Quantification of 3-D regional myocardial deformation: shape-based analysis of magnetic resonance images.

A comprehensive three-dimensional (3-D) shape-based approach for quantification of regional myocardial deformations was evaluated in a canine model (n = 8 dogs) with the use of cine magnetic resonance imaging. The shape of the endocardial and epicardial surfaces was used to track the 3-D trajectories of a dense field of points over the cardiac cycle. The shape-based surface displacements are integrated with a continuum biomechanics model incorporating myofiber architecture to estimate both cardiac- and fiber-specific endocardial and epicardial strains and shears for 24 left ventricular regions. Whereas radial and circumferential end-systolic strains were fairly uniform, there was a significant apex-to-base gradient in longitudinal strain and radial-longitudinal shear. We also observed transmural epicardial-to-endocardial gradients in both cardiac- and fiber-specific strains. The increase in endocardial strain was accompanied by increases in radial-longitudinal shear and radial-fiber shears in the endocardium, supporting previous theories of regional myocardial deformation that predict considerable sliding between myocardial fibers.

A new method for quantification of spatial and temporal parameters of endocardial motion: evaluation of experimental infarction using magnetic resonance imaging.

BACKGROUND: With the development of high-resolution myocardial imaging there has evolved a need for automated techniques that can accurately quantify regional function. OBJECTIVE: To develop a new method for quantification of spatial and temporal parameters of endocardial motion. DESIGN: Magnetic resonance images were analyzed using a unique, shape-based approach that tracks endocardial surface motion at defined points through the cardiac cycle by minimizing the bending energy. SETTING: Animal instrumentation was performed in the Nuclear Cardiology Experimental Research Laboratory at Yale University, New Haven, Connecticut. Magnetic resonance imaging was performed at the Yale New Haven Hospital Center. ANIMALS: Eight mongrel canines were used. INTERVENTIONS: Electrocardiograph-gated gradient-echo magnetic resonance images were obtained before and after occlusion of the left anterior descending coronary. Thirty-two points along automatically defined endocardial contours were tracked. Average displacements and cumulative path lengths were computed from end-diastole for each point over the entire cardiac cycle. The average cumulative path length was computed for each of four quarters of systole for the normal, border and infarct zones. Shape-based parameters of systolic motion were compared with the centreline approach. Infarct zone was defined by postmortem histochemical staining. MAIN RESULTS: Displacement and cumulative path length over the cardiac cycle decreased significantly in the infarct and border zones (P<0.05), but did not change in the normal zone (P was not significant). Temporal changes in motion were observed in all zones. Displacement measured using the shape-based algorithm was more consistent than cumulative path length when compared with systolic motion measured using the centreline method. CONCLUSIONS: An automated, shape-based approach permits quantitative evaluation of both spatial and temporal parameters of regional endocardial motion from high-resolution electrocardiograph-gated images. Analysis of endocardial motion and cumulative motion over the entire cardiac cycle discriminated infarcted from normal and border regions.

Estimation of 3D left ventricular deformation from echocardiography.

The quantitative estimation of regional cardiac deformation from 3D image sequences has important clinical implications for the assessment of viability in the heart wall. Such estimates have so far been obtained almost exclusively from Magnetic Resonance (MR) images, specifically MR tagging. In this paper we describe a methodology for estimating cardiac deformations from 3D echocardiography (3DE). The images are segmented interactively and then initial correspondence is established using a shape-tracking approach. A dense motion field is then estimated using a transversely isotropic linear elastic model, which accounts for the fiber directions in the left ventricle. The dense motion field is in turn used to calculate the deformation of the heart wall in terms of strain in cardiac specific directions. The strains obtained using this approach in open-chest dogs before and after coronary occlusion, show good agreement with previously published results in the literature. They also exhibit a high correlation with strains produced in the same animals using implanted sonomicrometers. This proposed method provides quantitative regional 3D estimates of heart deformation from ultrasound images.

Assessment of left ventricular ejection fraction with quantitative gated SPECT: accuracy and correlation with first-pass radionuclide angiography.

