Assessment of the reproducibility of baseline and hyperemic myocardial blood flow measurements with 15O-labeled water and PET.

PET with 15O-labeled water allows noninvasive quantification of myocardial blood flow (MBF) at baseline and during pharmacologically induced hyperemia to assess the coronary vasodilator reserve (CVR = hyperemic/baseline MBF). Despite widespread use of PET, its reproducibility during one study session has not been tested. Intravenous adenosine (Ado), a powerful coronary vasodilator with a very short decay time, is commonly used for the induction of hyperemia. However, it is not known whether Ado can induce tachyphylaxis after short-term repetitive administration. In this study, we aimed to test the reproducibility of PET assessment of CVR during Ado-induced hyperemia. METHODS: In 21 healthy volunteer men, baseline and Ado MBF were measured twice using PET with 15O-labeled water to obtain two CVR assessments within 1 h. RESULTS: There was no significant difference between the two baselines (0.89 +/- 0.14 versus 0.99 +/- 0.15 mL/min/g, mean difference 13% +/- 11%) or between the two hyperemic MBFs (3.51 +/- 0.45 versus 3.83 +/- 0.49 mL/min/g, mean difference 10% +/- 14%), resulting in comparable values of CVR (4.05 +/- 0.75 versus 3.93 +/- 0.72, mean difference 2% +/- 15%). The repeatability coefficient for MBF was 0.17 mL/min/g at baseline and 0.94 mL/min/g during hyperemia. The repeatability coefficient of the rate pressure product (RPP) was lower at baseline (1,304 mm Hg x beat/min) than during hyperemia (3,448 mm Hg x beat/min). CONCLUSION: Repeated measurements of MBF and CVR during the same study session were not significantly different, demonstrating the validity of the technique. The larger variability of hyperemic flow, as indicated by the larger repeatability coefficient, was paralleled by a greater variability of the RPP. This could mean that the greater variability of MBF during stress is more likely due to a variable response to Ado rather than to a measurement error.     

Quantitative evaluation of myocardial blood flow and ejection fraction with a single dose of (13)NH(3) and Gated PET.

To evaluate myocardial blood flow (MBF) and cardiac function with a single dose of (13)NH(3), electrocardiographically (ECG) gated PET acquisition was performed after a dynamic PET scan was obtained. Gated blood-pool (GBP) imaging with C(15)O PET was also performed to compare the left ventricular ejection fraction (LVEF) obtained using the 2 methods. METHODS: Six healthy volunteers and 34 patients with cardiovascular disease were studied. Each subject underwent dynamic PET scanning after a slow intravenous injection of approximately 740 MBq (13)NH(3), followed by ECG gated PET scanning. MBF images were calculated by the Patlak plot method. Before obtaining the (13)NH(3) scan, the GBP image was obtained with a bolus inhalation of C(15)O. Twenty patients also underwent left ventriculography (LVG) to compare the value of the LVEF obtained using this technique with that determined using the gated PET method. RESULTS: The mean regional value of MBF calculated for healthy volunteers in the resting condition was 0.61 +/- 0.10 mL/min/g. The LVEF obtained using GBP PET (EF(CO)) was consistent with that obtained using LVG. The LVEF calculated from gated (13)NH(3) scans (EF(NH3)) correlated well with EF(CO), although EF(NH3) slightly underestimated the LVEF (EF(NH3) = 0.97. EF(CO) - 2.94; r = 0.87). EF(NH3) was significantly different from EF(CO) in patients with a perfusion defect in the cardiac wall (EF(NH3) = 39% +/- 11% vs. EF(CO) = 45% +/- 11%; n = 19; P < 0.001), whereas no significant difference was found between them in subjects with no defect (EF(NH3) = 58% +/- 13% vs. EF(CO) = 61% +/- 10%; n = 21). CONCLUSION: Gated PET acquisition accompanied by obtaining a dynamic PET scan with a single dose of (13)NH(3) is a promising method for the simultaneous clinical evaluation of MBF and cardiac function. However, in patients with a defect in the cardiac wall, EF(NH3) showed a tendency to underestimate the EF compared with EF(CO).     

Beta-adrenergic blockade and myocardial perfusion in coronary artery disease: differential effects in stenotic versus remote myocardial segments.

Beta-adrenergic blocking agents are widely used in coronary artery disease (CAD), although their impact on myocardial blood flow (MBF) and coronary flow reserve (CFR) remains unclear. We studied the effect of long-term beta-blocker treatment (carvedilol or metoprolol) on coronary microcirculation in CAD patients using PET. METHODS: Regional and global resting and adenosine-induced hyperemic MBF and CFR were measured with 13N-ammonia and PET in 36 CAD patients before and after 12 wk of oral therapy with either carvedilol, 50 mg/d, or metoprolol, 100 mg/d. RESULTS: Beta-blockade decreased global resting MBF in proportion to cardiac work (from 0.86 +/- 0.20 to 0.77 +/- 0.14 mL/min/g, P < 0.05) without affecting global hyperemic flow. Hyperemic MBF was significantly lower in stenosis-dependent segments than in remote segments (1.76 +/- 0.64 vs. 2.04 +/- 0.67 mL/min/g, P < 0.05) at baseline but was comparable in both after treatment (2.02 +/- 0.68 vs. 1.90 +/- 0.78 mL/min/g, P = not statistically significant [NS]), resulting in a significant CFR increase in stenotic segments (+15%, P < 0.05) but not in remote segments (+9%, P = NS). CONCLUSION: The beneficial effect of beta-adrenergic blockade can be explained by the reduction in oxygen consumption (= decreased demand) but also by a modest improvement in vasodilator capacity (= increased supply). The improvement in CFR is found predominantly in stenosis-dependent rather than remote segments.     

