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Biomedical subjects

Shuji Tanada

Publications and source records attributed to Shuji Tanada.

34 records · Page 2Linked to original sources

Evaluation of simplified kinetic analyses for measurement of brain acetylcholinesterase activity using N-[11C]Methylpiperidin-4-yl propionate and positron emission tomography.

The applicability of two reference tissue-based analyses without arterial blood sampling for the measurement of brain regional acetylcholinesterase (AChE) activity using N-[11C]methylpiperidin-4-yl propionate ([11C]MP4P) was evaluated in 12 healthy subjects. One was a linear least squares analysis derived from Blomqvist's equation, and the other was the analysis of the ratio of target-tissue radioactivity relative to reference-tissue radioactivity proposed by Herholz and coworkers. The standard compartment analysis using arterial input function provided reliable quantification of k3 (an index of AChE activity) estimates in regions with low (neocortex and hippocampus), moderate (thalamus), and high (cerebellum) AChE activity with a coefficient of variation (COV) of 12% to 19%. However, the precise k3 value in the striatum, where AChE activity is the highest, was not obtained. The striatum was used as a reference because its time-radioactivity curve was proportional to the time integral of the arterial input function. Reliable k3 estimates were also obtained in regions with low-to-moderate AChE activity with a COV of less than 21% by striatal reference analyses, though not obtained in the cerebellum. Shape analysis, the previous method of direct k3 estimation from the shape of time-radioactivity data, gave k3 estimates in the cortex and thalamus with a somewhat larger COV. In comparison with the standard analysis, a moderate overestimation of k3 by 9% to 18% in the linear analysis and a moderate underestimation by 2% to 13% in the Herholz method were observed, which were appropriately explained by the results of computer simulation. In conclusion, simplified kinetic analyses are practical and useful for the routine analysis of clinical [11C]MP4P studies and are nearly as effective as the standard analysis for detecting regions with abnormal AChE activity.

Acetylcholinesterase↗

Neural damage due to temporal lobe epilepsy: dual-nuclei (proton and phosphorus) magnetic resonance spectroscopy study.

The aim of this study was to evaluate the usefulness of proton and phosphorus (1H and 31P) magnetic resonance spectroscopy (MRS) for temporal lobe epilepsy (TLE) patients, and to evaluate neural damage and metabolite dysfunction in the TLE patient brain. We performed 1H and 31P MRS of medial temporal lobes (MTL) in the same TLE patients (n = 14) with a relatively wide range of severity from almost seizure-free to intractable, and calculated the ratio of N-acetylasparate to choline-containing compounds and creatine + phosphocreatine (NAA/Cho + Cr) in 1H MRS and inorganic phosphate to all main peaks (%Pi) in 31P MRS. There was no significant correlation between NAA/(Cho + Cr) and %Pi in each side (ipsilateral, r = -0.20; contralateral, r =-0.19). The values of NAA/(Cho + Cr) showed a significant difference between ipsilateral and contralateral MTLs to the focus of TLE patients (P < 0.01, paired t-test). Although %Pi also had a tendency to show the laterality of TLE, there was no significance. Ipsilateral (r = -0.90, P < 0.0001) and contralateral (r = -0.70, P < 0.005) NAA/(Cho + Cr) decreases and contralateral %Pi increase (r = 0.81, P < 0.001) had significant correlation with seizure frequency. 1H MRS provides more important information concerning neuronal dysfunction in MTL of TLE patients than 31P MRS.

Adult↗

Physical performance evaluation of a 256-slice CT-scanner for four-dimensional imaging.

