Microsphere Flow Measurements Research Articles

Regional myocardial strain analysis via 2D speckle tracking echocardiography: validation with sonomicrometry and correlation with regional blood flow in the presence of graded coronary stenoses and dobutamine stress

BackgroundQuantitative regional strain analysis by speckle tracking echocardiography (STE) may be particularly useful in the assessment of myocardial ischemia and viability, although reliable measurement of regional strain remains challenging, especially in the circumferential and radial directions. We present an acute canine model that integrates a complex sonomicrometer array with microsphere blood flow measurements to evaluate regional myocardial strain and flow in the setting of graded coronary stenoses and dobutamine stress. We apply this unique model to rigorously evaluate a commercial 2D STE software package and explore fundamental regional myocardial flow-function relationships.MethodsSonomicrometers (16 crystals) were implanted in epicardial and endocardial pairs across the anterior myocardium of anesthetized open chest dogs (n = 7) to form three adjacent cubes representing the ischemic, border, and remote regions, as defined by their relative locations to a hydraulic occluder on the mid-left anterior descending coronary artery (LAD). Additional cardiac (n = 3) and extra-cardiac (n = 3) reference crystals were placed to define the cardiac axes and aid image registration. 2D short axis echocardiograms, sonometric data, and microsphere blood flow data were acquired at baseline and in the presence of mild and moderate LAD stenoses, both before and during low-dose dobutamine stress (5 μg/kg/min). Regional end-systolic 2D STE radial and circumferential strains were calculated with commercial software (EchoInsight) and compared to those determined by sonomicrometry and to microsphere blood flow measurements. Post-systolic indices (PSIs) were also calculated for radial and circumferential strains.ResultsLow-dose dobutamine augmented both strain and flow in the presence of mild and moderate stenoses. Regional 2D STE strains correlated moderately with strains assessed by sonomicrometry (Rradial = 0.56, p < 0.0001; Rcirc = 0.55, p < 0.0001) and with regional flow quantities (Rradial = 0.61, Rcirc = 0.63). Overall, correspondence between 2D STE and sonomicrometry was better in the circumferential direction (Bias ± 1.96 SD: − 1.0 ± 8.2% strain, p = 0.06) than the radial direction (5.7 ± 18.3%, p < 0.0001). Mean PSI values were greatest in low flow conditions and normalized with low-dose dobutamine.Conclusions2D STE identifies changes in regional end-systolic circumferential and radial strain produced by mild and moderate coronary stenoses and low-dose dobutamine stress. Regional 2D STE end-systolic strain measurements correlate modestly with regional sonomicrometer strain and microsphere flow measurements.

Single-scan rest/stress imaging: validation in a porcine model with 18F-Flurpiridaz.

18F-labeled myocardial flow agents are becoming available for clinical application but the ∼2hour half-life of 18F complicates their clinical application for rest-stress measurements. The goal of this work is to evaluate in a pig model a single-scan method which provides quantitative rest-stress blood flow in less than 15minutes. Single-scan rest-stress measurements were made using 18F-Flurpiridaz. Nine scans were performed in healthy pigs and seven scans were performed in injured pigs. A two-injection, single-scan protocol was used in which an adenosine infusion was started 4minutes after the first injection of 18F-Flurpiridaz and followed either 3 or 6minutes later by a second radiotracer injection. In two pigs, microsphere flow measurements were made at rest and during stress. Dynamic images were reoriented into the short axis view, and regions of interest (ROIs) for the 17 myocardial segments were defined in bull's eye fashion. PET data were fitted with MGH2, a kinetic model with time varying kinetic parameters, in which blood flow changes abruptly with the introduction of adenosine. Rest and stress myocardial blood flow (MBF) were estimated simultaneously. The first 12-14 minutes of rest-stress PET data were fitted in detail by the MGH2 model, yielding MBF measurement with a mean precision of 0.035ml/min/cc. Mean myocardial blood flow across pigs was 0.61 ± 0.11mL/min/cc at rest and 1.06 ± 0.19mL/min/cc at stress in healthy pigs and 0.36 ± 0.20mL/min/cc at rest and 0.62 ± 0.24mL/min/cc at stress in the ischemic area. Good agreement was obtained with microsphere flow measurement (slope = 1.061 ± 0.017, intercept = 0.051 ± 0.017, mean difference 0.096 ± 0.18ml/min/cc). Accurate rest and stress blood flow estimation can be obtained in less than 15min of PET acquisition. The method is practical and easy to implement suggesting the possibility of clinical translation.

In vivo quantification of regional myocardial blood flow: Validity of the fast‐exchange approximation for intravascular T1 contrast agent and long inversion time

In the present study we investigated the effects of water exchange between intra- and extravascular compartments on absolute quantification of regional myocardial blood flow (rMBF) using a saturation-recovery sequence with a rather long inversion time (TI, 176 ms) and a T1-shortening intravascular contrast agent (CMD-A2-Gd-DOTA). Data were acquired in normal and ischemically injured pigs, with radiolabeled microsphere flow measurements used as the gold standard. Five water exchange rates (fast, 6 Hz, 3 Hz, 1 Hz, and no exchange) were tested. The results demonstrate that the fast-exchange approximation may be appropriate for rMBF quantification using the described experimental setting. Relaxation rate change (DeltaR1) analysis improved the accuracy of the analysis of rMBF compared to the MR signal. In conclusion, the current protocol could provide sufficient accuracy for estimating rMBF assuming fast exchange and a linear relationship between signal and tissue concentration when quantification of precontrast T1 is not an option.

