Single photon emission computed tomography with technetium-99m hexakis 2-methoxyisobutyl isonitrile in acute myocardial infarction before and after thrombolytic treatment: assessment of salvaged myocardium and prediction of late functional recovery

Single photon emission computed tomography (SPECT) with technetium-99m hexakis 2-methoxyisobutyl isonitrile was investigated as a method to evaluate the results of intravenous thrombolytic treatment in 14 patients (11 men and 3 women) with acute myocardial infarction admitted to the coronary care unit within 4 h of the onset of symptoms. All patients received an injection of 740 MBq of the tracer before starting the thrombolytic therapy, and isonitrile tomography was performed 3 to 4 h later. The tomographic study was repeated 5 days after the acute event. The results of thrombolytic treatment were independently evaluated taking into account the clinical, electrocardiographic (ECG) and enzymatic data and the findings of left ventricular and coronary angiography. Furthermore, all patients were studied with two-dimensional echocardiography on admission, 5 days later and 1 month later. The site and extent of the perfusion defects on admission scintigraphy were consonant with the ECG and echocardiographic findings. A good correlation could be established between the 5 day scintigraphic estimate of infarct dimension and the enzymatic infarct size (r = 0.907, p less than 0.00002). The comparison between pre- and postthrombolytic treatment images enabled the identification of successful and unsuccessful reperfusion even in patients whose other noninvasive findings were inconclusive. Finally, the reduction in defect size predicted late functional improvement that was demonstrated by echocardiography performed 1 month later (r = 0.89, p less than 0.00005). The results of the study suggest the feasibility and the possible usefulness of isonitrile tomography in demonstrating the presence and size of myocardial damage and in assessing the extent of myocardial salvage after thrombolytic therapy in acute myocardial infarction.     

Early quantification of experimental myocardial infarction with technetium-99m glucoheptonate: scintigraphic and anatomic studies.

Recent advances in understanding of the pathophysiology of myocardial necrosis indicate the need for a noninvasive method that will allow detection and quantification of infarcts in the first few hours after the onset of infarction. Myocardial infarct scintigraphy using technetium-99m glucoheptonate is capable of detecting infarction in dogs and man within 4 to 6 hours of onset. Studies were performed in 45 dogs with acute myocardial infarction: 28 with with an anterior infarct, 5 with an inferior infarct, 6 with an anterior infarct studied after infusion of mannitol and 6 with ligation of the left anterior descending coronary coronary artery and reperfusion of the ischemic area. The dogs were given 20 m Ci of technetium-99m glucoheptonate 1 hour after coronary occlusion, subjected to imaging 5 to 9 hours later and then killed. The experiments revealed that (1) scintigraphic infarct size correlated with infarct weight for anterior (r = 0.85) and inferior (r = 0.88) infarcts; (2) technetium-99m glucoheptonate also concentrated in a rim of myocardium around the infarct that probably represented the ischemic zone; and (3) technetium-99m glucoheptonate uptake by infarcted myocardium could be greatly increased with mannitol and reperfusion.     

Serial quantitative planar technetium-99m isonitrile imaging in acute myocardial infarction: efficacy for noninvasive assessment of thrombolytic therapy

Technetium-99m isonitrile is a new myocardial perfusion imaging agent that accumulates according to the distribution of myocardial blood flow. However, unlike thallium-201, it does not redistribute over time. This imaging agent was used with serial quantitative planar imaging to assess the initial risk area of infarction, its change over time and the relation to infarct-related artery patency in 30 patients with a first acute myocardial infarction. Twenty-three of 30 patients were treated with recombinant tissue-type plasminogen activator (rt-PA) within 4 h after the onset of chest pain. Seven patients were treated in the conventional manner without thrombolytic therapy. Technetium-99m isonitrile was injected before or at the initiation of thrombolytic therapy, and imaging was performed several hours later. These initial images demonstrated the area at risk. Repeat imaging was performed 18 to 48 h later and at 6 to 14 days after the onset of myocardial infarction to visualize the ultimate extent of infarction. The initial area at risk varied greatly (range defect integral 2 to 61) both in patients treated with rt-PA and in those who received conventional treatment. For the total group, the initial imaging defect decreased in size in 20 patients and was unchanged or larger in 10 patients. Patients with a patent infarct-related artery had a significantly greater decrease in defect size than did patients with persistent coronary occlusion (-51 +/- 38% versus -1 +/- 26%, p = 0.0001). All patients with a decrease in defect size greater than 30% had a patent infarct-related artery. In 12 patients who also had predischarge quantitative exercise thallium-201 imaging, good agreement existed between the extent and severity of myocardial perfusion defect on the last technetium-99m isonitrile study before discharge and that noted on delayed thallium-201 imaging. It is concluded that serial planar technetium-99m isonitrile myocardial imaging in patients with acute myocardial infarction undergoing thrombolytic therapy offers a new quantitative noninvasive approach for assessment of the initial risk zone as well as the success of reperfusion.     

