真鍋 治

OBJECTIVES: To evaluate the diagnostic value of delayed contrast-enhanced computed tomography (DE-CT) for cardiac sarcoidosis (CS) in patients with or without implantable devices, including a quantitative comparison with late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). METHODS: Twenty-four patients (mean age, 64 ± 9 years; 17 women) with known or suspected CS underwent retrospective electrocardiogram-gated DE-CT at 80 kV with knowledge-based iterative model reconstruction. Fourteen patients without implantable devices also underwent LGE-CMR, while ten with pacemakers or implantable cardioverter-defibrillators did not. The presence of hyperenhanced myocardium was assessed visually and quantitatively using a 5-standard deviation threshold above the mean of remote myocardium. RESULTS: Inter-observer agreement for visual detection of hyperenhanced segments on DE-CT was excellent in patients with implantable devices and in those without (κ = 0.91 and κ = 0.94, respectively). Comparisons of the percent area of hyperenhanced myocardium between DE-CT and LGE-CMR on both per-patient and per-segment analyses showed good correlations (r = 0.96 and r = 0.83, respectively; p < 0.001). The sensitivity and specificity of DE-CT for the diagnosis of CS were 94% and 33%. CONCLUSIONS: The extent of hyperenhanced lesion with DE-CT showed good agreement with LGE-CMR results. DE-CT showed high sensitivity for detecting CS and may be useful particularly in patients with contraindications to CMR. KEY POINTS: • Delayed contrast-enhanced CT (DE-CT) can be applied to patients with implantable devices. • DE-CT can detect cardiac sarcoidosis (CS) lesions similarly to cardiac MRI. • DE-CT shows high sensitivity for detecting CS. • DE-CT may be useful particularly in patients with contraindications to cardiac MRI.

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.

Myocardial perfusion imaging using positron emission tomography (PET) allows both qualitative and quantitative measurement. The quantitative myocardial blood flow and coronary flow reserve (CFR) are reliable indices for evaluating functional severity, influenced by both epicardial stenosis and microvascular disease. Fractional flow reserve (FFR) also reflects physiological stenosis, which measures the pressure differences across a coronary artery stenosis during maximum hyperemia. Discordance between CFR and FFR has been noticed in estimating the functional significance of coronary stenosis. In this review, we summarize the feasibility of PET for the management of coronary artery disease compared to FFR.

We report a case of breast cancer detected as an incidental finding on 99mTc-MIBI scintigraphy. 99mTc-MIBI scintigraphy is usually used to evaluate cardiac perfusion or to detect ectopic parathyroid adenomas; however, it is also known to sensitively detect breast cancer. Accordingly, a few reports have described the incidental detection of breast cancer by 99mTc-MIBI scintigraphy performed to detect parathyroid adenoma. Our present case underscores the importance of attending to any incidental findings when searching for parathyroid adenomas using 99mTc-MIBI scintigraphy.

Diastolic dysfunction is important in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Sympathetic nervous hyperactivity may contribute to the development of diastolic dysfunction. The aim of this study was to determine the relationship between myocardial sympathetic innervation quantified by 11C-hydroxyephedrine PET and diastolic dysfunction in HFpEF patients. Methods: Forty-one HFpEF patients having an echocardiographic left ventricular ejection fraction of 40% or greater and 12 age-matched volunteers without heart failure underwent the echocardiographic examination and 11C-hydroxyephedrine PET. Diastolic dysfunction was classified into grades 0-3 by Doppler echocardiography. Myocardial sympathetic innervation was quantified using the 11C-hydroxyephedrine retention index (RI). The coefficient of variation of 17-segment RIs was derived as a measure of heterogeneity in myocardial 11C-hydroxyephedrine uptake. Results: Grade 2-3 diastolic dysfunction (DD2-3) was found in 19 HFpEF patients (46%). They had a significantly lower global RI (0.075 ± 0.018 min-1) than volunteers (0.123 ± 0.028 min-1, P < 0.001) and HFpEF patients with grade 0-1 diastolic dysfunction (DD0-1) (0.092 ± 0.024 min-1, P = 0.046). HFpEF patients with DD2-3 had the largest coefficient of variation of 17-segment RIs of the 3 groups (18.4% ± 7.7% vs. 14.1% ± 4.7% in HFpEF patients with DD0-1, P = 0.042 for post hoc tests). In multivariate logistic regression analysis, a lower global RI (odds ratio, 0.66 per 0.01 min-1; 95% confidence interval, 0.38-0.99; P = 0.044) was independently associated with the presence of DD2-3 in HFpEF patients. Conclusion: Myocardial sympathetic innervation was impaired in HFpEF patients and was associated with the presence of advanced diastolic dysfunction in HFpEF.

