【作者】 修雁；

【导师】 王建华； 石洪成； 严福华；

【作者基本信息】 复旦大学 ， 影像医学与核医学， 2009， 博士

【摘要】 目的:对⁹⁹Tc^m-ECD脑血流灌注显像图像分析方法、负荷试验方法以及相关的临床应用进行探讨;重点探讨SPECT脑血流灌注显像在甲亢患者脑功能研究中的应用价值;探讨甲亢患者脑灌注改变模式及其可能相关因素;分析甲亢患者抑郁、焦虑情绪以及认知功能改变,并探讨其可能相关因素。方法:1.SPECT脑血流灌注显像的方法学研究130例受试者共行169次SPECT脑血流灌注显像。显像剂为⁹⁹Tc^m-ECD,剂量约为1110MBq,显像仪器为Elscint Apex Sp-6或Marconi Irix三探头SPECT。其中,34例健康志愿者（男性20例,女性14例;平均年龄35.03±11.81岁）行静息脑血流灌注显像,分析⁹⁹Tc^m-ECD在正常成人脑组织中的分布模式,并比较目测及半定量方法的分析结果。另外选择28例健康志愿者（男性8例,女性20例;平均年龄35.8±9.41岁）行静息脑血流灌注显像,应用Brain search 1.10软件自动提取脑功能区及血流半定量值,并验证该方法的准确性。选择7例甲亢患者治疗前、后的静息SPECT脑血流灌注图像,应用SPM2.0软件进行位置矫正、归一化及平滑处理,以介绍本文中SPM分析甲亢患者脑血流灌注图像的方法。18例系统性红斑狼疮患者（男性1例,女性17例;平均年龄34±10.5岁）和11例健康对照者（男性3例,女性8例;平均年龄28.0±9.7岁）行静息脑血流灌注显像,并与CT进行比较。24例脑缺血性疾病患者（男性13例,女性11例,平均年龄60.0±13.2岁）和8例正常对照者（均为男性,平均年龄32.0±12.9岁）分别行静息及潘生丁负荷脑血流灌注显像。2.SPECT脑血流灌注显像在评价甲亢患者脑功能损害中的应用SPECT脑血流灌注显像37例临床确诊为甲亢的患者（男性10例,女性27例;平均年龄39.27±10.58岁）纳入病例组,分成短病程组（病程小于等于6个月,n=15）和长病程组（病程大于6个月,n=22）:其中,7例甲亢患者经治疗甲状腺功能恢复正常后评价其脑血流变化。年龄、性别、文化、婚姻相匹配的28例健康志愿者（男性8例,女性20例;平均35.8±9.41岁）纳入正常对照组。静脉注射⁹⁹Tc^m-ECD1110MBq后约30分钟应用Marconi Irix三探头SPECT采集静息脑血流灌注图像。组间脑血流灌注比较均应用统计参数图SPM2.0软件行体素对体素的团体t检验（FWE矫正,阈值设为0.05）。应用Brain search 1.1软件自动提取脑功能区及其血流半定量值,并结合相关指标分析甲亢患者脑血流灌注异常的可能相关因素。人格特征分析应用艾森克人格问卷（EPQ）对其中35例患者（2例未完成）及28例正常对照者行人格特征分析,并进行相关研究;分析7例患者治疗后人格特征变化。甲克患者情绪分析对37例甲亢患者和28例正常对照者应用抑郁自评量表（SDS）和焦虑自评量表（SAS）评价抑郁、焦虑情绪及其中7例患者治疗后情绪变化;并结合脑血流灌注及其他相关指标分析甲亢患者发生抑郁、焦虑的可能相关因素。甲亢患者认知功能评定对37例患者及28例正常对照者应用数字划消试验测定注意力,应用韦氏记忆量表甲测定记忆力;结合脑血流灌注及其他相关指标分析甲亢患者认知功能改变的可能相关因素;分析7例患者治疗后注意力、记忆力变化。结果:1.SPECT脑血流灌注显像的方法学研究⁹⁹Tc^m-ECD在脑不同部位中的分布差异较大,而相同部位个体间差异较小;半定量分析与目测分析结果相关性较好。脑区自动提取法提取脑区与解剖部位相符合,该方法显示部分脑区⁹⁹Tc^m-ECD摄取与应用感兴趣区半定量法所反映⁹⁹Tc^m-ECD的脑正常分布模式基本一致,但该方法能获取更多脑区的信息。SPM分析时图像预处理是研究结果准确、可靠的关键;SPM分析可直观显示有显著统计学意义的脑区。静息SPECT脑灌注显像探测系统性红斑狼疮患者脑部病变的灵敏度分别为67.7%和为80%;对有神经系统受累症状者,灵敏度为80%,CT仅为20%:无神经系统受累症状者,SPECT脑灌注显像灵敏度为70%。扣带回、颞顶叶是SLE患者脑部受损较常见部位。静息SPECT脑血流灌注显像和潘生丁负荷显像探测脑缺血病变的灵敏度分别为58.3%和83.3%。潘生丁可探测到四种不同的脑血管反应类型。2.SPECT脑血流灌注显像在评价甲亢患者脑功能损害中的应用SPECT脑血流灌注显像与正常对照组（n=28）比较,甲亢患者（n=37）边缘系统包括海马、海马旁回、前扣带回、后内嗅皮层、后旁嗅皮层、膝下皮层、杏仁体、尾状核以及额叶（上、中、下额回及内侧额回）血流灌注减低;右小脑吲部及脑干存在血流灌注减低（FWE矫正,p＜0.05）。短病程与长病程组患者血流灌注减低部位基本相似,长病程组血流减低范围稍大于短病程组。7例患者治疗后边缘系统包括海马旁回、钩回、前扣带回、颞叶脑血流灌注有改善（FWE矫正,p＜0.05）。甲亢患者钩回、左舌回、后扣带回、左枕下回、左视觉联合皮层、胼胝体下回脑血流与FT3呈显著负相关（p＜0.05）;左钩回、左舌回、左视觉联合皮层、左枕中回、枕下回、左后扣带回、左膝下皮层、左尾状核血流与FT4呈显著负相关（p＜0.05）;右枕中回血流与sTSH呈显著负相关（p＜0.05）。甲亢患者脑血流与TgAb、TRAb、TPOAb无显著相关（p＞0.05）。人格特征分析与正常对照组（n=28）比较,甲亢患者（n=35）具有情绪不稳定（神经质N）、精神质的人格特征（p＜0.05）;甲亢神经质维度N评分与丘脑、海马旁回、后内嗅皮层、苍白球、乳头体血流呈显著负相关（p＜0.05）;7例患者治疗后人格特征未见显著变化（p＞0.05）,但神经质维度N评分有明显减低趋势（t=1.883,p=0.092）。情绪分析与正常对照组（n=28）比较,甲亢患者（n=37）具有轻、中度抑郁和焦虑（p＜0.05）;短病程与长病程组患者间无显著差异（p＞0.05）。7例患者治疗后抑郁情绪明显改善(（p＜0.05）,而治疗后与治疗前及与对照组焦虑评分均无显著差异（p＞0.05）。边缘系统、丘脑及基底节血流与抑郁显著相关（p＜0.05）;右丘脑血流与焦虑显著相关（p＜0.05）。内倾而不稳定的人格特征以及胼胝体下回血流减低是抑郁发生的独立影响因素,不稳定的人格特征是焦虑发生的独立影响因素（p＜0.05）。认知功能评定与正常对照组（n=28）比较,长病程组患者（n=22）记忆力受损（p＜0.05）;短病程组（n=15）记忆力及所有患者注意力无明显受损（p＞0.05）。年龄、右尾状核、右腹前核、右乳头体血流是正常对照者注意力的独立影响因素,年龄、病程、FT4、右颞极、右尾状核、右听觉联合皮层血流是甲亢患者注意力的独立影响因素（p＜0.05）。年龄、注意力、右顶上小叶、右压后扣带皮层血流灌注是正常对照记忆力的影响独立因素,年龄、注意力、FT4、左丘脑、右杏仁体血流是甲亢患者记忆力的影响独立因素（p＜0.05）。记忆力、注意力与抑郁、焦虑、FT3、sTSH及自身抗体均无显著相关性（p＞0.05）。结论:⁹⁹Tc^m-ECD在不同部位脑组织中的分布差异较大;年龄会轻微改变其在某些部位的分布;脑功能自动提取法能准确、方便地提取功能脑区及血流半定量值;SPM分析可客观、直观地显示有统计意义脑区;SPECT脑血流灌注显像能够灵敏探测脑部缺血性病变;潘生丁负荷显像可提高脑缺血性病变检出的灵敏度、探测脑血管储备力。SPECT脑血流灌注显像能客观评价甲亢患者脑血流异常;甲亢患者边缘系统、额叶、右小脑吲部和脑干血流灌注减低,局部脑血流异常可能与甲状腺激素增高有关;经治疗甲状腺功能恢复正常后,患者脑血流灌注可能有改善;甲亢患者有明显抑郁、焦虑情绪,其发可能与内向而不稳定的个性特征及局部脑血流减低有关;治疗后抑郁明显改善,焦虑有改善;病程较长甲亢患者有记忆力受损,可能与丘脑、杏仁体等记忆相关脑区血流减低有关;甲亢患者注意力无明显受损。更多还原

