Pharmacological and metabolic parameters of [F]flubrobenguane in clinical imaging populations.

Background: Cardiac sympathetic nervous system molecular imaging has demonstrated prognostic value. Compared with meta-[C]hydroxyephedrine, [F]flubrobenguane (FBBG) facilitates reliable estimation of SNS innervation using similar analytical methods and possesses a more convenient physical half-life. The aim of this study was to evaluate pharmacokinetic and metabolic properties of FBBG in target clinical cohorts.

Serotonergic System Impacts Levodopa Response in Early Parkinson's and Future Risk of Dyskinesia.

Background: The serotonergic system is known to contribute to levodopa-derived dopamine release in advanced Parkinson's disease.

Objective: We investigated the role of the serotonergic system in determining response to treatment in early disease and risk for complications concurrently with dopaminergic alterations.

Methods: Eighteen patients with early and stable Parkinson's disease underwent multitracer positron emission tomography using [ C]dihydrotetrabenazine (vesicular monoamine transporter 2 marker), [ C]methylphenidate (dopamine transporter marker), [ C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB, serotonin transporter marker), and [ C]raclopride (D2 marker) to investigate relationships between striatal dopaminergic and serotonergic alterations and levodopa-induced dopamine release, related to motor response to treatment and risk for dyskinesias, using a novel joint pattern analysis.

Exercise increases caudate dopamine release and ventral striatal activation in Parkinson's disease.

Background: The objective of this study was to examine the effects of aerobic exercise on evoked dopamine release and activity of the ventral striatum using positron emission tomography and functional magnetic resonance imaging in Parkinson's disease (PD).

Methods: Thirty-five participants were randomly allocated to a 36-session aerobic exercise or control intervention. Each participant underwent an functional magnetic resonance imaging scan while playing a reward task before and after the intervention to determine the effect of exercise on the activity of the ventral striatum in anticipation of reward.

Joint pattern analysis applied to PET DAT and VMAT2 imaging reveals new insights into Parkinson's disease induced presynaptic alterations.

Most neurodegenerative diseases are known to affect several aspects of brain function, including neurotransmitter systems, metabolic and functional connectivity. Diseases are generally characterized by common clinical characteristics across subjects, but there are also significant inter-subject variations. It is thus reasonable to expect that in terms of brain function, such clinical behaviors will be related to a general overall multi-system pattern of disease-induced alterations and additional brain system-specific abnormalities; these additional abnormalities would be indicative of a possible unique system response to disease or subject-specific propensity to a specific clinical progression.

Habitual exercisers versus sedentary subjects with Parkinson's Disease: Multimodal PET and fMRI study.

Background: The benefits of exercise in PD have been linked to enhanced dopamine (DA) transmission in the striatum.

Objective: To examine differences in DA release, reward signaling, and clinical features between habitual exercisers and sedentary subjects with PD.

Methods: Eight habitual exercisers and 9 sedentary subjects completed [ C]raclopride PET scans before and after stationary cycling to determine exercise-induced release of endogenous DA in the dorsal striatum.

PBB3 imaging in Parkinsonian disorders: Evidence for binding to tau and other proteins.

Background And Objectives: To study selective regional binding for tau pathology in vivo, using PET with [ C]PBB3 in PSP patients, and other conditions not typically associated with tauopathy.

Methods: Dynamic PET scans were obtained for 70 minutes after the bolus injection of [ C]PBB3 in 5 PSP subjects, 1 subject with DCTN1 mutation and PSP phenotype, 3 asymptomatic SNCA duplication carriers, 1 MSA subject, and 6 healthy controls of similar age. Tissue reference Logan analysis was applied to each region of interest using a cerebellar white matter reference region.

Interpreting DTBZ binding data in rodent: Inherent variability and compensation.

