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.     

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.     

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.     

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.     

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.     

Quantification of regional myocardial blood flow using dynamic H2(15)O PET and factor analysis.

Because the use of factor analysis has been proposed for extracting pure physiologic temporal or spatial information from dynamic nuclear medicine images, factor analysis should be capable of robustly estimating regional myocardial blood flow (rMBF) using H2(15)O PET without additional C15O PET, which is a cumbersome procedure for patients. Therefore, we measured rMBF using time-activity curves (TACs) obtained from factor analysis of dynamic myocardial H2(15)O PET images without the aid of C15O PET. METHODS: H2(15)O PET of six healthy dogs at rest and during stress was performed simultaneously with microsphere studies using 85Sr, 46Sc, and 113SN: We performed factor analysis in two steps after reorienting and masking the images to include only the cardiac region. The first step discriminated each factor in the spatial distribution and acquired the input functions, and the second step extracted regional-tissue TACS: Image-derived input functions obtained by factor analysis were compared with those obtained by the sampling method. rMBF calculated using a compartmental model with tissue TACs from the second step of the factor analysis was compared with rMBF measured by microsphere studies. RESULTS: Factor analysis was successful for all the dynamic H2(15)O PET images. The input functions obtained by factor analysis were nearly equal to those obtained by arterial blood sampling, except for the expected delay. The correlation between rMBF obtained by factor analysis and rMBF obtained by microsphere studies was good (r = 0.95). The correlation between rMBF obtained by the region-of-interest method and rMBF obtained by microsphere studies was also good (r = 0.93). CONCLUSION: rMBF can be measured robustly by factor analysis using dynamic myocardial H2(15)O PET images without additional C15O blood-pool PET.     

Comparison of MRI and positron emission tomography for measuring myocardial perfusion reserve in healthy humans.

Myocardial perfusion reserve (MPR, defined as the ratio of the maximum myocardial blood flow (MBF) to the baseline) is an indicator of coronary artery disease and myocardial microvascular abnormalities. First-pass contrast-enhanced magnetic resonance imaging (CE-MRI) using gadolinium (Gd)-DTPA as a contrast agent (CA) has been used to assess MPR. Tracer kinetic models based on compartmental analysis of the CA uptake have been developed to provide quantitative measures of MBF by MRI. To study the accuracy of Gd-DTPA first-pass MRI and kinetic modeling for quantitative analysis of myocardial perfusion and MPR during dipyridamole infusion, we conducted a comparison with positron emission tomography (PET) in 18 healthy males (age = 40 +/- 14 years). Five planes were acquired at every second heartbeat with a 1.5T scanner using a saturation recovery turboFLASH sequence. A perfusion-related parameter, the unidirectional influx constant (Ki), was computed in three coronary artery territories. There was a significant correlation for both dipyridamole-induced flow (0.70, P = 0.001) and MPR (0.48, P = 0.04) between MRI and PET. However, we noticed that MRI provided lower MPR values compared to PET (2.5 +/- 1.0 vs. 4.3 +/- 1.8). We conclude that MRI supplemented with tracer kinetic modeling can be used to quantify myocardial perfusion.     

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.     

Reversible impairment of coronary flow reserve in takotsubo cardiomyopathy: A myocardial PET study

Background. The precise etiology of takotsubo cardiomyopathy remains unclear. The study of myocardial blood flow (MBF) and coronary flow reserve (CFR) by use of positron emission tomography might help in understanding this syndrome. Methods and Results. Three postmenopausal women underwent adenosine/rest perfusion with nitrogen 13 ammonia and metabolism with fluorine 18 fluorodeoxyglucose positron emission tomography, coronary angiography, cardiac magnetic resonance, and echocardiography in the acute phase of takotsubo cardiomyopathy and at 3 months’ follow-up, after normalization of left ventricular function. PET study was performed in 2 parts: the perfusion analysis with nitrogen ammonia and the metabolism of the heart using FDG. MBF and CFR were analyzed quantitatively in the acute phase and at follow-up. The images highlighted the impairment of tissue metabolism in the dysfunctioning left ventricular segments in the acute phase, mainly in the apical segments and progressively less in the medium segments. At the same time, a clear inverse metabolic/perfusion mismatch emerged, which normalized 3 months later. The quantitative analysis of MBF showed a reduction in the acute phase in apical segments in comparison to basal segments without differences between midventricular and basal segments. In the acute phase CFR proved to be reduced in apical versus basal segments. CFR impairment of apical segments recovered completely after 3 months. Conclusion. The acute phase of takotsubo cardiomyopathy is characterized by an inverse perfusion/metabolism mismatch with a reduction in CFR in the apical segments. However, the impairment of CFR and the reduction of metabolism in the apical segments recovered completely after 3 months.     

