation therapy regular after surgery. And the enrolled patients in this study from Tianjin Huanhu hospital between March 2013 and March 2015. The 20 patients were collected corresponding sequences of brain magnetic resonance imaging and deduced the lesions based on the flow diagram above. The gold standard to decide the lesions is according to the long-term clinical and radiographic follow-up. Compare the results of the flow diagram with the results of the gold standard, and the accuracy of the flow diagram method is obtained.Results 10 adult wistar rats were inoculated the C6 glioma cells suspension into the right caudate nucleus. The best time to obtain images of intracranial glioma model is the fourteenth to the twentieth days after inoculation through observed the growth of glioma by MRI scanning. 10 adult wistar rats were irradiated with X-rays, and all rats survived. At the 8 months after irradiation, the left cerebral hemisphere appeared abnormal high signal on T2 WI of 7 rats and two of them showed a big piece of high signal with no clear boundary. Six rats at the 14 th day after inoculation the C6 glioma cells suspension and six rats after irradiation 8 months were included the next study. The twelve rats were collected the brain MR imaging by Bruker 7T small animal MRI equipment. The MRI sequences including SE-T1 WI, T2 WI, DTI, MRS and DSC-MRI. Both of the leisons of the intracranial C6 glioma and the radiation necerosis appeared enhanced performance on T1 WI. The value of r FA?r ADC?Cho / Cr?Cho / NAA?NAA / Cr?r CBV and r CBF in the intracranial C6 glioma group and the cerebral radiation necrosis group is 0.49±0.02,0.31±0.04(P=0.00);0.98±0.03,1.45±0.18(P=0.001);2.43±0.73,1.17±0.24(P=0.02);0.67±0.31,0.91±0.22(P=0.15);4.70±2.86,1.36±0.50(P=0.03); 1.35±0.05,0.69±0.11 (P=0.00); 1.42±0.15,0.78±0.07(P=0.00),respectively. Based on the data above, we acquired a diagnosis equation flow diagram through statistical analysis combined with the clinical significance of each test index. The diagnosis equation flow diagram is considered the value of CHO / NAA and Cho / Cr of the lesions firstly. When the value of Cho / NAA? 3.0 and the value of Cho / Cr? 1.80, the lesion is inferred as glioma recurrence. And when the value of Cho / NAA < 3.0 and the value of Cho / Cr<1.80, the lesion is inferred as radiation-induced brain tissue necrosis. When the value of Cho / NAA and the value of Cho / Cr don't satisfied the both conditions above, the value of r CBV and r CBF will be taken into account to further determine the lesions. We considered the sum value of r CBV and r CBF and set the diagnostic threshold to 2.10. When the value is equal or greater than 2.10, the lesion is inferred as glioma recurrence. When the value is less than 2.10, the lesion is inferred as radiation-induced brain tissue necrosis. The accuracy of the diagnosis equation flow diagram was 100% in distinguishing C6 glioma from radiation necrosis in this animalexperiment. 20 patients with suspected glioma recurrence were collected the brain MR imaging. The sites of lesions were confirmed on CE-T1 WI and the data of lesions on MRS and DSC-MRI was analyzed. According to the diagnosis equation flow diagram above, 15 patients were inferred as glioma recurrence and 5 patients were inferred as radiation necrosis. There is only one patient's diagnosis different between the diagnosis equation flow diagram and the gold standard. The diagnosis equation flow diagram deduced a lesion as glioma recurrence, but the lesion as radiation necrosis based on the gold standard finally. To sum up, the diagnosis accuracy of the diagnosis equation flow diagram to distinguish glioma recurrence from cerebral radiation necrosis is 95%.Conclusions 10 ul C6 glioma cell suspension with 1 x 108 / ml was stereotactic injected into the right caudate nucleus of rats by micro injection pump can successfully established the model of intracranial C6 glioma. This kind of modeling method has the advantages of easy operation, high success rate and stability of model. 14 to 20 days after inoculation is the best time to obtain the MRI of glioma. A total dose of X-ray is 40 Gy, construction 1cm layer and radiation to cerebral hemisphere can be successfully established cerebral radiation necrosis model of rats. The signal change on T2 WI occurred 6 months after irradiation and the obvious radiation necrosis on T2 WI appeared at 8 months after irradiation. The diagnosis equation flow diagram acquired from the animal experiments has a high diagnostic accuracy to distinguish glioma recurrence from radiation necrosis in clinical and it can be popularized in clinical application. |
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