Myocardial Blood Flow Estimates Research Articles

Reproducibility and Accuracy of Quantitative Myocardial Blood Flow Assessment with 82Rb PET: Comparison with 13N-Ammonia PET

(82)Rb cardiac PET allows the assessment of myocardial perfusion with a column generator in clinics that lack a cyclotron. There is evidence that the quantitation of myocardial blood flow (MBF) and coronary flow reserve (CFR) with dynamic (82)Rb PET is feasible. The objectives of this study were to determine the accuracy and reproducibility of MBF estimates from dynamic (82)Rb PET by using our methodology for generalized factor analysis (generalized factor analysis of dynamic sequences [GFADS]) and compartment analysis.Reproducibility was evaluated in 22 subjects undergoing dynamic rest and dipyridamole stress (82)Rb PET studies at a 2-wk interval. The inter- and intraobserver variability of MBF quantitation with dynamic (82)Rb PET was assessed with 4 repeated estimations by each of 4 observers. Accuracy was evaluated in 20 subjects undergoing dynamic rest and dipyridamole stress PET studies with (82)Rb and (13)N-ammonia, respectively. The left ventricular and right ventricular blood pool and left ventricular tissue time-activity curves were estimated by GFADS. MBF was estimated by fitting the blood pool and tissue time-activity curves to a 2-compartment kinetic model for (82)Rb and to a 3-compartment model for (13)N-ammonia. CFR was estimated as the ratio of peak MBF to baseline MBF.The reproducibility of the MBF estimates in repeated (82)Rb studies was very good at rest and during peak stress (R(2)= 0.935), as was the reproducibility of the CFR estimates (R(2) = 0.841). The slope of the correlation line was very close to one for the estimation of MBF (0.986) and CFR (0.960) in repeated (82)Rb studies. The intraobserver reliability was less than 3% for the estimation of MBF at rest and during peak stress as well as for the estimation of CFR. The interobserver reliabilities were 0.950 at rest and 0.975 at peak stress. The correlation between myocardial flow estimates obtained at rest and those obtained during peak stress in (82)Rb and (13)N-ammonia studies was very good (R(2) = 0.857). Bland-Altman plots comparing CFR estimated with (82)Rb and CFR estimated with (13)N-ammonia revealed an underestimation of CFR with (82)Rb compared with (13)N-ammonia; the underestimation was within +/-1.96 SD.MBF quantitation with GFADS and dynamic (82)Rb PET demonstrated excellent reproducibility as well as intra- and interobserver reliability. The accuracy of the absolute quantitation of MBF with factor and compartment analyses and dynamic (82)Rb PET was very good, compared with that achieved with (13)N-ammonia, for MBF of up to 2.5 mL/g/min.

Estimation of absolute myocardial blood flow during first‐pass MR perfusion imaging using a dual‐bolus injection technique: Comparison to single‐bolus injection method

To compare the dual-bolus to single-bolus quantitative first-pass magnetic resonance myocardial perfusion imaging for estimation of absolute myocardial blood flow (MBF). Dogs had local hyperemia of MBF in the left anterior descending (LAD) coronary artery (intracoronary adenosine). Animals (n = 6) had sequential single- and dual-bolus perfusion studies with microsphere determination of absolute MBF. Perfusion imaging was performed using a saturation-recovery gradient-echo sequence. Absolute MBF was by Fermi function deconvolution and compared to transmural, endocardial, and epicardial microsphere values in the same region of interest (ROI). Signal and contrast were significantly higher for the dual-bolus perfusion images. The correlation with MBF by microspheres was r = 0.94 for the dual-bolus method and r = 0.91 for the single-bolus method. There was no significant difference between MRI and microsphere MBF values for control or hyperemic zones for transmural segments for either technique. When the ROI was reduced to define endocardial and epicardial zones, single-bolus MR first-pass imaging significantly overestimated MBF and had a significantly larger absolute error vs. microspheres when compared to dual-bolus perfusion. Both single-bolus and dual-bolus perfusion methods correlate closely with MBF but the signal and contrast of the dual-bolus images are greater. With smaller nontransmural ROIs where signal is reduced, the dual-bolus method appeared to provide slightly more accurate results.

