Kenneth Van Train

Identification of severe and extensive coronary artery disease by automatic measurement of transient ischemic dilation of the left ventricle in dual-isotope myocardial perfusion SPECT☆

OBJECTIVES This study sought to assess whether a transient ischemic dilation ratio, determined from automatically derived stress and rest left ventricular volumes during stress technetium-99m (Tc-99m) sestamibi/rest thallium-201 dual-isotope myocardial perfusion single-photon emission computed tomography (SPECT), is useful for the identification of patients with severe and extensive coronary artery disease. BACKGROUND Transient ischemic dilation of the left ventricle on stress/redistribution thallium-201 scintigraphy has been shown to be a clinically useful marker of severe and extensive coronary artery disease. However, in practice, its assessment is highly subjective. This study automatically assessed the transient ischemic dilation ratio on the basis of a previously described algorithm to estimate three-dimensional ventricular boundaries. METHODS Normal limits for the transient ischemic dilation ratio were developed using data from 54 patients with a low likelihood (< 5%) of coronary artery disease, and criteria for abnormality were developed based on data from 97 who under-went catheterization, of whom 34 had severe and extensive coronary artery disease, defined as > or = 90% stenosis in the proximal left anterior descending coronary artery or in two or more coronary arteries, and 63 had no coronary artery disease (15 patients) or mild to moderate coronary artery disease (48 patients). The criteria were then tested in a validation cohort of 77 additional patients who underwent catheterization, of whom 36 had severe and extensive coronary artery disease. The quantitative results of the dilation ratio were compared with the visual results of the dilation ratio and perfusion defect analysis. RESULTS For normal limits, receiver operating characteristic curve analysis showed that abnormal transient ischemic dilation ratio values corresponded to left ventricular endocardial volume ratios > 1.22 (mean +/- 2 SD). Transient ischemic dilation assessment using these criteria for abnormality showed high sensitivity (24 [71%] of 34) and very high specificity (60 [95%] of 63) for severe and extensive coronary artery disease. When the analysis was applied to the prospective catheterization group, similar sensitivity and specificity for severe and extensive coronary artery disease were observed (77% and 92%, respectively). Significant agreement (p = 0.0001) was found between the degree of transient ischemic dilation and the Tc-99m sestamibi defect extent, the latter assessed by semiquantitative visual analysis (summed stress score). CONCLUSIONS The automatic measurement of transient ischemic dilation in dual-isotope myocardial perfusion SPECT is a clinically useful marker that is sensitive and highly specific for detection of severe and extensive coronary artery disease.

Technical aspects of myocardial spect imaging with technetium-99m sestamibi

Most reports to date using single photon emission computed tomography (SPECT) with technetium-99m (Tc-99m) sestamibi have used acquisition parameters that were optimized for thallium-201. To fully utilize the superior imaging characteristics of Tc-99m sestamibi, there is a need to optimize the technical aspects of SPECT imaging for this agent. Performance can be enhanced through the careful selection of optimal radiopharmaceutical doses, imaging sequences, acquisition parameters, reconstruction filters, perfusion quantification methods and multidimensional methods for visualizing perfusion distribution. The current report describes theoretical considerations, phantom studies and preliminary patient results that have led to optimized protocols, developed at Emory University and Cedars-Sinai Medical Center, for same-day rest-stress studies, given existing instrumentation and recommended dose limits. The optimizations were designed to fit a low-dose-high-dose rest-stress same-day imaging protocol. A principal change in the acquisition parameters compared with previous Tc-99m sestamibi protocols is the use of a high-resolution collimator. The approach is being developed in both prone and supine positions. A new method for extracting a 3-dimensional myocardial count distribution has been developed that uses spherical coordinates to sample the apical region and cylindrical coordinates to sample the rest of the myocardium. New methods for visualizing the myocardial distribution in multiple dimensions are also described, with improved 2-dimensional, as well as 3- and 4-dimensional (3 dimensions plus time) displays. In the improved 2-dimensional display, distance-weighted and volume-weighted polar maps are used that appear to significantly improve the representation of defect location and defect extent, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effective risk stratification using exercise myocardial perfusion SPECT in women: Gender-related differences in prognostic nuclear testing