PURPOSE: Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. EXPERIMENTAL DESIGN: Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. RESULTS: All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. CONCLUSIONS: We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.

核医学検査を用いることにより,心筋血流・代謝の情報を非侵襲的,客観的に得ることができる.特に血流シンチでは,日本人により適したエビデンスが確立されている.狭心症が疑われた患者に対しては,虚血の有無・範囲,心筋viabilityを評価することにより治療方針の決定,予後評価を行うことが重要である.心筋血流PETを用いることにより,心筋血流量を定量値としても算出可能であり,多枝病変の検出や予後評価にも応用できる.(著者抄録)

Cartilaginous tumors of the larynx are uncommon neoplasms that sometimes mimic laryngeal cancers. There has been no report of F-FDG PET/CT for the evaluation of laryngeal cartilaginous tumors. We reported 3 cases of laryngeal cartilaginous tumors with the image findings, including CT, FDG PET/CT, and MRI and reviewed literatures. We concluded that the combination of a very high-signal mass on T2-weighted magnetic resonance images and lower FDG uptake might be diagnostic image characteristics for distinguishing laryngeal cartilaginous tumor from laryngeal cancer.

18F-fluoromisonidazole (FMISO) is a positron emission tomography (PET) tracer that accumulates in hypoxic tissues. We here present a case of suspected cardiac sarcoidosis which was detected with increased FMISO uptake.

Sarcoidosis is a multisystem disease pathologically characterized by non-caseating granuloma. Cardiac sarcoidosis (CS) remains an important prognostic factor of sarcoidosis patients. ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) has been applied as a noninvasive tool not only for CS diagnoses but also for the evaluation of therapeutic effects and prognoses. Visual assessment is a standard method to evaluate whether the ¹⁸F-FDG uptake is physiological or active inflammation due to the CS. A semi-quantitative assessment using the standardized uptake value (SUV) is a simple method for achieving a more accurate diagnosis. A volume-based analysis has been proposed as a new marker that can provide information about the improvement or prevention of heart failure and can be used to predict a further clinical event in CS patients. This is a brief review of the objective and quantitative assessments of the magnitude and extent of CS activity with the use of ¹⁸F-FDG PET.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology that is characterized by the formation of non-caseating granulomas at various sites in the body. Cardiac sarcoidosis (CS) has been underdiagnosed in the past due to a lack of imaging modalities with high sensitivity. CS may cause various symptoms including conduction disturbance, ventricular arrhythmias, cardiac dysfunction and sudden cardiac death, which account for an increased mortality rate in these patients. ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET) and late gadolinium-enhanced cardiac magnetic resonance imaging (LGE CMR) have played important roles in the recent guidelines for the diagnosis of CS. Each one possesses its own unique abilities and can contribute to early disease detection, assessment of disease activity, response to treatment, and risk stratification.<Br>However, further studies are necessary in order to establish the standard methods for clinical application of FDG PET and CMR.

