Pulmonary clearance of aerosolized 99mTc-DTPA in sarcoidosis I patients.

AIM: Sarcoidosis frequently affects the lungs of patients. Pulmonary clearance scintigraphy with Technetium-99m-diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) aerosol may assess pulmonary involvement of sarcoidosis patients. The study investigated early pulmonary involvement of sarcoidosis I patients by assessing the pulmonary clearance of inhaled (99m)Tc-DTPA aerosol and the character of pulmonary clearance though systemic steroid therapy. METHODS: The pulmonary clearance of (99m)Tc-DTPA aerosol was investigated in 24 patients with suspected stage I sarcoidosis and 20 non-smoking healthy controls over 18 months. The radiological finding was evaluated by chest computed radiography (CR) and high resolution computed tomography (HRCT) and the histological diagnosis was performed by transbronchial lung biopsy and/or Scalen node biopsy. The sarcoidosis I patients with ocular involvement underwent 1 year-systemic steroid therapy and were followed up over totally 18 months. RESULTS: The histological diagnosis was proved in 13 out of the 24 patients that had no lung filed involvement on CR and HRCT. Accelerated pulmonary clearance of (99m)Tc-DTPA was observed in 10 out of the 13 sarcoidosis I patients. Nine out of 13 sarcoidosis I patients underwent systemic steroid therapy due to ocular involvement and the accelerated pulmonary clearance responded to therapy and improved in all of the 9 over 18 months. CONCLUSIONS: Acceleration of (99m)Tc-DTPA pulmonary clearance may be observed in sarcoidosis I patients and the acceleration will respond to systemic steroid therapy. Pulmonary clearance scintigraphy with (99m)Tc-DTPA aerosol may be useful for assessing pulmonary involvement before radiological changes emerge and sarcoidosis I patients with accelerated pulmonary clearance may undergo systemic steroid treatment.

Comparison of patient doses in 256-slice CT and 16-slice CT scanners.

The 256-slice CT-scanner has been developed at the National Institute of Radiological Sciences. Nominal beam width was 128 mm in the longitudinal direction. When scanning continuously at the same position to obtain four-dimensional (4D) images, the effective dose is increased in proportion to the scan time. Our purpose in this work was to measure the dose for the 256-slice CT, to compare it with that of the 16-slice CT-scanner, and to make a preliminary assessment of dose for dynamic 3D imaging (volumetric cine imaging). Our group reported previously that the phantom length and integration range for dosimetry needed to be at least 300 mm to represent more than 90% of the line integral dose with the beam width between 20 mm and 138 mm. In order to obtain good estimates of the dose, we measured the line-integral dose over a 300 mm range in PMMA (polymethylmethacrylate) phantoms of 160 mm or 320 mm diameter and 300 mm length. Doses for both CT systems were compared for a clinical protocol. The results showed that the 256-slice CT generates a smaller dose than the 16-slice CT in all examinations. For volumetric cine imaging, we found an acceptable scan time would be 6 s to 11 s, depending on examinations, if dose must be limited to the same values as routine examinations with a conventional multidetector CT. Finally, we discussed the studies necessary to make full use of volumetric cine imaging.

Effect of calcium trisodium DTPA in rats with puncture wound contaminated by 90Y-chloride.

The efficacy of diethylenetriaminepentaacetate calcium trisodium (CaNa(3)DTPA) in a dose of 34.7 micromol kg(-1) as a function of its route of administration was investigated in rats with a puncture wound contaminated by (90)Y-chloride at a concentration of 2.55 MBq kg(-1). Approximately 60% of (90)Y-chloride at a puncture wound was absorbed into the body of rats over 72 h post-puncture and radioactivity in femoral bone increased during the timed-release of (90)Y. Intravenous administration of CaNa(3)DTPA (systemic treatment) at 15 min post-puncture reduced (90)Y at a puncture wound and in bone up to 75.6 and 84.3% of controls, respectively. Direct infiltration of CaNa(3)DTPA into a puncture wound site (local treatment) at 15 min post-puncture diminished radioactivity at the puncture wound and in bone up to 34.9 and 52.5% of controls, respectively. Thus, prompt local treatment may be effective for removing (90)Y from a puncture wound and minimising (90)Y-distribution to bone compared with systemic treatment.

The amygdala and Alzheimer's disease: positron emission tomographic study of the cholinergic system.

