Elevated serum endothelin-1 is an independent predictor of coronary microvascular dysfunction in non-obstructive territories in patients with coronary artery disease.

Endothelin-1 contributes to the constrictor response of the coronary arteries in patients with ischemia with normal coronary arteries. There is thus increasing evidence that endothelin-1 plays a role in coronary microvascular dysfunction (CMD). We investigated whether elevated endothelin-1 is associated with CMD in patients with coronary artery disease (CAD). We prospectively studied 49 consecutive CAD patients with 1- or 2-vessel disease (age 71 ± 10 years, 43 males). Myocardial blood flow (MBF) was measured by 15O-water PET/CT at rest and during stress, and the coronary flow reserve (CFR) was calculated by dividing the stress MBF by the rest MBF. A CFR of less than 2.0 in non-obstructive regions was defined as a marker of CMD. Eighteen out of 49 (37%) CAD patients had CMD. Endothelin-1 in patients with CMD was significantly higher than in those without CMD (2.27 ± 0.81 vs. 1.64 ± 0.48 pg/mL, P = 0.001). Accordingly, univariate ROC analysis showed that the continuous endothelin-1 levels significantly discriminated between the presence and absence of CMD (area under the curve = 0.746 [95%CI 0.592-0.899]). The dichotomous treatment of elevated endothelin-1 as 1.961 pg/mL or more yielded the optimal discriminatory capacity, with a sensitivity of 72.2% and a specificity of 71.0%. High endothelin-1 was still a significant predictor of CMD after adjusting for diabetes mellitus (odds ratio = 6.64 [1.75-25.22], P = 0.005). Endothelin-1 is associated with CMD in non-obstructive territories in patients with CAD, suggesting that endothelin-1 is a potential target for treating CMD in CAD patients.

A convolutional neural network-based system to classify patients using FDG PET/CT examinations.

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.

Quantification of myocardial blood flow with 11C-hydroxyephedrine dynamic PET: comparison with 15O-H2O PET.

BACKGROUND: 11C-hydroxyephedrine (HED) PET has been used to evaluate the myocardial sympathetic nervous system (SNS). Here we sought to establish a simultaneous approach for quantifying both myocardial blood flow (MBF) and the SNS from a single HED PET scan. METHODS: Ten controls and 13 patients with suspected cardiac disease were enrolled. The inflow rate of 11C-HED (K1) was obtained using a one-tissue-compartment model. We compared this rate with the MBF derived from 15O-H2O PET. In the controls, the relationship between K1 from 11C-HED PET and the MBF from 15O-H2O PET was linked by the Renkin-Crone model. RESULTS: The relationship between K1 from 11C-HED PET and the MBF from 15O-H2O PET from the controls' data was approximated as follows: K1  =  (1 - 0.891 * exp(- 0.146/MBF)) * MBF. In the validation set, the correlation coefficient demonstrated a significantly high relationship for both the whole left ventricle (r = 0.95, P < 0.001) and three coronary territories (left anterior descending artery: r = 0.96, left circumflex artery: r = 0.81, right coronary artery: r =  0.86; P < 0.001, respectively). CONCLUSION: 11C-HED can simultaneously estimate MBF and sympathetic nervous function without requiring an additional MBF scan for assessing mismatch areas between MBF and SNS.

Volume-based glucose metabolic analysis of FDG PET/CT: The optimum threshold and conditions to suppress physiological myocardial uptake.

OBJECTIVE: FDG PET/CT plays a significant role in the diagnosis of inflammatory heart diseases and cardiac tumors. We attempted to determine the optimal FDG uptake threshold for volume-based analyses and to evaluate the relationship between the myocardial physiological uptake volume in FDG PET and several clinical factors. METHODS: A total of 190 patients were retrospectively analyzed. The cardiac metabolic volume (CMV) was defined as a volume within the boundary determined by a threshold (SUVmean of blood pool × 1.5). RESULTS: The SUVmean of the blood pool measured in the descending aorta (DA) (r = 0.86, intraclass correlation coefficient [ICC] = 0.93, P < 0.0001) and that in the left ventricle (LV) cavity (r = 0.87, ICC = 0.90, P < 0.0001) showed high inter-operator reproducibility. However, the SUVmean in the LV cavity showed a significant correlation with the CMV (P = 0.0002, r = 0.26). The CMV in the patients who fasted < 18 hours were significantly higher (49.7  ±  73.2 vs. 18.0  ±  53.8 mL, P = 0.0013) compared to the patients with > 18-hour fasting. The multivariate analysis demonstrated that only the fasting period > 18 hours was independently associated with CMV = 0. CONCLUSION: Our findings revealed that the DA is suitable to decide the threshold for the volume-based analysis. The fasting time was significantly associated with the cardiac FDG uptake.

