Toward in vivo imaging of heart disease using a radiolabeled single-chain Fv fragment targeting tenascin-C.

Antibodies specific to a particular target molecule can be used as analytical reagents, not only for in vitro immunoassays but also for noninvasive in vivo imaging, e.g., immunoscintigraphies. In the latter case, it is important to reduce the size of antibody molecules in order to achieve suitable in vivo "diagnostic kinetics" and generate higher-resolution images. For these purposes, single-chain Fv fragments (scFvs; M(r) < 30 kDa) have greater potential than intact immunoglobulins (~150 kDa) or Fab (or Fab') fragments (~50 kDa). Our recent observation of enhanced tenascin-C (Tnc) expression at sites of cardiac repair after myocardial infarction prompted us to develop a radiolabeled scFv against Tnc for in vivo imaging of heart disease. We cloned the genes encoding the heavy and light chain variable domains of the mouse anti-Tnc monoclonal antibody 4F10, and combined them to create a single gene. The resulting scFv-4F10 gene was expressed in E. coli cells to produce soluble scFv proteins. scFv-4F10 has an affinity for Tnc (K(a) = 3.5 × 10(7) M(-1)), similar to the Fab fragment of antibody 4F10 (K(a) = 1.3 × 10(7) M(-1)) and high enough to be of practical use. A cysteine residue was then added to the C-terminus to achieve site-specific (111)In labeling via a chelating group. The resulting (111)In-labeled scFv was administered to a rat model of acute myocardial infarction. Biodistribution and quantitative autoradiographic studies indicated higher uptake of the radioactivity at the infarcted myocardium than the noninfarcted one. Single photon emission computed tomography (SPECT) provided in vivo cardiac images that coincided with the ex vivo observations. Our results will promote advances in diagnostic strategies for heart disease.

PET study of brain acetylcholinesterase in cerebellar degenerative disorders.

To elucidate characteristic changes of brain acetylcholinesterase (AChE) in cerebellar degenerative disorders. Eight patients with the cerebellar variant of multiple system atrophy (MSA-C), 7 patients with spinocerebellar ataxia type-3 (SCA-3), 3 patients with SCA-6, and 13 healthy age-matched volunteers participated in this study. Brain AChE activity was measured by [(11)C] N-methylpiperidin-4-yl propionate PET in all subjects. Brain AChE activities were significantly decreased in the thalamus (-27%) and the posterior lobe of cerebellar cortex (-36%) in patients with MSA-C and in the thalamus (-23%) in patients with SCA-3 compared with healthy controls (P < 0.01). Thalamic AChE activities of SCA-3 patients were negatively correlated with the unified Parkinson's disease rating scale motor subscore (P < 0.001). AChE activities were not significantly altered in the cerebral cortex in any disease group. Reduction of AChE activities in the thalamus and cerebellum in MSA and in the thalamus in SCA-3 suggest that cholinergic modulating drugs may have a role in the treatment of ataxia and other symptoms in these disorders.

Preliminary study: color map of hepatocellular carcinoma using dynamic contrast-enhanced 256-detector row CT.

To distinguish hepatocellular carcinoma (HCC) from normal liver tissue, a color map was made by dynamic contrast-enhanced 256-detector row CT developed at our institute. Dynamic enhanced CT of the liver of three patients with HCC was studied. The CT has 912 (transverse) x 256 (cranio-caudal) elements, each measuring approximately 0.5 mm x 0.5mm at the center of rotation. Scanning for 10 s (1.0 s/rotation) was started 30 s after intravenous injection of contrast medium. The reconstruction increment was 0.62 mm with a time interval of 0.1s and a matrix size of 512 x 512 x 256. Color maps were generated to show the gradient of the regression line of the time-density change. Due to volume acquisition, the 3D color map can be created using continuous 10-s scanning. The densities of the HCC and liver were decreased and increased during scanning, respectively. The HCC was detected clearly in the color map as a downward-sloping region. Dynamic enhanced 256-detector row CT could be useful for detecting malignant tumors in the liver with a short scan time.

Cardiac imaging using 256-detector row four-dimensional CT: preliminary clinical report.

