Myocardial uptake of (99m)Tc-N-NOET and (201)Tl during dobutamine infusion. Comparison with adenosine stress.

BACKGROUND: The myocardial uptake of (99m)Tc-sestamibi is attenuated by dobutamine stress, resulting in underestimation of ischemia. N-Ethyl-N-ethoxy-dithiocarbamato-N-(99m)Tc ((99m)Tc-N-NOET) is a new (99m)Tc-labeled perfusion agent that is highly extracted by the myocardium by a mechanism different from that defined for (99m)Tc-sestamibi. We therefore hypothesized that (99m)Tc-N-NOET uptake would not be attenuated by dobutamine and that (99m)Tc-N-NOET uptake would be comparable to (201)Tl uptake during dobutamine stress. METHODS AND RESULTS: In 28 open-chest dogs, after placement of a stenosis in the left anterior descending coronary artery that reduced flow reserve by >50%, adenosine (300 microgram. kg(-1). min(-1); n=15) or dobutamine (2.5 to 30 microgram. kg(-1). min(-1); n=13) was infused. During adenosine stress, the stenotic-to-normal activity ratio for (99m)Tc-N-NOET was 0.55+/-0.05. The stenotic-to-normal flow ratio was 0.33+/-0.04 at the time of (99m)Tc-N-NOET injection. During dobutamine stress, the stenotic-to-normal (99m)Tc-N-NOET activity ratio was 0.63+/-0.04, comparable to the (201)Tl activity ratio of 0.59+/-0.04. The stenotic-to-normal flow ratio was 0.47+/-0.04 at the time of (99m)Tc-N-NOET and (201)Tl injection. The relationship between (99m)Tc-N-NOET uptake and blood flow was comparable for adenosine and dobutamine stress, with no evidence of attenuation of (99m)Tc-N-NOET extraction by dobutamine. Conclusions-In the presence of coronary stenoses that reduced regional flow reserve, the myocardial uptake of (99m)Tc-N-NOET and (201)Tl are closely proportional to blood flow during both adenosine and dobutamine stress, suggesting that the adverse effect of dobutamine on (99m)Tc-sestamibi uptake is a tracer-specific phenomenon rather than a generalized effect. The clinical implication of this finding is that (99m)Tc-N-NOET might be preferable to (99m)Tc-sestamibi when used with dobutamine stress for detection of coronary stenoses.

99mTc-N-NOET myocardial uptake reflects myocardial blood flow and not viability in dogs with reperfused acute myocardial infarction.

BACKGROUND: N-Ethoxy-N-ethyl-dithiocarbamato-nitrido-(99m)Tc ((99m)Tc-N-NOET) is a new neutral lipophilic (99m)Tc-labeled myocardial perfusion agent with a high first-pass extraction fraction and delayed redistribution kinetics after transient ischemia comparable to what is observed with (201)Tl. It is unknown whether the uptake of this tracer reflects myocardial viability or just reperfusion flow in the setting of a reperfused myocardial infarction. METHODS AND RESULTS: In 13 anesthetized open-chest dogs, the left anterior descending coronary artery was occluded for 180 minutes, followed by 180 minutes of reperfusion. (201)Tl and (99m)Tc-N-NOET were injected after either 60 (group 1, n=9) or 175 (group 2, n=4) minutes of reperfusion. Myocardial blood flow was measured by radioactive microspheres, and (201)Tl and (99m)Tc-N-NOET tissue activities were determined by gamma-well counting. Normalized myocardial blood flow in the central infarct zone fell from 0.80+/-0. 03 (SEM) and 0.89+/-0.01 at baseline to 0.18+/-0.04 and 0.13+/-0.02 during the occlusion in groups 1 and 2, respectively. Normalized (201)Tl activity in these segments was 0.39+/-0.04 and 0.43+/-0.04 and reflected myocardial viability rather than reperfusion flow (P<0. 001). Normalized (99m)Tc-N-NOET activity in the same segments was 0. 84+/-0.08 and 0.64+/-0.03, respectively (P<0.01 versus (201)Tl; P=NS versus reperfusion flow) and more accurately reflected reperfusion flow (0.99+/-0.17 and 0.70+/-0.04) than residual viability. CONCLUSIONS: The myocardial uptake of (99m)Tc-N-NOET reflects reperfusion myocardial blood flow and not viability in a canine model of reperfused acute myocardial infarction. The clinical use of early (99m)Tc-N-NOET imaging to assess the success of coronary reperfusion in patients with acute myocardial infarction should be investigated.

