An improved model for the measurement of myocardial perfusion in human beings using N-13 ammonia

BACKGROUND: Oxygen 15 water and nitrogen 13 ammonia are widely used for the quantitative measurement of myocardial perfusion with positron emission tomography. However, blood flow obtained with N-13 ammonia by use of the conventional 2-compartment model frequently underestimates flow by 30% to 50% compared with O-15 water. We hypothesized that this discrepancy is a result of the model configuration of N-13 ammonia and investigated changes to the mathematical model to determine whether more accurate measurements of perfusion could be obtained. METHODS AND RESULTS: Twelve healthy volunteers were sequentially studied with O-15 water and N-13 ammonia at rest and during maximal coronary vasodilation with adenosine. Perfusion measurements obtained with the conventional and modified models were compared with values obtained with O-15 water. The conventional N-13 ammonia model underestimated flow by 37% +/- 16% at rest and by 20% +/- 24% with stress when compared with flows obtained with O-15 water. The modified model yielded flow values closer to the line of identity than the conventional model (y = 1.07x + 0.04 vs y = 0.69x + 0.08; respectively; P < .01). CONCLUSIONS: Model changes made N-13 ammonia myocardial blood flow estimates more comparable to those obtained with O-15 and may allow for better comparison of flows obtained with these two tracers in the future. Further efforts are warranted to evaluate the accuracy of flow models in human subjects.     

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.     

Assessment of myocardial viability in dysfunctional myocardium by resting myocardial blood flow determined with oxygen 15 water PET

BACKGROUND: There is controversy about the role of decreased resting blood flow as the pathophysiologic correlate of hibernating myocardium. The aim of this study was an absolute quantification of volumetric myocardial blood flow (MBFvol) in dysfunctional myocardium with different viability conditions as defined by fluorine 18 deoxyglucose (FDG) positron emission tomography (PET) while taking into consideration the functional recovery after revascularization. The impact of MBFvol in the diagnosis of functional recovery was also investigated. METHODS AND RESULTS: Forty-two patients with severe coronary artery disease and dysfunctional myocardium underwent resting oxygen 15 water PET, as well as FDG PET and technetium 99m tetrofosmin single photon emission computed tomography, all attenuation-corrected. Relative FDG and Tc-99m tetrofosmin uptake (normalized to the segment with 100% Tc-99m tetrofosmin uptake), as well as MBFvol (myocardial blood flow multiplied by the water-perfusable tissue fraction to account for the flow to the entire segment volume), were determined in 18 myocardial segments per patient. Viability in dysfunctional segments (estimated by ventriculography) with reduced Tc-99m tetrofosmin uptake of 70% or lower was classified as viable (FDG >70%, mismatch) or nonviable (FDG < or =70%, match). Fifteen patients underwent revascularization and were followed up. Mismatch segments with improved function were classified as hibernating myocardium. Mean MBFvol in viable myocardium was slightly reduced (0.60 +/- 0.02 mL x min(-1) x mL(-1)) compared with that in normokinetic myocardium (0.64 +/- 0.01 mL x min(-1) x mL(-1)) (P = .036) and was significantly higher than in nonviable myocardium (0.36 +/- 0.01 mL x min(-1) x mL(-1)) (P < .001). Receiver operating characteristic analysis confirmed an FDG uptake greater than 70% as the optimal threshold to predict functional recovery (diagnostic accuracy [ACC], 76%). MBFvol in hibernating myocardium (0.62 +/- 0.04 mL x min(-1) x mL(-1)) was not significantly reduced compared with that in normokinetic myocardium (0.66 +/- 0.02 mL x min(-1) x mL(-1)) and was significantly higher than in persistently dysfunctional myocardium (0.51 +/- 0.04 mL x min(-1) x mL(-1)) (P < .05). The ACC of MBFvol greater than 0.40 mL x min(-1) x mL(-1) as the threshold to predict functional recovery was 61% but did not improve the accuracy of FDG PET by itself. CONCLUSIONS: In patients with severe coronary artery disease and dysfunctional myocardium, MBFvol as determined with O-15 water differs significantly between viable and nonviable myocardium as determined by FDG PET and is not significantly reduced in hibernating compared with normokinetic myocardium. Therefore chronically reduced resting blood flow appears unlikely to be the pathophysiologic correlate of the functional state of hibernation. However, MBFvol does not improve the ACC of FDG PET by itself.     

