Myocardial Blood Flow Imaging Research Articles

Parametric imaging of myocardial blood flow with 82Rb PET: An accuracy and image quality analysis

BackgroundWe aimed to develop a framework for generating three-dimensional (3D) myocardial blood flow (MBF) images, computing their accuracy against clinically validated two-dimensional (2D) polar MBF maps of the left ventricle, and evaluating their improvements in image quality over relative myocardial perfusion imaging (MPI). MethodsN = 40 patients with a wide range of defect severities and uptake dynamics were retrospectively studied. The FlowQuant™ software was used to generate reference MPI and polar MBF maps and was adapted for voxel-wise MBF mapping. We evaluated agreement between parametric vs polar values for MBF at rest and stress and for reserve (stress/rest MBF). We also assessed improvements in image quality, assessed by signal-to-noise ratio, contrast-to-noise ratio, tissue-to-blood ratio, and defect severity, from relative MPI to MBF. ResultsThere was excellent agreement between 3D parametric and 2D polar maps for all flow parameters (interclass correlation coefficient >0.96), albeit with minimal bias (<8%) for rest and stress MBF at the patient level. Image quality substantially improved from MPI to MBF in every patient for all image-quality metrics (P < 0.0001) ConclusionsWe developed a robust methodology for producing highly accurate 3D MBF images exhibiting considerably improved image quality compared to relative MPI commonly used in clinical practice.

Warranty period of normal CCTA and [15O]H2O PET in chest pain patients

Abstract Background Normal coronary computed tomography angiography (CTA) and positron emission tomography (PET) are associated with an excellent prognosis. Hitherto, data on the warranty period of normal coronary CTA and normal myocardial blood flow (MBF) by PET are scarce. Purpose To determine the event-free period after normal coronary CTA and PET results. In addition, to determine whether PET MBF imaging confers additional prognostic value beyond coronary anatomy in symptomatic patients. Methods Patients with suspected but not previously diagnosed coronary artery disease (CAD) who underwent coronary CTA or [15O]H2O PET were categorized based upon coronary CTA as no CAD, non-obstructive CAD or obstructive CAD. A hyperemic MBF &amp;lt;2.3 ml/min/g was considered abnormal and indicative for ischemia. A cumulative risk below 5% against death and myocardial infarction (MI) was used to define the warranty period. Results Of 2575 included patients (mean age 61.4±9.9 years, 41% male) 1319 (51.2%) underwent coronary CTA only, 1237 (48.0%) underwent both coronary CTA and PET and 19 (0.74%) patients underwent PET imaging only. During a median follow-up of 7.0 years 163 deaths and 68 MIs occurred. The warranty period for patients without any CAD was &amp;gt;10 years. Patients with non-obstructive CAD had a 5 year warranty period. In patients with no, non-obstructive or obstructive CAD on CTA, normal PET extended the warranty period with ≥2 years. The warranty period of patients with non-obstructive CAD or normal perfusion varied between 2.5 and &amp;gt;10 years for patients with or without clinical risk factors. Conclusions As standalone imaging, the warranty period for a normal coronary CTA is &amp;gt;10 years, whereas patients with non-obstructive CAD have a warranty period of 5 years. Independent of coronary anatomy normal perfusion imaging has additional prognostic value and extends the warranty period by ≥2 years. Funding Acknowledgement Type of funding sources: None.

Measuring SPECT myocardial blood flow at the University of Ottawa Heart Institute

The introduction of new cardiac SPECT cameras has made it practical to do dynamic SPECT imaging and opened the door to performing myocardial blood flow (MBF) imaging with SPECT. In this paper, we describe in detail our approach to dynamic SPECT MBF imaging using a multi-pinhole cardiac SPECT camera and commercially available kinetic analysis software. We use a 1-day rest/stress protocol with 370 MBq injected at rest and 1,000 MBq at stress with a 1- to 2-hour interval between rest and stress imaging. The tracer is injected mechanically over 30 seconds using a syringe pump. Projection data are acquired in listmode for a duration of 11 minutes and then reframed into a dynamic series. Each image is reconstructed independently using vendor-supplied software. The dynamic images are corrected for residual activity and manually corrected for motion using rigid-body translation. The uptake rate constant, K1, is calculated using a 1-tissue-compartment kinetic model and converted to MBF using a previously determined extraction fraction correction.