Relationship between intelligence quotient (IQ) and cerebral metabolic rate of oxygen in patients with neurobehavioural disability after traumatic brain injury.

OBJECTIVE: Cerebral metabolism may play a significant role in neurobehavioural disability following traumatic brain injury (TBI). In this study, we examined the relationship between intelligence quotient (IQ) and the cerebral metabolic rate of oxygen (CMRO2) in the lateral prefrontal cortex, which was measured by 15O-labelled gas positron emission tomography (PET), in patients with TBI. MATERIALS AND METHODS: The subjects were 12 patients (eight males and four females) who suffered from neurobehavioural disability following TBI. Their mean age was 33.3 years. The cause of injury was traffic accidents in all patients and the mean period after injury was 44.8 months. These patients underwent 15O-labelled gas PET and tests using either the Wechsler Adult Intelligence Scale-Revised (WAIS-R) or the Wechsler Intelligence Scale for Children-Revised (WISC-R). Pearson's correlation between CMRO2 and total IQ (TIQ) was calculated. RESULTS: A statistically significant correlation was observed between TIQ and CMRO2 in the right Brodmann areas (BAs) 44 and 45. The lower the WAIS score, the higher the CMRO2 in both areas. CONCLUSION: Neurological function negatively correlated with the metabolism of oxygen. It was possible that changes in brain networks increased the neuronal activity in the undamaged areas and that the increased activity compensated for the function decline.

Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study.

PURPOSE: This investigation aimed to identify significant predictors of regional sympathetic denervation quantified by 11C-hydroxyephedrine (HED) positron emission tomography (PET) in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). METHODS: Included in the study were 34 patients (age 63 ± 15 years, 23 men) with HFpEF (left ventricular ejection fraction ≥40%) and 11 age-matched volunteers without heart failure. Cardiac magnetic resonance imaging was performed to measure left ventricular size and function, and the extent of myocardial late gadolinium enhancement (LGE). 11C-HED PET was performed to quantify myocardial sympathetic innervation that was expressed as a 11C-HED retention index (RI, %/min). To identify predictors of regional 11C-HED RI in HFpEF patients, we propose a multivariate mixed-effects model for repeated measures over segments with an unstructured covariance matrix. RESULTS: Global 11C-HED RI was significantly lower and more heterogeneous in HFpEF patients than in volunteers (P < 0.01 for all). Regional 11C-HED RI was correlated positively with systolic wall thickening (r = 0.42, P < 0.001) and negatively with the extent of LGE (r = -0.43, P < 0.001). Segments in HFpEF patients with a large extent of LGE had the lowest regional 11C-HED RI among all segments (P < 0.001 in post hoc tests). Multivariate analysis demonstrated that systolic wall thickening and the extent of LGE were significant predictors of regional 11C-HED RI in HFpEF patients (both P ≤ 0.001). CONCLUSION: Regional sympathetic denervation was associated with contractile dysfunction and fibrotic burden in HFpEF patients, suggesting that regional sympathetic denervation may provide an integrated measure of myocardial damage in HFpEF.

Quantification of myocardial blood flow with dynamic perfusion 3.0 Tesla MRI: Validation with (15) O-water PET.

