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Objective: Perfusable tissue fraction (PTF) and myocardial flow reserve (MFR) from 15 O-water dynamic positron emission tomography (PET) are parameters of myocardial viability. However, myocardial motion causes errors in these values. We aimed to develop accurate estimation of PTF and MFR in ischemic lesions using an electro-cardiogram (ECG)-gated dynamic myocardial PET with 15 O-water., Methods: Twenty-seven patients with ischemic heart disease were enrolled. All patients underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). List mode 3D PET data and ECG signals were acquired using Philips Gemini TF64 instrument. For each scan, 500 MBq of 15 O-water was infused slowly for 2 min, and the dynamic data were scanned for 6 min. Both non-gated dynamic images and ECG-gated diastolic dynamic images were reconstructed. On the myocardial PET images of each patient, the entire myocardial region of interest (ROI) was set and divided into 17 segments. Myocardial blood flow in the resting state (rest MBF), hyperemic state (stress MBF), PTF, and MFR in each segment were estimated from both non-gated and ECG-gated dynamic PET images. Coronary arteriograms were obtained for all patients. In total, 128 normal segments without stenosis and 50 ischemic segments with > 90% stenosis were evaluated., Results: In the ischemic myocardial segments, the PTF with ECG-gated PET was estimated as significantly lower than that with non-gated PET (0.63 ± 0.09 vs. 0.72 ± 0.08 [mL/mL], p < 0.001). The ECG-gated PET estimated a significantly lower PTF in the ischemic segments than in the normal segments (0.63 ± 0.09 vs. 0.67 ± 0.07 [mL/mL], p < 0.01). In the normal segments, the ECG-gated PET detected no significant difference in MFR compared with those from the non-gated PET (2.15 ± 0.76 vs. 2.24 ± 0.79, p = 0.28). However, in the ischemic myocardial segments, the MFR with ECG-gated PET was estimated as significantly lower than that with the non-gated PET (1.23 ± 0.29 vs. 1.69 ± 0.71, p < 0.001). The ECG-gated PET presented a significantly higher inter-observer reproducibility of PTF and rest MBF than the non-gated PET (p < 0.01). Neither stress MBF nor MFR yielded significant differences in inter-observer reproducibility between the ECG-gated and non-gated PET., Conclusions: The ECG-gated dynamic 15 O-water PET suppressed the myocardial motion effect and resulted in a lower PTF and MFR in ischemic myocardial lesions than the non-gated PET. The ECG-gated PET seemed to be better than the conventional non-gated dynamic PET for the detection of ischemic myocardial lesion., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

We created a handmade 3D-printed air sampler to effectively collect live airborne bacteria, and determined which environmental factors influenced the bacteria. Bacterial colony forming units (CFUs) in the air samples (n = 37) were monitored by recording the environmental changes occurring over time, then determining the presence/absence of correlations among such changes. The bacterial CFUs changed sharply and were significantly correlated with the DNA concentrations, indicating that the captured bacteria made up most of the airborne bacteria. Spearman's rank correlation analysis revealed significant correlations between the bacterial CFU values and some environmental factors (humidity, wind speed, insolation, and 24-h rainfall). Similarly the significant associations of CFU with humidity and wind speed were also found by multiple regression analysis with box-cox transformation. Among our panel of airborne bacteria (952 strains), 70 strains were identified as soil-derived Bacillus via the production of Escherichia coli- and Staphylococcus aureus-growth inhibiting antibiotics and by 16S rDNA typing. Soil-derived protozoa were also isolated from the air samples. We conclude that the airborne bacteria mainly derived from soil can alter in number according to environmental changes. Our sampler, which was created by easy-to-customize 3D printing, is a useful device for understanding the dynamics of live airborne bacteria., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2021 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Deep learning technology is now used for medical imaging. YOLOv2 is an object detection model using deep learning. Here, we applied YOLOv2 to FDG-PET images to detect the physiological uptake on the images. We also investigated the detection precision of abnormal uptake by a combined technique with YOLOv2. Using 3,500 maximum intensity projection (MIP) images of 500 cases of whole-body FDG-PET examinations, we manually drew rectangular regions of interest with the size of each physiological uptake to create a dataset. Using YOLOv2, we performed image training as transfer learning by initial weight. We evaluated YOLOv2's physiological uptake detection by determining the intersection over union (IoU), average precision (AP), mean average precision (mAP), and frames per second (FPS). We also developed a combination method for detecting abnormal uptake by subtracting the YOLOv2-detected physiological uptake. We calculated the coverage rate, false-positive rate, and false-negative rate by comparing the combination method-generated color map with the abnormal findings identified by experienced radiologists. The APs for physiological uptakes were: brain, 0.993; liver, 0.913; and bladder, 0.879. The mAP was 0.831 for all classes with the IoU threshold value 0.5. Each subset's average FPS was 31.60 ± 4.66. The combination method's coverage rate, false-positive rate, and false-negative rate for detecting abnormal uptake were 0.9205 ± 0.0312, 0.3704 ± 0.0213, and 0.1000 ± 0.0774, respectively. The physiological uptake of FDG-PET on MIP images was quickly and precisely detected using YOLOv2. The combination method, which can be utilized the characteristics of the detector by YOLOv2, detected the radiologist-identified abnormalities with a high coverage rate. The detectability and fast response would thus be useful as a diagnostic tool., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Kawakami, Hirata, Furuya, Kobayashi, Sugimori, Magota and Katoh.)

Background: As the number of PET/CT scanners increases and FDG PET/CT becomes a common imaging modality for oncology, the demands for automated detection systems on artificial intelligence (AI) to prevent human oversight and misdiagnosis are rapidly growing. We aimed to develop a convolutional neural network (CNN)-based system that can classify whole-body FDG PET as 1) benign, 2) malignant or 3) equivocal., Methods: This retrospective study investigated 3485 sequential patients with malignant or suspected malignant disease, who underwent whole-body FDG PET/CT at our institute. All the cases were classified into the 3 categories by a nuclear medicine physician. A residual network (ResNet)-based CNN architecture was built for classifying patients into the 3 categories. In addition, we performed a region-based analysis of CNN (head-and-neck, chest, abdomen, and pelvic region)., Results: There were 1280 (37%), 1450 (42%), and 755 (22%) patients classified as benign, malignant and equivocal, respectively. In the patient-based analysis, CNN predicted benign, malignant and equivocal images with 99.4, 99.4, and 87.5% accuracy, respectively. In region-based analysis, the prediction was correct with the probability of 97.3% (head-and-neck), 96.6% (chest), 92.8% (abdomen) and 99.6% (pelvic region), respectively., Conclusion: The CNN-based system reliably classified FDG PET images into 3 categories, indicating that it could be helpful for physicians as a double-checking system to prevent oversight and misdiagnosis.

Patient misidentification in imaging examinations has become a serious problem in clinical settings. Such misidentification could be prevented if patient characteristics such as sex, age, and body weight could be predicted based on an image of the patient, with an alert issued when a mismatch between the predicted and actual patient characteristic is detected. Here, we tested a simple convolutional neural network (CNN)-based system that predicts patient sex from FDG PET-CT images. This retrospective study included 6,462 consecutive patients who underwent whole-body FDG PET-CT at our institute. The CNN system was used for classifying these patients by sex. Seventy percent of the randomly selected images were used to train and validate the system; the remaining 30% were used for testing. The training process was repeated five times to calculate the system's accuracy. When images for the testing were given to the learned CNN model, the sex of 99% of the patients was correctly categorized. We then performed an image-masking simulation to investigate the body parts that are significant for patient classification. The image-masking simulation indicated the pelvic region as the most important feature for classification. Finally, we showed that the system was also able to predict age and body weight. Our findings demonstrate that a CNN-based system would be effective to predict the sex of patients, with or without age and body weight prediction, and thereby prevent patient misidentification in clinical settings.

