| 125I seeds are commonly used as radioactive seeds for permanent tissue implantation in brachytherapy.Because of its excellent radiophysical advantages,in recent years,more and more basic research and clinical reports have been applied to the treatment of spinal metastatic carcinoma.At present.There are still some questions and difficulties in the detail of 125I seed brachytherapy for spinal metastatic carcinoma.A new solution is proposed:Model of brachytherapy for spinal metastatic carcinoma by 125I seed implanted around tumor nargin.In this paper,the theoretical,technical and practical verification of the model has been carried out.The HVL of 125I seed rays in different BMD of cancellous bone,model verification and practical testing,clinical principle verification,device design and software development have been carried out.The study is divided into five parts:Part ?:Detection of 125I seed HVL of cancellous bone with different BMDObjective:To detect the HVL of 125I seeds in cancellous bone of different BMD and establish the equation of the relationship between BMD and HVL.Method:The spinal segment of osteoporosis was obtained and the BMD were measured by DXA and QCT.The thickness of cancellous bone sample in ROI was measured.The TLD and the standard 125I seed were placed on both sides of cancellous bone respectively,and the standard was unified:the central point of the TLD coincided with the central point of the 125I seed source,and the longitudinal axis of the 125I seed source coincided with the diagonal line of the TLD.According to the reading-dose conversion curve of the dosimeter fitted in front,the reading of the RGD3D thermoluminescence dose meter was converted into the dose of irradiation,which was used as the dose rate RDR measurement value(mGy/h)of 125I seed.Gradually reduce the thickness of cancellous bone and the dose rate measurement of 125I seed were measured repeatly.Finally,the thickness of cancellous bone mass and the dose rate of 125I seed were calculated,and the coordinate of dose-rate data of cancellous bone mass thickness-125I seed was obtained,and the EXCEL establishment table was input.After drawing the thickness dose rate conversion curve,the linear equation function of thickness dose rate relationship and fitting index R2 were obtained,and the corresponding bone density cancellous bone 125I seed ray HVL was calculated.Furthermore,according to the HVL of 125I seed rays of cancellous bone under different BMD,the linear equation and fitting index R2 were obtained by the same analysis method.The same method was used to detect and calculate the cortical bone of the vertebral body,and different bone cement ratios were applied to the 125 1 ray HVL.Results:The dose rate of cancellous bone mass thickness-125I seed source was linear,and the fitting index R2 was more than 0.9.By EXCEL linear analysis,linear equation of HVL relationship between cancellous bone and cancellous bone of different BMD was obtained:HVL=(324.59-BMD)/59.289,R2=0.8243.Due to the thickness of the cortex and the limitation of the equipment,it was not possible to complete the detection of the 125I seed HVL of the cortical bone of the vertebral body.?HVLPMMA1:11=7.5826mm,HVLpMMA3:2:1=5.374mm?Conclusion:There was a negative logarithmic relationship between the dose rate of cancellous bone thickness and 125I seed source,and the dose rate of 125I seed source decreased linearly with the increase of cancellous bone thickness.There was a negative linear relationship between BMDof vertebrae and 125I seed ray HVL.With the increase of vertebral cancellous BMD,the HVL of 125I seed ray showed a linear decrease in different ratio.Bone cement has a strong barrier/absorption effect to 125I rays.Part ?:Establishment of brachytherapy model of 125I seed tumor in spinal metastasesObjective:To establish a new 125I brachytherapy model for spinal metastases and to verify theoretically.Methods:First of all,a brachytherapy model of 125I seed tumor was established for spinal metastases.To remove part of the bone(mimic the osteolytic destruction area of the tumor)from the cancellous bone region of the specific BMD.125I(single exit activity 0.8 mCi,calibrated activity 0.73 mCi)was inserted manually into the margin bone of the tumor in the osteolytic destruction area of the tumor.The seed spacing was 3*HLV,the actual seed spacing?7mm.The diameter of the tumor was 20mm.After CT verification,Placement of TLD in posterior edge of vertebral body;intervertebral foramen;the transverse protuberance of the pedicle;45°of the vertebral margin;anterior vertebrae;the intervertebral disc above the tumor;tumor focus?The plane of the TLD element faces the tumor focus.The radiation dose rate and dose were measured.Then,the calculation of the relevant indicators of the model is completed:Pd,MPD,Mpd,Radiation dose-volume density,Radiation