We have developed a prototype 256-slice CT-scanner for four-dimensional (4D) imaging that employs continuous rotations of a cone-beam. Since a cone-beam scan along a circular orbit does not collect a complete set of data to make an exact reconstruction of a volume [three-dimensional (3D) image], it might cause disadvantages or artifacts. To examine effects of the cone-beam data collection on image quality, we have evaluated physical performance of the prototype 256-slice CT-scanner with 0.5 mm slices and compared it to that of a 16-slice CT-scanner with 0.75 mm slices. As a result, we found that image noise, uniformity, and high contrast detectability were independent of z coordinate. A Feldkamp artifact was observed in distortion measurements. Full width at half maximum (FWHM) of slice sensitivity profiles (SSP) increased with z coordinate though it seemed to be caused by other reasons than incompleteness of data. With regard to low contrast detectability, smaller objects were detected more clearly at the midplane (z = 0 mm) than at z = 40 mm, though circular-band like artifacts affected detection. The comparison between the 16-slice and the 256-slice scanners showed better performance for the 16-slice scanner regarding the SSP, low contrast detectability, and distortion. The inferiorities of the 256-slice scanner in other than distortion measurement (Feldkamp artifact) seemed to be partly caused by the prototype nature of the scanner and should be improved in the future scanner. The image noise, uniformity, and high contrast detectability were almost identical for both CTs. The 256-slice scanner was superior to the 16-slice scanner regarding the PSF, though it was caused by the smaller transverse beam width of the 256-slice scanner. In order to compare both scanners comprehensively in terms of exposure dose, noise, slice thickness, and transverse spatial resolution, K=Dsigma2ha3 was calculated, where D was exposure dose (CT dose index), sigma was magnitude of noise, h was slice thickness (FWHM of SSP), and a was transverse spatial resolution (FWHM of PSF). The results showed that the K value was 25% larger for the 16-slice scanner, and that the 256-slice scanner was 1.25 times more effective than the 16-slice scanner at the midplane. The superiority in K value for the 256-slice scanner might be partly caused by decrease of wasted exposure with a wide-angle cone-beam scan. In spite of the several problems of the 256-slice scanner, it took a volume data approximately 1.0 mm (transverse) x 1.3 mm (longitudinal) resolution for a wide field of view (approximately 100 mm long) along the zeta axis in a 1 s scan if resolution was defined by the FWHM of the PSF or the SSP, which should be very useful to take dynamic 3D (4D) images of moving organs.

Biophysical Phenomena↗

Changes in the pharmacokinetics of Gd-DTPA in experimental tumors after charged particle radiation: comparison with gamma-ray radiation.

We performed dynamic MRI to reveal the characteristic gadopentetate dimeglumine (Gd-DTPA) uptake in carbon-ion irradiated tumor and compare it with photon irradiation. Fibrosarcomas in C3H mice legs were irradiated with either 16 Gy of carbon ions (74 keV/mm) or an equivalent dose (30 Gy) of Cs-137 gamma-rays. Dynamic MRI was performed 1 or 6 days after irradiation when the tumors showed an initial growth delay or incipient regrowth, respectively. The enhancement pattern was visualized by mapping the maximum enhanced time (Tmax), relative signal intensity maximum (SImax), and time delay of starting enhancement (Td). Significantly larger Tmax and Td values were observed in the tumors 1 day after carbon-ion irradiation than in the nonradiated tumors (No-R) and tumors 1 day after gamma-ray irradiation. Among the selected pixels in the tumors 6 days after carbon irradiation, 77% had Tmax values of less than 120 sec, significantly more than in the No-R group. The Tmax maps for the tumors irradiated with gamma-rays showed a similar tendency to the carbon-irradiated ones, and only a significant difference was obtained between tumors 1 and 6 days after irradiation. Tmax and Td in the carbon-ion irradiated tumors were different from those in the gamma-ray-irradiated tumors. These treatment-specific kinetics may be useful in predicting the therapeutic efficacy of carbon-ion treatment.

Animals↗

Development of a dielectric equivalent gel for better impedance matching for human skin.

It would be useful to develop a tissue equivalent gel to improve the uniformity of the electromagnetic field in the human body, and for making a tissue equivalent dielectric human phantom. In this study, solid type, water based gelatin-honey gels were developed which have the electrical characteristics of skin tissue. It was demonstrated that a stable and homogeneous gel, with a relative dielectric constant epsilon ' chosen from desired ranges found in skin, can be made for 200-400 MHz.