Background: The in vitro micronucleus (MN) test is an important component of a genotoxicity test battery that evaluates chemicals. Although the standard method of manually scoring micronucleated (MNed) cells by microscope is a reliable and standard method, it is laborious and time-consuming. A high-throughput assay system for detecting MN cells automatically has long been desired in the fields of pharmaceutical development or environmental risk monitoring. Although the MN test per se cannot clarify whether the mode of MN induction is aneugenic or clastogenic, this clarification may well be made possible by combining the MN test with an evaluation of γH2AX, a sensitive marker of DNA double strand breaks (DSB). In the present study, we aimed to establish a high-content (HC) imaging assay that automatically detects micronuclei (MNi) and simultaneously measures γH2AX foci in human lymphoblastoid TK6 cells., Results: TK6 cells were fixed on the bottom of each well in 96-well plates hypotonically, which spreads the cells thinly to detach MNi from the primary nuclei. Then, the number of MNi and immunocytochemically-stained γH2AX foci were measured using an imaging analyzer. The system correctly judged 4 non-genotoxins and 13 genotoxins, which included 9 clastogens and 4 aneugens representing various genotoxic mechanisms, such as DNA alkylation, cross-linking, topoisomerase inhibition, and microtubule disruption. Furthermore, all the clastogens induced both γH2AX foci and MNi, while the aneugens induced only MNi, not γH2AX foci; therefore, the HC imaging assay clearly discriminated the aneugens from the clastogens. Additionally, the test system could feasibly analyze cell cycle, to add information about a chemical's mode of action., Conclusions: A HC imaging assay to detect γH2AX foci and MNi in TK6 cells was established, and the assay provided information on the aneugenic/clastogenic mode of action., Competing Interests: Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Aims: Coronary flow reserve (CFR) is an integrated measure of the entire coronary vasculature, and is a powerful prognostic marker in coronary artery disease (CAD). The extent to which coronary revascularization can improve CFR is unclear. This study aimed to evaluate the impact of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on CFR in patients with stable CAD., Methods and Results: In a prospective, multicentre observational study, CFR was measured by 15O-water positron emission tomography as the ratio of stress to rest myocardial blood flow at baseline and 6 months after optimal medical therapy (OMT) alone, PCI, or CABG. Changes in the SYNTAX and Leaman scores were angiographically evaluated as indicators of completeness of revascularization. Follow-up was completed by 75 (25 OMT alone, 28 PCI, and 22 CABG) out of 82 patients. The median SYNTAX and Leaman scores, and baseline CFR were 14.5 [interquartile range (IQR): 8-24.5], 5.5 (IQR: 2.5-12.5), and 1.94 (IQR: 1.67-2.66), respectively. Baseline CFR was negatively correlated with the SYNTAX (ρ = -0.40, P < 0.001) and Leaman scores (ρ = -0.33, P = 0.004). Overall, only CABG was associated with a significant increase in CFR [1.67 (IQR: 1.14-1.96) vs. 1.98 (IQR: 1.60-2.39), P < 0.001]. Among patients with CFR <2.0 (n = 41), CFR significantly increased in the PCI [1.70 (IQR: 1.42-1.79) vs. 2.21 (IQR: 1.78-2.49), P = 0.002, P < 0.001 for interaction between time and CFR] and CABG groups [1.28 (IQR: 1.13-1.80) vs. 1.86 (IQR: 1.57-2.22), P < 0.001]. The reduction in SYNTAX or Leaman scores after PCI or CABG was independently associated with the percent increase in CFR after adjusting for baseline characteristics (P = 0.012 and P = 0.011, respectively)., Conclusion: Coronary revascularization ameliorated reduced CFR in patients with obstructive CAD. The degree of improvement in angiographic CAD burden by revascularization was correlated with magnitude of improvement in CFR.

We have developed the method for dynamic 320-row multidetector computed tomography (MDCT)-derived quantitative coronary flow reserve (CFRCT) and hyperemic myocardial blood flow (MBFCT). We evaluated diagnostic value of CFRCT and hyperemic MBFCT for detecting obstructive coronary artery disease (CAD) in per-patient and per-vessel analysis, and their relations with the severity of CAD burden.Adenosine stressed and rest dynamic myocardial perfusion MDCT were prospectively performed in patients with known or suspected CAD. Per-patient and per-vessel MBFCT were estimated from dynamic perfusion images in rest and hyperemic phases, and per-patient and per-vessel CFRCT were calculated from the ratio of rest and hyperemic MBFCT. Degree of stenosis was evaluated by coronary CT angiography (CTA) and invasive coronary angiography (ICA). Obstructive stenosis was defined as ≥70% stenosis in ICA. CAD burden with MDCT was calculated by logarithm transformed coronary artery calcium (CAC) score and the CTA-adapted Leaman risk score (CT-LeSc). A logistic regression analysis was used to measure the receiver-operating characteristic curve and corresponding area under the curve (AUC) for the detection of obstructive CAD.Twenty-seven patients and 81 vessels were eligible for this study. Sixteen patients had obstructive CAD, and 31 vessels had obstructive stenosis. Using an optimal cutoff, the CFRCT and hyperemic MBFCT had the moderate diagnostic values in per-patient (AUC = 0.89 and 0.86, respectively) and per-vessel (AUC = 0.79 and 0.76, respectively). Per-patient CFRCT and hyperemic MBFCT exhibited a moderate inverse correlation with CAC score and the CT-LeSc.Per-patient and per-vessel CFRCT as well as hyperemic MBFCT had moderate diagnostic value for detecting obstructive CAD. These per-patient values exhibited a moderate inverse correlation with CAD burden. CFRCT and hyperemic MBFCT might add quantitative functional information for evaluating patients with CAD.

Background: Traumatic brain injury (TBI) causes brain dysfunction in many patients. Using C-11 flumazenil (FMZ) positron emission tomography (PET), we have detected and reported the loss of neuronal integrity, leading to brain dysfunction in TBI patients. Similarly to FMZ PET, I-123 iomazenil (IMZ) single photon emission computed tomography (SPECT) is widely used to determine the distribution of the benzodiazepine receptor (BZR) in the brain cortex. The purpose of this study is to examine whether IMZ SPECT is as useful as FMZ PET for evaluating the loss of neuronal integrity in TBI patients. The subjects of this study were seven patients who suffered from neurobehavioral disability. They underwent IMZ SPECT and FMZ PET. Nondisplaceable binding potential (BP ND ) was calculated from FMZ PET images. The uptake of IMZ was evaluated on the basis of lesion-to-pons ratio (LPR). The locations of low uptake levels were visually evaluated both in IMZ SPECT and FMZ PET images. We compared FMZ BP ND and (LPR-1) of IMZ SPECT., Results: In the visual assessment, FMZ BP ND decreased in 11 regions. In IMZ SPECT, low uptake levels were observed in eight of the 11 regions. The rate of concordance between FMZ PET and IMZ SPECT was 72.7%. The mean values IMZ (LPR-1) (1.95 ± 1.01) was significantly lower than that of FMZ BP ND (2.95 ± 0.80 mL/mL). There was good correlation between FMZ BP ND and IMZ (LPR-1) (r = 0.80)., Conclusions: IMZ SPECT findings were almost the same as FMZ PET findings in TBI patients. The results indicated that IMZ SPECT is useful for evaluating the loss of neuronal integrity. Because IMZ SPECT can be performed in various facilities, IMZ SPECT may become widely adopted for evaluating the loss of neuronal integrity.

