SPECT image analysis using statistical parametric mapping in patients with Parkinson's disease.

This study investigated alterations in regional cerebral blood flow (rCBF) in patients with Parkinson's disease using statistical parametric mapping (SPM). METHODS: Noninvasive rCBF measurements using 99mTc-ethyl cysteinate dimer (ECD) SPECT were performed on 28 patients with Parkinson's disease and 48 age-matched healthy volunteers. The Parkinson's disease patients were divided into two groups, 16 patients with Hoehn and Yahr stage I or II and 12 patients with Hoehn and Yahr stage III or IV. We used the raw data (absolute rCBF parametric maps) and the adjusted rCBF images in relative flow distribution (normalization of global CBF for each subject to 50 mL/100 g/min with proportional scaling) to compare these groups with SPM. RESULTS: In patients with stage I or II Parkinson's disease, we found a diffuse decrease in absolute rCBF in the whole brain with sparing of the central gray matter, hippocampus and right lower temporal lobe compared with healthy volunteers. Adjusted rCBF increased in both putamina and the right hippocampus. In patients with stage III or IV disease, rCBF decreased throughout the whole brain. Adjusted rCBF increased bilaterally in the putamina, globi pallidi, hippocampi and cerebellar hemispheres (dentate nuclei) and in the left ventrolateral thalamus, right insula and right inferior temporal gyrus. CONCLUSION: SPM analysis showed that significant rCBF changes in Parkinson's disease accompanied disease progression and related to disease pathophysiology in the functional architecture of thalamocortex-basal ganglia circuits and related systems.     

Check-ups with brain SPECT in electroconvulsive therapy in patients with severe drug-resistant depressive episodes and Parkinson's disease

We have studied three women (66,72 and 72 years) with Parkinson's disease of 11, 6 and 21 years of evolution and drug-resistant severe depressive episodes treated with electroconvulsive therapy (ECT). We have performed a brain SPECT (99mTc-HMPAO) before and after the ECT. The clinical improvement of the severe depressive episodes were measured using the Hamilton score. The first patient did not experience any clinical improvement (Hamilton score 42 to 42). In this patient the brain SPECT before treatment presented a reduced perfusion in the posterior parietal region, anterior cingulate cortex and medial frontal and parietal cortex. After the treatment, the brain SPECT did not present significant variations. The second patient presented a moderate clinical improvement (Hamilton score 46 to 36) and also presented moderate improvement in the neurological symptoms. The brain SPECT before the treatment showed reduced perfusion in the left temporal cortex and medium-posterior parietal cortex. After the treatment, it also did not reflect significant variations. The third patient experienced a very good response to the ECT sessions (Hamilton score 45 to 10) and also an improvement regarding the neurological symptoms. This patient presented a reduced perfusion in the medium-posterior parietal regions in the brain SPECT performed before the treatment; these regions presented a moderate improvement in the brain SPECT performed after the treatment. The patient who presented a significant neurological and psychiatric improvement also presented an improvement in the perfusion of the decreased areas in the brain SPECT and showed fewer alterations in the baseline brain SPECT compared with the others. The brain SPECT could have a prognostic (and confirmation) role regarding clinical improvement induced by ECT in resistant depression in Parkinson's disease. ECT is an alternative in treatment of severe depressive drug-resistant episodes associated to the Parkinson's disease.     

Dopamine transporter imaging with [123I]FP-CIT SPECT: potential effects of drugs

Background [¹²³I]N-ω-fluoropropyl-2β-carbomethoxy-3β-{4-iodophenyl}nortropane ([¹²³I]FP-CIT) single photon emission computed tomography (SPECT) is a frequently and routinely used technique to detect or exclude dopaminergic degeneration by imaging the dopamine transporter (DAT) in parkinsonian and demented patients. This technique is also used in scientific studies in humans, as well as in preclinical studies to assess the availability of DAT binding in the striatum. In routine clinical studies, but also in scientific studies, patients are frequently on medication and sometimes even use drugs of abuse. Moreover, in preclinical studies, animals will be anesthetized. Prescribed drugs, drugs of abuse, and anesthetics may influence the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. Discussion Here, we discuss the basic principle of how drugs and anesthetics might influence the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. We also review drugs which are likely to have a significant influence on the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. Additionally, we discuss the evidence as to whether frequently prescribed drugs in parkinsonian and demented patients may have an influence on the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. Finally, we discuss our recommendations as to which drugs should be ideally withdrawn before performing a [¹²³I]FP-CIT SPECT scan for routine clinical purposes. The decision to withdraw any medication must always be made by the specialist in charge of the patient’s care and taking into account the pros and cons of doing so.     