A 7-year warranty period for chest pain patients with a non-ischaemic [15O]H2O positron emission tomography: a follow-up of 273 individuals

Abstract Funding Acknowledgements Type of funding sources: None. Background A normal perfusion scan is associated with a favourable outcome. The aim of the present study is to determine the warranty period of normal hyperemic myocardial blood flow (MBF) derived with quantitative [15O]H2O positron emission tomography (PET) in symptomatic individuals with cardiovascular risk factors. Methods A total of 539 patients referred for baseline adenosine [15O]H2O PET MBF imaging because of suspected coronary artery disease (CAD) were investigated. A PET scan was considered normal if the hyperemic MBF was &amp;gt; 2.3 ml/min/g. The warranty period was predefined as &amp;lt; 2% annual event rate. The primary endpoint was a composite of late revascularizations, myocardial infarction and all-cause mortality. Results In a total of 273 patients (mean age 57.2 ± 9.1; 34.4% male) with a normal PET scan, 19 events occurred during a median follow-up of 6.8 years (interquartile range 4.9-7.7). Events included 10 late revascularizations, 2 myocardial infarctions and 7 deaths. The annual event rate exceeded 2% in the 8th year of follow-up, resulting in a warranty period of 7 years (see Figure 1). Conclusion In patients referred for suspected CAD a normal hyperemic perfusion derived by [15O]H2O PET confers a 7-year warranty period against late revascularization, myocardial infarction and all-cause mortality.

Selection of PET Camera and Implications on the Reliability and Accuracy of Absolute Myocardial Blood Flow Quantification.

PET scanner design and performance evaluation has been driven historically by the imaging requirements for whole-body imaging in oncology. Cardiac PET imaging for accurate quantification of myocardial blood flow (MBF) using short-lived tracers such as rubidium-82 imposes additional requirements for wide dynamic range and high count-rate accuracy. This paper examines the technical challenges encountered in cardiac imaging of myocardial perfusion and blood flow quantification. The newest PET-CT scanners using digital silicon photomultiplier technology have high absolute sensitivity (4-20%) and time-of-flight resolution (3-7cm) which further improves image quality. The concept of "integral" noise equivalent counts (iNEC) is introduced to compare scanner count-rate performance over the wide dynamic range encountered in MBF imaging with rubidium-82. The latest-generation digital PET scanners with wide axial field-of-view and enhanced time-of-flight resolution should enable accurate quantification of MBF, without any compromise in the quality of conventional ECG-gated myocardial perfusion images.

Quantitative myocardial blood flow imaging with integrated time-of-flight PET-MR

BackgroundThe use of integrated PET-MR offers new opportunities for comprehensive assessment of cardiac morphology and function. However, little is known on the quantitative accuracy of cardiac PET imaging with integrated time-of-flight PET-MR. The aim of the present work was to validate the GE Signa PET-MR scanner for quantitative cardiac PET perfusion imaging. Eleven patients (nine male; mean age 59 years; range 46–74 years) with known or suspected coronary artery disease underwent 15O-water PET scans at rest and during adenosine-induced hyperaemia on a GE Discovery ST PET-CT and a GE Signa PET-MR scanner. PET-MR images were reconstructed using settings recommended by the manufacturer, including time-of-flight (TOF). Data were analysed semi-automatically using Cardiac VUer software, resulting in both parametric myocardial blood flow (MBF) images and segment-based MBF values. Correlation and agreement between PET-CT-based and PET-MR-based MBF values for all three coronary artery territories were assessed using regression analysis and intra-class correlation coefficients (ICC). In addition to the cardiac PET-MR reconstruction protocol as recommended by the manufacturer, comparisons were made using a PET-CT resolution-matched reconstruction protocol both without and with TOF to assess the effect of time-of-flight and reconstruction parameters on quantitative MBF values.ResultsStress MBF data from one patient was excluded due to movement during the PET-CT scanning. Mean MBF values at rest and stress were (0.92 ± 0.12) and (2.74 ± 1.37) mL/g/min for PET-CT and (0.90 ± 0.23) and (2.65 ± 1.15) mL/g/min for PET-MR (p = 0.33 and p = 0.74). ICC between PET-CT-based and PET-MR-based regional MBF was 0.98. Image quality was improved with PET-MR as compared to PET-CT. ICC between PET-MR-based regional MBF with and without TOF and using different filter and reconstruction settings was 1.00.ConclusionsPET-MR-based MBF values correlated well with PET-CT-based MBF values and the parametric PET-MR images were excellent. TOF and reconstruction settings had little impact on MBF values.