Background: The quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR) are useful approaches for evaluating the functional severity of coronary artery disease (CAD). 15 O-water positron emission tomography (PET) is considered the gold standard method for MBF quantification. However, MBF measurements in 15 O-water PET with three-dimensional (3D) data acquisition, attenuation correction using computed tomography (CT), and time of flight have not been investigated in detail or validated. We conducted this study to evaluate the diagnostic potential of MBF measurements using PET/CT for a comparison of a control group and patients suspected of having CAD., Results: Twenty-four patients with known or suspected CAD and eight age-matched healthy volunteers underwent rest and pharmacological stress perfusion studies with 15 O-water PET/CT. The whole and three regional (left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) territory) MBF values were estimated. The CFR was computed as the ratio of the MBF during adenosine triphosphate-induced stress to the MBF at rest. The inter-observer variability was assessed by two independent observers. PET/CT using a 15 O-water dose of 500 MBq and 3D data acquisition showed good image quality. A strong inter-observer correlation was detected in both the whole MBF analysis and the regional analysis with high intra-class correlation coefficients (r > 0.90, p < 0.001). Regional MBF at rest (LAD, 0.82 ± 0.15 ml/min/g; LCX, 0.83 ± 0.17 ml/min/g; RCA, 0.71 ± 0.20 ml/min/g; p = 0.74), MBF at stress (LAD, 3.77 ± 1.00 ml/min/g; LCX, 3.56 ± 1.01 ml/min/g; RCA, 3.27 ± 1.04 ml/min/g; p = 0.62), and CFR (LAD, 4.64 ± 0.90; LCX, 4.30 ± 0.64; RCA, 4.64 ± 0.96; p = 0.66) of the healthy volunteers showed no significant difference among the three regions. The global CFR of the patients was significantly lower than that of the volunteers (2.75 ± 0.81 vs. 4.54 ± 0.66, p = 0.0002). The regional analysis of the patients demonstrated that the CFR tended to be lower in the stenotic region compared to the non-stenotic region (2.43 ± 0.81 vs. 2.95 ± 0.92, p = 0.052)., Conclusions: 15 O-water PET/CT with 3D data acquisition can be reliably used for the quantification of functional MBF and CFR in CAD patients.

In 3-dimensional PET/CT imaging of the brain with 15 O-gas inhalation, high radioactivity in the face mask creates cold artifacts and affects the quantitative accuracy when scatter is corrected by conventional methods (e.g., single-scatter simulation [SSS] with tail-fitting scaling [TFS-SSS]). Here we examined the validity of a newly developed scatter-correction method that combines SSS with a scaling factor calculated by Monte Carlo simulation (MCS-SSS). Methods: We performed phantom experiments and patient studies. In the phantom experiments, a plastic bottle simulating a face mask was attached to a cylindric phantom simulating the brain. The cylindric phantom was filled with 18 F-FDG solution (3.8-7.0 kBq/mL). The bottle was filled with nonradioactive air or various levels of 18 F-FDG (0-170 kBq/mL). Images were corrected either by TFS-SSS or MCS-SSS using the CT data of the bottle filled with nonradioactive air. We compared the image activity concentration in the cylindric phantom with the true activity concentration. We also performed 15 O-gas brain PET based on the steady-state method on patients with cerebrovascular disease to obtain quantitative images of cerebral blood flow and oxygen metabolism. Results: In the phantom experiments, a cold artifact was observed immediately next to the bottle on TFS-SSS images, where the image activity concentrations in the cylindric phantom were underestimated by 18%, 36%, and 70% at the bottle radioactivity levels of 2.4, 5.1, and 9.7 kBq/mL, respectively. At higher bottle radioactivity, the image activity concentrations in the cylindric phantom were greater than 98% underestimated. For the MCS-SSS, in contrast, the error was within 5% at each bottle radioactivity level, although the image generated slight high-activity artifacts around the bottle when the bottle contained significantly high radioactivity. In the patient imaging with 15 O 2 and C 15 O 2 inhalation, cold artifacts were observed on TFS-SSS images, whereas no artifacts were observed on any of the MCS-SSS images. Conclusion: MCS-SSS accurately corrected the scatters in 15 O-gas brain PET when the 3-dimensional acquisition mode was used, preventing the generation of cold artifacts, which were observed immediately next to a face mask on TFS-SSS images. The MCS-SSS method will contribute to accurate quantitative assessments., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Pefcalcitol, an analog of vitamin D 3 (VD 3 ), is an anti-psoriatic drug candidate that is designed to achieve much higher pharmacological effects, such as keratinocyte differentiation, than those of VD 3, with fewer side effects. Genotoxicity of the compound was evaluated in a rat skin micronucleus (MN) test., Results: In the rat skin MN test, pefcalcitol showed positive when specimens were stained with Giemsa, whereas neither an in vitro chromosome aberration test in CHL cells nor an in vivo bone marrow MN test in rats indicated clastogenicity. To elucidate the causes of the discrepancy, the MN specimens were re-stained with acridine orange (AO), a fluorescent dye specific to nucleic acid, and the in vivo clastogenicity of the compound in rat skin was re-evaluated. The MN-like granules that had been stained by Giemsa were not stained by AO, and AO-stained specimens indicated that pefcalcitol did not increase the frequency of micronucleated (MNed) cells. Histopathological evaluation suggested that the MN-like granules in the epidermis were keratohyalin granules contained in keratinocytes, which had highly proliferated after treatment with pefcalcitol., Conclusions: Pefcalcitol was concluded to be negative in the rat skin MN test. The present study demonstrated that Giemsa staining gave a misleading positive result in the skin MN test, because Giemsa stained keratohyalin granules.

Diastolic dysfunction is important in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Sympathetic nervous hyperactivity may contribute to the development of diastolic dysfunction. The aim of this study was to determine the relationship between myocardial sympathetic innervation quantified by 11 C-hydroxyephedrine PET and diastolic dysfunction in HFpEF patients. Methods: Forty-one HFpEF patients having an echocardiographic left ventricular ejection fraction of 40% or greater and 12 age-matched volunteers without heart failure underwent the echocardiographic examination and 11 C-hydroxyephedrine PET. Diastolic dysfunction was classified into grades 0-3 by Doppler echocardiography. Myocardial sympathetic innervation was quantified using the 11 C-hydroxyephedrine retention index (RI). The coefficient of variation of 17-segment RIs was derived as a measure of heterogeneity in myocardial 11 C-hydroxyephedrine uptake. Results: Grade 2-3 diastolic dysfunction (DD 2-3 ) was found in 19 HFpEF patients (46%). They had a significantly lower global RI (0.075 ± 0.018 min -1 ) than volunteers (0.123 ± 0.028 min -1 , P < 0.001) and HFpEF patients with grade 0-1 diastolic dysfunction (DD 0-1 ) (0.092 ± 0.024 min -1 , P = 0.046). HFpEF patients with DD 2-3 had the largest coefficient of variation of 17-segment RIs of the 3 groups (18.4% ± 7.7% vs. 14.1% ± 4.7% in HFpEF patients with DD 0-1 , P = 0.042 for post hoc tests). In multivariate logistic regression analysis, a lower global RI (odds ratio, 0.66 per 0.01 min -1 ; 95% confidence interval, 0.38-0.99; P = 0.044) was independently associated with the presence of DD 2-3 in HFpEF patients. Conclusion: Myocardial sympathetic innervation was impaired in HFpEF patients and was associated with the presence of advanced diastolic dysfunction in HFpEF., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Accelerated clearance of (99m)technetium-sestamibi (MIBI) has been observed after reperfusion therapy in patients with acute coronary syndrome (ACS), but the mechanisms have not been fully investigated. MIBI retention may depend on mitochondrial function. The clearance rate of (11)carbon-acetate reflects such mitochondrial functions as oxidative metabolism. The purpose of this study was to examine the mechanisms of accelerated MIBI clearance in ACS. We therefore compared it to oxidative metabolism estimated using (11)C-acetate positron emission tomography (PET)., Methods: Eighteen patients [mean age 69.2 ± 8.7 years, 10 males (56 %)] with reperfused ACS underwent MIBI single-photon emission computed tomography (SPECT), echocardiography, and (11)C-acetate PET within 3 weeks of the onset of ACS. MIBI images were obtained 30 min and 3 h after MIBI administration. Regional left ventricular (LV) function was evaluated by echocardiography. The measurement of oxidative metabolism was obtained through the mono-exponential fitting of the (11)C-acetate time-activity curve (k mono)., Results: Among 95 segments of reperfused myocardium, MIBI SPECT showed 64 normal segments (group N), 14 segments with accelerated MIBI clearance (group AC), and 17 segments with fixed defect (group F). Group AC showed lower k mono than group N (0.041 ± 0.009 vs 0.049 ± 0.010, p = 0.02). Group F showed lower k mono than group N (0.039 ± 0.012 vs 0.049 ± 0.010, p = 0.01). However, k mono was similar in group AC and group F (p = 0.99)., Conclusions: Segments with accelerated MIBI clearance showed reduced oxidative metabolism in ACS. Loss of MIBI retention may be associated with mitochondrial dysfunction.