OBJECTIVES This study was designed to evaluate the incremental prognostic value over clinical and exercise variables of rest thallium-201/exercise technetium-99m sestamibi single-photon emission computed tomography (SPECT) in women compared with men and to determine whether this test can be used to effectively risk stratify patients of both genders. BACKGROUND To minimize the previously described gender-related bias in the evaluation of coronary artery disease in women, there is a need to identify a noninvasive testing strategy that is able to accurately and effectively risk stratify women. METHODS We identified 4,136 consecutive patients (2,742 men, 1,394 women) who underwent dual-isotope SPECT. The incremental value of nuclear testing was determined using both a stepwise Cox proportional hazards model and Kaplan-Meier survival analysis. Receiver operating characteristic curve analysis was performed to determine test discrimination for high risk patients in men and women. RESULTS The patient population was followed up for 20 +/- 5 months for events (cardiac death or nonfatal myocardial infarction). During this time, 63 myocardial infarctions and 32 cardiac deaths occurred in the men, and 31 myocardial infarctions and 14 cardiac deaths occurred in the women. Nuclear testing significantly stratified both men and women irrespective of their rest electrocardiogram. Cox proportional hazards analysis revealed that nuclear testing added incremental prognostic value in both men and women after inclusion of the most predictive clinical exercise variables (overall chi-square 89 in men vs. 120 in women, p < 0.005). Kaplan-Meier survival analysis demonstrated that nuclear testing further stratified men and women with both intermediate to high and low prescan likelihoods of coronary artery disease (p < 0.005 for all). Receiver operating characteristic curve analysis demonstrated superior discrimination for the nuclear scan results in identifying high risk women than men (area under the curve: 0.84 +/- 0.03 vs 0.71 +/- 0.03 in men, p < 0005). The odds ratio comparing event rates in patients with women than in men, suggesting superior stratification using nuclear testing in women. CONCLUSIONS Dual-isotope myocardial perfusion imaging yields incremental prognostic value in both men and women. This modality identifies low risk women and men equally well but relatively high risk women more accurately than relatively high risk men and, thus, is able to stratify women more effectively than men.

Quantitative single photon emission computed thallium-201 tomography for detection and localization of coronary artery disease: optimization and prospective validation of a new technique

One hundred eight-three men underwent stress-redistribution thallium-201 myocardial perfusion tomography. After evaluation of various preprocessing filters in a phantom study, the Butterworth filter with a frequency cutoff of 0.2 cycles/pixel, order 5 (which provided optimal filter power) was used in the back projection algorithm of the patient studies. All short-axis and apical portions of vertical long-axis images were quantified by dividing each myocardial slice into 60 equal sectors and displaying the maximal count per sector as a linear profile. In a pilot group consisting of 20 normal men (less than 5% likelihood of coronary artery disease) and 25 men with coronary artery disease (greater than or equal to 50% coronary stenosis by angiography), profiles representing the lowest observed value below the mean normal profiles provided the best threshold for defining normal limits. Abnormal portions of the patient profiles were plotted on a two-dimensional polar map. The polar map was divided into 102 sectors, and sectors with a probability of greater than or equal to 80% for disease of each one of the three major coronary arteries were clustered to represent specific coronary artery territories. Receiver operating characteristic curve analysis for defect size showed that the optimal threshold for defining a definite perfusion defect was 12% for the left anterior descending and left circumflex and 8% for the right coronary artery territories. These criteria were prospectively applied to an additional 92 patients with angiographic coronary artery disease, 18 patients with normal coronary arteriograms and 28 patients with less than 5% likelihood of coronary disease. Sensitivity, specificity (in patients with normal coronary arteriograms) and normalcy rate (in patients with less than 5% likelihood of coronary artery disease) for overall detection of coronary disease were 96%, 56% and 86%, respectively. Sensitivity and specificity for identification of individual diseased vessels were, respectively, 78% and 85% for the left anterior descending, 79% and 60% for the left circumflex and 81% and 71% for the right coronary artery. These results were not significantly different from those of the pilot group. An optimized quantitative method for interpretation of stress thallium-201 myocardial perfusion tomography has been developed. Prospective application of this method indicates that the technique is accurate for the overall detection of coronary artery disease and identification of disease in individual arteries.