BACKGROUND: Quantitative gated single photon emission computed tomography (SPECT [QGS]) software is widely used for the assessment of left ventricular ejection fraction (LVEF). Potentially confounding variables that may affect the accuracy of quantitative analysis of LVEF remain undefined. This study evaluated the accuracy of QGS as a means of determining LVEF in a wide range of LVEF values; evaluated the effect of extracardiac activity, count statistics, heart size, and perfusion defects on the accuracy of QGS LVEF; and compared QGS LVEF obtained at rest with that obtained after stress. METHODS AND RESULTS: QGS-derived LVEF was compared with rest first-pass radionuclide angiography (FPRNA) LVEF in 400 electrocardiographic-gated SPECT studies. The overall correlation between QGS and FPRNA LVEF was only fair (r = 0.66, SEE = 11.85%). In 35 of the patient studies (9%) with high extracardiac activity, the automated software failed, and no correlation was obtained. In the remaining 365 patient studies (91%), left ventricular contours were successfully identified. In these studies, correlation was better (r = 0.74, SEE = 9.77%). Agreement was better for images with high counts (r = 0.81, SEE = 8.66%) than for images with low counts (r = 0.61, SEE = 11.17%). Patient studies with abnormal LVEF had better correlation (r = 0.77, SEE = 6.4%) than studies with normal LVEF (r = 0.46, SEE = 10.2%). Agreement between QGS LVEF and FPRNA LVEF was better in hearts with large end diastolic volumes (>104 mL) than in hearts with small volumes. Overall, mean QGS LVEF was lower than mean FPRNA LVEF (54%+/-14% vs. 58%+/-14%, P<.0001). There was no difference between mean rest and stress QGS LVEF in the same patients, even in patients with stress-induced ischemia. CONCLUSIONS: QGS is a valuable method for assessing resting LVEF. However, QGS LVEF is often lower than FPRNA LVEF. Accuracy is affected by high extracardiac activity, low count density, and small size of the left ventricle.

Acute ischemic dysfunction alters coronary flow reserve in remote nonischemic regions: potential mechanical etiology identified in an acute canine model.

BACKGROUND: Impaired coronary flow reserve (CFR) has been observed in remote nonischemic regions in patients after myocardial infarction. The mechanism for this impairment in remote nonischemic CFR remains undefined. This study evaluates the effect of progressive regional ischemic dysfunction on function in remote nonischemic regions, and the effect of the extent of dysfunction on remote nonischemic coronary flow and CFR. METHODS: In an anesthetized open-chest canine model (n = 7) of acute progressive distal and proximal left anterior descending (LAD) coronary artery occlusion, regional myocardial thickening fraction and coronary flow and CFR were measured with Doppler probes. CFR was assessed by an intracoronary injection of 36 microg of adenosine. Changes in thickening fraction and CFR were evaluated for isovolumic, ejection, and diastolic phases. Changes in resting regional flow were also assessed using radiolabeled microspheres. The extent of the ischemic area was defined as regions of myocardium with endocardial microsphere blood flow less than 0.3 mL/min/g. RESULTS: The ischemic area increased from 12% +/- 1% of left ventricle with distal occlusion to 30% +/- 2% of left ventricle with proximal occlusion (P < .001). The LAD thickening fraction decreased significantly from baseline (18% +/- 1%) to distal (-8% +/- 1%,) and proximal (-4% +/- 1%) occlusion (P < .001 for distal and proximal vs baseline). Isovolumic bulging in the LAD region was associated with a progressive increase in thickening fraction in the remote nonischemic left circumflex (LCX) artery region (baseline 12% +/- 1%; distal occlusion 15% +/- 2%, P = .014 vs baseline; proximal occlusion 17% +/- 2%, P = .02 vs baseline). Most of the increase in remote thickening fraction occurred during the isovolumic phase. There was no significant change in resting flow in remote nonischemic LCX regions or global hemodynamic parameters. However, there was a progressive decrease in remote nonischemic CFR (baseline 2.44 +/- 0.3), distal occlusion (2.19 +/- 0.31; P = .055 vs baseline), and proximal occlusion (1.79 +/- 0.22; P = 0.004 vs baseline, and P = .012 vs distal occlusion). A progressive decrease in CFR was noted in each phase of the cardiac cycle. CONCLUSION: In a canine model of acute progressive distal and proximal coronary occlusion, we observed a progressive decrease in CFR in remote nonischemic regions concurrent with an increase in the extent of ischemia. The decrease in remote nonischemic CFR was associated with ischemia-induced isovolumic bulging, which placed the remote regions at a mechanical disadvantage. These observations suggest a potential mechanical etiology for the observed impairment in remote CFR. Alterations in remote nonischemic CFR during acute ischemia may have important clinical implications for perfusion scintigraphy.

