真鍋 徳子

Purpose: The quantification of coronary flow reserve (CFR) calculated as the ratio of the myocardial blood flow (MBF) during adenosine triphosphate (ATP) stress to MBF at rest is a useful method for evaluating the functional severity of coronary artery disease (CAD) using ¹⁵O-H₂O positron emission tomography (PET). The shorter acquisition time may reduce dyspnea and other side effects of ATP stress and may also reduce the effect of body movements during data acquisition. However, the impact of the shorter data acquisition time on the accuracy of MBF quantification has not been studied. In this retrospective study, we evaluated the accuracy of the MBF and CFR values obtained with shorter scan times using ¹⁵O-H₂O PET.<Br>Methods: Thirty patients suspected of having CAD (22 males, 8 females; age 56.5&plusmn;8.8 yrs) and 17 healthy controls (17 males; age 27.7&plusmn;6.2 yrs) underwent PET during rest and PET with ATP stress dynamic ¹⁵O-H₂O. The MBF was estimated with a one-tissue compartment model analysis. MBF and CFR values were calculated using the first 2-min and 3-min PET data of ¹⁵O-H₂O as shorter data acquisitions. These data were compared to the standard 6-min PET acquisition data.<Br>Results: With the use of the 3-min data, the regions of interest (ROIs) in the left ventricular (LV) chamber and myocardium could be set for all of the subjects. The intraclass correlation coefficients (ICCs) between the 3-min data and 6-min data of the rest MBF, stress MBF and CFR were 0.869, 0.870, and 0.819 in the patients, and 0.912, 0.910, and 0.930 in the controls. The 3-min CFR data showed a significant difference between the patients and controls (2.22&plusmn;1.02 vs. 4.02&plusmn;1.50, p<0.01), as did the 6-min data (2.19&plusmn;0.92 vs. 4.16&plusmn;1.39, p<0.01). However, the CFR based on 2-min data did not show a significant difference (1.96&plusmn;1.66 vs. 2.73&plusmn;1.03, p=0.088). Using a receiver operating characteristic (ROC) analysis, we observed that both the 3-min and 6-min CFR data could be used to separate the CAD patients and controls.<Br>Conclusions: A 3-min, but not 2-min, scan with ¹⁵O-H₂O PET can be used for the quantitative evaluation of MBF and CFR.

PURPOSE: To compare the morphology and minimum apparent diffusion coefficient (ADC) values among breast cancer subtypes. METHODS: Ninety-three patients, who underwent breast MRI and collectively had 98 pathologically proven invasive carcinomas, were enrolled. Morphology was evaluated according to BIRADS-MRI. Minimum ADC was measured. Morphology and minimum ADC were compared among subtypes. Multivariate logistic regression analyses were used to identify the characteristics associated with different subtypes. RESULTS: Oval/round shape was significantly associated with triple-negative (TN) cancer (TN vs. non-TN: 90.9% vs. 45.2%; p=0.0123). Rim enhancement was significantly less frequent in Luminal A (Luminal A vs. non-Luminal A: 34.2% vs. 76.1%; p=0.0003). The minimum ADC of Luminal A was significantly higher than that of Luminal B (HER2-negative) (834 vs. 748×10(-6)mm(2)/s; p<0.025). The minimum ADC of the TN-special type was significantly higher than that of TN-ductal (997 vs. 702×10(-6)mm(2)/s; p<0.025). On the multivariate analysis comparing the characteristics associated with Luminal A vs. Luminal B (HER2-negative), the internal enhancement characteristics of the mass and minimum ADC were significant factors. CONCLUSION: Morphology and minimum ADC would be useful in distinguishing breast cancer subtypes.

BACKGROUND: Amino acids (AAs) are emerging as a new class of effective molecules in the etiology of obesity and diabetes mellitus. However, most investigations have focused on subjects with obesity and/or impaired glucose regulation; the possible involvement of AAs in the initial phase of glucose dysregulation remains poorly understood. Furthermore, little attention has been given to possible associations between the pattern/degree of fat deposition and the plasma AA profile. Our objective was therefore to determine the relationships between plasma AA concentrations and the type/degree of obesity and glucose regulation in Japanese adults with normal glucose tolerance. METHODS: Eighty-three subjects with normal glucose tolerance were classified as obese or nonobese and as visceral obesity or nonvisceral obesity. Correlations between the plasma levels of 23 AAs and somatometric measurements, visceral fat area (VFA), subcutaneous fat area (SFA), and 75-g oral glucose tolerance test results were analyzed. RESULTS: Obesity or visceral obesity was associated with higher levels of branched-chain AAs (isoleucine, leucine, and valine), lysine, tryptophan, cystine, and glutamate but lower levels of asparagine, citrulline, glutamine, glycine, and serine (p < 0.04). Age- and gender-adjusted analyses indicated that VFA was positively correlated with tryptophan and glutamate levels, whereas VFA and SFA were negatively correlated with citrulline, glutamine, and glycine levels (p < 0.05). The fasting and 2-h plasma glucose levels or the homeostasis model assessment of insulin resistance were positively correlated with valine, glutamate, and tyrosine levels but negatively correlated with citrulline, glutamine, and glycine levels. The homeostasis model assessment for the β-cell function index was positively correlated with leucine, tryptophan, valine, and glutamate levels but negatively correlated with citrulline, glutamine, glycine, and serine levels (p < 0.05). CONCLUSIONS: The present study identified specific associations between 10 AAs and the type/degree of obesity, and indices of glucose/insulin regulation, in Japanese adults with preserved glucose metabolism. With the growing concern about the increasing prevalence of obesity and diabetes, the possible roles of these AAs as early markers and/or precursors warrant further investigation.