复方磷酸可待因口服液依赖者多巴胺转运蛋白SPECT显像

目的 研究长期大剂量使用复方磷酸可待因口服液产生依赖对脑纹状体功能的损害.方法 29例复方磷酸可待因口服液依赖者、27例海洛因依赖者和31例健康志愿者分别行99Tcm-2β-[N,N＇-双（2-巯乙基）乙撑二胺基]甲基,3β-（4-氯苯基）托烷（TRODAT-1）SPECT显像,定性分析多巴胺转运蛋白（DAT）影像特征,同时定量分析3组受试者纹状体体积（V,cm3）、质量（m,g）和纹状体与全脑放射性比值（Ra,%）.使用SPSS 13.0软件对3组受试者的V、m和Ra进行t检验.结果 健康对照组双侧纹状体呈典型＂熊猫眼＂形态,DAT放射性分布均匀、对称;复方磷酸可待因口服液依赖者双侧纹状体外形变小,形态失常,放射性分布减低、缺损甚至紊乱,存在部分非特异性放射性分布;海洛因依赖者与其类似.复方磷酸可待因口服液依赖组双侧纹状体V=（23.68±4.94）cm3、m=（24.87±5.19）g、Ra=（5.01±0.88）%,均低于健康对照组的（35.39±4.42）cm3、（37.16±4.64）g和（7.93±0.86）%,t=-9.69,-9.69,-13.01,P均=0.000,高于海洛因依赖组的（18.87±4.66）cm3、（19.81±4.90）g和（4.26±1.02）%,t=3.74,3.74,2.96,P分别为0.000,0.000,0.005.结论 长期大剂量使用复方磷酸可待因口服液产生依赖可破坏纹状体功能,使纹状体部位DAT的分布、密度和活性减低,类似海洛因成瘾性脑病.     

Cognition and 99Tcm-HMPAO SPECT in Parkinson's disease.

99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) of brain was performed in 43 unselected patients with Parkinson's disease to evaluate whether low cerebral perfusion on SPECT correlated with cognitive impairment in the patients. All patients received neurological, Mini-Mental State Examination and a neuropsychological assessment. Eighteen (41.9%) of the 43 patients were demented. Thirty patients (69.8%) had abnormal SPECT: 17 had perfusion defects in cortical regions, eight in basal ganglia and five in both regions. Of the 22 patients with abnormal cortical perfusion, 15 (68.2%) were demented; only three (14.3%) of the 21 patients without cortical defect were demented (P < 0.01). Twelve of the 15 demented patients had low perfusion in the parietal region alone or in parietal and occipital regions. The cortical perfusion defects, present in 22 (51.2%) Parkinson's patients, are highly correlated with cognitive impairment. The pattern of SPECT abnormality in most demented patients with Parkinson's disease is similar to that seen in Alzheimer's disease, suggesting that the underlying pathophysiology for dementia in patients with Parkinson's disease may be similar to that in Alzheimer's disease.     

Serotonin transporters in the midbrain of Parkinson's disease patients: a study with 123I-beta-CIT SPECT.