Bicycle exercise stress in PET for assessment of coronary flow reserve: repeatability and comparison with adenosine stress.

PET allows absolute measurements of myocardial blood flow (MBF). The aim of the present study was to evaluate the feasibility and repeatability of supine bicycle exercise stress, compared with standard adenosine stress, in PET. METHODS: In 11 healthy volunteers, MBF was assessed at rest, during adenosine-induced (140 microg/kg/min over 7 min) hyperemia, and immediately after supine bicycle exercise (mean workload, 130 W, which is 70% of the predicted value) using PET and (15)O-H(2)O. The assessment was then repeated after 20 min. Coronary flow reserve (CFR) was calculated as hyperemic/resting MBF for adenosine stress and exercise stress. Repeatability was evaluated according to the method of Bland and Altman. RESULTS: No significant differences were found between the paired resting MBF (1.22 +/- 0.16 vs. 1.26 +/- 0.21 mL/min/g; mean difference, 3% +/- 11%) and the hyperemic MBF with adenosine stress (5.13 +/- 0.74 vs. 4.97 +/- 1.05; mean difference, -4% +/- 14%) or exercise stress (2.35 +/- 0.66 vs. 2.25 +/- 0.61; mean difference, -4% +/- 19%). CFR was reproducible with adenosine stress (4.23 +/- 0.62 vs. 4.05 +/- 1.06, P = not statistically significant; mean difference, -5% +/- 19%) and exercise stress (1.91 +/- 0.46 vs. 1.80 +/- 0.44, P = not statistically significant; mean difference, -5% +/- 15%). Repeatability coefficients for MBF were 0.26 (rest), 1.34 (adenosine stress), and 0.82 (exercise stress) mL/min/g. CONCLUSION: Assessment of CFR with (15)O-H(2)O and PET using bicycle exercise in the PET scanner is feasible and at least as repeatable as using adenosine stress.     

Assessment of myocardial perfusion by dynamic N-13 ammonia PET imaging: Comparison of 2 tracer kinetic models

BACKGROUND: Measurement of myocardial blood flow (MBF) by dynamic nitrogen 13 ammonia (NH(3)) positron emission tomography (PET) uses tracer kinetic modeling to analyze time-activity curves. We compared 2 commonly used models with 2 compartments (2C) and 3 compartments (3C) for quantification of MBF and coronary flow reserve (CFR). METHODS AND RESULTS: Seventy-seven patients underwent NH(3) PET at rest and during hyperemia. Time-activity curves for blood pool and myocardial segments were obtained from short-axis images of dynamic sequences. Model fitting of the 2C and 3C models was performed to estimate regional MBF. MBF values calculated by 2C and 3C models were 0.98 +/- 0.31 mL.min(-1).g(-1) and 1.11 +/- 0.37 mL.min(-1).g(-1), respectively, at rest (P < .0001) and 2.79 +/- 1.18 mL.min(-1).g(-1) and 2.46 +/- 1.02 mL.min(-1).g(-1), respectively, during hyperemia (P < .01), resulting in a CFR of 3.02 +/- 1.31 and 2.39 +/- 1.15 (P < .0001), respectively. Significant correlation was observed between the 2 models for calculation of resting MBF (r = 0.78), hyperemic MBF (r = 0.68), and CFR (r = 0.68). CONCLUSION: Measurements of MBF and CFR by 2C and 3C models are significantly related. However, quantification of MBF and CFR significantly differs between the methods. This difference needs to be considered when normal values are established or when measurements obtained with different methods need to be compared.     

Quantification of subendocardial and subepicardial blood flow using 15O-labeled water and PET: experimental validation.