Reproducibility and accuracy of gated SPECT for determination of left ventricular volumes and ejection fraction: experimental validation using MRI.

UNLABELLED: Quantitative gated SPECT (QGS) has been used for computation of left ventricular volumes and ejection fraction. This study evaluated, first, the effect of injected dose, time of imaging, and background activity on the reproducibility of QGS and, second, the accuracy of QGS, compared with cine MRI, for determining left ventricular volumes and ejection fractions in dogs with and without perfusion defects. METHODS: Sixteen dogs were subjected to either chronic occlusion of the circumflex artery (group I, no perfusion defect) or acute occlusion of the anterior descending coronary artery (group II, perfusion defect). Both groups underwent serial MRI and SPECT. RESULTS: ( QGS was very reproducible using the automated program (r = 0.99997). Correlation between left ventricular ejection fraction (LVEF) at 15 and 45 min was poor after the low-dose injection (r = 0.54; SE = 9%) and only fair after the high-dose injection (r = 0.77; SE = 5%). Correlation was poor in the presence of significant background activity (r = 0.36; SE = 12%). Correlation between QGS left ventricular volumes and MRI was good for group I (end-diastolic volume, r = 0.86; end-systolic volume, r = 0.81) and only fair for group II (end-diastolic volume, r = 0.66; end-systolic volume, r = 0.69). The overall LVEF correlation between QGS and MRI was poor (r = 0.51). QGS LVEF (mean +/- SD, 42% +/- 3%) overestimated MRI LVEF (29% +/- 2%). CONCLUSION: QGS provides a highly reproducible estimate of LVEF. However, QGS is affected by changes in background activity, time of imaging, and injected dose. In the presence of perfusion defects, QGS overestimated volume relative to MRI. The correlation between QGS- and MRI-derived LVEF was poor in this canine model.

Severe regional ischemia alters coronary flow reserve in the remote perfusion area.

BACKGROUND: Clinical and experimental studies suggest that coronary flow reserve (CFR) may be abnormal in regions remote from myocardial infarction. We sought to determine the possible relation among stenosis severity, ischemic dysfunction, and impairment of CFR in remote regions. METHODS AND RESULTS: In 7 open-chest dogs, acute graded left circumflex (LCX) ischemia was created and maintained based on measurement of the transstenotic (aortic-distal LCX) pressure gradient (measured in millimeters of mercury). Regional thickening was assessed with sonomicrometers. Regional myocardial flow was assessed at rest with radiolabeled microspheres. Doppler flow probes were placed on proximal LCX and left anterior descending (LAD) arteries to measure resting flow and CFR in response to intracoronary injection of adenosine (36 microg). These parameters were assessed under baseline conditions and during transstenotic gradients of 10, 20, 30, and 40 mm Hg. Increasing LCX stenosis severity caused progressive impairment of LCX CFR: baseline (2.22+/-0.10), stenosis 10 (1.80+/-0.06), stenosis 20 (1.56+/-0.08), stenosis 30 (1.30+/-0.04), and stenosis 40 (1.17+/-0.06) (P<.01 vs. baseline). Remote LAD CFR was not altered by mild to moderate LCX stenosis (baseline [2.33+/-0.19]; stenosis 10 [2.30+/-0.25]; stenosis 20 [2.15+/-0.26]). However, critical LCX stenosis producing mild to moderate reduction in thickening in the ischemic region was associated with a significant impairment of LAD CFR: stenosis 30 (1.90+/-0.26) and stenosis 40 (1.80+/-0.22) (P<.01 vs. baseline). These changes in remote CFR persisted after correction for changes in the rate-pressure product. CONCLUSION: In an acute canine model of progressive LCX coronary stenosis, CFR was impaired in both ischemic and remote nonischemic regions in association with mild to moderate ischemic-induced regional myocardial dysfunction. Thus pharmacologic vasodilation provoked only mild heterogeneity in CFR in the presence of a critical LCX stenosis as a result of concurrent reduction of LAD CFR. This phenomenon warrants further clinical and experimental investigation because it may affect detection of flow heterogeneity during acute ischemia (which induced myocardial dysfunction).

