Hinako Toyama

Auditory triggered mental imagery of shape involves visual association areas in early blind humans

Previous neuroimaging studies identified a large network of cortical areas involved in visual imagery in the human brain, which includes occipitotemporal and visual associative areas. Here we test whether the same processes can be elicited by tactile and auditory experiences in subjects who became blind early in life. Using positron emission tomography, regional cerebral blood flow was assessed in six right-handed early blind and six age-matched control volunteers during three conditions: resting state, passive listening to noise sounds, and mental imagery task (imagery of object shape) triggered by the sound of familiar objects. Activation foci were found in occipitotemporal and visual association areas, particularly in the left fusiform gyrus (Brodmann areas 19-37), during mental imagery of shape by both groups. Since shape imagery by early blind subjects does involve similar visual structures as controls at an adult age, it indicates their developmental crossmodal reorganization to allow perceptual representation in the absence of vision.

Improved Signal-to-Noise Ratio in Parametric Images by Cluster Analysis ☆

Parametric images are formed by analyzing the concentration history of every voxel in PET data sets. Because PET concentration data at the voxel level are rather noisy, noise propagation into the parametric image is often quite noticeable. To address this problem, a model-based clustering method has been developed to generate parametric images. The basic idea of the clustering method is to average over voxels whose concentration histories have the same shape. We applied the method to a two-parameter (K1, k2) compartment model of local cerebral blood flow. The statistic R = integral tC(t) dt/integral C(t) dt= integral te-k2t multiply sign in circle Ca(t) dt/integral e-k2t multiply sign in circle Ca(t) dt classifies curves in terms of k2, where C(t) and Ca(t) denote the tissue and blood concentration histories, respectively, and multiply sign in circle is the convolution operator. Simulation studies of noise propagation in the clustering statistic showed that 30% voxel noise yielded a 2% standard deviation in R. Parametric images of blood flow and partition coefficient were computed for an O15 study, with and without clustering. Cluster size affected bias, statistical precision, and computation time. With clusters of 400 voxels, the variance of the flow parameter was around 1/50 smaller with clustering, with negligible bias and a computation time of 30 s on a 64-MHz workstation for 15 x 128 x 128 images with MATLAB 5.1.

Template-Based Method for Multiple Volumes of Interest of Human Brain PET Images

Specific region-based analysis for the quantification of brain imaging is very time-consuming work and subject to errors in both accuracy and reproducibility. In this study, we assessed a two-step template-based method for defining volumes of interest (VOIs). The first step was the spatial transformation of the VOI template from a model MRI to an individual MRI with SPM99. The second step was to refine the transformed VOI to the individual gray matter of MRI using the intensity characteristics of this image with our developed software running on a PC type of computer. The reliability of the values of the final refined VOIs was investigated by comparing them to those of manually drawn VOIs. The template-based method was found to be both accurate and robust and can be used as a reliable alternative for the manual determination of VOIs.

Preserved benzodiazepine receptors in Alzheimer’s disease measured with C-11 flumazenil PET and I-123 iomazenil SPECT in comparison with CBF

This study evaluates the regional cerebral blood flow (CBF) with H215O-PET and the distribution of central benzodiazepine receptor (BZR) with C-11 flumazenil (FMZ) by PET and I-123 iomazenil (IMZ) by SPECT in Alzheimer’s disease (AD). In AD, whereas the CBF was diminished in the frontal, temporal, parietal, and occipital cortex, the distribution volume of FMZ and delayed activity of IMZ were relatively preserved in these cortices, suggesting that the BZR reduction, reflecting neuronal loss, is less prominent than the CBF suppression. The mini-mental state examination score (MMS) was weakly correlated with the CBF in the parietal cortex but not with BZR. It is speculated that the neuronal density reflected by BZR is less impaired than the neuronal function assessed with blood flow in the association cortex of AD.High correlation was found between the uptake of FMZ and the delayed activity of IMZ. The delayed image of IMZ-SPECT is clinically useful to evaluate the preservation of neuronal density in the affected temoporoparietal association cortex in AD.

A PET-MRI registration technique for PET studies of the rat brain.

Rat Brain Nobutaka Hayakawa, Koji Uemura, Kiichi Ishiwata, Yuhei Shimada, Nobuo Ogi, Tsukasa Nagaoka, Hinako Toyama, Keiichi Oda, Akira Tanaka, Kazutoyo Endo and Michio Senda POSITRON MEDICAL CENTER, TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY, TOKYO, JAPAN; SHOWA COLLEGE OF PHARMACEUTICAL SCIENCES, TOKYO, JAPAN; SCHOOL OF SCIENCE AND ENGINEERING, WASEDA UNIVERSITY, TOKYO, JAPAN; DEPARTMENT OF VETERINARY CLINICAL PATHOLOGY, UNIVERSITY OF TOKYO, TOKYO, JAPAN; AND DEPARTMENT

Adenosine A2A receptor imaging with [11C]KF18446 PET in the rat brain after quinolinic acid lesion: Comparison with the dopamine receptor imaging

We proposed [11C]KF18446 as a selective radioligand for mapping the adenosine A2A receptors being highly enriched in the striatum by positron emission tomography (PET). In the present study, we investigated whether [11C]KF18446 PET can detect the change in the striatal adenosine A2A receptors in the rat after unilateral injection of an excitotoxin quinolinic acid into the striatum, a Huntington’s disease model, to demonstrate the usefulness of [11C]KF18446. The extent of the striatal lesion was identified based on MRI, to which the PET was co-registered. The binding potential of [11C]KF18446 significantly decreased in the quinolinic acid-lesioned striatum. The decrease was comparable to the decrease in the potential of [11C]raclopride binding to dopamine D2 receptors in the lesioned striatum, but seemed to be larger than the decrease in the potential of [11C]SCH 23390 binding to dopamine D1 receptors.Ex vivo andin vitro autoradiography validated the PET signals. We concluded that [11C]KF18446 PET can detect change in the adenosine A2A receptors in the rat model, and will provide a new diagnostic tool for characterizing post-synaptic striatopallidal neurons in the stratum.