Absolute quantitation of myocardial blood flow with 201Tl and dynamic SPECT in canine: optimisation and validation of kinetic modelling

201Tl has been extensively used for myocardial perfusion and viability assessment. Unlike 99mTc-labelled agents, such as 99mTc-sestamibi and 99mTc-tetrofosmine, the regional concentration of 201Tl varies with time. This study is intended to validate a kinetic modelling approach for in vivo quantitative estimation of regional myocardial blood flow (MBF) and volume of distribution of 201Tl using dynamic SPECT. Dynamic SPECT was carried out on 20 normal canines after the intravenous administration of 201Tl using a commercial SPECT system. Seven animals were studied at rest, nine during adenosine infusion, and four after beta-blocker administration. Quantitative images were reconstructed with a previously validated technique, employing OS-EM with attenuation-correction, and transmission-dependent convolution subtraction scatter correction. Measured regional time-activity curves in myocardial segments were fitted to two- and three-compartment models. Regional MBF was defined as the influx rate constant (K(1)) with corrections for the partial volume effect, haematocrit and limited first-pass extraction fraction, and was compared with that determined from radio-labelled microspheres experiments. Regional time-activity curves responded well to pharmacological stress. Quantitative MBF values were higher with adenosine and decreased after beta-blocker compared to a resting condition. MBFs obtained with SPECT (MBF(SPECT)) correlated well with the MBF values obtained by the radio-labelled microspheres (MBF(MS)) (MBF(SPECT) = -0.067 + 1.042 x MBF(MS), p < 0.001). The three-compartment model provided better fit than the two-compartment model, but the difference in MBF values between the two methods was small and could be accounted for with a simple linear regression. Absolute quantitation of regional MBF, for a wide physiological flow range, appears to be feasible using 201Tl and dynamic SPECT.

Effect of Reconstruction Algorithms on Myocardial Blood Flow Measurement with 13N-Ammonia PET

Filtered backprojection (FBP) is the traditional method for 13N-NH3 PET studies. Ordered-subsets expectation maximization (OSEM) is popular for PET studies because of better noise properties. Scant data exist on the effect of reconstruction algorithms on quantitative myocardial blood flow (MBF) estimation. Twenty patients underwent dynamic acquisition rest/stress 13N-NH3 studies. In Part 1, 19 rest/stress image pairs were reconstructed by FBP (10-mm Hanning filter) and by OSEM with 28 subsets and 2 (OSEM2), 6 (OSEM6), or 8 iterations (OSEM8), and a 10-mm postreconstruction smoothing gaussian filter. In Part 2, 9 image pairs were reconstructed by FBP (10-mm Hanning filter) and by OSEM with 28 subsets, 8 iterations, and a gaussian 5-, 10-, or 15-mm postreconstruction smoothing filter. Average MBF (mL/min/mL of myocardium) was calculated using a 3-compartment model. Part 1: For rest MBF, the correlations between FBP and each of the OSEM algorithms were r2 = 0.71, 0.73, and 0.77, respectively. MBF by OSEM6 (0.98 +/- 0.48 [mean +/- SD]) and OSEM8 (0.96 +/- 0.46) was not significantly different from FBP (1.02 +/- 0.39), but OSEM2 (0.80 +/- 0.37) was significantly lower (P < 0.0003). With stress, the correlations were high between FBP and OSEM6 and OSEM8 (r2 = 0.85 and 0.90), and MBF by OSEM6 and OSEM8 was not significantly different from FBP. Part 2: Resting MBF correlated well between FBP and all OSEM smoothing filters (r2 = 0.82, 0.85, and 0.88). Rest MBF using postsmoothing 5- or 10-mm filters was not different from FBP but was significantly lower with the 15-mm filter (P < 0.05). With stress, the correlations were good between FBP and OSEM regardless of smoothing (r2 = 0.76, 0.77, and 0.79). However, MBF with postsmoothing 10- and 15-mm filters was significantly lower than by FBP (P < 0.05). Reconstruction algorithms significantly affect the estimation of quantitative blood flow data and should not be assumed to be interchangeable. Although aggressive smoothing may produce visually appealing images with reduced noise levels, it may cause an underestimation of absolute quantitative MBF. In selecting a reconstruction algorithm, an optimal balance between noise properties and diagnostic accuracy must be emphasized.

