Single Photon Emission Computed Tomography Perfusion Defect Research Articles

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker, in a porcine model of acute myocardial infarction.

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.

Assessing the impact of radiation‐induced changes in soft tissue density/thickness on the study of radiation‐induced perfusion changes in the lung and heart

Abnormalities in single photon emission computed tomography (SPECT) perfusion within the lung and heart are often detected following radiation for tumors in∕around the thorax (e.g., lung cancer or left-sided breast cancer). The presence of SPECT perfusion defects is determined by comparing pre- and post-RT SPECT images. However, RT may increase the density of the soft tissue surrounding the lung∕heart (e.g., chest wall∕breast) that could possibly lead to an "apparent" SPECT perfusion defect due to increased attenuation of emitted photons. Further, increases in tissue effective depth will also increase SPECT photon attenuation and may lead to "apparent" SPECT perfusion defects. The authors herein quantitatively assess the degree of density changes and effective depth in soft tissues following radiation in a series of patients on a prospective clinical study. Patients receiving thoracic RT were enrolled on a prospective clinical study including pre- and post-RT thoracic computed tomography (CT) scans. Using image registration, changes in tissue density and effective depth within the soft tissues were quantified (as absolute change in average CT Hounsfield units, HU, or tissue thickness, cm). Changes in HU and tissue effective depth were considered as a continuous variable. The potential impact of these tissue changes on SPECT images was estimated using simulation data from a female SPECT thorax phantom with varying tissue densities. Pre- and serial post-RT CT images were quantitatively studied in 23 patients (4 breast cancer, 19 lung cancer). Data were generated from soft tissue regions receiving doses of 20-50 Gy. The average increase in density of the chest was 5 HU (range 46 to -69). The average change in breast density was a decrease of -1 HU (range 13 to -13). There was no apparent dose response in neither the dichotomous nor the continuous analysis. Seventy seven soft tissue contours were created for 19 lung cancer patients. The average change in tissue effective depth was +0.2 cm (range -1.9 to 2.2 cm). The changes in HU represent a <2% average change in tissue density. Based on simulation, the small degree of density and tissue effective depth change is unlikely to yield meaningful changes in either SPECT lung or heart perfusion. RT doses of 20-50 Gy can cause up to a 46 HU increase in soft tissue density 6 months post-RT. Post-RT soft tissue effective depth may increase by 2.0 cm. These modest increases in soft tissue density and effective depth are unlikely to be responsible for the perfusion changes seen on post-RT SPECT lung or heart scans. Further, there was no clear dose response of the soft tissue density changes. Ultimately, the authors findings suggest that prior perfusion reports do reflect changes in the physiology of the lungs and heart.

Comparison of Dual-Energy Computed Tomography of the Heart With Single Photon Emission Computed Tomography for Assessment of Coronary Artery Stenosis and of the Myocardial Blood Supply

To evaluate the performance of dual-energy computed tomography (CT) for integrative imaging of the coronary artery morphology and the myocardial blood supply, 36 patients (15 women, mean age 57 +/- 11 years) with equivocal or incongruous single photon emission CT (SPECT) results were investigated by a single-contrast medium-enhanced, retrospectively electrocardiographic-gated dual-energy CT (DECT) scan with simultaneous acquisition of high and low x-ray spectra. Thirteen patients subsequently underwent invasive coronary angiography (ICA). The DECT data were used to reconstruct anatomic coronary CT angiographic images and to map the myocardial iodine distribution within the left ventricular myocardium. Two independent observers analyzed all DECT studies for stenosis and myocardial iodine defects. A segmental comparison was performed between the stress/rest SPECT perfusion defects and DECT iodine defects and between the ICA and coronary CT angiographic findings for stenosis. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were estimated, along with the kappa statistics. Overall, DECT had 92% sensitivity and 93% specificity, with 93% accuracy for detecting any type of myocardial perfusion defect seen on SPECT. Contrast defects at DECT correctly identified 85 (96%) of 89 fixed and 60 (88%) of 68 reversible myocardial perfusion defects. The interobserver agreement was very good (weighted kappa = 0.87). Compared with ICA, coronary CT angiography had 90% sensitivity, 94% specificity, and 93% accuracy for the detection of >50% stenosis. In conclusion, our initial experience suggests that DECT, as a single examination, might be promising for the integrative analysis of the coronary artery morphology and the myocardial blood supply and is in good agreement with ICA and SPECT.

