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Thallium reinjection after stress-redistribution imaging. Does 24-hour delayed imaging after reinjection enhance detection of viable myocardium?

BACKGROUND: Thallium reinjection immediately after conventional stress-redistribution imaging improves the detection of viable myocardium, as many myocardial regions with apparently "irreversible" thallium defects on standard 3-4-hour redistribution images manifest enhanced thallium uptake after reinjection. Because the 10-minute period between reinjection and imaging may be too short, the present study was designed to determine whether 24-hour imaging after thallium reinjection provides additional information regarding myocardial viability beyond that obtained by imaging shortly after reinjection. METHODS AND RESULTS: We studied 50 patients with chronic stable coronary artery disease undergoing exercise thallium tomography, radionuclide angiography, and coronary arteriography. Immediately after the 3-4-hour redistribution images were obtained, 1 mCi thallium was injected at rest, and images were reacquired at 10 minutes and 24 hours after reinjection. The stress, redistribution, reinjection, and 24-hour images were then analyzed qualitatively and quantitatively. Of the 127 abnormal myocardial regions on the stress images, 55 had persistent defects on redistribution images by qualitative analysis, of which 25 (45%) demonstrated improved thallium uptake after reinjection. At the 24-hour study, 23 of the 25 regions (92%) with previously improved thallium uptake by reinjection showed no further improvement. Similarly, of the 30 regions determined to have irreversible defects after reinjection, 29 (97%) remained irreversible on 24-hour images. These findings were confirmed by the quantitative analysis. The mean normalized thallium activity in regions with enhanced thallium activity after reinjection increased from 57 +/- 13% on redistribution studies to 70 +/- 14% after reinjection but did not change at 24 hours (71 +/- 14%). In regions with irreversible defects that were unaltered by reinjection, mean regional thallium activity did not differ from the reinjection to the 24-hour studies (57 +/- 17% and 58 +/- 17%, respectively). Twenty-four-hour imaging after reinjection showed improvement in only four of 35 irreversible regions (involving three of the 50 patients). CONCLUSIONS: These data indicate that thallium reinjection at rest after 3-4 hours of redistribution provides most of the clinically relevant information pertaining to myocardial viability in regions with apparently irreversible thallium defects. Hence, thallium reinjection may be used instead of 24-hour imaging in most patients in whom a persistent thallium defect is observed on conventional redistribution images.

Coronary Angiography↗

Relation between thallium uptake and contractile response to dobutamine. Implications regarding myocardial viability in patients with chronic coronary artery disease and left ventricular dysfunction.

BACKGROUND: Both thallium scintigraphy and dobutamine echocardiography have been used to assess myocardial viability. However, thallium uptake and the inotropic response to dobutamine are expressions of different cellular phenomena. The present study was undertaken to investigate the relation between the two methods in patients with chronic coronary artery disease and left ventricular dysfunction to derive insights into the mechanisms related to myocyte viability. METHODS AND RESULTS: Thirty patients (28 men and 2 women; age, 59 +/- 10 years) with chronic coronary artery disease and impaired left ventricular systolic function at rest (mean ejection fraction, 32 +/- 9%) were included in the study. Patients underwent transesophageal echocardiography during incremental doses of dobutamine from 2.5 to a maximum of 40 micrograms.kg-1.min-1 and single photon emission computed tomographic thallium scintigraphy using a stress-redistribution-reinjection protocol. The left ventricle was divided into 16 segments for analysis of echocardiographic and thallium images. Segmental myocardial contractile function was graded as normal, hypokinesis, akinesis, or dyskinesis at each incremental dose of dobutamine. Thallium uptake in each myocardial segment was graded on a 5-point scale from 0 (absent) to 2 (normal) for each of the stress, redistribution, and reinjection images. A segment was considered viable if the assigned thallium score was 1 or higher (normal uptake or only mild to moderate defect) in any of the stress, redistribution, or reinjection images. Among 472 myocardial segments available for analysis, 311 had resting wall motion abnormalities, of which 56% (173/311) showed contractile improvement with dobutamine (usually first observed at < or = 10 micrograms.kg-1.min-1) and 84% (262/311) were considered viable by thallium scintigraphy (P < .0001). Of the 262 segments considered viable by thallium, 167 (64%) had a contractile improvement with dobutamine; in contrast, only 6 of the 49 segments (12%) considered nonviable by thallium had a positive dobutamine response (P < .0001). Furthermore, a positive inotropic response to dobutamine was significantly related to the magnitude of thallium uptake: the proportion of segments with a positive dobutamine response rose with increasing magnitude of thallium uptake (P < .001). The disagreement between the two tests was related primarily to segments considered viable by thallium that did not show contractile improvement with dobutamine. CONCLUSIONS: These findings demonstrate the existence of a relation between thallium uptake and the inotropic response to dobutamine in patients with chronic coronary artery disease and left ventricular dysfunction. However, the proportion of segments showing a positive response to dobutamine is significantly lower than those with thallium uptake, suggesting that the cellular mechanisms responsible for a positive inotropic response to adrenergic stimulation require a higher degree of myocyte functional integrity than those responsible for thallium uptake.

