technetium-tc-99m-bicisate and Parkinson-Disease

The purpose of this study was to investigate the feasibility and utility of dual-isotope SPECT for differential diagnosis of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA).. Simultaneous (99m)Tc-ECD/123I-FP-CIT studies were performed in nine normal controls, five IPD patients, and five MSA patients. Projections were corrected for scatter, cross-talk, and high-energy penetration, and iteratively reconstructed while correcting for patient-specific attenuation and variable collimator response. Perfusion and dopamine transporter (DAT) function were assessed using voxel-based statistical parametric mapping (SPM2) and volume of interest quantitation. DAT binding potential (BP) and asymmetry index (AI) were estimated in the putamen and caudate nucleus.. Striatal BP was lower in IPD (55%) and MSA (23%) compared to normal controls (p<0.01) , and in IPD compared to MSA (p<0.05). AI was greater for IPD than for MSA and controls in both the caudate nucleus and the putamen (p<0.05). There was significantly decreased perfusion in the left and right nucleus lentiformis in MSA compared to IPD and controls (p<0.05).. Dual-isotope studies are both feasible in and promising for the diagnosis of parkinsonian syndromes.

Topics: Cysteine; Diagnosis, Differential; Feasibility Studies; Female; Humans; Image Enhancement; Male; Middle Aged; Multiple System Atrophy; Organotechnetium Compounds; Parkinson Disease; Radionuclide Imaging; Reproducibility of Results; Sensitivity and Specificity; Tropanes

Statistical parametric mapping was performed to investigate differences in regional cerebral blood flow (rCBF) between patients with idiopathic Parkinson's disease (IPD), patients with multiple system atrophy (MSA), and healthy volunteers. In addition, a voxel-based covariance analysis was performed with disease-specific parameters and clinical patient data such as disease duration, medication, and clinical subscores.. For this purpose, (99m)Tc-ethylcysteine dimer (ECD) SPECT was performed on 81 IPD patients (50 men, 31 women; age, 62.6 +/- 10.2 y), 15 MSA patients (9 men, 6 women; age, 61.5 +/- 9.2 y), and 44 age- and sex-matched healthy volunteers (27 men, 17 women; age, 59.2 +/- 11.9 y).. Significant hypoperfusion was observed in IPD compared with healthy subjects in a symmetric subcortical-cortical network including the basal ganglia, thalami, prefrontal and lateral frontal cortex, and parietooccipital cortex (voxel P value P(height) < 0.001, corrected for multiple comparisons). For MSA, only symmetric hypoperfusion was seen in the putamen and thalamus with respect to healthy subjects and to IPD (P(height) < 0.01, corrected). Prolonged disease duration or higher Hoehn and Yahr stage results in hypoperfusion of the posterior associative cortex. There is a negative correlation between perfusion of the caudate heads and limbic system and the standardized dosage of dopamine agonists in the patients with PD, whereas for MSA a bilateral decrease in putamen activity was noted (P(height) < 0.001, uncorrected). Cognitive performance was positively correlated with limbic perfusion and inversely correlated with posterior associative cortical areas, but not with prefrontal regions.. Voxel-based analysis of (99m)Tc-ECD perfusion SPECT shows detailed differences between IPD and MSA, which may be of use in the differentiation of both disease entities, and is able to elucidate cerebral perfusion correlates of disease severity, dopamine agonist medication, and cognitive performance.

Topics: Algorithms; Brain; Cysteine; Diagnosis, Differential; Female; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Multiple System Atrophy; Organotechnetium Compounds; Parkinson Disease; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon

The clinical differentiation between typical idiopathic Parkinson's disease (IPD) and atypical parkinsonian disorders such as multiple system atrophy (MSA) is complicated by the presence of signs and symptoms common to both forms. The goal of this study was to re-evaluate the contribution of brain perfusion single-photon emission tomography (SPET) with anatomical standardisation and automated analysis in the differentiation of IPD and MSA. This was achieved by discriminant analysis in comparison with a large set of age- and gender-matched healthy volunteers. Technetium-99m ethyl cysteinate dimer SPET was performed on 140 subjects: 81 IPD patients (age 62.6+/-10.2 years; disease duration 11.0+/-6.4 years; 50 males/31 females), 15 MSA patients (61.5+/-9.2 years; disease duration 3.0+/-2.2 years; 9 males/6 females) and 44 age- and gender-matched healthy volunteers (age 59.2+/-11.9 years; 27 males/17 females). Patients were matched for severity (Hoehn and Yahr stage). Automated predefined volume of interest (VOI) analysis was carried out after anatomical standardisation. Stepwise discriminant analysis with cross-validation using the leave-one-out method was used to determine the subgroup of variables giving the highest accuracy for this differential diagnosis. Between MSA and IPD, the only regions with highly significant differences in uptake after Bonferroni correction were the putamen VOIs. Comparing MSA versus normals and IPD, with putamen VOI values as discriminating variables, cross-validated performance showed correct classification of MSA patients with a sensitivity of 73.3%, a specificity of 84% and an accuracy of 83.6%. Additional input from the right caudate head and the left prefrontal and left mesial temporal cortex allowed 100% discrimination even after cross-validation. Discrimination between the IPD group alone and healthy volunteers was accurate in 94% of the cases after cross-validation, with a sensitivity of 91.4% and a specificity of 100%. The three-group classification (MSA, IPD and healthy volunteers) resulted in an overall accuracy of 86% post hoc, with 98% of normals, 78% of IPD and 93% of MSA correctly classified. These values were slightly lower after cross-validation: 96% for healthy volunteers, 77% for IPD and 67% for MSA. In conclusion, using age- and gender-matched healthy volunteer data and anatomical standardisation, it is possible to differentiate between IPD and MSA with high discriminating power in clinically relevant circums