Quantification of myocardial blood flow with 82Rb dynamic PET imaging

The PET tracer (82)Rb is commonly used to evaluate regional perfusion defects for the diagnosis of coronary artery disease. There is limited information on the quantification of myocardial blood flow and flow reserve with this tracer. The goal of this study was to investigate the use of a one-compartment model of (82)Rb kinetics for the quantification of myocardial blood flow. Fourteen healthy volunteers underwent rest and dipyridamole stress imaging with both (13)N-ammonia and (82)Rb within a 2-week interval. Myocardial blood flow was estimated from the time-activity curves measured with (13)N-ammonia using a standard two-compartment model. The uptake parameter of the one-compartment model was estimated from the time-activity curves measured with (82)Rb. To describe the relationship between myocardial blood flow and the uptake parameter, a nonlinear extraction function was fitted to the data. This function was then used to convert estimates of the uptake parameter to flow estimates. The extraction function was validated with an independent data set obtained from 13 subjects with documented evidence of coronary artery disease (CAD). The one-compartment model described (82)Rb kinetics very well (median R-square = 0.98). The flow estimates obtained with (82)Rb were well correlated with those obtained with (13)N-ammonia (r = 0.85), and the best-fit line did not differ significantly from the identity line. Data obtained from the subjects with CAD confirmed the validity of the estimated extraction function. It is possible to obtain accurate estimates of myocardial blood flow and flow reserve with a one-compartment model of (82)Rb kinetics and a nonlinear extraction function.

PET Imaging and Coronary Circulatory Function: Non-Invasive Mechanistic Insights and Cardiovascular Prognosis

The ability to determine regional myocardial blood flow (MBF) in absolute estimates by positron emission tomography (PET) contributes to the non-invasive identification and characterization of early stages of the development of coronary artery disease (CAD). Measurements of MBF at baseline, during pharmacologic vasodilation, or during physiologic stimuli, such as treadmill exercise or cold pressor testing (CPT), may permit a comprehensive assessment of the coronary circulatory function. By assessing alterations of MBF in absolute units (ml/g/min) in response to these stimuli, the functional consequences of morphological and/or functional changes in the coronary arteries may be identified before any angiographic-morphological changes are present. Thus, such measurements of MBF expand the diagnostic scope of conventional SPECT perfusion imaging to detect hemodynamically obstructive CAD, based on heterogeneity of relative myocardial perfusion, and early functional abnormalities of the coronary circulation in the absence of manifest CAD. Notably, invasive angiographic measures that indicate an impairment of endothelium-dependent coronary vascular function provide predictive information for future cardiovascular events. Consequently, it is intriguing to speculate that the non-invasive approach of PET flow-measurements to identify abnormal coronary circulatory function could serve as an important tool to identify individuals at increased risk for developing CAD and its atherothrombotic complications. MBF measurements by PET have been shown to allow the monitoring of beneficial effects of lifestyle modification, lipidlowering dietary changes, antioxidant interventions, effects of HMG-CoA reductase inhibitors, and effective glucoselowering therapy on coronary circulatory function. Whether such improvements in coronary vascular function do indeed translate into an improved clinical outcome in these patients and predict a reduction in cardiovascular events remains to be investigated. This review article describes PET-measured estimates of MBF, examines the responses of MBF to physiologic and pharmacologic stimuli and their relationship to coronary circulatory function, and examines the value of these measurements of MBF for monitoring medical intervention with regard to coronary vascular function.

Quantification of resting myocardial blood flow in a pig model of acute ischemia based on first‐pass MRI

Qualitative and semiquantitative contrast-enhanced (CE) dynamic perfusion MRI techniques are established as noninvasive diagnostic means of assessing coronary artery disease. However, to date quantification of myocardial blood flow (MBF) has not reached the same acceptance as MBF quantification with nuclear techniques. To validate quantification of MBF at rest using the extracellular contrast agent (CA) Gd-DTPA, we performed an animal study in a pig model of acute myocardial ischemia. We quantified MBF from MRI data with a mathematical model (MMID4) of the underlying vasculature. These MBF results were subsequently compared with the results from fluorescent microspheres. The study showed a correlation of r = 0.66 between MBF estimates obtained with MRI and those obtained with fluorescent microspheres. The correlation for ischemic and nonischemic myocardium was r = 0.86 and r = 0.47, respectively. In conclusion, quantification of resting MBF using MMID4 is a valid method under conditions of acute myocardial ischemia.

