Tc‐99m ethylene cysteinate dimer SPECT in the differential diagnosis of parkinsonism

Abstract

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.

Abnormal Metabolic Network Activity in Parkinson'S Disease: Test—Retest Reproducibility

“…However, it is important to note that although treatment-mediated changes in PDRP expression correlate significantly with improvement in UPDRS ratings, the metabolic and clinical disease descriptors are not interchangeable. Indeed, intersubject differences in these measures generally have less than 50% of their variability in common, as observed in correlations between PDRP scores and motor UPDRS ratings obtained at baseline or during therapy (e.g., Feigin et al, 2002;Lozza et al, 2004;Trošt et al, 2006). Thus, it is likely that the objective imaging-based network measure may provide unique information about disease severity or the Test-retest reliability of Parkinson's disease-related brain network Y Ma et al treatment response that is not captured by the simpler and more accessible clinical rating scales.…”

“…We have found that this disease is associated with a specific spatial covariance pattern involving metabolic abnormalities in basal ganglia thalamocortical functional/anatomic pathways (Eidelberg et al, 1994(Eidelberg et al, , 1997. Indeed, this PD-related covariance pattern (PDRP) has been detected in multiple independent patient populations scanned in the resting condition (Moeller et al, 1999;Feigin et al, 2002;Lozza et al, 2004;Asanuma et al, 2005).…”

Neuroimaging and therapeutics in movement disorders

“…This characteristic pattern (FIG. 1A) 1) has been validated in multiple populations of unmedicated PD patients 4,36,43 ; 2) can be detected early in the disease course 34 ; and 3) correlates consistently with disease severity and duration. 3,44 We also found that PDRP activity correlates with nigrostriatal dopamine deficiency as determined by [ 18 F]-fluorodopa PET 34,45 and with internal pallidal (GPi) single unit activity recorded during surgery.…”

“…1,2 Alternatively, disease-related changes in local brain function can be assessed with generalized tracers for regional cerebral metabolism and blood flow. 3,4 Brain imaging in movement disorders was originally introduced to visualize the pathological changes associated with different clinical syndromes. 5 Subsequently, these techniques have been used in longitudinal studies designed to assess disease progression 6,7 and the effects of potential neuroprotective strategies.…”

Evidence from biomarkers and surrogate endpoints

“…14,28 -31 Of these, the most promising appear to be imaging measures of either brain metabolism with 18 F-fluoro-2-deoxy-Dglucose and positron emission tomography (PET) or of cerebral blood flow as measured with SPECT. 32,33 Studies examining the diagnostic accuracy of these and other methods have been difficult, because they rely on comparisons with the clinical diagnosis (the gold standard), which is known to be inaccurate ϳ15-20% of the time. 34 Ideally, a new diagnostic test for PD should be evaluated by comparing the results with a known postmortem pathological result, but no large-scale study using this method has been reported.…”