Animal Experiment And Clinical Application Study On Quantitative Analysis Of Radiation-induced Injury Micro-changes With MR DWI

BackgroundRadiotherapy is one of the major therapeutic tool on malignant tumor and the radical cure tool on partial of them. According to WHO statistics in 1998, malignant tumor control rate of all over the body is 45%, operation occupis 22% and radiotherapy 18%. Over 70% malignant tumor patients had radiopeutic experience. However, X-ray can reasult in normal tissues injury at the same time of killing tumor cells. Radiotion injury of brain is a radioactive syndrome caused by various kinds of reason and one of the most serious long-term complications after pate malignant tumors radiotherapy. Following oncotherapy level improvement and life span unceasing prolongation, the incidence of radiation brain injury to go up year by year. Radiation brain injury impacts living quality, life span and prognosis of patients seriously.Ever since used non-trauma imaging and planning radiotherapy, the cognition to radiation brain injury has great improvement. Diffusion weighted imaging(DWI) is a molecular level magnetic resonance imaging. DWI can reflect hydrone space volume and geometry-shape in hixtiovyte micro-environment. It's value was sufficiently confirmed in cerebral ischemia during hyper-early diagnosis. The value and clinical significance of DWI has been displayed on diagnosis demyelinating disease in central nerves system. For this reason, it has vital application value to study micro-changes on radiation brain injury and hyper-early diagnosis.Objective1. To establish micro-changes animal model on early-term radiation brain injury.2. To measure ADC value of white matter and gray matter in dog brain and through observation ADC value and histological changes to assessment the value on DWI quantitative analysis micro-changes during radiation brain injury latent period.3. To summarize clinical and histological changes of radiation encephalopathy and correlated multiplicity.4. Through measurement temporal lobe ADC value on nasopharyngeal carcinoma(NPC) patients after radiotherapy with normal appearance on MRI and to assessment the value about DWI in detecting micuoscopic disease in normal appearing white matter(NAWM) and to research its development regular pattern.5. To assessment the clinical value and significance in quantitative analysis micro-changes of radiation brain injury with diffusion weighted imaging.Material and method1. Animal experiment To select 9 hybrid dogs. Age is from 1 to 3 years and weight from 10kg to 20kg. 4 dogs are female and 5 male. The irradiation applies 60Co device and single fraction. Exposure fiele size is 4 X 4cm ,distance 65cm and depth 3cm. Before and 2,4,8,10,12 weeks after irradiation, measurement dog brain ADC value respectively and comparison with before irradiation. Histological changes are observated under light microscope and electron microscope.2. Clinical application study(1) Normal control group 30 healthy volunteers are randomly secected. 19 patiens are male and 11 female. Age from 30 to 70 years and mean 50 years.All brain of them are normal on MRI and nervous system examination. The ADC values of temporal lobe white matter and gray matter are measured respectively. Measurement deck, position and region of interest in accordance with NAWM group.(2) NAWM group To select 40 post-radiotherapy with NPC patients whose brain MRI normal. All of them have 22 male and 18 female and KPS score are all over 60. Age ranged from 32 years to 71 years and average of 51 years. According to staging-standard in Fuzhou meeting, these patients are staged: Ti 7 cases, T2 13 cases, T3 12 cases, T4 8 cases;No 9 cases, Ni 11 cases, N2 15 cases, N3 5 cases;II-stage 8 cases, III-stage 23 cases, IVa-stage 9 cases. The ADC values of temporal lobe white matter and gray matter are measured respectively. Measurement deck, position and region of interest in accordance with normal control group.(3) Radiation brain injury group To select 46 post-radiotherapy with NPC patients whose brain MRI normal. All of them have 36 male and 15 female and KPS score are all over 60. Age ranged from 27 years to 69 years and average of 49.6 years. According to staging-standard in Fuzhou meeting, these patients are staged: Ti 8 cases, T2 15 cases, T314 cases, T4 9 cases;No 10 cases, Ni 13 cases, N2 17 cases, N3 6 cases;II-stage 11 cases, Ill-stage 25 cases, IVa-stage 10 cases. The ADC values of temporal lobe diseased region and corresponding opposite side region are measured respectively.3. Statistical analysis To use x dts expressing the measurement results and SPSS 10.0 statistical software analysis data. All these data analyzed with statistical method of one-way ANOVA, t-test, least-significant, correlative ang regression analysis.Reasult 1. Animal experiment(1) Animal reaction postirradiation All of the dogs postirradiation have decreased food appetite and activity after analepsia. D9 show up increased intracranial pressure caused by brain edema, such as walking unsteadiness, vomit. After a month, several dogs hair at exposure field becomes rarefaction and become hairless two month later. D6 dog is marked symptosis. Skin reaction happens three month later. Vagina of D5 dog bleed between 2 to 3 month and the hair surrounding exposure field become white and skin pigmentation.