【Abstract】 Objectives:To study the normal distribution patterns of ⁹⁹Tc^m-ECD in adult brain, analyze the SPECT image interpretaiton methods and the value of dipyridamole stress test in cerebrovascular diseases.The changes of regional cerebral blood flow（rCBF） in hyperthyroidism patients and its relations with mood disorders,cognition deficits and other hyperthyroidism related factors were intensely studied.Methods:1.SPECT cerebral blood flow perfusion imaging methodsTotal 169 SPECT scans were performed for 130 individuals.The images were acquired with Elscint Apex Sp-6 or Marconi Irix triple head SPECT 30mins after ⁹⁹Tc^m-ECD injection intravenously.The normal brain distribution patters of ⁹⁹Tc^m-ECD in 34 healthy volunteers（males2,females 14;mean age 35.03±11.81ys） were analyzed visually and semiquantitatively.Another 28 healthy volunteers（males 8,females 20;mean age 35.8±9.41ys） performed rest cerebral blood flow perfusion iamging.Brain anatomic and functional areas were extracted automatically with Brain search 1.10 software.Its accuracy was compared with ROI semiquantitive analysis.The method of SPM analysis for SPECT perfusion images was introduced.Eighteen systemic lupus erythematosus（SLE） patients（males 1,females 17;mean age 34±10.5ys） and 11 healthy controls （males 3,females 8;mean age 28.0±9.7ys） performed rest cerebral blood flow perfusion imaging,the results were analyzed and compared with CT scans.Twenty-four patients with cerebrovascutar diseases（males 13,females 11:mean age 60.0±13.2ys）and 8 male healthy controls（mean age 32.0±12.9ys） performed both rest cerebral blood flow perfusion imaging and dipyridamole stress test.The results were analyzed visually and semiquantitatively.2.SPECT rCBF imaging for brain dysfunctions in hypertyroidism patients SPECT cerebral blood flow perfusion imaging Thirty-seven hyperthyroidism patients（males 10,females 27;mean age 39.27±10.58 ys） were enrolled.The patients were divided into two subgroups:short duration group with duration equal or less than 6 months（n=15）,long duration group with duration more than 6 months（n=22）.Twenty-eight healthy volunteers matched for age,gender,education and marital with patients were included as controls.SPECT cerebral blood flow perfusion imaging was performed at rest after ⁹⁹Tc^m-ECD injection for all patients and controls.Statistical parametric mapping（SPM2）2.0 was used to investigate the differences of regional cerebral blood flow（rCBF） between different groups.The functional areas were extracted automatically with Brain search 1.10 software.The correlations between rCBF and age,gender,education,marrital state,thyroid hormones, autoimmune antibodies,disease duration were done for patients to explore the relationship of these factors.In 7 patients,rCBF changes were followed up 5month to lyear after euthyroid.Personality traits analysis The personality traits of 35 patients and 28 controls were assessed