The primary transmitter deficit is cholinergic in Alzheimer's disease (AD), and the amygdala receives a major cholinergic projection from the nucleus basalis of Meynert (Ch4), which may play an important role in the retention of affective conditioning and/or memory consolidation. We measured brain acetylcholinesterase (AChE) activity in 54 patients with AD and in 22 normal controls by positron emission tomography and N-[(11)C]methylpiperidin-4-yl acetate to characterize the cholinergic pathology in AD. The k(3) values were calculated as an index of AChE activity in a three-compartment model analysis using the metabolite-corrected arterial input function. The k(3) values were highly significantly reduced by 20% in the cerebral neocortex (P <0.0001 in the two-tailed t test), 14% in the hippocampus (P <0.001), and 33% in the amygdala (P <0.0001) in AD patients compared with normal controls. The k(3) values were significantly correlated with the Mini-Mental State Examination scores in both the cerebral cortex (P <0.001) and the amygdala (P <0.05) in AD patients, supporting the cholinergic hypothesis of cognitive dysfuncion in AD. Further studies are required, however, to elucidate the specific role of the cholinergic deficit in the amygdala in the emotional and behavioral symptoms in AD.

11C-choline PET for the detection of bone and soft tissue tumours in comparison with FDG PET.

We assessed and compared the usefulness of C-choline positron emission tomography (PET) with that of 2-[ F]fluoro-2-deoxy-D-glucose (FDG) PET for the differentiation between benign and malignant bone and soft tissue tumours. A total of 43 patients with 45 lesions were included. C-choline PET and FDG PET were performed from 5 and 40 min, respectively, after injection of 275-370 MBq tracer. PET data were evaluated by using the standardized uptake value (SUV) and were analysed according to the pathological data. C-choline uptake in malignancies was 4.9+/-2.1 (n=14), which was significantly higher than that in benign lesions (2.5+/-1.7, n=31) (P <0.0001). The sensitivity, specificity and accuracy of C-choline PET were 100%, 64.5% and 75.6%, respectively, when 2.59 of the SUV was used as the cut-off value. The FDG uptake in malignancies was 5.1+/-4.2 (n=14) and was also significantly larger than that in benign lesions 2.9+/-2.9 (n=31) (P<0.003). The sensitivity, specificity and accuracy of FDG PET were 85.7%, 41.9% and 55.6%, respectively (cut-off=1.83). The C-choline uptake in the lesions correlated with FDG uptake ( r=0.61, P<0.003). In receiver operating characteristic (ROC) analysis, the area under the ROC curve for C-choline PET (area=0.847) was higher than that for FDG PET (area=0.717). This study showed that C-choline PET was superior to FDG PET in differentiation between malignant and benign lesion in bone and soft tissue tumours. C-choline PET might be useful as a screening method for malignant bone and soft tissue tumours.

Distinctly abnormal brain metabolism in late-onset ornithine transcarbamylase deficiency.

OBJECTIVE: To assess alterations in brain metabolites in patients with late-onset ornithine transcarbamylase deficiency (OTCD). METHODS: Six unrelated, asymptomatic Japanese late-onset OTCD patients were analyzed by proton MRS ((1)HMRS) using a point-resolved spectroscopy technique (repetition and echo times, 5000 and 30 ms). Localized spectra for the centrum semiovale were acquired and absolute metabolite concentrations were calculated using an LCModel. RESULTS: Compared with age-matched controls, N-acetylaspartate and creatine concentrations were normal in all patients. The glutamine (Gln) plus glutamate concentration was increased in four patients, which progressed in proportion to the clinical stage. myo-inositol (mI) could not be detected in five symptomatic patients. A decreased choline (Cho) concentration was detected in two clinically severe patients. (1)HMRS after liver transplantation in one patient revealed the normalization of all metabolites. CONCLUSION: These findings suggest progression of neurochemical events in OTCD, i.e., mI depletion and Gln accumulation followed by Cho depletion, which is reverse of that in hepatic encephalopathy, i.e., Cho depletion followed by mI depletion and Gln accumulation.

Oncological diagnosis using positron coincidence gamma camera with fluorodeoxyglucose in comparison with dedicated PET.

