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.     

Histochemical correlates of (15)O-water-perfusable tissue fraction in experimental canine studies of old myocardial infarction.

A method has been proposed to quantitate the myocardial water-perfusable tissue fraction (PTF) in the area of hypoperfused asynergic segments using (15)O-water (H2(15)O) and PET. This study investigated the histochemical correlates of PTF (and perfusable tissue index, PTI) in a canine model of old myocardial infarction. METHODS: Myocardial infarction was produced in 12 mongrel dogs, and PET was performed 1 mo later, providing quantitative parametric images of PTF, regional myocardial blood flow (MBF), and extravascular density from H2(15)O, (15)O-carbon monoxide, and transmission datasets. At the end of scanning, the myocardium was sectioned, and the PET images were compared directly with the corresponding myocardial sections. RESULTS: The distribution of tissue necrosis identified by histochemical staining corresponded well with the defect in PTF but not in MBF. PTF agreed with the equilibrium images of myocardial H2(15)O distribution, obtained after injection of a large bolus of H2(15)O. The defect surface area identified on PTF agreed well quantitatively with the morphometric estimates of the surface area of myocardial infarction. PTI agreed with the absolute proportion of histochemically defined normal myocardium (0.87 +/- 0.09 and 0.83 +/- 0.08, respectively; P < 0.01). Both PTF and PTI decreased significantly in segments of myocardial infarction and showed a significant difference between the transmural and nontransmural myocardial infarction. CONCLUSION: The absolute mass and proportion of histochemically defined noninfarcted tissue may be quantitated with PTF and PTI in the area of myocardial infarction segments.     

Generation of parametric image of regional myocardial blood flow using H(2)(15)O dynamic PET and a linear least-squares method.

Although a parametric image of myocardial blood flow (MBF) can be obtained from H(2)(15)O PET using factor and cluster analysis, this approach is limited when factor analysis fails to extract each cardiac component. In this study, a linear least-squares (LLS) method for estimating MBF and generating a MBF parametric image was developed to overcome this limitation. The computer simulation was performed to investigate the statistical properties of the LLS method, and MBF values obtained from the MBF parametric images in dogs were compared with those obtained using the conventional region of interest (ROI) and invasive microsphere methods. METHODS: A differential model equation for H(2)(15)O in the myocardium was modified to incorporate the partial-volume and spillover effect. The equation was integrated from time 0 to each PET sampling point to obtain a linearlized H(2)(15)O model equation. The LLS solution of this equation was estimated and used to calculate the MBF, the perfusable tissue fraction (PTF), and the arterial blood volume fraction (V(a)). A computer simulation was performed using the input function obtained from canine experiments and the tissue time-activity curves contaminated by various levels of Poisson noise. The parametric image of the MBF, PTF, and V(a) was constructed using the PET data from dogs (n = 7) at rest and after pharmacologic stress. The regional MBF from the parametric image was compared with those produced by the ROI method using a nonlinear least-squares (NLS) estimation and an invasive radiolabeled microsphere technique. RESULTS: The simulation study showed that the LLS method was better than the NLS method in terms of statistical reliability, and the parametric images of the MBF, PTF, and V(a) using the LLS method had good image quality and contrast. The regional MBF values using the parametric image showed a good correlation with those using the ROI method (y = 0.84x + 0.40; r = 0.99) and the microsphere technique (y = 0.95x + 0.29; r = 0.96). The computation time was approximately 10 s for the 32 x 32 x 6 x18 (pixel x pixel x plane x frame) matrix. CONCLUSION: A noninvasive, very fast, and accurate method for estimating the MBF and generating a MBF parametric image was developed using the LLS estimation technique and H(2)(15)O dynamic myocardial PET.     

