Imaging Inflammation in a Patient with Epilepsy Due to Focal Cortical Dysplasia

BACKGROUND AND PURPOSE Evidence from animal models and examination of human epilepsy surgery specimens indicates that inflammation plays an important role in epilepsy. Positron emission tomography (PET) using [C11]PK11195, a marker of activated microglia, provides a means to visualize neuroinflammation in vivo in humans. We hypothesize that in patients with active epilepsy, [C11]PK11195 PET (PK-PET) may be able to identify areas of focally increased inflammation corresponding to the seizure onset zone. METHODS A young woman with intractable epilepsy underwent PK-PET as part of an approved research study. PK-PET results were compared with results from other clinical studies. RESULTS PK-PET revealed an area of focally increased radiotracer uptake in the right frontal lobe corresponding to this patient’s seizure focus as identified by ictal and interictal 18Ffluorodeoxyglucose (FDG)-PET and EEG. Routine brain magnetic resonance imaging (MRI) was initially considered normal, though high-resolution studies showed possible subtle dysplasia of the right frontal lobe. The patient underwent a right frontal lobe resection, and pathological evaluation showed focal cortical dysplasia with activated microglia. CONCLUSIONS PK-PET can identify neuroinflammation associated with subtle focal cortical dysplasia, and may therefore have a clinical role in guiding epilepsy surgery for patients with difficult-to-localize seizure foci

Neuroticism Associates with Cerebral in Vivo Serotonin Transporter Binding Differently in Males and Females

Background: Neuroticism is a major risk factor for affective disorders. This personality trait has been hypothesized to associate with synaptic availability of the serotonin transporter, which critically controls serotonergic tone in the brain. However, earlier studies linking neuroticism and serotonin transporter have failed to produce converging findings. Because sex affects both the serotonergic system and the risk that neuroticism poses to the individual, sex may modify the association between neuroticism and serotonin transporter, but this question has not been investigated by previous studies. Methods: Here, we combined data from 4 different positron emission tomography imaging centers to address whether neuroticism is related to serotonin transporter binding in vivo. The data set included serotonin transporter binding potential values from the thalamus and striatum and personality scores from 91 healthy males and 56 healthy females. We specifically tested if the association between neuroticism and serotonin transporter is different in females and males. Results: We found that neuroticism and thalamic serotonin transporter binding potentials were associated in both males and females, but with opposite directionality. Higher neuroticism associated with higher serotonin transporter binding potential in males (standardized beta 0.292, P = .008), whereas in females, higher neuroticism associated with lower serotonin transporter binding potential (standardized beta -0.288, P = .014). Conclusions: The finding is in agreement with recent studies showing that the serotonergic system is involved in affective disorders differently in males and females and suggests that contribution of thalamic serotonin transporter to the risk of affective disorders depends on sex.Peer reviewe

Functional Cerebral SPECT and PET Imaging

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PET Quantification in Molecular Brain Imaging Taking into Account the Contribution of the Radiometabolite Entering the Brain

A good understanding of the in vivo pharmacokinetics of radioligands is important for accurate PET quantification in molecular brain imaging. For many reversibly binding radioligands for which there exists a brain region devoid of molecular target binding sites called “reference tissue,” data analysis methods that do not require blood data including the standardized uptake value ratio of target-toreference tissue at a “fixed time point” (SUVR) and reference tissue model to estimate binding potential (BPND) are commonly used, the latter being directly proportional to the binding site density (Bavail). Theoretically, BPND is the tissue ratio minus 1 at equilibrium. It is generally believed that radioligands should not ideally produce radiometabolites that can enter the brain because they might complicate accurate quantification of specific binding of the parent radioligand. However, the tissue ratio that contains the contribution of radiometabolite can also be theoretically a valid parameter that reflects the target binding site density. This article describes the validation of the tissue ratio concept using, as an example of our recent PET data analysis approach for a novel radioligand, 11C-PBB3, to quantify pathological tau accumulations in the brain of Alzheimer’s disease patients in which the SUVR and reference tissue model methods using the cerebellar cortex as the reference tissue were validated by the dual-input graphical analysis model that uses the plasma parent and radiometabolite activity as input functions in order to take into account the contribution of the radiometabolite entering the brain

Neuromolecular basis of faded perception associated with unreality experience

Perceptual changes in shape, size, or color are observed in patients with derealization symptoms; however, the underlying neural and molecular mechanisms are not well understood. The current study explored the relationship between neural activity associated with altered colorfulness perception assessed by fMRI and striatal dopamine D₂ receptor availability measured by [¹¹C]raclopride PET in healthy participants. Inside an fMRI scanner, participants performed the saturation adaptation task, where they rated how much vivid/faded visual objects looked like real/unreal ones using a visual analog scale. We found that participants experienced greater unreality when they perceived fadedness than vividness despite physically identical saturation. The combined fMRI and PET analyses revealed that the faded perception-related activities of the dorsolateral prefrontal and parietal cortex were positively correlated with striatal D₂ receptor availability. This finding may help to understand the neuromolecular mechanisms of faded perception associated with feeling unreal in derealization symptoms

Visual evaluation of kinetic characteristics of PET probe for neuroreceptors using a two-phase graphic plot analysis

Objectives: In PET studies for neuroreceptors, tracer kinetics are described by the two-tissue compartment model (2-TCM), and binding parameters including the total distribution volume (VT), nondisplaceable distribution volume (VND), and binding potential (BPND) can be determined from model parameters estimated by kinetic analysis. The stability of binding parameter estimates depends on the kinetic characteristics of radioligands. To describe these kinetic characteristics, we previously developed a Two-phase graphic plot analysis in which VND and VT can be estimated from the x-intercept of regression lines for early and delayed phase, respectively. In this study, we applied this graphic plot analysis to visual evaluation of the kinetic characteristics of radioligands for neuroreceptors, and investigated a relationship between the shape of these graphic plots and the stability of binding parameters estimated by the kinetic analysis with 2-TCM in simulated brain tissue time-activity curves (TACs) with various binding parameters.Methods: 90-min TACs were generated with the arterial input function and assumed kinetic parameters according to 2-TCM. Graphic plot analysis was applied to these simulated TACs, and the curvature of the plot for each TAC was evaluated visually. TACs with several noise levels were also generated with various kinetic parameters, and the bias and variation of binding parameters estimated by kinetic analysis was calculated in each TAC. These bias and variation were compared with the shape of graphic plots.Results: The graphic plots showed larger curvature for TACs with higher specific binding and slower dissociation of specific binding. The quartile deviations of VND and BPND determined by kinetic analysis were smaller for radioligands with slow dissociation. Conclusions: The larger curvature of graphic plots for radioligands with slow dissociation might indicate a stable determination of VND and BPND by kinetic analysis. For investigation of the kinetics of radioligands, such kinetic characteristics should be considered