放射引起的视神经病变基础与临床研究

发布时间：2018-04-20 08:06

本文选题：放射引起的视神经病变 + 锰离子增强的磁共振扫描　；参考：《复旦大学》2011年硕士论文

【摘要】：第一部分大鼠放射引起的视交叉损伤动物模型的建立 [目的]放疗过程中由于视神经/视交叉受到过量照射而引起的视神经病变(Radiation-induced optic neuropathy, RION)是一种严重影响生活质量的并发症,其主要表现为突然性、无痛性、不可逆性的视觉丧失。其发病机制目前尚未完全明了。临床上尚无有效的治疗方法,神经营养因子及分子靶向治疗药物贝伐单抗具有潜在治疗放射引起的视神经病变的价值。本研究通过一次性大剂量30Gy照射大鼠视交叉,建立放射引起的视交叉损伤模型,为研究放射引起的视神经病变发病机制及寻找其有效治疗方法奠定基础。 [材料与方法]34只大鼠,4只未进行放射作为对照组,30只进行视交叉放射,随机分为放射后2个月组、放射后4个月组、放射后6个月组,分别于照射后2个月、4个月、6个月进行玻璃体内锰离子注射,24小时后行锰离子增强的磁共振(Manganese-enhanced magnetic resonance imaging, MEMRI)扫描,扫描后处死大鼠并进行病理学分析。病理学分析包括HE染色及Luxol Fast blue染色。根据视觉通路强化程度不同,对MEMRI图像进行评分。100倍光镜下对Luxol Fast blue染色进行相对光密度值分析,400倍光镜下对HE染色进行胶质细胞计数。部分大鼠进行电镜分析。 [结果]入组大鼠在饲养过程中死亡4只,在MEMRI扫描前因麻醉意外死亡6只。对照组、放射后2个组、放射后4个月组、放射后6个月组进行MEMRI扫描的分别有4只、5只、4只、11只,共24只；进行病理分析的分别有3只、7只、4只、7只,共21只。放射后6个月组所有大鼠视交叉均产生了明显的病理学变化,主要表现为：脱髓鞘病变,毛细血管增生,星形胶质细胞增多及间质纤维化。相关性分析显示,MEMRI图像视觉通路评分与放射后时间呈负相关,p=0.000; MEMRI图像中以视觉通路评分5分定义为RION,对照组、放射后2个组、放射后4个月组、放射后6个月组发生RION的比例分别为0/3,1/5,2/4,11/11,行卡方检验,x2=15.443,p=0.001；400倍光镜下Luxol Fast blue染色相对光密度值与视交叉放射后时间呈负相关,p=0.000;各组100倍光镜视野下星形细胞数分别为194±65、234±19、124±11,及345±98,相关性分析显示细胞数与放射后时间呈负相关,P=0.005。MEMRI图像显示放射后2个月组的5只大鼠中,1只出现视神经传导功能丧失,但病理学较其余4只未见明显改变。 [结论]本研究采用单次大剂量30Gy照射大鼠视交叉的方法,在放射后6个月时,观察到所有大鼠均明显地出现了视神经损伤相应的病理学改变,说明大鼠RION模型建立成功,达到预期目的。应用MEMRI对视觉通路功能完整性进行随访和半定量评估,可在视神经结构发生病理改变之前直观地提示视神经功能是否发生传导障碍,这为将来研究RION提供了一种良好的无创性功能检查方法。第二部分鼻腔副鼻窦肿瘤调强适形放疗后放射引起的视神经病变体积-剂量学分析 [目的]评估鼻腔副鼻窦肿瘤调强适形放疗(intensity modulated radiotherapy, IMRT)后放射引起的视神经病变(RION)的发生率及其与视神经/视交叉体积-剂量学参数的关系,从而为阐明RION在调强适形放疗条件下的耐受剂量及其相关危险因素提供参考依据。 [材料与方法]本研究纳入在2004年4月至2009年11月间,我院放疗科头颈部肿瘤治疗组采用IMRT治疗的59例无远处转移的鼻腔副鼻窦肿瘤患者。所有患者均随访满12个月且其TPS治疗计划资料皆完整。根据分割剂量、是否二次放疗将59例患者分为三组：初治常规分割治疗组(49例),初治大分割治疗组(6例),二次放疗组(4例)。采用Pinnacle 3治疗计划系统采集视神经/视交叉及靶区的体积-剂量学参数。 [结果]随访至2011年3月,59例鼻腔副鼻窦肿瘤患者中位随访时间27.3个月(范围：12-68)。3年局部控制率、无远处转移生存率、无进展生存率及总生存率分别为79.1%、77.9%、67.2%及75.5%。初治常规分割治疗组中1例患者发生RION,视神经、视交叉最大受量分别为69.28Gy和66.54Gy。二次放疗组中1例患者于第二次放疗后8个月发生右眼RION,该患者的右侧视神经、视交叉最大受量分别为65.86Gy和65.52Gy(第二次放疗分割次数为30次；初次放疗时间为15年前,当时的处方剂量为56Gy)。大分割放疗组中无发生RION病例。 [结论]采用IMRT治疗鼻腔副鼻窦肿瘤获得了较好的的近期疗效,但随访到2例患者发生RION。视神经／视交叉的最大受量、分割剂量及其是否进行二次放疗等为影响RION发生的危险因素,在制定放疗计划时应予充分考虑。
[Abstract]:The first part is the establishment of rat model of radiation induced optic chiasma injury.
[Objective] Radiation-induced optic neuropathy (RION), which is caused by excessive exposure to optic nerve / optic chiasma, is a serious complication which affects the quality of life seriously. Its main manifestations are sudden, painless, and irreversible visual loss. The pathogenesis is not yet fully understood. No effective treatment, neurotrophic factor and molecular targeted drug bevacizumab are of potential value for the treatment of optic neuropathy caused by radiation. In this study, a radiation induced optic cross injury model was established by irradiating the optic chiasma in rats with a one-time large dose of 30Gy, and the pathogenesis and the search for the optic neuropathy caused by radiation were studied. It lays the foundation for the effective treatment.
[materials and methods]34 rats, 4 without radiation as the control group, 30 of the optic chiasma radiation, randomly divided into 2 months after radiation, 4 months after radiation, 6 months after radiation, 2 months, 4 months, 6 months after the irradiation of manganese ions in the body, 24 hours after manganese enhanced magnetic resonance (Manganese-enhanced Magnetic resonance imaging, MEMRI) were scanned, and the rats were executed and the pathological analysis was performed. The pathological analysis included HE staining and Luxol Fast blue staining. According to the different enhancement degree of the visual pathway, the MEMRI image was scored by.100 times light microscopy, and the relative light density was analyzed for Luxol Fast, and 400 times the light mirror under the microscope. The glial cells were counted by color. Some rats were analyzed by electron microscope.