Biomimetic Materials↗

Detection of lung cancer with positron coincidence gamma camera using fluorodeoxyglucose in comparison with dedicated PET.

OBJECTIVE: Dual-head gamma cameras with sodium iodide (NaI) detectors operated in coincidence mode provide a new approach for imaging with positron-labeled tracers. The purpose of this study was to evaluate the feasibility of FDG imaging with positron coincidence detection gamma camera (PCD) in detecting lung tumor in comparison with FDG imaging with the dedicated positron emission tomography (PET). METHODS AND MATERIAL: Twenty-six lesions of 13 patients with suspected lung cancer were studied with both FDG PET and FDG PCD on the same day. Pulmonary lesions were analyzed visually and semi-quantitatively using the ratio of target-to-background counts (T/B ratio). RESULTS AND CONCLUSIONS: FDG PCD and FDG PET could detect visually 21 lesions (80.8%) and 23 lesions (88.0%), respectively. The mean T/B ratio and standard deviation (S.D.) of FDG PCD was 4.6 +/- 3.9, significantly lower than that of FDG PET (11.4 +/- 6.6, P<0.001). When pulmonary lesions were no more than 2.0 cm in diameter, the sensitivity of FDG PCD was 37.5%, significantly inferior to that of FDG PET (62.5%, P<0.001). There was no statistically significant difference of the sensitivity between the FDG PCD and FDG PET in lesions of more than 2.0 cm in diameter. FDG PCD with uniform attenuation correction was clinically available in detecting lung cancer. However, the sensitivity for small lesions less than 2.0 cm was limited. The application of measured attenuation correction and scatter correction may to be needed to improve the detectability of FDG PCD, especially for detecting small lung cancer.

Adult↗

Detection of experimental autoimmune myocarditis in rats by 111In monoclonal antibody specific for tenascin-C.

BACKGROUND: Although the identification of inflammatory infiltrates in endomyocardial biopsy specimens is necessary for the definite diagnosis of myocarditis, the biopsy test is invasive and is not sensitive. Therefore, a new diagnostic technique for the early and noninvasive evaluation of myocarditis has been awaited. Expression of tenascin-C (TNC), one of the oligometric extracellular glycoproteins, is induced in various pathological states, including inflammation, suggesting that TNC can be a molecular marker of myocarditis. METHODS AND RESULTS: An 111In anti-TNC monoclonal antibody Fab' fragment was injected intravenously into rats with experimental autoimmune myocarditis (EAM), and the biodistribution of this radiotracer was measured. Rapid clearance of radioactivity from the blood was observed in both EAM and control rats (<1% at 6 hours after injection). Myocardial uptake of the tracer was much higher in EAM rats than in control rats (7.54-, 4.39-, and 3.51-fold at 6, 24, and 48 hours after injection, respectively). By autoradiography, high radioactivities were clearly observed in the regions indicative of inflammation in EAM rats. Single-photon emission CT imaging demonstrated the focal myocardial uptake of 111In anti-TNC Fab' in vivo. CONCLUSIONS: Radiolabeled anti-TNC Fab' may be useful for the noninvasive diagnosis of myocarditis.

Animals↗

Age-related decline of serotonin transporters in living human brain of healthy males.

There is growing interest in serotonin transporter (5-HTT) function in the human brain, since alteration in 5-HTT has been suggested in a variety of neurophychiatric disorders. Age-related decline in postsynaptic 5-HT receptors has been demonstrated in postmortem human studies and in vivo imaging studies, and has been assumed to be related to changes in mental function in the normal aging process. However, few studies have investigated the aging effect on 5-HTT in human brain in vivo, since the availability of suitable ligands has been limited. To investigate the aging effect on 5-HTT in living human brain, we performed positron emission tomography (PET) scans with a selective ligand for 5-HTT, [11C](+)McN5652. We examined 28 healthy male volunteers aged between 20 and 79 years. The uptake was quantified in the thalamus and midbrain by graphical analysis with the cerebellum as a reference tissue, and binding potential (BP) was used for the index of 5-HTT binding. There was a significant age-related decline in BP in the thalamus and midbrain. The decline in [11C](+)McN5652 binding was 9.6% per decade in the thalamus and 10.5% per decade in the midbrain.