Myocardial tissue fraction--correction for partial volume effects and measure of tissue viability

We have compared two independent methods of correcting the systematic underestimation in measurements of myocardial radiotracer concentration due to wall motion and small transmural wall thickness in cardiac PET studies. The first technique was based on measurement of the tissue fraction by fitting 15O-labeled water dynamic PET data. The other technique involved the subtraction of the C15O-blood volume scan from the transmission data, producing an image of extravascular density. In normal myocardial regions, both values were observed to be about 60% of myocardial tissue density. The tissue fraction was approximately 10% larger than the extravascular density in normal tissue regions. The ratio of alpha/Dev indicates the proportion of the total extravascular tissue for a given ROI that is perfusable by water--independent of the partial volume effect. This ratio was confirmed to be the expected value in normal tissue regions but was reduced in regions of infarction. The use of 15O-water, C15O and transmission data may aid in the differentiation between perfusable and nonperfusable tissue in the infarcted myocardium.     

Effects of patient movement on measurements of myocardial blood flow and viability in resting 15O-water PET studies

Background

Patient movement has been considered an important source of errors in cardiac PET. This study was aimed at evaluating the effects of such movement on myocardial blood flow (MBF) and perfusable tissue fraction (PTF) measurements in intravenous ¹⁵O-water PET.

Methods

Nineteen ¹⁵O-water scans were performed on ten healthy volunteers and three patients with severe cardiac dysfunction under resting conditions. Motions of subjects during scans were estimated by monitoring locations of markers on their chests using an optical motion-tracking device. Each sinogram of the dynamic emission frames was corrected for subject motion. Variation of regional MBF and PTF with and without the motion corrections was evaluated.

Results

In nine scans, motions during ¹⁵O-water scan (inter-frame (IF) motion) and misalignments relative to the transmission scan (inter-scan (IS) motion) larger than the spatial resolution of the PET scanner (4.0 mm) were both detected by the optical motion-tracking device. After correction for IF motions, MBF values changed from 0.845 ± 0.366 to 0.780 ± 0.360 mL/minute/g (P < .05). In four scans with only IS motion detected, PTF values changed significantly from 0.465 ± 0.118 to 0.504 ± 0.087 g/mL (P< .05), but no significant change was found in MBF values.

Conclusions

This study demonstrates that IF motion during ¹⁵O-water scan at rest can be source of error in MBF measurement. Furthermore, estimated MBF is less sensitive than PTF values to misalignment between transmission and ¹⁵O-water emission scans.     

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.     

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^-5 x, 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. Received 25 April and in revised form 30 August 1999     

Assessment of myocardial blood flow using 15O-water and 1-11C-acetate in rats with small-animal PET.

This feasibility study was undertaken to determine whether myocardial blood flow (MBF, mL/g/min) could be quantified noninvasively in small rodents using microPET and 15O-water or 1-11C-acetate. METHODS: MBF was measured in 18 healthy rats using PET and 15O-water (MBF-W) under different interventions and compared with direct measurements obtained with microspheres (MBF-M). Subsequently, MBF was estimated in 24 rats at rest using 1-11C-acetate (MBF-Ace) and compared with measurements obtained with 15O-water. Using factor analysis, images were processed to obtain 1 blood and 1 myocardial time-activity curve per tracer per study. MBF-W was calculated using a well-validated 1-compartment kinetic model. MBF-Ace was estimated using a simple 1-compartment model to estimate net tracer uptake, K1 (K1 (mL/g/min) = MBF.E; E = first-pass myocardial extraction of 1-11C-acetate) and washout (k2 (min(-1))) along with F(BM) (spillover correction) after fixing F(MM) (partial-volume correction) to values obtained from 15O-water modeling. K1 values were converted to MBF values using a first-pass myocardial extraction/flow relationship measured in rats (E = 1.0-0.74.exp(-1.13/MBF)). RESULTS: In the first study, MBF-W correlated well with MBF-M (y = 0.74x + 0.96; n = 18, r = 0.91, P < 0.0001). However, the slope was different than unity, P < 0.05). Refitting of the data after forcing the intercept to be zero resulted in a nonbias correlation between MBF-W and MBF-M (y = 0.95x + 0.0; n = 18, r = 0.86, P < 0.0001) demonstrating that the underestimation of the slope could be attributed to the overestimation of MBF-W for 2 MBF-M values lower than 1.50 mL/g/min. In the second study, MBF-Ace values correlated well with MBF-W with no underestimation of MBF (y = 0.91x + 0.35; n = 24, r = 0.87, P < 0.0001). CONCLUSION: MBF can be quantified by PET using (15)O-water or 1-11C-acetate in healthy rats. Future studies are needed to determine the accuracy of the methods in low-flow states and to develop an approach for a partial-volume correction when 1-11C-acetate is used.     