Measurement of myocardial blood flow with oxygen-15 labelled water: comparison of different administration protocols

Positron emission tomography (PET) in conjunction with C¹⁵O₂ or H₂ ¹⁵O can be used to measure myocardial blood flow (MBF) and tissue fraction (TF), i.e. the fraction of the tissue mass in the volume of the region of interest. However, with C¹⁵O₂ inhalation, the tissue fraction in the septum is overestimated. Bolus injection of H₂ ¹⁵O together with arterial cannulation gives very precise results but is invasive. The purpose of this study was to develop a method which circumvents these problems. A four-parameter model with parameters for MBF, TF and spill-over fractions from both left and right ventricular cavities was developed. This method was compared with a three-parameter model (no right ventricular cavity spill-over) in both septal and non-septal regions of interest for three different administration protocols: bolus injection of H₂ ¹⁵O, infusion of H₂ ¹⁵O and inhalation of C¹⁵O₂. It was found that MBF can be measured with intravenous administration of H₂ ¹⁵O without the requirement for arterial cannulation. The four-parameter protocol with bolus injection was stable in clinical studies. The four-parameter model proved essential for the septum, where it gave highly significantly better fits than did the three-parameter model (P<0.00003 in each of 15 subjects). Administration of H₂ ¹⁵O together with this four-parameter model also circumvented the problem of overestimation of TF in the septum seen with C¹⁵O₂ inhalation. In addition, the radiation dose of H₂ ¹⁵O protocols is lower than that of C¹⁵O₂ inhalation. Using a left atrial input curve instead of a left ventricular cavity input curve gave the same mean MBF and TF. Received 30 January and in revised form 8 April 1998     

Assessment of myocardial perfusion by dynamic O-15-labeled water PET imaging: Validation of a new fast factor analysis

Background  Factor analysis (FA) is an established method for separating myocardium from blood pool by use of oxygen 15-labeled water and positron emission tomography for analyzing myocardial blood flow (MBF). Conventional FA methods generating images from sinograms (sinoFA) are time-consuming, whereas FA can be performed on the reconstructed images (reconFA) in a fraction of time. We validated the MBF values obtained by reconFA versus sinoFA. Methods and Results  In 23 volunteers (mean age, 26.6±3.4 years) MBF was calculated from sinoFA and reconFA and blindly reanalyzed 1 month later by the same observer. Intraobserver agreement and reconFA-versus-sinoFA agreement were assessed according to Bland and Altman (BA). Reproducibility proved excellent for global sinoFA (r=0.968; P<.001; BA limits, −0.617 to 0.676 mL·min⁻¹·g⁻¹) and slightly superior for reconFA (r=0.979; P<.001; BA limits, −0.538 to 0.558 mL·min⁻¹·g⁻¹), with wider limits of agreement for segmental MBF from sinoFA (r=0.777; P<.001; BA limits, −1.676 to 1.656 mL·min⁻¹·g⁻¹) and reconFA (r=0.844; P<.001; BA limits, −1.999 to 1.992 mL·min⁻¹·g⁻¹). In addition, sinoFA and reconFA showed excellent correlation (r=0.975, P<.001) and agreement (BA limits, −0.528 to 0.648 mL·min⁻¹·g⁻¹) for global and segmental values (r=0.955; P<.001; BA limits, −1.371 to 1.491 mL·min⁻¹·g⁻¹). Conclusions  Use of reconFA allows rapid and reliable quantitative MBF assessment with O-15-labeled water. This study was supported by a grant from the Swiss National Science Foundation (professorship grant PP00A-114706).     

Simultaneous cardiac output and regional myocardial perfusion determination with PET and nitrogen 13 ammonia

BACKGROUND: The purpose of this study was to evaluate the possibility of measuring cardiac output during positron emission tomography (PET) examination of myocardial perfusion with nitrogen 13 ammonia. METHODS AND RESULTS: In 7 patients undergoing right-sided cardiac catheterization for evaluation of heart failure and 6 patients who had undergone heart transplantation, a thermodilution catheter for continuous measurement of cardiac output was inserted. An N-13 ammonia scan of the heart was subsequently performed, and with use of factor analysis, the time-activity curve from the right ventricle was derived from the dynamic image sequence. The PET-derived cardiac output was subsequently obtained according to the Stewart-Hamilton principle as the amount of injected tracer divided by the area under the time-activity curve. PET-acquired cardiac output measurements correlated closely with the invasively determined values for a wide range of cardiac output values (P < .0001). The mean difference was 0.12 L/min, with an SD of 0.74 L/min. The interobserver variation was low, with a mean difference of 0.06 L/min and an SD of 0.46 L/min. CONCLUSIONS: Cardiac output determination with N-13 ammonia and PET appears to be both accurate and precise and can be performed simultaneously with measurement of myocardial perfusion.     