Limitations of dobutamine for enhancing flow heterogeneity in the presence of single coronary stenosis: implications for technetium-99m-sestamibi imaging.

UNLABELLED: Dobutamine is used as an alternative to exercise in conjunction with 99mTc-sestamibi SPECT perfusion imaging for detection of coronary artery disease. However, the use of quantitative dobutamine 99mTc-sestamibi SPECT imaging for enhanced detection of coronary stenosis has not been established. The goal of this study is to examine the effects of dobutamine stress on regional myocardial blood flow and relative myocardial 99mTc-sestamibi activity in the presence of a single-vessel stenosis. METHODS: In six open-chest dogs with left circumflex artery stenosis, radiolabeled microspheres were injected during baseline, severe stenosis and peak dobutamine stress (10 microg/kg/min). Technetium-99m-sestamibi was injected intravenously at peak dobutamine. Hearts were excised 20 min after 99mTc-sestamibi injection for SPECT imaging and post-mortem gamma-well counting. RESULTS: Dobutamine significantly increased heart rate, rate-pressure product and the first derivative of left ventricular pressure. Ischemic zone (left circumflex) myocardial blood flows (in ml/min/g) were: baseline, 0.92 +/- 0.15; stenosis, 0.65 +/- 0.16; and dobutamine, 1.19 +/- 0.38. Nonischemic zone myocardial blood flows were: baseline, 0.99 +/- 0.18; stenosis, 1.01 +/- 0.12; and dobutamine, 1.94 +/- 0.32 (p < 0.01 versus stenosis). Ischemic flows, expressed as percentages of nonischemic flows, were: baseline, 94% +/- 2%; stenosis, 63% +/- 11% (p < 0.05 versus baseline) and dobutamine, 60% +/- 12% (p was not significant versus stenosis). Technetium-99m-sestamibi activity in the ischemic zone (75% +/- 6% nonischemic) underestimated the relative flow deficit produced during dobutamine stress (p = 0.056). Myocardial 99mTc-sestamibi activity correlated with flow when flow was less than 1.0 ml/min/g. At higher flow ranges (1.0 ml/min/g-3.5 ml/min/g), 99mTc-sestamibi did not track flow. CONCLUSION: In a canine model of flow-limiting, single-vessel stenosis, dobutamine (10 microg/kg/min) did not augment flow heterogeneity. In addition, relative myocardial 99mTc-sestamibi activity underestimated microsphere flow at higher flows induced by dobutamine, leading to underestimation of ischemia. These findings suggest that dobutamine stress 99mTc-sestamibi scintigraphy may underestimate the relative flow deficit.

Extracardiac activity complicates quantitative cardiac SPECT imaging using a simultaneous transmission-emission approach.

UNLABELLED: Increased extracardiac activity confounds conventional cardiac SPECT image reconstruction using a filtered backprojection method. Others have proposed that simultaneously acquired transmission-emission (STE) images that are reconstructed with a maximum likelihood (ML) method incorporating a nonuniform attenuation correction would less likely be affected by the presence of extracardiac activity. However, this approach corrects only for decreased myocardial counts from attenuation and not for increased myocardial counts from extracardiac activity. Therefore, STE with nonuniform attenuation correction may also result in reconstruction artifacts when extracardiac activity is present. METHODS: Acquisitions of phantoms with nonuniform and uniform attenuation were performed using STE and conventional approaches, in the absence and presence of extracardiac activity. All acquisitions used a triple-headed SPECT camera. STE acquisitions used fanbeam collimation and a 153Gd transmission source. STE images were reconstructed using ML, with and without nonuniform attenuation correction. Reconstructed short-axis images were quantitated, and percentage variability for each count profile was calculated. RESULTS: In a nonuniform phantom configuration, STE reconstruction with nonuniform attenuation correction significantly improved image uniformity. This improvement in image uniformity was diminished with the addition of increasing extracardiac activity. In a uniform phantom, STE reconstruction with nonuniform attenuation correction significantly improved uniformity only in the presence of extracardiac activity. CONCLUSION: The addition of attenuation correction in the presence of extracardiac activity can have complex effects on ML reconstruction with nonuniform attenuation correction, which depends on the amount of extracardiac activity and pattern of attenuation.