Topics: Brain; Cysteine; Diagnosis, Differential; Discriminant Analysis; Female; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Multiple System Atrophy; Organotechnetium Compounds; Parkinson Disease; Radiopharmaceuticals; Reference Standards; Reference Values; Subtraction Technique; Tomography, Emission-Computed, Single-Photon

High-frequency stimulation of the internal pallidum is an effective surgical approach for patients with advanced Parkinson's disease suffering from motor fluctuations and L-dopa induced dyskinesia. To study the acute effects of internal pallidum stimulation, changes in cerebral blood flow were measured by means of a single-day split-dose protocol using 99Tc(m)-ECD SPET. Nine patients with advanced Parkinson's disease and with a clinical picture predominated by tremor and drug-induced dyskinesia, were imaged before and immediately after electrostimulation. Brain perfusion data were mirrored to the same electrode side (five left and four right implants), co-registered and analysed statistically on a voxel-by-voxel basis (Statistical Parametric Mapping) and by an automated volume-of-interest approach. Acute stimulation of the internal pallidum induced a significantly decreased perfusion in the ipsilateral thalamus and striatum, as well as in the right parietal cortex. For the subgroup of seven patients with effective motor score improvements, a significant correlation between thalamic and striatal perfusion changes and UPDRS III motor score was present (P = 0.04). These results suggest that effective stimulation of the internal globus pallidus may produce symptom relief through decreased activity in pallido-thalamo-cortical circuits.

Topics: Adult; Aged; Brain Mapping; Cerebrovascular Circulation; Cysteine; Electric Stimulation; Electrodes; Female; Globus Pallidus; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Organotechnetium Compounds; Parkinson Disease; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

This study investigated alterations in regional cerebral blood flow (rCBF) in patients with Parkinson's disease using statistical parametric mapping (SPM).. 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.. 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.. 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.

Topics: Adult; Aged; Brain; Brain Mapping; Cerebrovascular Circulation; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Parkinson Disease; Radiopharmaceuticals; Regional Blood Flow; Software; Tomography, Emission-Computed, Single-Photon

Cerebral microbleeds (CMBs) in patients with Parkinson's disease (PD) or dementia with Lewy bodies (DLB) have not been adequately studied.. This study aims to find a difference in the total number, prevalence, and common locations of CMBs between PD and DLB and evaluate 99 mTc-ECD SPECT subtraction images of these two diseases.. We examined 112 patients with PD (53 males and 59 females; age: 77.4±3.6 years) and 28 age-matched patients with DLB (15 males and 13 females; age: 77.1±6.7 years) using brain magnetic resonance imaging (MRI) and 99 mTc-ECD SPECT subtraction imaging.. The total number of CMBs was higher in patients with DLB (41.2%) than in those with PD (11.5%), and the prevalence was significantly higher in the former (0.7±1.1) than the latter (0.2±0.5, p < 0.05). The odds ratio was 5.4 (95% confidence interval [CI]: 1.7-17.4). Furthermore, CMBs were commonly located in the basal ganglia of patients with PD (6 out of 87 patients) but in the occipital lobe of patients with DLB (8 out of 17 patients). 99 mTc-ECD SPECT subtraction imaging indicated lower cerebral blood flow in the posterior cingulate gyrus among the patients with CMB-positive DLB than among those with CMB-positive PD; additionally, the cerebral blood flow was lower in the bilateral basal ganglia and midbrain among patients with CMB-positive DLB compared to those with CMB-negative DLB.. A reduction in occipital glucose metabolism may be related to CMBs in the occipital lobe of patients with DLB.