Prognostic value of dobutamine stress technetium-99m-sestamibi single-photon emission computed tomography myocardial perfusion imaging: stratification of a high-risk population.

OBJECTIVES: This work was undertaken to define the intrinsic cardiac risk of the patient population referred for dobutamine stress perfusion imaging and to determine whether dobutamine technetium-99m ((99m)Tc)-sestamibi single-photon emission computed tomography (SPECT) imaging is capable of risk stratification in this population. BACKGROUND: In animal models, dobutamine attenuates the myocardial uptake of (99m)Tc-sestamibi resulting in underestimation of coronary stenoses. Therefore, we hypothesized that the prognostic value of dobutamine stress (99m)Tc-sestamibi SPECT myocardial perfusion imaging might be impaired, owing to reduced detection of coronary stenoses. METHODS: We reviewed the clinical outcome of 308 patients (166 women, 142 men) who underwent dobutamine stress SPECT (99m)Tc-sestamibi imaging at our institution from September 1992 through December 1996. RESULTS: During an average follow-up of 1.9 +/- 1.1 years, there were 33 hard cardiac events (18 myocardial infarctions [MI] and 15 cardiac deaths) corresponding to an annual cardiac event rate of 5.8%/year, which is significantly higher than the event rate for patients referred for exercise SPECT imaging at our institution (2.2%/year). Event rates were higher after an abnormal dobutamine (99m)Tc-sestamibi SPECT study (10.0%/year) than after a normal study (2.3%/year) (p < 0.01), even after adjusting for clinical variables. In the subgroup (n = 29) with dobutamine-induced ST-segment depression and abnormal SPECT imaging, the prognosis was poor, with annual cardiac death and nonfatal MI rates of 7.9% and 13.2%, respectively. CONCLUSIONS: Patients referred for dobutamine perfusion imaging are a high-risk population, and dobutamine stress (99m)Tc-sestamibi SPECT imaging is capable of risk stratification in these patients.

Assessment of myocardial viability using 123I-labeled iodophenylpentadecanoic acid at sustained low flow or after acute infarction and reperfusion.

UNLABELLED: 123I-labeled iodophenylpentadecanoic acid (IPPA) is a synthetic fatty acid that may be useful for determination of myocardial viability. We investigated the uptake and clearance kinetics of this tracer in canine models of ischemia and infarction. METHODS: In protocol 1, 185 MBq (5 mCi) 123I-IPPA were injected intravenously in 19 dogs with 50% left anterior descending artery (LAD) flow reduction. In 9 dogs, 201TI was coinjected. In protocol 2, 5 dogs underwent LAD occlusion for 3 h, and 123I-IPPA was injected 60 min after reperfusion. All dogs had flow measured by microspheres, regional systolic thickening by ultrasonic crystals and measurements of postmortem risk area and infarct size. Tracer activities were quantified by gamma well counting and by serial imaging. RESULTS: In protocol 1 dogs with sustained low flow (50% +/- 4%) and absence of systolic thickening (-3.2% +/- 1%), 123I-IPPA defect magnitude (LAD/left circumflex artery [LCX] count ratios) decreased from 0.65 +/- 0.02 to 0.74 +/- 0.02 at 30 min and to 0.84 +/- 0.03 at 2 h (P < 0.01), indicative of rest redistribution. Final transmural 123I-IPPA LAD/LCX activity ratio (0.99 +/- 0.05) was significantly greater than the flow ratio (0.53 +/- 0.04) at injection, confirming complete rest redistribution. The final 123I-IPPA activity ratio was significantly greater than the 201TI ratio over the 2-h period (P < 0.01). In protocol 2 dogs that underwent 3 h of total LAD occlusion and reflow (infarct size = 51% +/- 13% of risk area), viability was overestimated with 123I-IPPA, because uptake averaged 64% of normal in the central necrotic region, where flow averaged < 10% of normal. CONCLUSION: These findings suggest that serial 123I-IPPA imaging may be useful for assessing myocardial viability under conditions of sustained low flow and myocardial asynergy, such as appears to exist in patients with chronic coronary artery disease and depressed left ventricular function. In contrast, 123I-IPPA given early after reperfusion following prolonged coronary occlusion overestimates the degree of viability and therefore may not provide useful information pertaining to the degree of myocardial salvage after reflow in the setting of acute myocardial infarction.