The purpose of this study was to assess the feasibility and accuracy of quantifying subendocardial and subepicardial myocardial blood flow (MBF) and the relative coronary flow reserves (CFR) using (15)O-labeled water (H(2)(15)O) and 3-dimensional-only PET. METHODS: Eight pigs were scanned with H(2)(15)O and (15)O-labeled carbon monoxide (C(15)O) after partially occluding the circumflex (n = 3) or the left anterior descending (n = 5) coronary artery, both at rest and during hyperemia induced by intravenous dipyridamole. Radioactive microspheres were injected during each of the H(2)(15)O scans. RESULTS: In a total of 256 paired measurements of MBF, ranging from 0.30 to 4.46 mL.g(-1).min(-1), microsphere and PET MBF were fairly well correlated. The mean difference between the 2 methods was -0.01 +/- 0.52 mL.g(-1).min(-1) with 95% of the differences lying between the limits of agreement of -1.02 and 1.01 mL.g(-1).min(-1). CFR was significantly reduced (P < 0.05) in the ischemic subendocardium (PET = 1.12 +/- 0.45; microspheres = 1.09 +/- 0.50; P = 0.86) and subepicardium (PET = 1.2 +/- 0.35; microspheres = 1.32 +/- 0.5; P = 0.39) in comparison with remote subendocardium (PET = 1.7 +/- 0.62; microspheres = 1.64 +/- 0.61; P = 0.68) and subepicardium (PET = 1.79 +/- 0.73; microspheres = 2.19 +/- 0.86; P = 0.06). CONCLUSION: Dynamic measurements using H(2)(15)O and a 3-dimensional-only PET tomograph allow regional estimates of the transmural distribution of MBF over a wide flow range, although transmural flow differences were underestimated because of the partial-volume effect. PET subendocardial and subepicardial CFR were in good agreement with the microsphere values.     

Repeatability of cold pressor test-induced flow increase assessed with H(2)(15)O and PET.

The aim of this study was to evaluate the repeatability of endothelium-related myocardial blood flow (MBF) responses to cold pressor testing (CPT) as assessed by PET. METHODS: In 10 age-matched control subjects (26.6 +/- 3.4 y) and 10 tobacco smokers (24.9 +/- 3.3 y) MBF was assessed at rest and after repeated CPT (CPT1 and CPT2, 40 min apart) using PET with H(2)(15)O. CPT was performed by a 2-min immersion of the subject's foot in ice water. MBF values were corrected for cardiac workload (rate.pressure product), and the repeatability of CPT-related MBF values was assessed according to Bland and Altman. RESULTS: Corrected MBF at CPT1 and CPT2 were comparable in control subjects (1.79 +/- 0.37 vs. 1.70 +/- 0.35 mL/min/g; P = not significant [NS]) and in smokers (1.97 +/- 0.42 vs. 1.80 +/- 0.41 mL/min/g; P = NS). Repeatability coefficients in control subjects and smokers were 0.46 mL/min/g (27% of the mean MBF) and 0.51 mL/min/g (27%), respectively. MBF increased significantly after CPT in both groups but tended to be lower in smokers (P = 0.08). CONCLUSION: PET measured MBF combined with CPT is a feasible and repeatable method for the evaluation of endothelium-related changes of MBF.     

Quantitative assessment of regional myocardial blood flow using oxygen-15-labelled water and positron emission tomography: a multicentre evaluation in Japan

Recently, a method has been proposed for the quantitative measurement of regional myocardial blood flow (MBF) using oxygen-15-labelled water and positron emission tomography (PET). A multicentre project was organized with the intention of evaluating the accuracy of this method, particularly as a multicentre clinical investigative tool. Each of seven institutions performed PET studies on more than five normal volunteers following a specified protocol. The PET study included a transmission scan, a 15O-carbon monoxide static scan and a 15O-water dynamic scan, thereby yielding MBF values which should have been independent of the spatial resolution of the PET scanner employed. Fifty-three subjects (aged 20-63 years, mean+/-SD 36+/-12 years) were studied at rest, and 31 of these subjects were also studied after dipyridamole in five institutions. Inter-institution consistency and intra-subject variation in MBF values were then evaluated. MBF averaged for all subjects was 0.93+/-0.34 ml min(-1) g(-1) at rest and 3.40+/-1.73 ml min(-1) g(-1) after the administration of dipyridamole, and the flow reserve (defined as the ratio of the two MBF values) was 3.82+/-2.12; these values are consistent with previous reports. Resting MBF values were significantly correlated with the heart rate-blood pressure product (RPP) (y=0.31+6.56E-5x, P<0.010), and RPP was in resting MBF observed in all institutions was well explained by the age-dependent RPP. No significant difference was observed in resting MBF among the institutions. Except in one institution, no significant difference was seen in dipyridamole MBF or myocardial flow reserve. No significant difference was found among the myocardial segments. Regional variation was reasonably small in five institutions, but was not acceptable in two institutions, which was attributed to the scanner performance. These observations suggest that the 15O-water PET technique is useful for a multicentre clinical study if the PET scanner can provide time-activity data with good count statistics.     

Absolute quantification of myocardial blood flow with H(2)(15)O and 3-dimensional PET: an experimental validation.

