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A synthetic approach to the heterodimeric bisindole alkaloid leucophyllidine is disclosed herein. An enantioenriched lactam building block, synthesized through palladium-catalyzed asymmetric allylic alkylation, served as the precursor to both hemispheres. The eburnamonine-derived fragment was synthesized through a Bischler–Napieralski/hydrogenation approach, while the eucophylline-derived fragment was synthesized by Friedländer quinoline synthesis and two sequential C−H functionalization steps. A convergent Stille coupling and phenol-directed hydrogenation united the two monomeric fragments to afford 16′-epi-leucophyllidine in 21 steps from commercial material.

We applied a desilylation procedure using SO 3 H silica gel, with the surface modified by alkylsulfonic acid groups, to silylated sugar, nucleoside, and alkaloid derivatives. The treatment with SO 3 H silica gel provided desilylated products in good to excellent yield. In the reactions of sugar and nucleoside derivatives, no silyl residue was detected in the crude products, but the crude products of the reaction of alkaloids contained small amounts of silyl residues. Even though the sugar and nucleoside derivatives had a labile glycosyl and C N bond, respectively, these bonds tolerated the reaction conditions. These outcomes suggested that the desilylation procedure using SO 3 H silica gel would be applicable to the deprotection of a variety of types of compounds protected by silyl groups. In a gram scale experiment, the desilylation procedure successfully proceeded without the observation of any silyl residue in the crude product.

We designed and synthesized novel δ opioid receptor (DOR) agonists 3a – i with an azatricyclodecane skeleton, which was a novel structural class of DOR agonists. Among them, 3b exhibited high values of binding affinity and potent agonistic activity for the DOR that were approximately equivalent to those of 2 which bore an oxazatricyclodecane skeleton. In vitro assays using the blood-brain barrier (BBB) permeability test kit supported the idea that 3b achieved an excellent BBB permeability by converting an oxygen atom of 2 to a carbon atom (methylene group) in the core skeleton. As a result, 3b showed potent antinociceptive effects.

We synthesized compounds 4a,c-f,h,i containing the oxazatricyclodecane structure from a novel rearrangement reaction product 2a. All the prepared compounds 4a,c-f,h,i exhibited full agonistic activities for the δ opioid receptor (DOR). Among them, the N-methyl derivative 4c was highly selective, and the most effective DOR agonist in functional assays. Subcutaneous administration of 4c produced dose-dependent and NTI (selective DOR antagonist)-reversible antinociception lacking any convulsive behaviors in the mice acetic acid writhing tests. The N-methyl derivative 4c is expected to be a promising lead compound for selective DOR agonists with a novel chemotype.

Nitrilase, which is found in plants and many types of bacteria, is known as the enzyme that catalyzes hydrolysis of a wide variety of nitrile compounds. While human nitrilase-like protein (NIT), which is a member of the nitrilase superfamily, has two distinct isozymes, NIT1 and NIT2, their function has not been well understood. In this study, we investigated whether human NIT1 and NIT2 are involved in the hydrolysis of drugs using vildagliptin as a substrate. We performed Western blot analysis using human liver samples to examine protein expression of human NIT in the liver, finding that human NIT1 and NIT2 were highly expressed in the liver cytosol. We established stable single expression systems of human NIT1 and NIT2 in HEK293 cells to clarify the contribution of human NIT to hydrolysis of vildagliptin. Although the formation of a carboxylic acid metabolite of vildagliptin (M20.7) was observed in human liver samples, M20.7 was not formed by incubating vildagliptin with HEK293 cells expressing human NIT1 or NIT2. This suggests that human NIT1 or NIT2 is not involved in the metabolism of vildagliptin. Further investigation using other drugs is needed to clarify the contribution of human NIT to drug metabolism.

Dual-laser micro-molecular tagging velocimetry (μMTV) for internal gaseous flows on the microscale has been successfully demonstrated. MTV is a non-intrusive optical technique suitable for gaseous flow measurement by using molecules as tracers. In our dual-laser μMTV technique, seeded NO2 molecules in a flow were tagged by photodissociation, producing NO molecules that can be distinguished from surrounding molecules. The tagged NO molecules were traced and visualized by laser-induced fluorescence. However, the fluorescence was in the deep ultraviolet region, and a reflective objective with a finite conjugate optical system was employed for imaging on the microscale. The seeded and tagged molecules of NO2 and NO are stable in the gas phase at around room temperature and atmospheric pressure. Thus, this technique is free from condensation at the walls and is feasible for measurements of internal gaseous flow on the microscale. To demonstrate the validity of our dual-laser μMTV technique, the cross-sectional flow velocity profile in a rectangular microchannel and flow velocities in a micronozzle were measured and compared with numerical results.

We describe the rearrangement of a carbamoylepoxy 4,5α-epoxymorphinan derivative that provided a novel 4,5α-epoxymorphinan derivative with an oxazatricyclodecane structure via an oxabicyclo[2.2.2]octane intermediate. We proposed the mechanism of the rearrangement reaction based on results observed in different deprotonation conditions. Epimerization occurred during rearrangement under reversible, but not irreversible, deprotonation conditions. The rearrangement product had a novel fundamental structure with moderate affinities for opioid receptors (Ki (μ)=47.7 nM, Ki (δ)=174.6 nM, and Ki (κ)=248.1 nM). Thus, the rearrangement products might have high potency as opioid ligands.