Cardiac studies in rats with /sup 11/C-acetate and PET: a comparison with /sup 13/N-ammonia

Regional myocardial blood flow (MBF) can be assessed noninvasively with dynamic positron emission tomography (PET) and /sup 13/N-ammonia or /sup 11/C-acetate. The latter can also be used to estimate the myocardial oxygen consumption (MVO2) from the same time-activity curve. In this work, we explore the feasibility of such techniques for evaluating myocardial parameters in normal and ischemic rats (/spl sim/350 g) by dynamic imaging with the Sherbrooke small animal PET scanner. Scans were acquired in list mode for /sup 13/N-ammonia and /sup 11/C-acetate as two consecutive 15-min dynamic scans separated by a 5-min interval, without moving the rat from the scanner. Regions of interest (ROIs) were defined on four segments of the myocardium to extract the time-activity curves. Three-compartment models were applied to fit the /sup 13/N-ammonia and /sup 11/C-acetate data with three and four rate constants, respectively, plus blood volume. A reasonable agreement was observed between MBF estimates extracted from /sup 13/N-ammonia and /sup 11/C-acetate. MVO2 estimates, as given by the k/sub 2/ rate constant, were obtained with good reproducibility, indicating that myocardial metabolism can reliably be assessed concurrently with MBF using /sup 11/C-acetate. It is concluded that myocardial blood flow and oxygen consumption can be evaluated in rats with small animal PET scanners through high-rate, list-mode, dynamic imaging and kinetic modeling of /sup 13/N-ammonia and /sup 11/C-acetate.

Carbon-11 acetate as a tracer of myocardial oxygen consumption

Estimation of myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF) is important for the understanding of various (patho)physiological mechanisms and diseases. Clearance rates of carbon-11 labelled acetate, determined with positron emission tomography, allow estimation of MVO2 on a segmental level and non-invasively. In addition, MBF can be determined from uptake rates. In this review, the background to estimation of MVO2 and MBF is discussed, as well as the currently available literature that has used 11C-acetate to estimate MVO2 and MBF.

A model-based method for myocardium flow estimation.

Results of the present study show that accurate estimates of myocardial blood flow may be obtained using a spatially distributed model of residual curves of an intravascular indicator. In order to improve myocardial blood flow reliability in blood flow estimates, also in presence of background noise inT/I curves, a wavelet-based denoising technique was successfully applied to residue curves.

Quantitative evaluation of myocardial blood flow with [13N]ammonia.

The clinical need for diagnostic tools that accurately assess the functional status of the heart in patients with coronary artery disease and their response to therapeutic interventions has driven the development of noninvasive PET imaging techniques for measuring myocardial blood flow. A method for the estimation of myocardial blood flow based upon the pharmacokinetic properties of [13N]ammonia measured with a PET imaging system is described in this review. The formation of the [13N]ammonia tracer kinetic model for quantitative estimates of myocardial blood flow is presented. In addition, methods for coupling the tracer kinetic model with a simple geometric model representing the heart and bloodpool are described to minimize the bias introduced by the limited image resolution achieved in PET studies of the heart. Studies that have been performed to demonstrate the quantitative capabilities of the [13N]ammonia technique are also presented.

Estimation of myocardial blood flow for longitudinal studies with 13N-labeled ammonia and positron emission tomography

Background. Although several modeling strategies have been developed and validated for quantification of myocardial blood flow (MBF) from 13N-labeled ammonia positron emission tomographic data, a comparison of noise characteristics of the various techniques in serial studies is lacking. Methods and Results. Dynamic 13N-labeled ammonia positron emission tomographic imaging was performed at baseline and after pharmacologic stress in (1) single studies of four dogs with concomitant measurement of microsphere blood flow and (2) initial and follow-up studies of eight normal volunteers. Data were obtained from short-axis images for the blood pool and myocardial regions corresponding to the three arterial vascular territories. Indexes of MBF were obtained by four distinct techniques: (1) University of California, Los Angeles, two-compartment model, (2) Michigan two-compartment model, and (3) a one-compartment model with variable blood volume term. Coronary flow reserve (CFR) was measured as the ratio of stress/rest MBF. The estimated standard deviation of the measurement error for the relative change between studies of rest and stress MBF and CFR was determined for each technique. Estimates of MBF from all techniques showed good correlation with microsphere blood flow ( r = 0.95 to 0.96) in canine myocardium. In human studies, similar mean estimates of MBF were found with all techniques. Techniques 1 and 3 showed the smallest interstudy variability in MBF and CFR. The estimated standard deviations for these techniques were approximately 20%, 30%, and 27% for rest MBF, stress MBF, and CFR, respectively. Conclusion. Noninvasive quantification of MBF and CFR from dynamic 13N-labeled ammonia positron emission tomography is most reproducible with technique 1 or 3. The ability to account for differences in myocardial partial volume gives preference to technique 3. However, substantial interstudy variability in regional MBF remains, suggesting the importance of procedural factors or real temporal fluctuations in MBF.

