早期帕金森病扩散张量成像的初步研究

目的 评价MRI扩散张量成像(DTI)技术在早期帕金森病(PD)中的诊断价值.资料与方法 对30名早期PD患者和30例匹配的健康老年对照组的黑质-纹状体区进行了常规MR平扫和DTI扫描,对双侧黑质-纹状体纤维环路穿越的部位:黑质致密部、底丘脑核、苍白球、壳核、尾状核连续层面的FA值和DCavg值进行测量和统计分析.结果 PD组黑质致密部、黑质致密部与底丘脑核之间部位的FA值显著低于对照组(P值<0.05).苍白球、壳核、尾状核等部位的FA值和DCavg值与对照组相比无显著差异.结论 DTI能无创性定量测量早期PD黑质.纹状体区病变的FA值和DCavg值,是对早期PD黑质.纹状体区进行定量评估的一种敏感的研究手段.     

DTI观察帕金森病患者黑质纹状体改变应用研究

目的:采用DTI研究帕金森病(Parkinson disease,PD)患者与对照组多个脑区各向异性分数(FA值)的差异。方法:收集2010年6月至2013年5月37例PD,其中男24例,女13例;随机选取22例健康志愿者作为对照组。PD患者采用Hoehn-Yahr分级,分为Ⅰ和Ⅱ级20例,Ⅲ和Ⅳ级17例;均行常规MRI扫描及DTI序列扫描,在所得FA图像上测量黑质纹状体各核团(双侧尾状核头、壳核、黑质)的FA值,确定各组有差异的FA值脑区。结果:PD组与对照组双侧尾状核头、壳核、黑质FA值差异有统计学意义(P0.05);其中早期PD患者黑质FA值与中晚期PD组差异有统计学意义(P0.05);早期PD患者尾状核头、壳核FA值与中晚期PD组差异无统计学意义(P0.05)。结论:DTI技术作为一种无创研究PD患者黑质纹状体生理改变的方法,提示黑质纹状体部位的FA值改变可能是诊断PD的线索。     

帕金森病MR应用研究进展

帕金森病（Parkinson’Sdisease,PD）是一种慢性选择性中脑黑质多巴胺能神经元缺失和纹状体多巴胺含量显著减少的中枢神经系统退变性疾病,于1817年由JamesParkinson首次报道。该病起病隐匿,进展缓慢,随年龄增长其患病率逐渐上升。临床上以静止震颤、运动迟缓、肌肉强直及姿势平衡障碍为主要特征表现。有研究表明,当PD患者出现临床症状时,已有60％～70％的黑质神经元变性,80％的纹状体多巴胺减少。此外,由于PD的病因及致病机制尚不明确,PD的传统诊断主要是依靠临床表现和诊断性多巴胺治疗,而不是依靠一定的客观指标。     

帕金森病小鼠模型纹状体多巴胺转运蛋白~(125)I-β-CIT的放射自显影

目的　观察不同损毁程度帕金森病 (PD)小鼠模型的纹状体多巴胺转运蛋白 (DAT)功能变化 ,探讨12 5I 甲基 3β (4 碘苯基 )托烷 2 β 羧酸盐 (β CIT)DAT显像的价值。 方法　根据注射MPTP天数不同 ,分为 1,3,5和 7d模型组和对照组 ,静脉注射12 5I β CIT 148kBq 2h后行放射自显影。高效液相色谱 电化学法 (HPLC ECD)检测纹状体多巴胺 (DA)及其代谢产物含量。免疫组化酪氨酸羟化酶 (TH)染色观察黑质和纹状体的病理变化。结果　与对照组相比 ,MPTP损毁的各组PD小鼠模型的纹状体 /皮层放射性比值分别降低 2 0 % ,42 % ,45 %和 5 2 % ;纹状体DA含量分别降低 47% ,75 % ,95 %和 95 % ;免疫组化TH染色可见黑质TH阳性神经元数量随MPTP损毁程度的加重而进一步减少。结论　不同损毁程度的PD小鼠模型DAT功能变化与生化和病理改变相一致 ,β CITDAT功能显像有助于PD的早期诊断和病情监测     