Whole body positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) has been widely used in various malignancies, but the clinical value of FDG-PET for endometrial cancer has not been fully investigated. The purpose of this study was to evaluate the usefulness of FDG-PET for preoperative evaluation of endometrial cancer. Forty female patients suspected of having endometrial cancer were included in this study. All patients underwent an FDG-PET or PET/CT scan, and images were interpreted visually. The diagnostic performance in detecting the primary tumor, regional nodal status, and distant metastasis was determined. In addition, the usefulness of PET was assessed in terms of additional information and clinical impact for therapeutic management. Of 40 patients, 30 were histologically confirmed to have endometrial cancer. The patient-based sensitivity and specificity of FDG-PET for primary tumors were 83 and 100%, respectively, and 100 and 100%, respectively, for nodal metastases. There were 12 distant metastases in 6 patients and two second primary cancers in two patients, which were all accurately diagnosed by PET on a patient-basis. PET yielded 12 additional findings in 10 patients, and had a bearing on the therapeutic management of four patients, including one patient with recurrent breast cancer. FDG-PET had a reasonably high diagnostic accuracy in endometrial cancer. Although the number of cases with clinical impact was limited, additional information by PET was obtained in one-third of the cases.

Purpose: This study was designed to investigate the specific cerebral blood flow (CBF) pattern in patients with idiopathic normal-pressure hydrocephalus (iNPH) and a predictive value for shunt responsiveness in a multicenter study (Study of Idiopathic Normal-Pressure Hydrocephalus on Neurological Improvement: SINPHONI). Methods: Eighty-four iNPH patients underwent shunt operations using MRI selection criteria from the SINPHONI and were subjected to CBF single photon emission computed tomography (SPECT). The perfusion patterns on SPECT were classified: anterior-dominant CBF reduction type (A type), posterior-dominant CBF reduction type (P type), and mixed or diffuse CBF reduction type (M type). The predictive value of the CBF pattern for favorable shunt outcome was evaluated. Results: Favorable outcomes were obtained in 76% (64/84) of patients, and shunt responsiveness was achieved in 85% (71/84) of patients. Areas of severely reduced relative CBF were demonstrated around the corpus callosum and in the sylvian fissure area, which included the effects of dilatations of the ventricles and sylvian fissures and relatively increased perfusion in the medial and lateral frontal, parietal, and occipital areas at high convexity. Forty-nine (58%) cases were A type, 25 (30%) cases were M type, and 10 (12%) cases were P type. A, M, and P type cases exhibited 83, 84, and 90% positive predictive values for shunt responsiveness, respectively. Mean modified Rankin scale and Mini-Mental State Examination scores of the A type group were significantly better than those of other groups. Conclusion: The iNPH patients showed various patterns of CBF reduction, but there was no significant difference in the predictive value among the three patterns, though CBF reduction patterns may suggest a severe condition of iNPH.

A new method has been developed for diffusible tracers, to quantify CBF at rest and after pharmacological stress from a single session of dynamic scans with dual bolus administration of a radiotracer. The calculation process consisted of three steps, including the procedures of incorporating background radioactivity contaminated from the previous scan. Feasibility of this approach was tested on clinical SPECT studies on 16 subjects. Two sequential SPECT scans, 30 min apart, were carried out on each subject, after each of two split-dose administrations of 111 MBq IMP. Of these, 11 subjects received acetazolamide at 10 min before the second IMP injection. Additional PET scans were also carried out on 6 subjects on a separate day, at rest and after acetazolamide administration. The other 5 subjects were scanned only at rest during the whole study period. Quantitative CBF obtained by this method was in a good agreement with those determined with PET (y(ml/100 g/min) = 1.07 × (ml/100 g/min) − 1.14, r = 0.94). Vasareactivity was approximately 40% over the whole cerebral area on healthy controls, which was consistent with a literature value. Reproducibility of CBF determined in the rest–rest study was 1.5 ± 5.7%. Noise enhancement of CBF images, particularly the second CBF, was reduced, providing reasonable image quality. Repeat assessment of quantitative CBF from a single session of scans with split-dose IMP is accurate, and may be applied to clinical research for assessing vascular reactivity in patients with chronic cerebral vascular disease.

Reports indicate that acetazolamide (ACZ) induces the vasodilation of all vessels in animal models, as well as in small and medium kidney vessels in animal models. However, the effect of ACZ on the renal circulation of patients with essential hypertension remains unknown. In this study we examined the effects of a carbonic anhydrase inhibitor, acetazolamide (ACZ), on the renal circulation of patients with essential hypertension.We directly infused 1000 mg of ACZ into the main renal arteries of 10 patients with essential hypertension who had undergone cardiac catheterization. We then evaluated the effects of ACZ upon heart rate, renal artery blood pressure (BP), renal artery cross-sectional area, renal Doppler blood flow velocity, renal blood flow (RBF), and renal vascular resistance (RVR).The infusion of ACZ was not associated with any significant changes in heart rate or in systolic or diastolic BP. However, the velocity-time integral was increased by 11.1% +/- 7.2%, from 17.6 +/- 1.8 to 20.0 +/- 3.7 cm (P = .009); RBF was increased by 39% +/- 21%, from 300 +/- 43 to 422 +/- 96 mL/min/m(2) (P = .002); and RVR was reduced by 38% +/- 20% from 24,351 +/- 2,291 to 17,651 +/- 2,731 dynes.sec.cm(-5) (P.01). In contrast the cross-sectional area of the renal artery did not change.The results of the present study demonstrated that ACZ has a potent vasodilatory effect on the renal circulation of patients with essential hypertension, leading to an obvious decrease in RVR and an increase in RBF.