Effects of Left Bundle-Branch Block on Cardiac Structure, Function, Perfusion, and Perfusion Reserve

We aimed to investigate the cardiac effects of left bundle-branch block (LBBB) using myocardial contrast echocardiography (MCE) to ascertain the value of MCE for detecting coronary artery disease (CAD) and to uncover the mechanism that affects the accuracy of single-photon emission computed tomography (SPECT) in these patients. Sixty-three symptomatic LBBB patients (group A), 10 left ventricular ejection fraction-matched control subjects without LBBB and no CAD (group B), and 10 normal control subjects (group C) underwent resting echocardiography. Rest and vasodilator MCE and SPECT were undertaken in LBBB patients. Septal (SW) and posterior wall (PW) thickness, thickening, quantitative myocardial blood flow (MBF), and MBF reserve were measured. SW/PW thickness and percentage thickening ratios were lower (P<0.01 and P<0.05, respectively) in group A compared with both groups B and C, but resting SW/PW MBF and MBF reserve ratios were similar in all 3 groups. MBF reserve but not MBF was reduced in groups A and B (2.2+/-0.7 versus 2.2+/-0.2; P=0.98) compared with group C (3.1+/-0.5; P<0.01). SW thickness was an independent predictor (P=0.006) of SPECT perfusion defects in LBBB patients without CAD. MCE (92%) had a sensitivity similar to SPECT (92%); however, the specificity of MCE (95%) was superior (P<0.0001) to SPECT (47%) for the detection of CAD. Despite asymmetrical reduction in SW thickness and function, MBF is preserved and MBF reserve is homogeneously reduced in LBBB patients with left ventricular systolic dysfunction. Because of partial volume effects, the accuracy of SPECT for detecting CAD was significantly compromised compared with MCE in this patient cohort.

Quantitative Measurement of Infarct Size by Contrast-Enhanced Magnetic Resonance Imaging Early After Acute Myocardial Infarction

Objectives The aim of this research was to evaluate kinetics and extent of myocardial contrast enhancement (CE) in comparison with single-photon emission computed tomography (SPECT) early after acute myocardial infarction (AMI). Background Quantification of infarct size serves as a surrogate end point in evaluating new therapies of AMI. Contrast-enhanced magnetic resonance imaging (CeMRI) of the myocardium is a promising new method for identification of irreversible tissue injury. Methods A total of 33 patients were examined by CeMRI and SPECT 7 ± 2 days after AMI and successful coronary intervention. After gadolinium-diethylenetraimine pentaacetic acid injection (0.2 mmol/kg), continuous short-axis slices of the left ventricle (LV) were acquired every 7 min up to 42 min using different inversion times (TI). Myocardial CE at each imaging time point was quantified and compared with corresponding SPECT perfusion defect. Results All patients showed myocardial CE in the infarct region. A constant TI for CeMRI resulted in a decrease of signal intensity and extent of CE on late acquisitions. With TI adjustment, infarct image intensity peaked at 21 min with a contrast of 478% of remote myocardium and remained at this level up to 42 min after contrast injection (437%); CE extent was stable over time and agreed well with SPECT within an average difference of 3% of the LV myocardium, yielding the best correlation at 28 min (r = 0.86). Conclusions In patients after AMI and successful reperfusion, CE is stable over time and matches well with SPECT perfusion defect; CeMRI under standardized conditions can accurately assess myocardial infarct size in vivo and may be attractive for serving as a surrogate end point early after AMI.

Quantitative measurement of infarct size by contrast-enhanced magnetic resonance imaging early after acute myocardial infarction: Comparison with single-photon emission tomography using Tc99m-sestamibi

The aim of this research was to evaluate kinetics and extent of myocardial contrast enhancement (CE) in comparison with single-photon emission computed tomography (SPECT) early after acute myocardial infarction (AMI). Quantification of infarct size serves as a surrogate end point in evaluating new therapies of AMI. Contrast-enhanced magnetic resonance imaging (CeMRI) of the myocardium is a promising new method for identification of irreversible tissue injury. A total of 33 patients were examined by CeMRI and SPECT 7 +/- 2 days after AMI and successful coronary intervention. After gadolinium-diethylenetraimine pentaacetic acid injection (0.2 mmol/kg), continuous short-axis slices of the left ventricle (LV) were acquired every 7 min up to 42 min using different inversion times (TI). Myocardial CE at each imaging time point was quantified and compared with corresponding SPECT perfusion defect. All patients showed myocardial CE in the infarct region. A constant TI for CeMRI resulted in a decrease of signal intensity and extent of CE on late acquisitions. With TI adjustment, infarct image intensity peaked at 21 min with a contrast of 478% of remote myocardium and remained at this level up to 42 min after contrast injection (437%); CE extent was stable over time and agreed well with SPECT within an average difference of 3% of the LV myocardium, yielding the best correlation at 28 min (r = 0.86). In patients after AMI and successful reperfusion, CE is stable over time and matches well with SPECT perfusion defect; CeMRI under standardized conditions can accurately assess myocardial infarct size in vivo and may be attractive for serving as a surrogate end point early after AMI.

