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Fujita W.,Kanazawa Medical University | Matsunari I.,The Medical and Pharmacological Research Center Foundation | Matsunari I.,Saitama University | Aoki H.,Kanazawa Medical University | And 2 more authors.
Annals of Nuclear Medicine | Year: 2016

Objectives: The aim of this study was to determine whether 11C-hydroxyephedrine (11C-HED) can predict adverse events including all-cause death in Japanese patients with left ventricular (LV) dysfunction. Background: Although 11C-HED PET has been used to assess cardiac sympathetic innervation in various disease conditions, data on their prognostic value are limited. Methods: Sixty patients (mean LVEF, 42 ± 14 %) with LV dysfunction (42 ischemic and 18 non-ischemic heart disease) underwent 11C-HED PET. Myocardial retention was calculated for 11C-HED PET as a measure of cardiac sympathetic neuronal integrity. Statistical analysis was performed using Cox proportional hazards regression and log-rank test. Results: Thirteen deaths (7 cardiac and 6 non-cardiac deaths) occurred during a mean follow-up period of 33 ± 23 months. The patients with death were associated with significantly lower 11C-HED retention (7.1 ± 2.1 vs 9.0 ± 2.4, p = 0.015) than those without death. The hazard ratio for global 11C-HED retention per unit (/min) was 0.762 (p = 0.039), which remained significant in multivariate analysis. When the patients were divided into the high (≥8.5) and low (<8.5) 11C-HED retention groups, the low 11C-HED retention group was associated with significantly poorer survival than the high 11C-HED retention group (p = 0.004). Conclusion: The low global 11C-HED retention is a marker of poor overall survival in patients with LV dysfunction in this study. © 2016 The Author(s)


Shima K.,Kanazawa University | Matsunari I.,The Medical and Pharmacological Research Center Foundation | Samuraki M.,Kanazawa University | Chen W.-P.,The Medical and Pharmacological Research Center Foundation | And 8 more authors.
Neurobiology of Aging | Year: 2012

To test the hypothesis that Alzheimer's disease (AD) patients with posterior cingulate/precuneus (PCP) atrophy would be a distinct disease form in view of metabolic decline. Eighty-one AD patients underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and structural magnetic resonance imaging (MRI). Positron emission tomography and voxel-based morphometry (VBM) Z-score maps were generated for the individual patients using age-specific normal databases. The patients were classified into 3 groups based on atrophic patterns (no-Hipp-PCP, atrophy in neither hippocampus nor PCP; Hipp, hippocampal atrophy; PCP, PCP atrophy). There were 16 patients classified as no-Hipp-PCP, 55 as Hipp, and 10 as PCP. The Mini Mental State Examination (MMSE) score was similar among the groups. The greater FDG decline than atrophy was observed in all groups, including the no-Hipp-PCP. The PCP group was younger, and was associated with a greater degree of FDG decline in PCP than the others. There are diverse atrophic patterns in a spectrum of AD. In particular, a subset of patients show PCP atrophy, which is associated with greater metabolic burden. © 2012 Elsevier Inc.


Samuraki M.,Kanazawa University | Matsunari I.,The Medical and Pharmacological Research Center Foundation | Chen W.-P.,The Medical and Pharmacological Research Center Foundation | Shima K.,Kanazawa University | And 4 more authors.
Neurobiology of Aging | Year: 2012

Apolipoprotein E (ApoE) ε4 is known as a genetic risk factor for Alzheimer's disease (AD). This study investigated the prevalence of imaging abnormalities suggestive of AD in cognitively normal ApoE ε4 carriers using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and voxel-based morphometry (VBM). Forty-five cognitive normal ApoE ε4 allele carriers and 45 noncarriers underwent both FDG positron emission tomography and magnetic resonance imaging (MRI). A total of 90 normal database sets were generated for the individual 45 ε4 carriers and 45 noncarriers. Mean z-scores in the predefined AD-specific regions of interest (ROI) were calculated for each ε4 carrier and noncarrier using the individually defined normal database. The prevalence of AD-like hypometabolism and atrophy in the ε4 carriers was 8.9% and 17.7%, respectively, and did not differ significantly from those in the noncarriers (8.9%, 8.8%). The majority of ε4 carriers showed preserved FDG uptake or gray matter concentration. © 2012 Elsevier Inc.


