Dissertation
Dissertation > Medicine, health > Oncology > Nervous system tumors

Assessment of Therapeutic Effect of Nanometer Drug in Rat C6 Gliomas with 7T Animal MRI

Author HuangBingCang
Tutor GengDaoYing
School Fudan University
Course Medical Imaging and Nuclear Medicine
Keywords animal MRI Glioma Rat Brain animal model Glioma Nanometer Drug Pathohistology Diffusion Weighted Imaging Magnetic resonance imaging Perfusion Weighted Imaging
CLC R739.4
Type PhD thesis
Year 2010
Downloads 223
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PURPOSE:To found the model of rat C6 glioma and study their changes with 7T animal MRI, including conventional MR imaging, DWI, MRS and PWI. Investigate MRI features of rat brain glioma and optimize imaging sequence and parameter.MATERIALS AND METHODS:40 SD rats with body weight 200g were choosed and implanted C6 glioma cells at right caudate nucleus of rat brain through stereotaxic apparatus to establish a rat brain glioma model. The location of needing is about 1mm near biparietal suture lateral and 3mm of the right of arcuate suture. The depth of needing is 5mm and drawing back lmm. The total needing liquid is 10ul with cell density of 2×105个/ul. The total needing time is about 10minutes. The needle is drawn after 5minutes. After 7 days of glioma cells implanting, all rats were examined with MRI to choose the rat glioma of the same size and location for study. The chosen 30 rats were examined with conventional MRI, DWI, MRS, and PWI. After MRI examination, the rats were sampled for electronic microscopy and pathology.RESULTS:The tumor developed after 7 days, its survival ratio was 100%. The average volume of glioma is 0.15CM3. C6 rat brain gliomas are proved by pathology and microscopy. There is long T1 and long T2 signal in routine MRI, high signal in DWI. The average rADC value is 0.70×10-3m/s. The baseline of MRS is stable and the ratio of area under peak of Cho/Cr, NAA/Cr, Lac/Cr, Lip/Cr and Cho/NAA is 1.22, 1.67,1.70,0.76,0.75, respectivelly. The PWI curve is stable and the average rrCBV value is 3.73.CONCLUSION:The model of rat brain gliomas could be established by implanting C6 glioma cells through stereotaxic apparatus. The 7T MRI images of all sequences are clear and stable, the optimal parameters of all 7T MRI sequences are found successfully, so they are useful for future experiment. PURPOSE:To study the change of HE, Ki37, VEGFR, CD31, TUNEL, Capase3 stain and microscopy of the treatment response in rat brain C6 gliomas with polymeric vesicles filled with doxorubicin target brain with transferrin. To offer fMRI with animal 7T MRI the contrast gold standard of treatment response with nanometer drug in rat C6 gliomas.MATERIALS AND METHODS:90 SD rats with body weight 200g were choosed and implanted C6 glioma cells at right caudate nucleus of rat brain through stereotaxic apparatus to establish a rat brain glioma model. After 7 days of glioma cells implanting, all rats were examined with MRI to choose the rat glioma of the same size and location for study. The chosen 72 rats were randomly divided into four groups, as Tf-PO-DOX (polymeric vesicles filled with doxorubicin target brain with transferring) group, PO-DOX (polymeric vesicles filled with doxorubicin no target brain with transferrin) group, DOX (liberation doxorubicin) group, control (normal sodium) group, vena caudalis injecting with Tf-PO-DOX, PO-DOX, DOX and normal sodium respectively at 9,12,15 days after implanting glioma cells. All rats were perfused and get samples at 10,13,16 days after glioma cells implanting respectively with 40% paraformaldehyde; examined with HE, Ki37, VEGFR, CD31, TUNEL, Capase3 stain and microscopy.RESULTS:By the contrast of control group, there were some changes in experimental groups, including no apparent change of the tumor volume, decreasing of cell density (HE stain) and cell proliferation (Ki-67 stain). Apoptosis glioma cells which were distributed in periph of glioma were found in experimental group and proved by microscopy. There were some changes in experimental group, including the positive percentage of TUNEL and Caspase 3 stain increasing, the positive percentage of VEGFR and CD34 decreasing. In these changes of experimental groups, the Tf-PO-DOX group was the most apparent, the PO-DOX group was seconday, and the DOX group was the lowest. There were statistical significance between Tf-PO-DOX group and control group (p<0.05)CONCLUSION:Glioma' dissertation">Glioma cells apoptosis could be induced, glioma cells proliferation and tumor microvessel could be restrained by Tf-PO-DOX (polymeric vesicles filled with doxorubicin target brain with transferrin). PURPOSE:To study the value of DWI quantitatelly in assessing the treatment response of polymeric vesicles filled with doxorubicin target brain with transferring in rat brain gliomas.MATERIALS AND METHODS:The establishment of the glioma model and the dividing of