Determinants of infarct size in reperfusion therapy for acute myocardial infarction.

BACKGROUND. Experimental animal studies have demonstrated that myocardium at risk, residual collateral flow, and duration of coronary artery occlusion are important determinants of final infarct size. The present study examined these variables in patients with acute myocardial infarction in relation to final infarct size. METHODS AND RESULTS. Myocardium at risk was assessed with hexakis(2-methoxyisobutyl isonitrile) technetium (I) (99mTc sestamibi) in 89 patients with first-time myocardial infarction (anterior, 48 patients; inferior, 41 patients). All patients had successful reperfusion therapy with either intravenous thrombolysis (32 patients) or primary coronary angioplasty (57 patients) within 24 hours of the onset of chest pain (4.7 +/- 3.9 hours; range, 0.5-21.5 hours) documented by coronary angiography. 99mTc sestamibi was injected intravenously before reperfusion therapy, and tomographic imaging was performed 1-6 hours later. Myocardium at risk was quantitated for each patient and expressed as a percentage of the left ventricle: 35 +/- 19%; range, 2-73%. Collateral flow was estimated by both invasive and noninvasive methods. Fifty-three patients with TIMI grade 0 or I flow who underwent primary coronary angioplasty had collateral flow graded angiographically (0-3) before the first balloon inflation. All patients had collateral flow estimated noninvasively from the acute sestamibi short-axis profile curve by three methods that assess the severity of the perfusion defect. Each of these three methods was significantly associated with angiographic collateral grade. Final infarct size was determined at hospital discharge by a second sestamibi study (17 +/- 17%; range, 0-59%). Myocardium at risk (r = 0.61, p less than 0.0001), angiographic collateral grade (p = 0.0003), and radionuclide estimates of collateral flow (r = 0.69-0.70, all p less than 0.0001) were all significantly associated with final infarct size. The time to reperfusion therapy was not significantly associated with final infarct size by univariate analysis (r = 0.18, p = 0.10). Two multivariate models were constructed to determine which variables were independently associated with final infarct size. In the invasive model, myocardium at risk, angiographic collateral grade with an interaction term for infarct location, and time to reperfusion were all independently significant and accounted for 70% of the variability in final infarct size. The noninvasive model, which substituted a radionuclide estimate of collateral flow for angiographic collateral grade, showed nearly identical results, accounting for 68% of the variability in infarct size in patients where the infarct artery was known to be occluded. When all patients were included (patients with and without acute angiography), the noninvasive model accounted for 59% of the variability in infarct size. CONCLUSIONS. Myocardium at risk, collateral flow, and duration of coronary occlusion are each independently associated with final infarct size and account for most of its variability. Ideally, all three parameters should be examined in evaluation of the efficacy of new treatment strategies for acute myocardial infarction.     

Effect of infarct location on myocardial salvage assessed by technetium-99m isonitrile.

To investigate the influence of infarct location on myocardial salvage, technetium-99m isonitrile was injected into 43 patients with a first myocardial infarction before early reperfusion therapy. Primary coronary angioplasty was performed in 22 patients and successful intravenous thrombolytic therapy was given to 15 patients, both within 6 h of the onset of chest pain. Patency of the infarct-related artery was confirmed by angiography in all 37 patients. In the remaining six patients (three with and three without early thrombolytic therapy) the infarct-related artery remained occluded. Single photon emission computed tomography was performed within 6 h of the administration of technetium-99m isonitrile and repeated at the time of hospital discharge. Radionuclide ejection fraction at discharge was significantly lower for patients with anterior infarction (0.41 +/- 0.12) than for those with inferior infarction (0.56 +/- 0.09, p less than 0.001). Early perfusion defect size, a measure of myocardium at risk, was greater in patients with anterior than in those with inferior infarction (52 +/- 9% vs. 18 +/- 10% of the left ventricle, p = 0.0001) as was final defect size (30 +/- 20% vs. 9 +/- 8%, p less than 0.01). The change in myocardial perfusion, an estimate of myocardial salvage, was also greater in patients with anterior infarction (24 +/- 16% vs. 10 +/- 7%, p less than 0.01). However, the proportion of jeopardized myocardium salvaged (salvage index) was not significantly different between patients with anterior or inferior infarction (0.49 +/- 0.34 vs. 0.59 +/- 0.35, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of myocardial infarction fraction using single photon emission computed tomography