Interobserver and interstudy variability of myocardial blood flow and flow-reserve measurements with nitrogen 13 ammonia-labeled positron emission tomography.

Experimental studies have shown that positron emission tomography (PET) with 13N-labeled ammonia provides accurate quantification of regional myocardial blood flow (MBF) under rest and stress conditions. To establish the clinical utility of this method, the interobserver variability and the temporal variability of serial measurements of blood flow and coronary flow reserve (CFR) must be known. This study investigated the interobserver and temporal reproducibility of 13N-labeled PET for measurement of MBF and CFR. Initial and follow-up 13N-labeled ammonia PET studies were performed at rest and during adenosine infusion in six normal volunteers and six patients with stable coronary artery disease. Two investigators analyzed dynamically acquired data from the initial studies and one investigator analyzed the follow-up studies. Time-activity curves of tissue tracer activity were derived by a semiautomated sampling routine. A three-compartment model and curve-fitting algorithm were used to determine estimates of MBF in five myocardial regions. The interobserver correlations for MBF and CFR were excellent (r = 0.96 and 0.93, respectively). The interstudy correlation was good for rest and stress MBF (r = 0.87). The estimates of CFR on the initial and follow-up studies demonstrated a fair correlation (r = 0.72). For individual myocardial regions, there was considerable interstudy variability of stress MBF and CFR, with a mean percent difference for CFR of 19% +/- 19% in normal volunteers and 38% +/- 16% in patients with coronary disease. In normal subjects, regional CFR was highly reproducible (95%) when the values were defined as either normal (> or = 2.5) or reduced (< 2.5). The interobserver of reproducibility of 13N-labeled ammonia PET estimates of regional MBF was excellent. The temporal reproducibility of MBF and CFR was fair, with individual regions demonstrating substantial interstudy variability.

Regional myocardial blood volume and flow: first-pass MR imaging with polylysine-Gd-DTPA.

The authors investigated the utility of an intravascular magnetic resonance (MR) contrast agent, poly-L-lysine-gadolinium diethylenetriaminepentaacetic acid (DTPA), for differentiating acutely ischemic from normally perfused myocardium with first-pass MR imaging. Hypoperfused regions, identified with microspheres, on the first-pass images displayed significantly decreased signal intensities compared with normally perfused myocardium (P < .0007). Estimates of regional myocardial blood content, obtained by measuring the ratio of areas under the signal intensity-versus-time curves in tissue regions and the left ventricular chamber, averaged 0.12 mL/g +/- 0.04 (n = 35), compared with a value of 0.11 mL/g +/- 0.05 measured with radiolabeled albumin in the same tissue regions. To obtain MR estimates of regional myocardial blood flow, in situ calibration curves were used to transform first-pass intensity-time curves into content-time curves for analysis with a multiple-pathway, axially distributed model. Flow estimates, obtained by automated parameter optimization, averaged 1.2 mL/min/g +/- 0.5 (n = 29), compared with 1.3 mL/min/g +/- 0.3 obtained with tracer microspheres in the same tissue specimens at the same time. The results represent a combination of T1-weighted first-pass imaging, intravascular relaxation agents, and a spatially distributed perfusion model to obtain absolute regional myocardial blood flow and volume.

In vivo myocardial kinetics of air-filled albumin microbubbles during myocardial contrast echocardiography. Comparison with radiolabeled red blood cells.