experiment groups was the same as Part One and Two. Rats in each group were examined with 7T DWI with many b factors at 10,13,16 days after glioma cells implanting respectively. The rADC values of all rats in each group were obtained by postprocessing. The results of DWI and rADC value and the cell density of HE staining and the apoptosis and proliferation index of immunohistochemistry were analyzed by comparison.RESULTS:The sensitivity of DWI increasing, its the signal to noise ratio decreasing with b factor larger. By the contrast of control group, the rADC value of all experimental groups were increasing, the Tf-PO-DOX group is the highest among experimental groups. There were statistical significance between the Tf-PO-DOX group and the control group (p<0.05). The increasing extent of rADC value will be more apparent with the times of treatment increasing. The rADC values were negative relative with the cell density and the proliferation index (r=-0.84,-0.61, respectivelly). There were plus relative between rADC value and the apoptosis index (r=0.78). CONCLUSION:Glioma cells proliferation in rat brain could be restrained by Tf-PO-DOX (polymeric vesicles filled with doxorubicin target brain with transferrin). The early microcosmic hydrone molecular movement which can offer indirectly the degree of tumor proliferation and apoptosis might be detected with 7T DWI and the rADC value, so 7T DWI is useful for clinc to evaluation of treatment plan, choice of new drug and prognosis estimation.PURPOSE:To study the value of 1H MRS quantitatelly in assessing the treatment response of polymeric vesicles filled with doxorubicin target brain with transferring in rat brain gliomas.MATERIALS AND METHODS::The establishment of the glioma model and the dividing of experiment groups was the same as Part One and Two. Rats in each group were examined with 1H MRS at 10,13,16 days after glioma cells implanting respectively. The ratio of area under peak (Cho/Cr, NAA/Cr, Cho/NAA, Lip/Cr, Lac/Cr) in all rats in each group were obtained by postprocessing. The results of Cho/Cr, NAA/Cr, Cho/NAA, Lip/Cr, Lac/Cr and the results of Ki-67 and TUNEL staining were analyzed by comparison.RESULTS:By the contrast of control group, there were some changes, including Cho/Cr and Cho/NAA descreasing, NAA/Cr, Lip/Cr, and Lac/Cr increasing in experiment groups. The change extent of the metabolin ratio will be more apparent with the times of treatment increasing. Among all experiment groups, the metabolin ratio change of the Tf-PO-DOX group was the most apparent. There were statistical significance between the Tf-PO-DOX group and control group. Cho/Cr was plus relative with the proliferation index(r=0.50). Lip/Cr were plus relative with the apoptosis index (r=0.74).CONCLUSION:Glioma cells proliferation in rat brain could be restrained by Tf-PO-DOX (polymeric vesicles filled with doxorubicin target brain with transferrin). The early treatment response (including the extent of glioma proliferation, apoptosis and microcosmic metabolin change) might be detected with 7T MRS and the metabolin ratio. This may help the clinc change the treatment plan in time, selecting new drug and prognosis judgement.PURPOSE:To study the value of PWI and rrCBV value in assessing the treatment response of polymeric vesicles filled with doxorubicin target brain with transferring in rat brain gliomas.MATERIALS AND METHODS:The establishment of the glioma model and the dividing of experiment groups was the same as Part One and Two. Rats in each group were examined by perfusion weighted imaging at 10,13,16 days after glioma cells implanting respectively. The PWI curve and rrCBV value in all rats in each group were obtained by postprocessing. The results of rrCBV value and the results of VEGFR, CD31, Ki-67 and TUNEL staining were analyzed by comparison.RESULTS:By the contrast of control group, the rrCBV value which were distributed in periph of glioma was decreasing in all experiment groups. The change extent of the metabolin ratio will be more apparent with the times of treatment increasing. Among all experiment groups, the rrCBV change of Tf-PO-DOX group was the most apparent. There were statistical significance between the Tf-PO-DOX group and control group (p<0.05). The rrCBV was plus relative with the results of VEGFR, CD31 and Ki-67 stain (r=0.83,0.77 and 0.74, respectivelly). The rrCBV was negative relative with the results of TUNEL staining (r=0.72).CONCLUSION:Glioma cells proliferation in rat brain could be restrained by Tf-PO-DOX (polymeric vesicles filled with doxorubicin target brain with transferrin). The microcirculation and vascularization can be reflected directly and dynamic by PWI curve. The tiny change of blood volume can be estimated objectively and quantitily by rrCBV. PWI is the powerful tool of therapeutic effect evaluation for the clinc and the nanometer research.

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