BACKGROUND: To develop and validate a method for quantifying myocardial blood flow (MBF) using dynamic perfusion magnetic resonance imaging (MBFMRI ) at 3.0 Tesla (T) and compare the findings with those of (15) O-water positron emission tomography (MBFPET ). METHODS: Twenty healthy male volunteers underwent magnetic resonance imaging (MRI) and (15) O-water positron emission tomography (PET) at rest and during adenosine triphosphate infusion. The single-tissue compartment model was used to estimate the inflow rate constant (K1). We estimated the extraction fraction of Gd-DTPA using K1 and MBF values obtained from (15) O-water PET for the first 10 subjects. For validation, we calculated MBFMRI values for the remaining 10 subjects and compared them with the MBFPET values. In addition, we compared MBFMRI values of 10 patients with coronary artery disease with those of healthy subjects. RESULTS: The mean resting and stress MBFMRI values were 0.76 ± 0.10 and 3.04 ± 0.82 mL/min/g, respectively, and showed excellent correlation with the mean MBFPET values (r = 0.96, P < 0.01). The mean stress MBFMRI value was significantly lower for the patients (1.92 ± 0.37) than for the healthy subjects (P < 0.001). CONCLUSION: The use of dynamic perfusion MRI at 3T is useful for estimating MBF and can be applied for patients with coronary artery disease.

Attenuated right ventricular energetics evaluated using ¹¹C-acetate PET in patients with pulmonary hypertension.

PURPOSE: The right ventricle (RV) has a high capacity to adapt to pressure or volume overload before failing. However, the mechanisms of RV adaptation, in particular RV energetics, in patients with pulmonary hypertension (PH) are still not well understood. We aimed to evaluate RV energetics including RV oxidative metabolism, power and efficiency to adapt to increasing pressure overload in patients with PH using (11)C-acetate PET. METHODS: In this prospective study, 27 patients with WHO functional class II/III PH (mean pulmonary arterial pressure 39.8 ± 13.5 mmHg) and 9 healthy individuals underwent (11)C-acetate PET. (11)C-acetate PET was used to simultaneously measure oxidative metabolism (k mono) for the left ventricle (LV) and RV. LV and RV efficiency were also calculated. RESULTS: The RV ejection fraction in PH patients was lower than in controls (p = 0.0054). There was no statistically significant difference in LV k mono (p = 0.09). In contrast, PH patients showed higher RV k mono than did controls (0.050 ± 0.009 min(-1) vs. 0.030 ± 0.006 min(-1), p < 0.0001). PH patients exhibited significantly increased RV power (p < 0.001) and hence increased RV efficiency compared to controls (0.40 ± 0.14 vs. 0.017 ± 0.12 mmHg·mL·min/g, p = 0.001). CONCLUSION: The RV oxidative metabolic rate was increased in patients with PH. Patients with WHO functional class II/III PH also had increased RV power and efficiency. These findings may indicate a myocardial energetics adaptation response to increasing pulmonary arterial pressure.

Quantification of myocardial blood flow using dynamic 320-row multi-detector CT as compared with ¹5O-H2O PET.

OBJECTIVES: This study introduces a method to calculate myocardium blood flow (MBF) and coronary flow reserve (CFR) using the relatively low-dose dynamic 320-row multi-detector computed tomography (MDCT), validates the method against (15)O-H2O positron-emission tomography (PET) and assesses the CFRs of coronary artery disease (CAD) patients. METHODS: Thirty-two subjects underwent both dynamic CT perfusion (CTP) and PET perfusion imaging at rest and during pharmacological stress. In 12 normal subjects (pilot group), the calculation method for MBF and CFR was established. In the other 13 normal subjects (validation group), MBF and CFR obtained by dynamic CTP and PET were compared. Finally, the CFRs obtained by dynamic CTP and PET were compared between the validation group and CAD patients (n = 7). RESULTS: Correlation between MBF of MDCT and PET was strong (r = 0.95, P < 0.0001). CFR showed good correlation between dynamic CTP and PET (r = 0.67, P = 0.0126). CFRCT in the CAD group (2.3 ± 0.8) was significantly lower than that in the validation group (5.2 ± 1.8) (P = 0.0011). CONCLUSIONS: We established a method for measuring MBF and CFR with the relatively low-dose dynamic MDCT. Lower CFR was well demonstrated in CAD patients by dynamic CTP. KEY POINTS: • MBF and CFR can be calculated using dynamic CTP with 320-row MDCT. • MBF and CFR showed good correlation between dynamic CTP and PET. • Lower CFR was well demonstrated in CAD patients by dynamic CTP.