with EPQ questionnaire.The personality traits were assessed again for 7 patients 5month to lyear after euthyroid.The correlation analyses were done between EPQ scores,rCBF,thyroid hormones and autoimmune antibodies.Mood disorders assessment The mood disorders of.37 patients and 28 controls were assessed with SDS rating scales for depression,SAS rating scales for anxiety.Mood changes were followed up for 7 patients 5month to lyear after euthyroid.The factors related to depression and anxiety were analyzed by one-way variance analysis and mutiple stepwise regression analysis.Cognition functions assessment Number cancellation test（NCT） Was performed for attention,Wechsler Memory Scales（WMS） was performed for memory assessment for all 37 patients and 28 healthy controls.Cognition changes were followed up for 7 patients 5month to lyear after euthyroid. The factors related to attention and memory were analyzed by one-way variance analysis and mutiple stepwise regression analysis.Results:1.SPECT cerebral blood flow perfusion imaging methods⁹⁹Tc^m-ECD distributed unevenly at different site of normal brain.The results of semiquantitive and visual analysis had high correlation （r=0.756,P＜0.05）.The brain functional areas extractd automatically was as the same as those analyzed visual]y.The uptake of ⁹⁹Tc^m-ECD in the same regions were similar to those by semiquantitatively before.The sensitivity of rest rCBF imaging for detecting SLE brain involvement was 67.7%by visual analysis,and 70%by semiquantitative analysis.The sensitivity of SPECT imaging was 80%for patients with obvious headache or vomit,however it was only 20%for CT scan.Cingulate gyrus and temporal-parietal region were the most involved regions.The sensitivity was improved from 58.3%to 83.3%after dipyridamole stress test for cerebrovascular diseases.Four different patterns of cerebrovascular reaction could be found with dipyridamole stress test.2.SPECT rCBF imaging for brain dysfunctions in hypertyroidism patients SPECT rCBF imaging for hyperthyroidism patients rCBF in limb system and frontal lobe,including hippocampus,parahippocampal gyrus,anterior cingulate,entorhinal cortex,subgenual,amygadala,caudate and superior frontal gyrus,middle frontal gyrus,inferior frontal gyrus,medial frontal gyrus were decreased significantly in SPM analysis.Culmen region of cerebellum and brain stem were also involved（FWE correction,P＜0.05）.There was no significant difference between rCBF of short duration group and long duration group,but the involved areas of long duration group were slightly larger than those of short duration group when compared to control group,rCBF was improved significantly for 7 patients after euthyroid（FWE correction,p＜0.05）.rCBF in left superior frontal gyrus were correlated negatively with age,positively with right rectal gyrus and parahippocampal gyrus（p＜0.05）.rCBF in uncus,left lingual gyrus,post cingulate,left occipital gyrus,left vision associated cortex and subcallosal gyrus were correlated negatively with FT3（p＜0.05） and which in left uncus,left lingual gyrus,left occipital gyrus,left vision associated cortex,posterior cingulate,caudate nucleus and