In Parkinson's disease (PD), both neuropathologic and biochemical studies suggest that serotonin (5-hydroxytryptamine [5-HT]) neurons are affected by the disease process. The integrity of 5-HT transporters was assessed in PD patients with SPECT using 2beta-carbomethoxy-3beta-(4-(123)I-iodophenyl)tropane ((123)I-beta-CIT), which binds with high affinity to both dopamine (DA) and 5-HT transporters. METHODS: Forty-five PD patients at relatively early stages (mean Hoehn-Yahr stage, 2.0 +/- 0.7; range, 1-3) and 7 age-matched healthy control subjects had 15 scans over a 24-h period after injection of (123)I-beta-CIT using a 3-head SPECT system. In the midbrain, the 5-HT transporter parameter k(3)/k(4) was estimated by 3 noninvasive methods: pseudoequilibrium ratio (R(PE)) method, area ratio (R(A)) method, and a modified graphic method that derives the ratio of ligand distribution volumes (R(V)). Striatal V(3)", the DA transporter parameter that is equivalent to k(3)/k(4), was measured using the images acquired at 24 h after tracer injection. All measures were derived using the cerebellum as the reference region. RESULTS: In control subjects, the (123)I-beta-CIT activity in the midbrain reached a peak at 91 +/- 21 min after injection and then washed out at a slow rate (1.1%/h +/- 0.5%/h). The peak specific uptake in the midbrain occurred at 315 +/- 46 min. In PD patients, the temporal patterns of the midbrain and cerebellar activity were not significantly different from those in control subjects. None of midbrain R(PE), R(A), and R(V) was significantly different between control subjects and PD patients, whereas striatal V(3)" was bilaterally reduced in all patients, being 32% lower than that of the control subjects (P = 0.002). In PD patients, none of the midbrain outcome measures was significantly correlated with either striatal V(3)" or motor or nonmotor symptom ratings, including the Hoehn-Yahr stage and the Unified Parkinson's Disease Rating Scale scores. When the studies of 7 PD patients with depression were analyzed separately, none of the midbrain outcome measures in these patients either was different significantly from control values or correlated with the Hamilton Depression Rating Scale score. CONCLUSION: These results suggest that DA and 5-HT transporters are differentially affected in PD, and 5-HT transporters in the midbrain region may not be affected in relatively early stages of PD. Alternatively, 5-HT transporters in the remaining neurons may be upregulated, thus raising the midbrain 5-HT transporter density to almost normal levels.     

Quantification of dopamine transporter by 123I-PE2I SPECT and the noninvasive Logan graphical method in Parkinson's disease.

(E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-methyl-phenyl) nortropane (PE2I), a cocaine analog, is a new, highly specific tracer for imaging dopamine transporter labeled with (123)I for in vivo SPECT. Its reversible binding on dopamine transporter and its rapid kinetics allow quantification of its binding potential according to a 3-compartment model. For quantification of distribution volume of reversible tracer, Logan developed a noninvasive and graphical method that allows accurate estimation of binding potential. In this study, we performed (123)I-PE2I SPECT on healthy volunteers and patients with Parkinson's disease (PD) to validate the Logan graphical method for quantification of (123)I-PE2I binding and to analyze the relationship between (123)I-PE2I SPECT and clinical features of this frequent degenerative disease. METHODS: Eight PD patients (3 women, 5 men; mean age, 64 +/- 7.9 y; disease duration range, 1-8 y, Hoehn and Yahr stage range, 1-2.5) and 8 age-matched healthy volunteers (4 women, 4 men; mean age, 61.5 +/- 9.5 y) were included in 2 centers and studied with SPECT. Four sequential SPECT imaging sessions of 15-min duration were performed from 5 to 65 min after bolus injection of 140 +/- 30 MBq of (123)I-PE2I. RESULTS: The kinetics of PE2I in healthy volunteers and PD patients were rapid, and the Logan graphical method allowed quantification of distribution volume ratio (DVR) in the caudate nucleus and putamen. (123)I-PE2I striatal specific binding was significantly reduced in PD patients, compared with healthy volunteers, in the caudate and putamen. The decrease of DVR in the putamen was significantly and inversely correlated to disease duration and Hoehn and Yahr stage. In asymmetric PD patients, (123)I-PE2I uptake was significantly more reduced in the putamen contralateral to the side with predominant clinical symptoms. However, (123)I-PE2I uptake was also significantly reduced in the ipsilateral putamen, compared with that in healthy volunteers, suggesting that (123)I-PE2I SPECT can detect nigrostriatal degeneration before the appearance of clinical symptoms. CONCLUSION: Our data indicate that the Logan graphical method is accurate for noninvasive quantification of PE2I and that (123)I-PE2I SPECT is a useful quantitative method for accurate estimation of nigrostriatal dopaminergic nerve terminal degeneration. The close relationships between SPECT findings and clinical data suggest that this method is useful for objectively following the progression of PD and for assessing the effect of potential neuroprotective treatments. Finally, our findings suggest that (123)I-PE2I SPECT can be used for preclinical and early diagnosis of PD.     

