Chietsugu Katoh

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: a study using oxygen 15–labeled water PET

BackgroundMyocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD.Methods and ResultsTwenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg · kg-1 · min-1) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 ± 0.54) than in group B (2.22 ± 0.87, P < .05), in group C (2.92 ± 1.21, P < .01), and in normal segments (3.86 ± 1.24, P < .001). CFR in group B was lower than in group C (P < .02) and in normal segments (P < .001). CFR in group C was lower than in normal segments (P < .02).ConclusionsAreas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.

Abnormal neuronal network in anorexia nervosa studied with I-123-IMP SPECT.

Single photon emission computed tomography was used to study 14 female patients with anorexia nervosa and 8 female normal comparison subjects. Automatic voxel-based analysis of the images was carried out using statistical parametric mapping (SPM) software. Statistics across the entire brain were displayed as Z scores (threshold: P<0.05). Compared with the normal comparison subjects, the anorectic patients were characterized by hypoperfusion in the medial prefrontal cortex and the anterior cingulate gyrus, and hyperperfusion in the thalamus and the amygdala-hippocampus complex. These results suggest that a dysfunction in neuronal circuitry may be related to anorexia nervosa.

Clinical role of 18 F-FDG PET for initial staging of patients with extrahepatic bile duct cancer

Abstract. In extrahepatic bile duct cancer, preoperative evaluation is important because only surgical excision of all detectable tumours is associated with improvement in 5-year survival. However, morphological imaging techniques, including computed tomography (CT), are still insufficient for accurate staging. The purpose of this study was to assess the additional value, in relation to CT, of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) for the evaluation of extrahepatic bile duct cancer. Thirty patients with extrahepatic bile duct cancer underwent both 18F-FDG PET and CT for initial staging. The results of the two modalities for evaluation of primary tumours and regional lymph nodes were compared with the final diagnoses based on pathological or clinical findings. The primary tumours were interpreted as malignant on the basis of CT in 24 (80%) of the patients, while 18F-FDG PET revealed increased 18F-FDG uptake in 18 (60%) of them. On the other hand, 18F-FDG PET showed focal accumulation of 18F-FDG in the bile duct in three of the six patients with equivocal findings on CT. The sensitivity, specificity and accuracy of CT for regional lymph node metastases were 54%, 59% and 57%, while those of 18F-FDG PET were 38%, 100% and 73%, respectively. The specificity of 18F-FDG PET for regional lymph node metastases was significantly higher than that of CT (P<0.01). Of 14 patients with N1 or N2 disease diagnosed by CT, only seven (50%) had a final diagnosis of regional lymph node metastasis. In these 14 patients, 18F-FDG PET accurately evaluated the N component of the disease in 12 patients (86%). In conclusion, in the initial staging of patients with extrahepatic bile duct cancer, 18F-FDG PET offers additional value in relation to CT in evaluating both the primary tumour and regional lymph nodes.

Myocardial Oxygen Consumption Is Unchanged but Efficiency Is Reduced in Patients With Essential Hypertension and Left Ventricular Hypertrophy

BACKGROUND Patients with hypertension and left ventricular hypertrophy (LVH) are prone to develop heart failure. We tested the hypothesis that compensatory LVH is associated with normalization of myocardial oxygen consumption and that this occurs at the expense of a decrease in the ratio between cardiac work and oxygen consumption (efficiency). METHODS AND RESULTS Nine hypertensive men with LVH (LVH+) (age 42+/-2 years), left ventricular mass index (LVMI) 161+/-8 g/m(2), blood pressure (BP) 145+/-16/88+/-10 mm Hg (mean+/-SD); 8 hypertensive men without LVH (LVH-) (age 39+/-5 years, LVMI 107+/-15 g/m(2), BP 140+/-15/90+/-11 mm Hg); and 10 normotensive men (CONT) were studied. Myocardial blood flow, oxygen consumption, and glucose uptake were measured during euglycemic hyperinsulinemia using PET techniques. LV dimensions, volumes, and workload were determined by echocardiography, and efficiency was calculated. Myocardial workload (2.5+/-0.8 versus 3.0+/-0.6 versus 2. 3+/-0.5 mm Hg. mL. min(-1). g(-1) for CONT versus LVH- versus LVH+; P<0.05, LVH- versus LVH+), myocardial blood flow (0.84+/-0.16 versus 1.06+/-0.22 versus 0.81+/-0.09 mL. g(-1). min, respectively; P<0.05, LVH- versus other groups) and oxygen consumption (0.09+/-0.02 versus 0.14+/-0.03 versus 0.11+/-0.01 ml. g(-1). min(-1), respectively; P<0. 05, LVH- versus other groups) were increased in the LVH- group. Myocardial efficiency was reduced in the LVH+ group (18.1+/-4.1% versus 15.1+/-2.3% versus 13.5+/-1.9%, respectively; P<0.05, LVH+ versus CONT). CONCLUSIONS Myocardial oxygen consumption per unit weight is increased in hypertensive patients without LVH but is normal in those with LVH. The normalization of oxygen consumption via hypertrophy occurs at the expense of efficiency, which may predispose hypertensive patients with LVH to heart failure.