Topics: Aged; Aged, 80 and over; Angiography, Digital Subtraction; Basal Ganglia; Cerebrovascular Circulation; Cysteine; Female; Glucose; Gyrus Cinguli; Humans; Intracranial Hemorrhages; Lewy Body Disease; Magnetic Resonance Angiography; Male; Mental Status and Dementia Tests; Mesencephalon; Neuropsychological Tests; Occipital Lobe; Organotechnetium Compounds; Parkinson Disease; Prevalence; Tomography, Emission-Computed, Single-Photon

Because it is often difficult to precisely diagnose and distinguish progressive supranuclear palsy (PSP) from corticobasal degeneration (CBD), multiple system atrophy-parkinsonism (MSA-P) and Parkinson's disease (PD) at the onset of the disease, we compared the patients and clarified the features of these diseases.. We compared 77 PSP, 26 CBD, 26 MSA-P and 166 PD patients from clinical and imaging points of view including cerebral blood flow (CBF) in the frontal eye field.. The clinical characteristics of PSP were supranuclear gaze disturbance, optokinetic nystagmus (OKN) impairment and falls at the first visit. On head MRI, midbrain tegmentum atrophy was much more frequently detected in PSP than in all of the other groups. Heart-to-mediastinum average count ratio (H/M) in iodine-123 meta-iodobenzyl guanidine ((123)I-MIBG) myocardial scintigraphy was not decreased in PSP, CBD, MSA-P and PD-Yahr 1 (-1), but patients of PD-2, 3, 4 and 5 showed a significant decrease compared with the PSP group. The CBF in the left frontal eye field of PD-3 group and that in right frontal eye field of PD-3 and PD-4 groups were lower than that of PSP group, although other groups showed a tendency without a significant decrease compared with PSP group.. PSP is distinguishable from CBD, MSA-P and PD even at the early stage with extra-ocular movement (EOM) disturbance, falls, atrophy of the midbrain tegmentum, and H/M in (123)I-MIBG myocardial scintigraphy, and the reduction of CBF in area 8 could serve as a supplemental diagnostic method for distinguishing PSP from PD-3 or PD-4.

Topics: 3-Iodobenzylguanidine; Aged; Aged, 80 and over; Basal Ganglia; Cerebral Cortex; Cerebrovascular Circulation; Cysteine; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Multiple System Atrophy; Neurodegenerative Diseases; Organotechnetium Compounds; Parkinson Disease; Parkinsonian Disorders; Radiopharmaceuticals; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon

The main clinical feature of dementia in Parkinson's disease is a dysexecutive syndrome. The neuropathology of PD dementia (PDD) is likely multifactorial and affects several neuronal populations. There is evidence that Parkinson's disease dementia is associated with a cholinergic deficit, supporting the therapeutic role of cholinesterase inhibitors, which are already first-line agents in the treatment of Alzheimer's disease. The paper includes short report on a pilot study with description of cognitive and imaging profiles in patients with mild to moderate stage of Parkinson disease dementia (PDD).. A random sample of 16 patients with clinical diagnostic criteria for probable PDD was included in the study. Patients were characterized with mild to moderate cognitive decline slightly depressive mood and moderate motor performance. Brain perfusion [(99m)Tc]ECD / SPECT and structural MRI with emphasis on evaluation of the degree of cortical atrophy and the medial temporal atrophy index was performed. All patients had detailed neuropsychological evaluation using a "cognitive process approach". Neuropsychological data were correlated voxel-wise with normalized brain perfusion images, creating whole-brain correlation maps.. Previously reported generalized cognitive impairment in PDD with predominant executive, visouspatial and attentional deficits was confirmed. Performance on specific cognitive measures was correlated with perfusion brain SPECT findings. It could be speculated that different pathological mechanisms underlie widespread significant brain perfusion decrements in temporal, parietal and frontal regions.

Topics: Aged; Antiparkinson Agents; Atrophy; Brain Mapping; Cerebral Cortex; Cholinesterase Inhibitors; Cysteine; Dementia; Female; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Organotechnetium Compounds; Parkinson Disease; Pilot Projects; Psychometrics; Statistics as Topic; Tomography, Emission-Computed, Single-Photon

Pathological gambling (PG) may develop in patients with Parkinson disease (PD) during dopamine replacement therapy, but the underlying neural correlates are still unclear.. To investigate resting state brain perfusion in PD patients with active PG compared with matched PD controls and healthy controls.. Case-control study.. Outpatient tertiary clinic.. Eleven right-handed PD patients with active PG according to Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) criteria, 40 matched PD controls, and 29 age-matched healthy controls.. All the participants underwent resting state brain perfusion single-photon emission computed tomography using technetium TC 99m ethylcysteinate dimer bicisate. All PD subjects were taking dopaminergic medication.. Statistical Parametric Mapping was used for data analysis (P<.005, false discovery rate corrected).. PD patients with PG showed resting state overactivity in a right hemisphere network that included the orbitofrontal cortex, the hippocampus, the amygdala, the insula, and the ventral pallidum. No areas of perfusion reduction were detected.. We found that PD patients with PG have abnormal resting state dysfunction of the mesocorticolimbic network possibly associated with a drug-induced overstimulation of relatively preserved reward-related neuronal systems. These findings support the concept that PG is a "behavioral" addictive disorder.