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.     

Parametric imaging of myocardial blood flow with 15O-water and PET using the basis function method.

Regional myocardial blood flow (MBF) can be measured with 15O-water and PET using the 1-tissue-compartment model with perfusable tissue fraction, which provides an MBF value that is free from the partial-volume effect. Studies with 15O-water have several advantages, such as the ability to repeat a scan. However, because of the short scanning time and the small distribution volume of 15O-water in the myocardium, the image quality of 15O-water is limited, impeding the computation of MBF and perfusable tissue fraction at the voxel level. We implemented the basis function method for generating parametric images of MBF, perfusable tissue fraction, and arterial blood volume (Va) with 15O-water and PET. The basis function method linearizes the solution of the 1-tissue-compartment model, which results in a computationally much faster method than the conventional nonlinear least-squares fitting method in estimating the parameters. METHODS: To validate the basis function method, we performed a series of PET studies on miniature pigs (n = 7). After acquisition of the transmission scan for attenuation correction and the 15O-CO scan for obtaining the blood-pool image, repeated PET scans with 15O-water were obtained with varying doses of adenosine or CGS-21680 (selective adenosine A(2a) receptor agonist). MBF, perfusable tissue fraction, and Va values of the myocardial region for each scan were computed using the basis function method and the nonlinear least-squares method, and the parameters estimated by the 2 methods were compared. RESULTS: MBF images generated by the basis function method demonstrated an increase in blood flow after administration of adenosine or CGS-21680. The MBF values estimated by the basis function method and by the nonlinear least-squares method correlated strongly. CONCLUSION: The basis function method produces parametric images of MBF, perfusable tissue fraction, and Va with 15O-water and PET. These images will be useful in detecting regional myocardial perfusion abnormalities.     

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.     

Optimization of flow reserve measurement using SPECT technology to evaluate the determinants of coronary microvascular dysfunction in diabetes

Purpose

The aim of this study was to validate a new method to measure regional myocardial perfusion reserve (MPR) with technetium-labelled tracers in patients with type 2 diabetes mellitus (DM2).

Methods

A total of 40 consecutive DM2 patients without history of coronary artery disease (CAD) and 7 control subjects were recruited. Dipyridamole myocardial blood flow index (MBF) was assessed by measuring first transit counts in the pulmonary artery and myocardial count rate from gated SPECT images using ^99mTc-labelled tracers. The corresponding MBF index was estimated 2 h later according to the same procedure. Regional myocardial perfusion reserve (MPR) was defined as the ratio between dipyridamole and baseline MBF using a 17-segment left ventricular (LV) model. Coronary flow reserve (CFR) was estimated by transthoracic contrast echo Doppler monitoring of flow velocity in the left anterior descending coronary artery (LAD) during the same session.

Results

Estimated MPR was higher in control subjects than in patients (3.36?±?0.66 vs 1.91?±?0.61, respectively, p?<?0.01). In patients, LAD CFR and LAD MPR were 2.01?±?0.78 vs 1.93?±?0.63, respectively (p?=?ns). The agreement between the two techniques was documented by their close correlation (r?=?0.92, p?<?0.001) and confirmed by the Bland-Altman analysis. Reversible perfusion defects occurred in 13 patients (32%) who showed similar MPR values as the remaining 27 (2.10?±?0.71 vs 1.83?±?0.71, respectively, p?=?ns). Finally, MPR was closely correlated with age (r?=??0.50, p?<?0.01) and time elapsed from the diagnosis of DM2 (r?=??0.51, p?<?0.01).

Conclusion

LV regional MPR can be accurately estimated with the broadly available single photon technology. Application of this method to DM2 patients documents the presence of a microvascular dysfunction homogeneously distributed throughout the LV walls and most frequently not associated with reversible perfusion defects.     

Dipyridamole-induced increased glucose uptake in patients with single-vessel coronary artery disease assessed with PET