PURPOSE: Along with the increase of detector rows on the z-axis and a faster gantry rotation speed, the spatial and temporal resolutions of the multislice computed tomography (CT) have been improved for noninvasive coronary artery imaging. We investigated the feasibility of the second specification prototype 256-detector row four-dimensional CT for assessing coronary artery and cardiac function. MATERIALS AND METHODS: The subjects were five patients with coronary artery disease. Contrast medium (40-60 ml) was intravenously administered at the rate of 3-4 ml/s. The patient's whole heart was scanned for 1.5 s to cover at least one cardiac cycle during breathholding without electrocardiographic gating. Parameters used were 0.5 mm slice thickness, 0.5 s/rotation, 120 Kv, and 350 mA, with a half-scan reconstruction algorithm (temporal resolution 250 ms). Twenty-six transaxial datasets were reconstructed at intervals of 50 ms. RESULTS: The assessability of the coronary arteries in AHA segments 1, 2, 3, 5, 6, 7, 9, and 11 was visually evaluated, resulting in 29 of 32 (90.9%) segments being assessable. Functional assessment was also performed using animated movies without banding artifacts in all cases. CONCLUSIONS: The 256-detector row four-dimensional CT can assess the coronary artery and cardiac function using data during 1.5 s without banding artifacts.

Molecular therapy of human neuroblastoma cells using Auger electrons of 111In-labeled N-myc antisense oligonucleotides.

UNLABELLED: Auger electrons can create breaks in nucleic acids, giving them possible therapeutic utility. We investigated the therapeutic effect of Auger electrons emitted by 111In-labeled phosphorothioate antisense oligonucleotides on human neuroblastoma cells in which N-myc was overexpressed. METHODS: Human SK-N-DZ neuroblastoma cells (5 x 10(6) cells) were treated with cationic reverse-phase evaporation vesicles (REVs) encapsulating 111In-labeled antisense (40 MBq/2 nmol of oligonucleotides/mumol of total phospholipids) that had an average diameter of 250 nm. Hybridization of the radiolabeled oligonucleotides with N-myc messenger RNA (mRNA), N-myc expression, and cell proliferation were investigated. The tumorigenicity of treated cells was analyzed in nude mice. Nonradiolabeled antisense, 111In-labeled sense, or empty cationic REVs were used as controls. RESULTS: 111In-Labeled antisense, which hybridized with N-myc mRNA, was detected in cells at 12 and 24 h after the initiation of treatment. Reduced N-myc expression and inhibited cell proliferation were shown in the same cells at 48 h after the completion of treatment. N-myc expression-suppressed cells produced intraperitoneal tumors in nude mice, but the average weight of the tumors was lower than that of tumors in control mice. CONCLUSION: Auger electrons emitted from 111In in close proximity to their target N-myc mRNA may prolong the time to cell proliferation in human neuroblastoma cells due to inhibition of the translation of N-myc. Auger electron therapy therefore has potential as an internally delivered molecular radiotherapy targeting the mRNA of a tumor cell.

A dose-finding study of duloxetine based on serotonin transporter occupancy.

RATIONALE: Positron emission tomography (PET) has been utilized for determining the dosage of antipsychotic drugs. To evaluate the dosage of antidepressants such as selective serotonin reuptake inhibitors, serotonin transporter occupancy (5-HTT) is also a useful index. OBJECTIVES: We investigated the degree of 5-HTT occupancy with different doses of the antidepressant duloxetine and the time-course of 5-HTT occupancy using PET. METHODS: PET scans with [11C]DASB were performed before and after a single administration of duloxetine (5-60 mg), and three consecutive scans were performed after a single dose or repeated doses of 60 mg of duloxetine. RESULTS: 5-HTT occupancies by duloxetine were increased by 35.3 to 86.5% with dose and plasma concentration increments. The ED50 value of 5-HTT occupancy was 7.9 mg for dose and 3.7 ng/ml for plasma concentration. In the time-course of 5-HTT occupancy, mean occupancies were 81.8% at 6 h, 71.9% at 25 h, and 44.9% at 53 h after a single administration, and 84.3% at 6 h, 71.9% at 49 h, and 47.1% at 78 h after repeated administrations. CONCLUSIONS: Based on 5-HTT occupancy, 40 mg and more of duloxetine was needed to attain 80% occupancy, and 60 mg of duloxetine could maintain a high level of 5-HTT occupancy with a once-a-day administration schedule.

Optimizing T2-weighted magnetic resonance sequences for surface coil microimaging of the eye with regard to lid, eyeball and head moving artifacts.