Although infarct size correlates generally with prognosis after acute myocardial infarction, an absolute measure of infarct size may have differing prognostic significance depending on absolute left ventricular mass. To test the hypothesis that single photon emission computed tomography can accurately measure myocardial infarct size as a percent of total left ventricular mass ("infarction fraction"), thallium-201 and technetium-99m pyrophosphate tomograms were acquired in 21 dogs 24 to 48 hours after fixed occlusion of the left anterior descending or circumflex coronary artery. Pathologic infarct weight was measured as the myocardial mass that showed no staining with triphenyltetrazolium chloride. Scintigraphic infarct mass by technetium-99m pyrophosphate was calculated from the total number of left ventricular volume elements (voxels) demonstrating technetium-99m pyrophosphate uptake X voxel dimension [( 0.476 cm]3) X specific gravity of myocardium (1.05 g/cm3). Scintigraphic left ventricular mass was calculated in a similar fashion using an overlay of the thallium-201 and technetium-99m pyrophosphate scans. The "infarction fraction" was calculated as: infarction fraction = infarct mass/left ventricular mass. There was good correlation between single photon emission computed tomography and pathologic measurements of infarct mass (technetium-99m pyrophosphate mass = 1.01 X pathologic infarct mass + 0.96; r = 0.98), left ventricular mass (single photon emission computed tomographic left ventricular mass = 0.60 X pathologic left ventricular mass + 37.4; r = 0.86) and "infarction fraction" (single photon emission computed tomographic infarction fraction = 1.09 X pathologic infarction fraction - 1.7; r = 0.94).(ABSTRACT TRUNCATED AT 250 WORDS)     

Significance of technetium-99m/thallium-201 overlap on simultaneous dual emission computed tomography in acute myocardial infarction

To examine the significance of technetium-99m pyrophosphate/thallium-201 scintigraphic overlap as an indicator of identifying early coronary reperfusion (less than or equal to 3 hours), 32 patients, in whom coronary recanalization was attempted for acute myocardial infarction (AMI), underwent myocardial imaging 3 days after the onset of AMI. The imaging was performed by simultaneous dual emission computed tomography, which allows simultaneous recording of technetium-99m pyrophosphate and thallium-201 images and comparison between both images in the same slice. The patients were separated into 3 groups: 9 patients in whom reperfusion was successful and showed scintigraphic overlap (group A), 12 with successful recanalization but no overlap (group B) and 11 with neither coronary reflow nor overlap (group C). No patient in whom reperfusion failed showed scintigraphic overlap (p less than 0.05). Groups A and B were comparable in age, infarct vessel, collateral circulation, residual coronary stenosis and cumulative release of creatine kinase-MB isoenzyme. However, compared with group B, group A had a shorter interval between onset of AMi and reflow (2.5 +/- 0.8 vs 4.8 +/- 1.3 hours, p less than 0.001). The presence of scintigraphic overlap identified early coronary reflow with a sensitivity of 80%, specificity of 91%, positive predictive accuracy of 89% and negative predictive accuracy of 83%. Thus, technetium-99m/thallium-201 overlap on dual emission computed tomography can be used as an index of documenting early recanalization and might reflect the presence of salvaged myocardium adjacent to the necrotic tissue.     

Planar myocardial scintigraphy with 99mTc sestamibi for the evaluation of the infarct area and the efficacy of the thrombolytic therapy]