Quantitative analysis of coronary endothelial function with generator-produced 82Rb PET: comparison with 15O-labelled water PET

Purpose

Endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis. ⁸²Rb is a generator-produced positron emission tomography (PET) myocardial perfusion tracer that is becoming more widely used. We aimed to (1) develop a method for quantitative assessment of coronary endothelial function using the myocardial blood flow (MBF) response during a cold pressor test (CPT) in smokers, measured using ⁸²Rb PET, and (2) compare the results with those measured using ¹⁵O-water PET.

Methods

MBF was assessed at rest and during the CPT with ⁸²Rb and ¹⁵O-water in nine controls and ten smokers. A one-compartment model with tracer extraction correction was used to estimate MBF with both tracers. CPT response was calculated as the ratio of MBF during the CPT to MBF at rest.

Results

At rest, measurements of MBF for smokers vs controls were not different using ¹⁵O-water (0.86?±?0.18 vs 0.70?±?0.13, p?=?0.426) than they were using ⁸²Rb (0.83?±?0.23 vs 0.62?±?0.20, p?=?0.051). Both methods showed a reduced CPT response in smokers vs controls (¹⁵O-water, 1.03?±?0.21 vs 1.42?±?0.29, p?=?0.006; ⁸²Rb, 1.02?±?0.28 vs 1.70?±?0.52, p?<?0.001). There was high reliability [intraclass correlation coefficients: 0.48 (0.07, 0.75)] of MBF measurement between ⁸²Rb and ¹⁵O-water during the CPT.

Conclusion

Using a CPT, ⁸²Rb MBF measurements detected coronary endothelial dysfunctions in smokers. ⁸²Rb MBF measurements were comparable to those made using the ¹⁵O-water approach. Thus, ⁸²Rb PET may be applicable for risk assessments or evaluation of risk factor modification in subjects with coronary risk factors.     

Parametric imaging of myocardial viability using 15O-labelled water and PET/CT: comparison with late gadolinium-enhanced CMR

Purpose

The perfusable tissue index (PTI) is a marker of myocardial viability. Recent technological advances have made it possible to generate parametric PTI images from a single [¹⁵O]H₂O PET/CT scan. The purpose of this study was to validate these parametric PTI images.

Methods

The study population comprised 46 patients with documented or suspected coronary artery disease who were studied with [¹⁵O]H₂O PET and late gadolinium-enhanced (LGE) cardiac magnetic resonance imaging (CMR).

Results

Of the 736 myocardial segments included, 364 showed some degree of LGE. PTI and perfusable tissue fraction (PTF) diminished with increasing LGE. The areas under the curve of the PTI and PTF, used to predict (near) transmural LGE on CMR, were 0.86 and 0.87, respectively. Optimal sensitivity and specificity were 91?% and 73?% for PTI and 69?% and 87?% for PTF, respectively.

Conclusion

PTI and PTF assessed with a single [¹⁵O]H₂O scan can be utilized as markers of myocardial viability in patients with coronary artery disease.     

Quantification of regional myocardial blood flow estimation with three-dimensional dynamic rubidium-82 PET and modified spillover correction model

Purpose

Myocardial blood flow (MBF) estimation with ⁸²Rubidium (⁸²Rb) positron emission tomography (PET) is technically difficult because of the high spillover between regions of interest, especially due to the long positron range. We sought to develop a new algorithm to reduce the spillover in image-derived blood activity curves, using non-uniform weighted least-squares fitting.