Background: Comprehensive evaluation of endothelium-dependent and endothelium-independent vascular functions in peripheral arteries and coronary arteries in smokers has never been performed previously. Through the use of brachial artery ultrasound and oxygen-15-labeled water positron emission tomography (PET), we sought to investigate peripheral and coronary vascular dysfunctions in smokers., Methods and Results: Eight smokers and 10 healthy individuals underwent brachial artery ultrasound at rest, during reactive hyperemia [250mmHg cuff occlusion (flow-mediated dilatation (FMD)], and following sublingual nitroglycerin (NTG) administration. Myocardial blood flow (MBF) was assessed through O-15-labeled water PET at rest, during adenosine triphosphate (ATP) administration, and during a cold pressor test (CPT). Through ultrasound, smokers were shown to have significantly reduced %FMD compared to controls (6.62±2.28% vs. 11.29±2.75%, p=0.0014). As assessed by O-15-labeled water PET, smokers were shown to have a significantly lower CPT response than were controls (21.1±9.5% vs. 50.9±16.9%, p=0.0004). There was no relationship between %FMD and CPT response (r=0.40, p=0.097). Endothelium-independent vascular dilatation was similar for both groups in terms of coronary flow reserve with PET (p=0.19). Smokers tended to have lower %NTG in the brachial artery (p=0.055)., Conclusions: Smokers exhibited impaired coronary endothelial function as well as peripheral brachial artery endothelial function. In addition, there was no correlation between PET and ultrasound measurements, possibly implying that while smokers may have systemic vascular endothelial dysfunction, the characteristics of that dysfunction may be different in peripheral arteries and coronary arteries., (Copyright © 2016. Published by Elsevier Ltd.)

Objective: (11)C-acetate has been applied for evaluation of myocardial oxidative metabolism and can simultaneously estimate myocardial blood flow (MBF). We developed a new method using two-parameter spillover correction to estimate regional MBF (rMBF) with (11)C-acetate PET in reference to MBF derived from (15)O-H2O PET. The usefulness of our new approach was evaluated compared to the conventional method using one-parameter spillover correction., Methods: Sixty-three subjects were examined with (11)C-acetate and (15)O-H2O dynamic PET at rest. Inflow rate of (11)C-acetate (K1) was compared with MBF derived from (15)O-H2O PET. For the derivation, the relationship between K1 and MBF from (15)O-H2O was linked by the Renkin-Crone model in 20 subjects as a pilot group. One-parameter and two-parameter corrections were applied to suppress the spillover between left ventricular (LV) wall and LV cavity. Validation was set using the other 43 subjects' data. Finally, rMBFs were calculated using relational expression derived from the pilot-group data., Results: The relationship between K1 and MBF derived from (15)O-H2O PET was approximated as K1 = [1-0.764 × exp(-1.001/MBF)] MBF from the pilot data using the two-parameter method. In the validation set, the correlation coefficient between rMBF from (11)C-acetate and (15)O-H2O demonstrated a significantly higher relationship with the two-parameter spillover correction method than the one-parameter spillover correction method (r = 0.730, 0.592, respectively, p < 0.05)., Conclusion: In (11)C-acetate PET study, the new two-parameter spillover correction method dedicated more accurate and robust myocardial blood flow than the conventional one-parameter method.

Objectives: The purpose of this study was to compare myocardial blood flow (MBF) and myocardial flow reserve (MFR) estimates from rubidium-82 positron emission tomography ((82)Rb PET) data using 10 software packages (SPs) based on 8 tracer kinetic models., Background: It is unknown how MBF and MFR values from existing SPs agree for (82)Rb PET., Methods: Rest and stress (82)Rb PET scans of 48 patients with suspected or known coronary artery disease were analyzed in 10 centers. Each center used 1 of 10 SPs to analyze global and regional MBF using the different kinetic models implemented. Values were considered to agree if they simultaneously had an intraclass correlation coefficient >0.75 and a difference <20% of the median across all programs., Results: The most common model evaluated was the Ottawa Heart Institute 1-tissue compartment model (OHI-1-TCM). MBF values from 7 of 8 SPs implementing this model agreed best. Values from 2 other models (alternative 1-TCM and Axially distributed) also agreed well, with occasional differences. The MBF results from other models (e.g., 2-TCM and retention) were less in agreement with values from OHI-1-TCM., Conclusions: SPs using the most common kinetic model-OHI-1-TCM-provided consistent results in measuring global and regional MBF values, suggesting that they may be used interchangeably to process data acquired with a common imaging protocol., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: (123)I-metaiodobenzylguanidine (MIBG) has been used to estimate cardiac sympathetic nervous innervation. Heterogeneous MIBG distribution is mainly associated with high physiological MIBG uptakes in the liver. We postulate that prone position acquisition might be especially effective for MIBG, providing for separation from high liver uptake similar to that provided by perfusion single-photon emission computed tomography (SPECT). We investigated whether prone-position acquisition improved MIBG image quality by comparing our results to those acquired using supine MIBG and high-quality (11)C-hydroxyephedrine (HED) positron emission tomography/computed tomography PET/CT., Methods: Ten male volunteers (body mass index (BMI) 22.7 ± 3.4) underwent prone and supine MIBG and HED PET. Relative regional tracer uptake was estimated in early MIBG and HED. Acquired images were divided into 17 segments and were grouped into 4 regions: anterior, inferior, septum, and lateral. For each patient, the inferior/anterior ratio was calculated., Results: The quality of images acquired using prone MIBG was better than that using supine MIBG (p < 0.05). Inferior and septum relative MIBG uptake was reduced in comparison with anterior or lateral MIBG uptake in the supine position (inferior vs. anterior: 69.0 ± 5.6 vs. 82.3 ± 4.6 %, p < 0.01; septum vs. lateral: 66.2 ± 5.1 vs. 81.9 ± 5.4 %, p < 0.01). Prone MIBG showed a significantly higher inferior/anterior uptake ratio in comparison with supine MIBG (n = 24, seg: 92.2 ± 7.2 vs. 83.6 ± 5.7 %, p < 0.05). However, intergroup differences in uptake ratio were demonstrated among prone and supine MIBG and HED. HED PET/CT still showed a higher uptake ratio in comparison with prone MIBG SPECT (103.9 ± 8.0 vs. 92.2 ± 7.2 %, p < 0.05)., Conclusion: Even in normal male subjects, standard supine MIBG imaging showed reduced inferior and septum uptake. Uptake with prone MIBG imaging showed a significant improvement over that with supine imaging and was closer to uptake for HED PET/CT. This improvement may be the result of preventing intense uptake by the liver. Prone data acquisition may be a viable alternative in evaluating regional abnormalities using MIBG SPECT in men.