We investigated a new method for the synthesis of [15O]CO and [15O]CO2 that did not require heating, which might be useful for rapid supply in clinical use. The target gas, N2 with a small amount of added CO, was irradiated with deuteron to give [15O]CO. The [15O]CO2 was produced by passing a mixture of the purified [15O]CO and dry O2 through a manganese dioxide–cupric oxide (MnO2–CuO) catalyst at room temperature. The chemical yields of [15O]CO and [15O]CO2 of the new method were 4.5±0.1 and 4.0±0.1 MBq/ml, respectively, and were higher than those of conventional methods (1.9±0.1 MBq/ml of [15O]CO and 3.6±0.1 MBq/ml of [15O]CO2). The radiochemical purities of both [15O]CO and [15O]CO2 were over 99.9%. Each quality of [15O]CO and [15O]CO2 was suitable for clinical PET. The new method would remarkably shorten the preparation time for [15O]CO and [15O]CO2 production. Namely, the start of inhalation of the [15O]gases is not restricted by the production procedure of [15O]CO and [15O]CO2.

Background— Increasing evidence points to a role for circulating endothelial progenitor cells, including populations of CD34- and CD133-positive cells present in peripheral blood, in maintenance of the vasculature and neovascularization. Immature populations, including CD34-positive cells, have been shown to contribute to vascular homeostasis, not only as a pool of endothelial progenitor cells but also as a source of growth/angiogenesis factors at ischemic loci. We hypothesized that diminished numbers of circulating immature cells might impair such physiological and reparative processes, potentially contributing to cerebrovascular dysfunction. Methods and Results— The level of circulating immature cells, CD34-, CD133-, CD117-, and CD135-positive cells, in patients with a history of atherothrombotic cerebral ischemic events was analyzed to assess possible correlations with the degree of carotid atherosclerosis and number of cerebral infarctions. There was a strong inverse correlation between numbers of circulating CD34- and CD133-positive cells and cerebral infarction. In contrast, there was no correlation between the degree of atherosclerosis and populations of circulating immature cells. Analysis of patients with cerebral artery occlusion revealed a significant positive correlation between circulating CD34- and CD133-positive cells and regional blood flow in areas of chronic hypoperfusion. Conclusions— These results suggest a possible contribution of circulating CD34- and CD133-positive cells in maintenance of the cerebral circulation in settings of ischemic stress. Our data demonstrate the utility of a simple and precise method to quantify circulating CD34-positive cells, the latter providing a marker of cerebrovascular function.

Background and Purpose— Perfusion-weighted magnetic resonance imaging (PWI) is a reliable and semiquantitative method for estimating cerebral hemodynamics. We sought to evaluate the potential of PWI for assessing cerebral blood flow (CBF) and metabolism compared with positron emission tomography (PET) in patients with chronic occlusive carotid disease. Methods— In 24 patients with chronic unilateral occlusive carotid disease, time-to-peak (TTP) delay (TTP-D) measured by PWI was compared with CBF, cerebral blood volume (CBV), and oxygen extraction fraction (OEF) obtained by PET. TTP indicates the time from the start of PWI to the bolus peak. TTP-D indicates the difference in TTP values between the occlusive and contralateral hemispheres. TTP-D was compared between patients with normal and reduced CBF/CBV and also between patients with normal and elevated OEF. Results— TTP-D in patients with reduced CBF/CBV was significantly longer than that in patients with normal CBF/CBV (3.4±1.8 versus 1.4±0.7 seconds; P r =0.710, P P Conclusions— TTP-D ≥4 seconds is considered to indicate a high risk of hemodynamic failure. The measurement of TTP-D by PWI appears to provide important clinical information for evaluating cerebral hemodynamics in chronic occlusive carotid disease.

The present study examines whether or not baseline and acetazolamide (ACZ) Tc-99m MAG3 renography can assess renal blood flow reserve.Renography proceeded for 50 min after sequential injections of 370 MBq Tc-99m MAG3 for baseline renography and 10 min after a 1,000 mg injection of ACZ for ACZ renography. Effective renal plasma flow of renal cortex (cERPF) in each kidney and the percentage change in cERPF of those parameters (deltaERPF) were obtained before and after the administration of ACZ in 10 subjects without hypertension or diabetes (normal group), in 10 with essential hypertension (hypertensive group) and in 10 who had Type 2 diabetes with hypertension (diabetic group). A placebo test was performed in the 10 without hypertension or diabetes using distilled water instead of ACZ (placebo group).The placebo test performed in the 10 without hypertension or diabetes using distilled water instead of ACZ indicated that the parameter variance between the two types of renogram was below 3.2%. The cERPF of baseline and ACZ Tc-99m MAG3 renography and deltaERPF in the normal, hypertensive and diabetic groups were 89 +/- 10 and 110 +/- 10 ml/min, 89 +/- 14 and 117 +/- 22 ml/min, 100 +/- 23 and 112 +/- 23 ml/min, respectively, and 24.5 +/- 13.5%, 26.0 +/- 9.7% and 12.3 +/- 11.1%, respectively. The difference in the cERPF value was significant in the normal and hypertensive groups whereas this did not change in the diabetic group before or after ACZ administration.We suggested that the deltaERPF determined by baseline and ACZ Tc-99m MAG3 renography is a useful parameter for assessing renal blood flow reserve.