BACKGROUND: Breast MRI protocols have been improved by using a combination of dynamic scans for bilateral breasts and high-resolution imaging for a single breast which can be obtained during dynamic scans by recent technological advances. The purpose of this study was to compare high-resolution imaging during dynamic scans (HR-intra) with high-resolution imaging obtained post dynamic scans (HR-post). METHODS: Fifty-five women with pathologically proven breast cancer who underwent breast dynamic scans at 3-T MRI from February to September 2009 were enrolled in this study. Tumoral contrasts to the background breast tissue were compared by three radiologists independently in a blinded fashion. Results of visual assessment were categorized into three groups as follows: HR-intra being better (IB), equal (E), and HR-post being better (PB). The contrast to noise ratio (CNR) of the tumor and the signal to noise ratio of the normal breast gland (SNR) were compared between HR-intra and HR-post. RESULTS: Two patients were excluded because of poor MR imaging quality. Three radiologists separately categorized 64.2, 79.2, and 77.4 % of lesions as IB. The CNR of the tumor of HR-intra (mean ± SD = 6.9 ± 4.0) was significantly higher than that of HR-post (6.0 ± 3.7, p < 0.0001). The SNR of the normal breast gland of HR-intra (9.5 ± 1.7) was significantly lower than that of HR-post (10.0 ± 1.9, p < 0.0001). CONCLUSION: HR-intra during dynamic MRI provided earlier and better tumor to normal breast gland contrast than HR-post.

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.

PURPOSE: Although noninvasive and highly informative, transabdominal ultrasonography (US) is not yet an accepted means of staging colorectal cancer preoperatively. This prospective study evaluated the diagnostic accuracy of US in preoperative staging of patients with resectable colon cancers. METHODS: A total of 98 patients with primary colon cancer diagnosed by colonoscopy at our institute between January, 2011 and June, 2014 underwent preoperative ultrasonographic tumor staging. Depth of tumor infiltration (T-stage) was assessed by standard means (i.e., extent of mural involvement), analyzing agreement in US and histopathology determinations. RESULTS: All but two colon cancers (at splenic flexure) were detected by US (98%, 96/98). Compared with histopathology, overall accuracy of US in determining T-stage was 64% (61/96), indicating moderate reproducibility (κ coefficient 0.48; 95% CI 0.35-0.62; p < 0.001). Using a three-tier approach of graded muscularis propria (MP) involvement (Tis/T1, below MP; T2, within MP; and T3/T4, beyond MP), diagnostic agreement increased to 89% (85/96), with good agreement (κ coefficient 0.77; 95% CI 0.64-0.90; p < 0.001). No tumor characteristics or patient demographics influenced diagnostic agreement at any site in the colon. CONCLUSIONS: Given the potential to yield valuable information while limiting patient discomfort, US should be reconsidered as a means of assessing colon cancer.