Topics: Aged; Brain; Brain Mapping; Case-Control Studies; Cysteine; Female; Functional Laterality; Gambling; Humans; Male; Middle Aged; Neuropsychological Tests; Organotechnetium Compounds; Parkinson Disease; Retrospective Studies; Tomography, Emission-Computed, Single-Photon

We examined clinical presentations, neuropsychological findings, and perfusion patterns of (99m)Tc-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) in patients with early stage dementia with Lewy bodies (DLB) (n = 17) and Parkinson's disease (PD) (n = 16), with age-matched healthy controls (n = 10). Seven paired regions of interest (ROIs) were drawn manually including inferior frontal, temporal, parietal, occipital, parieto-occipital junction, striatum and thalamus for semiquantitative measurement. Neuropsychological tests were applied for clinical correlation. The SPECT results showed significant hypoperfusion in DLB group in frontal, parietal, thalamus, temporal ROIs compared with controls (P < 0.01) whilst signals in temporal areas was significantly reduced compared with PD group (P < 0.05). Neuropsychological tests showed that DLB patients had deficits in mental manipulation, short-term memory, abstract thinking, drawing and semantic verbal fluencies (P < 0.05, compared with control). In addition, DLB group had lower scores than those with PD in mental manipulation, drawing and semantic verbal fluency (P < 0.05). Our study showed that even in early stages of DLB, neuropsychological and perfusion patterns were evident and may be different from PD group, despite they shared certain similarities both in neuropsychological and image findings compared with age-matched controls.

Topics: Aged; Aged, 80 and over; Brain; Cerebrovascular Circulation; Cognition Disorders; Cysteine; Diagnosis, Differential; Disease Progression; Early Diagnosis; Female; Humans; Lewy Body Disease; Male; Middle Aged; Neuropsychological Tests; Organotechnetium Compounds; Parkinson Disease; Predictive Value of Tests; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

Extradural motor cortex stimulation (EMCS) has been proposed as alternative to deep brain stimulation (DBS) in the treatment of Parkinson's disease (PD). Its mechanisms of action are still unclear. Neuroimaging evidenced motor cortical dysfunction in PD that can be reversed by therapy. We performed left hemisphere EMCS surgery in six advanced PD patients fulfilling CAPSIT criteria for DBS with the exception of age >70 years. After 6 months, we measured regional cerebral blood flow (rCBF) at rest with SPECT and Tc-99m cysteinate dimer bicisate off-medication with stimulator off and on. Clinical assessment included Unified Parkinson's Disease Rating Scale part II and III, Abnormal Involuntary Movement Scale and mean dopaminergic medication dosage. We used statistical parametric mapping for imaging data analysis. Clinically we observed no mean changes in motor scales, although blinded evaluation revealed some benefit in individual patients. We found significant rCBF decrements in the pre-central gyrus, pre-motor cortex and caudate nucleus bilaterally, left prefrontal areas and right thalamus. Perfusion increments were found in cerebellum bilaterally. EMCS determined significant modulation of neuronal activity within the cortico-basal ganglia-thalamo-cortical motor loop in our cohort of advanced PD patients. However, these effects were paralleled by mild and variable clinical efficacy.

Topics: Aged; Brain; Cerebrovascular Circulation; Cohort Studies; Cysteine; Electric Stimulation Therapy; Electrodes, Implanted; Female; Humans; Image Processing, Computer-Assisted; Male; Motor Cortex; Neural Pathways; Organotechnetium Compounds; Parkinson Disease; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Spatial covariance analysis has been used with FDG PET to identify a specific metabolic network associated with Parkinson's disease (PD). In the current study, we utilized a new, fully automated voxel-based method to quantify network expression in ECD SPECT images from patients with classical PD, patients with multiple system atrophy (MSA), and healthy control subjects.. We applied a previously validated voxel-based PD-related covariance pattern (PDRP) to quantify network expression in the ECD SPECT scans of 35 PD patients, 15 age- and disease severity-matched MSA patients, and 35 age-matched healthy control subjects. PDRP scores were compared across groups using analysis of variance. The sensitivity and specificity of the prospectively computed PDRP scores in the differential diagnosis of individual subjects were assessed by receiver operating characteristic (ROC) analysis.. PDRP scores were significantly increased (p < 0.001) in the PD group relative to the MSA and control groups. ROC analysis indicated that the overall diagnostic accuracy of the PDRP measures was 0.91 (AUC). The optimal cutoff value was consistent with a sensitivity of 0.97 and a specificity of 0.80 and 0.71 for discriminating PD patients from MSA and normal controls, respectively.. Our findings suggest that fully automated voxel-based network assessment techniques can be used to quantify network expression in the ECD SPECT scans of parkinsonian patients.