PURPOSE: To acquire high-resolution magnetic resonance (MR) images, we developed a new blinking artifact reduced pulse (BARP) sequence with a surface coil specialized for microscopic imaging (47 mm in diameter). MATERIALS AND METHODS: To reduce eye movement, we ascertained that the subjects' eyes were kept open and fixated to the target in the 1.5-T MR gantry. To reduce motion artifacts from blinking, we inserted rest periods for blinking (1.5 s within every 5 s) during MR scanning (T2-weighted fast spin echo; repetition time, 5 s; echo time, 100 ms; echo train, 11; matrix, 256 x 128; field of view, 5 cm; 1-mm thickness x 30 slices). Three scans (100 s x 3) were performed for each normal subject, and they were added together after automatic adjustment for location to reduce quality loss caused by head motion. RESULTS: T2-weighted MR images were acquired with a high resolution and a high signal-to-noise ratio. Motion artifacts were reduced with BARP, as compared with those with random blinking. Intraocular structures such as the iris and ciliary muscles were clearly visualized. Because the whole eye can be covered with a 1-mm thickness by this method, three-dimensional maps can easily be generated from the obtained images. CONCLUSION: The application of BARP with a surface coil of the human eye might become a useful and widely adopted procedure for MR microimaging.

Physical evaluation of the weighted Feldkamp algorithms applied to the 256-detector row CT scanner for volumetric cine imaging.

RATIONALE AND OBJECTIVES: To improve effective scan time and image quality in cone-beam computed tomography (CT), Parker's weighting function (half scan [HS]-Feldkamp-Davis-Kress [FDK]) extended to a larger range up to 2pi was proposed as new half-scan algorithm (NHS-FDK). We conducted a practical physical evaluation of NHS-FDK and HS-FDK using 256-detector row CT. MATERIALS AND METHODS: Three types of weighting function (full-scan [FS-FDK], HS-FDK, and NHS-FDK) were evaluated by using 256-detector row CT for five variables, ie, point spread function, image noise, CT number uniformity, Feldkamp artifact, temporal resolution, and clinical evaluation. RESULTS: Image noise, Feldkamp artifact, and temporal resolution were dependent on weighting function. Image noise magnitude was independent of projection angle for all regions of interest with FS-FDK, but showed a symmetric pattern with projection angle with HS-FDK and NHS-FDK. With regard to temporal resolution, NHS-FDK did not remove the motion artifact in the heart except in such slower motion organs as the pulmonary vessels, whereas HS-FDK reduced the motion artifact in the heart. HS-FDK had an even more incomplete data region in the Radon space than FS-FDK, suggesting that it would provide poor image quality distant to the midplane in the longitudinal direction. In practical testing in human subjects, HS-FDK showed inferior performance in all variables except temporal resolution. CONCLUSION: Despite its inferiority to FS-FDK for static objects, HS-FDK may be useful in chest imaging. Contrary to previous findings using static images, NHS-FDK failed to show advantages over HS-FDK or FS-FDK in a moving phantom and human subjects.

Noise properties for three weighted Feldkamp algorithms using a 256-detecotor row CT-scanner: case study for hepatic volumetric cine imaging.

In cone-beam geometry, image quality may be degraded or artifacts may occur if the cone angle is substantially wide. This is because a cone-beam scan along a circular orbit does not collect the complete set of data required to make an exact reconstruction of all volumetric data. To increase temporal resolution and thus image quality in cone-beam geometry, Silver proposed the new half-scan algorithm (NHS-FDK), which extends Parker's weighting function (HS-FDK) by utilizing a larger range up to 2pi. Here, we evaluated these algorithms for hepatic contrast-enhanced CT in cine scan mode using a 256-detector row CT. The full-scan (FS-FDK) images show uniform distribution of the image noise and CT-number uniformity. Image noise and CT-number uniformity with HS-FDK and NHS-FDK images follow the initial projection angle. HS-FDK images therefore have more changeable higher intensity (brighter) and a lower intensity (darker) areas than respective FS-FDK and NHS-FDK images. We concluded that, considering the trade-off between image quality and temporal resolution, the NHS-FDK algorithm is useful in volumetric cine imaging for the abdomen.

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.

Estimation of plasma IC50 of donepezil hydrochloride for brain acetylcholinesterase inhibition in monkey using N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) and PET.

