Yuuki Tomiyama

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

AbstractObjectivesThis 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 15O-H2O positron-emission tomography (PET) and assesses the CFRs of coronary artery disease (CAD) patients.MethodsThirty-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).ResultsCorrelation 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).ConclusionsWe 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.

Effects and safety of 131I-metaiodobenzylguanidine (MIBG) radiotherapy in malignant neuroendocrine tumors: Results from a multicenter observational registry

Effective treatments for malignant neuroendocrine tumors are under development. While iodine-131 metaiodobenzylguanidine (¹³¹I-MIBG) radiotherapy has been used in the treatment of malignant neuroendocrine tumors, there are few studies evaluating its therapeutic effects and safety in a multicenter cohort. In the current study, we sought to evaluate the effects and safety of ¹³¹I-MIBG therapy for conditions including malignant pheochromocytoma and paraganglioma within a multicenter cohort. Forty-eight malignant neuroendocrine tumors (37 pheochromocytoma and 11 paraganglioma) from four centers underwent clinical ¹³¹I-MIBG radiotherapy. The tumor responses were observed before and 3 to 6 months after the ¹³¹I-MIBG radiotherapy in accordance with RECIST criteria. We also evaluated the data for any adverse effects. The four centers performed a total of 87 ¹³¹I-MIBG treatments on 48 patients between January 2000 and March 2009. Of the treatments, 65 were evaluable using RECIST criteria. One partial response (PR), 40 stable disease (SD), and 9 progressive disease (PD) in malignant pheochromocytoma were observed after each treatment. Fourteen SD and one PD-were observed in paraganglioma. Patients with normal hypertension (systolic blood pressure (BP) > 130 mmHg) showed significantly reduced systolic BP after the initial follow-up (n=10, 138.1±8.2 to 129.5±13.5 mmHg, P=0.03). In adult neuroendocrine tumors with a treatment-basis analysis, there were side effects following 41 treatments (47.1%) and most of them (90.2%) were minor. In this multicenter registry, PR or SD was achieved in 84.6% of the treatment occasions in adult neuroendocrine tumors through ¹³¹I-MIBG radiotherapy. This indicated that most of the ¹³¹I-MIBG radiotherapy was performed safely without significant side effects.

Quantification of myocardial blood flow with dynamic perfusion 3.0 Tesla MRI: Validation with 15o‐water PET

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 15O‐water positron emission tomography (MBFPET).

Targeted Chemoradiation in Metastatic Colorectal Cancer: A Phase I Trial of 131I-huA33 with Concurrent Capecitabine

huA33 is a humanized antibody that targets the A33 antigen, which is highly expressed in intestinal epithelium and more than 95% of human colon cancers but not other normal tissues. Previous studies have shown huA33 can target and be retained in a metastatic tumor for 6 wk but eliminated from normal colonocytes within days. This phase I study used radiolabeled huA33 in combination with capecitabine to target chemoradiation to metastatic colorectal cancer. The primary objective was safety and tolerability of the combination of capecitabine and 131I-huA33. Pharmacokinetics, biodistribution, immunogenicity, and tumor response were also assessed. Methods: Eligibility included measurable metastatic colorectal cancer, adequate hematologic and biochemical function, and informed consent. An outpatient scout 131I-huA33 dose was followed by a single-therapy infusion 1 wk later, when capecitabine was commenced. Dose escalation occurred over 5 dose levels. Patients were evaluated weekly, with tumor response assessment at the end of the 12-wk trial. Tumor targeting was assessed using a γ camera and SPECT imaging. Results: Nineteen eligible patients were enrolled. The most frequently observed toxicity included myelosuppression, gastrointestinal symptoms, and asymptomatic hyperbilirubinemia. Biodistribution analysis demonstrated excellent tumor targeting of the known tumor sites, expected transient bowel uptake, but no other normal tissue uptake. 131I-huA33 demonstrated a mean terminal half-life and serum clearance suited to radioimmunotherapy (T1/2β, 100.24 ± 20.92 h, and clearance, 36.72 ± 8.01 mL/h). The mean total tumor dose was 13.8 ± 7.6 Gy (range, 5.1–26.9 Gy). One patient had a partial response, and 10 patients had stable disease. Conclusion: 131I-huA33 achieves specific targeting of radiotherapy to colorectal cancer metastases and can be safely combined with chemotherapy, providing an opportunity to deliver chemoradiation specifically to metastatic disease in colorectal cancer patients.

Impaired myocardial sympathetic innervation is associated with diastolic dysfunction in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study

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.

Accurate quantitative measurements of brachial artery cross-sectional vascular area and vascular volume elastic modulus using automated oscillometric measurements: comparison with brachial artery ultrasound.