Quantitative gated single photon emission computed tomography imaging: a counts-based method for display and measurement of regional and global ventricular systolic function.

BACKGROUND: Gated single photon emission computed tomography imaging allows simultaneous determination of myocardial perfusion and function. Quantitative perfusion measurements can be based on regional tracer uptake, but function measurements ordinarily require endocardial and epicardial edge detection, which is problematic because of the inherently low spatial resolution and image noise in single photon emission computed tomography images. This article presents methods for quantification of both function and perfusion that do not require edge detection. METHODS AND RESULTS: In SPECT imaging the partial volume effect causes changes in myocardial wall thickness to be reflected as changes in pixel counts in pixels representing the myocardial wall. This effect allows an estimation of changes in myocardial wall thickness by comparing pixel counts in end-systolic images with corresponding pixel counts in end-diastolic images. This article first describes a standard method to quantify myocardial perfusion by sampling myocardial tracer activity at rest and stress. The same method is then used to sample tracer activity in diastolic and systolic images. A new method is developed to convert the diastolic and systolic samples into quantitative estimates of regional wall thickening. A method is then developed to convert the regional wall thickening fractions into a global left ventricular ejection fraction. A normal database is presented. Receiver operating characteristic analysis is used to establish normal limits. CONCLUSION: This method requires no edge detection or geometric boundary estimates. Computer results are presented in a simple and intuitive format, which is uniform for parameters of both perfusion and function. The method is robust and produces relatively few false-positive results.

Validation of a new counts-based gated single photon emission computed tomography method for quantifying left ventricular systolic function: comparison with equilibrium radionuclide angiography.

BACKGROUND: Because myocardial wall thickness is smaller than the spatial resolution of single photon emission computed tomography (SPECT) imaging, changes in myocardial wall thickness are related to changes in maximum pixel counts via the partial volume effect, allowing for quantification of regional systolic wall thickening. We have developed a new gated SPECT method for computing the global left ventricular ejection fraction (LVEF) based entirely on changes in maximum regional myocardial counts during systolic contraction. This new method is independent of endocardial edge detection or other geometric measurements. METHODS AND RESULTS: In 23 patients the gated SPECT method was validated by comparison with radionuclide angiography. The correlation between computed LVEFs was excellent (slope = 0.97, r = 0.91). The measurement of LVEF by gated SPECT was highly reproducible, with minimal intraoperator (slope = 0.97, r = 0.97) or interoperator (slope = 1.00, r = 0.97) variability. Measurements of regional thickening indexes were also reproducible, with a mean intraoperator correlation coefficient of 0.89 +/- 0.05 (range 0.79 to 0.95) for the 14 myocardial regions. Finally, the measurement of LVEF was not significantly influenced by changes in reconstruction filter parameters over a range of cutoff frequencies from 0.16 to 0.28. CONCLUSIONS: This new counts-based gated SPECT method for measuring global left ventricular systolic function correlates well with radionuclide angiography, is highly reproducible, and has theoretic advantages over geometric methods.

Myocardial uptake and redistribution of 99mTc-N-NOET in dogs with either sustained coronary low flow or transient coronary occlusion: comparison with 201Tl and myocardial blood flow.