Methods

Fourteen volunteers underwent imaging with both 3-dimensional (3D) ⁸²Rb and ¹⁵O-water PET at rest and during pharmacological stress. Whole left ventricular (LV) ⁸²Rb MBF was estimated using a one-compartment model, including a myocardium-to-blood spillover correction to estimate the corresponding blood input function Ca(t)^whole. Regional K1 values were calculated using this uniform global input function, which simplifies equations and enables robust estimation of MBF. To assess the robustness of the modified algorithm, inter-operator repeatability of 3D ⁸²Rb MBF was compared with a previously established method.

Results

Whole LV correlation of ⁸²Rb MBF with ¹⁵O-water MBF was better (P?<?.01) with the modified spillover correction method (r?=?0.92 vs r?=?0.60). The modified method also yielded significantly improved inter-operator repeatability of regional MBF quantification (r?=?0.89) versus the established method (r?=?0.82) (P?<?.01).

Conclusion

A uniform global input function can suppress LV spillover into the image-derived blood input function, resulting in improved precision for MBF quantification with 3D ⁸²Rb PET.     

Properties of an ideal PET perfusion tracer: New PET tracer cases and data

An ideal positron emission tomography (PET) tracer should be highly extractable by the myocardium and able to provide high-resolution images, should enable quantification of absolute myocardial blood flow (MBF), should be compatible with both pharmacologically induced and exercise-induced stress imaging, and should not require an on-site cyclotron. The PET radionuclides nitrogen-13 ammonia and oxygen-15 water require an on-site cyclotron. Rubidium-82 may be available locally due to the generator source, but greater utilization is limited because of its relatively low myocardial extraction fraction, long positron range, and generator cost. Flurpiridaz F 18, a novel PET tracer in development, has a high-extraction fraction, short positron range, and relatively long half-life (as compared to currently available tracers), and may be produced at regional cyclotrons. Results of early clinical trials suggest that both pharmacologically and exercise-induced stress PET imaging protocols can be completed more rapidly and with lower patient radiation exposure than with single-photon emission computerized tomography (SPECT) tracers. As compared to SPECT images in the same patients, flurpiridaz F 18 PET images showed better defect contrast. Flurpiridaz F 18 is a potentially promising tracer for assessment of myocardial perfusion, measurement of absolute MBF, calculation of coronary flow reserves, and assessment of cardiac function at the peak of the stress response.     

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).     

Does myocardial fibrosis hinder contractile function and perfusion in idiopathic dilated cardiomyopathy? PET and MR imaging study

PURPOSE: To prospectively evaluate, by using positron emission tomography (PET) and magnetic resonance (MR) imaging, the interrelationships between regional myocardial fibrosis, perfusion, and contractile function in patients with idiopathic dilated cardiomyopathy (DCM). MATERIALS AND METHODS: The study protocol was approved by the hospital ethics committee, and all subjects gave written informed consent. Sixteen patients with idiopathic DCM (mean age, 54 years +/- 11 [standard deviation]; nine men) and six healthy control subjects (mean age, 28 years +/- 2; five men) were examined with PET and MR tissue tagging. Oxygen 15-labeled water and carbon monoxide were used as tracers at PET to assess myocardial blood flow (MBF) and the perfusable tissue index (PTI), which is inversely related to fibrosis. MBF was determined at rest and during pharmacologically induced hyperemia. Maximum circumferential shortening (E(cc)) was determined with MR tissue tagging. Student t tests were performed for comparison of data sets, and linear regression was used to investigate the association between parameters. RESULTS: Mean global hyperemic MBF (2.23 mL/min/mL +/- 0.73), E(cc) (-10.5% +/- 2.9), and PTI (0.95 +/- 0.10) were lower in the patients with DCM than in the control subjects (4.33 mL/min/mL +/- 0.85, -17.4% +/- 0.6, and 1.09 +/- 0.12, respectively; P < .05 for all). In the patients with DCM, regional PTI was related to E(cc) (r = -0.21, P = .009) but not to resting or hyperemic MBF. Furthermore, regional E(cc) was correlated to both resting (r = -0.28, P = .004) and hyperemic MBF (r = -0.29, P < .001). In addition, the ratio of left ventricular end-diastolic volume to mass, as a reflection of wall stress, was related to global hyperemic MBF (r = -0.52, P = .047) and to global E(cc) (r = 0.69, P = .003). CONCLUSION: In idiopathic DCM, the extent of myocardial fibrosis is related to the impairment in contractile function, whereas fibrosis and perfusion do not seem to be interrelated. The degree of impairment of hyperemic myocardial perfusion is related to contractility and end-diastolic wall stress.     

