Yukio Tateno

AGE-RELATED CHANGES IN HUMAN D1 DOPAMINE RECEPTORS MEASURED BY POSITRON EMISSION TOMOGRAPHY

The effects of age on the binding parameters of11C-SCH23390, the highly selective ligand for central D1 dopamine receptors, at specific binding sites in the brain were studied. Seventeen healthy male volunteers (20–72 years old) participated. Regional radioactivity in the brain was followed for 40 min by positron emission tomography (PET). A high accumulation of radioactivity was observed in the striatum and there was a conspicuous accumulation in the neocortex. A two-compartment model was used to obtain quantitative estimates of rate constants of association (k3) and dissociation (k4). The binding potential (k3/k4) of the dopamine D1 receptors in the striatum and frontal cortex decreased by 35% and 39%, respectively, with age. The value of k3 decreased by 58% in the striatum and 83% in the frontal cortex, whereas the value of k4 decreased by 35% in the striatum and 72% in the frontal cortex with age.

D1 dopamine receptor binding in mood disorders measured by positron emission tomography

D1 dopamine receptor binding in mood disorders was studied by positron emission tomography (PET) using11C-SCH23390. Ten patients with bipolar mood disorders and 21 normal controls were studied in the drug-free state. The patients were in euthymic (N=6), depressed (N=3) and manic (N=1) states. Regional radioactivity in the brain was followed for 40 min by PET. A two-compartment model was used to obtain the binding potential (k3/k4) for the striatum and frontal cortex. The binding potentials for the frontal cortex for the patients were significantly lower than those for normal controls, whereas those for striatum were not significantly different. These findings suggest that D1 dopamine receptors in the frontal cortex may be in a different state in patients with bipolar mood disorders.

Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission tomography.

Using positron emission tomography (PET) and [11C]N-methylspiperone (NMSP), we examined 5-HT2 receptors in the cortex of schizophrenic patients in whom we previously observed decreased prefrontal D1 receptor binding. The subjects were 10 neuroleptic-naive schizophrenic patients, 7 schizophrenic patients who were drug-free but had previously been treated with neuroleptics, and 12 normal controls. A non-significant trend towards decreased prefrontal [11C]NMSP binding was observed in the neuroleptic-treated patients, suggesting a possible effect of previous neuroleptic treatment on the alteration in cortical 5-HT2 function. However, the neuroleptic-naive patients showed no noticeable difference in cortical [11C]NMSP binding compared to controls. Our results do not rule out the role of 5-HT2 function as a crucial site of therapeutic activity of schizophrenia, but they do suggest that cortical 5-HT2 receptors might not be primarily involved in the pathophysiology of schizophrenia.

Detection of benzodiazepine receptor occupancy in the human brain by positron emission tomography

Benzodiazepine receptor occupancy in the brain following oral administration of clonazepam (CZP) with a dose of 30 μg/kg in six healthy young men and a further dose of 50 μg/kg in one of the subjects was estimated by carbon-11 labeled Ro15-1788 and positron emission tomography (PET). The effects of CZP on the latency of auditory event-related potentials (P300) were also studied. Overall brain 11C uptake was depressed and the % inhibition of 11C uptake in the gray matter of the brain at 30 min after [11C]Ro15-1788 injection was 15.3–23.5% (mean, n=6) following 30 μg/kg CZP when compared with that in the control experiment without any previous treatment. The 11C uptake in the cerebral cortex in the subject who received both doses decreased in a dose-related manner after 30 μg/kg and 50 μg/kg CZP. The P300 latency was prolonged significantly by 30 μg/kg CZP [31.6±16.3 ms (mean±SD, n=6), P<0.05]. The P300 latency in the same subject was prolonged in a dose-related manner by 30 μg/kg and 50 μg/kg CZP. The technique using [11C]Ro15-1788 and PET permits comparison of the pharmacological effects with the percentage of receptor sites which benzodiazepines occupy in the human brain. P300 also seems to be useful to investigate the pharmacological effects of benzodiazepines.