BACKGROUND: Nuclear cardiology permits the estimation of myocardial infarction size and the result of the thrombolytic therapy. The aim of the study was to demonstrate the feasibility of the planar myocardial scintigraphy with tecnetium-99m-sestamibi in the coronary intensive care unit for the early identification of the infarct size and the results of the thrombolytic therapy. MATERIAL AND METHODS: We studied 15 patients affected by a first acute myocardial infarction (AMI), 10 anterior and 5 inferior wall, treated with thrombolysis (APSAC 30U i.v.) within and interval of 3 hours from the symptoms onset, tecnetium-99m-sestamibi was injected before thrombolysis and after 3 +/- 1 hours the planar imaging was registered with a mobile gamma-camera. Scintigraphic evaluation was repeated after 24 hours and before patient discharge. Within 48 hours from the thrombolytic therapy the coronary angiography was performed for the demonstration of patency of the infarct-related artery. The left ventricle myocardial perfusion was divided in the 3 planar projections into 13 segments. The perfusion in each segment was evaluated with a perfusion score: 0 = normal, 1 = moderately reduced, 2 = severely reduced, 3 = absent. The sum of the hypoperfused segments represented the infarct size. A perfusion score improvement greater than 40% was considered a marker of reperfusion. RESULTS: The infarct size involved 4.2 +/- 1.5 segments in the anterior and 2 +/- 0.8 segments in the inferior wall infarctions (p < 0.05). The scintigraphic imaging made 24 hours after AMI allowed the diagnosis of coronary reperfusion in 10 patients. The coronarography demonstrated the infarct related artery patency in 14 patients. The nuclear imaging at patient discharge provided the diagnosis or reperfusion in 11 cases and demonstrated an improvement of the myocardial perfusion score in 8 cases. CONCLUSIONS: In patients with AMI treated with thrombolysis the scintigraphic imaging with tecnetium-99m-sestamibi is feasible with a mobile gamma-camera in the intensive coronary care unit. The quality of planar imaging is good and allows the evaluation of myocardial infarct size and the efficiency of thrombolytic therapy. An earlier scintigraphic imaging should be taken into consideration for a more timely non-invasive evaluation of patients who need coronary angiography and, if necessary, a rescue-PTCA.     

Quantification of myocardial injury produced by temporary coronary artery occlusion and reflow with technetium-99m-pyrophosphate

Previously, technetium-99m-stannous pyrophosphate (99mTc-PPi) has been used to localize and estimate the size of myocardial infarcts in animals after permanent coronary artery occlusion. This study tested the hypothesis that 99mTc-PPi accurately sizes myocardial infarctions produced by temporary coronary artery occlusion and reflow in dogs. Three groups of dogs were studied: group A underwent 3 hr of occlusion followed by 2 hr of reperfusion, with 99mTc-PPi injected 10 min after reflow (n = 10); group B underwent 3 hr of occlusion followed by 2 hr of reperfusion, with 99mTc-PPi injected 90 min after reflow (n = 11); and group C underwent 3 hr of occlusion followed by reflow with 99mTc-PPi injected at 10 min and again at 48 hr after reflow (n = 5). Myocardial slices from group A and B dogs were imaged in vitro. Group C dogs were imaged with single photon-emission computed tomography (SPECT) in vivo, and myocardial slices were imaged in vitro at the conclusion of the study. The extent of myocardial infarction was defined with triphenyltetrazolium chloride (TTC) staining, and coronary blood flow was estimated with radioactive microspheres. In addition, transmural myocardial tissue samples were taken from the center of the myocardial infarction, the lateral portion of the myocardial infarction, the normal myocardium adjacent to the lateral aspect of the infarcts, and from the normal myocardium and counted for 99mTc-PPi activity. A significant correlation was found between infarct size determined by areas of increased 99mTc-PPi uptake and that estimated from TTC staining for both group A (r = .89) and group B animals (r = .98).(ABSTRACT TRUNCATED AT 250 WORDS)     

Detection and sizing of myocardial ischemia and infarction by nuclear magnetic resonance imaging in the canine heart

The usefulness of NMR imaging to size infarcted and hypoperfused, ischemic myocardium was assessed in 16 dogs which underwent coronary artery occlusion and reperfusion. During occlusion, technetium-99 microspheres were injected into the left atrium. Following death, the hearts were excised and underwent NMR imaging with a 0.35 tesla magnet, using multiple spin-echo pulse sequences. The epicardium of the heart was marked to indicate the level of the NMR cross-sectional tomographic image. The heart was subsequently breadloafed into 5 mm sections and the corresponding NMR cross-section was flagged for analysis. Autoradiography was performed to measure the hypoperfused, at-risk zone, and triphenyltetrazolium chloride staining was used to measure infarct size. For the flagged tomographic slice, the size of the NMR abnormality correlated well (r = 0.95), and was comparable to the actual hypoperfused, at-risk zone of the left ventricle. However, NMR estimates of infarct size correlated less well (r = 0.75) with the pathologic measure, and significantly overestimated actual infarct size (p less than 0.005). The T1 and T2 values were consistently increased (p less than 0.0005) in both the hypoperfused and infarct zones, compared to normal myocardium. We conclude that NMR imaging can detect acute myocardial ischemia and infarction, but overestimates infarct size and corresponds better to the area of hypoperfused, ischemic myocardium. In this excised canine heart occlusion-reperfusion model, the NMR abnormality corresponded best to the area including both infarction and the surrounding ischemic region.     