PURPOSE: Previous radiological investigations have generally shown the superiority of metabolic imaging in distinguishing high-grade from low-grade glioma, but the presence of an oligodendroglial component may affect the diagnostic accuracy. We investigated the diagnostic accuracy of PET imaging using (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) in distinguishing high-grade from low-grade glioma, in correlation with the oligodendroglial component. METHODS: The study population comprised adult patients who underwent preoperative PET imaging using both MET and FDG within 1 week and successful excision of the tumour tissue, which confirmed WHO grade II-IV glioma. We examined the tumour metabolic activity in terms of lesion-to-normal uptake ratios (L/N ratio) in both MET PET and FDG PET images. We assessed the correlation between the imaging results and the histological findings to determine the diagnostic accuracy of receiver operating characteristics (ROC) analysis in detecting high-grade tumours. RESULTS: We studied 46 patients with glioma (13 low-grade and 33 high-grade), including 26 with an oligodendroglial components. The L/N ratios of the PET images showed significantly higher metabolic activities in high-grade gliomas than in low-grade gliomas for both MET (4.29 ± 1.22 and 2.36 ± 0.72, respectively; p < 0.0001) and FDG (1.72 ± 0.91 and 0.77 ± 0.26, respectively; p = 0.0007) images, although significant overlaps in L/N ratio were observed between high-grade and low-grade gliomas. Excluding the 26 patents with an oligodendroglial component improved the separation for both MET (4.62 ± 1.14 vs. 2.16 ± 0.63; p < 0.001) and FDG (1.76 ± 0.87 vs. 0.71 ± 0.14; p < 0.05) images. The ROC analyses demonstrated the clinical utility of the metabolic radiotracers in distinguishing high-grade from low-grade gliomas, showing similar AUC values for MET (0.91) and FDG (0.92). Excluding the 26 patents with an oligodendroglial component also further improved the diagnostic accuracy for both MET (AUC 0.98), and FDG (AUC 1.00) images. The metabolic radiotracers were significantly correlated with the MIB-1 labelling index (R = 0.52, p < 0.05 for MET; R = 0.52, p < 0.05, for FDG) only in gliomas without an oligodendroglial component. CONCLUSION: For better characterization of gliomas and for risk assessment, the results of metabolic PET imaging should be revised after obtaining the pathological report, because oligodendroglial differentiation may positively influence the substrate metabolism and thus complicated the preoperative evaluation.

BACKGROUND: Symptoms and signs and indices of right heart function are predictors of clinical outcomes in patients with pulmonary hypertension (PH). However, the significance of right atrial (RA) indices has not been sufficiently investigated. We investigated whether RA parameters predict outcomes in patients with pre-capillary PH. METHODS: Study subjects were 68 patients with pre-capillary PH. RA size and function (systolic, reservoir, and conduit functions) were evaluated by cardiac magnetic resonance imaging. RESULTS: During the mean follow-up period of 24 months, 16 of 68 patients experienced clinical worsening (CW), defined as hospitalization because of right heart failure, lung transplantation, or PH-related death. Kaplan-Meier and log-rank test showed that World Health Organization functional class, pericardial effusion, increased brain natriuretic peptide concentration, reduced right ventricular ejection fraction (RVEF), increased minimum RA volume index, and decreased RA reservoir volume were associated with CW-free survival. The combination of RVEF and RA reservoir function was a better predictor of CW-free survival. In univariate Cox hazard proportional analysis, CW was associated with the RA reservoir volume index (hazard ratio [HR] = 0.80). In multivariate analysis, CW was associated with World Health Organization functional class (HR = 4.3), RA minimum volume index (HR = 1.07), and RA reservoir volume index (HR = 0.73). CONCLUSIONS: RA volume and reservoir function and their combined use with RVEF are novel predictors of CW in patients with pre-capillary PH.

PURPOSE: To determine whether the preoperative pancreatic apparent diffusion coefficient (ADC) can be used to predict the development of postoperative pancreatic anastomotic failure (PAF). MATERIALS AND METHODS: We retrospectively examined the cases of 79 patients who underwent pancreatic head resection between January 2010 and October 2013. The patients underwent 1.5-T MR imaging including diffusion-weighted imaging before surgery. The main pancreatic duct diameter (MPD), the pancreatic parenchymal thickness (PT), and the ADC of the pancreatic remnant parenchyma were measured. Two radiologists blinded to the patients' outcomes performed the measurements. The imaging parameters were compared between the patients who developed PAF and those who did not. The cut-off ADC for the development of PAF was calculated with a receiver operating characteristic analysis. RESULTS: The imaging parameters were highly correlated between the two observers. The MPD and PT did not differ significantly among the patients. The mean pancreatic ADCs were significantly higher in the patients with PAF than in those without PAF. An ADC higher than 1.50 × 10(-3) mm(2)/s (Az = 0.719, observer-1) or 1.35 × 10(-3) mm(2)/s (Az = 0.752, observer-2) was optimal for predicting the development of postoperative PAF. CONCLUSION: Measuring the preoperative non-tumorous pancreatic ADC may be useful for the prediction of a postoperative PAF.

In this study, we aimed to compare fat-suppression homogeneity on breast MR imaging by using dual-source parallel radiofrequency excitation and image-based shimming (DS-IBS) with single-source radiofrequency excitation with volume shim (SS-Vol) at 3 Tesla. Twenty patients were included. Axial three-dimensional T1-weighted turbo-field-echo breast images with DS-IBS and SS-Vol were obtained. Fat suppression was scored with four grade points. The contrast of the pectoral muscle and the fat in each breast area was obtained in the head medial, head lateral, foot medial, and foot lateral areas. The axillary space was calculated and compared between DS-IBS and SS-Vol. The average DS-IBS score was significantly higher than that of SS-Vol. The mean contrasts of fat in the foot lateral areas and axillary spaces on DS-IBS images were significantly higher than on SS-Vol images.