The purpose of this study was to assess a 3-dimensional (3D)-only PET scanner (ECAT EXACT3D) for its use in the absolute quantification of myocardial blood flow (MBF) using H(2)(15)O. METHODS: Nine large white pigs were scanned with H(2)(15)O and C(15)O before and after partially occluding the circumflex (n = 4) or the left anterior descending (n = 5) coronary artery at rest and during hyperemia induced by intravenous dipyridamole. Radioactive microspheres labeled with either (57)Co or (46)Sc were injected during each of the H(2)(15)O scans, which allowed comparison between microsphere and PET measurements of regional MBF. PET analyses of 3D acquisition data were performed using filtered backprojection reconstruction and region-of-interest definition by factor and cluster analysis techniques and single-compartment model quantification. RESULTS: The Hanning filter applied in image reconstruction resulted in a left atrial blood volume recovery factor of 0.84 +/- 0.06. Differences between repeated measurements of recovery were small (mean, -0.8%; range, -6.6% to 3.6%). In 256 paired measurements of MBF ranging from 0.05 to 4.4 mL. g(- 1). min(-1), microsphere and PET measurements were fairly well correlated. The mean difference between the 2 methods was - 0.11 mL. g(-1). min(-1) and the limits of agreement (+2 SD) were -0.82 and 0.60 mL. g(-1). min(-1) (Bland-Altman plot). CONCLUSION: Dynamic measurements with H(2)(15)O using a 3D-only PET tomograph provide reliable and accurate measurements of absolute regional MBF over a wide flow range. The 3D acquisition technique can reduce the radiation dose to the subject while maintaining adequate counting statistics.     

Assessment of the long-term reproducibility of baseline and dobutamine-induced myocardial blood flow in patients with stable coronary artery disease.

Although physical exercise is the preferred stimulus for cardiac stress testing, pharmacologic agents are useful in patients who are unable to exercise. Previous studies have demonstrated short-term repeatability of exercise and adenosine stress, but little data exist regarding dobutamine (Dob) stress or the long-term reproducibility of pharmacologic stressors in coronary artery disease (CAD) patients. PET allows accurate, noninvasive quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR). The aim of the study was to investigate the long-term reproducibility of Dob stress on MBF and CFR in CAD patients using PET. METHODS: Fifteen patients with chronic stable angina and angiographically proven CAD (>70% stenosis in at least 1 major coronary artery) underwent PET with (15)O-labeled water and Dob stress at baseline (time [t] = 0) and after 24 wk (t = 24). MBF at rest and MBF during Dob stress were calculated for the whole left ventricle, the region subtended by the most severe coronary artery stenosis (Isc), and remote myocardium subtended by arteries with minimal or no disease (Rem). Reproducibility was assessed using the Bland-Altman (BA) repeatability coefficient and was also expressed as a percentage of the mean value of the 2 measurements (%BA). RESULTS: Dob dose (30 +/- 11 vs. 031 +/- 11 microg/kg/min; P = not significant [ns]) and peak Dob rate.pressure product (20,738 +/- 3,947 vs. 20,047 +/- 3,455 mm Hg x beats/min; P = ns) were comparable at t = 0 and t = 24. There was no significant difference in resting or Dob MBF (mL/min/g) between t = 0 and t = 24 for the whole left ventricle (1.03 +/- 0.19 vs. 1.10 +/- 0.20 and 2.02 +/- 0.44 vs. 2.09 +/- 0.57; P = ns for both), Isc (1.05 +/- 0.24 vs. 1.10 +/- 0.26 and 1.79 +/- 0.53 vs. 1.84 +/- 0.62; P = ns for both), or Rem (1.03 +/- 0.23 vs. 1.10 +/- 0.26 and 2.27 +/- 0.63 vs. 2.26 +/- 0.63; P = ns for both) territories. Global (1.98 +/- 0.40 vs. 1.90 +/- 0.46; P = ns) and regional CFR (Isc: 1.65 +/- 0.40 vs. 1.67 +/- 0.47, and Rem: 2.25 +/- 0.57 vs. 2.06 +/- 0.51; P = ns) were reproducible. The BA repeatability coefficients (and %BA) for MBF in ischemic and remote territories were 0.3 (28%) and 0.26 (24%) at rest and 0.49 (27%) and 0.58 (26%) during Dob stress. CONCLUSION: In patients with clinically stable CAD, Dob induces reproducible changes in both global and regional MBF and CFR over a time interval of 24 wk. The reproducibility of MBF and CFR with Dob was comparable with the short-term repeatability reported for adenosine and physical exercise in healthy subjects.     

Estimation of myocardial blood flow and myocardial flow reserve by <Superscript>99m</Superscript>Tc-sestamibi imaging: comparison with the results of [<Superscript>15</Superscript>O]H<Subscript>2</Subscript>O PET

We developed a noninvasive method to quantitatively estimate the myocardial blood flow (MBF) index and flow reserve (MFR) using dynamic and static data obtained with technetium-99m sestamibi, and compared the results with MBF and MFR measured by oxygen-15-labeled water ([(15)O]H(2)O) PET. Twenty patients with coronary artery disease (CAD) and nine normal subjects underwent both (99m)Tc-sestamibi and PET studies within 2 weeks. From the anterior view, dynamic data were acquired for 2 min immediately after the injection of (99m)Tc-sestamibi, and planar static images were also obtained after 5 min at rest and during ATP stress (0.16 mg kg(-1) min(-1) for 5 min) on another day. The area under the time-activity curve on the aortic arch (Aorta ACU), myocardial weight with the SPET image (M), and the myocardial count on the planar image for 1 min (C(m)) were obtained. The MBF index (MBFI) was calculated as follows: MBFI=Cm/Aorta ACU x 100M. MFR was measured by dividing the MBFI at ATP stress by MBFI at rest. The MBFI measured by (99m)Tc-sestamibi was significantly correlated with MBF obtained using [(15)O]H(2)O PET (MBFI=13.174+11.732 x MBF, r=0.821, P<0.001). Furthermore, MFR measured by (99m)Tc-sestamibi was well correlated with that obtained using [(15)O]H(2)O PET, with some underestimation (r=0.845, P<0.001). MFR using (99m)Tc-sestamibi in patients with CAD was significantly lower than that in normal subjects (CAD: 1.484+/-0.256 vs normal: 2.127+/-0.308, P<0.001). These data suggest that the MBFI and MFR can be measured with (99m)Tc-sestamibi. This may be useful for the quantitative assessment of CAD, especially in those patients with diffuse coronary disease.     