136 Quantification of Septal and Whole Slice Myocardial Blood Flow by Myocardial Perfusion CMR is Similar in Healthy Volunteers

Introduction First pass myocardial perfusion CMR allows quantification of myocardial blood flow (MBF). MBF estimation with whole-heart tissue response may be useful in a variety of systemic diseases, but can be limited by suboptimal imaging in one or more segments. The interventricular septum (IVS) offers an attractive target for MBF imaging, as it offers higher signal and less partial volume artefact from blood pool. It has been proposed that T1 measurements taken from the IVS are more reliable than measurements form an entire short axis slice. We hypothesised that MBF estimation from the IVS would be similar to whole-heart estimation. Methods Nine healthy volunteers underwent CMR at 3.0T (Philips Achieva TX, 32 channel receiver coil). First-pass perfusion imaging in three short-axis LV slices was performed during administration of 0.075 mmol/L/kg of gadobutrol at basal, mid-ventricular and apical short-axis slices. This protocol was performed following 3 min of 140 mcg/kg/min adenosine for stress perfusion and repeated 15 min later at rest. MBF estimation was performed using Fermi deconvolution (PMI v.0.4, [Sourbron, 2009]) with basal blood pool providing the arterial input. Tissue response with whole mid-ventricular myocardium and limited IVS contours were compared. Myocardial perfusion reserve (MPR) was calculated by dividing stress MBF by rest MBF. Adequate haemodynamic response was defined as heart rate increase ≥10/min or blood pressure decrease ≤10 mmHg or presence of significant chest discomfort or dyspnoea. Results Mean age was 42 ± 11, 7 males (78%). All patients had adequate haemodynamic response. Whole-heart MBF estimation was 358 ± 137 ml/100 ml/min at stress and 137 ± 48 ml/100 ml/min at rest. Septal MBF was 374 ± 144 ml/100 ml/min at stress and 145 ± 60 at rest. Whole-heart MPR was 2.8 ± 1.02 and septal MPR was 2.81 ± 1.05. There was excellent agreement between whole-heart and septal MBF estimates at stress (r = 0.98; p Conclusion Limited septal quantification of MBF is similar to whole-heart ROI. This technique may simplify MBF estimation for those with suboptimal imaging outside of the septum or low myocardial signal.

Technical Advances and Clinical Applications of Quantitative Myocardial Blood Flow Imaging With Cardiac MRI

The recent FAME 2 study highlights the importance of myocardial ischemia assessment, particularly in the post-COURAGE trial era of managing patients with stable coronary artery disease. Qualitative assessment of myocardial ischemia by stress cardiovascular magnetic resonance imaging (CMR) has gained widespread clinical acceptance and utility. Despite the high diagnostic and prognostic performance of qualitative stress CMR, the ability to quantitatively assess myocardial perfusion reserve and absolute myocardial blood flow remains an important and ambitious goal for non-invasive imagers. Quantitative perfusion by stress CMR remains a research technique that has yielded progressively more encouraging results in more recent years. The ability to safely, rapidly, and precisely procure quantitative myocardial perfusion data would provide clinicians with a powerful tool that may substantially alter clinical practice and improve downstream patient outcomes and the cost effectiveness of healthcare delivery. This may also provide a surrogate endpoint for clinical trials, reducing study population sizes and costs through increased power. This review will cover emerging quantitative CMR techniques for myocardial perfusion assessment by CMR, including novel methods, such as 3-dimensional quantitative myocardial perfusion, and some of the challenges that remain before more widespread clinical adoption of these techniques may take place.

Quantification of septal and whole slice myocardial blood flow by myocardial perfusion CMR is similar in healthy volunteers

Background First pass myocardial perfusion CMR allows quantification of myocardial blood flow (MBF). MBF estimation with whole-heart tissue response may be useful in a variety of systemic diseases, but can be limited by suboptimal imaging in one or more segments. The interventricular septum (IVS) offers an attractive target for MBF imaging, as it offers higher signal and less partial volume artefact from blood pool. It has been proposed that T1 measurements taken from the IVS are more reliable than measurements from an entire short axis slice. We hypothesised that MBF estimation from the IVS would be similar to whole-heart estimation.