Coronary artery disease (CAD) is one of the major causes of death in Japan. Fractional flow reserve with angiography is a well validated method for identifying significant focal stenosis, but is not applied for the estimation of hyperemic vasodilatory capacity in the myocardium. Coronary flow reserve (CFR) estimated from sequential myocardial perfusion images obtained by blood flow tracers and positron emission tomography (PET) is a quantitative value. CFR is regulated not only by focal stenoses but also by diffuse atherosclerosis and coronary microvascular dysfunction (CMD) in patients with CAD. Accordingly, low CFR is shown to be a strong predictor of cardiac death in combination with anatomical disease burden. Optimal medical therapies such as beta-blockers, angiotensin converting enzyme (ACE) inhibitors, statins, and medications for diabetes could increase CFR by improving CMD at the early stage of CAD. It is also important to clarify the effects of coronary revascularization for focal stenoses on CFR. This paper focuses on the application of CFR estimated by cardiac PET to the evaluation of per-patient atherosclerotic burden and microvascular dysfunction.

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

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

BACKGROUND: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a benign lymphoid proliferation or malignant lymphoma in patients who have been treated with MTX. MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Here we evaluated the diagnostic accuracy and predictive value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for MTX-LPD. METHODS: We retrospectively investigated the cases of 15 patients clinically suspected of having MTX-LPD. A total of 324 anatomic regions (207 nodal and 117 extranodal regions) were assessed by (18)F-FDG PET/CT and by multi-detector row CT (MDCT). Each anatomic region was classified as either malignant or benign. The uptake of (18)F-FDG was assessed semi-quantitatively with the standardized uptake value maximum (SUVmax), the whole-body metabolic tumor volume (WBMTV), and the whole-body total lesion glycolysis (WBTLG) in order to investigate predictive factors of spontaneous regression after the withdrawal of MTX. RESULTS: MTX-LPD lesions were observed in 92/324 (28.4 %) regions. (18)F-FDG PET/CT showed 90.2 % sensitivity, 97.4 % specificity, and 95.4 % accuracy, values which were significantly higher than those of MDCT (59.8, 94.8, and 84.9 %, respectively. p < 0.002). After the withdrawal of MTX, 9/15 patients (60.0 %) achieved complete response (CR). The SUVmax, WBMTV and WBTLG values of the CR patients were 9.2 (range 2.8-47.1), 44.3 (range 0-362.6) ml, 181.8 (range 0-2180.9) ml, respectively, which were not significantly different from those of the non-CR patients: 10.6 (range 0-24.9), 15.7 (range 0-250.1) ml, and 97.4 (range 0-1052.1) ml. CONCLUSIONS: Although (18)F-FDG PET/CT was a useful tool to detect MTX-LPD lesions, none of the (18)F-FDG PET parameters before the withdrawal of MTX could be used to predict CR after the withdrawal of MTX.

PURPOSE: Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. METHODS: This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). RESULTS: In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. CONCLUSIONS: FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor.

BACKGROUND: The physiological uptake of 18F-fluorodeoxyglucose (FDG) in the heart often interferes with the accurate diagnosis of inflammatory cardiac diseases (CDs). Unfractionated heparin (UFH) administration may suppress its uptake through the alteration of myocardial metabolism. PURPOSE: To clarify the effectiveness of UFH administration to suppress the physiological FDG uptake in the heart. MATERIAL AND METHODS: The physiological FDG uptake in the heart was compared among 178 patients who fasted less than 18 h, 37 patients who fasted more than 18 h, and 64 patients who fasted more than 18 h and were administered UFH (UFH-CD group) prior to FDG PET/CT. Free fatty acid (FFA), triglyceride, insulin, and blood glucose levels were measured after UFH administration. Myocardial FDG uptake was evaluated by visual assessment and on the basis of maximum standardized uptake value (SUVmax). RESULTS: In the UFH-CD group, the FFA level increased 15 min after UFH administration (P < 0.01). Blood glucose and insulin levels remained unchanged (P = NS). FDG physiological uptake was observed in 69% of the patients who fasted less than 18 h, 38% of the patients fasted more than 18 h, and 22% of the UFH-CD group (P < 0.01 for trend). SUVmax decreased in the UFH-CD group compared with the patients who fasted less than 18 h (P < 0.01) and the patients who fasted more than 18 h (P = 0.029). CONCLUSION: UFH administration and fasting more than 18 h could effectively suppress FDG physiological uptake in the heart and can be a useful method of detecting inflammatory CDs and tumors.