Adult↗

Measurement of the electrical properties of human skin and the variation among subjects with certain skin conditions.

In this study the dielectric properties are reported for human skin tissues over the frequency range 1-450 MHz at 36 degrees C. Healthy volunteers, collagen disease patients and dialysis patients are studied in order to investigate, primarily, the variability among (1) different regions of one individual, (2) the same region among different individuals and (3) skin conditions due to diseases. Considerable differences exist among the skin dielectric properties obtained from different regions of one individual body. Although region dependence is observed, larger variability is found even in the same skin region among individuals.

Collagen↗

Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia.

BACKGROUND: The clinical efficacy of dopamine D2 receptor antagonism on the psychotic symptoms of schizophrenia has been widely demonstrated. However, most in vivo imaging studies have not been able to detect significant changes in striatal D2 receptors in schizophrenia. On the other hand, a number of studies have reported abnormalities in the cerebral cortex of schizophrenia. The aim of this study was to examine the extrastriatal D2 receptors of patients with schizophrenia. METHODS: Eleven drug-naive male patients with schizophrenia were examined with positron emission tomography using carbon 11-labeled FLB 457. Symptoms were assessed using the Brief Psychiatric Rating Scale. Eighteen healthy controls were used for comparison. Region-of-interest analysis was performed using the reference tissue method, and binding potential (BP) was used for the index of dopamine D2 receptor binding. RESULTS: The BP value was significantly lower, by about 12.5%, in the anterior cingulate cortex in drug-naive patients with schizophrenia than in healthy controls. A significant negative correlation was observed between BP in the anterior cingulate cortex and the positive symptom score on Brief Psychiatric Rating Scale. CONCLUSIONS: The lower BP values indicate fewer D2 receptors in the anterior cingulate cortex in patients with schizophrenia. Alterations in D2 receptor function in the extrastriatal region may underlie the positive symptoms of schizophrenia.

Adult↗

Positron emission tomography: quantitative measurement of brain acetylcholinesterase activity using radiolabeled substrates.

A new method for quantitative measurement of brain acetylcholinesterase (AChE) activity in living human brain using positron emission tomography (PET) is described. We tested several radiolabeled lipophilic acetylcholine analogs, e.g., N-methylpiperidyl esters, which readily entered the brain via the blood-brain barrier, were hydrolyzed selectively by AChE, and were then trapped in the brain. Among them, and tested and N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) was chosen as the tracer for PET. Quantitative measurement of cortical AChE was accomplished by fitting the time course of cerebral radioactivity concentration measured by PET and the metabolite-corrected arterial plasma input function using a nonlinear least-squares fitting method. Normal control studies of subjects with a wide range in age (24-89 years) showed no decrease in AChE activity in the cerebral cortex with age. Studies on patients with Alzheimer's disease demonstrated a widespread reduction of AChE activity in the cerebral cortex (more profound in early-onset than in late-onset Alzheimer's disease). Parkinson's disease and progressive supranuclear palsy, clinically similar disorders, could be differentiated with [11C]MP4A/PET studies. Simple methods without using an arterial input function are also proposed. The method provides a quantitative measure of the cholinergic aspect of brain function and proved to be useful in diagnosis of neurodegenerative disorders including Alzheimer's disease.

Acetylcholinesterase↗

19F-magnetic resonance spectroscopy and chemical shift imaging for schizophrenic patients using haloperidol decanoate.