Coronary Disease↗

Thallium in fractions of soil formed on floodplain terraces.

Two soils formed on the floodplain terrace of a rivulet flowing through the zinc-lead ore exploration area polluted with thallium and one soil from a floodplain terrace of the reference area were investigated in terms of thallium distribution between soil fractions. Such type of soil is formed on river floodplain terraces next to the main river channel and its composition records the history of river pollution. A sequential extraction of soil according to the BCR protocol was performed with an additional initial stage of extraction with water. Apart from labile thallium, thallium entrapped in the residual parent matter was also determined. Thallium was determined by flow-injection differential-pulse anodic stripping voltammetry. In all three cases, the major fraction is thallium entrapped in parent matter. Top soil from the polluted area contains 49.3% thallium entrapped in the residual parent matter, the bottom soil contains 41% while the reference soil contains 80% in this fraction. The major part of labile thallium is located in the reducible fraction (27.7% of total thallium in the top soil, 27% in the bottom soil and 12.4% of the reference soil). Second in terms of significance is the fraction of oxidizable thallium. The top soil contains 12% of total thallium concentration, the bottom soil contains 19% of total concentration, while the reference soil contains 4.1% of total concentration. The acid soluble/exchangeable fraction of thallium has almost the same significance as the oxidizable fraction. The top soil contains 10.4% of the total concentration, while the bottom soil contains 12% of the total concentration. Water soluble thallium concentration is very small. Comparison of the top and the bottom soil show that thallium has not been transported from the river channel onto the floodplain terrace over a long period.

Poland↗

Thallium 201 for assessment of myocardial viability.

Left ventricular (LV) performance is reduced in a large subset of patients with chronic coronary artery disease (CAD) and LV dysfunction on the basis of regionally ischemic or hibernating myocardium rather than irreversibly infarcted tissue. The detection of dysfunctional but viable myocardium is clinically relevant since regional and global LV function in such patients will improve after revascularization procedures; however, the identification of patients with such potentially reversible LV dysfunction is difficult. Although thallium 201 imaging may be of value in detecting viable myocardium if regions with perfusion defects during exercise demonstrate redistribution of thallium on a 3- to 4-hour resting image, thallium defects often appear persistently "fixed" within regions of severely ischemic or hibernating myocardium. It has been shown that up to 50% of regions with apparently irreversible thallium defects will improve in function after revascularization. Thus, standard exercise-redistribution thallium scintigraphy may not differentiate LV dysfunction arising from infarcted versus hibernating myocardium. The precision with which thallium imaging identifies viable myocardium can be improved greatly by additional studies once 4-hour redistribution imaging demonstrates an irreversible thallium defect. These additional studies include late (24-hour) redistribution imaging, repeat imaging after thallium reinjection, or a combination of thallium reinjection followed by late imaging. Several recent studies suggest that thallium reinjection techniques, by demonstrating thallium uptake in dysfunctional regions with apparently irreversible defects, predict improvement after revascularization with similar predictive accuracy as that achieved using metabolic imaging with positron emission tomography (PET). Studies directly comparing such thallium methods and PET, which thus far involve only small numbers of patients, suggest that the assessment of regional metabolic activity using PET and the assessment of regional thallium activity using single photon emission computed tomography provide concordant results. These findings, if confirmed by larger ongoing studies, suggest that thallium reinjection imaging is a convenient, clinically accurate, and relatively inexpensive method with which to identify viable myocardium in patients with chronic CAD and LV dysfunction.