Proteobacterium Escherichia coli strains harboring wide-transfer-range conjugative plasmids are able to transfer these plasmids to several yeast species. Whole plasmid DNA is mobilizable in the transkingdom conjugation phenomenon. Owing to the availability of various conjugative plasmids in bacteria, the horizontal DNA transfer has potential to occur between various bacteria and eukaryotes. In order to know host factor genes involved in such conjugation, we systematically tested the conjugability of strains among a yeast library comprising single-gene-knockout mutants in this study. This genome-wide screen identified 26 host chromosomal genes whose absence reduced the efficiency of the transkingdom conjugation. Among the 26 genes, 20 are responsible for vacuolar ATPase activity, while 5 genes (SHP1, CSG2, CCR4, NOT5, and HOF1) seem to play a role in maintaining the cell surface. Lack of either ZUO1 gene or SSZ1 gene, each of which encodes a component of the ribosome-associated cytoplasmic molecular chaperone, also strongly affected transkingdom conjugation., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

A novel single-nucleotide polymorphism (SNP) in the 3'-untranslated region of the human dihydrofolate reductase (DHFR) gene with enhanced expression was identified in 2001. In 2007, it was reported that this SNP, DHFR C829T, was located close to a microRNA binding site and contributed to the stability of mRNA. Many researchers have analyzed this SNP in several races including Asians and Caucasians. However, the mutation allele is not yet confirmed in most populations. In this study, we reinvestigated the frequency of this SNP using three methods. First, this SNP in genomic DNA was analyzed by a PCR-restriction fragment length polymorphism method. Second, this SNP in mRNA was analyzed by a single nucleotide extension method following a reverse transcription reaction. Third, the mRNA expression level was analyzed by a real-time PCR method. The findings in our study, regarding the discovery of this SNP, suggest that the SNP is an artifact caused by contamination by the genomic DNA of the pseudogene DHFRP1. This study is a reinvestigation of a newly discovered genetic polymorphism.

Background: Myocardial blood flow (MBF) can be measured with positron emission tomography (PET) and its quantification should provide diagnostic information beyond that obtained through standard visual analysis. However, this possibility has not been fully studied with PET and generator-produced rubidium-82 (⁸²Rb). We evaluated regional MBF in segments with and without ischemia using ⁸²Rb PET in patients with coronary artery disease (CAD)., Methods and Results: Rest and stress ⁸²Rb PET and coronary angiography were performed for 12 patients with CAD. Based on angiography and relative ⁸²Rb perfusion images, segments were classified into 4 groups (Group A: myocardial ischemia with >70% diameter stenosis; Group B: no ischemia with stenosis; Group C: no ischemia without stenosis; Group D: ischemia without stenosis). Rest MBF was similar among the 4 groups. Groups A and B showed reduced hyperemic MBF compared with Group C (P < 0.05 vs. Group C) [Group A (n=16) 1.28 ± 0.58 ml·min⁻¹·g⁻¹; Group B (n=11) 1.72 ± 0.64 ml·min⁻¹·g⁻¹; Group C (n=9) 2.60 ± 1.09 ml·min⁻¹·g⁻¹; Group D (n=2) 2.33 ml·min⁻¹·g⁻¹]. Coronary flow reserves were inversely correlated with percent diameter stenosis (r=0.76, P < 0.0001)., Conclusions: Segments with ischemia and coronary stenosis had reduced hyperemic MBF. Segments with coronary stenosis without ischemia also had reduced hyperemic MBF compared with non-stenotic segments. MBF quantification using ⁸²Rb PET may provide additional diagnostic information.

Aims: Coupling factor 6 (CF6) induces hypertension by attenuating the endothelial generation of prostacyclin. However, intracellular signalling of CF6 in the resistance arteriole vascular smooth muscle cells (VSMCs) that are directly related to vasoconstriction has not been determined. Here we investigated the direct effect of exogenous CF6 on Ca2+ signalling in cultured VSMCs and the in vivo role of endogenous CF6 in the genesis of hypertension using CF6 transgenic (TG) mice., Methods and Results: CF6 induced a monophasic increase in the intracellular free Ca2+ concentration ([Ca2+]i) through nifedipine-sensitive Ca2+ channels in A7r5 cells, a cell line of VSMCs, and enhanced the angiotensin II-induced spike phase of [Ca2+]i to a greater degree in VSMCs derived from spontaneously hypertensive rats (SHRs). In the mesenteric arterioles obtained from CF6-TG mice that manifested hypertension, angiotensin II-induced vasoconstriction was enhanced, compared with wild-type mice, and its enhancement was abolished by an anti-CF6 antibody. Pre-treatment with PP1, a tyrosine kinase c-Src inhibitor, blocked CF6-induced increase in Ca2+ signalling in VSMCs and vasoconstriction in TG mice. The receptor of CF6 was F1 motor of adenosine triphosphate (ATP) synthase with a higher affinity in SHRs. CF6 decreased intracellular pH via activation of ATPase activity and led to c-Src activation to a greater degree in SHR-derived VSMCs., Conclusion: CF6 causes hypertension by directly enhancing Ca2+ signalling in VSMCs and vasoconstriction in the mesenteric arteriolar network via c-Src activation.

Unlabelled: We evaluated whether myocardial beta-adrenergic receptor (beta-AR) density, as determined by 11C-CGP12177 PET, could predict improvement of cardiac function by beta-blocker carvedilol treatment in patients with idiopathic dilated cardiomyopathy (IDC)., Methods: Ten patients with IDC (left ventricular ejection fraction [LVEF]<45%) were studied. Myocardial beta-AR density was estimated using 11C-CGP12177 PET before treatment with carvedilol. Changes of LVEF in response to dobutamine infusion (DeltaLVEF-dobutamine) were also measured by echocardiography. Changes of LVEF (DeltaLVEF-carvedilol) were evaluated after 20 mo of carvedilol treatment., Results: Baseline myocardial beta-AR density significantly correlated with DeltaLVEF-carvedilol (r=-0.88, P<0.001). In contrast, DeltaLVEF-dobutamine did not correlate with DeltaLVEF-carvedilol (P=0.65). Myocardial beta-AR density was the significant multivariate independent predictor of DeltaLVEF-carvedilol (beta=-0.88, P<0.001) among univariate predictors, including functional class (r=0.76, P<0.05), plasma norepinephrine (r=0.85, P<0.01), LVEF (r=-0.64, P<0.05), and age as confounding factors. Furthermore, myocardial beta-AR density was significantly correlated with plasma norepinephrine (r=-0.79, P<0.01) and LVEF (r=0.70, P<0.05)., Conclusion: Myocardial beta-AR density is more tightly related to improvement of LVEF-carvedilol than is cardiac contractile reserve in patients with IDC. Patients with decreased myocardial beta-AR have higher resting adrenergic drive, as reflected by plasma norepinephrine, and may receive greater benefit from being treated by antiadrenergic drugs.

Unlabelled: An autoradiography method revealed intratumoral inhomogeneity in various solid tumors. It is becoming increasingly important to estimate intratumoral inhomogeneity. However, with low spatial resolution and high scatter noise, it is difficult to detect intratumoral inhomogeneity in clinical settings. We developed a new PET system with CdTe semiconductor detectors to provide images with high spatial resolution and low scatter noise. Both phantom images and patients' images were analyzed to evaluate intratumoral inhomogeneity., Methods: This study was performed with a cold spot phantom that had 6-mm-diameter cold sphenoid defects, a dual-cylinder phantom with an adjusted concentration of 1:2, and an "H"-shaped hot phantom. These were surrounded with water. Phantom images and (18)F-FDG PET images of patients with nasopharyngeal cancer were compared with conventional bismuth germanate PET images. Profile curves for the phantoms were measured as peak-to-valley ratios to define contrast. Intratumoral inhomogeneity and tumor edge sharpness were evaluated on the images of the patients., Results: The contrast obtained with the semiconductor PET scanner (1.53) was 28% higher than that obtained with the conventional scanner (1.20) for the 6-mm-diameter cold sphenoid phantom. The contrast obtained with the semiconductor PET scanner (1.43) was 27% higher than that obtained with the conventional scanner (1.13) for the dual-cylinder phantom. Similarly, the 2-mm cold region between 1-mm hot rods was identified only by the new PET scanner and not by the conventional scanner. The new PET scanner identified intratumoral inhomogeneity in more detail than the conventional scanner in 6 of 10 patients. The tumor edge was sharper on the images obtained with the new PET scanner than on those obtained with the conventional scanner., Conclusion: These phantom and clinical studies suggested that this new PET scanner has the potential for better identification of intratumoral inhomogeneity, probably because of its high spatial resolution and low scatter noise.