BACKGROUND: The aim of this study was to determine the relationship between vasodilatation-induced ischemia and poststress glucose uptake. Coronary vasodilators may induce myocardial ischemia due to coronary steal through collateral circulation or transmural blood flow redistribution with diminished subendocardial perfusion. Myocardial ischemia can be demonstrated by increased glucose uptake as previously shown in patients with exercise-induced ischemia. METHODS AND RESULTS: We studied 11 patients with single-vessel disease and no history of myocardial infarction. Five patients had no collateral circulation, and 6 had angiographic evidence of collateral vessels. We measured myocardial blood flow (MBF) and glucose uptake at baseline and after the administration of dipyridamole (0.56 mg/kg) with positron emission tomography, using O-15 water and fluorine 18 deoxyglucose (FDG) as perfusion and glucose tracers. MBF at baseline was 0.82 +/- 0.13 mL/g/min in normal areas and 0.80 +/- 0.15 mL/g/min in areas supplied by stenotic arteries. MBF during dipyridamole was 2.05 +/- 0.66 and 1.19 +/- 0.66 mL/g/min in normal areas and areas with stenotic arteries, respectively (P < or = .001). FDG uptake at baseline was 1.36 +/- 0.55 in normal areas and 1.57 +/- 0.62 in areas supplied by stenotic arteries. FDG uptake after dipyridamole infusion was 1.79 +/- 1.1 and 4.04 +/- 0.84 in normal areas and areas with stenotic arteries, respectively (P < or =.001). MBF and FDG uptake were not different between patients with collateral circulation and those without collateral circulation. CONCLUSIONS: Increased myocardial glucose uptake was consistently observed after dipyridamole administration in those areas with diminished coronary vasodilatory capacity. The similar MBF and FDG findings in patients with and without collateral circulation may indicate that transmural blood flow redistribution appears to be a possible mechanism of dipyridamole-induced myocardial ischemia.     

Quantitative myocardial perfusion analysis with a dual-bolus contrast-enhanced first-pass MRI technique in humans

PURPOSE: To compare fully quantitative and semiquantitative analysis of rest and stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) using a dual-bolus first-pass perfusion MRI method in humans. MATERIALS AND METHODS: Rest and dipyridamole stress perfusion imaging was performed on 10 healthy humans by administering gadolinium contrast using a dual-bolus protocol. Ventricular and myocardial time-signal intensity curves were generated from a series of T1-weighted images and adjusted for surface-coil intensity variations. Corrected signal intensity curves were then fitted using fully quantitative model constrained deconvolution (MCD) to quantify MBF (mL/min/g) and MPR. The results were compared with semiquantitative contrast enhancement ratio (CER) and upslope index (SLP) measurements. RESULTS: MBF (mL/min/g) estimated with MCD averaged 1.02 +/- 0.22 at rest and 3.39 +/- 0.59 for stress with no overlap in measures. MPR was 3.43 +/- 0.71, 1.91 +/- 0.65, and 1.16 +/- 0.19 using MCD, SLP, and CER. Both semiquantitative parameters (SLP and CER) significantly underestimated MPR (P < 0.001) and failed to completely discriminate rest and stress perfusion. CONCLUSION: Rest and stress MBF (mL/min/g) and MPR estimated by dual-bolus perfusion MRI fit within published ranges. Semiquantitative methods (SLP and CER) significantly underestimated MPR.     

Use of wavelet transforms in analysis of time-activity data from cardiac PET.

Because of its intrinsic quantitative properties, PET permits measurement of myocardial perfusion and metabolism in absolute terms (i.e., mL/g/min). However, quantification has been limited by errors produced in image acquisition, selection of regions of interest, and data analysis. The goal of this study was to evaluate a newly developed, novel, wavelet-based noise-reduction approach that can objectively extract biologic signals hidden within dynamic PET data. METHODS: Quantification of myocardial perfusion using dynamic PET imaging with 82Rb, H2(15)O, and 13NH3 was selected to evaluate the effects of the wavelet-based noise-reduction protocol. Dynamic PET data were fitted to appropriate mathematic models before and after wavelet-based noise reduction to get flow estimates. Time-activity curves, precision, accuracy, and differentiating capacity derived from the wavelet protocol were compared with those obtained from unmodified data processing. A total of 84 human studies was analyzed, including 43 at rest (18 82Rb scans, 18 H2(15)O scans, and 7 13NH3 scans) and 41 after coronary hyperemia with dipyridamole (17 82Rb scans, 17 H2(15)O scans, and 7 13NH3 scans). RESULTS: For every tracer tested under all conditions, the wavelet method improved the shape of blood and tissue time-activity curves, increased estimate-to-error ratios, and maintained fidelity of flow in regions as small as 0.85 cm3. It also improved the accuracy of flow estimates derived from 82Rb to the level of that achieved with H2(15)O, which was not affected markedly by the wavelet process. In studies of patients with coronary disease, regional heterogeneity of myocardial perfusion was preserved and flow estimates in infarcted regions were differentiated more easily from normal regions. CONCLUSION: The wavelet-based noise-reduction method effectively and objectively extracted tracer time-activity curves from data with low signal-to-noise ratios and improved the accuracy and precision of measurements with all tracer techniques studied. The approach should be generalizable to other image modalities such as functional MRI and CT and, therefore, improve the ability to quantify dynamic physiologic processes.     

Use of the left ventricular time-activity curve as a noninvasive input function in dynamic oxygen-15-water positron emission tomography.