Improvement in the estimation of perfusable tissue fraction and myocardial flow reserve in the ischemic myocardial lesions using ECG-gated dynamic myocardial PET with 15O-water.

OBJECTIVE: Perfusable tissue fraction (PTF) and myocardial flow reserve (MFR) from 15O-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 15O-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 15O-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 15O-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.

Interrelation between myocardial oxidative metabolism and diastolic function in patients undergoing surgical ventricular reconstruction.

PURPOSE: Diastolic function is impaired in patients with end-stage heart failure. Favorable structural changes by surgical ventricular reconstruction (SVR) are thought to improve diastolic function, however, previous studies reported the contradictory results. We hypothesized that cardiac oxidative metabolism and diastolic dysfunction might improve in parallel to the reduction of left ventricular chamber size after SVR. METHODS: We studied 11 patients underwent SVR associated with mitral valve repair for end-stage heart failure due to dilated cardiomyopathy. Diastolic function was assessed by echocardiography and myocardial oxidative metabolism was measured by the monoexponential clearance (k-mono) of (11)C-acetate positron emission tomography at baseline and 1 month after SVR. RESULTS: All patients had preoperative severe diastolic dysfunction [E/A 4.11 ± 1.18, deceleration time (DT) 134 ± 26 ms]. The study patients were divided into 2 groups according to the changes in diastolic function after SVR; unchanged or worsened diastolic function in 6 patients (55 %, Non-responder) and improved diastolic function in 5 (45 %, Responder). K-mono and wall stress decreased only in responder. The changes in k-mono before and after SVR correlated with those in deceleration time (r = -0.63; p < 0.05) and wall stress (r = 0.75; p < 0.01). CONCLUSIONS: Improvement of diastolic dysfunction in patients with end-stage heart failure by SVR was in parallel to that in oxidative metabolism. It suggests that SVR reduced excessive metabolism during the diastolic phase, in part, via the improvement in diastolic function and the reduction in LV wall stress.

A convolutional neural network-based system to estimate the arterial plasma radioactivity curve in 18 F-FDG dynamic brain PET study.

PURPOSE: Quantitative images of metabolic activity can be derived through dynamic PET. However, the conventional approach necessitates invasive blood sampling to acquire the input function, thus limiting its noninvasive nature. The aim of this study was to devise a system based on convolutional neural network (CNN) capable of estimating the time-radioactivity curve of arterial plasma and accurately quantify the cerebral metabolic rate of glucose (CMRGlc) directly from PET data, thereby eliminating the requirement for invasive sampling. METHODS: This retrospective investigation analyzed 29 patients with neurological disorders who underwent comprehensive whole-body 18 F-FDG-PET/CT examinations. Each patient received an intravenous infusion of 185 MBq of 18 F-FDG, followed by dynamic PET data acquisition and arterial blood sampling. A CNN architecture was developed to accurately estimate the time-radioactivity curve of arterial plasma. RESULTS: The CNN estimated the time-radioactivity curve using the leave-one-out technique. In all cases, there was at least one frame with a prediction error within 10% in at least one frame. Furthermore, the correlation coefficient between CMRGlc obtained from the sampled blood and CNN yielded a highly significant value of 0.99. CONCLUSION: The time-radioactivity curve of arterial plasma and CMRGlc was determined from 18 F-FDG dynamic brain PET data using a CNN. The utilization of CNN has facilitated noninvasive measurements of input functions from dynamic PET data. This method can be applied to various forms of quantitative analysis of dynamic medical image data.

Quantification of regional myocardial blood flow estimation with three-dimensional dynamic rubidium-82 PET and modified spillover correction model.