BACKGROUND: (18)F-fluorodeoxyglucose (FDG) PET plays an important role in the detection of cardiac involvement sarcoidosis (CS). However, diffuse left ventricle (LV) wall uptake sometimes makes it difficult to distinguish between positive uptake and physiological uptake. The aims of this study were to evaluate the effects of 18-h fasting with low-carbohydrate diet (LCD) vs a minimum of 6-h fasting preparations on diffuse LV FDG uptake and free fatty acid (FFA) levels in patients with suspected CS. METHODS: Eighty-two patients with suspected CS were divided into 2 preparation protocols: one with a minimum 6-h fast without LCD preparation (group A, n = 58) and the other with a minimum 18-h fast with LCD preparation (group B, n = 24). All patients also received intravenous unfractionated heparin (UFH; 50 IU/kg) before the injection of FDG. RESULTS: Group A showed a higher percentage of diffuse LV uptake than did group B (27.6 vs 0.0%, P = .0041). Group B showed higher FFA levels (1159.1  ±  393.0, 650.5  ±  310.9 μEq/L, P < .0001) than did group A. Patients with diffuse LV uptake (n = 16) showed lower FFA levels than did other patients (n = 66) (432.1  ±  296.1, 888.4  ±  381.4 μEq/L, P < .0001). UFH administration significantly increased FFAs in both groups, even in the patients with diffuse LV FDG uptake. CONCLUSIONS: The 18-h fast with LCD preparation significantly reduced diffuse LV uptake and increased FFA levels. In particular, the FFA level was significantly lower in patients with LV diffuse uptake than in patients without LV diffuse uptake. Acutely increasing plasma FFA through the use of UFH may not have a significant role in reducing physiological LV FDG uptake.

PURPOSE: Cardiac sarcoidosis (CS) is a cause of conduction system disease (CSD). (18)F-Fluorodeoxyglucose-positron emission tomography (FDG PET) and cardiac magnetic resonance (CMR) are used for detection of CS. The relative diagnostic value of these has not been well studied. The aim was to compare these imaging modalities in this population. METHODS: We recruited steroid-naive patients with newly diagnosed CSD due to CS. All CS patients underwent both imaging studies within 12 weeks of each other. Patients were classified into two groups: group A with chronic mild CSD (right bundle branch block and/or axis deviation), and group B with new-onset atrioventricular block (AVB, Mobitz type II or third-degree AVB). RESULTS: Thirty patients were included. Positive findings on both imaging studies were seen in 72 % of patients (13/18) in group A and in 58 % of patients (7/12) in group B. The remainder (28 %) of the patients in group A were positive only on CMR. Of the patients in group B, 8 % were positive only on CMR and 33 % were positive only on FDG PET. Patients in group A were more likely to be positive only on CMR, and patients in group B were more likely to be positive only on FDG PET (p = 0.02). Patients in group B positive only on FDG PET underwent CMR earlier relative to their symptomatology than patients positive only on CMR (median 7.0, IQR 1.5 - 34.3, vs. 72.0, IQR 25.0 - 79.5 days; p = 0.03). CONCLUSION: The number of positive FDG PET and CMR studies was different in patients with CSD depending on their clinical presentation. This study demonstrated that CMR can adequately detect cardiac involvement associated with chronic mild CSD. In patients presenting with new-onset AVB and a negative CMR study, FDG PET may be useful for detecting cardiac involvement due to CS.

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.

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.