In vivo imaging of adenovirus-mediated over-expression of dopamine D2 receptors in rat striatum by positron emission tomography.

PET was used to provide in vivo imaging of the over-expression of dopamine D2 receptor (D2R) induced by adenovirus vector-mediated gene transfer in rat striatum. The uptake of three kinds of D2R-specific ligands, [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone, measured by PET was higher in the striatum injected with the vectors for D2R than the contralateral striatum injected with a control vector 2–3 days after injection. However, the uptake of [11C]SCH 23390, a dopamine D1 receptor specific ligand, or [11C]β-CIT-FP, a dopamine transporter specific tracer, was not different between bilateral striata. Co-injection of excess unlabeled raclo-pride inhibited the uptake of [11C]raclopride. At day 16 the increased uptake of [11C]raclopride declined to basal level, consistent with past in vitro assessment of this vector. In vivo imaging of D2R will permit longitudinal assessment of the eficiency of this and similar vectors in rat brain that can be related to functional changes being observed.

Posthyperventilatory Steal Response in Chronic Cerebral Hemodynamic Stress A Positron Emission Tomography Study

BACKGROUND AND PURPOSE The alteration of regional cerebral blood flow (CBF) during and after hyperventilation was measured using positron emission tomography (PET) to determine the circulatory response induced by daily respiratory changes in the cerebral area under chronic hemodynamic stress. METHODS Three normal volunteers and 12 patients with an obstruction of major cerebral arteries underwent PET measurements of the CBF after an injection of H2(15)O: (1) in the resting condition, (2) during hyperventilation (HV scan), (3) 1 to 3 minutes after hyperventilation (post-HV scan), (4) during the inhalation of 5% CO2, and (5) after an injection of acetazolamide. Eleven patients also underwent a 15O gas study to measure CBF, oxygen extraction fraction (OEF), and cerebral blood volume (CBV). RESULTS (1) In 9 patients, the CBF value in the post-HV scan was lower than that in the HV scan in 1 or more regions in the area of the obstructed arteries, although the PaCO2 level during the post-HV scan was higher than that during the HV scan in all patients. All control regions in the patients and in the normal volunteers showed an elevated CBF in the post-HV scan compared with the HV scan. (2) The negative post-HV response (posthyperventilatory steal) was prominent in 4 patients with moyamoya vessels and in another 5 patients with atherosclerotic disease who had PET evidence of hemodynamic stress (elevated CBV or OEF). (3) The regional pre- to post-HV change in CBF was significantly correlated with the CBF responses to acetazolamide and CO2. CONCLUSIONS Vasodilatation after the termination of hyperventilation in the normal areas induces a steal response in the cerebral area suffering from hemodynamic stress and may cause profound hypoperfusion in everyday situations. This phenomenon may be important to our understanding of the clinical symptoms and the natural course of chronic cerebral occlusive disease bearing hemodynamic stress.

Intrasubject correlation between static sean and distribution volume images for [11C]flumazenil PET

Accumulation of [11C]flumazenil (FMZ) reflects central nervous system benzodiazepine receptor (BZR). We searched for the optimal time for a static PET scan with FMZ as semi-quantitative imaging of BZR distribution. In 10 normal subjects, a dynamic series of decay-corrected PET scans was performed for 60 minutes, and the arterial blood was sampled during the scan to measure radioactivity and labeled metabolites. We generated 13 kinds of “static scan” images from the dynamic scan in each subject, and analyzed the pixel correlation for these images versus distribution volume (DV) images. We also analyzed the time for the [11C]FMZ in plasma and tissue to reach the equilibrium. The intra-subject pixel correlation demonstrated that the “static scan” images for the period centering around 30 minutes post-injection had the strongest linear correlation with the DV image. The ratio of radioactivity in the cortex to that in the plasma reached a peak at 40 minutes after injection. Considering the physical decay and patient burden, we conclude that the decay corrected static scan for [11C]FMZ PET as semi-quantitative imaging of BZR distribution is to be optimally acquired from 20 to 40 minutes after injection.

Quantitative Analysis for Estimating Binding Potential of the Brain Serotonin Transporter with [11C]McN5652:

[11C](+)McN5652 is a selective serotonin reuptake inhibitor with subnanomolar potency for the serotonin transporter, and is currently being used for positron emission tomography studies. However, quantification of the regional [11C](+)McN5652 binding potential in vivo is a controversial issue because of its complex characteristics. The authors examined the regional differences in nonspecific binding and proposed simple methods for estimating the binding potential of [11C](+)McN5652. The regional difference in nonspecific binding was evaluated by the activity ratio of the thalamus compared with the cerebellum for inactive-isomer [11C](−)McN5652 and [11C](+)McN5652 saturation studies. The distribution volume of the thalamus was approximately 1.16 times larger than that of the cerebellum. The thalamus-to-cerebellum distribution volume ratio was estimated by nonlinear least square and graphical methods, with and without arterial input function. The graphical method with k2′ without blood sampling was practical and most applicable for estimation of the distribution volume ratio because this method is more stable than the nonlinear least square method in the simulation study. Binding potential estimated with the distribution volume ratio of [11C](+)McN5652 and the correction with distribution volume ratio of [11C](−)McN5652 represent the most reliable parameters for the assessment of serotonin transporter binding.