Alignment of 3-dimensional cardiac structures in O-15-labeled water PET emission images with mutual information

Background  The aim of this study was to develop a method to correct the heart position between two oxygen 15-labeled water cardiac positron emission tomography (PET) image sets to be able to use the equivalent regions of interest for the quantification of the perfusion values in the same myocardial segments. Methods and Results  Independent component analysis was applied to the dynamic image sets (simulated phantom and 6 rest-pharmacologic stress and 10 rest-rest image sets of healthy female volunteers) acquired at different time points to separate the cardiac structures (ventricles and myocardium). The separated component images from independent component analysis from the 2 studies of the same individual were aligned with a normalized mutual information-based registration method. The alignment parameters were applied to position the regions of interest in the floating image sets for calculation of the myocardial blood flow values. In the rest case the mean myocardial blood flow value was 0.76 ± 0.12 mL · g±1 · min±1 for the manual method and 0.79 ± 0.10 mL · g±1 · min±1 for the proposed method (by use of the right ventricle component in the alignment), and in the stress case these values were 3.39 ± 0.70 mL · g±1 · min±1 and 4.01 ± 0.71 mL · g±1 · min±1, respectively. No statistically significant difference was found between the methods. Conclusion  In the tests with the phantom and patient images the alignment of cardiac structures was shown to be successful. The alignment could be done without the use of information from the myocardial compartment. This study was supported by TEKES Drug 2000 Technology Program, Graduate School of Tampere University, and Academy of Finland (project No. 213462) (Finnish Centre of Excellence Program [2006-2011]).     

The suitability of gamma camera coincidence systems for nitrogen 13-labeled ammonia myocardial perfusion imaging: A quantitative comparison with full-ring PET

BACKGROUND: The aim of this study was to examine the quality of nitrogen 13-labeled ammonia (NH(3)) perfusion data from coincidence-capable gamma camera positron emission tomography (GC-PET) systems compared with that from full-ring positron emission tomography (FR-PET). METHODS AND RESULTS: The performance parameters of the GC-PET system were examined and found adequate for imaging at the activity levels used clinically. We studied 15 patients who underwent stress and rest N-13-labeled NH(3) perfusion imaging on FR-PET and GC-PET systems. Quantitative analysis of perfusion values showed that GC-PET uptake was significantly lower than FR-PET uptake in 67.6% of segments. Bland-Altman analysis showed that the mean difference between FR-PET and GC-PET values was from 5.3% to 5.9%. Stress FR-PET identified 49 segments as having impaired perfusion, 46 (93.9%) of which were also identified by GC-PET. Fifty-six additional segments were identified as abnormal by GC-PET. These findings indicated a general overestimation of defect size on GC-PET. Analysis of the degree of perfusion reduction also found that GC-PET tended to overestimate defect contrast. These findings are similar to those previously found by workers examining fluorine 18-fluorodeoxyglucose uptake by both techniques. CONCLUSIONS: Good concordance was shown between GC-PET and FR-PET systems for N-13-labeled NH(3) perfusion imaging, although further work is required to optimize the technique.     

Clinical evaluation of iterative reconstruction (ordered-subset expectation maximization) in dynamic positron emission tomography: Quantitative effects on kinetic modeling with N-13 ammonia in healthy subjects