Predicting radiotherapy‐induced cardiac perfusion defects

The purpose of this work is to compare the efficacy of mathematical models in predicting the occurrence of radiotherapy-induced left ventricular perfusion defects assessed using single-photon emission computed tomography (SPECT). The basis of this study is data from 73 left-sided breast/ chestwall patients treated with tangential photon fields. The mathematical models compared were three commonly used parametric models [Lyman normal tissue complication probability (LNTCP), relative serialty (RS), generalized equivalent uniform dose (gEUD)] and a nonparametric model (Linear discriminant analysis--LDA). Data used by the models were the left ventricular dose--volume histograms, or SPECT-based dose-function histograms, and the presence/absence of SPECT perfusion defects 6 months postradiation therapy (21 patients developed defects). For the parametric models, maximum likelihood estimation and F-tests were used to fit the model parameters. The nonparametric LDA model step-wise selected features (volumes/function above dose levels) using a method based on receiver operating characteristics (ROC) analysis to best separate the groups with and without defects. Optimistic (upper bound) and pessimistic (lower bound) estimates of each model's predictive capability were generated using ROC curves. A higher area under the ROC curve indicates a more accurate model (a model that is always accurate has area = 1). The areas under these curves for different models were used to statistically test for differences between them. Pessimistic estimates of areas under the ROC curve using dose-volume histogram/ dose-function histogram inputs, in order of increasing prediction accuracy, were LNTCP (0.79/0.75), RS (0.80/0.77), gEUD (0.81/0.78), and LDA (0.84/0.86). Only the LDA model benefited from SPECT-based regional functional information. In general, the LDA model was statistically superior to the parametric models. The LDA model selected as features the left ventricular volumes above approximately 23 Gy (V23), essentially volume in field, and 33 Gy (V33), as best separating the groups with and without defects. In conclusion, the nonparametric LDA model appears to be a more accurate predictor of radiotherapy-induced left ventricular perfusion defects than commonly used parametric models.

Myocardial SPECT perfusion defect size compared to infarct size by delayed gadolinium‐enhanced magnetic resonance imaging in patients with acute or chronic infarction

Single photon emission computed tomography (SPECT) perfusion imaging has been considered a reference method for non-invasive estimation of infarct size in man. Recently, delayed gadolinium-enhanced magnetic resonance imaging (DE-MRI) has evolved as an accurate tool to quantify infarct size. Therefore, the present study was designed to compare perfusion defect size by SPECT to hyperenhanced volume by DE-MRI. DE-MRI was performed in 30 patients. Fourteen were patients with revascularized first-time acute infarctions, eight revascularized chronic infarctions, and eight clinically referred non-revascularized patients. SPECT was performed in the same patients and analysed by a commercial package. The hypoperfused volume by SPECT was larger than the hyperenhanced volume by DE-MRI by 8 +/- 8 ml (6% +/- 5 percentage points), 10 +/- 18 ml (6% +/- 11 percentage points), and 26 +/- 30 ml (12% +/- 10 percentage points) in the acute, chronic and clinical populations, respectively. Left ventricle wall volume was smaller by SPECT in all settings. The SPECT perfusion defect size was comparable with but generally slightly larger than the hyperenhanced volume by DE-MRI in both absolute and relative terms in patients with acute and chronic infarction. The results may be related to systematic differences between modalities but could also be influenced by biological phenomena such as wall thinning or hypoperfused but viable myocardium.