五子衍宗丸对帕金森病小鼠脑组织中神经营养因子及凋亡相关基因表达的影响

目的 观察五子衍宗丸对帕金森病(PD)小鼠脑内黑质纹状体神经营养因子分泌和脑组织中细胞凋亡相关基因表达的影响。方法 建立神经毒素MPTP诱导的PD小鼠模型，通过行为步态实验、爬杆实验及脑黑质纹状体区酪氨酸羟化酶(TH)阳性神经元的病理学检测，观察五子衍宗丸的治疗效果；采用免疫荧光、RT-qPCR和Western blotting法检测小鼠黑质纹状体中脑源性神经营养因子(BDNF)、胶质细胞源性神经营养因子(GDNF)、睫状神经营养因子(CNTF)及细胞凋亡相关基因Bcl-2、Bax、caspase-3、caspase-9表达水平的变化。结果 与PD模型组比较，五子衍宗丸治疗可明显减少PD小鼠四肢向前运动的平均摆动时间(P<0.05)和爬杆时间(P<0.001)，增高TH阳性细胞数和TH蛋白表达水平(P<0.05)；五子衍宗丸治疗后，PD小鼠黑质纹状体中BDNF、GDNF蛋白和CNTF及Bcl-2 mRNA表达水平明显增高(P<0.05)，而Bax、caspase-3和caspase-9表达水平明显降低(P<0.05)。结论 五子衍宗丸具有治疗PD的潜力，其...     

雌激素对PD模型大鼠黑质纹状体通路的保护作用及其机制探讨

目的研究雌激素（Estrogen）对6-羟基多巴（6-OHDA）制备的去卵巢（OVX）帕金森病（PD）模型大鼠黑质纹状体通路的保护作用及其可能机制。方法应用6-OHDA两点注射单侧损毁内侧前脑束（MFB）制备OVXPD模型大鼠,侧脑室给予17-β雌二醇（17-βestradiol,1μg/5μl）,观察大鼠旋转行为、黑质酪氨酸羟化酶（TH）基因表达、黑质铁染色阳性细胞数量和纹状体内多巴胺（DA）及其代谢产物含量的变化。结果雌激素用药组可明显减少阿朴吗啡诱导的PD模型大鼠单侧旋转行为（P〈0.01）。在损毁侧黑质,雌激素用药组TH基因的表达较PD模型组明显增加（P〈0.01）;纹状体DA及其代谢产物亦较PD模型组显著升高（P〈0.01）。黑质铁染色阳性细胞数量较PD模型组明显减少（P〈0.01）。结论雌激素对PD模型大鼠黑质DA能神经元有明显的保护作用,其作用机制可能与降低铁负载有关。     

帕金森病小鼠模型纹状体多巴胺转运蛋白^125I— β—CIT的放射自显影

目的 观察不同损毁程度帕金森病（PD）小鼠模型的纹状体多巴胺转运蛋白（DAT）功能变化,探讨^125I-甲基3β-（4－碘苯基）托烷－2β-羧酸盐（β-CIT）DAT显像的价值。方法 根据注射MPP天数不同,分为1,3,5和7d模型组和对照组,静脉注射^125I- β-GIT 148 kBq 2h后行放射自显影。高效液相色谱－电化学法（HPLC－ECD）检测纹状体多巴胺（DA）及其代谢产物含量。免组化酪氨酸羟化酶（TH）染色观察黑质和纹状体的病理变化。结果 与对照组相比,MPTP损毁的各组PD小鼠模型的纹状体／皮层放射性比值分别降低20％,42％,45％和52％;纹状体DA含量降低47％,75％,95%几95％;免疫组化TH染色可见黑质TH阳性神经元数量随MPTP损毁程度的加重而进一步减少。结论 不同损毁程度的PD小鼠模型DAT功能变化与生化和病理改变相一致,β-CIT DAT功能显像有助于PD的早期诊断和病情监测。     

帕金森病脑18F-FDG PET显像临床研究

目的：探讨帕金森病（PD）患者18F－脱氧葡萄糖（FDG）PET脑代谢显像的影像学特征及其临床意义。方法：静脉注射18F－FDG后行脑断层显像，获得33例PD患者及32例正常人纹状体，丘脑，黑质，顶叶，颞叶，额叶，枕叶，海马单位面积放射性计数与小脑计数的比值（Rcl/cb)，并与MRI进行对照。结果：正常人脑PET显像可见大脑各叶，基底节，丘脑，中脑及小脑放射性分布均匀对称。PD患者的PET异常率为96．97％，MRI异常率为30．30％，PD患者黑质，纹状体，丘脑及大脑半球各叶代谢低于正常人，差异有非常显著性（P＜0．001），并与症状严重程度有关，症状重侧肢体对侧脑半球的黑质，纹状体，丘脑及额叶代谢较另侧降低，PD患者PET显像特征：非对称性黑质（93．94％），纹状体（69．70％），丘脑（36．36％）代谢减低，非对称性纹状体或丘脑代 谢轻度增高，占15．15％，非对称性大脑各叶代谢下降，其中以颞叶（51．52％），额叶（39．39％），海马（45．46％）为著，非对称性额叶，颞叶，海马代谢轻度增高占9．09％，结论：在除外脑内结构特异性损害基础上，18F－FDG，PET发现单侧或不对称性双侧黑质，经纹体，丘脑代谢减低或轻度增高有助PD的早期诊断。     