Topics: Algorithms; Brain; Cysteine; Female; Humans; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Male; Middle Aged; Multiple System Atrophy; Organotechnetium Compounds; Parkinson Disease; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Signal Transduction; Tomography, Emission-Computed, Single-Photon

Progressive supranuclear palsy (PSP) is an akinetic-rigid syndrome that can be difficult to differentiate from Parkinson's disease (PD), particularly at an early stage. [99mTc]ethyl cysteinate dimer (ECD) SPECT could represent a widely available tool to assist in the differential diagnosis. In this study we used voxel-based analysis and Computerised Brain Atlas (CBA)-based principal component analysis (PCA) of [99mTc]ECD SPECT data to test whether: (1) specific patterns of rCBF abnormalities can differentiate PSP from controls and PD; (2) networks of dysfunctional brain regions can be found in PSP vs controls and PD.. Nine PD patients, 16 PSP patients and ten controls were studied with [99mTc]ECD SPECT using a brain-dedicated device (Ceraspect). Voxel-based analysis was performed with statistical parametric mapping. PCA was applied to volume of interest data after spatial normalisation to CBA.. The voxel-based analysis showed hypoperfusion of the anterior cingulate and medial frontal cortex in PSP compared with controls and PD. In PSP patients the rCBF impairment extended to the pre-supplementary motor area and prefrontal cortex, areas involved in executive function and motor networks. Compared with PSP patients, PD patients showed a mild rCBF decrease in associative visual areas which could be related to the known impairment of visuospatial function. The PCA identified three principal components differentiating PSP patients from controls and/or PD patients that included groups of cortical and subcortical brain regions with relatively decreased (cingulate cortex, prefrontal cortex and caudate) or increased (parietal cortex) rCBF, representing distinct functional networks in PSP.. Anterior cingulate hypoperfusion seems to be an early, distinct brain abnormality in PSP as compared with PD.

Topics: Cysteine; Diagnosis, Differential; Female; Gyrus Cinguli; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Organotechnetium Compounds; Parkinson Disease; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Supranuclear Palsy, Progressive; Tomography, Emission-Computed, Single-Photon

Clinical differential diagnosis in parkinsonism can be difficult especially at early stages. We investigated whether combined perfusion and dopamine transporter (DAT) imaging can aid in the differential diagnosis of parkinsonian disorders: idiopathic Parkinson's disease (IPD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), dementia with Lewy bodies (LBD), and essential tremor (ET).. One hundred twenty-nine patients were studied, retrospectively (69 males; 24 MSA, 12 PSP, 8 LBD, 27 ET, and 58 IPD; mean disease duration, 3.5 +/- 3.7 y). Diagnosis was based on established clinical criteria after follow-up of 5.5 +/- 3.8 y in a university specialist movement disorders clinic. Group characterization was done using a categoric voxel-based design and, second, a predefined volume-of-interest approach along Brodmann areas (BA) and subcortical structures, including striatal asymmetry and anteroposterior indices. Stepwise forward discriminant analysis was performed with cross-validation (CV) using the leave-one-out technique.. Characteristic patterns for perfusion and DAT were found for all pathologies. In the parkinson-plus group, MSA, PSP, and LBD could be discriminated in 100% (+CV) of the cases. When including IPD, discrimination accuracy was 82.4% (99% without CV). 2beta-Carbomethoxy-3beta-(4-iodophenyl)nortropane imaging as a single technique was able to discriminate between ET and neurodegenerative forms with an accuracy of 93.0% (+CV); inclusion of perfusion information augmented this slightly to 97.4% (+CV).. Dual-tracer DAT and perfusion SPECT in combination with discrimination analysis allows an automated, accurate differentiation between the most common forms of parkinsonism in a clinically relevant setting.