Coronary Disease↗

The effect of hypoxia on thallium kinetics in cultured chick myocardial cells.

To assess the effect of hypoxia on cellular thallium-201 (201Tl) uptake and washout independent of coronary flow, we studied thallium kinetics during normoxia and hypoxia in cultured chick ventricular cells. Monolayers of contracting ventricular cells grown on coverslips were placed in a chamber and perfused to asymptote with media containing 201Tl. Perfusates were equilibrated with 5% CO2-95% air or 5% CO2-95% nitrogen for normoxia and hypoxia, respectively. Washout thallium kinetics were then observed during perfusion with unlabeled media. Twenty paired experiments were performed, randomly alternating the sequence of normoxia and hypoxia. Pharmacokinetics for thallium were determined by computer using standard formulae. Thallium uptake and washout were best described by assuming that intracellular thallium was contained within a single compartment. Cellular thallium uptake, as well as transfer rate constants for thallium uptake and for thallium washout during normoxia and hypoxia, were compared using paired t-tests. During normoxia and hypoxia, respectively, thallium uptake was 22 +/- 7% and 19 +/- 7% of asymptote (p less than 0.01); the compartmental rate constant for uptake by the cell was 0.16 +/- 0.07 min-1 and 0.15 +/- 0.06 min-1 (N.S.); and the transfer rate constant for washout from the cell was 0.26 +/- 0.06 min-1 and 0.23 +/- 0.05 min-1 (p less than 0.01). We conclude that there was a small (14%) decrease in thallium uptake during hypoxia. The rate of thallium uptake and washout was slightly less during hypoxia, although only the rate of washout was significantly less. These data show that cellular accumulation of thallium and the rate of washout of thallium were minimally decreased by hypoxia independent of blood flow.

Animals↗

Preoperative evaluation of myocardial viability by thallium-201 imaging in patients with old myocardial infarction who underwent coronary revascularization.

The myocardial uptake and redistribution in thallium scintigraphy and the regional wall motion by echocardiography were evaluated by a semi-quantitative method in 42 patients who previously had myocardial infarction (50 target vessels) and underwent coronary revascularization. The aim of this study was to elucidate the significance of the initial image, delayed image and redistribution on thallium-201 scintigraphy for clinical diagnosis of the myocardial viability. As a semi-quantitative analysis, we used a bull's-eye display for thallium image and centerline method for echocardiographic wall motion, and compared the results before and after revascularization. As a result, the thallium grade improved postoperatively in all 17 areas which preoperative had showed redistribution, and also in 11 of the 32 areas without preoperative redistribution. The sensitivity, specificity and accuracy of preoperative thallium redistribution for predicting myocardial viability were 61%, 100% and 78%, respectively, when the postoperative improvement in the thallium grade was used as the standard. The postoperative probability of improvement in the thallium grade increased in proportion to the preoperative thallium grade (delayed image) (p less than 0.01). There was no correlation between the preoperative thallium delayed image and postoperative improvement in wall motion. Postoperative improvement in thallium image and wall motion could not be predicted from the preoperative wall motion. Thus, postoperative improvement in thallium images can be anticipated if redistribution is present on the preoperative thallium image, and the preoperative thallium delayed image is useful for predicting myocardial viability. Improvement in wall motion could not be predicted preoperatively by these methods.

Adult↗

Correlation of thallium uptake with left ventricular wall thickness by cine magnetic resonance imaging in patients with acute and healed myocardial infarcts.