原发性帕金森病黑质神经轴突分散性及密度的影像研究

正摘要目的应用神经轴索导向分散性及密度成像(NODDI)技术定量分析帕金森病(PD)黑质致密部(SNpc)和纹状体变化。方法 58例PD病人和36例年龄及性别匹配的正常对照组行DWI扫描。比较两组间黑质及基底节的细胞内体积分数(Vic)、定向扩散指数(OD)、各向同性体积分数     

帕金森病的磁共振成像研究进展

帕金森病(Parkinson disease,PD)是一种常见于中老年人的慢性进行性中枢神经变性疾病.以静止性震颤、肌强直、运动迟缓及姿态异常等为典型的临床表现.黑质多巴胺能神经元变性、丢失及黑质-纹状体系统变性是PD的主要病理改变.笔者仅就近年来PD的MRI及磁共振波谱(MRS)、扩散张量成像(DTI)研究进展综述如下:     

PET measurements of dopaminergic pathways in the brain.

Positron emission tomography (PET) measurements of dopaminergic pathways have revealed several new insights into the role of dopamine in the pathophysiology and pharmacology of brain diseases such as Parkinson's disease (PD), dystonia and schizophrenia. PET studies of regional blood flow or metabolism identifies sites of regional pathology. Drug-induced changes in flow or metabolism indicate the function of dopamine-mediated pathways. Measurements of radioligand binding in vivo with PET reveals abnormalities associated with specific diseases and the actions of various drugs that affect the dopaminergic system. Finally, PET measurements of the uptake of analogues of levodopa provide clues to the function of dopamine pathways potentially important for diagnosis and treatment of disease like PD.     

多巴胺转运蛋白显像剂11C-β-CFT在帕金森病中的应用研究

帕金森病(PD)是全球第二大最常见的神经退行性疾病, 与患者年龄、激素水平、生活习惯及基因遗传等相关因素密切相关, 且与大脑多巴胺能神经元的结构和功能差异有关。常规的影像学检查在PD的早期发现、预后评估、术前分级等方面存在一些不足。11C-甲基-N-2β-甲基酯-3β-(4-氟-苯基)托烷(11C-β-CFT)是一种多巴胺转运蛋白正电子显像剂, 与多巴胺转运体的结合具有高度特异性, 同时受患者治疗药物因素的干扰较小, 是一种良好的临床诊断类的显像剂。目前, 11C-β-CFT已应用于人类神经病学方面疾病的研究, 如精神分裂症、PD等, 11C-β-CFT PET显像可以评价疾病病理、生理过程, 便于临床诊断及监测疾病治疗效果等。笔者就近年来11C-β-CFT PET显像在PD中的应用作一综述。     

SPECT study with I-123-Ioflupane (DaTSCAN) in patients with essential tremor. Is there any correlation with Parkinson’s disease?

Objectives

The differential diagnosis between essential tremor (ET) and Parkinson??s disease (PD) may be, in some cases, very difficult on clinical grounds alone. In addition, it is accepted that a small percentage of ET patients presenting symptoms and signs of possible PD may progress finally to a typical pattern of parkinsonism. Ioflupane, N-u-fluoropropyl-2a-carbomethoxy-3a-(4-iodophenyl) nortropane, also called FP-CIT, labelled with ¹²³I (commercially known as DaTSCAN) has been proven to be useful in the differential diagnosis between PD and ET and to confirm dopaminergic degeneration in patients with parkinsonism. The aim of this study is to identify dopaminergic degeneration in patients with PD and distinguish them from others with ET using semi-quantitative SPECT ¹²³I-Ioflupane (DaTSCAN) data in comparison with normal volunteers (NV), in addition with the respective ones of patients referred as suffering from ET, as well as, of patients with a PD diagnosis at an initial stage with a unilateral presentation of motor signs.

Methods

Twenty-eight patients suffering from ET (10 males plus 18 females) and 28 NV (12 males and 16 females) were enroled in this study. In addition, 33 patients (11 males and 22 females) with an established diagnosis of PD with unilateral limb involvement (12 left hemi-body and 21 right hemi-body) were included for comparison with ET. We used DaTSCAN to obtain SPECT images and measure the radiopharmaceutical uptake in the striatum (S), as well as the caudate nucleus (CN) and putamen (P) in all individuals.