Unlabelled: The repeatability of rest and hyperemic myocardial blood flow (MBF) measurements using 82Rb PET has not been evaluated. The aim of this study was to investigate the short-term repeatability of such measurements., Methods: Fifteen healthy volunteers underwent rest and pharmacologic stress 82Rb PET, repeated 60 min apart., Results: There was no significant difference in repeated rest MBF (0.77+/-0.25 vs. 0.82+/-0.25 mL/min/g, P=0.31; mean difference, 6.18%+/-12.22%) or repeated hyperemic MBF (3.35+/-1.37 vs. 3.39+/-1.37 mL/min/g, P=0.81; mean difference, 1.17%+/-13.64%). The repeatability coefficients were 0.19 mL/min/g for rest MBF and 0.92 mL/min/g for hyperemia., Conclusion: MBF using 82Rb is highly reproducible using a same-day short-term repeatability protocol. Serial MBF measurements with 82Rb PET should have the ability to quantify the acute effects of therapeutic interventions on MBF.

Real-time quantitative polymerase chain reaction (RQ-PCR) has been accepted as integral part of the management of patients with hematologic malignancies. Whereas standardization efforts of RQ-PCR, initiated by Europe Against Cancer (EAC) group, have been gradually widespread in the world, Japanese laboratories use their individual protocol for RQ-PCR analysis. Therefore, we assessed the variability of quantitative results obtained from 4 different laboratories in Japan, including 3 companies and Tohoku University Hospital, using identical peripheral blood or bone marrow samples of patients in chronic myeloid leukemia (CML; n = 11) and acute myeloid leukemia (AML; n = 2). RQ-PCR was designed to quantify the copy numbers of disease-specific fusion chimeras; BCR-ABL (CML) and AML1-ETO (AML). In 5 out of 13 samples, the quantitative results from 4 laboratories varied more than 10 times (up to 712 times). Thus, we next sought to determine factors affecting the variability of RQ-PCR results across laboratories, by sending back RNA and cDNA samples from each company to Tohoku University, and they were further proceed to yield quantitative data. The main difference between companies and Tohoku University was probably due to the difference of blood separation method (Blood lysis or Ficoll-Hypaque). On the other hand, the variability among 4 laboratories was the most noticeable in the PCR step, mainly attributable to the difference of primer/probe sequence among laboratories. In conclusion, our analyses indicate the importance to limit both preanalytical (sample processing) and analytical (RQ-PCR) interlaboratory variability for RQ-PCR protocol, and the need of further efforts on standardization program in Japan.

Unlabelled: Cardiac sympathetic function plays an important role in the regulation of left ventricular (LV) function and the pathophysiology of LV dysfunction. (11)C-CGP-12177 ((11)C-CGP) has been used to assess myocardial beta-adrenergic receptor (beta-AR) density in vivo using PET. The aim of this study is to measure myocardial beta-AR density in patients with nonischemic cardiomyopathy and to compare the measurements with various standard parameters of heart failure (HF), particularly with presynaptic function assessed by (123)I- metaiodobenzylguanidine ((123)I-MIBG) imaging., Methods: (11)C-CGP PET was performed on 16 patients with nonischemic cardiomyopathy and 8 age-matched healthy volunteers using a double injection method. A (11)C-CGP dynamic scan for 75 min was performed after the injection of (11)C-CGP with a high specific activity. After 30 min, (11)C-CGP with a low specific activity was injected. The beta-AR density of the whole LV was calculated on the basis of the graphical analysis method. Additionally, beta-AR density was compared with LV ejection fraction (LVEF), sympathetic presynaptic function assessed using (123)I-MIBG kinetics, and neurohormonal parameters., Results: The beta-AR density of patients was significantly lower than that of healthy volunteers (3.80 +/- 0.96 vs. 7.70 +/- 1.92 pmol/mL; P < 0.0001). In the patients, beta-AR density correlated significantly with LVEF (r = 0.62, P < 0.05). Furthermore, beta-AR density correlated significantly with the (123)I-MIBG washout rate (r = -0.68, P < 0.01) and delayed heart-to-mediastinum ratio (H/M ratio) (r = 0.61, P < 0.05). On the other hand, the correlation between beta-AR density and early H/M ratio was not significant (r = 0.40, P = 0.13). The beta-AR density of patients with severe HF (New York Heart Association functional [NYHA] class III) was significantly lower than that of those with NYHA functional class I or class II HF (3.24 +/- 0.96 vs. 4.24 +/- 0.73 pmol/mL; P < 0.05)., Conclusion: A reduction in beta-AR density measured by (11)C-CGP PET was observed in patients with nonischemic cardiomyopathy. This downregulation may be due to the increased presynaptic sympathetic tone as assessed by (123)I-MIBG imaging.

Objectives: We aimed to compare the effects of the angiotensin II receptor blocker (ARB) olmesartan versus the calcium channel blocker (CCB) amlodipine on coronary endothelial dysfunction in patients with hypertension., Background: Angiotensin II receptor blockers are thought to have greater beneficial effects than CCBs on coronary vasomotion by directly blocking action of angiotensin II., Methods: Twenty-six patients with untreated essential hypertension were prospectively assigned to treatment with either olmesartan (27.7 +/- 12.4 mg/day, n = 13) or amlodipine (5.6 +/- 1.5 mg/day, n = 13) for 12 weeks. Changes of corrected myocardial blood flow (DeltaMBF) and coronary vascular resistance (DeltaCVR) from rest to cold pressor were measured by using 15O-water and positron emission tomography before and after treatment. Blood biomarkers including lipids, glucose, insulin, high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and superoxide dismutase (SOD) were also measured., Results: Olmesartan and amlodipine reduced blood pressure (BP) to the same extent (-28.7 +/- 16.2 mm Hg vs. -26.7 +/- 10.8 mm Hg). In the olmesartan group, DeltaMBF tended to be greater (-0.15 +/- 0.19 ml/g/min vs. 0.03 +/- 0.17 ml/g/min, p = 0.09 by 2-way analysis of variance), and DeltaCVR was significantly decreased (7.9 +/- 23.5 mm Hg/[ml/g/min] vs. -16.6 +/- 18.0 mm Hg/[ml/g/min], p < 0.05) after treatment, whereas these parameters did not change in the amlodipine group (DeltaMBF: -0.15 +/- 0.12 ml/g/min vs. -0.12 +/- 0.20 ml/g/min; DeltaCVR: 6.5 +/- 18.2 mm Hg/[ml/g/min] vs. 4.8 +/- 23.4 mm Hg/[ml/g/min]). Serum SOD activity tended to increase (4.74 +/- 4.77 U/ml vs. 5.57 +/- 4.74 U/ml, p = 0.07 by 2-way analysis of variance) only in the olmesartan group., Conclusions: Olmesartan, but not amlodipine, improved endothelium-dependent coronary dilation in hypertensive patients independent of BP reduction. These beneficial effects on coronary vasomotion might be via an antioxidant property of ARBs.

Background: Elevated plasma plasminogen activator inhibitor-1 (PAI-1) is related to cardiovascular events, but its role in subclinical coronary microvascular dysfunction remains unknown. Thus, in the present study it was investigated whether elevated plasma PAI-1 activity is associated with coronary microvascular dysfunction in hypertensive patients., Methods and Results: Thirty patients with untreated essential hypertension and 10 age-matched healthy controls were studied prospectively. Myocardial blood flow (MBF) was measured by using (15)O-water positron emission tomography. Clinical variables associated with atherosclerosis (low-density lipoprotein-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, homeostasis model assessment (HOMA-IR), and PAI-1 activity) were assessed to determine their involvement in coronary microvascular dysfunction. Adenosine triphosphate (ATP)-induced hyperemic MBF and coronary flow reserve (CFR) were significantly lower in hypertensive patients than in healthy controls (ATP-induced MBF: 2.77+/-0.82 vs 3.49+/-0.71 ml x g(-1) x min(-1); p<0.02 and CFR: 2.95 +/-1.06 vs 4.25+/-0.69; p<0.001). By univariate analysis, CFR was positively correlated with HDL-cholesterol (r=0.46, p<0.02), and inversely with HOMA-IR (r=-0.39, p<0.05) and PAI-1 activity (r=-0.61, p<0.001). By multivariate analysis, elevated PAI-1 activity remained a significant independent determinant of diminished CFR., Conclusions: Elevated plasma PAI-1 activity was independently associated with coronary microvascular dysfunction, which suggests that plasma PAI-1 activity is an important clue linking hypofibrinolysis to the development of atherosclerosis.