Early noninvasive detection of reperfusion and infarct by intravenous technetium 99m pyrophosphate scintigraphy following thrombolysis

To determine whether technetium-99-pyrophosphate accumulation immediately after intravenous thrombolysis can serve as a marker of reperfusion and infarct size, 17 patients with acute myocardial infarction were studied. Immediately after thrombolysis 10 mCi of technetium-99m pyrophosphate were injected intravenously. Coronary and left ventricular angiography were then performed in all patients, revealing patent coronary arteries in 13 patients. In all patients, 0.3 and 0.5 mCi of thallium-201 were injected into the right and left coronary artery, respectively, followed by planar scintigraphy. 6 patients with patent coronary arteries and a large thallium-201 defect had massive (more than one third of the cardiac silhouette) pyrophosphate accumulation (group A), whereas 7 patients with a small or no thallium-201 defect in the presence of a patent infarct artery had either focal or no pyrophosphate accumulation (group B). In contrast, 4 patients with an occluded infarct artery showed no acute pyrophosphate uptake despite a large thallium-201 defect (group C). Emission computed tomography confirmed the planar scintigraphic data in group A patients and revealed small thallium-201 defects and focal pyrophosphate accumulation in group B patients with negative planar scintigrams. Global and regional ejection fractions in the infarct area, measured from the acute and follow-up left ventricular angiograms, were higher in group A than in group B and C patients. It is concluded that early intravenous technetium-99m pyrophosphate scintigraphy in patients with acute myocardial infarction undergoing intravenous thrombolysis may serve as an indicator of reperfusion and infarct size.     

Determinants of infarct size after thrombolytic treatment in acute myocardial infarction

Both experimental and single-center clinical studies have shown that myocardium at risk, residual collateral flow, and duration of coronary occlusion are important determinants of final infarct size. The purpose of this study was to replicate these results on a multicenter basis to demonstrate that perfusion imaging using different camera and computer systems can provide reliable assessments of myocardium at risk and collateral flow. Sequential tomographic myocardial perfusion imaging with technetium-99 (Tc-99m) sestamibi was performed in 74 patients with first time myocardial infarction, who were enrolled in a multicenter, randomized, double-blind, placebo-controlled pilot study of poloxamer 188 as ancillary therapy to thrombolysis. All patients underwent thrombolysis within 6 hours of the onset of chest pain. Tc-99m sestamibi was injected intravenously at the initiation of thrombolytic therapy, and tomographic imaging was performed 1 to 6 hours later to assess myocardium at risk. Collateral flow was estimated noninvasively from the acute sestamibi images by 3 methods that assess the severity of the perfusion defect. Final infarct size was determined at hospital discharge by a second sestamibi study. Myocardium at risk (r = 0.61, p <0.0001) and radionuclide estimates of collateral flow (r = 0.58 to 0.66, all p <0.0001) were significantly associated with final infarct size. These associations were independent of the treatment center. On a multivariate basis, myocardium at risk (p = 0.003), the radionuclide estimate of collateral flow (p = 0.03), and treatment arm (p = 0.04) were all independent determinants of infarct size. Time to thrombolytic therapy showed only a trend (p = 0.10). The treatment center was not significant (p = 0.42). Myocardium at risk and collateral flow are important determinants of infarct size that are independent of treatment center. Tomographic imaging with Tc-99m sestamibi can provide noninvasive assessments of these parameters in multicenter trials of thrombolytic therapy.     

Estimates of myocardium at risk and collateral flow in acute myocardial infarction using electrocardiographic indexes with comparison to radionuclide and angiographic measures

