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Biomedical subjects

H R Schelbert

Publications and source records attributed to H R Schelbert.

At least 91 records · Page 5Linked to original sources
PubMed1992

Detection of coronary artery disease with positron emission tomography and rubidium 82.

Myocardial blood flow was evaluated in 31 subjects with not only visual but also, for the first time, circumferential profile analysis of rubidium 82 (82Rb) images acquired with positron emission tomography. Fifteen were control subjects and 16 subjects had significant coronary artery disease, defined as 50% or greater diameter stenosis in a major coronary artery or a first-order branch. Simultaneous 82Rb images at three myocardial levels were obtained before and after intravenous dipyridamole plus handgrip stress. In patients with significant coronary artery disease, visual analysis correctly identified significant disease in 26 (76%) of 34 arteries and its absence in 12 (86%) of 14 normal arteries. According to circumferential profile analysis, these numbers were 91% and 86%, respectively. Thus circumferential analysis of 82Rb images, obtained before and after intravenous dipyridamole plus handgrip stress, yielded improved sensitivity and comparable specificity compared with visual analysis.

Coronary Disease↗
PubMed1992

Comparison of maximal myocardial blood flow during adenosine infusion with that of intravenous dipyridamole in normal men.

OBJECTIVE: This study compared quantitatively the efficacy of intravenous adenosine and dipyridamole for pharmacologic induction of myocardial hyperemia. BACKGROUND: Pharmacologic vasodilation is used increasingly for induction of myocardial hyperemia in conjunction with radionuclide imaging of myocardial blood flow. Although both intravenous dipyridamole and adenosine have been used, the magnitude of hyperemia induced by these agents and the hyperemia to baseline blood flow ratios have not been quantified and compared. METHODS: Twenty normal volunteers were studied with dynamic positron emission tomography (PET) and intravenous nitrogen-13 ammonia. Myocardial blood flow was quantified with a two-compartment tracer kinetic model. RESULTS: Myocardial blood flow at rest averaged 1.1 +/- 0.2 ml/min per g and increased significantly to 4.4 +/- 0.9 ml/min per g during adenosine and 4.3 +/- 1.3 ml/min per g after dipyridamole administration. Hyperemia to baseline flow ratios averaged 4.3 +/- 1.6 for adenosine and 4.0 +/- 1.3 for dipyridamole. The average flow ratios and the maximal flows achieved were similar for both agents, but there was considerable variation in the individual response to these agents, as indicated by the range of hyperemia to baseline flow ratios (from 2.0 to 8.4 for adenosine and from 1.5 to 5.8 for dipyridamole). In addition, the hyperemic responses to dipyridamole and to adenosine differed by greater than 1 ml/min per g in nine subjects. CONCLUSIONS: Despite these inter- and intraindividual differences, we conclude that both agents are equally effective in producing myocardial hyperemia.

Adenosine↗
PubMed1992

Quantitative assessment of prolonged metabolic abnormalities in reperfused canine myocardium.

BACKGROUND: Prolonged metabolic abnormalities have been demonstrated previously in postischemic myocardium, including relative increases in glucose uptake and abnormal fatty acid kinetics. However, quantitative metabolic information is limited, and the time course of changes in MVO2 in postischemic myocardium is unknown. To address these issues, chronically instrumented dogs were studied serially over 1 month after transient left anterior descending coronary artery (LAD) occlusion, using positron emission tomography. METHODS AND RESULTS: Dynamic imaging protocols were used in conjunction with tracer kinetic models to quantify blood flow and metabolic rates. Myocardial sectors were defined as normal, predominantly reversibly injured, and infarct-containing, based on occlusion blood flow images and postmortem histochemistry. Myocardial blood flow and metabolism were homogeneous at baseline. During LAD occlusion for 3 hours, myocardial blood flow in reversibly injured and infarct-containing sectors (determined with 13NH3) was decreased to 46% and 23%, respectively, of blood flow in normal tissue. MVO2, determined with [1-11C]acetate, was decreased less than myocardial blood flow, consistent with increased oxygen extraction in the ischemic tissue. After reperfusion, blood flow normalized rapidly in reversibly injured tissue but remained depressed in infarct-containing sectors. Regional myocardial function, assessed by two-dimensional echocardiography, was severely depressed during occlusion and did not improve significantly until 1 week after reperfusion. MVO2 remained depressed after reperfusion in both reversibly injured and infarct-containing sectors, did not improve from occlusion levels until 1 week after reperfusion, and remained significantly depressed 1 month after reperfusion even in reversibly injured sectors; [1-11C]palmitate kinetics were also abnormal in postischemic tissue. As reported previously, glucose metabolic rates were increased relative to baseline in normal but not in postischemic tissue 3 hours after reperfusion. Subsequently, glucose metabolism tended to be higher in postischemic relative to normal myocardium. CONCLUSIONS: The results demonstrate decreased oxidative metabolism in postischemic tissue, with concomitant abnormalities in palmitate kinetics and glucose metabolism. Oxidative metabolism and regional function demonstrated a parallel recovery with time.