PURPOSE: Myocardial blood flow (MBF) estimation with (82)Rubidium ((82)Rb) positron emission tomography (PET) is technically difficult because of the high spillover between regions of interest, especially due to the long positron range. We sought to develop a new algorithm to reduce the spillover in image-derived blood activity curves, using non-uniform weighted least-squares fitting. METHODS: Fourteen volunteers underwent imaging with both 3-dimensional (3D) (82)Rb and (15)O-water PET at rest and during pharmacological stress. Whole left ventricular (LV) (82)Rb MBF was estimated using a one-compartment model, including a myocardium-to-blood spillover correction to estimate the corresponding blood input function Ca(t)(whole). Regional K1 values were calculated using this uniform global input function, which simplifies equations and enables robust estimation of MBF. To assess the robustness of the modified algorithm, inter-operator repeatability of 3D (82)Rb MBF was compared with a previously established method. RESULTS: Whole LV correlation of (82)Rb MBF with (15)O-water MBF was better (P < .01) with the modified spillover correction method (r = 0.92 vs r = 0.60). The modified method also yielded significantly improved inter-operator repeatability of regional MBF quantification (r = 0.89) versus the established method (r = 0.82) (P < .01). CONCLUSION: A uniform global input function can suppress LV spillover into the image-derived blood input function, resulting in improved precision for MBF quantification with 3D (82)Rb PET.

Long-term smoking causes more advanced coronary endothelial dysfunction in middle-aged smokers compared to young smokers.

PURPOSE: Smoking cessation has been shown to normalize the coronary endothelial dysfunction in healthy young smokers. However, its effect has not been explored in middle-aged smokers with a longer history of smoking. Therefore, we compared the effects of smoking cessation on coronary vasomotor response between both young and middle-aged smokers and identified the predictor for its improvement. METHODS: This study investigated 14 young healthy smokers (age 25.2 ± 2.3 years), 13 middle-aged smokers (age 42.0 ± 6.5 years) and 10 non-smokers. Myocardial blood flow (MBF) was measured by using (15)O-water positron emission tomography (PET). RESULTS: At baseline, the ratio of MBF during the cold pressor test (CPT) to that at rest (MBF(CPT/rest)), the index of coronary endothelial function, was significantly decreased in both young and middle-aged smokers compared to non-smokers (1.24 ± 0.20 and 1.10 ± 0.39 vs 1.53 ± 0.18, p < 0.05 and p < 0.001, respectively). The ratio of MBF during adenosine triphosphate infusion to that at rest was significantly decreased in middle-aged smokers compared to young smokers and non-smokers (3.34 ± 1.52 vs 4.43 ± 0.92 and 4.69 ± 1.25, p < 0.05, respectively). MBF(CPT/rest) at 1 month after smoking cessation significantly increased in young smokers, but not in middle-aged smokers. By multivariate analysis, baseline serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) was an independent predictor for the changes in MBF(CPT/rest) after smoking cessation (ß = -0.45, p < 0.05). CONCLUSION: Coronary endothelial dysfunction was reversible by short-term smoking cessation in young smokers, but not in middle-aged smokers, which was associated with serum MDA-LDL levels. Long-term smoking exposure could lead to more advanced coronary endothelial dysfunction and atherosclerosis possibly via oxidative stress.

Incremental diagnostic value of regional myocardial blood flow quantification over relative perfusion imaging with generator-produced rubidium-82 PET.

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.

Translocator protein imaging with 18F-FEDAC-positron emission tomography in rabbit atherosclerosis and its presence in human coronary vulnerable plaques.

BACKGROUND AND AIMS: This study aimed to investigate whether N-benzyl-N-methyl-2-[7,8-dihydro-7-(2-[18F]fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide (18F-FEDAC), a probe for translocator protein (TSPO), can visualize atherosclerotic lesions in rabbits and whether TSPO is localized in human coronary plaques. METHODS: 18F-FEDAC-PET of a rabbit model of atherosclerosis induced by a 0.5% cholesterol diet and balloon injury of the left carotid artery (n = 7) was performed eight weeks after the injury. The autoradiography intensity of 18F-FEDAC in carotid artery tissue sections was measured, and TSPO expression was evaluated immunohistochemically. TSPO expression was examined in human coronary arteries obtained from autopsy cases (n = 16), and in human coronary plaques (n = 12) aspirated from patients with acute myocardial infarction (AMI). RESULTS: 18F-FEDAC-PET visualized the atherosclerotic lesions in rabbits as high-uptake areas, and the standard uptake value was higher in injured arteries (0.574 ± 0.24) than in uninjured arteries (0.277 ± 0.13, p < 0.05) or myocardium (0.189 ± 0.07, p < 0.05). Immunostaining showed more macrophages and more TSPO expression in atherosclerotic lesions than in uninjured arteries. TSPO was localized in macrophages, and arterial autoradiography intensity was positively correlated with macrophage concentration (r = 0.64) and TSPO (r = 0.67). TSPO expression in human coronary arteries was higher in AMI cases than in non-cardiac death, or in the vulnerable plaques than in early or stable lesions, respectively. TSPO was localized in macrophages in all aspirated coronary plaques with thrombi. CONCLUSIONS: 18F-FEDAC-PET can visualize atherosclerotic lesions, and TSPO-expression may be a marker of high-risk coronary plaques.