Objectives. This study sought to determine the accuracy of the initial 12-lead electrocardiogram (ECG) in predicting final infarct size after direct coronary angioplasty for myocardial infarction and to examine which physiologic variables known to be determinants of outcome the ST segment changes most closely reflect.Background. Myocardium at risk, collateral flow and time to reperfusion have been shown to be independent physiologic predictors of infarct size in animal and clinical models. However, such measurements may be difficult to perform on a routine basis in patients with myocardial infarction. The standard 12-lead ECG is inexpensive and readily available.Methods. Sixty-seven patients with acute myocardial infarction, ST segment elevation and duration of chest pain <12 h had an initial injection of technetium-99m sestamibi. Tomographic imaging was performed 1 to 8 h later (after direct coronary angioplasty), and the images were quantified to measure perfusion defect size (myocardium at risk) and severity (a measure of collateral flow). Contrast agent injection and tomographic acquisition were repeated at hospital discharge to measure infarct size. The ST segment elevation score was calculated for each patient according to infarct location and using previously described formulas.Results. ST segment elevation score correlated closest with the radionuclide measure of collateral flow (r = −0.44, p ≤ 0.0001), as well as an angiographic measure of collateral flow (r = −0.38, p = 0.05). Although ST segment elevation score correlated weakly with the magnitude of myocardium at risk by technetium-99m sestamibi, it was not as strong as infarct location alone in predicting myocardium at risk ([mean ± SD] anterior 51 ± 13% left ventricle vs. inferior 17 ± 10% left ventricle, p < 0.0001). ST segment elevation score was weakly associated with final infarct size (r = 0.34, p = 0.005). A multivariate ECG model was constructed with infarct location as a surrogate for myocardium at risk, ST segment elevation score as a surrogate for estimated collateral flow, and elapsed time to reperfusion from onset of chest pain. All three variables were independently associated with infarct size.Conclusions. The initial standard 12-lead ECG can provide insight into myocardium at risk and, to a greater extent, collateral flow and can consequently provide some estimate of subsequent infarct size. However, the confidence limits for such predictors are wide.     

Predictors of infarct size after primary coronary angioplasty in acute myocardial infarction from pooled analysis from four contemporary trials

Determinates of infarct size in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) have been incompletely characterized, in part because of the limited sample size of previous studies. Databases therefore were pooled from 4 contemporary trials of primary or rescue PCI (EMERALD, COOL-MI, AMIHOT, and ICE-IT), in which the primary end point was infarct size assessed using technetium-99m sestamibi single-photon emission computed tomographic imaging, measured at the same core laboratory. Of 1,355 patients, infarct size was determined using technetium-99m sestamibi imaging in 1,199 patients (88.5%), at a mean time of 23 +/- 15 days. Median infarct size of the study population was 10% (interquartile range 0% to 23%; mean 14.9 +/- 16.1%). Using multiple linear regression analysis of 18 variables, left anterior descending infarct artery, baseline Thrombolysis In Myocardial Infarction grade 0/1 flow, male gender, and prolonged door-to-balloon time were powerful independent predictors of infarct size (all p <0.0001). Other independent correlates of infarct size were final Thrombolysis In Myocardial Infarction grade <3 flow (p = 0.0001), previous AMI (p = 0.005), symptom-onset-to-door time (p = 0.021), and rescue angioplasty (p = 0.026). In conclusion, anterior infarction, time to reperfusion, epicardial infarct artery patency before and after reperfusion, male gender, previous AMI, and failed thrombolytic therapy were important predictors of infarct size after angioplasty in patients with AMI assessed using technetium-99m sestamibi imaging and should be considered when planning future trials of investigational drugs or devices designed to enhance myocardial recovery.     

Technetium-99m isonitrile myocardial uptake at rest. I. Relation to severity of coronary artery stenosis

To determine the potential of planar technetium-99m methoxybutyl isonitrile myocardial imaging as a method of detecting totally occluded or severely stenosed coronary arteries, the regional distribution of technetium-99m isonitrile at rest was compared with the coronary anatomy in 38 patients with prior myocardial infarction who underwent coronary arteriography. Left ventricular technetium-99m isonitrile tracer uptake at rest was assessed in the three major coronary vascular territories. When qualitative rest technetium-99m isonitrile uptake was markedly reduced or absent (grade 0), there was a 91% probability of finding a totally occluded or severely stenosed coronary artery. When qualitative tracer uptake was reduced (grade 1) or normal (grade 2), it excluded all territories supplied by a totally occluded vessel with poor collateral flow. Quantitative technetium-99m isonitrile uptake (mean +/- 1 standard deviation) in territories supplied by an occluded coronary artery with poor collateral flow (42 +/- 21%) was lower than in territories supplied by a vessel with less than 50% stenosis (87 +/- 10%) and 50 to 99% stenosis (74 +/- 19%) (p less than 0.001). Furthermore, technetium-99m isonitrile uptake in areas supplied by an occluded coronary artery with good collateral flow (61 +/- 23%) was lower than in areas supplied by a vessel with less than 50% stenosis (87 +/- 10%) (p less than 0.001). Because rest technetium-99m isonitrile imaging detects coronary occlusion with poor collateral flow, this method may be useful in assessing patients with acute myocardial infarction.     