Quantitative myocardial blood flow imaging: not all flow is equal

Quantitative myocardial blood flow imaging: not all flow is equal

Effect of Type 2 Diabetes Mellitus on Epicardial Adipose Tissue Volume and Coronary Vasomotor Function

Patients with coronary artery disease and/or type 2 diabetes mellitus (DM) generally exhibit more epicardial adipose tissue (EAT) than healthy controls. Recently, it has been proposed that EAT affects vascular function and structure by secreting proinflammatory and vasoactive substances, thereby potentially contributing to the development of cardiovascular disease. In the present study, the interrelation of EAT, coronary vasomotor function, and coronary artery calcium was investigated in patients with and without DM, who were evaluated for coronary artery disease. Myocardial blood flow (MBF) was assessed at rest and during adenosine-induced hyperemia using [(15)O]-water positron emission tomography combined with computed tomography to quantify coronary artery calcium and EAT in 199 patients (46 with DM). In this cohort (mean age 58 ± 10 years), the patients with DM had a greater body mass index, heart rate, and systolic blood pressure at rest (all p <0.05). Coronary artery calcium and the EAT volumes were comparable between those with and without DM. Both patient groups showed comparable MBF at rest and coronary vascular resistance. A lower hyperemic MBF and coronary flow reserve (CFR) and greater hyperemic coronary vascular resistance (all p <0.05) was observed in the patients with DM. A pooled analysis showed a positive association of EAT volume with hyperemic coronary vascular resistance but not with the MBF at rest, hyperemic MBF, or coronary vascular resistance at rest. In the group analysis, the EAT volume was inversely associated with hyperemic MBF (r = -0.16, p = 0.05) and CFR (r = -0.17, p = 0.04) and positively with hyperemic coronary vascular resistance (r = 0.26, p = 0.002) only in patients without DM. Multivariate regression analysis, adjusted for age, gender, and body mass index, showed an independent association between the EAT volume and hyperemic MBF (β = -0.16, p = 0.02), CFR (β = -0.16, p = 0.04), and hyperemic coronary vascular resistance (β = 0.25, p <0.001) in the non-DM group. In conclusion, these results suggest a role for EAT in myocardial microvascular dysfunction; however, once DM has developed, other factors might be more dominant in contributing to impaired myocardial microvascular dysfunction.

Short-term repeatability of resting myocardial blood flow measurements using rubidium-82 PET imaging

BackgroundRubidium-82 (82Rb) PET imaging has been proposed for routine myocardial blood flow (MBF) quantification. However, few studies have investigated the test-retest repeatability of this method. The aim of this study was to optimize same-day repeatability of rest MBF imaging with a highly automated analysis program (FlowQuant) using image-derived input functions and dual spillover corrections (SOC). MethodsTest-retest repeatability of resting left-ventricle (LV) MBF was measured in patients (n = 27) with suspected coronary artery disease (CAD) and healthy volunteers (n = 9). The effects of scan-time, reconstruction, and quantification methods were assessed with correlation and Bland-Altman repeatability coefficients. ResultsFactors affecting rest MBF included gender, suspected CAD, and SOC (P < .001). Significant test-retest correlations were found using all analysis methods tested (r > 0.79). The best repeatability coefficient for same-day MBF was 0.20 mL/minute/g using a 6-minute scan-time, iterative reconstruction, SOC, resting rate-pressure-product (RPP) adjustment, and left atrium input function. This protocol was significantly less variable than standard protocols using filtered back-projection reconstruction, longer scan-time, no SOC, or LV input function. ConclusionAbsolute MBF can be measured with good repeatability using FlowQuant analysis of 82Rb PET scans with a 6-minute scan time, iterative reconstruction, dual SOC, RPP-adjustment, and an image-derived input function in the left atrium cavity.

Comparing Novel Positron Emission Tomography Myocardial Perfusion Imaging with Conventional Single-Photon Emission Computed Tomography

For myocardial blood flow imaging, single-photon emission computed tomography (SPECT) technology is widely accepted by the cardiological community. It is supported by rich literature and has acceptable diagnostic accuracy. However it does have limitations with false positive studies especially in women and obese patients and underestimates the multivessel coronary disease. Positron emission tomography (PET) technology appears to be able to improve diagnostic accuracy in detecting coronary disease. It offers qualitatively better images with shorter acquisition times and lower radiation burden on patients and personnel. It has the advantage of absolute quantification of myocardial blood flow for multivessel coronary disease diagnosis and is superior in the assessment of myocardial viability. In absolute terms it is an expensive method but avoiding the cost of additional diagnostic tests in equivocal studies makes it cost effective. Its availability is improving and it is expected to help in advancing nuclear cardiology.