Striatal dopamine transporter function in dementia with Lewy bodies and Parkinson's disease

The aim of this study was to compare parkinsonian features and loss of striatal dopamine transporter (DAT) function in patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PD), matched for age and disease duration. Twenty patients with DLB, 24 PD patients and 10 matched controls were examined with SPET using a dual-head camera and the dopamine-transporter ligand ¹²³I-#-CIT (148 MBq). Moreover, in a subgroup of patients (16 DLB and 20 PD patients), subscores of the Unified Parkinson's Disease Rating Scale (UPDRS) - motor examination (ME) subscale were obtained during "practical off", i.e. 12 h following withdrawal of antiparkinsonian therapy. Compared with controls, striatal/cerebellar (S/C) ratios of DAT binding were significantly reduced in both DLB and PD, deficits being more marked in DLB patients (controls 7.2ǃ.2, DLB 3.3ǃ, PD 4.2ǃ.4; means-SD). The side-to-side differences in the S/C ratios were lower in the DLB group and the controls than in PD patients (0.4ǂ.4, 0.2ǂ.2 and 0.6ǂ.3, respectively, P<0.05). The total UPDRS-ME scores during practical-off were significantly higher in the DLB than in the PD group (41.2ᆠ.7 vs 26.6ᆣ.3, P<0.01). The side-to-side differences of the summed UPDRS extremity subscores were smaller in the DLB than in the PD group (2.2DŽ.3 vs 7.4Dž.9, P<0.0001). Our findings suggest that parkinsonism evolves largely symmetrically and progresses more rapidly with more severe loss of striatal dopamine transporter function in DLB compared to PD. Whether these findings are helpful in the differential diagnosis of DLB and PD needs to be examined in further studies.     

帕金森病脑部葡萄糖代谢和脑多巴胺转运体PET显像特点的临床研究

目的 探讨18F-FDG脑代谢联合11C-甲基-N-2β-甲基酯-3β（4-F苯基）托烷（11C-CFT）脑多巴胺转运体（DAT）PET双显像在帕金森病（PD）诊断与病情严重程度评估中的应用价值。 方法 对55例不同严重程度的PD患者及30名健康对照者分别行18F-FDG脑代谢显像和11C-CFT脑DAT PET显像检查,通过勾画ROI,比较PET图像中不同严重程度的PD患者与健康对照者中脑基底节区葡萄糖代谢及DAT分布的差异,分析18F-FDG PET、11C-CFT PET显像在不同严重程度PD评估中的作用及特点。 结果 与健康对照者相比,18F-FDG PET显像中PD患者脑葡萄糖代谢改变主要为双侧基底节区壳核对称性代谢增高,同时部分患者伴有大脑皮质不同程度代谢减低;11C-CFT PET显像中PD患者双侧尾状核、壳核前、中、后部表现为DAT分布不同程度减低。单侧症状者或双侧症状者均以患侧对侧基底节区壳核DAT分布减低明显,并以壳核后部DAT分布减低为著。 结论 18F-FDG PET联合11C-CFT PET双显像在PD诊断及病情严重程度评估中有应用价值。     