Noninvasive recording of arterial input functions using regions of interest (ROIs) in the left ventricular (LV) chamber obviates the need for arterial cannulation in PET, but it is compromised by the limited recovery coefficient of the LV chamber and by statistical noise. In the present study, a new mathematical model has been developed, which corrects for the spillover of radioactivity both from the myocardium into the LV ROI and the blood into the myocardial ROI. The method requires the measurement of a time-activity curve in the LV chamber during the dynamic H2(15)O PET study and the measurement of the recovery coefficient of the LV ROI using a 15O-carbon monoxide (C15O) scan and venous blood sampling. This approach was successfully validated against direct measurements of the arterial input function using an on-line beta detector in five greyhounds undergoing dynamic H2(15)O PET imaging. This technique also yielded myocardial blood flow (MBF) values which were not significantly different from those obtained with the beta-probe analyses (maximum difference less than 2%), provided that the LV ROIs were sufficiently large to provide good counting statistics. When this model was not applied for large ROIs (small recovery in LV ROI), systematic overestimations in MBF compared with beta-probe analysis (e.g., a factor by 40% for a recovery coefficient of 0.7) were observed. Thus, this technique enabled the prediction of an accurate input function using the LV time-activity curve, and hence, noninvasive quantification of MBF without arterial cannulation.     

Relationship between brachial artery flow-mediated dilation and coronary flow reserve in patients with peripheral artery disease.

The aim of this study was to assess the relationship between brachial artery flow-mediated dilation (FMD) and coronary flow reserve (CFR) in patients with peripheral artery disease (PAD). METHODS: Thirty patients who had PAD, who showed no cardiac symptoms, and who had normal stress SPECT cardiac imaging results and 28 control subjects underwent brachial artery FMD assessment by ultrasound and dipyridamole 99mTc-sestamibi imaging. Myocardial blood flow (MBF) was estimated by measuring first-transit counts in the pulmonary artery and myocardial counts from SPECT images. Estimated CFR was expressed as the ratio of MBF at stress to MBF at rest. RESULTS: Patients with PAD were separated into 2 groups according to the median value of overall FMD (6.85%): group 1 (n=15) with FMD above the median (mean+/-SD, 8.78%+/-1.3%) and group 2 (n=15) with FMD below the median (mean+/-SD, 5.14%+/-0.94%). FMD was significantly higher in control subjects (11.4%+/-3.4%) than in both groups of PAD patients (P<0.001 for both). In control subjects, estimated CFR was 2.2+/-0.4-significantly higher than CFR in both groups of PAD patients (P<0.001 for both). In addition, in PAD patients of group 1, estimated CFR was 1.5+/-0.4-higher than CFR in group 2 (1.0+/-0.4) (P<0.01). When all PAD patients were considered, a significant correlation between FMD and estimated CFR was observed (r=0.56, P<0.005). CONCLUSION: Estimated CFR is significantly lower in patients with PAD than in control subjects, and CFR impairment correlates with the degree of peripheral endothelial dysfunction.     

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.     

Estimation of coronary flow reserve by Tc-99m sestamibi imaging in patients with coronary artery disease: Comparison with the results of intracoronary Doppler technique

BACKGROUND: This study compared coronary flow reserve (CFR) estimated by technetium 99m sestamibi imaging with the results obtained with intracoronary Doppler in patients with coronary artery disease. Intraobserver and interobserver reproducibility of the radionuclide-estimated CFR was also assessed. METHODS AND RESULTS: Fourteen consecutive patients (mean age, 54 +/- 7 years) with documented coronary artery disease in whom percutaneous coronary intervention was planned underwent dipyridamole (0.74 mg/kg) sestamibi imaging and intracoronary Doppler within 5 days. Myocardial blood flow (MBF) was estimated by measurement of first transit counts in the pulmonary artery and myocardial counts from single photon emission computed tomography images. Estimated CFR was expressed as the ratio of stress MBF to rest MBF. In the study vessels, CFR was 1.36 +/- 0.43 as estimated by sestamibi and 1.39 +/- 0.42 by intracoronary Doppler ( P = .69). A significant relationship between CFR estimated by sestamibi and CFR obtained by intracoronary Doppler was observed ( r = 0.85, P < .001). On Bland-Altman analysis, the mean difference between CFR by sestamibi and by Doppler was 0.03 and the intraclass correlation coefficients for intraobserver and interobserver reproducibility were high (all P < .001) for both global and regional CFR. CONCLUSIONS: This study demonstrates a good agreement between CFR estimated by sestamibi imaging and by intracoronary Doppler results and a lack of intraobserver and interobserver variability of this noninvasive approach.