Search

Background and Purpose: Dopamine and glutamate reciprocally regulate each other in some of the neurocircuits affected by Parkinson's disease (PD). The objective of this pilot study was to explore relationships between these neurotransmitter systems with positron emission tomography., Methods: The sample consisted of nine patients with PD and eight healthy volunteers (HVs). Dynamic images of the brain were acquired after the IV administration of ∼370 MBq (10 mCi) of [ 11 C]PE2i, a dopamine transporter (DaT) imaging agent, and ∼185 MBq (∼5 mCi) of [ 18 F]FPEB, a selective metabotropic glutamate receptor 5 (mGluR5) antagonist. Multiple volumes of interest were semiautomatically placed on contemporaneously acquired MRI scans. Nondisplaceable binding potentials (BP ND ) were calculated with the Logan reference tissue model using cerebellar white matter as the reference region., Results: The findings showed that average [ 18 F]FPEB BP ND values were slightly more than 20% higher in PD than HVs in several mesocortical regions, including the bilateral putamen (P = .01), hippocampus (P = .02), and amygdala (P = .05). Average [ 11 C]PE2i BP ND was significantly reduced by about half or more in patients with PD in the bilateral caudate (P < .001) and putamen (P < .001)., Conclusions: mGluR5 seems upregulated in strategic dopaminergic brain regions adversely affected by PD. The findings seem to confirm that DaT tracers are better discriminatory biomarkers for diagnosing PD; however, mGluR5 tracers might deserve further exploration as potential biomarkers of response in clinical trials., (© 2018 by the American Society of Neuroimaging.)

Background and Purpose: Neuroinflammation has been implicated in the pathophysiology of Parkinson's disease (PD), which might be influenced by successful neuroprotective drugs. The uptake of [ 11 C](R)-PK11195 (PK) is often considered to be a proxy for neuroinflammation, and can be quantified using the Logan graphical method with an image-derived blood input function, or the Logan reference tissue model using automated reference region extraction. The purposes of this study were (1) to assess whether these noninvasive image analysis methods can discriminate between patients with PD and healthy volunteers (HVs), and (2) to establish the effect size that would be required to distinguish true drug-induced changes from system variance in longitudinal trials., Methods: The sample consisted of 20 participants with PD and 19 HVs. Two independent teams analyzed the data to compare the volume of distribution calculated using image-derived input functions (IDIFs), and binding potentials calculated using the Logan reference region model., Results: With all methods, the higher signal-to-background in patients resulted in lower variability and better repeatability than in controls. We were able to use noninvasive techniques showing significantly increased uptake of PK in multiple brain regions of participants with PD compared to HVs., Conclusion: Although not necessarily reflecting absolute values, these noninvasive image analysis methods can discriminate between PD patients and HVs. We see a difference of 24% in the substantia nigra between PD and HV with a repeatability coefficient of 13%, showing that it will be possible to estimate responses in longitudinal, within subject trials of novel neuroprotective drugs., (© 2018 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.)

Objective: Post-operative delirium is associated with pre-operative cognitive difficulties and diminished functional independence, both of which suggest that brain pathology may be present in affected individuals prior to surgery. Currently, there are few studies that have examined imaging correlates of post-operative delirium. To our knowledge, none have examined the association of delirium with existing structural pathology in pre-operative cancer patients. Here, we present a novel, retrospective strategy to assess pre-operative structural brain pathology and its association with post-operative delirium. Standard of care structural magnetic resonance imaging (MRIs) from a cohort of surgical candidates prior to surgery were analyzed for white matter hyperintensities and cerebral atrophy., Methods: We identified 23 non-small cell lung cancer patients with no evidence of metastases in the brain pre-operatively, through retrospective chart review, who met criteria for post-operative delirium within 4 days of surgery. 24 age- and gender-matched control subjects were identified for comparison to the delirium sample. T1 and fluid-attenuated inversion recovery sequences were collected from standard of care pre-operative MRI screening and assessed for white matter pathology and atrophy., Results: We found significant differences in white matter pathology between groups with the delirium group exhibiting significantly greater white matter pathology than the non-delirium group. Measure of cerebral atrophy demonstrated no significant difference between the delirium and non-delirium group., Conclusions: In this preliminary study utilizing standard of care pre-operative brain MRIs for assessment of structural risk factors to delirium, we found white matter pathology to be a significant risk factor in post-operative delirium. Limitations and implications for further investigation are discussed., (Copyright © 2013 John Wiley & Sons, Ltd.)