Myocardial reperfusion imaging: basic principals and clinical applications

In recent years, radionuclide imaging techniques have gained increasing popularity in clinical practice to evaluate regional myocardial perfusion and viability in patients with acute myocardial infarction who have undergone reperfusion therapy. Myocardial thallium-201 (Tl-201) or technetium-99m methoxyisobutyl isonitrile (Tc-99m Sestamibi) scintigraphy can be used for detecting and localizing areas of necrosis when injected at rest and can be used in conjunction with exercise or pharmacological stress testing for predischarge risk stratification and determining prognosis. In the presence of residual blood flow, uptake of Tl-201 by myocardial cells is not altered unless irreversible membrane injury is present. Postischemic myocardial "stunning" alone does not affect Tl-201 extraction. Tl-201 administered very soon after reperfusion is established may reflect more the hyperemic flow state rather than the degree of myocardial salvage. Initial myocardial uptake of Tc-99m Sestamibi after intravenous injection is also proportional to blood flow. When injected during coronary occlusion, the pattern of uptake of Tc-99m Sestamibi accurately delineates the "area of risk." When injected several hours after coronary reperfusion, the uptake pattern accurately reflects the degree of residual myocardial viability. Serial Tc-99m Sestamibi imaging in patients with myocardial infarction receiving thrombolytic therapy showed that patients with a patent infarct vessel had a significant reduction in defect size compared with prethrombolysis images.     

Primary angioplasty in myocardial infarction: assessment of improved myocardial perfusion with technetium-99m isonitrile.

Technetium-99m-hexakis-2-methoxy-2-isobutyl-isonitrile (technetium-99m isonitrile) is a new radiopharmaceutical compound that reflects myocardial perfusion. Its kinetics, especially its lack of redistribution after intravenous administration, permits the assessment of changes in myocardial perfusion without delay of therapy. Tomographic images at rest were obtained immediately and 6 to 10 days later in 17 consecutive patients undergoing successful primary angioplasty during their first transmural myocardial infarction. Thirteen patients had anterior infarction. The initial (acute) defect size before angioplasty of 48 +/- 17% of the left ventricle decreased significantly (p less than 0.0001) to 29 +/- 19% on the late scans. There was no correlation between the time to therapy and the reduction in defect size. Twelve of the 17 patients, including 7 of the 11 patients treated after 4 h, demonstrated a definite reduction in the initial defect size. Eight patients with angiographically proved persistent coronary occlusion underwent a similar imaging sequence. The initial defect size in this group remained unchanged on the late scans (24 +/- 16% versus 26 +/- 18%, p = NS). Primary angioplasty is an effective approach toward salvaging myocardium; comparison with thrombolytic drug therapy must await the results of controlled clinical trials.     

Experimental studies of the physiologic properties of technetium-99m isonitriles

Recently, efforts have been directed at the development of technetium-99m (Tc-99m)-labeled isonitrile compounds for assessment of regional perfusion and viability after experimental myocardial infarction or ischemia. One of the most promising of these agents, Tc-99m sestamibi, has undergone rather extensive laboratory investigation. Like thallium-201 (Tl-201), the uptake of Tc-99m sestamibi in myocardial tissue is proportional to myocardial blood flow after intravenous injection. Similar to other diffusible indicators, Tc-99m sestamibi underestimates blood flow at high flow rates. In low flow regions, the myocardial uptake of this agent is higher relative to nonischemic uptake than is microsphere-determined blood flow. This is attributed to increased extraction at low flows. This first-pass myocardial extraction fraction for Tc-99m sestamibi is less than that for Tl-201. However, Tc-99m sestamibi has a higher parenchymal cell permeability and higher volume of distribution than T;-201. Tc-99m sestamibi shows minimal "delayed redistribution" after initial intravenous administration. Uptake of Tc-99m sestamibi is not altered by myocardial "stunning" or with ischemic dysfunction produced by sustained low coronary flow. The uptake of the isonitrile is still proportional to blood flow in these situations. In intact animal models, myocardial uptake of Tc-99m sestamibi during coronary occlusion delineates the in vivo area at risk. When Tc-99m sestamibi is administered after reperfusion following variable periods of preceding coronary occlusion, Tc-99m sestamibi uptake delineates the area of viable myocardium that is salvaged and not simply the degree of reflow. This suggests that serial Tc-99m sestamibi imaging might be useful in assessing the efficacy of coronary reperfusion after thrombolytic therapy.     