Background. The purpose of this study was to investigate the quantitative properties of ordered-subset expectation maximization (OSEM) on kinetic modeling with nitrogen 13 ammonia compared with filtered backprojection (FBP) in healthy subjects. Methods and Results. Cardiac N-13 ammonia positron emission tomography (PET) studies from 20 normal volunteers at rest and during dipyridamole stimulation were analyzed. Image data were reconstructed with either FBP or OSEM. FBP- and OSEM-derived input functions and tissue curves were compared together with the myocardial blood flow and spillover values. The late area under the OSEM input functions during dipyridamole is overestimated by 30% (P<.0001) relative to FBP. Conversely, the area under the late part of the OSEM tissue curves is underestimated by 20% (P<.0001) compared with FBP during both rest and dipyridamole. These differences in tissue and input functions cause the resting myocardial blood flow to be underestimated by 15% (P<.0001). During dipyridamole, the OSEM flow is underestimated by 25% (P<.0001) relative to FBP, causing the myocardial flow reserve to be underestimated by 10% (P<.0001). Large inter-regional differences in FBP and OSEM flow values were observed with a flow underestimation of 45% (rest/dipyridamole) in the septum and of 5% (rest) and 15% (dipyridamole) in the lateral myocardial wall. Conclusions. OSEM reconstruction of myocardial perfusion images with N-13 ammonia and PET produces high-quality images for visual interpretation. However, compared with FBP, OSEM is associated with substantial underestimation of perfusion on quantitative imaging. Our findings indicate that OSEM should be used with precaution in clinical PET studies. An abstract of this article was presented at the 6th International Conference of Nuclear Medicine, Florence 2003, April 29–May 1, 2003.     

Quantitative measurement of regional myocardial blood flow in patients with coronary artery disease by intravenous injection of13N-ammonia in positron emission tomography

Measurement of myocardial blood flow with¹³N-ammonia, a technique previously employed sucessfully in animal experiments, was introduced into clinical use to study patients with coronary artery disease. This advance has become possible by the development of a high resultion gated scan positron emission tomographic (PET) scanner equipped with a real time decay correction mechanism, HEADTOME-IV. The information obtainable includes myocardial size and wall motion as well as the absolute quantity of blood flow in various myocardial regions. The technique is simple but requires continuous arterial blood withdrawal for calculation of the arterial input function time integral. The alternative to this technique, i.e. the computation of intra left ventricular blood pool activity by PET is also discussed.     

Proposal of blood volume-corrected model for quantification of regional cerebral blood flow with H2 15O-PET and its application to AVF

Purpose It is generally assumed that vascular tracer activity is negligible in the quantification of regional cerebral blood flow (rCBF) with H₂¹⁵O and positron emission tomography (PET) under normal conditions. We attempted to surpass the assumption of abnormal vascular conditions where the vascular tracer activity is significant by introducing the vascular component into the model. Materials and methods H₂¹⁵O-dynamic and C¹⁵O PET scans were performed in an arteriovenous fistula (AVF) patient. Time–activity curves of regions of interest (ROIs) were analyzed with nonlinear least-square approximation to estimate the rCBF and fractional arterial blood volume (v_a) simultaneously with the proposed model and the standard model. Results The proposed model curve showed a fit to the time–activity curve of H₂¹⁵O at an ROI containing an enlarged vascular space induced by the AVF. The relation between the estimated v_a and CBV obtained with C¹⁵O-PET revealed that the ratio of v_a to CBV was approximately 0.23. The estimated rCBF with the proposed model in nonlesion ROIs corresponded to those of the standard model, with the estimated V_d 0.94 ml/ml. Conclusion The results supported the hypothesis that the blood volume-corrected model is applicable to the quantification of rCBF in a region with abnormal vascular structure. Furthermore, one of the advantages of the model is the feasibility of simultaneous estimation of the rCBF and arterial blood volume with dynamic-H₂¹⁵O PET 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^-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     

Left atrial versus left ventricular input function for quantification of the myocardial blood flow with nitrogen-13 ammonia and positron emission tomography

Flow quantitation with nitrogen-13 ammonia (¹³NH₃) and positron emission tomography (PET) is dependent on an accurate blood time-activity curve. This is conveniently derived from the PET images by drawing a region of interest in the left ventricular cavity. The blood time-activity curve obtained in this way, however, may contain spillover from the myocardial wall. The purpose of this study was to analyse the effect of wall to blood pool spillover. Additionally, we analysed the application of a left atrial input function. Using computer simulations, we investigated the effect of spillover from the myocardial wall to the left ventricular input function and the effect of time delay on the left ventricular input function. An oxygen-15 carbon monoxide PET study of seven normal volunteers was used to investigate possible recovery issues regarding the left atrial input function. Finally, ¹³NH₃ studies of 31 normal volunteers during rest and dipyridamole stimulation were analysed using either a left atrial or a left ventricular input function. The simulation studies showed that myocardial wall to blood pool spillover causes a considerable underestimation of the regional blood flow values in hyperaemic flow studies. Neither time delay nor recovery issues prevent flow quantitation with a left atrial input function. The ¹³NH₃ studies revealed no significant difference between the resting blood flow values, whereas the hyperaemic blood flow values were underestimated by 8% (P<0.01) on average (up to 40% individually) when using a left ventricular input function compared with a left atrial input function. Spillover of activity from the left ventricular wall to the blood time-activity curve is of importance in hyperaemic flow studies using ¹³NH₃. Application of a left atrial input function is a possible solution to these issues.An abstract of this paper was presented at the Society of Nuclear Medicine meeting in San Antonio, 1997.     