UNLABELLED: The red nucleus (RN) is a pair of small gray matter structures located in the midbrain and involved in muscle movement and cognitive functions. This retrospective study aimed to investigate the metabolism of human RN and its correlation to other brain regions. METHODS: We developed a high-resolution semiconductor PET system to image small brain structures. Twenty patients without neurologic disorders underwent whole-brain scanning after injection of 400 MBq of (18)F-FDG. The individual brain (18)F-FDG PET images were spatially normalized to generate a surface projection map using a 3-dimensional stereotactic surface projection technique. The correlation between the RN and each voxel on the cerebral and cerebellar cortices was estimated with Pearson product-moment correlation analysis. RESULTS: Both right and left RNs were visualized with higher uptake than that in the background midbrain. The maximum standardized uptake values of RN were 7.64 ± 1.92; these were higher than the values for the dentate nucleus but lower than those for the caudate nucleus, putamen, and thalamus. The voxel-by-voxel analysis demonstrated that the right RN was correlated more with ipsilateral association cortices than contralateral cortices, whereas the left RN was equally correlated with ipsilateral and contralateral cortices. The left RN showed a stronger correlation with the motor cortices and cerebellum than the right RN did. CONCLUSION: Although nonspecific background activity around RNs might have influenced the correlation patterns, these metabolic relationships suggested that RN cooperates with association cortices and limbic areas to conduct higher brain functions.

PURPOSE: (11)C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis. METHODS: The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement. RESULTS: Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor (N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis (P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not reach statistical significance (P = NS). CONCLUSION: MTV and TLMU may be useful for predicting outcome in patients with astrocytic tumor.

A 55-year-old woman underwent radiosurgery for a left cerebral hemisphere arteriovenous malformation (AVM) and developed radiation-induced necrosis causing a massive edema in the surrounding brain tissues. Despite various therapies, the edema expanded to the ipsilateral hemisphere and induced neurological symptoms. The radiation-induced necrotic lesion was surgically removed 4 years after radiosurgery. While the preoperative FDG PET revealed severe hypometabolism in the left cerebrum, the necrotomy significantly ameliorated the brain edema, glucose metabolism (postoperative FDG PET), and symptoms. This case indicates that radiation necrosis-induced neurological deficits may be associated with brain edema and hypometabolism, which could be reversed by appropriate necrotomy.

PURPOSE: The predictive value of FDG PET at thyroid remnant ablation was evaluated in comparison to radioiodine uptake in high-risk patients with differentiated thyroid cancer. PATIENTS AND METHODS: One hundred forty-one patients who underwent radioiodine therapy (RIT) after total thyroidectomy and received at least 1 further RIT due to suspected metastases were retrospectively analyzed. Patients had not received RIT previously. FDG PET was performed before thyroid remnant ablation. Thyroid-stimulating hormone-stimulated serum thyroglobulin (Tg) was measured for biochemical response assessment (change of Tg between the first and second RIT, ΔTg). RESULTS: Biochemical response could be evaluated in 80 patients; survival data could be obtained for 88 patients (maximum, 124 months). Biochemical response was significantly better in patients with radioiodine-positive metastases compared with patients with radioiodine-negative metastases (median ΔTg I+, 55.8% vs I-, 112.6%; P < 0.01). Regarding survival, deaths occurred later in patients with radioiodine-positive metastases compared with radioiodine-negative patients; however, there was no significant difference regarding overall survival (I+, 61.3% vs I-, 58.2%; P > 0.05). Patients with FDG-positive metastases at thyroid remnant ablation showed a poorer biochemical response compared with patients with FDG-negative metastases (median ΔTg FDG+, 77.5% vs FDG-, 53.2%; P < 0.05), and these groups also differed significantly regarding survival (overall survival FDG+, 48.5% vs FDG-, 100%, P < 0.05). CONCLUSIONS: At thyroid remnant ablation, FDG PET is more predictive for long-term survival, whereas radioiodine uptake is more important for short-term response. FDG PET performed at thyroid remnant ablation might represent a useful tool for management of high-risk patients with differentiated thyroid 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.