Topics: Algorithms; Brain; Cysteine; Diagnosis, Differential; Discriminant Analysis; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Male; Organotechnetium Compounds; Parkinson Disease; Pattern Recognition, Automated; Perfusion; Radiopharmaceuticals; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon; Tropanes

To investigate the pattern of regional cerebral blood flow (rCBF) deficits in Parkinson's disease patients in relation to cognitive decline and to assess the clinical usefulness of single photon emission tomography (SPET) scanning in differentiation between Parkinson's disease patients with dementia and those without cognitive deficits.. We performed Tc-ECD SPET in 60 patients with idiopathic Parkinson's disease (F: 25, M: 35), with average age of 68.4 years (SD+/-7.3, range 51-81 years). All patients were examined neurologically with the assessment of stage and severity of Parkinson's disease (Hoehn-Yahr scale, UPDRS, Schwab-England scale). Detailed neuropsychological examination was performed in each Parkinson's disease patient. On the basis of DSM-IV criteria of dementia and the results obtained in psychological examination, the whole group was divided into three subgroups: I, with no cognitive changes (n = 17); II, with mild cognitive impairment (n = 25); and III, with dementia (n = 18).. There was noticeable significant decrease of perfusion in all areas in Parkinson's disease patients when compared to the age-matched control group of healthy volunteers (n = 20). In group III, perfusion was significantly decreased (when compared to groups I and II), particularly in parietal and temporal areas with the predominance of the left side. Regression analysis revealed two independent factors related to dementia: decrease of perfusion within left temporal lobe and its increase within left thalamus.. Parkinson's disease patients with dementia showed left temporo-parietal hypoperfusion as compared to a group of patients without dementia, which resembles perfusion deficits described in Alzheimer's disease. The hypoperfusion of the left temporal lobe with increase of rCBF within the left thalamus might be clinically useful in discrimination of Parkinson's disease patients with dementia against those without cognitive impairment.

Topics: Aged; Aged, 80 and over; Brain; Cerebrovascular Circulation; Cognition Disorders; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Parkinson Disease; Prognosis; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

Positron emission tomography (PET) and network analysis have been used to identify a reproducible pattern of regional metabolic covariation that is associated with idiopathic Parkinson's disease (PD). The activity of this PD-related pattern can be quantified in individual subjects and used to discriminate PD patients from atypical parkinsonians. Because PET is not commonly available, we sought to determine whether similar discrimination could be achieved using more routine single photon emission computed tomography (SPECT) perfusion methods. Twenty-three subjects with PD (age, 63 +/- 9 years), 22 subjects with multiple system atrophy (MSA; age, 64 +/- 7 years), and 20 age-matched healthy controls (age, 62 +/- 13 years) underwent SPECT imaging of regional cerebral perfusion with Tc-99m ethylene cysteinate dimer (ECD). Using network analysis, we determined whether a PD-related pattern existed in the SPECT data, and whether its expression discriminated PD from MSA patients. Additionally, we compared the accuracy of group discrimination achieved by this pattern with that of the PET-derived PD-related pattern applied to the SPECT data. Network analysis of the SPECT data identified a significant pattern characterized by relative increases in cerebellar, lentiform, and thalamic perfusion covarying with decrements in the frontal operculum and in the medial temporal cortex. Subject scores for this pattern discriminated PD patients from controls (P < 0.01) and from MSA patients (P < 0.03). Subject scores for the PET-derived PD-related pattern computed in the individual SPECT scans more accurately distinguished PD patients from controls (P < 0.005) and from MSA patients (P = 0.0002). A significant PD-related covariance pattern can be identified in SPECT perfusion data. Moreover, the disease related pattern identified previously with PET can be applied to individual SPECT perfusion scans to provide group discrimination between PD patients, healthy controls, and individuals with MSA. Because of significant individual subject overlap between groups, however, the clinical utility of this method in the differential diagnosis of Parkinsonism remains uncertain.

Topics: Aged; Brain; Cysteine; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Multiple System Atrophy; Nerve Net; Organotechnetium Compounds; Parkinson Disease; Parkinsonian Disorders; Regional Blood Flow; Sensitivity and Specificity; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

Cognitive abnormalities have been reported in a large percentage of patients with Parkinson's disease (PD). Often cognitive changes are sub-clinical and involve frontal lobe function. In other occasions they develop into full dementia. Functional neuroimaging may help characterize these abnormalities. We have studied brain perfusion with SPECT and the tracer ECD in 44 PD patients, 22 presenting with normal cognitive function and 22 with clinical and neuropsychological signs of dementia. Compared with 21 healthy controls, demented PD patients showed significant perfusion decrements in all cortical areas, particularly temporal and parietal regions; in the non-demented cohort reductions were limited to the frontal lobe area. These results suggest that brain perfusion abnormalities are present in PD patients. It is speculated that different pathological mechanisms underlie perfusion differences.