Myocardial infarction (MI) is characterized by cellular necrosis which undergoes fibrotic transformation over time. Cine magnetic resonance imaging (MRI) offers high-resolution 3-dimensional images of the left ventricular myocardium, allowing sampling of the myocardial wall thickness over the entire left ventricle. Tomographic (single-photon emission computed tomography [SPECT]) thallium images also provide 3-dimensional information on the location and level of thallium uptake, which has been shown to correlate with myocardial viability. The purposes of this study were: (1) to examine the relation between both end-diastolic and end-systolic wall thickness and normalized thallium-201 uptake over the left ventricle in a group of patients with MI, (2) to examine the relation between regional wall thickening and normalized thallium uptake, and (3) to examine the relation between thallium uptake and wall thickness both early and late after infarction. Twenty-four patients with MI underwent stress, redistribution, and reinjection thallium SPECT imaging and cine MRI within several days. Seventeen patients underwent imaging late after infarction and 7 underwent imaging early after infarction. Normalized thallium activity was correlated with MRI wall thicknesses at both end-diastole and end-systole for 18 segments for each ventricle. In addition, end-diastolic and end-systolic wall thicknesses were grouped by their corresponding thallium activity levels into percentiles. End-systolic wall thickness correlated significantly with normalized thallium uptake in 14 of 18 segments, end-diastolic wall thickness in only 4 of 18 segments, and wall thickening in only 3 of 18 segments. Mean values for end-diastolic and end-systolic wall thicknesses corresponding to severely reduced (<50%) normalized thallium activity were 9.9 +/- 1.1 and 8.5 +/- 0.6, respectively. Using receiver-operating curve analysis, end-systolic wall performed as a better diagnostic parameter than end-diastolic wall for identifying severely reduced thallium activity levels. For all levels of thallium activity, end-diastolic wall thicknesses were all thinner late versus early after MI, whereas end-systolic wall thickness was thinner only in the segments corresponding to severely reduced thallium activity. Based on these results, end-systolic wall thickness is the best noninvasive anatomic parameter of myocardial scar.

Adult↗

Analysis of the degree of pulmonary thallium washout after exercise in patients with coronary artery disease.

An abnormal increase in pulmonary thallium activity may be visualized on post-stress thallium images in patients with coronary artery disease. Because this increased pulmonary thallium activity usually disappears by the time of redistribution imaging, this study was designed to assess whether measurement of the degree of pulmonary thallium washout between stress and redistribution might improve the detection of increased pulmonary thallium activity in patients with coronary artery disease. Quantitative analysis revealed abnormal (that is, greater than 2 standard deviations of normal values) pulmonary thallium washouts in 59 (64%) of 92 patients with coronary artery disease, but in only 2 (25%) of 8 subjects with angiographically normal arteries (p less than 0.06). By comparison, the visual analysis of pulmonary thallium washout and use of initial pulmonary to myocardial thallium ratio were significantly (p less than 0.05) less sensitive in detecting abnormality in patients with coronary artery disease. Abnormal pulmonary thallium washout was related to both the anatomic extent and functional severity of disease: it occurred with greatest frequency in patients with multivessel disease and in those with exercise-induced left ventricular dysfunction (p less than 0.005). When added to the quantitative analysis of myocardial scintigraphy, the analysis of pulmonary thallium washout increased the detection of coronary artery disease from 84 to 93% (p less than 0.05), but the sample size was too small to assess specificity. Thus, the analysis of pulmonary thallium washout is a useful diagnostic variable because it: 1) provides an objective measurement of abnormal pulmonary thallium activity and is more sensitive than other methods; 2) correlates with both the extent of coronary artery disease and the degree of exercise-induced left ventricular dysfunction, and 3) improves the sensitivity of quantitative myocardial thallium scintigraphy to detect the presence of coronary artery disease.

Aged↗

Comparison of gadolinium-enhanced MR and thallium-201 single photon emission computed tomography in pediatric brain tumors.