OBJECTIVES: To determine the added discriminative value of detailed quantitative characterization of background parenchymal enhancement in addition to the tumor itself on dynamic contrast-enhanced (DCE) MRI at 3.0 Tesla in identifying "triple-negative" breast cancers. MATERIALS AND METHODS: In this Institutional Review Board-approved retrospective study, DCE-MRI of 84 women presenting 88 invasive carcinomas were evaluated by a radiologist and analyzed using quantitative computer-aided techniques. Each tumor and its surrounding parenchyma were segmented semi-automatically in 3-D. A total of 85 imaging features were extracted from the two regions, including morphologic, densitometric, and statistical texture measures of enhancement. A small subset of optimal features was selected using an efficient sequential forward floating search algorithm. To distinguish triple-negative cancers from other subtypes, we built predictive models based on support vector machines. Their classification performance was assessed with the area under receiver operating characteristic curve (AUC) using cross-validation. RESULTS: Imaging features based on the tumor region achieved an AUC of 0.782 in differentiating triple-negative cancers from others, in line with the current state of the art. When background parenchymal enhancement features were included, the AUC increased significantly to 0.878 (p<0.01). Similar improvements were seen in nearly all subtype classification tasks undertaken. Notably, amongst the most discriminating features for predicting triple-negative cancers were textures of background parenchymal enhancement. CONCLUSIONS: Considering the tumor as well as its surrounding parenchyma on DCE-MRI for radiomic image phenotyping provides useful information for identifying triple-negative breast cancers. Heterogeneity of background parenchymal enhancement, characterized by quantitative texture features on DCE-MRI, adds value to such differentiation models as they are strongly associated with the triple-negative subtype. Prospective validation studies are warranted to confirm these findings and determine potential implications.

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.

PURPOSE: Cardiac sarcoidosis is most commonly found in the left ventricular (LV) free wall. Presence in the right ventricle (RV) is less common but might be useful for detecting cardiac involvement of sarcoidosis. (18)F-fluorodeoxyglucose ((18)F-FDG) PET has been used to detect LV regions with cardiac sarcoidosis. However, the same has not been done for RV involvement. The aims of the current study were to evaluate RV (18)F-FDG uptake and its relationship to the distribution of LV wall (18)F-FDG-positive segments in the LV, and to evaluate whether patients with positive RV (18)F-FDG uptake met the 1993 diagnostic criteria of the Japanese Ministry of Health and Welfare (JMHW) guidelines regarding sarcoidosis with suspected cardiac involvement. METHOD: Fifty-nine biopsy-proven extra-cardiac sarcoidosis patients (age 56.1 ± 14.7 years) with suspected cardiac involvement based on abnormal electrocardiography or echocardiography findings underwent fasting (18)F-FDG PET or PET/CT. The LV wall was divided into 17 segments and RV uptake was also evaluated. RESULT: Among 59 patients, 35 (59.3%) showed some abnormal (18)F-FDG uptake in the RV and/or LV wall. With respect to the RV wall, 13 (22.0%) showed abnormal (18)F-FDG uptake. The number of LV-involved segments was 4.8 ± 2.4 in the patients with RV (18)F-FDG uptake, which was significantly higher than in the patients without RV uptake, 1.8 ± 2.2 (P < 0.0001). Patients with RV uptake more frequently met the diagnostic criteria of the 1993 JMHW guidelines (n = 27), than did those without RV uptake (84.6 vs. 34.8%, P = 0.0033). CONCLUSION: (18)F-FDG PET identified RV involvement less frequently than LV involvement in this study population. However, patients who had RV uptake showed a greater number of LV-involved segments and met the JMHW diagnostic criteria more frequently. Although RV uptake is less frequent, (18)F-FDG RV uptake may be useful in diagnosing cardiac involvement in sarcoidosis. CLINICAL TRIAL REGISTRATION: UMIN000006533.

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.

OBJECTIVE: The objective of this study was to determine the prevalence and risk factor (RF) correlates of aortic plaque (AP) detected by cardiovascular magnetic resonance (CMR), which mainly shows noncalcified plaques, and by noncontrast computed tomography (CT), which best depicts calcified plaques, in community-dwelling adults. APPROACH AND RESULTS: A total of 1016 Framingham Heart Study Offspring cohort members (64 ± 9 years; 474 men) underwent CMR and CT of the aorta. Potential RFs for AP (age; sex; body mass index; blood pressure; low-density lipoprotein and high-density lipoprotein cholesterol; fasting glucose; C-reactive protein; prevalent hypertension, diabetes mellitus, smoking; use of antihypertensive, diabetes mellitus, or lipid-lowering drugs) were compared between participants, with zero versus nonzero AP by CMR and by CT. Candidate RFs attaining P<0.05 for difference with either imaging modality were entered into multivariable logistic regression models adjusting for age, sex, and other RFs. Odds ratios were calculated for modality-specific prevalence of AP. Associations between RFs and continuous measures of AP were assessed using Tobit regression. Prevalence of CMR and CT AP was 49% and 82%, respectively. AP burdens by CMR and CT were correlated, r=0.28, P<0.0001. Increasing age and smoking were associated with prevalent AP by both CMR and CT. Additionally, prevalent AP by CMR was associated with female sex and fasting glucose and prevalent AP by CT with hypertension treatment and adverse lipid profile. CONCLUSIONS: AP by CMR and CT are both associated with smoking and increasing age, but other RFs differ between calcified and noncalcified AP. The relative predictive value of AP detected by CMR versus by CT for incident cardiovascular events remains to be determined.