Myocardial perfusion imaging with technetium-99m sestamibi SPECT in the evaluation of coronary artery disease

Technetium-99m (Tc-99m) sestamibi is a new myocardial perfusion imaging agent that offers significant advantages over thallium-201 (Tl-201) for myocardial perfusion imaging. The results of the current clinical trials using acquisition and processing parameters similar to those for Tl-201 and a separate (2-day) injection protocol suggest that Tc-99m sestamibi and Tl-201 single photon emission computed tomography (SPECT) provide similar information with respect to detection of myocardial perfusion defects, assessment of the pattern of defect reversibility, overall detection of coronary artery disease (CAD) and detection of disease in individual coronary arteries. Tc-99m sestamibi SPECT appears to be superior to Tc-99m sestamibi planar imaging because the former provides a higher defect contrast and is more accurate for detection of disease in individual coronary arteries. Research is currently under way addressing optimization of acquisition and processing of Tc-99m sestamibi studies and development of quantitative algorithms for detection and localization of CAD and sizing of transmural and nontransmural myocardial perfusion defects. It is expected that with the implementation of the final results of these new developments, further significant improvement in image quality will be attained, which in turn will further increase the confidence in image interpretation. Development of algorithms for analysis of end-diastolic myocardial images may allow better evaluation of small and nontransmural myocardial defects. Furthermore, gated studies may provide valuable information with respect to regional myocardial wall motion and wall thickening. With the implementation of algorithms for attenuation and scatter correction, the overall specificity of Tc-99m sestamibi SPECT should improve significantly because of a substantial decrease in the occurrence of attenuation-related image artifacts.(ABSTRACT TRUNCATED AT 250 WORDS)

Technetium 99m sestamibi in the assessment of chronic coronary artery disease

Extensive work has already been performed with regard to both planar and single photon emission computed (SPECT) technetium 99m sestamibi studies. Before widespread application of optimized acquisition and processing methods, clinical results between 99mTc sestamibi and thallium 201 were remarkably similar. It is anticipated that as techniques for 99mTc sestamibi planar and SPECT imaging become optimized, improvements in sensitivity and specificity for detection of coronary artery disease, over those observed with 201TI, might be forthcoming. This expectation is based on the improved image quality inherent in the use of the 99mTc agent with its higher count rate and higher energy. This improvement in image quality may be a principal reason for laboratories to switch from 201TI to 99mTc sestamibi imaging. It is anticipated that, with improved imaging characteristics, it will be easier for the average community hospital to obtain higher quality planar or SPECT imaging using 99mTc sestamibi rather than 201TI. In addition to improved image quality, the characteristics of 99mTc sestamibi allow gated planar or SPECT perfusion images to be obtained. It has been suggested that stress-gated SPECT sestamibi studies may provide all the information contained in a stress-rest nongated 99mTc sestamibi study, thereby potentially increasing patient throughput, a major concern with SPECT. Throughput can also be increased by using dual-isotope approaches with rest 201TI and stress technetium sestamibi acquisitions, employing either separate or simultaneous imaging with which the entire study can be accomplished in less than 2 hours. With simultaneous dual-isotope acquisition, camera time can be reduced by 50%. Finally, 99mTc sestamibi offers the advantage of the ability to perform first-pass exercise ventricular function and SPECT myocardial perfusion studies with a single injection of tracer. Regarding the assessment of myocardial viability, results to date suggest a very high degree of concordance between 201TI and 99mTc sestamibi studies using either planar or SPECT acquisition techniques. Correlative rest studies with both tracers will be of particular interest, as will preoperative and postoperative and position emission tomography correlation studies.

Pharmacologic stress dual-isotope myocardial perfusion single-photon emission computed tomography

Separate-acquisition rest thallium-201/exercise technetium-99m sestamibi (sestamibi) dual-isotope single-photon emission computed tomography (SPECT) has been shown to be effective for assessment of myocardial perfusion and viability. The present study was designed to validate the dual-isotope approach when used in conjunction with pharmacologic stress. All patients had rest 201TI SPECT followed immediately by adenosine (n = 82) or dipyridamole (n = 50) infusion and sestamibi injection. Sestamibi SPECT was performed 1 hour later. The entire study lasted < 2.5 hours. The patient population was categorized into three groups: 51 consecutive patients with coronary angiography and no previous myocardial infarction (group I), 58 consecutive patients with a low prescintigraphic test likelihood of coronary artery disease (group II), and 23 consecutive catheterized patients with remote Q-wave myocardial infarction (group III). For group I patients, the sensitivity and specificity for dual-isotope SPECT were 92% (35 of 38) and 85% (11 of 13), respectively, when > or = 50% coronary artery narrowing was considered significant and were 97% (34 of 35) and 81% (13 of 16) respectively, when > or = 70% narrowing was considered significant. The normalcy rate among the 58 patients of group II was 96%. Comparisons for pattern of stress-defect reversibility demonstrated that of the 97 stress defects within the infarct zones (group III), 15% were reversible and 85% were nonreversible. In contrast, of the 227 stress defects within the diseased (> or = 50% stenosis) vessel zones of the group I patients, 93% were reversible and 7% were noreversible (p < 0.001 vs group III). In conclusion, separate acquisition rest 201-TI/pharmacologic stress sestamibi dual-isotope SPECT is an efficient myocardial perfusion imaging protocol with high accuracy for detection and assessment of angiographically significant coronary artery disease.