Usefulness of a 3D-printing air sampler for capturing live airborne bacteria and exploring the environmental factors that can influence bacterial dynamics.

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.

Myocardial oxidative metabolism is increased due to haemodynamic overload in patients with aortic valve stenosis: assessment using 11C-acetate positron emission tomography.

PURPOSE: The relationship between myocardial oxidative metabolism and pressure overload in aortic valve stenosis (AS) is not fully elucidated. We identified the determinants of myocardial oxidative metabolism by measuring its changes after aortic valve replacement (AVR) in patients with AS. METHODS: Myocardial 11C-acetate clearance rate constant (Kmono), an index of oxidative metabolism, was measured non-invasively by using positron emission tomography in 16 patients with moderate to severe AS and 7 healthy controls. The severity of AS was assessed by echocardiography. Of 16 patients, 5 were reexamined at 1 month after AVR. RESULTS: Kmono was significantly higher in patients with AS than healthy controls by 42% (0.068±0.014 vs 0.048±0.007/min, p<0.01). Kmono was significantly correlated with age (r=0.58, p<0.01), left ventricular (LV) mass index (r=0.61, p<0.01) and estimated systolic LV pressure (r=0.81, p<0.001) measured by echocardiography. By multivariate analysis, estimated LV systolic pressure was an independent predictor of Kmono (ß=0.93, p<0.01). After AVR, Kmono (from 0.075±0.012 to 0.061±0.014/min, p=0.043) and LV mass index (from 183±49 to 124±41 g/ml2, p=0.043) were significantly decreased despite no significant changes in rate-pressure product. CONCLUSION: Myocardial oxygen metabolism was increased in patients with AS, which was decreased after AVR. The increased myocardial oxidative metabolism in AS was largely attributable to the pressure overload of the LV.

Quantitative analysis of coronary endothelial function with generator-produced 82Rb PET: comparison with 15O-labelled water PET.

PURPOSE: Endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis. 82Rb is a generator-produced positron emission tomography (PET) myocardial perfusion tracer that is becoming more widely used. We aimed to (1) develop a method for quantitative assessment of coronary endothelial function using the myocardial blood flow (MBF) response during a cold pressor test (CPT) in smokers, measured using 82Rb PET, and (2) compare the results with those measured using 15O-water PET. METHODS: MBF was assessed at rest and during the CPT with 82Rb and 15O-water in nine controls and ten smokers. A one-compartment model with tracer extraction correction was used to estimate MBF with both tracers. CPT response was calculated as the ratio of MBF during the CPT to MBF at rest. RESULTS: At rest, measurements of MBF for smokers vs controls were not different using 15O-water (0.86±0.18 vs 0.70±0.13, p=0.426) than they were using 82Rb (0.83±0.23 vs 0.62±0.20, p=0.051). Both methods showed a reduced CPT response in smokers vs controls (15O-water, 1.03±0.21 vs 1.42±0.29, p=0.006; 82Rb, 1.02±0.28 vs 1.70±0.52, p<0.001). There was high reliability [intraclass correlation coefficients: 0.48 (0.07, 0.75)] of MBF measurement between 82Rb and 15O-water during the CPT. CONCLUSION: Using a CPT, 82Rb MBF measurements detected coronary endothelial dysfunctions in smokers. 82Rb MBF measurements were comparable to those made using the 15O-water approach. Thus, 82Rb PET may be applicable for risk assessments or evaluation of risk factor modification in subjects with coronary risk factors.

Development of Combination Methods for Detecting Malignant Uptakes Based on Physiological Uptake Detection Using Object Detection With PET-CT MIP Images.

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.