Validation of myocardial perfusion reserve measurements using regularized factor images of H(2)(15)O dynamic PET scans.

The use of H(2)(15)O PET scans for the measurement of myocardial perfusion reserve (MPR) has been validated in both animal models and humans. Nevertheless, this protocol requires cumbersome acquisitions such as C(15)O inhalation or (18)F-FDG injection to obtain images suitable for determining myocardial regions of interest. Regularized factor analysis is an alternative method proposed to define myocardial contours directly from H(2)(15)O studies without any C(15)O or FDG scan. The study validates this method by comparing the MPR obtained by the regularized factor analysis with the coronary flow reserve (CFR) obtained by intracoronary Doppler as well as with the MPR obtained by an FDG acquisition. METHODS: Ten healthy volunteers and 10 patients with ischemic cardiopathy or idiopathic dilated cardiomyopathy were investigated. The CFR of patients was measured sonographically using a Doppler catheter tip placed into the proximal left anterior descending artery. The mean velocity was recorded at baseline and after dipyridamole administration. All subjects underwent PET imaging, including 2 H(2)(15)O myocardial perfusion studies at baseline and after dipyridamole infusion, followed by an FDG acquisition. Dynamic H(2)(15)O scans were processed by regularized factor analysis. Left ventricular cavity and anteroseptal myocardial regions of interest were drawn independently on regularized factor images and on FDG images. Myocardial blood flow (MBF) and MPR were estimated by fitting the H(2)(15)O time-activity curves with a compartmental model. RESULTS: In patients, no significant difference was observed among the 3 methods of measurement-Doppler CFR, 1.73 +/- 0.57; regularized factor analysis MPR, 1.71 +/- 0.68; FDG MPR, 1.83 +/- 0.49-using a Friedman 2-way ANOVA by ranks. MPR measured with the regularized factor images correlated significantly with CFR (y = 1.17x - 0.30; r = 0.97). In the global population, the regularized factor analysis MPR and FDG MPR correlated strongly (y = 0.99x; r = 0.93). Interoperator repeatability on regularized factor images was 0.126 mL/min/g for rest MBF, 0.38 mL/min/g for stress MBF, and 0.34 for MPR (19% of mean MPR). CONCLUSION: Regularized factor analysis provides well-defined myocardial images from H(2)(15)O dynamic scans, permitting an accurate and simple measurement of MPR. The method reduces exposure to radiation and examination time and lowers the cost of MPR protocols using a PET scanner.     

Improvement of algorithm for quantification of regional myocardial blood flow using 15O-water with PET.

(15)O-Water and dynamic PET allow noninvasive quantification of myocardial blood flow (MBF). However, complicated image analyzing procedures are required, which may limit the practicality of this approach. We have designed a new practical algorithm, which allows stable, rapid, and automated quantification of regional MBF (rMBF) using (15)O-water PET. We designed an algorithm for setting the 3-dimensional (3D) region of interest (ROI) of the whole myocardium semiautomatically. Subsequently, a uniform input function was calculated for each subject using a time-activity curve in the 3D whole myocardial ROI. The uniform input function allows the mathematically simple and robust algorithm to estimate rMBF. METHODS: Thirty-six volunteers were used in the static (15)O-CO and dynamic (15)O-water PET studies. To evaluate the reproducibility of the estimates, a repeated (15)O-water scan was obtained under resting condition. In addition, to evaluate the stability of the new algorithm in the hyperemic state, a (15)O-water scan was obtained with adenosine triphosphate. This algorithm includes a procedure for positioning a 3D ROI of the whole myocardium from 3D images and dividing it into 16 segments. Subsequently, the uniform input function was calculated using time-activity curves in the whole myocardial ROI and in the LV ROI. The uniform input function allowed this simple and robust algorithm to estimate the rMBF, perfusable tissue fraction (PTF), and spillover fraction (Va) according to a single tissue compartment model. These estimates were compared with those calculated using the original method. A simulation study was performed to compare the effects of errors in PTF or Va on the MBF using the 2 methods. RESULTS: The average operating time for positioning a whole myocardial ROI and 16 regional myocardial ROIs was <5 min. The new method yielded less deviation in rMBF (0.876 +/- 0.177 mL/min/g, coefficient of variation [CV] = 20.2%, n = 576) than those with the traditional method (0.898 +/- 0.271 mL/min/g, CV = 30.1%, n = 576) (P < 0.01). In the hyperemic state, the new method yielded less deviation in rMBF (3.890 +/- 1.250 mL/min/g, CV = 32.1%) than those with the traditional method (3.962 +/- 1.762 mL/min/g, CV = 44.4%) (P < 0.05). This method yielded significantly higher reproducibility of rMBF (r = 0.806, n = 576) than the original method (r = 0.756, n = 576) (P < 0.05). Our new method yielded a better correlation in the repeated measurement values of rMBF and less variability among the regions in the myocardium than with the original theory of the (15)O-water technique. The simulation study demonstrated fewer effects of error in the PTF or Va on the MBF value with the new method. CONCLUSION: We have developed a technique for an automated, simplified, and stable algorithm to quantify rMBF. This software is considered to be practical for clinical use in myocardial PET studies using (15)O-water with a high reproducibility and a short processing time.     