Topics: Aged; Brain; Cerebrovascular Circulation; Cognition Disorders; Cysteine; Female; Frontal Lobe; Humans; Male; Middle Aged; Neuropsychological Tests; Organotechnetium Compounds; Parkinson Disease; Radiopharmaceuticals; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

Four patients with Parkinson's disease (PD) achieved excellent improvement of their unilateral tremor by chronic deep brain stimulation (DBS) of the contralateral ventral intermediate (Vim) nucleus of the thalamus. Repeated measurements of cerebral blood flow were obtained 14 days apart off and on stimulation using 99mTc-ECD SPECT. Subjects were scanned at rest and the data were compared with those of normal healthy volunteers. During stimulation, there were highly significant deactivations in the motor area and supplementary motor area on the electrode side and in the prefrontal area and the anterior cingulum bilaterally. No cerebellar deactivation was detected. We conclude that the mechanism responsible for suppression of parkinsonian tremor by thalamic stimulation is deactivation of thalamocortical activity.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Cerebral Cortex; Cysteine; Electric Stimulation Therapy; Female; Humans; Male; Middle Aged; Motor Cortex; Neural Pathways; Organotechnetium Compounds; Parkinson Disease; Prefrontal Cortex; Radiopharmaceuticals; Thalamus; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Tremor

Various parameters are currently used for the semi-quantitative assessment of dopamine D2 receptors and differ according to the delineation of the striatal region of interest (ROI) and the choice of the reference ROI. The aim of this study was to assess the value of different ROI approaches in differentiating patients with normal or increased numbers of D2 dopamine receptors (group 1 = Parkinson's disease, n = 8) from patients with decreased dopamine D2 receptors (group 2 = other extrapyramidal syndromes, n = 9) using 123I-iodolisuride SPET (ILIS-SPET). 123I-iodolisuride (190 +/- 31 MBq) and 99Tcm-ethyl cysteinate dimer (99Tcm-ECD) perfusion SPET were performed in the same position, with a dual-headed gamera camera equipped with fan beam collimators. Both a geometric approach (ellipse, circle or rectangle) and an anatomical approach using the CT scan and perfusion SPET as anatomical guides were used to draw striatal and reference ROIs. A total of 33 different parameters were calculated for each patient, indicating the ratio of counts between the striatal and reference ROIs (frontal, occipital cortex or cerebellum) and the asymmetry between the right and left striatum. More significant differences between group 1 and group 2 were found by using geometric ROIs than by using anatomical ROIs. The most discriminant ratios were the caudate/occipital, caudate/frontal and striatum/occipital ratios (P = 0.001, P = 0.002, P = 0.003 respectively). A close correlation was found between the striatum/caudate and striatum/occipital ratios, but not between the striatum/frontal and striatum/occipital ratios or between the striatum/frontal and striatum/caudate ratios. We conclude that the occipital cortex is the best reference for the semi-quantitative evaluation of dopamine D2 receptors as the frontal cortex could include some dopamine D2 receptor-bound radioligand, and that the caudate/occipital ratio is an appropriate parameter for differentiating Parkinson's disease from non-Parkinson extrapyramidal syndrome by 123I-iodolisuride SPET.

Topics: Adult; Aged; Basal Ganglia Diseases; Brain; Brain Chemistry; Caudate Nucleus; Corpus Striatum; Cysteine; Female; Frontal Lobe; Humans; Iodine Radioisotopes; Lisuride; Male; Occipital Lobe; Organotechnetium Compounds; Parkinson Disease; Perfusion; Radiopharmaceuticals; Receptors, Dopamine D2; Tomography, Emission-Computed, Single-Photon

External radioactive reference markers have been used to localize the canthomeatal (CM) line and correct for head rotation in perfusion brain SPECT. This ensures that regardless of the subject's head position or rotation under the SPECT camera, reconstructed transaxial slices are reoriented parallel to the CM line. This study was undertaken to demonstrate the value of external radioactive reference markers in dopamine SPECT imaging.. We compared visual and marker methods of reorienting the transaxial slices between dopamine and perfusion brain SPECT studies, respectively. These consisted of imaging normal controls and patients with Alzheimer's or Parkinson's disease using a triple-head camera. Intra- and interoperator variability of the visual and marker methods of reorientation was determined for both perfusion and dopamine studies.. In both intra- and interoperator studies, the variability of image reorientation was significantly reduced (P = 0.0066 and 0.014, respectively) by using the marker method on dopamine images. The variability of reorientation using the marker method for a single operator with dopamine images was 3.0% coefficient of variation (CV), and for the interoperator study (5 different operators) this was 7.0% CV.. This study demonstrated that SPECT imaging of the dopamine system with external radioactive reference markers significantly reduced the variability of determining the angle of reorientation. This resulted in a standardized and consistent method of reorienting transaxial slices, allowing comparison within and between subjects of pre- and postsynaptic dopamine SPECT studies.