Despite its usefulness in adults with cerebral gliomas, indications for thallium-201 single-photon emission computed tomography (SPECT) in pediatric brain tumor patients are not well defined. We prospectively compared thallium SPECT with gadolinium-enhanced MR (Gd-MR) to determine if thallium SPECT provides clinically useful information that cannot be derived from Gd-MR. We studied 24 pediatric brain tumor patients, 7 at presentation and 17 during therapy. MR imaging included T2 and pre- and postgadolinium T1 images. Thallium SPECT was done within 48 h of MR imaging; thallium indices were calculated for 12 of 14 lesions which showed thallium uptake. Surgery and/or clinical follow-up are available in all patients. The tumors included pilocytic astrocytoma (7), medulloblastoma (5), brainstem glioma or glioblastoma (4), germinoma (3), optic glioma (2), mixed glioma (1), primitive neuroectodermal tumor (1), and choroid plexus carcinoma (1). Among the primary tumors, compared to MR, thallium SPECT was false-negative for tumor in 1 patient and true-positive in 6 patients. Among the patients studied while on therapy, compared to MR, thallium SPECT was true-negative for tumor in 7, true-positive in 5, false-negative in 3, and false-positive in 2. In both groups of patients, thallium SPECT underestimated tumor burden as nonenhancing regions of the tumors were not thallium-avid. Thallium indices did not correlate with histologic grade, biologic aggressiveness, or tumor type. We were unable to establish indications for the use of thallium SPECT in this setting as there was little clinically useful information derived from thallium SPECT that was not provided by Gd-MR.

Adolescent↗

Myocardial thallium-201 kinetics in normal and ischemic myocardium.

The initial myocardial uptake of thallium-201 depends on myocardial blood flow distribution. The phenomenon of delayed thallium redistribution after transiently or chronically altered myocardial perfusion has been described. The net myocardial accumulation of thallium-201 after injection depends upon the net balance between continuing myocardial extraction from low levels of recirculating thallium in the blood compartment and the net rate of efflux of thallium from the myocardium into the extracardiac blood pool. These experiments were designed to measure separately the myocardial extraction and intrinsic myocardial efflux of thallium-201 at normal and at reduced rates of myocardial blood flow. The average myocardial extraction fraction at normal blood flow in 10 anesthetized dogs was 82 +/- 6% (+/- SD) at normal coronary arterial perfusion pressures and increased insignificantly, to 85 +/- 7%, at coronary perfusion pressures of 10--35 mm Hg. At normal coronary arterial perfusion pressures in 12 additional dogs, the intrinsic thallium washout in the absence of systemic recirculation had a half-time (T 1/2) of 54 +/- 7 minutes. The intrinsic cellular washout rate began to increase as distal perfusion pressures fell below 60 mm Hg and increased markedly to a T 1/2 of 300 minutes at perfusion pressures of 25--30 mm Hg. A second, more rapid component of intrinsic thallium washout (T 1/2 2.5 minutes) representing approximately 7% of the total initially extracted myocardial thallium was observed. The faster washout component is presumed to be due to washout of interstitial thallium unextracted by myocardial cells, whereas the slower component is presumed due to intracellular washout. The net clearance time of thallium measured after i.v. injection is much longer than the intrinsic myocardial cellular washout rate because of continuous replacement of myocardial thallium from systemic recirculation. Myocardial redistribution of thallium-201 in states of chronically reduced perfusion cannot be the result of increased myocardial extraction efficiency, but rather, is the result of the slower intrinsic cellular washout rate at reduced perfusion levels.

Animals↗

Differential uptake and apparent 201Tl washout after thallium reinjection. Options regarding early redistribution imaging before reinjection or late redistribution imaging after reinjection.