Results

Qualitative (Visual) interpretation of the SPECT data did not find any difference in the uptake of the radiopharmaceutical at the level of the S, CN and P between NV and ET patients. Reduced accumulation of the radiopharmaceutical uptake was found in the P of all PD patients. Semiquantitative analysis revealed significant differences between NV and ET patients in the striatum, reduced in the latter. There was also a significant reduction in the tracer accumulation in the left putamen of patients with right hemi-parkinsonism compared to ET and NV. Patients with left hemi-parkinsonism, demonstrated reduced radioligand uptake in the right putamen in comparison with ET and NV. Clinical follow-up of 20 patients with ET at (so many months afterwards) revealed no significant change in clinical presentation, particularly no signs of PD. Follow-up DaTSCAN performed in 10 of them (so many months afterwards) was negative in all but one. This one had an equivocal baseline study which deteriorated 12?months later.

Conclusions

Our results do not support the hypothesis of a link between essential tremor and Parkinson??s disease. However, it appears that ET patients have a small degree of striatal dopaminergic degeneration. If this is due to alterations in the nigrostriatl pathway or of other origin it is not clear. Follow-up studies of essential tremor patients are warranted to assess progression of disease and to understand better the possible cause for striatal dopaminergic degeneration.     

帕金森病多模态MRI研究进展

帕金森病(PD)是一种发生率仅次于阿尔茨海默病的神经退行性疾病,其病理改变为黑质内多巴胺能神经元的缺失,引起纹状体内多巴胺含量的减少,进而引起一系列临床症状。早期神经影像检查多采用结构MRI研究局部脑区的改变,随着多模态MRI的发展,从血流动力学、脑白质纤维束成像、代谢水平以及功能连接等不同角度可以对PD行进一步研究及评价,从而为PD的临床诊断、治疗及预后提供更多的影像依据。就多模态MRI技术在PD中的研究进展予以综述。     

Logistic discriminant parametric mapping: a novel method for the pixel-based differential diagnosis of Parkinson's disease.

Positron emission tomography (PET) and single-photon emission tomography (SPET) imaging of the dopaminergic system is a powerful tool for distinguishing groups of patients with neurodegenerative disorders, such as Parkinson's disease (PD). However, the differential diagnosis of individual subjects presenting early in the progress of the disease is much more difficult, particularly using region-of-interest analysis where small localized differences between subjects are diluted. In this paper we present a novel pixel-based technique using logistic discriminant analysis to distinguish between a group of PD patients and age-matched healthy controls. Simulated images of an anthropomorphic head phantom were used to test the sensitivity of the technique to striatal lesions of known size. The methodology was applied to real clinical SPET images of binding of technetium-99m labelled TRODAT-1 to dopamine transporters in PD patients (n=42) and age-matched controls (n=23). The discriminant model was trained on a subset (n=17) of patients for whom the diagnosis was unequivocal. Logistic discriminant parametric maps were obtained for all subjects, showing the probability distribution of pixels classified as being consistent with PD. The probability maps were corrected for correlated multiple comparisons assuming an isotropic Gaussian point spread function. Simulated lesion sizes measured by logistic discriminant parametric mapping (LDPM) gave strong correlations with the known data (r(2)=0. 985, P<0.001). LDPM correctly classified all PD patients (sensitivity 100%) and only misclassified one control (specificity 95%). All patients who had equivocal clinical symptoms associated with early onset PD (n=4) were correctly assigned to the patient group. Statistical parametric mapping (SPM) had a sensitivity of only 24% on the same patient group. LDPM is a powerful pixel-based tool for the differential diagnosis of patients with PD and healthy controls. The diagnosis of disease even before clinical symptoms become apparent may be possible, and ultimately this technique could be most useful in differentiating between several neurodegenerative disorders, incorporating images of multiple neuroreceptor systems.     

The use of SPECT in the diagnosis of Parkinson's disease.

This article looks briefly at the latest efforts to develop an objective diagnostic marker for Parkinson's disease on single-photon emission computed tomography (SPECT). Traditionally, the diagnosis of idiopathic Parkinson's disease has been based on clinical criteria. However, these predict the pathologic diagnosis in only 80% of patients suspected of having the disease. Since a correct diagnosis is essential for prognosis, effective treatment and research, the search has continued for objective markers. The latest developments in nuclear medicine have come the closest in making such a marker clinically available. These developments are based on SPECT and positron-emission tomographic imaging of the basal ganglia using specific radio-labelled dopaminergic-receptor tracers. SPECT radiotracers target either the pre- or postsynaptic component of the dopaminergic system in the basal ganglia. These techniques show great promise in the early diagnosis of PD as well as in measuring its progression.     