Increasing vascular diameter and attenuated vascular elasticity may be reliable markers for atherosclerotic risk assessment. However, previous measurements have been complex, operator-dependent or invasive. Recently, we developed a new automated oscillometric method to measure a brachial artery’s estimated area (eA) and volume elastic modulus (VE). The aim of this study was to investigate the reliability of new automated oscillometric measurement of eA and VE. Rest eA and VE were measured using the recently developed automated detector with the oscillometric method. eA was estimated using pressure/volume curves and VE was defined as follows (VE=Δ pressure/ (100 × Δ area/area) mm Hg/%). Sixteen volunteers (age 35.2±13.1 years) underwent the oscillometric measurements and brachial ultrasound at rest and under nitroglycerin (NTG) administration. Oscillometric measurement was performed twice on different days. The rest eA correlated with ultrasound-measured brachial artery area (r=0.77, P<0.001). Rest eA and VE measurement showed good reproducibility (eA: intraclass correlation coefficient (ICC)=0.88, VE: ICC=0.78). Under NTG stress, eA was significantly increased (12.3±3.0 vs. 17.1±4.6 mm2, P<0.001), and this was similar to the case with ultrasound evaluation (4.46±0.72 vs. 4.73±0.75 mm, P<0.001). VE was also decreased (0.81±0.16 vs. 0.65±0.11 mm Hg/%, P<0.001) after NTG. Cross-sectional vascular area calculated using this automated oscillometric measurement correlated with ultrasound measurement and showed good reproducibility. Therefore, this is a reliable approach and this modality may have practical application to automatically assess muscular artery diameter and elasticity in clinical or epidemiological settings.

Feasibility of Quantifying Myocardial Blood Flow with a Shorter Acquisition Time Using 15 O-H 2 O PET

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 15 O-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 15 O-H2O PET. Methods: Thirty patients suspected of having CAD (22 males, 8 females; age 56.5±8.8 yrs) and 17 healthy controls (17 males; age 27.7±6.2 yrs) underwent PET during rest and PET with ATP stress dynamic 15 O-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 15 O-H2O as shorter data acquisitions. These data were compared to the standard 6-min PET acquisition data. 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±1.02 vs. 4.02±1.50, p<0.01), as did the 6-min data (2.19±0.92 vs. 4.16±1.39, p<0.01). However, the CFR based on 2-min data did not show a significant difference (1.96±1.66 vs. 2.73±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. Conclusions: A 3-min, but not 2-min, scan with 15 O-H2O PET can be used for the quantitative evaluation of MBF and CFR.

Anatomical and Functional Estimations of Brachial Artery Diameter and Elasticity Using Oscillometric Measurements with a Quantitative Approach.

Noninvasive vascular function measurement plays an important role in detecting early stages of atherosclerosis and in evaluating therapeutic responses. In this regard, recently, new vascular function measurements have been developed. These new measurements have been used to evaluate vascular function in coronary arteries, large aortic arteries, or peripheral arteries. Increasing vascular diameter represents vascular remodeling related to atherosclerosis. Attenuated vascular elasticity may be a reliable marker for atherosclerotic risk assessment. However, previous measurements for vascular diameter and vascular elasticity have been complex, operator-dependent, or invasive. Therefore, simple and reliable approaches have been sought. We recently developed a new automated oscillometric method to measure the estimated area (eA) of a brachial artery and its volume elastic modulus (VE). In this review, we further report on this new measurement and other vascular measurements. We report on the reliability of the new automated oscillometric measurement of eA and VE. Based on our findings, this measurement technique should be a reliable approach, and this modality may have practical application to automatically assess muscular artery diameter and elasticity in clinical or epidemiological settings. In this review, we report the characteristics of our new oscillometric measurements and other related vascular function measurements.

Diagnostic value of quantitative coronary flow reserve and myocardial blood flow estimated by dynamic 320 MDCT scanning in patients with obstructive coronary artery disease

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

Kinetic Analysis for Cardiac PET

Objective: PET has the ability to evaluate functional information as well as visualization of radiotracer uptake. Compartmental model is a basic idea to analyze dynamic PET data. C-HED has been the most frequently used PET tracer for the evaluation of cardiac sympathetic nervous system (SNS) function. The washout of norepinephrine from myocardium is associated with increasing SNS activity in heart failure (HF). However, the existence of washout of 11C-HED from the myocardium is controversial. Although “retention index” (RI) is commonly calculated to quantify the uptake of HED, RI is not purely able to distinguish washout parameter and uptake parameter. Therefore, in this study, we aimed to evaluate whether HED was washed out from the myocardium using compartment model analysis.