Donepezil hydrochloride is a potent and selective inhibitor for brain acetylcholinesterase (AChE) and is currently used worldwide for the treatment of Alzheimer's disease. Until now, there is no in vivo study on the relation between the plasma concentration and the brain AChE inhibition. The purpose of this study was to estimate in vivo plasma IC(50) of donepezil in living monkeys by measuring plasma donepezil concentration (LC/MS/MS) and brain AChE activity with positron emission tomography (PET) and N-[(11)C]methylpiperidin-4-yl acetate, which is an acetylcholine analog recently developed by us for quantifying in vivo brain AChE activity. PET scans with donepezil at two doses, 100 microg/kg (donepezil-1; N=5) or 250 microg/kg (donepezil-2; N=5), were performed using the same monkeys at 4-week intervals. Before each PET scan, baseline PET scans (N=10 in total) were performed without donepezil. The plasma donepezil concentrations 14 min after intravenous injection were proportional to the doses, 17.2+/-2.9 ng/ml (donepezil-1) and 44.0+/-5.0 ng/ml (donepezil-2), and the mean AChE inhibitions in four neocortical regions as evaluated by PET were also dose-dependent, 27% (donepezil-1) and 53% (donepezil-2). In IC(50) estimation, measured plasma donepezil concentrations were corrected for the change during PET scan. The IC(50) values (estimate+/-SE) were 42+/-9.0 (ng/ml; donepezil-1), 34+/-3.2 (donepezil-2), and 37+/-4.1 (combined data). The present method may be useful for in vivo evaluation of other AChE inhibitors and novel drugs.

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.

[(11)C]methionine positron emission tomography and survival in patients with bone and soft tissue sarcomas treated by carbon ion radiotherapy.

PURPOSE: The development of the novel carbon ion radiotherapy (CIRT) in the treatment of refractory cancers has resulted in the need for a way to accurately evaluate patient prognosis. We evaluated whether L-[methyl-(11)C]-methionine (MET) uptake and its change after CIRT were the early survival predictors in patients with unresectable bone and soft tissue sarcomas. EXPERIMENTAL DESIGN: MET positron emission tomography was prospectively performed in 62 patients with unresectable bone and soft tissue sarcomas before and within 1 month after CIRT. Tumor MET uptake was measured with the semiquantitative tumor:nontumor ratio (T/N ratio). The MET uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analysis. RESULTS: The overall median survival time was 20 months. Patients with a baseline T/N ratio of 6 (2-year survival rate: 69.4% versus 32.3%; P = 0.01). Patients with a post-CIRT ratio of 4.4 (2-year survival rate: 63.7% versus 41.3%; P = 0.01). A significant higher survival rate was observed in patients with post-therapeutic MET uptake change of >30% than patients in lower change group (2-year survival rate: 74.6% versus 41.6%; P = 0.049). The multivariate analysis showed that both baseline and post-CIRT T/N ratio were statistically significant independent predictors of patient survival. Tumors with larger T/N ratio had a significantly poorer prognosis. CONCLUSIONS: MET uptake as measured by either baseline or post-CIRT T/N ratio was an independent predictor of survival in patients with bone and soft tissue sarcomas treated by carbon ion radiotherapy, whereas post-therapeutic MET uptake change might have potential value for the same purpose.

Clinical potentials of the prototype 256-detector row CT-scanner.

RATIONALE AND OBJECTIVES: To evaluate clinical potentials of the 256-detector row computed tomography (CT) in healthy volunteers. MATERIALS AND METHODS: Eight healthy males (22-63 years) participated in the present study. They underwent a noncontrast-enhanced examination with a contiguous axial scan mode either for head, chest, abdomen, or pelvis. Dose was the same as routinely used for multislice CT examinations. Image quality was interpreted by three board-certified radiologists. RESULTS: With the 256-detector row CT, 0.5-0.8 mm isotropic volumetric data could be acquired in one rotation. Main promising findings are as follows. Three-dimensional structures were visualized clearly in the multiple planes without secondary reconstruction, whereas the axial images had nearly the same image quality as conventional CT. Shading or streak artifacts were observed at the edge of the scan region. The latter are also known as Feldkamp artifacts. Coronal chest images showed a motion artifact from the heart beating. CONCLUSION: The 256-detector row CT promises to be useful in clinical applications with its ability to provide three-dimensional visualization of fine structures. The Feldkamp artifacts observed did not generally affect interpretation of images. Investigations are now continuing on image correction along the craniocaudal direction to improve the overall image quality.

Elevated Serum IgG4 Complicated by Pericardial Involvement with a Patchy (18)F-FDG Uptake in PET/CT: Atypical Presentation of IgG4-related Disease.

IgG4-related pericardial involvement has rarely been reported and its clinical features remain unknown. We herein report a case of a 50-year-old woman with pericarditis who presented with a fever, elevated C-reactive protein levels, elevated serum IgG4 concentrations, and thickened pericardium with a patchy (18)F-fluorodeoxyglucose (FDG) uptake. A biopsy specimen of (18)F-FDG accumulated in the mediastinal lymph nodes revealed an abundant infiltration of IgG4-bearing plasma cells without fibrosis. Moderate-dose glucocorticoids promptly resolved the physical, serological, and imaging abnormalities, thus indicating a relatively acute and reversible nature of IgG4-related pericardial involvement.

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.

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.

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.

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.

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.