Haloperidol decanoate is widely used in the maintenance treatment of schizophrenia and other psychotic disorders, but knowledge concerning its pharmacokinetics at the injected region is very limited. Because the chemical structure of haloperidol contains fluorine, in vivo 19F-magnetic resonance (MR) spectroscopy (repetition time (TR) = 1 s) and chemical shift imaging (CSI; TR = 1 s, pixel size = 15 x 15 mm) were performed in schizophrenic patients who were treated with haloperidol decanoate (three men and one woman) to measure its diachronic change at the injection point and visualize its local distribution after intramuscular injection. 19F signals (T1 time = 365 ms) were obtained at the haloperidol decanoate-injected region. The decrease rate of the signal-to-noise ratio (SNR) by 19F-MR spectroscopy seemed large in comparison with that of the plasma haloperidol concentration. The distribution was clearly visualized by 19F-CSI for a few days after the injection, but after 1 week could no longer be seen. Although the slow-release characteristics of depot neuroleptics have been explained by the slow diffusion of esterified neuroleptics from the oil vehicle, this result may suggest that there are other mechanisms involved in maintaining the plasma haloperidol concentration. In vivo 19F-MR spectroscopy and CSI are potentially applicable for the pharmacokinetic analysis of haloperidol and other drugs containing fluorine in their structure.

Adult↗

Shielding effects of body - shields for 3D PET.

We analyzed basic physics characteristics of body-shields which have been considered for screening out radioactivity outside the field of view (OFOV) in positron emission tomography (PET). Phantom experiments were performed with simple rectangular body-shields. A Monte Carlo simulation technique was used to analyze the experimental results and to simulate cases that were not examined experimentally. It was confirmed that the body-shields effectively reduced unwanted radiations from OFOV radioactivity for one of the latest commercial PET scanners, the ECAT EXACT HR(+). The geometrical conditions were the most important factor in determining the shielding effect. The shield thickness should be large enough to keep the shield-scatter component low. The body-shield should be carefully designed to minimize the gap between the body-shield and radioactive distribution as much as possible to maximize the shielding effects, and to be applicable to clinical diagnoses.

Equipment Design↗

Extrastriatal dopamine D2 receptor density and affinity in the human brain measured by 3D PET.

The aim of the present study was to quantify the density and affinity of human extrastriatal dopamine D2 receptors using positron emission tomography (PET). [(11)C]FLB-457, a high-affinity dopamine D2 receptor antagonist with various specific radioactivities (SA) was used. Eight healthy male subjects, age 20-35 yr, participated twice or three times at different SAs (1-279 GBq/ µmol), and serial dynamic scans were performed in the 3D data acquisition mode. The peak of the specific binding was not well defined with high SA due to the flatness of the curves after 60 min but was observed within the PET measurement. In the experiment with low SA, the peak came earlier than that with high SA. Scatchard analysis was performed using the maximal specific binding value (transient equilibrium) and the radioactivity in the cerebellum as free ligand concentration. The highest density was observed in the thalamus (2.3+/-0.6 pmol/ml), followed by the temporal cortex (1.5+/-0.5 pmol/ml), hippocampus (1.4+/-0.5 pmol/ml), parietal cortex (0.9+/-0.4 pmol/ml), frontal cortex (0.8+/-0.2 pmol/ml) and occipital cortex (0.7+/-0.3 pmol/ml). There was no significant difference in K(d) values in these six regions. The present results demonstrate that dopamine D2 receptor densities in the extrastriatal regions were only 2-8% of that in the striatum. Although the density of extrastriatal dopamine D2 receptor was low, significant regional differences were observed in the present study, as reported in postmortem studies.

Journal Article↗

Four-dimensional computed tomography (4D CT)--concepts and preliminary development.

Four-dimensional computed tomography (4D CT) is a dynamic volume imaging system of moving organs with an image quality comparable to that of conventional CT. 4D CT will be realized by several technical breakthroughs for dynamic cone-beam CT: (1) a large-area two-dimensional (2D) detector; (2) high-speed data transfer system; (3) reconstruction algorithms; (4) ultra-high-speed reconstruction computer; and (5) high-speed, continuously rotating gantry. Among these, development of the 2D detector is one of the main tasks because it should have as wide a dynamic range and as high a data acquisition speed (view rate) as present CT detectors. We are now developing a 4D CT scanner together with the key components. It will take one volume image in 0.5 sec with a 3D matrix of 512 x 512 x 512. This paper describes the concepts and designs of the 4D CT system, as well as preliminary development of the 2D detector.

Equipment Design↗