Spectral analysis of99mTc-HMPAO for estimating cerebral blood flow: A comparison with H2 15O PET

Cerebral blood flow (CBF) can be quantified non-invasively using the brain perfusion index (BPI), which is determined using radionuclide angiographic data obtained through the use of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO). The BPI is generally calculated using graphical analysis (GA). In this study, BPI was measured using spectral analysis (SA), and the usefulness of SA was compared with that of GA. Thirteen patients with various brain diseases and four healthy male volunteers were examined using radionuclide angiography with 99mTc-HMPAO. The BPI was measured for each subject using both SA and GA. In the four healthy volunteers, the BPI was examined at rest and after the intravenous administration of 1 g of acetazolamide (ACZ). An H2(15)O PET examination was also performed in the 13 patients; the BPIS and BPIG values were compared with the CBF measurements obtained using H2(15)O PET (CBFPET). The BPI values obtained by SA (BPIS) (x) and by GA (BPIG) (y) were correlated (y = 0.568x + 0.055, r = 0.901) in the 13 patients and four healthy volunteers at rest, although the BPIG values were underestimated by 36.1 +/- 7.5% (mean +/- SD) compared with the BPIS values. The degree of underestimation tended to increase with increasing BPIS values. The increase in the BPIS was 32.1 +/- 8.0% after the intravenous administration of ACZ, while the increase in BPIG was only 8.1 +/- 2.8%. This discrepancy was considered to be the result of the BPIG values being affected by the first-pass extraction fraction of the tracer. Although both BPIS and BPIG values were significantly correlated with the CBFPET values, the correlation coefficient for BPIS was higher than that for BPIG (BPIS: r = 0.881; BPIG: r = 0.832). These results suggest that SA produces a more reliable BPI for quantifying CBF using 99mTc-HMPAO than the conventional method using GA. The SA method should be especially useful for activation studies involving pharmacological intervention and/or clinical cases with an increased CBF.     

Parametric renal blood flow imaging using [<Superscript>15</Superscript>O]H<Subscript>2</Subscript>O and PET

Purpose  The quantitative assessment of renal blood flow (RBF) may help to understand the physiological basis of kidney function and allow an evaluation of pathophysiological events leading to vascular damage, such as renal arterial stenosis and chronic allograft nephropathy. The RBF may be quantified using PET with H₂ ¹⁵O, although RBF studies that have been performed without theoretical evaluation have assumed the partition coefficient of water (p, ml/g) to be uniform over the whole region of renal tissue, and/or radioactivity from the vascular space (V _A. ml/ml) to be negligible. The aim of this study was to develop a method for calculating parametric images of RBF (K ₁, k ₂) as well as V _A without fixing the partition coefficient by the basis function method (BFM). Methods  The feasibility was tested in healthy subjects. A simulation study was performed to evaluate error sensitivities for possible error sources. Results  The experimental study showed that the quantitative accuracy of the present method was consistent with nonlinear least-squares fitting, i.e. K _1,BFM=0.93K _1,NLF−0.11 ml/min/g (r=0.80, p<0.001), k _2,BFM=0.96k _2,NLF−0.13 ml/min/g (r=0.77, p<0.001), and V _A,BFM=0.92V _A,NLF−0.00 ml/ml (r=0.97, p<0.001). Values of the Akaike information criterion from this fitting were the smallest for all subjects except two. The quality of parametric images obtained was acceptable. Conclusion  The simulation study suggested that delay and dispersion time constants should be estimated within an accuracy of 2 s. V _A and p cannot be neglected or fixed, and reliable measurement of even relative RBF values requires that V _A is fitted. This study showed the feasibility of measurement of RBF using PET with H₂ ¹⁵O.     