Measurement of heritability of myocardial blood flow by positron emission tomography: the Twins Heart Study

ObjectiveTo estimate the heritability of myocardial blood flow (MBF) and coronary flow reserve (CFR) measured with positron emission tomography (PET).DesignCross-sectional twin study.SettingGeneral clinical research centre of a university hospital at...

Parametric imaging of myocardial blood flow and viability using [15O]H2O and PET/CT

PET using [15O]H2O is a powerful tool for imaging coronary artery disease, being capable of quantifying myocardial blood flow and coronary flow reserve. Historically, its application in the clinic has remained limited due to technical and infrastructural difficulties and the lack of clinically useful images of myocardial blood flow. Recently, several of these difficulties have been overcome. This review provides a comparison of [15O]H2O with the other most widely used myocardial blood flow tracers, [13N]NH3 and 82Rb. In addition, an overview is given of tracer kinetic modeling of [15O]H2O data and of calculating parametric images of both myocardial blood flow and myocardial viability.

Coronary risk factors and myocardial blood flow in patients evaluated for coronary artery disease: a quantitative [15O]H2O PET/CT study

BackgroundThere has been increasing interest in quantitative myocardial blood flow (MBF) imaging over the last years and it is expected to become a routinely used technique in clinical practice. Positron emission tomography (PET) using [15O]H2O is the established gold standard for quantification of MBF in vivo. A fundamental issue when performing quantitative MBF imaging is to define the limits of MBF in a clinically suitable population. The aims of the present study were to determine the limits of MBF and to determine the relationship among coronary artery disease (CAD) risk factors, gender and MBF in a predominantly symptomatic patient cohort without significant CAD.MethodsA total of 128 patients (mean age 54 ± 10 years, 50 men) with a low to intermediate pretest likelihood of CAD were referred for noninvasive evaluation of CAD using a hybrid PET/computed tomography (PET/CT) scanner. MBF was quantified with [15O]H2O at rest and during adenosine-induced hyperaemia. Obstructive CAD was excluded in these patients by means of invasive or CT-based coronary angiography.ResultsGlobal average baseline MBF values were 0.91 ± 0.34 and 1.09 ± 0.30 ml·min−1·g−1 (range 0.54–2.35 and 0.59–2.75 ml·min−1·g−1) in men and women, respectively (p < 0.01). However, no gender-dependent difference in baseline MBF was seen following correction for rate–pressure product (0.98 ± 0.45 and 1.09 ± 0.30 ml·min−1·g−1 in men and women, respectively; p = 0.08). Global average hyperaemic MBF values were 3.44 ± 1.20 ml·min−1·g−1 in the whole study population, and 2.90 ± 0.85 and 3.78 ± 1.27 ml·min−1·g−1 (range 1.52–5.22 and 1.72–8.15 ml·min−1·g−1) in men and women, respectively (p < 0.001). Multivariate analysis identified male gender, age and body mass index as having an independently negative impact on hyperaemic MBF.ConclusionGender, age and body mass index substantially influence reference values and should be corrected for when interpreting hyperaemic MBF values.

Estimation of perfusion and arterial transit time in myocardium using free‐breathing myocardial arterial spin labeling with navigator‐echo

Arterial spin labeling (ASL) provides noninvasive measurement of tissue blood flow, but sensitivity to motion has limited its application to imaging of myocardial blood flow. Although different cardiac phases can be synchronized using electrocardiography triggering, breath holding is generally required to minimize effects of respiratory motion during ASL scanning, which may be challenging in clinical populations. Here a free-breathing myocardial ASL technique with the potential for reliable clinical application is presented, by combining ASL with a navigator-gated, electrocardiography-triggered TrueFISP readout sequence. Dynamic myocardial perfusion signals were measured at multiple delay times that allowed simultaneous fitting of myocardial blood flow and arterial transit time. With the assist of a nonrigid motion correction program, the estimated mean myocardial blood flow was 1.00 ± 0.55 mL/g/min with a mean transit time of ∼ 400 msec. The intraclass correlation coefficient of repeated scans was 0.89 with a mean within subject coefficient of variation of 22%. Perfusion response during mild to moderate stress was further measured. The capability for noninvasive, free-breathing assessment of myocardial blood flow using ASL may offer an alternative approach to first-pass perfusion MRI for clinical evaluation of patients with coronary artery disease.