[results] 4 rats were killed during the feeding process, and 6 were killed by anaesthesia before MEMRI scan. The control group, 2 groups after radiation, 4 months after radiation and 6 months after radiation, 4, 5, 4, 11, 24, 3, 7, 4, 7, respectively. The main manifestations were demyelinating disease, capillary proliferation, astrocytosis, and interstitial fibrosis. The correlation analysis showed that the visual pathway score of MEMRI images was negatively correlated with the post radiation time, and the visual pathway score of 5 was defined as RION in the MEMRI image, p=0.000. In the control group, 2 groups after radiation and 4 months after radiation, the proportion of RION in 6 months after radiation was 0/3,1/5,2/4,11/11, respectively, with chi square test, x2=15.443, p=0.001; the relative light density value of Luxol Fast blue staining under 400 times of light microscopy was negatively correlated with the time after optic cross radiation, p=0.000, and the number of astrocytes under the 100 times of the optical microscope in each group, respectively. For 194 + 65234 + 19124 + 11 and 345 + 98, the correlation analysis showed that the number of cells was negatively correlated with the time after radiation. P=0.005.MEMRI images showed that 1 of the 5 rats in the 2 month group were lost in the optic nerve conduction function, but there were no significant changes in pathology compared with the rest of 4.
[Conclusion] in this study, a single large dose of 30Gy was used to irradiate the optic chiasma in rats. The pathological changes of the optic nerve injury were observed in all rats at 6 months after radiation, indicating that the rat model of RION was successfully established and achieved the desired purpose. The functional integrity of the visual pathway was followed up and half quantified by MEMRI. Evaluation can directly indicate whether the optic nerve function has conduction disturbance before the optic nerve structure changes, which provides a good method of noninvasive functional examination for the future study of RION.
The second part volume dosimetry analysis of radiation induced optic neuropathy after intensity modulated radiation therapy for sinonasal paranasal sinuses
[Objective] to evaluate the relationship between the incidence of optic neuropathy (RION) and the relationship with optic nerve / optic cross volume and dosimetry parameters after intensity modulated radiotherapy (IMRT), so as to clarify the tolerance dose and related risk factors of RION under the condition of intensity adjustment and conformal therapy. A reference.
[materials and methods] from April 2004 to November 2009, 59 cases of nasal paranasal sinus tumor without distant metastasis were treated by IMRT in the head and neck tumor treatment group of the Department of radiotherapy in our hospital. All patients were followed up for 12 months and the data of the TPS treatment plan were complete. According to the cut dose, 59 patients were divided by two radiotherapy. Three groups: the primary treatment group (49 cases), the primary treatment group (6 cases) and the two radiotherapy group (4 cases). The volume and dosimetry parameters of optic nerve / optic chiasma and target area were collected by the Pinnacle 3 treatment planning system.
[results] follow up to March 2011, 59 cases of nasal paranasal sinus tumor patients were followed up for 27.3 months (range: 12-68).3 years local control rate, no distant metastasis survival rate, no progression survival rate and total survival rate of 79.1%, 77.9%, 67.2% and 75.5%. primary treatment group of 1 patients with RION, optic nerve, optic chiasma maximum receiving The right eye RION was found in 1 patients in the two radiotherapy group of 69.28Gy and 66.54Gy., respectively, 8 months after second radiotherapy. The right optic nerve, the maximum optic chiasm was 65.86Gy and 65.52Gy (second times of radiotherapy 30 times; the initial radiotherapy time was 15 years ago, then the prescription dose was 56Gy). There were no cases of RION.
[Conclusion] the use of IMRT to treat nasal paranasal sinus tumors has obtained good short-term effect, but follow-up to the maximum dose of RION. optic nerve / optic chiasma in 2 patients, divided dose and two radiotherapy are the risk factors affecting the occurrence of RION, and should be fully considered in the formulation of the radiotherapy plan.

【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R774.6

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