Myocardial contrast echocardiography (MCE) is a new technique for assessing myocardial perfusion that uses intracoronary injections of microbubbles of air. Because these microbubbles have a mean diameter of 4.3 +/- 0.3 microns and an intravascular rheology similar to that of red blood cells (RBCs), we hypothesized that their mean myocardial transit rates recorded on echocardiography would provide an estimation of regional myocardial blood flow in the in vivo beating heart. Accordingly, blood flow to the left anterior descending coronary artery (LAD) of 12 open-chest anesthetized dogs (group I) was adjusted to 4 to 6 flows (total of 60 flows), and microbubbles and radiolabeled RBCs were injected into the LAD in a random order at each stage. The mean myocardial RBC transit rates were measured by fitting a gamma-variate function to time-activity plots generated by placing a miniature CsI2 probe over the anterior surface of the heart, and the mean myocardial microbubble transit rates were measured from time-intensity plots derived from off-line analysis of MCE images obtained during the injection of microbubbles. An excellent correlation was noted between flow (measured with an extracorporeal electromagnetic flow probe) and mean myocardial RBC transit rate (y = 2.83 x 10(-3)x + 0.01, r = .96, SEE = 0.02, P < .001). A close correlation was also noted between mean RBC and microbubble myocardial transit rates (y = 1.01x + 0.01, r = .89, SEE = 0.02, P < .001). Despite its theoretical advantages, a lagged normal density function did not provide a better fit to the MCE data than the gamma-variate function.(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive quantification of regional myocardial perfusion with rubidium-82 and positron emission tomography. Exploration of a mathematical model.

Positron emission tomography (PET) centers without cyclotrons use generator-produced rubidium-82 (82Rb) for assessment of myocardial perfusion. The aim of the present study was to determine whether myocardial blood flow could be assessed quantitatively with 82Rb and PET. Because the myocardial extraction fraction of 82Rb varies inversely and nonlinearly with flow and cannot be measured conveniently with PET, we used an experimentally derived mathematical function defining the relation between single-pass extraction fraction of 82Rb and flow to obviate the necessity of measuring the extraction fraction directly. Myocardial blood flow in absolute terms (ml/g/min) was estimated from dynamic PET scans after intravenous administration of 82Rb in intact dogs and compared with flows measured with radiolabeled microspheres. In 36 comparisons in 13 dogs studied at rest, or after coronary occlusion, reperfusion, or after coronary hyperemia induced with intravenous dipyridamole, over the flow range from 0.2 to 2.0 ml/g/min, estimates of perfusion with rubidium correlated well with flows measured concomitantly with microspheres, although there was a slight underestimation of flow with rubidium (flow by 82Rb = 0.92 x flow by microspheres-0.021, r = 0.83). In general, estimates of flow in ischemic regions were less reliable than estimates for regions with normal flow. Thus, although the relation between myocardial extraction and retention of 82Rb and flow can vary under a variety of physiological and pathophysiological conditions, this study demonstrates the ability to obtain quantitative estimates of myocardial blood flow with 82Rb and PET under carefully defined conditions without measuring the extraction fraction directly.

Quantitation of myocardial blood flow with H2 15O and positron emission tomography: assessment and error analysis of a mathematical approach.

Quantitation of regional myocardial blood flow (MBF) in absolute terms with positron emission tomography (PET) has been difficult to achieve in part because of errors induced by the relatively low spatial resolution of current tomographic instruments. We previously demonstrated that MBF could be accurately measured over a wide range of flows after intravenous administration of H2 15O when the arterial input function and myocardial radiotracer content were measured directly. To extend this quantitative approach for noninvasive estimates of MBF with PET. We recently developed and implemented a novel mathematical approach whereby partial volume and spillover effects were estimated along with flow within the operational one-compartment flow equation. Noninvasive estimates of flow correlated closely with flow measured directly with radiolabeled microspheres. In the present study, with the use of a commercially available cardiac phantom, we assessed our ability to obtain true time-activity curves from observed PET data contaminated by partial volume and spillover effects. Computer simulations demonstrated that the approach developed is relatively insensitive to most potential sources of error, but is sensitive to timing discrepancies between the arterial input function and the tissue time-activity curve. Implementation of this approach provides accurate quantitation of regional MBF in absolute terms and should be useful in noninvasive evaluation of the efficacy of treatments designed to enhance nutritional perfusion in human subjects.