The purpose of this study was to compare the utility of a dual-head positron coincidence detection gamma camera (PCD) with that of dedicated positron emission tomography (PET) in the imaging of various malignancies using (18)F-fluorodeoxyglucose (FDG). 25 patients with known or suspected malignancies at various sites underwent imaging with both methods, and diagnostic performance on a lesion basis was compared. Tumour lesions were analyzed visually and semi-quantitatively using the ratio of tumour-to-background counts (T/B ratio). FDG PCD and FDG PET visually detected 34 (72.3%) lesions and 37 (78.7%) lesions, respectively. The mean T/B ratio and standard deviation (SD) of FDG PCD was 3.5+/-3.3, significantly lower than that of FDG PET (8.4+/-7.1, p<0.001). When tumour lesions were less than 2.0 cm in diameter, the sensitivity of FDG PCD was 37.5%, significantly inferior to that of FDG PET (50.0%, p<0.01). Sensitivity between FDG PCD and FDG PET in lesions of more than 2.0 cm diameter showed no statistically significant difference. This study indicates that FDG imaging with a dual-head coincidence detection gamma camera can provide suitable diagnostic performance for lesions greater than 2.0 cm diameter, but performed significantly worse than dedicated PET for lesions smaller than this.

Brain N-acetylaspartate is elevated in Pelizaeus-Merzbacher disease with PLP1 duplication.

OBJECTIVE: To assess alterations in brain metabolites of patients with Pelizaeus-Merzbacher disease (PMD) with the proteolipid protein gene 1 (PLP1) duplications using quantitative proton MRS. METHODS: Five unrelated male Japanese patients with PMD with PLP1 duplications were analyzed using automated proton brain examination with the point resolved spectroscopy technique (repetition and echo time of 5,000 and 30 msec). Localized spectra in the posterior portion of the centrum semiovale were acquired, and absolute metabolite concentrations were calculated using the LCModel. RESULTS: Absolute concentrations of N-acetylaspartate (NAA), creatine (Cr), and myoinositol (MI) were increased by 16% (p < 0.01), 43% (p < 0.001), and 31% (p < 0.01) in patients with PMD as compared with age-matched controls. There was no statistical difference in choline concentration. CONCLUSION: The increased concentration of NAA, which could not be detected by previous relative quantitation methods, suggests two possibilities: axonal involvement secondary to dysmyelination, or increased cell population of oligodendrocyte progenitors. Elevated Cr and MI concentrations may reflect the reactive astrocytic gliosis. Our study thus emphasizes the importance of absolute quantitation of metabolites to investigate the disease mechanism of the dysmyelinating disorders of the CNS.

Kinetic analysis of [(11)C]MP4A using a high-radioactivity brain region that represents an integrated input function for measurement of cerebral acetylcholinesterase activity without arterial blood sampling.

N -[(11)C]methylpiperidin-4-yl acetate ([(11)C]MP4A) is an acetylcholine analog. It has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET). [(11)C]MP4A is specifically hydrolyzed by AChE in the brain to a hydrophilic metabolite, which is irreversibly trapped locally in the brain. The authors propose a new method of kinetic analysis of brain AChE activity by PET without arterial blood sampling, that is, reference tissue-based linear least squares (RLS) analysis. In this method, cerebellum or striatum is used as a reference tissue. These regions, because of their high AChE activity, act as a biologic integrator of plasma input function during PET scanning, when regional metabolic rates of [(11)C]MP4A through AChE (k(3); an AChE index) are calculated by using Blomqvist's linear least squares analysis. Computer simulation studies showed that RLS analysis yielded k(3) with almost the same accuracy as the standard nonlinear least squares (NLS) analysis in brain regions with low (such as neocortex and hippocampus) and moderately high (thalamus) k(3) values. The authors then applied these methods to [(11) C]MP4A PET data in 12 healthy subjects and 26 patients with Alzheimer disease (AD) using the cerebellum as the reference region. There was a highly significant linear correlation in regional k(3) estimates between RLS and NLS analyses (456 cerebral regions, [RLS k(3) ] = 0.98 x [NLS k(3) ], r = 0.92, P < 0.001). Significant reductions were observed in k(3) estimates of frontal, temporal, parietal, occipital, and sensorimotor cerebral neocortices (P < 0.001, single-tailed t-test), and hippocampus (P = 0.012) in patients with AD as compared with controls when using RLS analysis. Mean reductions (19.6%) in these 6 regions by RLS were almost the same as those by NLS analysis (20.5%). The sensitivity of RLS analysis for detecting cortical regions with abnormally low k 3 in the 26 patients with AD (138 of 312 regions, 44%) was somewhat less than NLS analysis (52%), but was greater than shape analysis (33%), another method of [(11)C]MP4A kinetic analysis without blood sampling. The authors conclude that RLS analysis is practical and useful for routine analysis of clinical [(11)C]MP4A studies.

Trihalomethane removal by activated carbon fiber.