Mizutani A.,Kanazawa University | Matsunari I.,The Medical and Pharmacological Research Center Foundation | Kobayashi M.,Kanazawa University | Nishi K.,Kanazawa University | And 5 more authors.
EJNMMI Physics | Year: 2015

Background: The aims of this study were (1) to evaluate the impact of injection dose, post-reconstruction filtering, and collimator choice on image quality of myocardial perfusion single-photon emission computed tomography (SPECT) using cadmium-zinc telluride (CZT) detectors and (2) to determine how these factors affect measured infarct size in the in vivo rat. Methods: Twenty-four healthy and eight myocardial infarct (MI) rats underwent myocardial perfusion SPECT imaging after injection of various doses (25 to 200 MBq) of 99mTc-tetrofosmin using a standard (STD) five-pinhole collimator and high-sensitivity (HS) five-pinhole collimator. Image quality score, contrast-to-noise ratio, sharpness index, coefficient of variation (CV), and measured defect size were assessed as measures of image quality. Results: The image quality score increased and CV decreased as a function of injection dose. The contrast-to-noise ratio increased and sharpness index decreased as a function of Gaussian kernel size. When STD and HS were compared, HS tended to show higher image quality score and lower CV than STD. The use of post-reconstruction filter significantly improved image quality score and lessened CV. The reproducibility of defect size measurements, as assessed by intraclass correlation coefficients (ICC), between the collimators was poor-to-moderate (ICC = −0.31~0.57) with low (25 MBq) injection dose and with no or light (1.5-mm kernel size) filtering, whereas it was good-to-excellent (ICC = 0.75~0.97) with high (200 MBq) dose or low dose with heavy (2.5-mm kernel size) filtering. The filtering-related reproducibility was poor (ICC = −0.18~0.17) for STD with low injection dose, whereas it was good-to-excellent (ICC = 0.79~0.89) for HS. Furthermore, there was a filtering-related underestimation of defect size particularly with the use of heavy smoothing. Conclusions: Appropriate imaging setting is important to obtain high quality images and thereby reliable measurements using a preclinical myocardial SPECT in the rat. When only a low injection dose (25 MBq) is allowed, we would recommend to use HS with light (1.5-mm kernel size) filtering. © 2015, Mizutani et al.; licensee Springer.


PubMed | The Medical and Pharmacological Research Center Foundation, Osaka University, Nagasaki University and Kanazawa University
Type: Journal Article | Journal: Annals of nuclear medicine | Year: 2016

Simultaneous acquisition of (99m)Tc and (123)I was evaluated using a preclinical SPECT scanner with cadmium zinc telluride (CZT)-based detectors.10-ml cylindrical syringes contained about 37MBq (99m)Tc-tetrofosmin ((99m)Tc-TF) or 37MBq (123)I-15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid ((123)I-BMIPP) were used to assess the relationship between these SPECT radioactive counts and radioactivity. Two 10-ml syringes contained 100 or 300MBq (99m)Tc-TF and 100MBq (123)I-BMIPP to assess the influence of (99m)Tc upscatter and (123)I downscatter, respectively. A rat-sized cylindrical phantom also contained both 100 or 300MBq (99m)Tc-TF and 100MBq (123)I-BMIPP. The two 10-ml syringes and phantom were scanned using a pinhole collimator for rats. Myocardial infarction model rats were examined using 300MBq (99m)Tc-TF and 100MBq (123)I-BMIPP. Two 1-ml syringes contained 105MBq (99m)Tc-labeled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) and 35MBq (123)I-labeled N--fluoropropyl-2-carbomethoxy-3-(4-iodophenyl) nortropane ((123)I-FP-CIT). The two 1-ml syringes were scanned using a pinhole collimator for mice. Normal mice were examined using 105MBq (99m)Tc-HMPAO and 35MBq (123)I-FP-CIT.The relationship between SPECT radioactive counts and radioactivity was excellent. Downscatter contamination of (123)I-BMIPP exhibited fewer radioactive counts for 300MBq (99m)Tc-TF without scatter correction (SC) in 125-150keV. There was no upscatter contamination of (99m)Tc-TF in 150-175keV. In the rat-sized phantom, the radioactive count ratio decreased to 4.0% for 300MBq (99m)Tc-TF without SC in 125-150keV. In the rats, myocardial images and radioactive counts of (99m)Tc-TF with the dual tracer were identical to those of the (99m)Tc-TF single injection. Downscatter contamination of (123)I-FP-CIT was 4.2% without SC in 125-150keV. In the first injection of (99m)Tc-HMPAO and second injection of (123)I-FP-CIT, brain images and radioactive counts of (99m)Tc-HMPAO with the dual tracer in normal mice also were the similar to those of the (99m)Tc-HMPAO single injection. In the first injection of (123)I-FP-CIT and second injection of (99m)Tc-HMPAO, the brain images and radioactive counts with the dual tracer were not much different from those of the (123)I-FP-CIT single injection.Dual-tracer imaging of (99m)Tc- and (123)I-labeled radiotracers is feasible in a preclinical SPECT scanner with CZT detector. When higher radioactivity of (99m)Tc-labeled radiotracers relative to (123)I-labeled radiotracers is applied, correction methods are not necessarily required for the quantification of (99m)Tc- and (123)I-labeled radiotracers when using a preclinical SPECT scanner with CZT detector.