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.

OBJECTIVE: Application of the electrocardiographically (ECG) gated positron emission tomography (PET) technique with (11)C-hydroxyephedrine (HED) would allow the simultaneous assessment of cardiac sympathetic and contractile functions. However, there are uncertainties regarding the diagnostic accuracy of left ventricular (LV) volume measurements using ECG-gated HED-PET. The purpose of this study was to clarify the minimal requirement of count statistics to measure LV volumes with ECG-gated HED-PET and to investigate the reliability of the measurements. METHODS: Five healthy volunteers and 11 patients with heart failure underwent a 40-min list-mode PET scan after an injection of HED (197 ± 35 MBq). The list-mode data were histogrammed into multiple sets of acquisition periods at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0 Mcount/bin and reconstructed into corresponding gated images using an iterative algorithm. The LV end-diastolic volume (LVEDV), the LV end-systolic volume (LVESV), and the LV ejection fraction (LVEF) were calculated in each acquisition period. These values were compared with those obtained by cardiac magnetic resonance imaging (MRI). Possible effects of HED retention on the accuracy of the volume measurements were investigated. RESULTS: Collecting less than 4.0 Mcount/bin resulted in noisy cardiac images. The lower counts resulted in underestimation in the volume measurements. Reasonably accurate volume measurements required equal to or greater than 6.0 Mcount/bin. This corresponded to 7.0 ± 1.9 min (range, 4.0-10.3 min) for the acquisition period. Volumetric results using the 6.0 Mcount/bin data highly correlated with cardiac MRI (LVEDV: r = 0.85, p < 0.0001; LVESV: r = 0.89, p < 0.0001; LVEF: r = 0.77, p < 0.01). The HED retention did not affect the volumetric results compared to the MRI volumetry. CONCLUSIONS: The volumetric accuracy with ECG-gated HED-PET was affected by the count statistics rather than the HED retention. LV volume measurements were feasible with 10-min acquisition period for most of the patients. This technique allows the simultaneous assessment of cardiac sympathetic and contractile functions without the need for an additional injection or scanning time, thus reducing overall costs for diagnostic imaging.

BACKGROUND: Fractional flow reserve (FFR) measured on catheterization is now widely used for the diagnosis of functional myocardial ischemia in patients with coronary artery disease (CAD). FFR, however, is invasive and carries potential procedural complications. Therefore, the aim of this study was to compare the diagnostic capability in functionally significant stenosis identified on FFR, between cardiac magnetic resonance myocardial perfusion imaging (CMR-MPI), single-photon emission computed tomography MPI (SPECT-MPI), and dobutamine stress echocardiography (DSE) in patients with CAD. METHODS AND RESULTS: A total of 25 patients who had at least 1 angiographic stenosis ≥50% on coronary angiography was studied. CMR-MPI, SPECT-MPI and DSE were done before FFR measurement. FFR was measured in all 3 major epicardial coronary arteries. Out of 71 vascular territories excluding 4 territories due to inadequate imaging, 29 (41%) had FFR <0.80. The sensitivity of CMR-MPI was significantly higher than that of SPECT-MPI and DSE (P=0.02 and P=0.001, respectively). The area under the receiver operating characteristic curve (AUC) for CMR-MPI (AUC, 0.92) was significantly greater than for SPECT-MPI (AUC, 0.73; P=0.006) and DSE (AUC, 0.69; P<0.001). CONCLUSIONS: CMR-MPI performed well in the detection of functionally significant stenosis defined according to FFR, and had the highest diagnostic sensitivity among the 3 modalities tested in patients with CAD.