Object. The purpose of this study was to evaluate cerebral hemodynamic and metabolic features in patients with arteriovenous malformations (AVMs) by using positron emission tomography (PET) scanning. Methods. Twenty-four patients with supratentorial cerebral AVMs participated in PET studies in which 15O inhalation steady-state methods were used. The authors recorded the values of regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), the regional oxygen extraction fraction (rOEF), and the regional cerebral metabolic rate of O2 (rCMRO2) at three designated regions of interest (ROIs) in each patient. These ROIs included perilesional (ROI-p), ipsilateral remote (ROI-i), and contralateral symmetrical (ROI-c) brain regions. To identify the factors that exert a direct effect on the hemodynamics of brains affected by AVM, we also separated the lesions according to their size and flow type shown on angiograms, and grouped the patients according to the presence or absence of progressive neurological deficits. We then compared the PET parameters at different ROIs in individual patients and evaluated the mean values obtained for all 24 patients according to AVM flow type and size, and the presence or absence of progressive neurological deficits. Conclusions. Overall, mean rCBV and rOEF values were significantly higher in ROI-p than in ROI-c (p = 0.00046 and p = 0.015, respectively). No significant differences were seen between the ROI-i and ROI-c with respect to rCBF, rCBV, and rOEF. Mean rCMRO2 values were similar in the three ROIs; however, the mean rCBF was significantly lower in the ROI-p than in the ROI-c in patients with high-flow AVMs (p = 0.019), large AVMs (p = 0.017), and progressive neurological deficits (p = 0.021). Furthermore, the mean rOEF values were significantly higher in the ROI-p than in the ROI-c in patients with high-flow AVMs (p = 0.005), large AVMs (p = 0.019), and progressive neurological deficits (p = 0.017). The PET studies revealed hemodynamic impairment characterized by decreased rCBF and increased rOEF and rCBV values in the ROI-p of patients with large, high-flow AVMs regardless of whether they exhibited progressive neurological deficits.

However, extracranial and intracranial arterial bypass surgery (EC/IC BYPASS) was denied by the randomized study, some patients may be suitable for surgery after selecting areas of misery perfusion. Steady-state O-15 positron emission tomography (PET) showed cerebral blood flow of 31.6±4.1 (ml/100 g/min) with acetazolamide reactivity of 30.6±5.4 (%) in misery perfused areas. The authors examined whether or not patients could be selected for surgery through combining cerebral blood flow (CBF) measurements with vasoreactivity determined by I-123 IMP (IMP; N-isopropyl-p-[I-123]-iodoamphetamine) single-photon emission-computed tomography (SPECT), which has good linearization at high flow ranges. Cerebral blood flow was quantified immediately after PET in 24 patients by counting I-123 IMP in arterial blood 10 min after injection. The CBF in the middle-cerebral arterial territories (MCA) was obtained by selecting regions of interest and comparing the fit between O-15 H2O and I-123 IMP using a nonlinear PS model curve. In 48 MCA areas, the CBF correlation between brain PET and IMP brain SPECT was close according to the equation, PET=12.4+0.46×IMP; r=0.743 (p

Desired/undesired speech discrimination is as important as speech/non-speech discrimination to achieve useful applications such as speech interfaces and teleconferencing systems. Conventional methods of voice activity detection (VAD) utilize the directional information of sound sources to distinguish desired from undesired speech. However, these methods have to utilize multiple microphones to estimate the directions of sound sources. Here, we propose a new method to discriminate desired from undesired speech with a single microphone. We assumed that the desired talkers would be close to the microphone, and the proposed method could distinguish close/distant-talking speech from observed signals based on the kurtosis of the linear prediction (LP) residual signals. The experimental results revealed that the proposed method could distinguish close-talking speech from distant-talking speech within a 10% equal error rate (EER) in ordinary reverberant environments with less processing time.

The purpose of this study was to determine whether pretreatment quantitative and visual parameters seen on PET/CT using (18)F-FDG add prognostic information for clinical staging in patients with head and neck cancer.We enrolled 108 patients with histologically proven oral, oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinomas who underwent FDG PET/CT before treatment and, later, definitive therapy in our study. PET/CT parameters-maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and uptake pattern (sphere-shaped or ring-shaped)-were recorded. The prognostic value of these parameters was evaluated using univariate and multivariate Cox regression analyses.In the univariate analysis, all of the FDG PET/CT parameters--SUVmax (10 g/mL) of the primary tumor, MTV (20 cm(3)), TLG (70 g), and uptake pattern (ring-shaped)--were significantly associated with negative effects on disease-specific survival (DSS) and disease-free survival (DFS). In the multivariate analysis, the MTV and uptake pattern remained associated with DSS after corrections for the Union for International Cancer Control (UICC) stage and definitive therapy (p = 0.023 and0.001, respectively). Another multivariate model that included MTV as a continuous variable, uptake pattern, and UICC stage showed that the uptake pattern remained significantly associated with DSS, whereas the association between DSS and MTV was not significant (p0.001 and = 0.332, respectively).Our data indicate that the pretreatment PET/CT parameters had prognostic value. In particular, a qualitative factor, uptake pattern, provided better prognostic information to the clinical staging of head and neck squamous cell carcinomas than the other PET/CT parameters.

The authors report abnormal Tc-99m sestamibi (MIBI) and Tl-201 uptake in a 62-year-old patient with histologically and biochemically proved myeloma. Tl-201 imaging was undertaken for tumor evaluation, and 3 days later a Tc-99m MIBI study showed diffuse and focal marrow uptake with focal skull lesions, whereas Tl-201 did not show skull lesions. After treatment, follow-up Tc-99m MIBI whole-body imaging was performed and the marrow uptake was decreased.