The quantitative evaluation of myocardial blood flow and myocardial FDG uptake in the infarcted lesions with Q-wave and without Q-wave determined by O-15 water, FDG and PET]

Cardiac PET elicits an accurate relationship between myocardial blood flow (MBF) and tissue viability, which is evaluated by myocardial FDG uptake (MFU). To differentiate reversible tissue from necrotic tissue after the ischemic event, we from necrotic tissue after the ischemic event, we measured absolute MBF and MFU in patients with myocardial infarction. The MBF obtained by O-15 water and dynamic PET was accurately corrected by employing a tissue fraction (a) for the partial volume effect, including wall-motion effect. MFU was also corrected by using the tissue fraction. The subjects consisted of 5 patients with non-Q-wave infarction and 7 patients with Q-wave infarction. The regions of interest were selected from the infarcted area, each corresponding to regions with Q-wave or non-Q-wave. The MBFs in regions with Q wave (0.36 +/- 0.14 ml/min/g) were lower than those without Q wave (0.74 +/- 0.29 ml/min/g) (p less than 0.005). MFUs in regions without Q-wave (0.061 +/- 0.028) were higher than those with Q-wave (0.038 +/- 0.017) (p less than 0.05). The highest threshold of MBF in regions where Q-wave was detected was 0.55 ml/min/g. It is concluded that we will able to find the threshold of electrophysiological dysfunction in the infarcted region with this method.     

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.     

Comparison of microsphere-equivalent blood flow (15O-water PET) and relative perfusion (99mTc-tetrofosmin SPECT) in myocardium showing metabolism-perfusion mismatch.

Myocardial perfusion imaging with (99m)Tc-tetrofosmin is based on the assumption of a linear correlation between myocardial blood flow (MBF) and tracer uptake. However, it is known that (99m)Tc-tetrofosmin uptake is directly related to energy-dependent transport processes, such as Na(+)/H(+) ion channel activity, as well as cellular and mitochondrial membrane potentials. Therefore, cellular alterations that affect these energy-dependent transport processes ought to influence (99m)Tc-tetrofosmin uptake independently of blood flow. Because metabolism ((18)F-FDG)-perfusion ((99m)Tc-tetrofosmin) mismatch myocardium (MPMM) reflects impaired but viable myocardium showing cellular alterations, MPMM was chosen to quantify the blood flow-independent effect of cellular alterations on (99m)Tc-tetrofosmin uptake. Therefore, we compared microsphere-equivalent MBF (MBF_micr; (15)O-water PET) and (99m)Tc-tetrofosmin uptake in MPMM and in "normal" myocardium. METHODS: Forty-two patients with severe coronary artery disease, referred for myocardial viability diagnostics, were examined using (18)F-FDG PET and (99m)Tc-tetrofosmin perfusion SPECT. Relative (18)F-FDG and (99m)Tc-tetrofosmin uptake values were calculated using 18 segments per patient. Normal myocardium and MPMM myocardium were classified using a previously validated (99m)Tc-tetrofosmin SPECT/(18)F-FDG PET score. In addition, (15)O-water PET was performed to assess kinetic-modeled MBF (MBF_kin), the water-perfusable tissue fraction (PTF), and the resulting MBF_micr (MBF_kin x PTF), which is comparable to tracer uptake values. (99m)Tc-tetrofosmin uptake and MBF_micr values were calculated for all normal and MPMM segments and averaged within their respective classifications. RESULTS: Mean relative (99m)Tc-tetrofosmin uptake was 86% +/- 1% in normal myocardium and 56% +/- 1% in MPMM, showing a significant difference (P < 0.001), as was expected from the classification. Contrary to these findings, mean MBF_micr in MPMM myocardium was 0.60 +/- 0.03 mL x min(-1) x mL(-1), which did not significantly differ from normal myocardium (0.64 +/- 0.01 mL x min(-1) x mL(-1)). All values are given as mean +/- SEM. CONCLUSION: Differences between reduced (99m)Tc-tetrofosmin uptake and the unchanged MBF_micr in MPMM myocardium suggest that the pathophysiologic basis of MPMM is not a blood flow reduction but cellular alterations that affect uptake and retention of (99m)Tc-tetrofosmin independently of blood flow. Therefore, it seems that perfusion deficits in MPMM myocardium are greatly overestimated by (99m)Tc-tetrofosmin and that it tends to give false-positive findings.     