Coronary microangiopathy in type 2 diabetic patients: relation to glycemic control, sex, and microvascular angina rather than to coronary artery disease.

Coronary microangiopathy is a major complication in diabetics. However, the presence of independent factors in association with coronary microangiopathy in patients with non-insulin-dependent diabetes mellitus (NIDDM) or the difference in coronary microangiopathy between diabetics with coronary artery disease (CAD) and those with microvascular angina is unclear. METHODS: Nineteen patients with NIDDM and microvascular angina, 18 patients with NIDDM and CAD, and 17 age-matched control subjects were studied. Myocardial segments that were perfused by angiographically normal coronary arteries were studied. The baseline myocardial blood flow (MBF) and the MBF during dipyridamole administration were measured using PET and 13N-ammonia, after which the myocardial flow reserve (MFR) was calculated to assess coronary microangiopathy. RESULTS: The baseline MBF was comparable among NIDDM patients with microvascular angina, NIDDM patients with CAD, and control subjects. However, the MBF during dipyridamole administration was significantly lower in NIDDM patients with microvascular angina (126 +/- 42.7 mL/min/100 g) than that in either NIDDM patients with CAD (210 +/- 70.1 mL/min/100 g; P < 0.01) or control subjects (293 +/- 159 mL/min/100 g; P < 0.01), as was the MFR (NIDDM with microvascular angina, 1.90 +/- 0.73; NIDDM with CAD, 2.59 +/- 0.81 [P < 0.01]; control subjects, 3.69 +/- 1.09 [P < 0.01]). Multivariate stepwise regression analysis showed that, among the factors considered, glycemic control was independently related to the MFR (r = 0.838; P < 0.05). CONCLUSION: Glycemic control appears to be essential for coronary microangiopathy in NIDDM.     

PET-measured responses of MBF to cold pressor testing correlate with indices of coronary vasomotion on quantitative coronary angiography.

The aims of this study were to determine whether responses in myocardial blood flow (MBF) to the cold pressor testing (CPT) method noninvasively with PET correlate with an established and validated index of flow-dependent coronary vasomotion on quantitative angiography. METHODS: Fifty-six patients (57 +/- 6 y; 16 with hypertension, 10 with hypercholesterolemia, 8 smokers, and 22 without coronary risk factors) with normal coronary angiograms were studied. Biplanar end-diastolic images of a selected proximal segment of the left anterior descending artery (LAD) (n = 27) or left circumflex artery (LCx) (n = 29) were evaluated with quantitative coronary angiography in order to determine the CPT-induced changes of epicardial luminal area (LA, mm(2)). Within 20 d of coronary angiography, MBF in the LAD, LCx, and right coronary artery territory was measured with (13)N-ammonia and PET at baseline and during CPT. RESULTS: CPT induced on both study days comparable percent changes in the rate x pressure product (%DeltaRPP, 37% +/- 13% and 40% +/- 17%; P = not significant [NS]). For the entire study group, the epicardial LA decreased from 5.07 +/- 1.02 to 4.88 +/- 1.04 mm(2) (DeltaLA, -0.20 +/- 0.89 mm(2)) or by -2.19% +/- 17%, while MBF in the corresponding epicardial vessel segment increased from 0.76 +/- 0.16 to 1.03 +/- 0.33 mL x min(-1) x g(-1) (DeltaMBF, 0.27 +/- 0.25 mL x min(-1) x g(-1)) or 36% +/- 31% (P 相似文献   

Comparison of myocardial blood flow induced by adenosine triphosphate and dipyridamole in patients with coronary artery disease