Efficacy of platelet depletion in counteracting the detrimental effect of acute hypercholesterolemia on infarct size and the no-reflow phenomenon in rabbits undergoing coronary artery occlusion-reperfusion.

It has recently been demonstrated that acute hypercholesterolemia per se, independently of its atherogenic effect, increases the extent of myocardial injury in rabbits undergoing coronary artery occlusion-reperfusion. Estimation of myocardial blood flow after reperfusion indicated that this deleterious effect was due to a vascular obstruction that limited the efficacy of reperfusion. The goal of this study was to evaluate the role played by platelets in contributing to the occurrence of this deleterious effect. Accordingly, New Zealand White rabbits were fed a standard laboratory chow diet (plasma cholesterol 67 +/- 12 mg/dl) or a 2% cholesterol-enriched diet for 3 days (plasma cholesterol 329 +/- 70 mg/dl). In a first series of experiments autologous platelets were labeled with 111In-oxine. After labeling, platelets were reinjected in the same animal and 30 min later coronary artery occlusion (CAO) was induced. CAO was maintained for 30 min followed by 5.5 hr of reperfusion. The animals were then killed, their hearts were excised, and each left ventricle was divided into ischemic and normally perfused samples. Myocardial samples were then counted in a gamma counter. Platelet accumulation ratio, i.e., 111In activity in the ischemic myocardium per gram of tissue divided by 111In activity in the normal myocardium per gram of tissue, was calculated. The ratio was 2.4 +/- 0.2 (mean +/- SEM) in controls (n = 7) and 10.3 +/- 1.0 in the cholesterol-fed group (n = 6, p less than .001), indicating that a marked accumulation of platelets occurs in the ischemic myocardium of hypercholesterolemic rabbits. To evaluate the importance of this phenomenon, another series of experiments was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantification of regional myocardial blood flow in vivo with H215O.

Using H215O (half-life = 2.1 min) we demonstrated that a modification of the tissue autoradiographic approach permitted quantitation of myocardial blood flow in open-chest dogs by direct assay of myocardial tissue and that noninvasive estimation with positron-emission tomography (PET) delineated relative myocardial blood flow in intact dogs. In open-chest anesthetized dogs, the single-pass extraction fraction of H215O averaged 96 +/- 5% at flows of 80 to 100 ml/100 g/min. This high extraction fraction did not differ significantly over the range of 12 to 238 ml/100 g/min. Myocardial blood flow calculated after a 60 sec intravenous infusion of H215O and direct analysis of tissue correlated well with results obtained with microspheres (r = .94, n = 9 dogs). Subsequently the approach was adapted for preliminary use with PET. Estimation of myocardial content of radiolabeled H2O after intravenous infusion of 20 to 30 mCi of H215O was corrected for vascular pool radioactivity with the use of tomographic data obtained after administration of C15O by inhalation to label red blood cells. Tomograms obtained in vivo in six dogs with either normal or reduced regional blood flow correlated closely with the tomographically detectable distribution of 68Ga-labeled microspheres (r = .93) and with postmortem microsphere distribution (r = .95). The technique accurately reflects myocardial blood flow. With the use of PET, rapid sequential noninvasive estimation of relative regional myocardial blood flow has been demonstrated that should ultimately permit improved objective assessment of nutritional blood flow in patients in response to medical and surgical interventions designed to augment perfusion.

Estimation of regional myocardial blood flow using computed tomography: a stochastic formulation.

Previously, we have presented a deterministic formulation for estimation of regional myocardial blood flow (RMBF) using X-ray computed tomography (CT) [1]. Quantitation of RMBF with the deterministic theory requires computing the zeroth and first moments of extrapolated myocardial contrast enhancement (CT numbers versus time) curves. This extrapolation is a potential source of error in the presence of recirculation, especially in myocardial regions with reduced flows. In the present paper, a stochastic approach for parameter estimation is undertaken, which renders an optimal RMBF estimate based upon the least squares error criteria. Random measurement errors are minimized, curve extrapolation is avoided, and the accuracy of RMBF estimates is predicted. The advantages of the stochastic versus the deterministic approach are demonstrated in the results obtained from the in vivo estimation of RMBF in normal and acutely ischemic myocardium of dogs.