Early estimation of acute myocardial infarct size soon after coronary reperfusion using emission computed tomography with technetium-99m pyrophosphate

Early appearance of positive findings on a technetium-99m pyrophosphate scan has been shown to be associated with the presence of a reperfused acute myocardial infarction (AMI). Early technetium-99m pyrophosphate imaging was performed by emission computed tomography to evaluate reperfusion and to test the feasibility of estimating infarct size soon after coronary reperfusion based on acute positive tomographic findings. Twenty-seven patients with transmural AMI who were treated with intracoronary urokinase infusion followed by percutaneous transluminal coronary angioplasty underwent pyrophosphate imaging 8.7 +/- 2.1 hours after the onset of AMI. None of the 8 patients in whom reperfusion was unsuccessful had acute positive findings. Of 19 patients in whom reperfusion was successful, 17 had acute positive findings (p less than 0.001). In these 17, tomographic infarct volumes were determined from reconstructed transaxial images. The threshold for areas of increased pyrophosphate uptake within the infarct was set at 60% of peak activity by the computerized edge-detection algorithm. The total number of pixels in all transaxial sections showing increased tracer uptake were added and multiplied by a size factor and 1.05 g/cm3 muscle to determine infarct volume. The correlations of tomographic infarct volumes with peak serum creatine kinase (CK) levels (r = 0.82) and with cumulative release of CK-MB isoenzyme (r = 0.89) were good. Moreover, the time to positive imaging was significantly shorter than that to peak CK level (8.5 +/- 2.3 vs 10.4 +/- 2.2 hours, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantification of area at risk during coronary occlusion and degree of myocardial salvage after reperfusion with technetium-99m methoxyisobutyl isonitrile

Serial myocardial imaging with technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI) has been proposed for evaluating myocardial salvage after reperfusion. To define 99mTc-MIBI uptake before and after reperfusion, 17 open-chest dogs underwent 3 hours of left anterior descending artery occlusion and 3 hours of reperfusion. 99mTc-MIBI was injected during occlusion (group 1) or after 90 minutes of reperfusion (group 2). Myocardial 99mTc-MIBI activity was correlated with microsphere flow during occlusion and reperfusion. Anatomic risk area and infarct area were defined by postmortem vital staining and correlated with the perfusion defects defined by analysis of 99mTc-MIBI macroautoradiographs and gamma camera images of myocardial slices. The left ventricle was divided into 96 segments for gamma well counting. Flow and 99mTc-MIBI activity were normalized to nonischemic values. Myocardial segments were grouped, based on occlusion flow, into zones: severely ischemic (less than or equal to 30% nonischemic), moderately ischemic (greater than 30%, less than or equal to 60% nonischemic), mildly ischemic (greater than 60%, less than or equal to 90% nonischemic), and nonischemic (greater than 90%, less than or equal to 120% nonischemic). Among dogs injected with 99mTc-MIBI during coronary occlusion (group 1), myocardial 99mTc-MIBI activity correlated linearly with occlusion flow for both endocardial (r = 0.91) and transmural (r = 0.91) segments. The risk area defined by 99mTc-MIBI autoradiography (group 1) correlated with the postmortem risk area (rho = 0.94) but was 29% smaller than the anatomic risk area (p = 0.03), reflecting the contribution of collateral flow. Among dogs injected with 99mTc-MIBI after reperfusion (group 2), myocardial 99mTc-MIBI did not correlate with reperfusion flow in either endocardial or transmural segments. Among group 2 dogs, myocardial 99mTc-MIBI activity was significantly less than reperfusion flow at the time of injection in the severely ischemic (25 +/- 5% versus 74 +/- 24% nonischemic, p = 0.002), moderately ischemic (54 +/- 12% versus 96 +/- 15% nonischemic, p = 0.001), and mildly ischemic (84 +/- 6% versus 93 +/- 3% nonischemic, p = 0.002) zones. The defect area defined by 99mTc-MIBI autoradiography (group 2) correlated very closely with the postmortem infarct area (rho = 0.98). Thus, the myocardial uptake of 99mTc-MIBI during coronary occlusion correlates with occlusion flow and reflects the "area at risk." When 99mTc-MIBI was given after 90 minutes of reperfusion following 3 hours of coronary occlusion, the myocardial activity was significantly reduced compared with reperfusion flow in both necrotic and perinecrotic regions, reflecting myocardial viability more than the degree of reperfusion.