Significance of<Superscript>123</Superscript>I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson’s disease and related disorders: It can be a specific marker for Lewy body disease

Recently, reliable and clear evidence for the usefulness of 123I-MIBG scintigraphy in the diagnosis of Parkinson's disease (PD) has been accumulated and it has become increasingly popular as one of the most accurate means of diagnosing the disease. PD, one of the most common neurodegenerative disorders, is characterized by resting tremor, rigidity, bradykinesia or akinesia, and postural instability. The disease is characterized pathologically by distinctive neuronal inclusions called Lewy bodies in many surviving cells of dopaminergic neurons of the substantia nigra pars compacta and other specific brain regions. Furthermore Lewy body type degeneration in the cardiac plexus has been observed in PD. In PD, cardiac MIBG uptake is reduced markedly even in the early disease stages; therefore, MIBG imaging can be used as an indicator of the presence of PD rather than disease severity. Other parkinsonian syndromes such as multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration demonstrate normal cardiac MIBG uptake or only mild reduction of MIBG uptake, indicating that MIBG imaging is a powerful method to differentiate PD from other parkinsonian syndromes. Dementia with Lewy bodies (DLB) also shows severe reduction of MIBG uptake, whereas Alzheimer's disease (AD) demonstrates normal MIBG uptake, permitting differentiation of DLB from AD using MIBG scintigraphy. In pure autonomic failure, which shares similar pathological findings with PD and is thought to be associated with diffuse loss of sympathetic terminal innervation, cardiac MIBG uptake also decreases markedly. Considering all the data together, marked reduction of cardiac MIBG uptake seems to be a specific marker of Lewy body disease and thus extremely useful in the differentiation from other diseases with similar symptoms without Lewy bodies.     

Logistic discriminant parametric mapping: a novel method for the pixel-based differential diagnosis of Parkinson’s disease

Positron emission tomography (PET) and single-photon emission tomography (SPET) imaging of the dopaminergic system is a powerful tool for distinguishing groups of patients with neurodegenerative disorders, such as Parkinson’s disease (PD). However, the differential diagnosis of individual subjects presenting early in the progress of the disease is much more difficult, particularly using region-of-interest analysis where small localized differences between subjects are diluted. In this paper we present a novel pixel-based technique using logistic discriminant analysis to distinguish between a group of PD patients and age-matched healthy controls. Simulated images of an anthropomorphic head phantom were used to test the sensitivity of the technique to striatal lesions of known size. The methodology was applied to real clinical SPET images of binding of technetium-99m labelled TRODAT-1 to dopamine transporters in PD patients (n=42) and age-matched controls (n=23). The discriminant model was trained on a subset (n=17) of patients for whom the diagnosis was unequivocal. Logistic discriminant parametric maps were obtained for all subjects, showing the probability distribution of pixels classified as being consistent with PD. The probability maps were corrected for correlated multiple comparisons assuming an isotropic Gaussian point spread function. Simulated lesion sizes measured by logistic discriminant parametric mapping (LDPM) gave strong correlations with the known data (r ²=0.985, P<0.001). LDPM correctly classified all PD patients (sensitivity 100%) and only misclassified one control (specificity 95%). All patients who had equivocal clinical symptoms associated with early onset PD (n=4) were correctly assigned to the patient group. Statistical parametric mapping (SPM) had a sensitivity of only 24% on the same patient group. LDPM is a powerful pixel-based tool for the differential diagnosis of patients with PD and healthy controls. The diagnosis of disease even before clinical symptoms become apparent may be possible, and ultimately this technique could be most useful in differentiating between several neurodegenerative disorders, incorporating images of multiple neuroreceptor systems. Received 8 April and in revised form 23 June 1999     

Evaluation of [I]β-CIT binding with SPECT in controls, early and late Parkinson's disease

The main neuropathological feature in Parkinson's disease (PD) is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine in the striatum. Recently, a new radioligand (β-CIT) for single photon emission computed tomography (SPECT) became available for in vivo imaging of the dopamine transporter on nerve endings of dopaminergic neurons in the striatum. The present results demonstrate that [¹²³I]-β-CIT SPECT allows a discrimination between early and late PD patients. In our opinion, these preliminary data suggest that [¹²³I]-β-CIT SPECT should be used from now on in longitudinal studies (such as the DATATOP study) in which the effects of (putative) neuroprotective interventions in PD are monitored.