Myocardial perfusion imaging with adenosine triphosphate (ATP) has been used increasingly to diagnose coronary artery disease (CAD) and assess risk for this disease. This study compared absolute myocardial blood flow (MBF) and myocardial flow reserve index (MFR) with ATP and dipyridamole (DIP) in patients with CAD. MBF was quantified by 15O-H2O PET in 21 patients with CAD (17 male, 4 female), aged 55 to 81 years. MBF was measured at rest, during intravenous injection of ATP (0.16 mg/kg/min), and again after DIP infusion (0.56 mg/kg). Regions of interest were drawn in nonischemic and ischemic segments based on findings from thallium-201 (201T1) scintigraphy and coronary angiography (CAG). Absolute MBF values and indexes of MFR were calculated in nonischemic and ischemic segments. Intravenous injection of ATP and DIP significantly increased MBF in nonischemic (2.4 +/- 0.9 and 2.1 +/- 0.8 ml/g/min, respectively; p < 0.01, for both) and in ischemic segments (1.3 +/- 0.4 and 1.5 +/- 0.4 ml/g/min, respectively; p < 0.01, for both). There was a significant difference in MBF values between ATP and DIP in nonischemic segments (p < 0.05), which was not observed in ischemic segments. In nonischemic segments, ATP produced higher MFR than DIP (2.1 +/- 0.8 and 1.8 +/- 0.7, respectively; p < 0.05), while no significant difference was observed in ischemic segments (1.5 +/- 0.6 and 1.7 +/- 0.3, respectively). ATP produced a greater hyperemia than DIP between the ischemic and nonischemic myocardium in patients with CAD. ATP is as effective as DIP for the diagnosis of CAD.     

Absolute quantification of myocardial blood flow with 13N-ammonia and 3-dimensional PET.

The aim of this study was to compare 2-dimensional (2D) and 3-dimensional (3D) dynamic PET for the absolute quantification of myocardial blood flow (MBF) with (13)N-ammonia ((13)N-NH(3)). METHODS: 2D and 3D MBF measurements were collected from 21 patients undergoing cardiac evaluation at rest (n = 14) and during standard adenosine stress (n = 7). A lutetium yttrium oxyorthosilicate-based PET/CT system with retractable septa, enabling the sequential acquisition of 2D and 3D images within the same patient and study, was used. All 2D studies were performed by injecting 700-900 MBq of (13)N-NH(3). For 14 patients, 3D studies were performed with the same injected (13)N-NH(3) dose as that used in 2D studies. For the remaining 7 patients, 3D images were acquired with a lower dose of (13)N-NH(3), that is, 500 MBq. 2D images reconstructed by use of filtered backprojection (FBP) provided the reference standard for MBF measurements. 3D images were reconstructed by use of Fourier rebinning (FORE) with FBP (FORE-FBP), FORE with ordered-subsets expectation maximization (FORE-OSEM), and a reprojection algorithm (RP). RESULTS: Global MBF measurements derived from 3D PET with FORE-FBP (r = 0.97), FORE-OSEM (r = 0.97), and RP (r = 0.97) were well correlated with those derived from 2D FBP (all Ps < 0.0001). The mean +/- SD differences in global MBF measurements between 3D FORE-FBP and 2D FBP and between 3D FORE-OSEM and 2D FBP were 0.01 +/- 0.14 and 0.01 +/- 0.15 mL/min/g, respectively. The mean +/- SD difference in global MBF measurements between 3D RP and 2D FBP was 0.00 +/- 0.16 mL/min/g. The best correlation between 2D PET and 3D PET performed with the lower injected activity was found for the 3D FORE-FBP reconstruction algorithm (r = 0.95, P < 0.001). CONCLUSION: For this scanner type, quantitative measurements of MBF with 3D PET and (13)N-NH(3) were in excellent agreement with those obtained with the 2D technique, even when a lower activity was injected.     

Effect of caffeine intake on myocardial hyperemic flow induced by adenosine triphosphate and dipyridamole.

The aims of this study were (a). to compare absolute myocardial blood flow (MBF) during adenosine triphosphate (ATP) infusion with that after dipyridamole administration without caffeine intake and (b). to evaluate the effect of caffeine intake on the hyperemic flow induced by these coronary vasodilator agents. METHODS: MBF was quantified with (15)O-labeled water and PET at rest, during ATP infusion (0.16 mg/kg/min for 9 min), and after dipyridamole administration (0.56 mg/kg over 4 min) after a 24-h abstinence from caffeine (baseline evaluation) in 10 healthy volunteers. Within 2 wk, the same PET studies were repeated after caffeine intake to evaluate the effect of caffeine on the hyperemic flow induced by these pharmacologic agents (caffeine study). Myocardial flow reserve (MFR), defined as the ratio of hyperemic to resting blood flow, was also evaluated. RESULTS: Resting MBF in baseline and caffeine studies did not differ significantly (0.79 +/- 0.29 vs. 0.75 +/- 0.31 mL/min/g, P = 0.88). Without caffeine intake, MBF during ATP infusion was significantly higher than that after dipyridamole administration (3.70 +/- 0.67 vs. 3.00 +/- 0.79 mL/min/g, P = 0.003), whereas there was no significant difference in MFR between ATP and dipyridamole stress (5.15 +/- 1.64 vs. 4.11 +/- 1.44, P = 0.07). After caffeine intake, the hyperemic flows induced by ATP and dipyridamole were not significantly different (1.68 +/- 0.37 vs. 1.52 +/- 0.40 mL/min/g, P = 0.50). MFR estimated by ATP and dipyridamole also did not differ significantly in the caffeine studies (2.44 +/- 0.88 vs. 2.25 +/- 0.94, P = 0.73). MBF during ATP infusion and after dipyridamole administration were significantly lower in the caffeine studies than that in the baseline evaluation (1.68 +/- 0.37 vs. 3.70 +/- 0.67 mL/min/g, P < 0.0001, and 1.52 +/- 0.40 vs. 3.00 +/- 0.79 mL/min/g, P < 0.0001, respectively). CONCLUSION: This study demonstrates that ATP has the potential to induce greater hyperemia than dipyridamole, whereas hyperemic responses to ATP and dipyridamole are similarly attenuated after caffeine intake. These findings suggest that abstinence from caffeine before ATP stress testing may be needed.     