BACKGROUND: Because thallium reinjection enhances the identification of viable myocardium, many laboratories have adopted the routine practice of performing reinjection imaging instead of 3-4-hour redistribution imaging. This approach assumes that the stress-reinjection protocol provides the necessary information regarding both exercise-induced ischemia and myocardial viability. Because apparent "washout" of thallium may occur between redistribution and reinjection studies, we examined the limitations created by eliminating 3-4-hour redistribution images. METHODS AND RESULTS: We studied 50 patients with chronic stable coronary artery disease by exercise thallium tomography, radionuclide angiography, and coronary arteriography. Immediately after the 3-4-hour redistribution images, 1 mCi thallium was injected at rest, and images were reacquired both 10 minutes and 24 hours after reinjection. The stress, redistribution, reinjection, and 24-hour images were then analyzed quantitatively, and the magnitude of change in regional thallium activity after reinjection was termed "differential uptake." Of the 127 abnormal myocardial regions on the stress images, 55 (43%) demonstrated either complete or partial reversibility on 3-4-hour redistribution images. After reinjection, 14 of these regions (25%) demonstrated apparent thallium washout due to low differential uptake of thallium, which was only 46 +/- 20% of that observed in normal regions. As a result, the relative thallium activity, which was 55 +/- 13% during stress (relative to normal regions) and increased significantly to 75 +/- 13% on 3-4-hour redistribution studies (p less than 0.001), decreased to only 58 +/- 13% after thallium reinjection. At 24 hours, redistribution again developed in all 14 regions, resulting in a relative thallium activity of 71 +/- 16% (p less than 0.03), which was similar to that achieved on 3-4-hour redistribution images. Twelve of the 14 regions (86%) exhibiting apparent washout after reinjection were supplied by a totally occluded coronary artery, of which eight (67%) had normal wall motion at rest. In contrast, only 41% of the regions with either improved or unchanged thallium uptake after reinjection were supplied by a totally occluded coronary artery (p less than 0.05). CONCLUSIONS: These data indicate that regions with thallium defects that are reversible on 3-4-hour redistribution images may demonstrate apparent washout of thallium after reinjection due to low differential uptake. Although this occurs in only a small fraction of regions (8%) identified as abnormal on exercise images, these regions represent approximately 25% of regions showing redistribution. Such defects would appear irreversible if redistribution imaging is not performed before reinjection. However, these same myocardial regions also redistribute further after reinjection and are identified as reversible on 24-hour images. Thus, one of two imaging options, either stress-redistribution-reinjection imaging or stress-reinjection-24-hour imaging, may be used for a comprehensive assessment of myocardial ischemia and viability.

Coronary Angiography↗

The interference of uptake of thallium-201 in cultured rat myocardial cells with existence of potassium related pharmaceuticals--a preliminary report.

Thallium-201 myocardial perfusion imaging is wildly used to detect and assess the extent of jeopardized myocardial ischemia in the coronary artery disease and the viability of myocardium post infarction. In recent years, there has been a great deal of pharmacological development of blockers and openers of potassium channel. In this study, we will discuss the interference of uptake of thallium-201 ion in cultured neonatal rat myocytes with existence of a variety of pharmacological agents. The cultures of neonatal rat myocardial cells were incubated with different agents such as potassium chloride, sodium-potassium ATPase pump inhibitor (ouabain), cesium compound, variable potassium channel blockers (4 AP, TEA and glibenclamide) and their openers (minoxidil, and cromakalim). The radioactivity of intracellular thallium-201 that could enter rat myocardial cells was detected by gamma counter sixty minutes after thallium-201 was added. In this study we found that thallium and potassium ions behave in an analogous manner in cultured rat myocardial cells. Both 2.5 mM and 5 mM concentration of extracellular potassium ion significantly result in reduction of thallium-201 ion influx in rat myocardial cells. 0.5 mM ouabain, an inhibitor of sodium-potassium ATPase pump, reduced about 40% of influx of thallium-201 ion in cultured rat myocardial cells via active transport. Combination of both potassium ion and ouabain inhibit most of thallium-201 ions influx in myocardial cells, but it is not completely inhibited. Cesium, a potassium antagonist, also interferes with the uptake of thallium-201 in cultured rat myocytes in our study. The most interesting finding in our investigation is that potassium channel blockers such as TEA and glibenclamide, inhibit the influx of thallium-201 in myocytes. However, potassium channel openers have no overt effect on influx of thallium-201 in cultured rat myocytes. We indirectly observe about 60% of influx of thallium-201 ion into cultured rat myocardial cells via active sodium-potassium ATPase pump. Potassium, cesium and potassium channel blockers, such as TEA and glibenclamide, inhibited the different percentage of influx of thallium-201 in cultured rat myocardial cells in this study.

Adenosine Triphosphate↗