PURPOSE: The staging of endometrial cancer requires surgery which carries the risk of morbidity. FDG PET/CT combined with anatomical imaging may reduce the number of unnecessary lymphadenectomies by demonstrating the risk of extrapelvic infiltration. The purpose of this study was to optimize FDG PET/CT diagnostic criteria for risk assessment in endometrial cancer after first-line risk triage with MRI. METHODS: The study population comprised 37 patients who underwent curative surgery for the treatment of endometrial cancer. First, the risk of extrapelvic infiltration was triaged using MRI. Second, multiple glucose metabolic profiles of the primary lesion were assessed with FDG PET/CT, and these were correlated with the histopathological risk of extrapelvic infiltration including lymphovascular space invasion (LVSI) and high-grade malignancy (grades 2 and 3). The results of histological correlation were used to adjust FDG PET/CT diagnostic criteria. RESULTS: Presurgical assessment using MRI was positive for deep (>50 %) myometrial invasion in 17 patients. The optimal FDG PET/CT diagnostic criteria vary depending on the results of MRI. Specifically, SUVmax (≥16.0) was used to indicate LVSI risk with an overall diagnostic accuracy of 88.2 % in patients with MRI findings showing myometrial invasion. High-grade malignancy did not correlate with any of metabolic profiles in this patient group. In the remaining patients without myometrial invasion, lesion glycolysis (LG) or metabolic volume were better indicators of LVSI than SUVmax with the same diagnostic accuracy of 80.0 %. In addition, LG (≥26.9) predicted high-grade malignancy with an accuracy of 72.2 %. Using the optimized cut-off criteria for LVSI, glucose metabolic profiling of primary lesions correctly predicted lymph node metastasis with an accuracy of 73.0 %, which was comparable with the accuracy of visual assessment for lymph node metastasis using MRI and FDG PET/CT. CONCLUSION: FDG PET/CT diagnostic criteria may need adjustment based on the anatomical information provided by MRI. The optimized criteria can predict the risk of pathology-proven LVSI correctly in 83.8 % of patients before surgery, and thus would improve presurgical treatment planning.

BACKGROUND: Living liver donation is associated with size-dependent complications. The resectable size and its safety margin should be defined for the safety of donors. The purpose of the present study was to determine if the current partial hepatectomies are done under the safety margin of the resectable size, by measuring asialoglycoprotein receptor (ASGPR) function of donor's remnant liver. MATERIAL AND METHODS: Seventy-four living donors (age 35±11 years) underwent Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (Tc-99m GSA) scintigraphy at postoperative week 1. We evaluated the scintigraphic results using established parameters of GSA uptake (LHL15) and its clearance from the blood pool (HH15). Based on the literature, we consider HH15 <0.55 to indicate normal ASGPR function, and 0.55£ HH15 <0.65 to indicate mild impairment. In terms of the hepatic uptake, we consider LHL15>0.93 to indicate normal ASGPR function, and 0.87< LHL15 £0.93 to indicate mild impairment. RESULTS: The average resected size was 337±170 mL, corresponding to 28±12% of the original donor's whole liver volume. No donors showed 0.65≤ HH15 or LHL15 <0.87, suggesting moderate or severely impaired ASGPR function. However, larger resection size (35-53%) was positively associated with higher HH15 values (R=0.53, p<0.001). In the range of HH15 (0.35-0.64) among present donors, higher HH15 values did not affect the regeneration volume (R=0.03, p=NS). CONCLUSIONS: Larger partial resection (≥35% of the original liver volume) may impair postsurgical ASGPR function, but smaller resection (<35%) was considered to be under the safety margin of the hepatectomy. Although mildly impaired postsurgical ASGPR function did not indicate poor prognosis, careful attention may be required for donors undergoing larger (³35%) partial resection.

Cardiac sarcoidosis (CS) increases the risk of cardiovascular event such as conduction abnormalities, ventricular arrhythmia and heart failure in patients with sarcoidosis. Recently the Heart Rhythm Society (HRS) issued a consensus on the detection of CS. In this report, ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) is employed in the diagnosis of CS. In 2012, the Japanese Ministry of Health, Labor, and Welfare (JMHLW) approved cardiac ¹⁸F-FDG PET for the detection of inflammatory lesions in CS. The clinical use of ¹⁸F-FDG PET has significantly increased worldwide. However, a study protocol and diagnostic criteria still need to be established.