3D versus 2D dynamic 82Rb myocardial blood flow imaging in a canine model of stunned and infarcted myocardium

Previous studies have shown the ability of rubidium-82 ((82)Rb) positron emission tomography (PET) imaging to quantitatively measure myocardial blood flow (MBF), many of which are performed using two-dimensional (2D) imaging. Three-dimensional (3D) imaging provides increased sensitivity and may result in decreased costs owing to a reduction in the required injected activity of radiotracer. This study compares 2D and 3D (82)Rb PET MBF results obtained in the same imaging session. Three-dimensional and 2D (82)Rb perfusion imaging was performed in canines on a GE Discovery LS PET/CT scanner at rest and during hyperemia in stunned and infarcted tissue. MBF (ml/min/g) was determined using a 1-compartment model and an extraction correction of the uptake rate and analyzed using a standard 17-segment model. A strong, significant correlation was present (rho = 0.95, P<0.0001). Average 3D MBF values were slightly lower at rest and higher during stress versus 2D. MBF results in normal, stunned, and infarcted tissue differed by 7% on average and significant increases in MBF from rest to hyperemia were noted with both the techniques. These results imply that MBF results obtained in 3D are comparable with traditional 2D imaging. Therefore, it may be possible to use 3D imaging with lower administered activity, helping to reduce costs and patient dose without compromising quantitative information.

The radiotracer99m Tc-MIBI is not genotoxic for human peripheral blood lymphocytes at diagnostic radioactive dose

The radiotracer technetium-99m methoxyisobutyl isonitrile ((99m)Tc-MIBI) has been widely used for myocardial blood flow imaging. We investigated the genotoxicity of (99m)Tc-MIBI in cultured human lymphocytes at the same concentration used in patients. Radioactivity doses were determined in whole blood at 5 min post-injection of 20 mCi (99m)Tc-MIBI in patients. Subsequently, whole blood of human volunteers was incubated with 1, 2.3, 4 or 8 microCi (99m)Tc-MIBI. After a 30-min incubation, the lymphocytes were stimulated with a mitogen to assay for micronuclei in cytokinesis-blocked binucleated cells. The frequency of micronuclei in samples treated with this radiopharmaceutical up to 2-fold (8 microCi) the concentration of (99m)Tc-MIBI normally found in the blood of patients was not more than in control lymphocyte cultures. We concluded that there is no increased induction of micronuclei in lymphocytes incubated with (99m)Tc-MIBI at the radioactivity doses used for diagnostic purposes.

Parametric image of myocardial blood flow generated from dynamic H2 15O PET using factor analysis and cluster analysis

Algorithm-based parametric imaging of myocardial blood flow (MBF), as measured by H2(15)O PET, has been the goal of many research efforts. A method for generating parametric images of regional MBF by factor and cluster analysis on H2(15)O dynamic myocardial PET was validated by its comparison with gold-standard MBF values determined invasively using radiolabelled microspheres. Right and left ventricular blood pool activities and their factor images were obtained by the application of factor analysis to dynamic frames. By subtraction of the factor images multiplied by their corresponding values on the factors from the original dynamic images for each frame, pure tissue dynamic images were obtained, from which arterial blood activities were excluded. Cluster analysis that averaged pixels having time-activity curves with the same shape was applied to pure tissue images to generate parametric MBF images. The usefulness of this method for quantifying regional MBF was evaluated using canine experiment data. H2(15)O PET scans and microsphere studies were performed on seven dogs at rest and after pharmacological stress. The image qualities and the contrast of parametric images obtained using the proposed method were significantly improved over either the tissue factor images or the parametric images obtained using a conventional method. Regional MBFs obtained using the proposed method correlated well with those obtained by the region of interest method (r = 0.94) and by the microsphere technique (r = 0.90). A non-invasive method is presented for generating parametric images of MBF from H2(15)O PET, using factor and cluster analysis.