Assessment of Coronary Function in Children With a History of Kawasaki Disease Using 15O-Water Positron Emission Tomography

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 15O-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.

Repeatability of Rest and Hyperemic Myocardial Blood Flow Measurements with 82Rb Dynamic PET

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.

Plasma Interleukin-6 and Tumor Necrosis Factor-α Can Predict Coronary Endothelial Dysfunction in Hypertensive Patients

Coronary endothelial function is impaired in hypertension; however, the severity of this impairment varies among patients. We aimed to identify the predictors of coronary endothelial dysfunction among clinical variables related to hypertension and atherosclerosis. Twenty-seven untreated, uncomplicated essential hypertensive patients and 10 age-matched healthy controls were studied prospectively. Myocardial blood flow (MBF) was measured by using 15O-water positron emission tomography (PET) at rest and during a cold pressor test (CPT). Coronary vascular resistance (CVR) during CPT was used as a marker of coronary endothelial function. Serum low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, malondialdehyde-LDL, homeostasis model assessment, high-sensitivity C-reactive protein (hs-CRP), and plasma interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α were also measured. CVR during CPT was significantly higher in hypertensive patients than in healthy controls (114±26 vs. 94±12 mmHg/[mL/g/min]; p<0.05). By univariate analysis, CVR during CPT was correlated with LDL cholesterol (r=0.38, p<0.05), IL-6 (r=0.46, p<0.02), and TNF-α (r=0.39, p<0.05) in hypertensive patients. By multivariate analysis, IL-6 and TNF-α were significant independent predictors of CVR during CPT. Elevated plasma IL-6 and TNF-α levels were independent predictors of coronary endothelial dysfunction in hypertensive patients. These results suggest that plasma IL-6 and TNF-α might be useful for identifying the high risk subgroup of hypertensive patients with coronary endothelial dysfunction and provide an important clue to link systemic inflammation to the development of coronary atherosclerosis.

Myocardial beta-Adrenergic Receptor Density Assessed by 11C-CGP12177 PET Predicts Improvement of Cardiac Function After Carvedilol Treatment in Patients with Idiopathic Dilated Cardiomyopathy

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

Evaluating performance of a pixel array semiconductor SPECT system for small animal imaging

ObjectivesSmall 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.MethodsWe employed an MGC1500 (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 of99mTc. We measured the FWHM of the99mTc 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, anin vivo myocardial perfusion SPECT study was performed with a rat.ResultsWith 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 werey = 0.0 9x+ 0.031 (r2 = 0.999) for our system andy = 0.018* + 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/m/)/cm]. Our system provided clear images of the rat myocardium, sufficient for practical use in small animal imaging.ConclusionsOur 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. Key words: semiconductor detectors, small animal imaging, single photon emission computed tomography

Decreased Myocardial β-Adrenergic Receptor Density in Relation to Increased Sympathetic Tone in Patients with Nonischemic Cardiomyopathy

Cardiac sympathetic function plays an important role in the regulation of left ventricular (LV) function and the pathophysiology of LV dysfunction. 11C-CGP-12177 (11C-CGP) has been used to assess myocardial β-adrenergic receptor (β-AR) density in vivo using PET. The aim of this study is to measure myocardial β-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 123I- metaiodobenzylguanidine (123I-MIBG) imaging. Methods: 11C-CGP PET was performed on 16 patients with nonischemic cardiomyopathy and 8 age-matched healthy volunteers using a double injection method. A 11C-CGP dynamic scan for 75 min was performed after the injection of 11C-CGP with a high specific activity. After 30 min, 11C-CGP with a low specific activity was injected. The β-AR density of the whole LV was calculated on the basis of the graphical analysis method. Additionally, β-AR density was compared with LV ejection fraction (LVEF), sympathetic presynaptic function assessed using 123I-MIBG kinetics, and neurohormonal parameters. Results: The β-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, β-AR density correlated significantly with LVEF (r = 0.62, P < 0.05). Furthermore, β-AR density correlated significantly with the 123I-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 β-AR density and early H/M ratio was not significant (r = 0.40, P = 0.13). The β-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 β-AR density measured by 11C-CGP PET was observed in patients with nonischemic cardiomyopathy. This downregulation may be due to the increased presynaptic sympathetic tone as assessed by 123I-MIBG imaging.