Influence of O-methylated metabolite penetrating the blood-brain barrier to estimation of dopamine synthesis capacity in human L-[β-(11)C]DOPA PET.

O-methyl metabolite (L-[β-(11)C]OMD) of (11)C-labeled L-3,4-dihydroxyphenylalanine (L-[β-(11)C]DOPA) can penetrate into brain tissue through the blood-brain barrier, and can complicate the estimation of dopamine synthesis capacity by positron emission tomography (PET) study with L-[β-(11)C]DOPA. We evaluated the impact of L-[β-(11)C]OMD on the estimation of the dopamine synthesis capacity in a human L-[β-(11)C]DOPA PET study. The metabolite correction with mathematical modeling of L-[β-(11)C]OMD kinetics in a reference region without decarboxylation and further metabolism, proposed by a previous [(18)F]FDOPA PET study, were implemented to estimate radioactivity of tissue L-[β-(11)C]OMD in 10 normal volunteers. The component of L-[β-(11)C]OMD in tissue time-activity curves (TACs) in 10 regions were subtracted by the estimated radioactivity of L-[β-(11)C]OMD. To evaluate the influence of omitting blood sampling and metabolite correction, relative dopamine synthesis rate (kref) was estimated by Gjedde-Patlak analysis with reference tissue input function, as well as the net dopamine synthesis rate (Ki) by Gjedde-Patlak analysis with the arterial input function and TAC without and with metabolite correction. Overestimation of Ki was observed without metabolite correction. However, the kref and Ki with metabolite correction were significantly correlated. These data suggest that the influence of L-[β-(11)C]OMD is minimal for the estimation of kref as dopamine synthesis capacity.Journal of Cerebral Blood Flow & Metabolism advance online publication, 6 November 2013; doi:10.1038/jcbfm.2013.187

Impact of spillover from white matter by partial volume effect on quantification of amyloid deposition with [(11)C]PiB PET.

High non-specific uptake of [(11)C]Pittsburgh compound B ([(11)C]PiB) in white matter and signal spillover from white matter, due to partial volume effects, confound radioactivity measured in positron emission tomography (PET) with [(11)C]PiB. We aimed to reveal the partial volume effect in absolute values of kinetic parameters for [(11)C]PiB, in terms of spillover from white matter. Dynamic data acquired in [(11)C]PiB PET scans with five healthy volunteers and eight patients with Alzheimer\u27s disease were corrected with region-based and voxel-based partial volume corrections. Binding potential (BPND) was estimated using the two-tissue compartment model analysis with a plasma input function. Partial volume corrections significantly decreased cortical BPND values. The degree of decrease in healthy volunteers (-52.7 ± 5.8%) was larger than that in Alzheimer\u27s disease patients (-11.9 ± 4.2%). The simulation demonstrated that white matter spillover signals due to the partial volume effect resulted in an overestimation of cortical BPND, with a greater degree of overestimation for lower BPND values. Thus, an overestimation due to partial volume effects is more severe in healthy volunteers than in Alzheimer\u27s disease patients. Partial volume corrections may be useful for accurately quantifying Aβ deposition in cortical regions

Changes in effective diffusivity for oxygen in the capillary bed during neural activation and deactivation measured by PET

Objectives: According to a model for the regulation of cerebral oxygen delivery proposed by Hyder et al., the relation between cerebral blood flow (CBF) and cerebral oxygen extraction fraction (OEF) can be expressed using the effective diffusivity for oxygen in the capillary bed (D) as OEF=1-exp(-D/CBF). In this study, changes in D during neural activation and deactivation were estimated from changes in CBF and OEF measured by PET in humans during neural activation and deactivation observed in crossed cerebellar diaschisis (CCD) caused by contralateral supratentorial lesions.Methods: CBF, cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO2) and OEF were measured in each of 7 healthy men at rest and during performance of a right hand motor task. D values were calculated for each condition. CBF, CBV, CMRO2 and OEF for CCD and unaffected sides were measured in 11 patients with cerebrovascular disease, and D values were calculated for both sides.Results: Changes in CBF, CBV, CMRO2, OEF, and D during neural activation in the left precentral gyrus were 48+-23%, 14+-25%, 11+-13%, -24+-8%, and 5+-14%, respectively. Changes in CBF, CBV, CMRO2, OEF, and D in CCD side (neural deactivation) as compared to unaffected side were -27+-8%, -25+-32%, -20+-9%, 10+-6%, and -17+-10%, respectively.Conclusions: The degree of changes in D during neural activation was smaller than during neural deactivation. Since the D value is proportional to capillary blood volume, the degree of changes in capillary blood volume during neural activation might be smaller than during neural deactivation, corresponding to smaller degree of changes in CBV during neural activation as compared with neural deactivation. Further studies to investigate changes in capillary blood volume during neural activation and deactivation using microscope in animals will be required.Society of Nuclear Medicine and Molecular Imaging 2013 Annual Meetin