Superficial temporal artery - middle cerebral artery (STA-MCA) bypass surgery might improve the cerebral blood flow (CBF) but fail to reduce the risk of post-surgical events such as ischaemic stroke. In this study, we studied retrospectively whether the risk of post-surgical events corresponded to the change in resting CBF and/or the change in vasoreactivity observed before and after STA-MCA surgery using N-isopropyl-I-123-p-iodoamphetamine (123I-IMP) brain single-photon emission tomography (SPET). 123I-IMP brain SPET images obtained at rest and following acetazolamide challenge both before and after STA-MCA surgery were studied in 30 patients. Resting CBF was estimated semiquantitatively using the resting count ratios of the middle cerebral artery (MCA) area to the cerebellum. Acetazolamide c hallenge was assumed to result in an average increase in flow of 40% in the cerebellum. The vasoreactive response was then estimated as the ratio of the change in counts (acetazolamide - rest) to the resting cerebellar counts multiplied by 1.4. We classified 14 patients (50.5 +/- 19.3 years) into group I, who h a change in their resting CBF from before to after surgery of10%, and 16 patients (54.0 +/- 18.8 years) into group II, who had a change in their resting CBF from before to after surgery of ¿leq10%. Oxygen-15 positron emission tomography (PET) studies were performed in five patients from group I and five patients from group II. One post-surgical event occurred in group I while there were eight post-surgical events in group II (P0.05). Resting CBF improved by 20.4% +/- 7.5% in group I and by 0.9% +/- 6.9% in group II patients after surgery (P0.001). No significant difference in the improvement in vasoreactivity was observed between group I patients (32.6% +/- 17.7%) and group II patients (24.6% +/- 15.6%) following surgery. Patients in the group I PET subset showed normalization of oxygen extraction fraction (OEF) from 0.59 +/- 0.09 before surgery to 0.46 +/- 0.06 after surgery (P0.05), while patients in the group II PET subset showed no statistical difference in OEF before surgery (0.58 +/- 0.14) and after surgery (0.54 +/- 0.05). We conclude that the outcome of STA-MCA bypass surgery can be predicted by the improvement in resting CBF but not by the improvement in vasoreactivity.

Luxury perfusion characterized by depressed metabolism compared with CBF might be changed by decreasing cerebral perfusion pressure during the sitting position. A 77-yr-old man with subacute cerebral infarction was studied with brain X-ray computed tomography (CT), raise-up test with 99mTc-d,1-hexamethylpropyleneamine oxime (HMPAO) brain single photon emission tomography (SPECT) and positron emission tomography (PET). Brain X-ray CT revealed a low-density area in the left middle cerebral artery (MCA) anterior area. Raise-up 99mTc-HMPAO brain SPECT revealed decreased uptake in the left MCA anterior area in the sitting position and subsequent supine 99mTc-HMPAO brain SPECT revealed hot accumulation there. PET study in the supine position demonstrated some differences between CBF and the cerebral metabolic rate for oxygen in the left MCA anterior area, indicating luxury perfusion. CBF in the area of luxury perfusion might be decreased during the sitting or standing position and increased during the supine position by dysautoregulation of the cerebral vessels in the luxury perfusion during the subacute infarct.

In an investigation of myocardial metabolic abnormalities in hypertrophic myocardium, the myocardial glucose metabolism was evaluated with F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in 32 patients with hypertrophic cardiomyopathy, and the results were compared with those in 9 patients with hypertensive heart disease. F-18-FDG PET study was performed in the fasting and glucose-loading states. The myocardial regional %dose uptake was calculated quantitatively. The average regional %dose uptake in the fasting state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was significantly higher than that in the patients with hypertensive heart disease (0.75 +/- 0.34%, 0.65 +/- 0.25%, and 0.43 +/- 0.22%/100 g myocardium, respectively). In contrast, the average %dose uptake in the glucose-loading state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was not significantly different from that in patients with hypertensive heart disease (1.17 +/- 0.49%, 0.80 +/- 0.44% and 0.99 +/- 0.45%, respectively). The patients with apical hypertrophy had also low %dose uptake in the fasting state (0.38 +/- 0.21%) as in the hypertensive heart disease patients, so that the characteristics of asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy are considered to be high FDG uptake throughout the myocardium in the fasting state. Patients with apical hypertrophy are considered to belong to other disease categories metabolically. F-18-FDG PET study is useful in the evaluation of the pathophysiologic diagnosis of patients with hypertrophic cardiomyopathy.

Takayasu arteritis is a chronic inflammatory angiopathy involving the cerebral arteries. We performed upright and supine 99 Tc m -HMPAO brain single photon emission tomography (SPET) to investigate the cerebral perfusion pattern in eight patients with Takayasu arteritis, and we compared the results with those acquired using 123 I-IMP and acetazolamide in six patients. SPET images were evaluated visually and semi-quantitatively. Hypoperfusion was visually detected in all eight patients during the provocative upright test with 99 Tc m -HMPAO, and in three of six tested using acetazolamide and 123 I-IMP. Semiquantitative analysis revealed that the mean cortical-to-cerebellar ratio in the upright position was significantly changed compared to that in the supine position in the right frontal area (from 0.86 ± 0.07 to 0.91 ± 0.09; P < 0.05). Change was also seen in the left frontal area (from 0.85 ± 0.08 to 0.91 ± 0.08; P < 0.05). No significant change was seen in other cortical areas with the upright test or in any areas with the acetazolamide test. We postulate that reduced arterial compliance may cause frontal postural hypoperfusion in patients with Takayasu arteritis due to poor functioning of autoregulation and arterial stenosis or occlusion. We conclude that the provocative upright test with 99 Tc m -HMPAO brain SPET can detect abnormal patterns of cerebral perfusion in patients with Takayasu arteritis that might be missed by brain SPET using 123 I-IMP and acetazolamide.