The present study examined whether tricuspid annular plane systolic excursion (TAPSE) can simply predict right ventricular ejection fraction (RVEF) in patients with pulmonary hypertension (PH). The TAPSE cut-off value to predict reduced RVEF was also evaluated. The association between TAPSE and cardiac magnetic resonance imaging (CMRI)-derived RVEF was examined in 53 PH patients. The accuracy of the prediction equation to calculate RVEF using TAPSE was also evaluated. In PH patients, TAPSE was strongly correlated with CMRI-derived RVEF in PH patients (r = 0.86, p < 0.0001). We then examined the accuracy of the two equations: the original regression equation (RVEF = 2.01 × TAPSE + 0.6) and the simplified prediction equation (RVEF = 2 × TAPSE). Bland-Altman plot showed that the mean difference ± limits of agreement was 0.0 ± 10.6 for the original equation and -0.6 ± 10.6 for the simplified equation. Intraclass correlation coefficient was 0.84 for the original and 0.82 for the simplified equation. Normal RVEF was considered to be ≥40% based on the data from 53 matched controls, and the best TAPSE cut-off value to determine reduced RVEF (<40%) was calculated to be 19.7 mm (sensitivity 88.9%, specificity 84.6%). A simple equation of RVEF = 2 × TAPSE enables easy prediction of RVEF using TAPSE, an easily measurable M-mode index of echocardiography. TAPSE of 19.7 mm predicts reduced RVEF in PH patients with clinically acceptable sensitivity and specificity.

BACKGROUND: The relations between subclinical atherosclerosis and inflammatory biomarkers have generated intense interest but their significance remains unclear. We sought to determine the association between a panel of biomarkers and subclinical aortic atherosclerosis in a community-based cohort. METHODS AND RESULTS: We evaluated 1547 participants of the Framingham Heart Study Offspring cohort who attended the 7th examination cycle and underwent both cardiovascular magnetic resonance imaging (CMR) and assays for 10 biomarkers associated with atherosclerosis: high-sensitivity C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, interleukin-18, lipoprotein-associated phospholipase-A2 activity and mass, monocyte chemoattractant protein-1, P-selectin, and tumor necrosis factor receptor-2. In logistic regression analysis, we found no significant association between the biomarker panel and the presence of aortic plaque (global P=0.53). Using Tobit regression with aortic plaque as a continuous variable, we noted a modest association between biomarker panel and aortic plaque volume in age- and sex-adjusted analyses (P=0.003). However, this association was attenuated after further adjustment for clinical covariates (P=0.09). CONCLUSIONS: In our community-based cohort, we found no significant association between our multibiomarker panel and aortic plaque. Our results underscore the strengths and limitations of the use of biomarkers for the identification of subclinical atherosclerosis and the importance of traditional risk factors.

PURPOSE: Cardiac involvement in sarcoidosis is one of the leading causes of death associated with abnormalities of the conduction system. (18)F-FDG PET is useful for detecting inflammatory lesions in cardiac sarcoidosis. However, the relationship between ECG abnormalities and focal (18)F-FDG uptake has not been studied. The aim of this study was to evaluate the relationship between electrocardiogram (ECG) abnormalities and the location of elevated myocardial (18)F-FDG uptake in patients with sarcoidosis. METHODS: Included in the study were 50 patients (56.3 ± 14.9 years old) with histologically proven sarcoidosis with suspected cardiac involvement based on ECG or echocardiography. All patients had fasted for at least 6 h and were given unfractionated heparin (50 IU/kg) intravenously to reduce the physiological (18)F-FDG uptake in the myocardium. The left ventricle (LV) wall was divided into 17 segments by visual analysis. Obvious accumulation in each segment was defined as positive. RESULTS: Of the 50 patients, 33 showed some ECG abnormalities, including atrioventricular (AV) block in 13. Patients with abnormal ECG findings had a higher number of regions with (18)F-FDG uptake than patients without ECG abnormality (3.48 ± 2.73 vs. 1.41 ± 2.09 regions, p = 0.0051). Among ECG abnormalities, the predictor for interventricular septum wall (18)F-FDG involvement was AV block (p = 0.0025). CONCLUSION: Patients with ECG abnormalities showed a higher number of abnormal (18)F-FDG myocardial uptake regions than patients without ECG abnormalities. In particular, focal (18)F-FDG uptake in the interventricular septum in cardiac sarcoidosis was associated with AV block. Therefore, determination of regional (18)F-FDG distribution might contribute to patient management in cardiac sarcoidosis.

BACKGROUND: Few studies have focused on right atrial (RA) structure and function in pulmonary hypertension (PH). We sought to evaluate RA volume and phasic function using cardiac magnetic resonance (CMR), and to examine their clinical relevance in PH. METHODS: We prospectively studied 50 PH patients and 21 control subjects. RA volume and indices of phasic function (reservoir volume, ejection fraction [EF], and conduit volume) were evaluated by CMR. RESULTS: Maximum RA volume index was significantly higher in PH patients (56 [44-70] ml/m(2)) than in controls (40 [30-48] ml/m(2)) (p<0.001). Reservoir volume index was significantly lower in PH than in controls (p<0.001), but conduit volume index was higher in PH than in controls (p=0.008). RA EF was similar when comparing the two groups (p=0.925). Interestingly, RA EF was increased in PH patients with WHO functional class III patients as compared with controls (p<0.001) but was reduced in advanced PH patients with WHO functional class IV (p<0.01). Maximum RA volume and RA EF significantly correlated with pulmonary hemodynamic indices, atrial and brain natriuretic hormone levels, and CMR-derived right ventricular indices. By contrast, RA reservoir volume correlated with cardiac index and 6-minute walk distance. CONCLUSIONS: PH is associated with increased size, decreased reservoir function, and increased conduit function of the right atrium. RA systolic function indicated by RA EF increases in patients with mild to moderate PH but decreases in patients with advanced PH. Varying associations between RA indices and conventional PH indices suggest their unique role in the management of PH.