Coronary collateral development during chronic ischemia: serial assessment using harmonic myocardial contrast echocardiography

OBJECTIVESWe sought to characterize collateral development in an experimental model of chronic myocardial ischemia by using myocardial contrast echocardiography (MCE).BACKGROUNDCoronary collaterals maintain myocyte viability during myocardial ischemia. The natural history and determinants of collateral development are difficult to study serially in vivo.METHODSThe left anterior descending coronary artery (LAD) in nine dogs was encircled (day 0) with a hydraulic occluder and ameroid constrictor to enable reversible and gradual total LAD occlusion, respectively. Myocardial contrast echocardiography was performed using intravenous injection of perfluorocarbon gas-containing microbubbles during two-dimensional harmonic echocardiographic imaging. Myocardial contrast echocardiography images and radiolabeled microsphere flow measurements were obtained during transient LAD occlusion on day 0. Over the ensuing six weeks, MCE imaging was performed during LAD occlusion at 10-day intervals.RESULTSMyocardial contrast echocardiography risk area size (expressed as a percent of the left ventricular short axis slice) decreased over the course of six weeks (32% ± 3% on day 0, 21% ± 3% at day 10, 5 ± 3% at day 20, 1% ± 1% at day 30 and 1% ± 1% at day 42, p ≤ 0.001 vs. day 0). Radiolabeled microsphere-derived LAD flow, normalized to left circumflex flow, correspondingly increased between day 0 and day 42 (0.14 ± 0.02 to 0.90 ± 0.07, p < 0.02).CONCLUSIONSCollateral development occurs relatively early and rapidly in this chronic canine model. Myocardial contrast echocardiography using harmonic imaging and intravenous injection of microbubbles can uniquely track the spatial and temporal course of collateral growth, and may be a powerful tool for noninvasively mapping the efficacy of therapeutic angiogenic strategies in vivo.

Accuracy of right ventricular output estimated by Doppler echocardiography in the sheep fetus

Our goal was to determine whether Doppler ultrasonographic estimation of fetal right ventricular output was accurate enough to evaluate fetal cardiac performance before the technique can be applied with confidence to the human fetus. The accuracy of this method has not been validated experimentally. We compared the right ventricular output measured by Doppler echocardiography with that determined from a transit-time ultrasonic flowmeter placed around the fetal pulmonary trunk and to that determined by microsphere technique. We obtained 72 Doppler flow measurements and 16 microsphere flow measurements in six fetuses. There was a fair correlation between cardiac output estimated by Doppler echocardiography performed transabdominally and that determined by a transit-time flowmeter (r = 0.76). The correlation was excellent when Doppler echocardiography was performed by the trans-uterine approach (r = 0.94). There was also an excellent correlation between right ventricular output determined by a transit-time flowmeter and that by microsphere technique (r = 0.94). Doppler echocardiographic estimation of fetal right ventricular cardiac output is thus feasible and accurate.

Distribution of perfusate flow during vasodilation in isolated guinea pig heart.

The purpose of this study was to determine the effect of vasodilation on the distribution of perfusate flow in the isolated guinea pig heart. Hearts were perfused retrogradely through the aorta with oxygenated Krebs-Henseleit buffer solution at 37 degrees C. Regional myocardial flows were measured with 15-micron radioactive microspheres. Each heart was subdivided into 45 pieces (average size 44 mg), and heterogeneity of flow was quantified as the relative dispersion (standard deviation/mean). Under control conditions at a perfusion pressure of 46 mmHg (60 cm water), the relative dispersion of left ventricular (LV) flow was 30 +/- 2% (n = 8). Vasodilation was induced via infusion of dipyridamole (10(-5) M). When flow was held constant at the resting value, relative flow dispersion increased to 43 +/- 6% (n = 8). When perfusion pressure was held constant and flow allowed to increase, relative dispersion fell to 20 +/- 5% (n = 5). Heterogeneity for the heart as a whole was higher than for the left ventricle but followed the same pattern with vasodilation. In a separate series of hearts (n = 5) equipped with LV balloons but without microsphere flow measurements, vasodilation at constant flow decreased LV pressure development, dP/dt, and O2 consumption. Vasodilation at constant pressure increased O2 consumption, but did not increase LV pressure or dP/dt. We conclude that vasodilation in this preparation will increase flow heterogeneity during constant-flow perfusion but decrease heterogeneity during constant-pressure perfusion. Furthermore, increased flow heterogeneity can compromise ventricular function.

Measurement of heterogeneous myocardial blood flow.

Inert gas measurements of myocardial blood flow have been compared to simultaneous radioactive microsphere flow measurements. Average flow per unit weight agreed within 20% in 20 of 24 comparisons. With the inert gas technique flows up to 580 ml/min/100 g could be measured. Semilogarithmically plotted desaturation curves were distinctively curvilinear. It is concluded that the shape of the washout curve is a function of the underlying flow pattern.