Comparison of gated N-13 ammonia PET and gated Tc-99m sestamibi SPECT for quantitative analysis of global and regional left ventricular function

Background  The aim of this study was to compare global and regional left ventricular function in patients with coronary artery disease (CAD), obtained by use of Cedars-Sinai quantitative gated single photon emission computed tomography (QGS), for gated nitrogen 13 ammonia (NH₃) positron emission tomography (PET) and technetium 99m sestamibi (MIBI) single photon emission computed tomography (SPECT). Methods and Results  Fifty-one patients with CAD underwent gated N-13 NH₃ PET and gated MIBI SPECT. The end-diastolic volume, end-systolic volume, and ejection fraction were calculated by use of QGS. The quantitative regional wall motion (WM) and wall thickening (WT) scores for 20 segments in the myocardium were also measured by QGS. The end-diastolic volume, end-systolic volume, and ejection fraction measured by N-13 NH₃ PET showed highly significant correlation with those measured by MIBI SPECT (r=0.97, r=0.97, and r=0.84, respectively). The mean correlation of WM and WT on an individual patient basis between N-13 NH₃ PET and MIBI SPECT was 0.81 and 0.84, respectively. The circumferential variation of WM and TT in 20 segments showed a similar pattern with N-13 NH₃ PET and MIBI SPECT. Conclusion  Gated N-13 NH₃ PET combined with QGS provides information on both global and regional left ventricular function comparable to that obtained by gated Tc-99m perfusion myocardial SPECT in CAD patients.     

Measurement of regional cerebral blood flow and oxygen utilisation in patients with cerebral tumours using 15O and positron emission tomography: Analytical techniques and preliminary results

Summary Regional cerebral blood flow and oxygen utilisation have been studied in 8 patients with brain tumours using continuous inhalation of C¹⁵O₂ and ¹⁵O₂ and positron emission tomography. The methods used to analyse the regional cerebral pathophysiology are presented. A relative uncoupling between oxygen consumption and blood flow was observed in all tumours as indicated by a decreased regional fractional extraction of oxygen (rOER). This suggests that a major proportion of these tumours had sufficient blood supply to meet oxygen metabolic demand. A decrease of blood flow in grey matter was found both in the affected and contralateral hemispheres of the brain. Matched reductions of flow and oxygen utilisation were observed in oedematous tissue.     

Non-invasive estimation of hepatic blood perfusion from H2 15O PET images using tissue-derived arterial and portal input functions

Purpose  The liver is perfused through the portal vein and the hepatic artery. When its perfusion is assessed using positron emission tomography (PET) and ¹⁵O-labeled water (H₂ ¹⁵O), calculations require a dual blood input function (DIF), i.e., arterial and portal blood activity curves. The former can be generally obtained invasively, but blood withdrawal from the portal vein is not feasible in humans. The aim of the present study was to develop a new technique to estimate quantitative liver perfusion from H₂ ¹⁵O PET images with a completely non-invasive approach. Methods  We studied normal pigs (n = 14) in which arterial and portal blood tracer concentrations and Doppler ultrasonography flow rates were determined invasively to serve as reference measurements. Our technique consisted of using model DIF to create tissue model function and the latter method to simultaneously fit multiple liver time–activity curves from images. The parameters obtained reproduced the DIF. Simulation studies were performed to examine the magnitude of potential biases in the flow values and to optimize the extraction of multiple tissue curves from the image. Results  The simulation showed that the error associated with assumed parameters was <10%, and the optimal number of tissue curves was between 10 and 20. The estimated DIFs were well reproduced against the measured ones. In addition, the calculated liver perfusion values were not different between the methods and showed a tight correlation (r = 0.90). Conclusion  In conclusion, our results demonstrate that DIF can be estimated directly from tissue curves obtained through H₂ ¹⁵O PET imaging. This suggests the possibility to enable completely non-invasive technique to assess liver perfusion in patho-physiological studies.     

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: A study using oxygen 15-labeled water PET

BACKGROUND: Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD. METHODS AND RESULTS: Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg. kg(-1). min(-1)) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P <.05), in group C (2.92 +/- 1.21, P <.01), and in normal segments (3.86 +/- 1.24, P <.001). CFR in group B was lower than in group C (P <.02) and in normal segments (P <.001). CFR in group C was lower than in normal segments (P <.02). CONCLUSIONS: Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.