subgenual were correlated negatively with FT4（p＜0.05）.rCBF in middle occiptal gyrus was correlated negatively with sTSH（p＜0.05）.There were no significant correlations between rCBF and TgAb,TRAb,TPOAb.Personality traits analysis Hyperthyroidism patients had much more neuroticism and psychoticism characteristics compared with controls,which had not changed significantly after euthyroid.There were no correlations between personality traits and thyroid hormones, autoimmune antibodies.The scores of neuroticism were correlated negatively with rCBF in thalamus,parahippocampal gyrus,posterior entorhinal cortex,globus pallidus and mammilary body（p＜0.05）.Mood disorders assessment Compared to healthy controls,patients had slight to moderate depression and anxiety（p＜0.05）.There were no significant difference between short and long duraton group（p＞0.05）.The depression mood was improved significantly after euthyroid （p＜0.05）.However,the improvement was less significant for anxiety after euthyroid（p＞0.05）.There were no significant correlations between depression,anxiety and age,gender,marrital,education,duration,thyroid hormones,autoimmune antibodies for both patients and controls（p＞0.05）.rCBF in limb system,thalamus,basal ganglia were correlated negatively with depression,and which in right talamus was correlated negatively with anxiety（p＜0.05）.The personality traits of introversion and unstable mood,also decreased rCBF in subcallosal gyrus were independent factors for depression and the unstable mood was independent factor for anxiety in hyperthyroidism patients（p＜0.05）. Cognition functions assessment Patients with long duration had significant memory deficits（p＜0.05）,no memory deficits were found for short duration patients.No attention deficits were found in both patients and controls（p＞0.05）.rCBF in right temporal,right caudate,right auditory associated cortex,age and duration were independent factors for attention of patients（p＜0.05）.rCBF in right halamus,right amygdala,age and attention,FT4 were independent factors for memory of patients（p＜0.05）.There were no significant correlations between attention,memory and depression,anxiety,FT3,sTSH and autoimmune antibodies（p＞0.05）.Conclusion:SPECT rCBF imaging is sensitive in detecting ischemic cerebrovascular diseases,dipyridamole stress test can improve the sensitivity further and can reflect the cerebraovascular reaction.Brain functional areas extraction is an accurate and convient method,and SPM analysis is a sensitive and objective method for image interpretation. SPECT rCBF imaging is valuable for hyperthyroidism brain function assessment.Hypoperfusion in limb system,frontal lobe,cerebellar and brain stemare shown for hyperthyroidism patients,which might be related to elevated concentrations of thyroid hormones.Impaired rCBF might be decreased after euthyroid.Hyperthyroidism patients have obvious depression and anxiety,which might be associated with special personality traits and rCBF impariment.Memory deficits are significant for longer duration patients,which might be accompanied by rCBF in thalamus and amygdala.No attention deficits are found for hyperthyroidism patients.更多还原