PubMed | The Medical and Pharmacological Research Center Foundation, TU Munich, Kanazawa Medical University and Kanazawa University
Type: Journal Article | Journal: EJNMMI physics | Year: 2015

The aims of this study were (1) to evaluate the impact of injection dose, post-reconstruction filtering, and collimator choice on image quality of myocardial perfusion single-photon emission computed tomography (SPECT) using cadmium-zinc telluride (CZT) detectors and (2) to determine how these factors affect measured infarct size in the in vivo rat.Twenty-four healthy and eight myocardial infarct (MI) rats underwent myocardial perfusion SPECT imaging after injection of various doses (25 to 200MBq) of (99m)Tc-tetrofosmin using a standard (STD) five-pinhole collimator and high-sensitivity (HS) five-pinhole collimator. Image quality score, contrast-to-noise ratio, sharpness index, coefficient of variation (CV), and measured defect size were assessed as measures of image quality.The image quality score increased and CV decreased as a function of injection dose. The contrast-to-noise ratio increased and sharpness index decreased as a function of Gaussian kernel size. When STD and HS were compared, HS tended to show higher image quality score and lower CV than STD. The use of post-reconstruction filter significantly improved image quality score and lessened CV. The reproducibility of defect size measurements, as assessed by intraclass correlation coefficients (ICC), between the collimators was poor-to-moderate (ICC=-0.31~0.57) with low (25MBq) injection dose and with no or light (1.5-mm kernel size) filtering, whereas it was good-to-excellent (ICC=0.75~0.97) with high (200MBq) dose or low dose with heavy (2.5-mm kernel size) filtering. The filtering-related reproducibility was poor (ICC=-0.18~0.17) for STD with low injection dose, whereas it was good-to-excellent (ICC=0.79~0.89) for HS. Furthermore, there was a filtering-related underestimation of defect size particularly with the use of heavy smoothing.Appropriate imaging setting is important to obtain high quality images and thereby reliable measurements using a preclinical myocardial SPECT in the rat. When only a low injection dose (25MBq) is allowed, we would recommend to use HS with light (1.5-mm kernel size) filtering.


PubMed | The Medical and Pharmacological Research Center Foundation
Type: Journal Article | Journal: Nuclear medicine communications | Year: 2011

F-FDG PET with voxel-based statistical image analysis plays an important role in the diagnosis of Alzheimers disease (AD). However, the effect of an age-matched and sex-matched or mismatched normal database (NDB) on the diagnostic performance of F-FDG PET has not yet been investigated systematically. The aim of this study was to determine whether an age-matched and sex-matched NDB is necessary for the detection of AD using F-FDG PET.We generated 11 NDB sets for F-FDG PET, including six age-specific NDB sets consisting of participants ranging in age from 20 to 70 years, one age-non-specific NDB set, one age-matched NDB set, two sex-specific NDB sets, each consisting of 20 men or 20 women, and one sex-matched NDB set. The average z-scores in predefined AD-specific regions of interest of the PET images were calculated using those NDB sets and a receiver-operating characteristic analysis was carried out to assess the diagnostic performance of F-FDG PET to discriminate 46 patients with AD from 50 normal controls.There was no significant difference in each area under the receiver-operating characteristic curve using either age-matched/mismatched NDB sets or sex-matched/mismatched NDB sets.The diagnostic performance of F-FDG PET was rather insensitive to differences in age or sex in the NDB, indicating that exact age-matched or sex-matched NDB may not be essential for discriminating patients with AD from normal participants using F-FDG PET.


PubMed | The Medical and Pharmacological Research Center Foundation, TU Munich and Kanazawa Medical University
Type: Journal Article | Journal: Annals of nuclear medicine | Year: 2016