Topics: Alzheimer Disease; Brain; Carrier Proteins; Case-Control Studies; Cocaine; Cysteine; Dopamine Plasma Membrane Transport Proteins; Humans; Iodine Radioisotopes; Membrane Glycoproteins; Membrane Transport Proteins; Nerve Tissue Proteins; Organotechnetium Compounds; Parkinson Disease; Radiopharmaceuticals; Receptors, Dopamine; Reproducibility of Results; Tomography, Emission-Computed, Single-Photon

Dementia of the Alzheimer-type (DAT) is characterized by progressive cognitive decline, variably combined with frontal lobe release signs, parkinsonian symptoms and myoclonus. The features of diffuse Lewy body disease (DLBD), the second most common cause of degenerative dementia, include progressive cognitive deterioration, often associated with levodopa-responsive parkinsonism, fluctuations of cognitive and motor functions, psychotic symptoms (visual and auditory hallucinations, depression), hypersensitivity to neuroleptics and orthostatic hypotension. A recent report suggests that positron emission tomography studies in patients with degenerative dementia may be useful in the differential diagnosis of DAT and DLBD. However, the diagnostic role of single-photon emission tomography (SPET) studies remains to be established. The aim of this study was therefore to evaluate regional cerebral perfusion [with either technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) or 99mTc-ethyl cysteinate dimer (99mTc-ECD) SPET] and striatal dopamine transporter density [using iodine-123 2 beta-carboxymethoxy-3 beta-[4-iodophenyl]tropane (123I-beta-CIT) SPET] in patients with DAT and DLBD. Six patients with probable DAT and seven patients with probable DLBD were studied. Blinded qualitative assessment by four independent raters of 99mTc-HMPAO or 99mTc-ECD SPET studies revealed bilateral temporal and/or parietal hypoperfusion in all DAT patients. There was additional frontal hypoperfusion in two patients and occipital hypoperfusion in one patient. In the DLBD group, regional cerebral perfusion had a different pattern. In addition to temporoparietal hypoperfusion there was occipital hypoperfusion resembling a horseshoe defect in six of seven patients. In the DAT group, the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was 2.5 +/- 0.4, with an increase to 5.5 +/- 1.1 18 h after tracer injection. In comparison, in the DLBD patients the mean 3-h striatal/cerebellar ratio of 123I-beta-CIT binding was significantly reduced to 1.7 +/- 0.3, with a modest increase to 2.1 +/- 0.4 18 h after tracer injection (P < 0.05, Scheffe test, ANOVA). These results suggest that 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT SPET may contribute to the differential diagnosis between DAT and DLBD, showing different perfusion patterns and more severe impairment of dopamine transporter function in DLBD than in DAT.

Topics: Aged; Alzheimer Disease; Brain; Carrier Proteins; Case-Control Studies; Cocaine; Cysteine; Dementia; Diagnosis, Differential; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Organotechnetium Compounds; Oximes; Parkinson Disease; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Topics: Alzheimer Disease; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Cysteine; Humans; Organotechnetium Compounds; Parkinson Disease; Tomography, Emission-Computed, Single-Photon

Regional cerebral perfusion was assessed in six patients with asymmetric Parkinson's disease (PD) of mild to moderate severity and in six matched normal subjects using 99mTc-bicisate single photon emission computed tomography (SPECT). Regional activity was normalized to whole-brain activity. Each subject was studied twice, separated by 15.2 +/- 9.2 and 18.0 +/- 4.8 days in normals and PD patients, respectively. There was low intrasubject scan-rescan variability in normals, with all regions showing an average intrasubject difference in repeat studies of < 3%. In PD patients after chronic oral antiparkinsonian drugs had been withdrawn, as compared with normal subjects, there was increased perfusion in the caudate and lenticular nuclei contralateral to the worst affected extremities. This increased basal ganglia perfusion was attenuated by chronic oral therapy. The clinical relevance of these changes is indicated by the high positive correlation between various measures of clinical PD severity and the lenticular perfusion. These differences in basal ganglia perfusion measured with 99mTc-bicisate SPECT in mild to moderate, asymmetric PD may be secondary to increased metabolic demand resulting from alterations of synaptic activity.

Topics: Adult; Antiparkinson Agents; Brain; Cerebrovascular Circulation; Cysteine; Female; Humans; Male; Middle Aged; Organotechnetium Compounds; Parkinson Disease; Reference Values; Tomography, Emission-Computed, Single-Photon