Age-related changes in human muscarinic acetylcholine receptors measured by positron emission tomography

The effects of age on the binding parameters of [11C]N- methyl-4-piperidylbenzilate ([11C]NMPB), a specific muscarinic cholinergic receptor ligand, were studied. Eighteen healthy male volunteers (18-75 years old) participated. Regional radioactivity in the brain was followed for 60 min by positron emission tomography (PET). Uptake of [11C]NMPB continuously increased in all brain areas with the exception of the cerebellum. For the quantification of receptor binding, a compartment model, in which radioactivity in the cerebellum was used as an input function, was used. The binding parameter, K3, of muscarinic acetylcholine receptors in eight brain regions (pons, hippocampus, frontal cortex, striatum, temporal cortex, thalamus, occipital cortex, parietal cortex) showed an age-related decrease of about 45% over the age range.

Image processing for computer‐aided diagnosis of lung cancer by CT (LSCT)

This paper reports a special-purpose CT for early detection of lung cancer and presents the basic idea. The parallel use of the following two systems is investigated as the diagnosis-support image display method needed in such a system, and a satisfactory result is obtained. (1) The maximum intensity projection (MIP) is applied as a means to realize the two-dimensional projection display from the three-dimensional information composed of 40 slices of lung tissue while retaining the information concerning the pathological shadows. When the simple MIP is applied, there is a large disturbance due to unnecessary organ signals. Consequently, a method is developed in which unnecessary information is deleted by thresholding; (2) The automatic recognition of candidates for the pathological shadows is applied to each slice. Only the CT image containing a shadow candidate is displayed on CRT, which helps to reduce greatly the number of cross sections to be displayed. In the automatic recognition of the pathological shadow, the quoit filter recently developed by the authors is employed.

Image processing for computer-aided diagnosis of lung cancer screening system by CT (LSCT)

In this paper, we report the image processing technique for computer-aided diagnosis of lung cancer screening system by CT (LSCT). LSCT is the newly developed mobile-type CT scanner for the mass screening of lung cancer by our project team. In this new LSCT system, one essential problem is the increase of image information to be diagnosed by a doctor to about 30 slices per patient from 1 X-ray film. To solve this difficult problem, we are trying to reduce the image information drastically to be displayed for the detector by image processing techniques. We propose a new method named Variable-New-Quoit filter for the automatic recognition of the pathological shadow candidates. Our computer aided diagnosis system can satisfactorily reduce the number of CT cross sections by this method, containing the abnormal shadow candidates.

Quoit filter-a new filter based on mathematical morphology to extract the isolated shadow, and its application to automatic detection of lung cancer in X-ray CT

We propose a new algorithm named Quoit filter (Q-filter) to extract the isolated but low amplitude shadow located in the background which has extremely high amplitude fluctuation. Q-filter is a kind of mathematical morphology and its formulation is quite simple. This simplicity brings about a unique merit that output from this filter is analytically expressive for the case of analytical input shapes like ball, cone, or rotation of cosine function, which have characteristics of rotation symmetry and monotonic decreasing from the origin. This Q-filter is composed of two sequential operations named Q Trans. and Q Inv. Trans., Q Trans. corresponds to extracting feature parameters like a matched filter from the input image having a nonideal isolated shadow, and Q Inv. Trans. corresponds to restoring isolated images using extracted feature parameters. This filter is applied to detecting the cancer candidate shadow automatically in the CT cross sections of lung areas, aiming to reduce drastically the number of cross sections to be diagnosed by the doctor.

Proposed System for Ultrafast Computed Tomography

Construction of a new ultrafast scanner system suitable for dynamic computed tomography is now under consideration, with development soon to begin. This system will be characterized by an electronically controlled X-ray generator with wide angle double diffraction, which will permit transverse axial images to be taken in times as short as 0.01 second.

Positologica: A Positron ECT Device with a Continuously Rotating Detector Ring

A rotary positron emission computed tomography device is developed for human brain and animal studies. The device utilizes 64 rectangular BGO detectors arranged at unequal spacing on a circular ring. The detector ring is continuously rotated at a constant speed of 60 rpm or less. This single continuous motion of the ring with the detector array provides excellent sampling characteristics and high detector redundancy. The device has a field of view 24 cm in diameter with a slice thickness adjustable from 1 cm to 2 cm. Measured width of system response to a 2 mm diameter line source is 5.8 mm FWHM at the center and less than 9 mm FWHM within a circle 16 cm in diameter. Measured sensitivity including scattered coincidence events is about 17 kcps/pCi/ml for a 20 cm diameter water phantom and 2 cm thick slice.