Clinical evaluation of Parkinson's disease using 123I-IMP SPECT

N-isopropyl-p[123I]iodoamphetamine (123I-IMP) SPECT and regional cerebral blood flow (rCBF) studies were performed in 20 patients with Parkinson's disease (PD) and 8 normal subjects. RCBF was measured by the arterial blood sampling method which used the microsphere model. We analyzed seven factors which might be related to the rCBF in PD, i.e., age, stage, duration of the disease, cerebral atrophy, severity of dementia, laterality of symptoms and motor disability score (MDS; the degree of akinesia, rigidity, tremor, gait disturbance, freezing and pulsion sign). Compared with normal subjects, global CBF (supratentorial mean rCBF) was reduced 21.8% in PD. In particular, rCBF in the basal ganglia and that of frontal cortex were reduced 25.3%, 24.8%, respectively. Distribution patterns of rCBF in PD were almost as same as those in normals except for cerebellum. The reduction of both rCBFs in the basal ganglia and parietal cortex significantly correlated with MDS (p less than 0.05, respectively). Especially, akinesia was closely correlated to the reduction of rCBF in the parietal cortex (p less than 0.02). Moreover, we observed a significant relationship between cerebral atrophy and reduction of rCBF in each region except for cerebellum. However, there was no significant correlation between the severity of dementia and reduction of rCBF, even in the frontal cortex or parietal cortex. These data show that the severity of dementia in PD may be connected with other factors except for rCBF. 123I-IMP SPECT study is a useful method for clinical evaluation of PD.     

Dopamine transporter imaging (123)I-FP-CIT (DaTSCAN) SPET in differential diagnosis of dopa-responsive dystonia and young-onset Parkinson's disease

Dopa-responsive dystonia (DRD) is a genetic disorder characterized by childhood onset dystonia, dominant inheritance, diurnal symptoms fluctuation and positive levodopa response. Adult-onset DRD is frequently combined with parkinsonism and can be mistaken with young onset Parkinson's disease (YOPD). Both conditions are caused by dopamine deficiency, due to nigral cells' loss in YOPD, and due to enzymatic defects in dopamine synthesis in DRD. Single photon emission tomography (SPET) with (123)I-N--fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane ((123)I-FP-CIT)-DaTSCAN is a sensitive neuroimaging method for the assessment of nigrostriatal dopaminergic system integrity and degeneration. Our aim was to evaluate the usefulness of (123)I-FP-CIT( DaTSCAN) SPET in the differential diagnosis of DRD and YOPD in clinical practice. Brain SPET with (123)I-FP-CIT was performed in 13 patients (7 males, 6 females), age 20-58 years, with mean age of onset of their disease, 29 years, eleven patients with early onset parkinsonian symptoms and 2 with genetically proved DRD. The images were evaluated by visual and semiquantitative analyses (ROI). The ratio of specific-striatal to non specific-occipital binding was calculated. Ten out of 11 patients with YOPD had decreased accumulation of DaTSCAN in striatum, especially in putamen, that is typical findings for Parkinson's disease. In three patients DaTSCAN was normal with symmetric tracer uptake in both striata, caudate nucleus and putamen and the diagnosis of DRD was suspected. Two patients with initial dystonic symptoms and genetically proved DRD had normal DaTSCAN. In one patient after normal DaTSCAN findings the initial diagnosis of YOPD was changed to the diagnosis of DRD. Region of interest (ROI) analyses have shown significantly lower(123)I-FP-CIT binding ratios in YOPD than in DRD in all 3 regions of interest: striatum (1.95±0.32) vs (2.76±0.10) P<0.001, putamen (1.76±0.25) vs (2.84±0.14) P<0.0001 and caudate nucleus (2.37±0.51) vs (3.27±0.14) P<0.01. In conclusion, our results indicate that DaTSCAN is an objective neuroimaging method able to distinguisch neurodegenerative disease YOPD from DRD and clarify a clinical dilemma, which is important for the treatment, prognosis and genetic counseling of patients and their families.     

Striatal dopamine transporter function in dementia with Lewy bodies and Parkinson's disease.