We examined the feasibility of myocardial 123I-MIBG, 201TlCl, magnetic resonance imaging (MRI) and ultrafast computed tomography (UFCT) for the early detection of left ventricular involvements in 15 patients with arrhythmogenic right ventricular dysplasia (ARVD). Radionuclide ventriculography (RNV) and myocardial imaging with 123I-MIBG, 201TlCl, MRI and UFCT were performed in all 15 patients and in 10 normal subjects. The patients' scans were visually interpreted by two nuclear medicine physicians taking into consideration the extent score (ES) and severity score (SS) calculated by using the bull's-eye view in relation to normal data derived from the normal subjects. The left ventricular ejection fraction (LVEF) was measured by RNV. Fourteen (93%) patients showed regional 123I-MIBG defects, while 12 (80%) patients showed regional 201TlCl defects. The ES and SS were higher in 123I-MIBG than 201TlCl (ES: 31.5 +/- 18.5 vs. 17.5 +/- 18.2, p0.01, SS: 34.8 +/- 42.2 vs. 16.9 +/- 37.5, p0.01). Abnormal UFCT and MRI findings suggesting fatty involvements of the LV myocardium were demonstrated in 7 patients (Group B), while 7 patients showed regional 123I-MIBG defects without abnormal UFCT and MRI findings (Group A). 123I-MIBG was significantly more sensitive than UFCT and MRI (p0.05), although one patient, an exception, showed abnormal UFCT findings for the apex of the LV myocardium without abnormal 123I-MIBG and MRI findings. The LVEF, as a measure of LV systolic function, was better preserved in Group A than in Group B (59.3 +/- 3.6 vs. 45.8 +/- 5.8, p0.01). The present findings indicated that myocardial imaging with 123I-MIBG sensitively detects myocardial damage in patients with ARVD in the early stage when cardiac systolic function is still preserved.

It is crucial to predict drug effectiveness in chronic disease, such as dilated cardiomyopathy (DCM), in which the left ventricular (LV) function might be improved by beta-blocker therapy. As the functional improvement effected by beta-blocker therapy takes more than 2 months, we investigated whether iodine-123 metaiodobenzylguanidine (123I-MIBG) imaging could be used to predict drug effectiveness. We studied 13 patients (11 men and two women; mean age, 43+/-13 years) with DCM and seven normal subjects (six men and one woman; mean age, 48+/-16 years). We obtained myocardial single-photon emission tomography (SPET) images 15 min and 4 h after administration of 123I-MIBG (111 MBq). Studies were performed in the patients with DCM before and 1 and 3 months after the administration of metoprolol and in the normal subjects. We calculated the regional 123I-MIBG washout rate (r-WR) in the SPET image, and the global 123I-MIBG washout rate (g-WR) and heart-mediastinum activity ratio (H/M) using the anterior planar image. We classified patients into those showing a/=5% increase in LV ejection fraction (LVEF) at 3 months compared with LVEF values before the treatment (group I, n=7) and those showing a5% increase in LVEF (group II, n=6). In group I, the r-WR values at pretreatment and at 1 month and 3 months of treatment, respectively, were 36%+/-19%, 29%+/-14%* and 25%+/-13%* in the anterior segment, 39%+/-17%, 33%+/- 17%** and 28%+/-17%* in the lateral segment, 36%+/- 16%, 31%+/-14%* and 22%+/-12%** in the septal segment and 40%+/-11%, 37%+/-19% and 31%+/-18%* in the inferior segment; the g-WR was 45%+/-11%, 43%+/-10% and 34%+/-9%*, respectively (* P0.05, ** P0.01 vs pretreatment). In group II, there were no significant changes in regional or global parameters during the 3-month period. In normal subjects, the r-WR values in each of the anterior, lateral, septal and inferior segments were significantly lower than those in groups I and II. These values were 18%+/-9%, 18%+/-15%, 20%+/-12% and 21%+/-15%, respectively. This study demonstrated that with regional assessment 123I-MIBG SPET imaging can be used to predict the functional improvement of LVEF at 1 month of beta-blocker therapy in patients with DCM.

✓ In patients with intracranial dural arteriovenous fistulas (AVFs), clinical symptoms and angiographic findings vary. The relevance of disturbed venous drainage to clinical symptoms and prognosis has been recognized. However, the roles of cerebral hemodynamics and metabolism, which are impaired by shunt flow or disturbed venous drainage, have not been fully evaluated. The authors studied the cerebral hemodynamic and metabolic status in 10 patients with intracranial dural AVFs using positron emission tomography (PET) scanning. Ten patients with dural AVFs underwent a PET study before treatment. The regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rOEF), regional cerebral metabolic rate of oxygen (rCMRO2), and regional cerebral blood volume (rCBV) were measured using the 15O-labeled gas inhalation steady-state method. The PET parameters that were obtained were analyzed and compared with the patients' neurological and angiographic findings. In six of the 10 patients, a PET study was also performed after treatment. Before treatments, all four patients with cerebral symptoms showed a severe reduction in rCBF and a mild elevation in the rOEF. The areas showing reduced rCBF corresponded with areas in which retrograde venous drainage into the cortical veins and delayed parenchymal circulation were seen on angiograms. In another two patients with occlusion of the affected sinus and/or retrograde drainage into the cortical veins, mild abnormalities were demonstrated in rCBF mapping. In the remaining four patients, all PET parameters except rCBV were within normal limits and venous flow was not impaired on the angiograms. In four patients who underwent surgical excision or transvenous embolization of the affected sinus, the cerebral hemodynamics and metabolism were improved, as were the clinical symptoms. In two patients who underwent transarterial embolization of the feeding vessels only or craniotomy, no hemodynamic improvement was achieved. Our results indicate that hemodynamic insufficiency detected by the PET study corresponded well with cerebral symptoms and angiographic findings of retrograde venous drainage into the cortical veins and delayed parenchymal circulation, but not with sinus occlusion or arterial blood supply. Eradication or prevention of retrograde venous drainage from the affected sinus into the cortical veins should be a treatment goal in patients with dural AVFs.