BACKGROUND: 99mTc-N-NOET (NOET) is a new myocardial perfusion imaging agent that redistributes over time. We sought to better define the redistribution kinetics of NOET using open-chest canine models of sustained low coronary flow (protocol 1) and transient coronary occlusion followed by reflow (protocol 2). METHODS AND RESULTS: In protocol 1 (n=10), NOET and 201Tl were injected during low flow in the left anterior descending coronary artery (LAD) that was sustained for 2 hours. Protocol 2 dogs (n=6) were injected with NOET during 20 minutes of LAD occlusion followed by 2 hours of reflow. In both protocols, serial NOET planar images were acquired, and myocardial flow and 2-hour tracer activities were determined by gamma-well counting. Defect resolution was observed on images in both protocols. Initial defect count ratios, reflecting flow disparity at injection (0.66+/-0.03 and 0.57+/-0.04, respectively), increased over 2 hours (0.73+/-0.02 and 0.75+/-0.04, respectively; P<.001 versus initial). Quantitative imaging showed that NOET redistribution resulted from greater clearance from normal areas versus low-flow or transiently occluded areas. In protocol 1, 2-hour NOET and 201Tl stenotic-to-normal tissue activity ratios were similar (0.76+/-0.06 versus 0.73+/-0.04, P=NS) and higher than injection flow ratios (0.52+/-0.06 and 0.56+/-0.07, respectively, P<.001), consistent with tracer redistribution. In protocol 2, NOET redistributed to an even greater extent (injection flow ratio, 0.27+/-0.04; 2-hour tissue activity ratio, 0.84+/-0.03, P<.001). CONCLUSIONS: NOET is the first 99mTc-labeled myocardial imaging agent with kinetics similar to 201Tl in experimental models, permitting redistribution imaging. NOET appears to be a promising agent for assessing patients with coronary artery disease.

Effects of dobutamine stress on myocardial blood flow, 99mTc sestamibi uptake, and systolic wall thickening in the presence of coronary artery stenoses: implications for dobutamine stress testing.

BACKGROUND: Although dobutamine stress is used with both 99mTc sestamibi (sestamibi) myocardial perfusion imaging and echocardiography for detecting coronary artery stenoses, the impact of stenosis severity on test end points (myocardial sestamibi uptake and systolic thickening, respectively) has not been clearly defined. METHODS AND RESULTS: In 15 open-chest dogs, dobutamine (2.5 to 30 microg x kg(-1) x min(-1)) was infused after placement of an LAD stenosis that reduced (n=8) or abolished (n=7) flow reserve. In dogs with reduced flow reserve, the stenotic-to-normal sestamibi activity ratio (0.86+/-0.03) significantly underestimated the approximately 2-to-1 dobutamine-induced flow disparity at the time of sestamibi injection (flow ratio, 0.53+/-0.04; P<.001). Stenotic-zone thickening increased at low but not at higher doses of dobutamine (2.9+/-0.4 versus 4.2+/-0.4 mm in normal zone at peak dobutamine; P=.055) but did not fall below baseline (2.7+/-0.3 mm). Similarly, in dogs with absent flow reserve, the sestamibi activity ratio (0.78+/-0.02) underestimated the approximately 2.5-to-1 dobutamine-induced flow disparity (flow ratio, 0.41+/-0.05; P<.001), and failure to increase systolic thickening was observed in the stenotic zone (2.7+/-0.4 versus 4.6+/-0.3 mm in the normal zone at peak stress, P<.01). In both groups of dogs, myocardial sestamibi uptake and image defect magnitudes were less than expected for the dobutamine-induced hyperemia, suggesting that dobutamine adversely affects myocardial sestamibi binding. Finally, a significant reduction in stenotic-zone thickening was seen during postdobutamine recovery, consistent with myocardial stunning. CONCLUSIONS: In the presence of stenoses that reduced or abolished regional flow reserve, (1) myocardial sestamibi uptake significantly underestimated the dobutamine-induced flow heterogeneity, (2) a "failure to increase systolic thickening" rather than a reduction in thickening was observed during dobutamine stress, and (3) myocardial stunning was observed during postdobutamine recovery.