[11C]-dihydrotetrabenazine (DTBZ) Positron Emission Tomography was used to evaluate the vesicular monoamine transporter type 2 as an index of dopaminergic function in the striatum of adult Sprague-Dawley rats obtained from two different animal sources (Charles River Laboratories [CR] or UBC's Animal Care Centre [ACC]) and later submitted to two different unilateral lesions of the nigro-striatal pathway. The results showed a significant difference in the striatal binding potential (BP(ND)) at baseline (before lesioning) between the CR and ACC groups providing evidence that the origin of the animals, possibly due to differences in early environmental factors or breeding conditions associated with different animal vendors plays a role in the development of the adult dopaminergic system. Further, in both animal models, an increase in DTBZ BP(ND) was observed, after unilateral intervention, in the striatum contralateral to the lesion, likely reflecting compensatory effects.

A scan without evidence is not evidence of absence: Scans without evidence of dopaminergic deficit in a symptomatic leucine-rich repeat kinase 2 mutation carrier.

Introduction: The basis for SWEDD is unclear, with most cases representing PD mimics but some later developing PD with a dopaminergic deficit.

Methods: We studied a patient initially diagnosed with SWEDD (based on (18)F-dopa PET) who developed unequivocal PD associated with a leucine-rich repeat kinase 2 p.G2019S mutation.

Exploring the effects of coexisting amyloid in subcortical vascular cognitive impairment.

Background: Mixed pathology, particularly Alzheimer's disease with cerebrovascular lesions, is reported as the second most common cause of dementia. Research on mixed dementia typically includes people with a primary AD diagnosis and hence, little is known about the effects of co-existing amyloid pathology in people with vascular cognitive impairment (VCI). The purpose of this study was to understand whether individual differences in amyloid pathology might explain variations in cognitive impairment among individuals with clinical subcortical VCI (SVCI).

Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers.

Objective: In this prospective cohort study, we investigated cerebral glucose metabolism reductions on [(18)F]-fluorodeoxyglucose (FDG)-PET in progranulin (GRN) mutation carriers prior to frontotemporal dementia (FTD) onset.

Methods: Nine mutation carriers (age 51.5 ± 13.

Direct intranigral administration of an ubiquitin proteasome system inhibitor in rat: behavior, positron emission tomography, immunohistochemistry.

Several independent lines of research suggest that disruption of the ubiquitin proteasome system (UPS) may play a role in the pathophysiology of Parkinson's disease. Direct intracerebral injection of UPS inhibitors (e.g.

Positron emission tomography kinetic modeling algorithms for small animal dopaminergic system imaging.

Small animal positron emission tomography (PET) imaging allows in vivo quantification of lesion- or treatment-induced neurochemical changes in animal models of disease. Important for quantification are the kinetic modeling methods used to determine biologically-relevant parameters of tracer-tissue interaction. In this work, we evaluate modeling algorithms for the dopaminergic tracers (11)C-dihydrotetrabenazine (DTBZ), (11)C-methylphenidate (MP), and (11)C-raclopride (RAC), used to image the dopaminergic system in the unilateral 6-hydroxydopamine lesioned rat model of Parkinson's disease.

Accurate event-driven motion compensation in high-resolution PET incorporating scattered and random events.

With continuing improvements in spatial resolution of positron emission tomography (PET) scanners, small patient movements during PET imaging become a significant source of resolution degradation. This work develops and investigates a comprehensive formalism for accurate motion-compensated reconstruction which at the same time is very feasible in the context of high-resolution PET. In particular, this paper proposes an effective method to incorporate presence of scattered and random coincidences in the context of motion (which is similarly applicable to various other motion correction schemes).

System matrix modelling of externally tracked motion.

Background And Aim: In high-resolution emission tomography imaging, even small patient movements can considerably degrade image quality. The aim of this work was to develop a general approach to motion-corrected reconstruction of motion-contaminated data in the case of rigid motion (particularly brain imaging) which would be applicable to any PET scanner in the field, without specialized data-acquisition requirements.

Methods: Assuming the ability to externally track subject motion during scanning (e.