Quantification of cerebral blood flow and oxygen metabolism with 3-dimensional PET and 15O: validation by comparison with 2-dimensional PET.

Quantitative PET with (15)O provides absolute values for cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF), which are used for assessment of brain pathophysiology. Absolute quantification relies on physically accurate measurement, which, thus far, has been achieved by 2-dimensional PET (2D PET), the current gold standard for measurement of CBF and oxygen metabolism. We investigated whether quantitative (15)O study with 3-dimensional PET (3D PET) shows the same degree of accuracy as 2D PET. METHODS: 2D PET and 3D PET measurements were obtained on the same day on 8 healthy men (age, 21-24 y). 2D PET was performed using a PET scanner with bismuth germanate (BGO) detectors and a 150-mm axial field of view (FOV). For 3D PET, a 3D-only tomograph with gadolinium oxyorthosilicate (GSO) detectors and a 156-mm axial FOV was used. A hybrid scatter-correction method based on acquisition in the dual-energy window (hybrid dual-energy window [HDE] method) was applied in the 3D PET study. Each PET study included 3 sequential PET scans for C(15)O, (15)O(2), and H(2)(15)O (3-step method). The inhaled (or injected) dose for 3D PET was approximately one fourth of that for 2D PET. RESULTS: In the 2D PET study, average gray matter values (mean +/- SD) of CBF, CBV, CMRO(2), and OEF were 53 +/- 12 (mL/100 mL/min), 3.6 +/- 0.3 (mL/100 mL), 3.5 +/- 0.5 (mL/100 mL/min), and 0.35 +/- 0.06, respectively. In the 3D PET study, scatter correction strongly affected the results. Without scatter correction, average values were 44 +/- 6 (mL/100 mL/min), 5.2 +/- 0.6 (mL/100 mL), 3.3 +/- 0.4 (mL/100 mL/min), and 0.39 +/- 0.05, respectively. With the exception of OEF, values differed between 2D PET and 3D PET. However, average gray matter values of scatter-corrected 3D PET were comparable to those of 2D PET: 55 +/- 11 (mL/100 mL/min), 3.7 +/- 0.5 (mL/100 mL), 3.8 +/- 0.7 (mL/100 mL/min), and 0.36 +/- 0.06, respectively. Even though the 2 PET scanners with different crystal materials, data acquisition systems, spatial resolution, and attenuation-correction methods were used, the agreement of the results between 2D PET and scatter-corrected 3D PET was excellent. CONCLUSION: Scatter coincidence is a problem in 3D PET for quantitative (15)O study. The combination of both the present PET/CT device and the HDE scatter correction permits quantitative 3D PET with the same degree of accuracy as 2D PET and with a lower radiation dose. The present scanner is also applicable to conventional steady-state (15)O gas inhalation if inhaled doses are adjusted appropriately.     

Effect of mental stress on myocardial blood flow and vasomotion in patients with coronary artery disease.

In patients with coronary artery disease (CAD), mental stress may provoke ischemic electrocardiograph changes and abnormalities in regional and global left ventricular function. However, little is known about the underlying myocardial blood flow response (MBF) in these patients. METHODS: We investigated the hemodynamic, neurohumoral, and myocardial blood flow responses to mental stress in 17 patients with CAD and 17 healthy volunteers of similar age. Mental stress was induced by asking individuals to solve mathematic subtractions in a progressively challenging sequence; MBF was quantified at rest and during mental stress using 13N ammonia PET. RESULTS: Mental stress induced significant (P < 0.01) and comparable increases in rate-pressure product, measured in beats per minute x mm Hg, in both patients (from 7826 +/- 2006 to 10586 +/- 2800) and healthy volunteers (from 8227 +/- 1272 to 10618 +/- 2468). Comparable increases also occurred in serum epinephrine (58% in patients versus 52% in healthy volunteers) and norepinephrine (22% in patients versus 27% in healthy volunteers). Although MBF increased in patients (from 0.67 +/- 0.15 to 0.77 +/- 0.18 mL/min/g, P < 0.05) and healthy volunteers (from 0.73 +/- 0.13 to 0.95 +/- 0.22 mL/min/g, P < 0.001), the magnitude of flow increase was smaller in patients (14% +/- 17%) than in healthy volunteers (29% +/- 14%) (P = 0.01). The increase in MBF during mental stress correlated significantly with changes in cardiac work in healthy volunteers (r = 0.77; P < 0.001) but not in patients. CONCLUSION: Despite similar increases in cardiac work and comparable sympathetic stimulation in CAD patients and healthy volunteers, CAD patients exhibit an attenuated blood flow response to mental stress that may contribute to mental stress-induced ischemic episodes in daily life.