Comparison of SPECT using technetium-99m agents and thallium-201 and PET for the assessment of myocardial perfusion and viability

This report reviews the applications of tomographic imaging with current and new tracers in assessing myocardial perfusion and viability. Multiple studies with thallium-201 (TI-201) single photon emission computed tomography (SPECT) imaging for the detection of coronary artery disease (CAD) have demonstrated high sensitivity, high rates of normalcy and high reproducibility. In assessing viability, fixed defects are frequently detected in viable zones in 4-hour studies with TI-201 imaging. Redistribution imaging performed 18 to 72 hours after injection or reinjection of TI-201 before 4-hour redistribution imaging has been shown to improve accuracy of viability assessment. TI-201 SPECT studies are limited by the suboptimal physical properties of TI-201, which result in variable image quality. The 2 new technetium-99m (Tc-99m) - labeled myocardial perfusion tracers offer the ability to inject much higher amounts of radioactivity, making it possible to assess ventricular function as well as myocardial perfusion from the same injection of radiotracer. Tc-99m sestamibi has very slow myocardial clearance, which allows for prolonged imaging time and results in image quality superior to that obtained with TI-201 and Tc-99m teboroxime. The combination of minimal redistribution of Tc-99m sestamibi and high count rates makes gated SPECT imaging feasible, and also permits assessment of patients with acute ischemic syndromes by uncoupling the time of injection from the time of imaging. The combination of high image quality and first-pass exercise capabilities may lead to a choice of this agent over TI-201 for assessment of chronic CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive quantification of the extent of jeopardized myocardium in patients with single-vessel coronary disease by stress thallium-201 single-photon emission computerized rotational tomography

In 22 patients with single-vessel coronary artery disease and no history of infarction, stress Tl-201 rotational tomography was used to quantify the extent of jeopardized myocardium. The vertical long- and short-axis tomograms were quantified by means of maximum-count circumferential profile analysis. The scintigraphic extent of jeopardized myocardium was expressed as the percentage of profile points falling 2.5 standard deviations below a previously established mean normal profile and was correlated to a quantitatively expressed angiographic extent of jeopardized myocardium. The extent of jeopardized myocardium varied from 1% to 55% by tomography and 8% to 50% by angiography and correlated with an r = 0.79 and a 10% standard error of the estimate. Defect intensity, reflecting the mean depth by which the abnormal points fell below the normal value of greater than or equal to 10%, was 100% specific for a coronary stenosis of greater than or equal to 70%. In conclusion, this study demonstrates that: patients with single-vessel disease have highly variable extents of hypoperfused myocardium defined by Tl-201 tomography and coronary arteriography, there is a fair relationship between angiographic jeopardy score and perfusion defects by Tl-201 tomography during exercise, and Tl-201 tomography may be used to noninvasively determine the extent of hypoperfused myocardium in coronary artery disease.

Thallium-201 stress-redistribution myocardial rotational tomography: development of criteria for visual interpretation

Despite high sensitivity and specificity for overall detection of coronary artery disease (CAD), planar stress-redistribution thallium-201 (Tl-201) scintigraphy remains suboptimal in localizing disease, because of overlap of myocardial segments. Single photon emission computerized tomography (SPECT), by providing three-dimensional representation of myocardial Tl-201, offers promise for improved localization of CAD. In 50 consecutive patients (22 normal and 28 with CAD), who underwent SPECT stress-redistribution Tl-201 imaging, we systemically developed visual interpretive criteria for perfusion abnormality on SPECT. For overall detection of disease, the best criterion for abnormality was greater than or equal to 8 sectors of moderately decreased Tl-201 uptake. With this criterion, the true positive and true negative rates for overall detection of disease were 96% and 91%, respectively. The best criterion for significant defect in the anterior or posterior coronary circulation was greater than or equal to 3 sectors of moderately decreased Tl-201 uptake. With this criterion, the true positive and true negative rates for anterior circulation disease were 71% and 100%, respectively. With respect to posterior circulation disease, the true positive and true negative rates were 100% and 50%, respectively. Regarding identification of dual circulation disease, the true positive and true negative rates were 71% and 82%, respectively.