PURPOSE: To investigate the specific imaging findings of multidetector row CT (MDCT) and PET/CT with(18)F-FDG in cardiac dominant diffuse large B-cell lymphoma (DLBCL) in comparison with other cardiac tumours. METHODS: Five patients with DLBCL and 12 patients with other cardiac tumours including pericardial tumours were retrospectively reviewed. Among the patients with other cardiac tumours, seven had metastatic tumours, three had benign tumours, and two had other malignant cardiac tumours. The location of the cardiac mass, the encasement of the coronary artery surrounded by the mass, and pericardial effusion were evaluated using MDCT. The disease activity of the cardiac tumour was also evaluated by PET/CT. RESULTS: Four of the five DLBCL patients had primarily right-sided cardiac lesions, which was seen significantly more frequently in DLBCL than in other cardiac tumours (p = 0.028). All cardiac DLBCL lesions were located around the atrioventricular groove and encased the coronary arteries. ECG-gated cardiac MDCT showed that there was no apparent stenosis of the coronary arteries. Large amounts of pericardial effusion were seen in all DLBCL patients. PET/CT revealed significantly higher FDG uptake in DLBCL than in other cardiac malignant tumours, with no overlap (p = 0.0007). CONCLUSION: The combination of a right-sided cardiac mass with a large pericardial effusion and no apparent stenosis of the encased coronary artery revealed by MDCT and a high maximum standard uptake value were the specific findings in cardiac dominant DLBCL.

UNLABELLED: The metabolic activity of the primary tumor is an important variable in (18)F-FDG PET interpretation for presurgical staging, because this activity is likely to affect the possibility of detection of malignant involvement in lymph nodes (LNs). The purpose of this study was to reevaluate the diagnostic accuracy of (18)F-FDG PET/CT for the presurgical staging of esophageal squamous cell carcinoma (SCC) in correlation with the (18)F-FDG avidity of the primary lesions. METHODS: One hundred fifty-six patients (mean age ± SD, 61.4 ± 8.0 y) underwent (18)F-FDG PET/CT before surgical esophagectomy and LN dissection. LN metastasis was identified using the fusion of PET and CT images with increased (18)F-FDG uptake greater than the background activity of the adjacent structures. The results of the patients' (18)F-FDG PET/CT examinations for LN involvement were compared with the histopathologic results to investigate the diagnostic accuracy of (18)F-FDG PET/CT for tumor staging. In addition, we examined the correlation between the diagnostic accuracy of (18)F-FDG PET/CT for LN involvement and the (18)F-FDG avidity of the primary lesions, to investigate the effect of tumor aggressiveness on the diagnosis of LN metastasis. RESULTS: The diagnostic accuracy of (18)F-FDG PET/CT for LN metastasis showed a low sensitivity, ranging from 29.3% to 53.3%, whereas the specificity was higher than 89.8% in regional thoracic nodes and in remote areas of the cervical and abdominal regions. The (18)F-FDG uptake of the primary lesions positively correlated with that of the metastatic LNs in the thoracic field (R = 0.52, P < 0.05). As a result, our receiver-operating-characteristic analyses demonstrated an area under the curve value of 0.73, with the optimal cutoff value at a maximum standardized uptake value of 3.3 in patients with mid to high (18)F-FDG avidity in the primary lesions (maximum standardized uptake value ≥ 5). CONCLUSION: This study showed that the avidity of the primary esophageal SCCs affected the detectability of lymph nodal metastases. If primary lesions of esophageal SCC present with a low (18)F-FDG uptake, PET/CT may have a limited role for initial staging because of low sensitivity to detect lymph node metastases.