Unlabelled: Cigarette smoking is one of the risk factors of cardiovascular diseases and is related to abnormal peripheral and coronary vascular vasomotion. Coronary vascular endothelial dysfunction is caused by chronic smoking in smokers without epicardial coronary artery stenosis. The coronary endothelial vasomotion abnormality is restored by interventions such as l-arginine or vitamin C infusion. However, to our knowledge, the effect of smoking cessation on coronary vasomotor response has not been elucidated. Therefore, the aim of this study was to assess the effect of smoking cessation on coronary vasomotor response by quantitative myocardial blood flow (MBF) measurement using (15)O-water and PET., Methods: Fifteen young smokers (Brinkman index > 100; mean age +/- SD, 26 +/- 4 y) with no evidence of heart disease or cardiovascular risk factors, except for smoking, and age-matched nonsmokers (n = 12) were enrolled in this study. MBF was measured at rest, during the cold pressor test (CPT), before and at 1 and 6 mo after smoking cessation. In addition, MBF measurement during adenosine triphosphate (ATP) infusion was performed before and at 6 mo after smoking cessation. In nonsmokers, MBF was measured at rest, during ATP infusion, and during the CPT., Results: MBF at rest and during ATP infusion did not differ between smokers and nonsmokers (0.73 +/- 0.12 vs. 0.80 +/- 0.15 mL/g/min and 3.15 +/- 1.43 vs. 3.69 +/- 0.76 mL/g/min, respectively; P = not significant). In contrast, MBF during the CPT in smokers was lower than that in nonsmokers (0.90 +/- 0.19 vs. 1.12 +/- 0.28 mL/g/min; P < 0.05). There was no significant difference in MBF either at rest or during ATP infusion between before and after smoking cessation, but MBF during the CPT increased at 1 mo in comparison with before cessation of smoking (0.90 +/- 0.19 vs. 1.02 +/- 0.22 mL/g/min; P < 0.01). An improvement of MBF response to the CPT was preserved at 6 mo after smoking cessation., Conclusion: Coronary vasomotor abnormality assessed by MBF response to the CPT was improved at 1 mo after smoking cessation. These findings indicate that coronary endothelial dysfunction may be reversible within 1 mo after smoking cessation in healthy young smokers.

Objectives: Small animal imaging has recently been focused on basic nuclear medicine. We have designed and built a small animal SPECT imaging system using a semiconductor camera and a newly designed collimator. We assess the performance of this system for small object imaging., Methods: We employed an MGC 1500 (Acrorad Co.) camera including a CdTe semiconductor. The pixel size was 1.4 mm/pixel. We designed and produced a parallel-hole collimator with 20-mm hole length. Our SPECT system consisted of a semiconductor camera with the subject holder set on an electric rotating stage controlled by a computer. We compared this system with a conventional small animal SPECT system comprising a SPECT-2000H scanner with four Anger type cameras and pinhole collimators. The count rate linearity for estimation of the scatter was evaluated for a pie-chart phantom containing different concentrations of 99mTc. We measured the FWHM of the 99mTc SPECT line source along with scatter. The system volume sensitivity was examined using a flood source phantom which was 35 mm long with a 32-mm inside diameter. Additionally, an in vivo myocardial perfusion SPECT study was performed with a rat., Results: With regards to energy resolution, the semiconductor camera (5.6%) was superior to the conventional Anger type camera (9.8%). In the count rate linearity evaluation, the regression lines of the SPECT values were y = 0.019x + 0.031 (r2 = 0.999) for our system and y = 0.018x + 0.060 (r2 = 0.997) for the conventional system. Thus, the scatter count using the semiconductor camera was less than that using the conventional camera. FWHMs of our system and the conventional system were 2.9 +/- 0.1 and 2.0 +/- 0.1 mm, respectively. Moreover, the system volume sensitivity of our system [0.51 kcps/(MBq/ ml)/cm] was superior to that of the conventional system [0.44 kcps/(MBq/ml)/cm]. Our system provided clear images of the rat myocardium, sufficient for practical use in small animal imaging., Conclusions: Our SPECT system, utilizing a semiconductor camera, permits high quantitative analysis by virtue of its low scatter radiation and high sensitivity. Therefore, this system may contribute to molecular imaging of small animals and basic medical research.

Background: The aims of this study were to develop a method for quantitative estimation of the myocardial blood flow index (MBFI) and myocardial flow reserve (MFR) of the whole left ventricle using (99m)technetium (Tc-99m)-sestamibi imaging., Methods and Results: Twenty-two patients with suspected coronary artery disease and 7 controls underwent both Tc-99m-sestamibi imaging and O-15 water positron emission tomography (PET). The global MBFI was calculated on the basis of the microsphere model from the ratio of the myocardial count to the area under the time - activity curve on the aortic arch. The regional MBFI was calculated from the relative distributions of Tc-99m-sestamibi uptake values. The regional MBFI and MFR (Tc-MFR) obtained using single-photon emission computed tomography were compared with the myocardial blood flow (MBF) and MFR (PET-MFR) obtained using PET as the gold standard. Regional MBFI significantly correlated with the MBF obtained using PET. Regional Tc-MFR also correlated with the regional PET-MFR, with some underestimation., Conclusion: These results indicate that regional MBF and MFR may be estimated by dynamic Tc-99m-sestamibi imaging and can be used for the early detection and estimation of the functional severity of coronary lesions without the need for a PET camera.

Unlabelled: The recovery of function in myocardium defined as viable by (18)F-FDG PET may differ from that defined by dobutamine stress echocardiography (DSE). The aim of this study was to investigate the difference in the oxidative metabolic response between myocardial segments with preserved contractile reserve (CR) and those without CR, in segments with and without preserved glucose metabolism (GM), using (11)C-acetate PET., Methods: Twenty patients with previous myocardial infarction (left ventricular ejection fraction, 37.1% +/- 16.5%) underwent dynamic (11)C-acetate PET at rest and during dobutamine (7.5 microg/kg/min) infusion. GM was evaluated using (18)F-FDG PET and CR was evaluated using DSE. Dysfunctional segments were divided into 3 groups: group A (n = 26) with preserved CR and GM, group B (n = 15) without CR but with preserved GM, and group C (n = 41) without CR and without preserved GM., Results: Resting oxidative metabolism (k mono = monoexponential clearance rate) was preserved in group A and group B (0.052 +/- 0.011/min vs. 0.051 +/- 0.012/min, P = not significant) but was reduced in group C (0.040 +/- 0.015/min) (P < 0.03 vs. group A and group B). The change in k mono, as a measure of the metabolic response to low-dose dobutamine, was significantly higher in group A (0.018 +/- 0.012) than that in group B (0.0075 +/- 0.0096, P < 0.03) and group C (0.0080 +/- 0.012, P < 0.005)., Conclusion: Viable segments based on (18)F-FDG PET have preserved resting oxidative metabolism. However, segments without CR but with preserved GM show a reduction in the oxidative metabolic response to low-dose dobutamine infusion. The decrease in CR may be related to the reduction in the metabolic response to inotropic stimulation despite preservation of tissue viability on (18)F-FDG PET.