We report on a 47-year-old woman who experienced an Eisenmenger reaction (mean pulmonary artery pressure: 86 mm Hg) induced by atrial septal defect. Radionuclide myocardial scans with 99mTc-MIBI and 123I-BMIPP showed increased uptake to the right ventricular myocardium, whereas the 123I-MIBG scan disclosed no uptake to the right ventricular myocardium. The scans showed no apparent abnormality in the left ventricular myocardium. These findings suggest that the right ventricular myocardium was viable but denervated due to severe pulmonary hypertension. The mechanism of right ventricular failure may be closely related to sympathetic denervation.

OBJECTIVE : When the efficacy of extracranial/intracranial bypass surgery is discussed, can we include the patients with extensive collateral circulation through the bypass and those with poor collateral circulation in the same group ? The bypass function should be determined not by the patency of the bypass but by the extent of collateral circulation through the bypass. We retrospectively analyzed our patients to determine whether the extent of bypass flow can be predicted from the results of preoperative studies. METHODS : In 51 hemispheres of 44 consecutive patients who underwent extracranial/intracranial bypass surgery, correlation between the extent of bypass flow and the preoperative results of angiographic and stimulated cerebral blood flow studies were investigated. RESULTS : The bypass function is highly predictable with the aid of preoperative studies. In 11 hemispheres that showed both retrograde spontaneous circulation via leptomeningeal anastomoses and decreased reactivity to acetazolamide of cerebral blood flow in an area distal to the arterial lesion, collateral circulation through the bypass developed well and reactivity to acetazolamide improved. In all of 13 hemispheres that showed normal reactivity to acetazolamide, the bypass was patent but the collateral circulation did not develop well. In only 4 of 24 hemispheres with spontaneous antegrade circulation distal to the lesion was there satisfactory collateral circulation through the bypass. CONCLUSION : Our results indicate that improvement of the hemodynamic status by bypass surgery should be expected only in patients with both spontaneously developed leptomeningeal anastomoses and decreased reactivity to acetazolamide.

Conventional near-field talker localization methods with microphone-array calculate spatial spectrum in each scanning position of discretized space and each frequency. Hence, elapsed time is increased and real-time processing is difficult. Real-time processing is important for achieving the natural interaction with the speech interfaces. To overcome this problem, we newly propose a talker localization method based on Multi-resolution Scanning in Frequency Domain (MSFD). MSFD utilizes lower spatial resolution in the lower frequency band and higher spatial resolution in the higher frequency band to reduce elapsed time. We also propose a calculation method for suitable spatial resolution at each frequency on the basis of the variances of phase differences among microphones. The results of evaluation experiment indicated that the proposed MSFD could reduce the elapsed time without degrading the localization accuracy.

O—Si bonds in various alkyl and aryl silyl ethers are efficiently cleaved by a new SO3H silica gel on which alkylsulfonic acid group are immobilized.

We examined the safety and the clinical usefulness of oxygen-15 water produced by the automated synthesis system (Sumitomo Heavy Industries, type 01) by means of positron emission tomography (PET) . This clinical trial involved 60 patients with various diseases. No side effects were observed by subjective and objective symptoms, physical findings, and laboratory tests. In all 60 cases, the PET images of good quality were obtained. In 95% of the cases, PET provided equivalent or better clinical information compared with other clinical examinations. The overall assessment of the clinical usefulness demonstrated that the method was useful or extremely useful in 59 cases (98%) .

A 66-year-old man with an abdominal aortic aneurysm confirmed by CT had bilateral swelling of the lower extremities with pain radiating to the back. Radionuclide venography and pulmonary scintigraphy demonstrated occlusion of the inferior vena cava and multiple pulmonary emboli, with a hot spot in the liver. Surgery revealed a ruptured abdominal aortic aneurysm that occluded the inferior vena cava, fistula formation, and extensive thrombosis of the inferior vena cava proximal to the occlusion site. Radionuclide venography was useful in detecting venous obstruction and the collateral formation represented by the hot spot in the liver as complications of the ruptured abdominal aortic aneurysm, and in assessing the improvement of pulmonary embolism by medical therapy.

Percutaneous transvenous mitral commissurotomy (PTMC) has recently been used to treat mitral stenosis. The aim of this study was to evaluate the usefulness of radionuclide perfusion lung scanning in assessing the effect of PTMC on the relief of lung congestion. We studied 30 patients (7 males and 23 females, mean age 55 years). Perfusion lung scannings were performed within 1 week before and after PTMC. We calculated the ratio of activity in the upper quarter to that in the lower quarter of the right lung (U/L) as an index of lung congestion. After PTMC, the mean mitral valve area increased from 1.1 +/- 0.3 to 1.9 +/- 0.4 cm2, the mean left atrial pressure decreased from 14.8 +/- 6.3 to 9.1 +/- 3.5 mmHg, the mean pulmonary artery pressure decreased from 22.7 +/- 8.6 to 17.4 +/- 6.3 mmHg, and the U/L ratio decreased significantly from 0.89 +/- 0.40 to 0.68 +/- 0.24 (p < 0.0001). The U/L ratio showed greater improvement (4.5%) in patients whose NYHA class improved (n = 19) than in those whose NYHA class did not improve after PTMC. The U/L ratio was closely related to mitral valve area, and left atrial and pulmonary artery pressures. The change in the U/L ration before and after PTMC also reflected symptomatic improvement. In conclusion, U/L ratios obtained from perfusion lung scannings before and after PTMC reflect mitral valve area and pressures, and can be used to assess lung congestion relief after PTMC.