(2) MRI appearance Dog brains are normal at 2,4 weeks postirradiation. At 8 weeks postirradiation, dogs showed brain atrophy display local cortex thinning, sulcus widening and ventriculomegaly. To twelveth week, two sides of cerebral gemisphere is atrophy but MRI appearance has not abnormal signal intensity. The white matter, gray matter and whole brain tissue ADC value of dog brain tissue at pre-irradiation are 71.893+4.969 mm2/s, 69.767+4.327 mm2/s, 70.83+4.742 mm /s respectively. Second week postirradiation are 63.66+5.956 mm2/s, 60.99 + 7.082 mm/s, 62.325 + 6.626 mm2/s respectively. ADC value than ones of pre-irradiation decreasd obviously and variance has statistical significance, P< 0.0001;Fourth week postirradiation are 68.39 + 5.12 mm2/s, 65.687 + 6.798 mm2/s, 67.038+6.12 mm2/s respectively. ADC value than ones of pre-irradiation decreasd obviously and variance has statistical significance,P<0.01;Eighth week postirradiation are 67.652+4.597 mm2/s, 66.957+5.337 mm2/s, 67.463+4.965 mm2/s respectively. ADC value than ones of pre-irradiation decreasd obviously and variance has statistical significance. P<0.05;Tenth week postirradiation are 64.8±5.98 mm2/s, 65.567 + 5.725 mm2/s, 65.183 + 5.817 mm2/s respectively. ADC value than ones of pre-irradiation decreasd obviously and variance has statistical significance, F<0.001;Twelveth week postirradiation are 66.393 + 6.908 mm2/s, 63.453 ±5.69 mm2/s, 64.923 + 6.447 mm2/s respectively. ADC value than ones of pre-irradiation decreasd obviously and variance has statisticalsignificance, P<0.0001.(3) Pathohistologic changes By light microscope, temporal lobe, end-lobe, cerebellum and brain stem of dog brain show cytotoxicity edema and pyknosis. Surrounding mater and vessels was infiltrated by lymph cell, mononuclear cell. Small vessels wall thickening and hemorrhage;By electron microscope, we can view myelin sheath structure degeneration, rarefaction and solution. Glial cell edema, pyknosis and axon vacuity and in of it mitochondrion swell, lysosome mult, organelle vacuolization , oligodendrocyte degeneration and necrosis. Vessel wall becomes thickening, endothelial cell overgrowth and even ablating.2. Clinical analysis on the patients of radiation brain injuryIn 46 patients of radiation brain injury, half temporal lobe lesion are 21 cases(45.7%), bilateralis lesion are 25 cases(54.3%);Latent period is range from 17 months to 82 months and mean 37 months;Clinical sympotoms include: 15cases of headache and dizziness, 21 cases of remenbrance decrescence, 11 cases of dysphagia, 11 cases of one side extremity somatasthenia, 6 cases of ataxia and 6 cases of conscious disturbance. Upper bound of cranial base field, dose of cranial base and re-radiation are the influence factors to radiation brain injury and have statistical significance, P<0.0001,0.01 and 0.01 respectively.3. Temporal lobe ADC value of postradiotherapy NAWM groupADC average value of temporal lobe is (0.767± 0.135 ) X 10"3mm2/s. ADC value of temporal lobe white matter is (0.759+0.139) X 10"3mm2/s. Variance has not statistical significance (f=0.203, P=0.420);ADC value of temporal lobe gray matter is (0.892 ± 0.122) X 10"3 mm2/s and variance has statistical significance to comparison with ADC value of white matter (t=-3.937, P=0.000);ADC value of white matter at post-radiotherapy compared with one of normal control group, the variance has statistical significance, P<0.05;To compare ADC value of temporal lobe gray matter at post-radiotherapy with one of normal controlgroup, its ADC value develop decreasing tendency but the variance has notstatistical significance.4. ADC value of radiation brain injuryIn white matter edema stage, the ADC average value of focal zone is (1.493 ±0.255) X 103mm2/s and the ADC average value of control plot is (0.788 ± 0.102 ) X 10"3mm2/s. To compare with them, the variance has statistical significance, P<0.0001;In white matter necrosis stage, the ADC average value of focal zone is (2.602 ±0.380) X10~3mm2/s and the ADC average value of control plot is (1.716±0.162) X 10"3mm2/s. To compare with them, the variance has statistical significance, P<0.0001;The ADC average value of gray matter focal zone is (1.517 ±0.106) X 10"3mm2/s and the ADC average value of control plot is (0.916 ±0.037) X10"3mm2/s. To compare with them, the variance has statistical significance, i><0.0001.Conclusion1. Latent period of radiation brain injury is range from 17 months to 82 months and mean 37 months;In many clinical factors, upper bound of cranial base field, dose of cranial base and re-radiation are the most important influence factors to radiation brain injury.2. Temporal lobe ADC value of post-radiotherapy patients with NAWM decreased obviously and in accordance with the results of animal experiment. Tts main basic pathohistology is microstructure pathohistology changes such as cytotoxic edema, vascular endothelial cell damage and myelin sheath of white matter rarefaction and so on.3. After radiation brain injury development ,ADC value increasing obviously prognosticates vascular edema, white matter demyelination and cellulose necrosis. All of these limits the water diffusion.4. Diffusion weighted imaging is a extremely sensitive imaging technique to detect hydrone micro-diffusion movement in vivo. At early stage of brain tissue postirradiation, we can detect the changes of brain tissue ADC value. This changes is a most important significance for studying NAWM in latent period. Brain tissue ADC value can use as a quantization index for detecting micro-pathohistologic changes during latent period of radiation brain injury.5. By light microscope, temporal lobe, end-lobe, cerebellum and brain stem of dog brain show cytotoxicity edema and pyknosis. Surrounding mater and vessels was infiltrated by lymph cell, mononuclear cell. Small vessels wall thickening and hemorrhage;By electron microscope, we can view myelin sheath structure degeneration, rarefaction and solution. Glial cell edema, pyknosis and axon vacuity and in of it mitochondrion swell, lysosome mult, organelle vacuolization , oligodendrocyte degeneration and necrosis. Vessel wall becomes thickening, endothelial cell overgrowth and even ablating.