dose-surface area density,Calculation of "Cold Point" radiation dose and Seed spacing in irradiated area,The efficiency of brachytherapy was calculated.Results:the model of brachytherapy for 125I seed tumor with metastatic carcinoma was established successfully.The initial irradiation dose rates(cGy/h)of the posterior edge of vertebral body(cortical absence),intervertebral foramen,transverse process of pedicle,45°of vertebral margin,front of vertebral edge,superior intervertebral disc,and 125I position of tumor center are 1.52,0.25,0.22,0.30,0.42,0.91,4.10 respectively.The 6 half-life doses(cGy)were 3179.76,524.62,458.65,619.41,867.85,1895.76 and 10323.55 respectively.The posterior margin of vertebral body(absence of cortex),intervertebral foramen,anterior transverse process of pedicle,45 0 of vertebral margin,front of vertebral edge,and superior disc surface dose(cGy/cm2)of the lesion were 19873.50,3278.91,2866.54,3871.33,5424.09,11848.52 respectively.Based on the simplified model of 125I seeds as point source,the six half-life radiation doses max(cGy)of 1*HVL,1.5*HVL,2*HVL HVL and 3*HVL cancellous bone outside the implantation site were 5300,4770,2650,1320 respectively.Calculation of tumor irradiation boundary at 1*HVL,1.5*HVL,2*HVL and 3*HVL outside seed implantation site,The body density(cGy/cm3)in the tumor area was 516.2,424.9,400.7,293.8.Surface density(cGy/cm2)299.4,267.0,271.1,227.2.Calculation of "cold point" radiation dose in the irradiated area:The radiation dose of 6 half-life "cold point" was the lowest at 509cGy-1022 cGy when the implantation spacing was 3*HVL and the implantation spacing was 2*HVL.Conclusion:The edge distribution of 125I seed tumor in spinal metastatic carcinoma was detected by experiments.The radiation dose distribution in the model of brachytherapy was measured.It is proved that the model has a good dose distribution effect.Through theoretical calculation,it is proved that Max=3*HVL,can still kill tumor cells and block tumor cells.The brachytherapy model of 125I seed tumor with spinal metastases has higher radiation efficiency and better conformal characteristics:1.Conformal distribution of tumor-seed space,radiation dose-conformal of tumor.2.The conformal of cell activity and seed irradiation dose within the tumor can kill the tumor by 125I radiation,control the progress of the tumor,and intercept the progress of the infiltrating body.Part ?:PVP combined with 125I implantation in the treatment of metastatic spinal carcinomaObjective:Verification the possibility and effect of coaxial puncture-seed implantation technique used in PVP combined with 125I implantation in the treatment of Spinal metastatic carcinoma in principle.Method:From May 2014 to May 2016,88 patients(45 males,43 females)with spinal metastases in our hospital were collectedaged aged 29 to 79 years(mean:56 years).Under the guidance of DSA,PVP(n=30)and PVPI(n=58)were performed.Among the patients undergoing PVPI operation,28 cases were operated by the technique of tumor edge distribution of controllable distribution of seeds.The physical index of irradiation,imaging evaluation,the pain score of VAS and the survival rate were evaluated(postoperative,urvival time,calculated the postoperative survival rate of 6m 12m and 24m).Drawing Kaplan Meier Curve of patient Survival data.The VAS score of preoperative and postoperative pain was analyzed statistically.Result:PVP or PVPI were successfully performed in 88 patients.Each PVPI patients implanted 10-30 seeds(mean:22 seeds).The range of total activity of seeds was 6.4-20.4mCi.MPD=90?140Gy.spinal cord dosage ?40 Gy;Other endangering the dose of the organ<25 Gy.65 patients were followed up in hospital and 23 by telephone for 6-24 months.79 patients died,the causes of which include:tumor progression leading to multiple organ failure and other diseases.Imaging examination showed that the seeds distributed in the edge of the tumor,in the edge of the bone cement body.The distribution effect is good.Seed distribution biasmax?1.8cm.After 72 hours of operation,the intractable pain in the patients was significantly relieved than that before operation.The VAS score was compared with Wilcoxon rank sum test(P<0.05),The difference is statistically significant.The 6 m and 12 m,24m survival rates after operation were 92%and 40.8%,10.2%.Conclusion:1.After prebending,the controllable seed distribution can be realized by single needle placement through pedicle of vertebrae,which is required by TPS;2.Compared with the technique of multi-needle puncture,single needle puncture has a comparative advantage;3.In PVPI operation of spinal metastatic carcinoma,the location of seed distribution can be relatively concentrated on the edge of tumor and bone region around tumor edge in bone cement distribution area,so as to increase radiation efficiency.Part ?:The development of 125I seed source spinal tumor edge implant auxiliary operation instrument and software systemObjective:Design the instrument to realize the progressive multi-cone edge seed implantation under the single-channel coaxial puncture and realize the requirement of brachytherapy model of 125I seed tumor edge distribution for spinal metastases,then design and compile the supporting software for the implant model.It is helpful to monitor and evaluate the effect of brachytherapy during the operation.Method:To reconstruct the existing PVP needle,design and manufacture a complete set of degree of depth-guide sleeve,angle disc,and complete single-channel coaxial puncture multi-cone edge seed implantation on the human vertebral body which simulates the osteolytic destruction of tumor.To realize brachytherapy with 125I seed tumor edge distribution for spinal metastases.At the same time,the software of operation assistant classifies the space coordinate system of tumor itself and the detection and monitoring coordinate system into the same space system.Based on the spatial geometric positioning and trigonometric function calculation,the number of implanted seed sources and seed implantation path and three-dimensional space coordinates can be determined.After seed source implantation,the quality of seed source implantation can be verified without the target tissue image,and the spatial distribution of the actual seed source in the target area can be analyzed immediately.Result:Design and manufacture of apparatus have achieved the desired effect,Progressive multi-cone edge seed implantation under single-channel coaxial puncture.The software can be used to monitor and evaluate the operation and improve the operation efficiency.Conclusion:The model of brachytherapy with 125I seed tumor edge distribution for spinal metastases can be achieved by the single channel coaxial puncture with progressive multi-cone edge seed implantation.The auxiliary software system can effectively accomplish the function of intraoperative detection and immediate evaluation.Part ?:Role of IL6 in 125I particle induced radiation myelitisObjective:To evaluate the role of IL6 in radiation myelitis and to find a feasible intervention method.Method:A total of 5 suspected cases with radiation myelitis were screened and the levels of IL6 in peripheral blood and cerebrospinal fluid were detected.The levels of IL-6,changes of NT and iNOS in the spinal cord of RM rats were detected by RT-PCR,Western blot,BCA and immunohistochemistry;the changes of the corresponding indexes after application of IL6 antibody,PERK interference agent and iNOS inhibitor aminoguanidine were observed.Result:The level of IL-6 in cerebrospinal fluid(CSF)was positively correlated with total NO level.IL-6 is involved in the death of 125I-induced radiation spinal cord cell.IL-6 can regulate ROS related factors and activate PERK signaling pathway.After the interference of PERK,it also decreased the apoptosis of spinal cord neurons induced by RM and the expression of NT and iNOS.The secretion level of IL6 was detected by ELISA,and we see amin also significantly inhibited the secretion of IL6 induced by 125I.Conclusion:After screening for inflammatory factors before and after 125I treatment,it was found that the level of IL-6 was significantly increased and positively correlated with NO level,after antagonizing IL-6 and iNOS,the death rate of spinal cord neurons caused by 125I was significantly reduced;further study on the mechanism showed that IL6 could increase the expression of NT and iNOS,activate the PERK-eIF2a signaling pathway,silence the PERK on this pathway,and attenuate the death of spinal cord neurons caused by 125I,and decrease the levels of NT and iNOS;the in vivo experiments on 125I rat models showed that aminoguanidine,an iNOS inhibitor,significantly decreased the inflammatory response induced by 125I and the level of IL 6.Different from the 125I seed implantation brachytherapy mode for soft tissue tumors,brachytherapy for bone tumors should have its own characteristics.Especially in the treatment of spinal metastatic carcinoma,these characteristics need more attention:1.The types of tissue in tumor focus and its surrounding area are complex,especially the barrier/absorption effect of bone tissue to radiation needs more attention;2.There are organs and tissues that are highly sensitive to radiation in the spinal area.In order to avoid serious collateral damage,high attention should be paid to the improvement of radiation therapy efficiency at the same time;3.Due to the lack of efficient monitoring and guiding equipment,how to achieve real-time monitoring and real-time evaluation is the key to improve the efficiency of operation and reduce the error.This study is helpful to solve the above difficulties. |
PDF Full Text Request