For the safety of drinking water, trihalomethanes are removed by adsorption onto activated carbon fiber from single-component solutions. The amounts adsorbed onto adsorbents with large surface area and/or pore volume were small. Stronger surface hydrophobicity of adsorbent was correlated with a larger amount of trihalomethanes adsorbed. A trihalomethane with bromine was adsorbed to a greater extent than that with chlorine. The differences in the amounts adsorbed among trihalomethanes can be explained by the polarity of trihalomethane molecules. The amount of trihalomethanes adsorbed was mainly dominated by the strength of hydrophobicity of activated carbon fibers.

Long-term assessment of posttransplant renal prognosis with 31 P magnetic resonance spectroscopy.

BACKGROUND: 31P-magnetic resonance spectroscopy (MRS) has been widely used to study pretransplantation renal viability, and although some had discussed posttransplant renal viability, no one has examined long-term posttransplant renal prognosis. We discuss the use of 31P-MRS to assess the long-term prognosis from the time when MRS was performed. METHODS: We studied 20 patients with renal allografts. 1.5 Tesla clinical magnetic resonance imaging (MRI) and 15 cm surface coil was used for 31P-MRS. Localized 31P-MRS was done using image selected in vivo spectroscopy (ISIS) method. Individual peaks were fitted by Lorenzian line-shapes with a least square method and peak area ratios were calculated. RESULTS: A beta-adenosine triphosphate/inorganic phosphate (beta-ATP/Pi) ratio >1.2 had sensitivity of 92.8%, specificity of 100%, and accuracy of 95% for predicting 3-year renal survival; a beta-ATP/Pi ratio >1.2 had sensitivity of 90.9%, specificity of 66.7%, and accuracy of 76.9% for predicting 5-year renal survival. We compared 31P-MRS spectra data between the survived group and failed group. The survived group had significantly higher beta-ATP/Pi, alpha-ATP/Pi, and phosphodiester (PDE)/Pi ratios than the failed group. CONCLUSIONS: We discussed the beta-ATP/Pi value as a parameter for predicting long-term survival of a transplanted kidney from the time when MRS was performed. A value above 1.2 suggests a high probability of 3-year renal survival, whereas a value over 2.5 indicates that the transplanted kidney could survive over 5 years. 31P-MRS may be useful for predicting long-term survival of transplanted kidneys, but additional studies are needed.

Age-related reduction of extrastriatal dopamine D2 receptor measured by PET.

Although the aging effect of dopamine D2 receptor in the striatum is well-documented, the effect of age on the extrastriatal dopamine D2 receptor has not been fully examined. Since the density of extrastriatal dopamine D2 receptor is very low, suitable ligands are limited. In this study, we used [11C]FLB 457 to quantify the extrastriatal dopamine D2 receptor in the living human brain. Twenty-seven healthy male subjects aged from 21 to 82 years participated in the positron emission tomography study. Extrastriatal [11C]FLB 457 binding was quantified with a reference tissue model using cerebellum as a reference region. Binding potentials corresponding to Bmax/Kd were used to evaluate age-related change. We found age-related decreases of D2 receptor binding in all measured extrastriatal regions. The decrease of D2 receptor binding was 13.8% per decade in frontal cortex, 12.0% in temporal cortex, 13.4% in parietal cortex, 12.4% in occipital cortex, 12.2% in hippocampus, and 4.8% in thalamus. These findings suggest that the amounts of D2 receptor declines in all brain regions as part of the normal aging process.

Dose relationship of limbic-cortical D2-dopamine receptor occupancy with risperidone.

RATIONALE: It has been suggested that the antipsychotic effect of antipsychotics is mediated by the antagonism of the dopamine D2 receptor in the limbic-cortical regions. Risperidone has an atypical property, but its effect on limbic-cortical regions has not been evaluated. OBJECTIVES: In this study, we examined the relationship among doses of risperidone and limbic-cortical dopamine D2 receptor occupancy using positron emission tomography. METHODS: Seven patients with schizophrenia were scanned during the steady state with risperidone. Their occupancies in limbic-cortical regions were determined using positron emission tomography with [11C]FLB 457. RESULTS: The average occupancy ranged from 38% to 80% on doses of 1-6 mg/day. The saturation curve plotted against the drug level fit the data well. CONCLUSIONS: Our results demonstrate that the D2 receptor occupancy with risperidone in the limbic-cortical regions seems to be similar to that of previous reports regarding the striatum, and it would be comparable to that of typical antipsychotics.