Complication models to predict radiation-induced cardiac toxicity in patients with breast cancer

758 Background: Predicting the risk of radiation therapy (RT) induced normal tissue complications is important during RT field design. A widely employed formalism for predicting complication, though sparsely validated with clinical data, is the Kutcher normal tissue complication probability (NTCP) model. We herein examine the validity of the NTCP model, in comparison to other statistical models, as a predictor of left ventricle perfusion defects caused by tangential RT to the left-breast/chest wall. Methods: Since 1998, we have been conducting an IRB-approved prospective clinical trial in patients receiving left-sided tangential photon therapy (46–50 Gy at 1.8–2 Gy/fx) to assess RT-induced changes in cardiac function. Patients had pre-RT and 6-month post-RT SPECT (single photon emission computed tomography) cardiac perfusion scans. The datasets of 68 patients with normal pre-RT SPECT scans form the basis of this report. Of these patients, 19 had SPECT perfusion defects at 6 months. The left ventricle dose-volume histograms (DVH) of all patients were used to generate the NTCP model and two other statistical discriminants: generalized equivalent uniform dose (GEUD), and linear discriminant analysis (LDA). GEUD converted the nonuniform dose distribution into an equivalent uniform dose. LDA used a linear combination of step-wise selected DVH features to optimally separate the groups with and without defects. To compare the three models, we used receiver operating characteristic (ROC) curves that plot sensitivity and specificity as a function of discriminant value. A higher ROC curve, and hence higher area under the curve, implies a better model. Results: The areas under the curve for NTCP, GEUD, and LDA were 0.81, 0.81, and 0.91, respectively. The ROC curves for NTCP and GEUD were exactly coincident. LDA was a better predictor than both (p = 0.03). Conclusions: In the breast cancer patient population studied, the widely used NTCP model was a worse predictor of RT induced cardiac toxicity than the simpler linear discriminant analysis. (Supported by DOD award BC010663. Thanks to UNC for PLUNC software.) No significant financial relationships to disclose.

Complication models to predict radiation-induced cardiac toxicity in patients with breast cancer

758 Background: Predicting the risk of radiation therapy (RT) induced normal tissue complications is important during RT field design. A widely employed formalism for predicting complication, though sparsely validated with clinical data, is the Kutcher normal tissue complication probability (NTCP) model. We herein examine the validity of the NTCP model, in comparison to other statistical models, as a predictor of left ventricle perfusion defects caused by tangential RT to the left-breast/chest wall. Methods: Since 1998, we have been conducting an IRB-approved prospective clinical trial in patients receiving left-sided tangential photon therapy (46–50 Gy at 1.8–2 Gy/fx) to assess RT-induced changes in cardiac function. Patients had pre-RT and 6-month post-RT SPECT (single photon emission computed tomography) cardiac perfusion scans. The datasets of 68 patients with normal pre-RT SPECT scans form the basis of this report. Of these patients, 19 had SPECT perfusion defects at 6 months. The left ventricle dose-volume histograms (DVH) of all patients were used to generate the NTCP model and two other statistical discriminants: generalized equivalent uniform dose (GEUD), and linear discriminant analysis (LDA). GEUD converted the nonuniform dose distribution into an equivalent uniform dose. LDA used a linear combination of step-wise selected DVH features to optimally separate the groups with and without defects. To compare the three models, we used receiver operating characteristic (ROC) curves that plot sensitivity and specificity as a function of discriminant value. A higher ROC curve, and hence higher area under the curve, implies a better model. Results: The areas under the curve for NTCP, GEUD, and LDA were 0.81, 0.81, and 0.91, respectively. The ROC curves for NTCP and GEUD were exactly coincident. LDA was a better predictor than both (p = 0.03). Conclusions: In the breast cancer patient population studied, the widely used NTCP model was a worse predictor of RT induced cardiac toxicity than the simpler linear discriminant analysis. (Supported by DOD award BC010663. Thanks to UNC for PLUNC software.) No significant financial relationships to disclose.

Long-term prediction of major ischemic events by exercise thallium-201 single-photon emission computed tomography: Incremental prognostic value compared with clinical, exercise testing, catheterization and radionuclide angiographic data