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.     

Optimal scan time of oxygen-15-labeled water injection method for measurement of cerebral blood flow

We investigated the optimal scan time for obtaining the maximal signal-to-noise (S/N) ratio in cerebral blood flow (CBF) measured by PET imaging following 15O-water bolus injection. We performed sequential measurements with dynamic scans of six subjects injected at rest while listening to white noise. Each dynamic data set was edited into images corresponding to different scan times and were calibrated to CBF images by the table look-up method. For each scan time, we evaluated a pixel-by-pixel standard deviation of the CBF for sequential measurements. The S/N-ratio of CBF in the gray matter was 10.2 +/- 1.7 and 13.6 +/- 2.9 at a 40 and 120 sec scan time, respectively. The gain of the 120-sec over 40-sec scan time corresponds to an 80% increase in the number of trials to reach the same S/N-ratio in a stimulation-activation study. The simulation study supported the results, in which the maximal S/N-ratio of the CBF was demonstrated to be 90 and 120 sec at a CBF of 80 and 60 ml/100 ml/min, respectively. It is concluded that the optimal scan time of the 15O-water bolus injection method is in the interval from 90 to 120 sec.     

Reproducibility of measurements of regional myocardial blood flow in a model of coronary artery disease: Comparison of H215O and 13NH3 PET techniques.

PET absolute myocardial blood flow (MBF) with H(2)15O and 13NH3 are widely used in clinical and research settings. However, their reproducibility with a 16-myocardial segment model has not been examined in chronic coronary artery disease (CAD). We examined the short-term reproducibility of PET H(2)15O MBF and PET 13NH3 MBF in an animal model of chronic CAD. METHODS: Twelve swine (mean weight +/- SD, 38 +/- 5 kg) underwent percutaneous placement of a copper stent in the mid circumflex coronary artery, resulting in an intense inflammatory fibrotic reaction with luminal stenosis at 4 wk. Each animal underwent repeated resting MBF measurements by PET H(2)15O and PET 13NH3. Attenuation-corrected images were analyzed using commercial software to yield absolute MBF (mL/min/g) in 16 myocardial segments. MBF was also normalized to the rate.pressure product (RPP). RESULTS: By Bland-Altman reproducibility plots, the mean difference was 0.01 +/- 0.18 mL/min/g and 0.01 +/- 0.11 mL/min/g, with confidence limits of +/-0.36 and +/-0.22 mL/min/g for uncorrected regional PET H(2)15O MBF and for uncorrected regional PET 13NH3 MBF, respectively. The repeatability coefficient ranged from 0.09 to 0.43 mL/min/g for H(2)15O and from 0.09 to 0.18 mL/min/g for 13NH3 regional MBF. RPP correction did not improve reproducibility for either PET H(2)15O or PET 13NH3 MBF. The mean difference in PET H(2)15O MBF was 0.03 +/- 0.14 mL/min/g and 0.02 +/- 0.19 mL/min/g for infarcted and remote regions, respectively, and in PET 13NH3 MBF was 0.03 +/- 0.11 mL/min/g and 0.00 +/- 0.09 mL/min/g for infarcted and remote regions, respectively. CONCLUSION: PET H(2)15O and PET 13NH3 resting MBF showed excellent reproducibility in a closed-chest animal model of chronic CAD. Resting PET 13NH3 MBF was more reproducible than resting PET H(2)15O MBF. A high level of reproducibility was maintained in areas of lower flow with infarction for both isotopes.