Quantification of technetium 99m-labeled sestamibi single-photon emission computed tomography based on mean counts improves accuracy for assessment of relative regional myocardial blood flow: experimental validation in a canine model.

BACKGROUND: Quantification of single-photon emission computed tomographic (SPECT) images is generally based on determination of maximal counts on radial sectors of short-axis slices. We hypothesized that analysis of mean counts may reduce estimation error. METHODS AND RESULTS: We compared quantitative 99mTc-labeled sestamibi (MIBI) SPECT based on maximal myocardial counts with that based on mean myocardial counts for accuracy of quantifying relative regional myocardial perfusion in a canine model of permanent left anterior descending coronary artery occlusion. MIBI and radiolabeled microspheres were injected during left anterior descending coronary artery occlusion. Relative microsphere myocardial blood flow was expressed as a percentage of normal (left circumflex coronary artery territory) blood flow. SPECT imaging was performed in vivo and ex vivo. Relative MIBI uptake on SPECT short-axis slices was quantified with normalized circumferential profiles based on maximal and mean counts. In vivo and ex vivo SPECT relative myocardial count density was compared to relative myocardial blood flow in six dogs. In the comparisons, percent errors in estimating the relative blood flow and relative flow deficit with MIBI SPECT imaging were calculated. There was an excellent correlation between absolute myocardial tissue MIBI activity and regional myocardial blood flow for each of the six dogs (r = 0.90 to 0.98). The correlations between relative myocardial count density on SPECT and relative blood flow for individual sectors were similar for maximal and mean count profiles (maximal, 0.79 to 0.83; mean, 0.77 to 0.82). Comparing the nadirs of in vivo and ex vivo circumferential count profiles, the correlations were slightly better (maximal, 0.82 to 0.91; mean, 0.87 to 0.91). Average percent errors in assessing relative blood flow and relative flow deficit were decreased significantly by use of mean count profiles (p < 0.05). CONCLUSIONS: Relative SPECT count density with either maximal or mean count profiles correlated well with relative myocardial blood flow. Compared with maximal count profiles, quantification with mean count profiles improved estimation of relative flow.

Technetium-99m-nitroimidazole (BMS181321): a positive imaging agent for detecting myocardial ischemia.

UNLABELLED: A new technetium-99m-labeled nitroimidazole (BMS181321) has been proposed for positive imaging of myocardial ischemia. METHODS: An in vivo open-chest canine model of partial coronary occlusion and pacing-induced demand ischemia was used to correlate myocardial retention of BMS181321, following an intravenous injection at peak stress, with regional microsphere blood flow. Postmortem measurements of myocardial BMS181321 activity and flow were correlated with in vivo planar and ex vivo SPECT images. Myocardial and hepatic clearance of BMS181321 was derived from ROI analysis of serial planar images. RESULTS: Anaerobic metabolism was documented in the ischemic region by selective venous and arterial sampling for lactate and oxygen consumption. Normalized myocardial BMS181321 activity (165% +/- 42% nonischemic) in the central ischemic region (flow < 0.3 ml/min/gm) was significantly greater than activity in normal regions (p < 0.05). Quantitative circumferential analysis of SPECT images revealed a comparable increase in myocardial BMS181321 activity in the ischemic region. Sixty minutes after injection of BMS181321, liver activity was 423% of ischemic myocardial activity. CONCLUSION: BMS181321 was preferentially retained in ischemic but viable canine myocardium and was inversely related to regional myocardial blood flow. Although enhanced retention of BMS181321 was detectable by ex vivo SPECT imaging, an unfavorable heart-to-liver ratio was observed with in vivo planar imaging which may limit its use in clinical myocardial imaging.