This study sought to evaluate the prognostic role of exercise thallium-201 (Tl-201) single-photon emission computed tomography (SPECT) in patients with known or suspected coronary artery disease. Compared with planar Tl-201 scintigraphy, Tl-201 SPECT allows enhanced assessment of myocardial perfusion abnormalities. However, the long-term prognostic value of exercise Tl-201 SPECT has not been ascertained and compared with that of other techniques of investigation. Predictors of ischemic events were sought in 217 patients with known or suspected coronary artery disease who underwent exercise Tl-201 SPECT, coronary angiography and rest radionuclide angiography and who initially received medical therapy. Predictive values were determined using Cox proportional hazards regression models. During a mean (+/- SD) follow-up period of 70 +/- 19 months, 29 patients had a major ischemic event (cardiac death or myocardial infarction). Total extent of exercise defects was the best independent predictor by Tl-201 SPECT of major events (p < 0.001) and provided additional prognostic information compared with clinical, exercise testing and catheterization variables (p < 0.02). Extent of reversible Tl-201 SPECT perfusion defects provided additional prognostic information compared with extent of irreversible defects (p < 0.001) and was the sole Tl-201 SPECT variable providing additional prognostic information compared with radionuclide left ventricular ejection fraction (p < 0.02). Total extent of exercise Tl-201 SPECT defects is a powerful long-term predictor of major ischemic events that enhances the prediction provided by clinical, exercise testing and coronary angiographic data. In view of its prognostic significance, extent of reversible Tl-201 SPECT defects might provide original information about improving prognosis by coronary revascularization.

Submaximal exercise thallium-201 SPECT for assessment of interventional therapy in patients with acute myocardial infarction

Submaximal thallium-201 stress testing has been shown to provide important diagnostic and prognostic information in patients with acute myocardial infarction. The purpose of this investigation was to evaluate the diagnostic value of early submaximal stress testing and thallium-201 single photon emission computed tomography (SPECT) after interventional therapy. Scintigraphic results from 56 patients with infarctions, who underwent acute thrombolytic therapy, angioplasty, or both, were compared with late (6 weeks) functional outcome as assessed by radionuclide ventriculography and with results of discharge coronary angiography. A linear correlation was found between the extent of thallium-201 SPECT perfusion defect and late ventricular function ( r = 0.74, p < 0.01). Forty-two percent of patients with large SPECT perfusion defects had normal left ventricular ejection fractions, suggesting an overestimation of infarct size by early imaging. Sensitivity and specificity of thallium-201 SPECT for detection of coronary artery stenosis in noninfarct territories was 57% and 46%, respectively, indicating limited diagnostic definition of extent of underlying coronary artery disease. Results of follow-up coronary angiography showed a significant relationship between the size of the initial perfusion defect and early restenosis or reocclusion of the infarct artery. Thus the extent of early thallium-201 perfusion defects correlates with late functional outcome but appears to overestimate the degree of injury. Submaximal thallium-201 stress testing allows only limited characterization of underlying coronary artery disease. Early assessment of infarct size may identify a patient population at high risk for reocclusion of the infarct artery.

Altered myocardial perfusion in patients with angina pectoris or silent ischemia during exercise as assessed by quantitative thallium-201 single-photon emission computed tomography.

The extent of abnormally perfused myocardium was compared in patients with and without chest pain during treadmill exercise from a large, relatively low-risk consecutive patient population (n = 356) referred for quantitative thallium-201 single-photon emission computed tomography (SPECT). All patients had concurrent coronary angiography. Patients were excluded if they had prior coronary angioplasty or bypass surgery. Tomographic images were assessed visually and from computer-generated polar maps. Chest pain during exercise was as frequent in patients with normal coronary arteries (12%) as in those with significant (greater than 50% stenosis) coronary artery disease (CAD) (14%). In the 219 patients with significant CAD, silent ischemia was fivefold more common than symptomatic ischemia (83% versus 17%, p = 0.0001). However, there were no differences in the extent, severity, or distribution of coronary stenoses in patients with silent or symptomatic ischemia. Our major observation was that the extent of quantified SPECT perfusion defects was nearly identical in patients with (20.9 +/- 15.9%) and without (20.5 +/- 15.6%) exertional chest pain. The sensitivity for detecting the presence of CAD was significantly improved with quantitative SPECT compared with stress electrocardiography (87% versus 65%, p = 0.0001). Although scintigraphic and electrocardiographic evidence of exercise-induced ischemia were comparable in patients with chest pain (67% versus 73%, respectively; p = NS), SPECT was superior to stress electrocardiography for detecting silent myocardial ischemia (52% versus 35%, respectively; p = 0.01). The majority of patients in this study with CAD who developed ischemia during exercise testing were asymptomatic, although they exhibited an angiographic profile and extent of abnormally perfused myocardium similar to those of patients with symptomatic ischemia. The prognostic significance of quantified perfusion defects detected by SPECT remains to be assessed.