Single photon emission computed tomography (SPECT) with acetazolamide challenge has increasingly been used for evaluating hemodynamic reserve in stroke patients. The accuracy of this test, however, has not been validated with positron emission tomography (PET). In 14 patients who had occlusive disease of the internal carotid artery or the trunk of the middle cerebral artery (MCA) with minimal or no infarction on computed tomography (CT) and magnetic resonance imaging (MRI), we compared acetazolamide reactivity on SPECT with N-isopropyl- p-[123I]-iodoamphetamine to hemodynamic parameters determined with gas inhalation labeled 15O steady-state PET studies. The asymmetry index (AI)—i.e., the percentage of the activity rate of the ischemic MCA territory versus the contralateral one, was determined by SPECT. Acetazolamide reactivity expressed as ΔAI, or change in AI after acetazolamide challenge, was significantly lower in seven patients than −8.4%, the lower limit of the 95% confidence interval for the normal reactivity. Values of ipsilateral CBF, cerebral blood volume (CBV)/CBF, and oxygen extraction fraction (OEF) and contralateral OEF were significantly different between patients with normal and reduced acetazolamide reactivity. Values of AAI were correlated with OEF ( r = −0.87; p < 0.001) and CBV/CBF ( r = −0.56; p < 0.05). All patients with OEF >0.52, the mean + 2 SD calculated from five normal volunteers, also had reduced acetazolamide reactivity, while the patients with normal OEF values had normal reactivity. The present study has demonstrated that SPECT studies with an acetazolamide challenge can detect the Stage II hemodynamic failure.

SPECT can provide valuable diagnostic and treatment response information in large-scale multicenter clinical trials. However, SPECT has been limited in providing consistent quantitative functional parametric values across the centers, largely because of a lack of standardized procedures to correct for attenuation and scatter. Recently, a novel software package has been developed to reconstruct quantitative SPECT images and assess cerebral blood flow (CBF) at rest and after acetazolamide challenge from a single SPECT session. This study was aimed at validating this technique at different institutions with a variety of SPECT devices and imaging protocols. Methods: Twelve participating institutions obtained a series of SPECT scans on physical phantoms and clinical patients. The phantom experiments included the assessment of septal penetration for each collimator used and of the accuracy of the reconstructed images. Clinical studies were divided into 3 protocols, including intrainstitutional reproducibility, a comparison with PET, and rest–rest study consistency. The results from 46 successful studies were analyzed. Results: Activity concentration estimation (Bq/mL) in the reconstructed SPECT images of a uniform cylindric phantom showed an interinstitution variation of ±5.1%, with a systematic underestimation of concentration by 12.5%. CBF values were reproducible both at rest and after acetazolamide on the basis of repeated studies in the same patient (mean ± SD difference, −0.4 ± 5.2 mL/min/100 g, n = 44). CBF values were also consistent with those determined using PET (−6.1 ± 5.1 mL/min/100 g, n = 6). Conclusion: This study demonstrates that SPECT can quantitatively provide physiologic functional images of rest and acetazolamide challenge CBF, using a quantitative reconstruction software package.

In order to evaluate the lung and brain uptake of 99mTc ethyl cysteinate dimer (99mTc-ECD) and N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP), alternative body scans were carried out in 15 cases of cerebrovascular disease. The biodistribution of 99mTc-ECD was 5.5 +/- 0.7%, 3.8 +/- 0.7% in the brain; 13.1 +/- 3.7%, 2.2 +/- 1.2%, in the lung at 15 min and at 4 hours, respectively, whereas that of 123I-IMP was 3.9 +/- 1.4%, 5.0 +/- 1.0% in the brain; 32.2 +/- 7.6%, 12.7 +/- 3.3%, in the lung at 15 min and at 4 hours, respectively. 99mTc-ECD accumulated in comparatively high amounts in the brain but remained low in the lung in the early image compared to 123I-IMP. However there was a high inverse correlation between brain and lung uptake of 123I-IMP (r = -0.82), but not of 99mTc-ECD (r = -0.18). We concluded that 99mTc-ECD had a better biodistribution in terms of low lung accumulation than 123I-IMP in brain SPECT.

It is important in patient management to evaluate coronary arterial involvement in aortitis syndrome. Twenty-one cases of aortitis syndrome who experienced chest pain were examined using exercise thallium scintigraphy. The patients were divided into 4 groups according to the angiographic findings. There were five patients with left main coronary arterial involvement (group A), four with left or right coronary arterial involvement (group B), nine with aortic regurgitation (group C), and three with pulmonary arterial involvement (group D). In groups A and B, all patients had positive ECGs and thallium perfusion defects. Group A patients showed extensive anterolateral perfusion defects, which were compatible with left main coronary arterial involvement. Groups C and D patients, who had normal coronary arteries, showed no remarkable perfusion defects although five had positive ECG findings. Thus, the sensitivity and specificity of exercise scintigraphy for detection of myocardial ischemia were 9/9 and 12/12, while those of stress ECG were 9/9 and 7/12 (58%), respectively. it is recommended that exercise thallium scintigraphy be used for detecting clinically occult but significant coronary arterial involvement in aortitis syndrome with chest pain.

A conformational analysis of kappa opioid receptor agonists, TRK-820 and U-50,488H indicated an active conformation of TRK-820 in which the C-ring was in the boat form with the 14-OH interacting with the amide nitrogen. Based on the obtained active conformation of TRK-820, we designed and synthesized a novel kappa agonist KNT-63 with oxabicyclo[2.2.2]octane skeleton. KNT-63 showed profound antinociceptive effects via the kappa receptor which were as potent as that of TRK-820.