The aim of this study was to compare parkinsonian features and loss of striatal dopamine transporter (DAT) function in patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PD), matched for age and disease duration. Twenty patients with DLB. 24 PD patients and 10 matched controls were examined with SPET using a dual-head camera and the dopamine-transporter ligand 123I-beta-CIT (148 MBq). Moreover, in a subgroup of patients (16 DLB and 20 PD patients), subscores of the Unified Parkinson's Disease Rating Scale (UPDRS)-motor examination (ME) subscale were obtained during "practical off", i.e. 12 h following withdrawal of antiparkinsonian therapy. Compared with controls, striatal/cerebellar (S/C) ratios of DAT binding were significantly reduced in both DLB and PD, deficits being more marked in DLB patients (controls 7.2 +/- 1.2, DLB 3.3 +/- 1, PD 4.2 +/- 1.4; means +/- SD). The side-to-side differences in the S/C ratios were lower in the DLB group and the controls than in PD patients (0.4 +/- 0.4. 0.2 +/- 0.2 and 0.6 +/- 0.3, respectively, P<0.05). The total UPDRS-ME scores during practical-off were significantly higher in the DLB than in the PD group (41.2 +/- 12.7 vs 26.6 +/- 15.3, P<0.01). The side-to-side differences of the summed UPDRS extremity subscores were smaller in the DLB than in the PD group (2.2 +/- 2.3 vs 7.4 +/- 3.9, P<0.0001). Our findings suggest that parkinsonism evolves largely symmetrically and progresses more rapidly with more severe loss of striatal dopamine transporter function in DLB compared to PD. Whether these findings are helpful in the differential diagnosis of DLB and PD needs to be examined in further studies.     

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.     

Technetium HMPAO SPECT study in dementia with Lewy bodies, Alzheimer's disease and idiopathic Parkinson's disease.

The aim of this study was to compare the regional cerebral blood flow measurements studied by SPECT in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) to determine the contribution of SPECT to the differential diagnosis of these two diseases. METHODS: SPECT analysis with 99mTc-hexamethyl propyleneamine oxime (HMPAO) was performed in 20 patients with probable DLB, 20 patients with probable AD and 20 patients with idiopathic Parkinson's disease (IPD). Ten pairs of regions of interest were analyzed. Tracer uptake was expressed as a corticocerebellar activity ratio. RESULTS: Compared with IPD, in the DLB group there was a global decrease of HMPAO uptake in cortical regions of interest except in the posterior frontal and occipital regions; in the AD group there was limited left temporal and parietal hypoperfusion. In the DLB group, frontal HMPAO uptake was significantly lower than in the AD group. Two predictive scores were established by a factorial discriminant analysis from six left cortical indices (medial frontal, lateral frontal, posterior frontal, temporoparietal, parietal and parietooccipital) and the Mini-Mental State Examination, which correctly classified 53 of 60 patients (88%) (DLB, 18 of 20; AD, 16 of 20; IPD, 19 of 20). CONCLUSION: These findings indicate the presence of diffuse cortical abnormalities in DLB and suggest that SPECT may be useful in discriminating in vivo DLB from AD, revealing mainly frontal hypoperfusion in the former group. We estimate that SPECT study increases the possibility of separating DLB and AD because both disorders share different patterns of cerebral blood flow abnormality.     

多巴胺D2受体乃131I-epidepride显像对帕金森病的临床研究

目的 评价多巴胺D2受体显像剂131I-(s)-(-)-N-[(1-乙基-2-吡咯烷基)甲基]-5-碘-2,3-二甲氧基苯甲酰胺(epidepride)对帕金森病(PD)的临床应用价值.方法 PD患者38例(H/YⅠ～Ⅳ级,病程4个月～6年),健康对照组12例,静脉注射131I-epidepride 18.5 MBq 3 h后行SPECT显像,并应用感兴趣区(ROI)技术计算纹状体/枕叶放射性(ST/OC)比值,分析ST/OC比值与PD患者临床严重程度的相关性.采用SPSS 10.0软件对数据进行校正t检验,配对t检验及Spearman相关分析.结果 对照组131I-epidepride显像示双侧纹状体内有高度放射性浓聚,纹状体显示清晰,双侧基本对称,额叶、颞叶、顶叶、枕叶及小脑放射性较低.与健康对照组比较,PD患者ST内131I-epide-pride浓聚增加,但差异无统计学意义.早期PD患者(H/Y Ⅰ级)病侧肢体的对侧ST放射性显著增加、体积增大(壳核尤为显著),与同侧ST相比差异有统计学意义(t=7.89,P＜0.05).ST/OC比值与PD临床严重程度(H/Y分级)无明显相关性(r=0.12,P＞0.05).结论 多巴胺D2受体131I-Epi-depride SPECT显像有助于了解PD患者ST内突触后膜的多巴胺D2受体变化,PD患者D2上调,在偏侧PD中以病变对侧壳核尤为显著.ST/OC比值与PD临床严重程度无相关性.     