The aim of this study was to determine whether (11)C-hydroxyephedrine ((11)C-HED) can predict adverse events including all-cause death in Japanese patients with left ventricular (LV) dysfunction.Although (11)C-HED PET has been used to assess cardiac sympathetic innervation in various disease conditions, data on their prognostic value are limited.Sixty patients (mean LVEF, 4214%) with LV dysfunction (42 ischemic and 18 non-ischemic heart disease) underwent (11)C-HED PET. Myocardial retention was calculated for (11)C-HED PET as a measure of cardiac sympathetic neuronal integrity. Statistical analysis was performed using Cox proportional hazards regression and log-rank test.Thirteen deaths (7 cardiac and 6 non-cardiac deaths) occurred during a mean follow-up period of 3323months. The patients with death were associated with significantly lower (11)C-HED retention (7.12.1 vs 9.02.4, p=0.015) than those without death. The hazard ratio for global (11)C-HED retention per unit (/min) was 0.762 (p=0.039), which remained significant in multivariate analysis. When the patients were divided into the high (8.5) and low (<8.5) (11)C-HED retention groups, the low (11)C-HED retention group was associated with significantly poorer survival than the high (11)C-HED retention group (p=0.004).The low global (11)C-HED retention is a marker of poor overall survival in patients with LV dysfunction in this study.


PubMed | the Medical and Pharmacological Research Center Foundation and Kanazawa University
Type: Journal Article | Journal: Journal of Alzheimer's disease : JAD | Year: 2015

Microbleeds (MBs) are frequently observed in Alzheimers disease (AD); however, the relevance to AD pathophysiology has not been elucidated.We investigated correlation of MBs, especially cerebral amyloid angiopathy (CAA)-related MBs with cognitive function, gray matter volume, and glucose metabolism in AD.We performed magnetic resonance imaging including T2*-weighted imaging sequence for 206 patients with AD. Among them, 158 AD patients with no focal brain lesions except for MBs were investigated with cognitive tests, voxel-based morphometry, and 18F-fluorodeoxyglucose positron emission tomography in a cross-sectional observational study.Of the 158 patients with no hemorrhagic and/or ischemic stroke lesions except for MBs, 27 patients had MBs, in which 17 patients showed CAA-related MBs that located only in cortex/subcortex (CAA-related MBs), and 10 patients showed CAA-unrelated MBs that located in deep regions regardless of the presence of MBs in cortical/subcortical regions. There were slightly but significant differences in cognitive functions between the patients without MBs, those with CAA-related MBs, and those with CAA-unrelated MBs. MBs were recognized frequently in the occipital lobe in the patients with CAA-related MBs. The patients with CAA-related MBs showed gray matter atrophy in the temporal lobe and cerebellum, and glucose hypometabolism in the temporal lobe compared with those without MBs.Our results indicate that MBs, particularly CAA-related MBs would cause gray matter atrophy and glucose hypometabolism in AD.


PubMed | The Medical and Pharmacological Research Center Foundation, National Center for Global Health and Medicine, Mie University and Kanazawa University
Type: | Journal: EJNMMI research | Year: 2015

Tenascin-C (TNC), an extracellular matrix glycoprotein, is expressed transiently in distinct areas in association with active tissue remodeling. This study aimed to explore how ischemic postconditioning (PC) affects myocardial expression of TNC and ventricular remodeling using (125)I-labeled anti-TNC antibody ((125)I-TNC-Ab) in a rat model of ischemia and reperfusion.In control rats (n=27), the left coronary artery (LCA) was occluded for 30 min followed by reperfusion for 1, 3, 7, and 14 days. PC (n=27) was performed just after the reperfusion. At the time of the study, (125)I-TNC-Ab (1.0 to 2.5 MBq) was injected. Six to 9 h later, to verify the area at risk, (99m)Tc-MIBI (100 to 200 MBq) was injected intravenously just after the LCA reocclusion, with the rats sacrificed 1 min later. Dual tracer autoradiography was performed to assess (125)I-TNC-Ab uptake and area at risk. To examine the ventricular remodeling, echocardiography was performed 2 M after reperfusion in both groups.In control rats, (125)I-TNC-Ab uptake ratio at 1 day after reperfusion was 3.730.71 and increased at 3 days (4.650.87), followed by a significant reduction at 7 days (2.910.55, P<0.005 vs 3 days) and14 days (2.010.17, P<0.005 vs 1 and 3 days). PC attenuated the (125)I-TNC-Ab uptake throughout the reperfusion time from 1 to 14 days; 2.590.59 at 1 day, P<0.05: 3.100.42 at 3 days, P<0.005: 1.930.37 at 7 days, P<0.05: 1.400.07 at 14 days, P<0.001. In echocardiography, PC reduced the ventricular end-diastolic and systolic dimensions (1.000.06 cm to 0.830.14 cm (P<0.05) and 0.900.15 cm to 0.620.19 cm (P<0.05), respectively) and prevented a decline of ventricular percentage fractional shortening (10.53.7 to 28.210.7, P<0.005).These data indicate that (125)I-TNC-Ab imaging may be a way to monitor myocardial injury, the subsequent repair process, and its response to novel therapeutic interventions like PC by visualizing TNC expression.

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