OBJECTIVE: Systemic oxidative stress is associated with insulin resistance and obesity. We tested the hypothesis that systemic oxidative stress is linked to lower aerobic capacity and skeletal muscle dysfunction in metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS: The incremental exercise testing with cycle ergometer was performed in 14 male patients with MetS and 13 age-, sex-, and activity-matched healthy subjects. Systemic lipid peroxidation was assessed by serum thiobarbituric acid reactive substances (TBARS), and systemic antioxidant defense capacity was assessed by serum total thiols and enzymatic activity of superoxide dismutase (SOD). To assess skeletal muscle energy metabolism, we measured high-energy phosphates in the calf muscle during plantar flexion exercise and intramyocellular lipid (IMCL) in the resting leg muscle, using (31)P- and (1)proton-magnetic resonance spectroscopy, respectively. RESULTS: Serum TBARS were elevated (12.4 ± 7.1 vs. 3.7 ± 1.1 μmol/L; P < 0.01), and serum total thiols and SOD activity were decreased (290.8 ± 51.2 vs. 398.7 ± 105.2 μmol/L, P < 0.01; and 22.2 ± 8.4 vs. 31.5 ± 8.5 units/L, P < 0.05, respectively) in patients with MetS compared with healthy subjects. Peak VO2 and anaerobic threshold normalized to body weight were significantly lower in MetS patients by 25 and 31%, respectively, and inversely correlated with serum TBARS (r = -0.49 and r = -0.50, respectively). Moreover, muscle phosphocreatine loss during exercise was 1.4-fold greater in patients with MetS (P < 0.05), and IMCL content was 2.9-fold higher in patients with MetS (P < 0.01), indicating impaired skeletal muscle energy metabolism, and these indices positively correlated with serum TBARS (r = 0.45 and r = 0.63, respectively). CONCLUSIONS: Systemic oxidative stress was associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in patients with MetS.

We compared peak circumferential strain (Ecc) values with spatial modulation of magnetization (SPAMM) and strain-encoded (SENC) magnetic resonance (MR) imaging at 3 tesla. Correlation coefficients of the averaged peak Ecc values of the 2 methods were statistically significant. However, the average peak Ecc value was significantly lower with SPAMM (-13.5%±3.3%) than with SENC (-21.6%±3.4%) (P<0.0001). The SENC method showed higher circumferential strain than the SPAMM method at 3T.

The aim of this study was to explore whether the regional peak longitudinal (LS) and circumferential strains (CS) at the right ventricular (RV) free wall could be used to identify global RV dysfunction in relation to RV ejection fraction (RVEF) and plasma concentration of brain natriuretic peptide (BNP) in pulmonary hypertension (PH). A total of 37 consecutive patients diagnosed with PH and 13 healthy control subjects were included. Fast strain encoded and routine cine MRI was performed. The LS and CS at three RV levels were quantified and their relations with RVEF and BNP were investigated. Receiver operating characteristic (ROC) analysis was employed to assess the diagnostic utility of strain encoded MRI for the detection of low RVEF. Significant correlations with LS were observed for RVEF and BNP. Compared to CS, LS showed better correlation with RVEF. The mid-ventricular level of RV was the most sensitive site for evaluation of RV dysfunction. According to our ROC analysis, LS showed higher sensitivity and specificity to detect low RVEF. Compared to CS, LS showed stronger correlations with RVEF and BNP and could be a good detector of RV dysfunction in PH.

BACKGROUND: This study investigated the major clinical determinants of late gadolinium enhancement (LGE) at ventricular insertion points (VIPs) commonly seen in patients with pulmonary hypertension (PH). METHODS: Forty-six consecutive PH patients (mean pulmonary artery pressure ≥25 mmHg at rest) and 21 matched controls were examined. Right ventricular (RV) morphology, function and LGE mass volume at VIPs were assessed by cardiac magnetic resonance (CMR). Radial motion of the left ventricular (LV) wall and interventricular septum (IVS) was assessed by speckle-tracking echocardiography. Paradoxical IVS motion index was then calculated. Univariate and multivariate regression analysis were conducted to characterize the relationship between LGE volume at VIPs and PH-related clinical indices, including the paradoxical IVS motion index. RESULTS: Mean pulmonary arterial pressure (MPAP) of PH patients was 38±9 mmHg. LGE at VIPs was observed in 42 of 46 PH patients, and the LGE volume was 2.02 mL (0.47-2.99 mL). Significant correlations with LGE volume at VIPs were observed for MPAP (r = 0.50) and CMR-derived parameters [RV mass index (r = 0.53), RV end-diastolic volume index (r = 0.53), RV ejection fraction (r = -0.56), and paradoxical IVS motion index (r = 0.77)]. In multiple regression analysis, paradoxical IVS motion index alone significantly predicted LGE volume at VIPs (p<0.001). CONCLUSIONS: LGE at VIPs seen in patients with PH appears to reflect altered IVS motion rather than elevated RV pressure or remodeling. Long-term studies would be of benefit to characterize the clinical relevance of LGE at VIPs.

We report the usefulness of F-FDG PET/CT for the detection and therapy evaluation of the infective vegetation. A 64-year-old man with history of aortic valve replacement presented with 2 months of fever without identifiable cause. Echocardiogram showed no inflammation vegetation or abnormality of mechanical valve function. FDG PET/CT with 50 IU/kg IV heparin revealed focal uptakes near the mechanical aortic valve. After antibiotics therapy, fever was ameliorated, and FDG PET/CT findings showed markedly decreased uptake of the lesions. FDG PET/CT is a powerful tool to detect endocarditis even in patients with no anatomical abnormalities.