Sensitivity and specificity of 99mTc-TRODAT-1 SPECT imaging in differentiating patients with idiopathic Parkinson's disease from healthy subjects.

The imaging of dopamine transporter (DAT) with (99m)Tc-TRODAT-1 ([2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)]-(99m)Tc-technetium) and SPECT has been recently proposed to be a valuable and feasible means of assessment of the integrity of dopamine neurons. The purpose of this study was to further investigate the clinical correlations and the age-specific sensitivity and specificity of this new approach in the diagnosis of patients with idiopathic Parkinson's disease (PD) that manifests in patients >50 y of age. METHODS: SPECT imaging with (99m)Tc-TRODAT-1 was conducted in 78 consecutive PD patients and in 40 age-matched healthy subjects. The images were obtained 4 h after the intravenous injection of the tracer. The ratios of specific striatal binding to nonspecific occipital binding were calculated. S/O represents the ratio for whole striatal binding, whereas P/O and C/O represent the putamen and caudate nucleus, respectively. Statistical analyses of the sensitivity and specificity of these ratios in different age-specific subgroups were performed. The correlations between these ratios and clinical assessments were also analyzed. The age-related declines in the striatal binding in both patients and controls were given particular focus. RESULTS: The S/O, C/O, and P/O ratios decreased significantly both contralaterally and ipsilaterally to the dominant symptomatic side in the PD group (P < 0.0001). The mean reduction of binding was found in the order of putamen (contralateral side, -81%; ipsilateral side, -67%) and caudate nucleus (contralateral side, -46%; ipsilateral side, -40%). The sensitivity and specificity of both P/O and S/O ratios were 100% in discriminating PD patients from healthy subjects in the age-specific groups. The binding ratios correlated negatively with the Unified Parkinson's Rating Scale and Hoehn and Yahr (H-Y) staging. Of particular interest, the binding of the striatum contralateral to the asymptomatic side in H-Y stage I patients also decreased significantly. The age-related decline of these ratios was significant in the control group. CONCLUSION: We have demonstrated that (99m)Tc-TRODAT-1 SPECT has a high sensitivity and specificity for measuring the decrement of DAT in PD patients. In addition to its wide availability, we suggest that this new approach may serve as a diagnostic marker for PD.     

Dopamine transporter concentration is reduced in asymptomatic Machado-Joseph disease gene carriers.

Dopamine transporter (DAT) binding is decreased in Machado-Joseph disease (MJD) patients. To further investigate the DAT activity in asymptomatic MJD (aMJD) gene carriers, we performed this prospective study using (99m)Tc-TRODAT-1 ([(99m)Tc][2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]-methyl](2-mercaptoethyl)amino]ethyl]amino]ethane-thiolato(3-)-N2,N2',S2,S2]oxo-[1R-(exo-exo)])) brain SPECT on 5 aMJD gene carriers, 10 age-matched MJD patients, and 10 age-matched healthy control subjects. METHODS: Brain SPECT images were acquired 4 h after intravenous injection of 925 MBq (25 mCi) (99m)Tc-T RODAT-1, which is known to bind specifically to the DAT on the nigrostriatal terminals. By fusing these SPECT images with a striatal atlas, obtained from MRI, binding of this tracer in the entire striatum was measured and the uptake values in bilateral striatal areas were compared between these 3 groups. RESULTS: The uptake values of the aMJD gene carriers (P < 0.001) and MJD patients (P < 0.001) displayed a significant reduction compared with those of the control subjects. The reduction was more severe in the MJD patient group (P < 0.05). Bilateral putamen-to-caudate ratios were significantly lower in the aMJD gene carrier and MJD patient groups (P < 0.001). The dopamine neuronal activity, as represented by the tracer binding, was more prominently affected in the putamen in these patients and gene carriers. CONCLUSION: (99m)Tc-TRODAT-1 brain SPECT is capable of detecting early alteration of dopamine neurons in the striatal region. Significantly, the results suggest that this impairment of presynaptic dopamine function actually occurs at an early stage, which was previously unrecognized in these aMJD gene carriers.     

Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson's disease.

We studied the correlation of striatal dopamine transporter (DAT) imaging with anxiety and depression symptoms in Parkinson's disease (PD). METHODS: Patients with idiopathic PD (n = 76) and age-matched healthy volunteers (n = 46) underwent SPECT brain scans with (99m)Tc-TRODAT-1, a radiolabeled tropane that selectively binds to the DAT. TRODAT-1 distribution volume ratios, a reflection of DAT availability, were calculated from the SPECT scan data for 6 regions of interest (ROIs) in the caudate and putamen. The association between neuropsychiatric symptoms (anxiety, depression, and fatigue) and DAT availability was explored for both subject groups, and the impact of disease severity on this association was examined in the PD group. RESULTS: PD patients showed lower DAT availability than did healthy volunteers in all examined regions (for all ROIs, P < 0.001). In PD patients, higher individual affective measures (for anxiety, r = -0.30 and P = 0.01; and for depression, r = -0.24 and P = 0.05) and total affect scores (r = -0.31; P = 0.01) were associated with diminished left anterior putamen DAT availability. The association between total affect scores and DAT availability was present only in the subset of patients with less severe PD (r = -0.35; P = 0.04), but subjects with the highest DAT availability did not show high total affect scores. No association between neuropsychiatric measures and DAT availability was found in the controls. CONCLUSION: These preliminary findings suggest that decreased DAT availability may be necessary for but not invariably associated with the development of affective symptoms in PD. This suggestion is consistent with previous research showing a link between depression and basal ganglia impairment, particularly involving the left hemisphere, and extends this finding to include anxiety.     

慢性实验性帕金森病模型猴多巴胺转运蛋白显像研究

目的　探讨多巴胺系统功能显像对帕金森病 (PD)的诊断价值。方法　对 5只正常猴及 6只经颈动脉注射 1 甲基 4 苯基 1,2 ,3,6 四氢吡啶 (MPTP) 30个月的PD模型猴进行99Tcm 2 β [N ,N′ 双 (2 巯乙基 )乙撑二胺基 ]甲基 ,3β (4 氯苯基 )托烷 (TRODAT 1)SPECT显像 ,经图像处理 ,计算正常及PD模型猴纹状体特异摄取比值 (SURs)。结果　正常猴纹状体在 30 ,6 0 ,12 0 ,15 0 ,180及 2 4 0minSURs分别为 0 5 4 9,0 792 ,0 84 8,0 96 5 ,0 96 9和 0 96 4 ;MPTP模型猴 3h双侧纹状体比值 [健侧 (左侧 ,L) 损毁侧 (右侧 ,R) (L R) =1 32 8± 0 30 8]明显高于对照猴 (L R =1 0 16± 0 0 12 ,t=9 87,P <0 0 5 ) ;损毁侧纹状体 枕叶摄取比值为 0 385± 0 32 6 ,明显低于对侧 (0 795± 0 4 2 6 )及对照猴 (R :0 790± 0 2 4 4 ,L :0 819± 0 2 4 9;t分别为 8 5 6 ,9 4 2和 8 93,P均 <0 0 5 )。结论　99Tcm TRODAT 1SPECT脑显像能反映PD模型猴脑多巴胺能突触前功能的变化。