Unlabelled: (15)O-Water and dynamic PET allow noninvasive quantification of myocardial blood flow (MBF). However, complicated image analyzing procedures are required, which may limit the practicality of this approach. We have designed a new practical algorithm, which allows stable, rapid, and automated quantification of regional MBF (rMBF) using (15)O-water PET. We designed an algorithm for setting the 3-dimensional (3D) region of interest (ROI) of the whole myocardium semiautomatically. Subsequently, a uniform input function was calculated for each subject using a time-activity curve in the 3D whole myocardial ROI. The uniform input function allows the mathematically simple and robust algorithm to estimate rMBF., Methods: Thirty-six volunteers were used in the static (15)O-CO and dynamic (15)O-water PET studies. To evaluate the reproducibility of the estimates, a repeated (15)O-water scan was obtained under resting condition. In addition, to evaluate the stability of the new algorithm in the hyperemic state, a (15)O-water scan was obtained with adenosine triphosphate. This algorithm includes a procedure for positioning a 3D ROI of the whole myocardium from 3D images and dividing it into 16 segments. Subsequently, the uniform input function was calculated using time-activity curves in the whole myocardial ROI and in the LV ROI. The uniform input function allowed this simple and robust algorithm to estimate the rMBF, perfusable tissue fraction (PTF), and spillover fraction (Va) according to a single tissue compartment model. These estimates were compared with those calculated using the original method. A simulation study was performed to compare the effects of errors in PTF or Va on the MBF using the 2 methods., Results: The average operating time for positioning a whole myocardial ROI and 16 regional myocardial ROIs was <5 min. The new method yielded less deviation in rMBF (0.876 +/- 0.177 mL/min/g, coefficient of variation [CV] = 20.2%, n = 576) than those with the traditional method (0.898 +/- 0.271 mL/min/g, CV = 30.1%, n = 576) (P < 0.01). In the hyperemic state, the new method yielded less deviation in rMBF (3.890 +/- 1.250 mL/min/g, CV = 32.1%) than those with the traditional method (3.962 +/- 1.762 mL/min/g, CV = 44.4%) (P < 0.05). This method yielded significantly higher reproducibility of rMBF (r = 0.806, n = 576) than the original method (r = 0.756, n = 576) (P < 0.05). Our new method yielded a better correlation in the repeated measurement values of rMBF and less variability among the regions in the myocardium than with the original theory of the (15)O-water technique. The simulation study demonstrated fewer effects of error in the PTF or Va on the MBF value with the new method., Conclusion: We have developed a technique for an automated, simplified, and stable algorithm to quantify rMBF. This software is considered to be practical for clinical use in myocardial PET studies using (15)O-water with a high reproducibility and a short processing time.

Unlabelled: Recent studies have clarified that hemodynamically compromised patients are at high risk for subsequent stroke. The acetazolamide test is widely used to detect the patients with hemodynamic compromise due to occlusive carotid artery disease. Previous studies have suggested that patients with impaired reactivity to acetazolamide had an increased oxygen extraction fraction (OEF) on PET. However, the underlying pathophysiology has not been defined in patients with reduced blood flow and preserved reactivity to acetazolamide due to carotid occlusive diseases regardless of a normal appearance on MRI. This study aimed to clarify hemodynamic and metabolic parameters in such patients, using (15)O gas and (11)C-flumazenil (FMZ) PET., Methods: Our study included 15 patients who had reduced cerebral blood flow (CBF) and preserved cerebrovascular reactivity (CVR) to acetazolamide in the ipsilateral middle cerebral artery territory due to occlusive carotid diseases on N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) SPECT. We determined the CBF, cerebral metabolic rate for oxygen (CMRO(2)), cerebral blood volume (CBV), and OEF using (15)O gas PET. The binding potential for (11)C-FMZ was also measured in 5 patients. All patients were medically treated and followed-up during a mean period of 2.7 y., Results: (15)O gas PET scans revealed that the ipsilateral CBF and CMRO(2) were reduced to 80% +/- 11% (P < 0.0001) and 78% +/- 8% (P < 0.0001) of the contralateral side, respectively. However, there was no significant side-to-side difference in the CBV and OEF. The ipsilateral binding potential for (11)C-FMZ was also significantly reduced to 82% +/- 2% of the contralateral side (P < 0.05), being very similar to the asymmetry of the CBF and CMRO(2). No patients suffered further ischemic stroke in the ipsilateral hemisphere during the follow-up period., Conclusion: Our results strongly suggest that a reduced CBF and a normal CVR characterize oxygen hypometabolism probably due to ischemia-related neuronal loss-namely, incomplete infarction. Such an ischemic lesion is not hemodynamically compromised and is at very low risk for a subsequent ischemic stroke even if the patient is medically treated.

Background and Purpose: Blood vessels are usually conspicuous on dynamic CT perfusion images. The presence of large vessels may lead to overestimation of the quantitative value of cerebral blood flow (CBF). We evaluated the efficacy of the vascular-pixel elimination (VPE) method in quantitative CT perfusion imaging, in comparison with positron emission tomography (PET)., Methods: Five healthy volunteers underwent CT perfusion and PET studies. A four-channel multi-detector row CT scanner was used. Dynamic cine scanning was performed after bolus injection of an intravenous contrast agent. CT-CBF was calculated by the central volume principle and deconvolution method. PET was performed after infusion of (15)O-labeled water. PET-CBF was calculated by using a nonlinear least squares method. Average CBF values of the whole section, gray matter, and white matter with both CT and PET were compared after image registration. The comparison was performed with and without VPE. In the VPE method, the vascular pixels were defined by the cerebral blood volume value of the pixel. The threshold of VPE was changed from 5 to 20 mL/100 g. Pixel-by-pixel correlation between CT-CBF and PET-CBF and linear regression analysis were also performed., Results: Without VPE, CT-CBF was overestimated in all subjects. As the VPE threshold decreased, CT-CBF decreased and the correlation coefficient increased. The best correlation was observed at a VPE threshold of 8 mL/100 g in four of the five subjects. Average CT-CBF values, without VPE, of the whole section, gray matter, and white matter were 59.01, 66.73, and 42.53 mL/100 g/min, respectively. With VPE (threshold, 8 mL/100 g), average CT-CBF values of the whole section, gray matter, and white matter were 45.56, 52.75, and 30.38, respectively. The corresponding PET-CBF values were 46.86, 50.89, and 38.20 mL/100 g/min, respectively., Conclusion: Vascular pixels should be excluded from the calculation of CT-CBF to avoid overestimation of the CBF values. If vascular pixels are excluded, CBF calculation with CT perfusion imaging is considerably accurate.

Background: Coronary abnormalities after Kawasaki disease (KD) may be associated with endothelial dysfunction due to intimal hypertrophy. The purpose of this study was to evaluate myocardial flow reserve (MFR) and endothelial function in regressed aneurysmal regions after KD. Methods and Results- Subjects were 12 patients aged 16.0+/-2.6 years who suffered from KD at 1.7+/-1.5 years and 12 normal subjects aged 26.5+/-3.4 years. MFR and endothelial function were estimated, respectively, by changes in myocardial blood flow (MBF) during ATP infusion and by that during cold pressor test using (15)O-water positron emission tomography. Data from 24 regressed aneurysmal regions were compared with those from the corresponding regions (n=36) in the control group. Although the MBF at rest in the regressed aneurysmal regions was similar to that in controls, the MBF at a hyperemic state induced by ATP infusion in the regressed aneurysmal regions was significantly lower than that in the control regions. Therefore, the MFR in regressed aneurysmal regions was significantly lower than that in controls (3.53+/-0.95 versus 4.60+/-1.14; P<0.05). MBF at rest and during the cold pressor test did not change in the control regions, but it was significantly reduced in regressed aneurysmal regions. The ratio of MBF during the cold pressor test to MBF at rest was significantly lower in regressed aneurysmal regions than in control regions (0.67+/-0.15 versus 1.00+/-0.15; P<0.05)., Conclusions: MFR and endothelial function are often impaired in regressed aneurysmal regions after KD, and tomography enables the noninvasive evaluation of coronary function.