Positron emission tomographic measurement of brain acetylcholinesterase activity using N-[(11)C]methylpiperidin-4-yl acetate without arterial blood sampling: methodology of shape analysis and its diagnostic power for Alzheimer's disease.

N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) is a radiotracer that has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET) using a standard compartment model analysis and a metabolite-corrected arterial input function. In the current study, the authors evaluated the applicability of a simple kinetic analysis without blood sampling, namely shape analysis. First, the authors used computer simulations to analyze factors that affect the precision and bias of shape analysis, then optimized the shape analysis procedure for [11C]MP4A. Before shape analysis execution, the later part of dynamic PET data except for the initial 3 minutes were smoothed by fitting to a bi-exponential function followed by linear interpolation of 8 data points between each of adjacent scan frames. Simulations showed that shape analysis yielded estimates of regional metabolic rates of [11C]MP4A by AChE (k3) with acceptable precision and bias in brain regions with low k3 values such as neocortex. Estimates in regions with higher k3 values became progressively more inaccurate. The authors then applied the method to [11C]MP4A PET data in 10 healthy subjects and 20 patients with Alzheimer's disease (AD). There was a highly significant linear correlation in regional k3 estimates between shape and compartment analyses (300 neocortical regions, [shape k3] = 0.93 x [NLS k3], r = 0.89, P < 0.001). Significant reductions in k3 estimates of frontal, temporal, parietal, occipital, and sensorimotor cerebral cortices in patients with AD as compared with controls were observed when using shape analysis (P < 0.013, two-tailed t-test), although these reductions (17% to 20%) were somewhat less than those obtained by compartment analysis (22% to 27%). The sensitivity of shape analysis for detecting neocortical regions with abnormally low k3 in the 20 patients with AD (92 out of 200 regions, 46%) also was somewhat less than compartment analysis (136 out of 200 regions, 68%). However, taking its simplicity and noninvasiveness into account, the authors conclude that quantitative measurement of neocortical AChE activity with shape analysis and [11C]MP4A PET is practical and useful for clinical diagnosis of AD.

Effect of donepezil on brain acetylcholinesterase activity in patients with AD measured by PET.

Acetylcholinesterase (AChE) activities in the brain of three patients with AD were measured once before and once during donepezil treatment (5 mg/d in two patients, 3 mg/d in one patient) using PET and N-[11C]methylpiperidin-4-yl acetate. Donepezil reduced k(3) values, an index of AChE activity, in the cerebral cortex by 39 +/- 5%. All patients showed some degree of symptomatic improvement, and it was concluded that this improvement was likely caused by improved cholinergic activity by inhibition of AChE in the brain.

Epidemiological study on improving the QOL and oral conditions of the aged--Part 1: The relationship between the status of tooth preservation and QOL.

In part 1 of this epidemiological study, a survey was conducted for all senior citizens aged 70 and over who resided in a mountainous village in the mid-section of Hyogo Prefecture. It focused on the relationship among the number of existing teeth, life environment, health status, and activities of daily living; and the correlation between oral status and QOL was analyzed. The daily activities of individuals were compared between those having one or more teeth and others who were totally edentulous. Subsequently, it was found that for both males and females, the odds ratio was significantly high for the dentulous individuals, in comparison with edentulous individuals, to exhibit a behavior indicative of a better QOL (such as "opportunity for conversation with family members or others)", "regular physical activities", and "attend meetings or group outings"). The result of this survey indicates that the presence of teeth is very closely related to one's daily activities. It was concluded that preventing tooth loss is vital for maintaining the masticatory function; so to prevent tooth loss, periodontal disease must be averted.

Epidemiological study on improving the QOL and oral conditions of the aged--Part 2: Relationship between tooth loss and lifestyle factors for adults men.

Oral health in early- and mid-adulthood is essential for the improvement of one's QOL, this study was investigated to include an epidemiological analysis of the relationship between tooth loss and life style, such as smoking, regular exercise, and the food habits of approximately 2,000 employees. Compared with the group with mild or no periodontal disease (CPI of 0, 1, or 2), the frequency of tooth loss in the group with advanced periodontal disease (CPI of 4) was 2.00 times (odds ratio, 2.00; 95% confidence limit, 1.37 to 2.93). The probability of tooth loss showed statistical significance in relation to smoking, alcohol drinking, and frequency of meals. Compared with non-smokers, the probability that current smokers will lose teeth is 1.53 times greater (odds ratio, 1.53; 95% confidence limit, 1.20 to 1.96). It was concluded that periodontal disease and smoking must be averted for preventing tooth loss.