Acetates↗
PubMed1992

Quantification of regional myocardial blood flow using 13N-ammonia and reoriented dynamic positron emission tomographic imaging.

BACKGROUND: Regional myocardial blood flow has been quantified using transaxial positron emission tomographic (PET) imaging and tracer kinetic modeling. However, the use of transaxial images limits the accuracy of regional partial volume corrections and the localization of the quantified regional flow values. The purpose of the present study was to overcome both problems by calculating regional flows from reoriented short-axis PET images. METHODS AND RESULTS: Twelve experiments were performed in four dogs. 13N-ammonia was injected intravenously while microspheres were administered into the left atrium during baseline, hyperemic, and low-flow conditions. Serial transaxial frames were acquired with a 15-plane PET scanner and reoriented into short-axis frames. The arterial input function and eight regional myocardial tissue activity curves were derived from the reoriented frames. The arterial input functions were corrected for ammonia metabolites, and the myocardial tissue curves were corrected for spillover of activity, partial volume effects, and heterogeneities in the image's spatial resolution introduced during reorientation. Corrections for regional partial volume were based on estimates of the regional myocardial activity thickness derived from reoriented diastolic images of the heart. The myocardial 13N-ammonia kinetics were described with a two-pool compartmental model. Values of regional myocardial blood flow by PET correlated linearly with those by microspheres (slope, 0.94; y intercept, 0.06 ml/min/g; r = 0.93) over a wide range of flows. CONCLUSIONS: Regional myocardial blood flow can be measured accurately and noninvasively from serially acquired and reoriented short-axis 13N-ammonia images, thus overcoming limitations inherent to the use of transaxially acquired images and permitting a more complete evaluation of regional blood flows throughout the left ventricular myocardium.

Ammonia↗
PubMed1992

Positron emission tomography detects metabolic viability in myocardium with persistent 24-hour single-photon emission computed tomography 201Tl defects.

BACKGROUND: Four-hour 201Tl redistribution images underestimate myocardial viability in patients with coronary artery disease (CAD). Because 4-hour defects often redistribute late, delayed imaging may enhance assessment of tissue viability. Myocardial metabolic activity was therefore assessed with positron emission tomography (PET) in 26 CAD patients with impaired ventricular function (ejection fraction, 32.1 +/- 13.9%) and 24-hour single-photon emission computed tomography (SPECT) 201Tl defects. METHODS AND RESULTS: On circumferential profile analysis, PET ischemia was defined by preserved glucose metabolism in hypoperfused myocardium, and PET infarction was defined by concordant reductions in perfusion and metabolism. On 19 stress-redistribution and seven rest-redistribution SPECT studies, four observers visually scored 201Tl activity in eight segments on a scale from 0 (normal) to 3 (complete defect). Using an improvement in visual score > or = 0.75 to define redistribution, there were 100 fixed, 17 partially reversible, and 12 completely reversible defects. PET identified tissue metabolic activity in 51 (51%) segments with fixed defects (21 PET ischemia, 30 PET normal) and nine (53%) segments with partially reversible defects (five PET ischemia, four PET normal). When grouped by 24-hour score, the proportion of fixed defects with metabolic activity varied from 84% (scores < or = 1.4) to 15% (scores > 2.6). For partially reversible defects, only 53% with scores < 2.0 and one of two with scores > or = 2.0 were considered metabolically viable on PET. Of 12 completely reversible defects, six (50%) were normal, five (42%) had PET ischemia, and one (8%) had PET infarction. The proportion of fixed defects with metabolic activity did not depend on whether a rest or stress study was performed or on the change in visual score used to define 201Tl redistribution (0.25, 0.50, 0.75, and 1.00). CONCLUSIONS: In CAD patients, PET identifies glucose metabolic activity in the majority of fixed 24-hour 201Tl defects. However, very severe (near-complete) 24-hour 201Tl defects are less likely to exhibit metabolic activity on PET imaging than are defects with less-pronounced reductions in segmental 201Tl activity.

Coronary Angiography↗
PubMed1992

A new noninvasive quantification of renal blood flow with N-13 ammonia, dynamic positron emission tomography, and a two-compartment model.

In order to determine if dynamic positron emission tomography (PET) and N-13 ammonia can be used to quantitate regional RBF (rRBF) noninvasively, six anesthetized dogs were examined with PET imaging after an iv bolus administration of 5 mCi of N-13 ammonia. Renal time activity curves and the arterial input function were derived from regions of interest drawn over the renal cortex and abdominal aorta, respectively. For calculation of rRBF, less than 120 s of the initial data were used to minimize contamination by plasma metabolites of N-13 radioactivity. rRBF was quantitated with a two-compartment model, and the results were compared with simultaneously acquired microsphere blood flow measurement. Fourteen experiments were performed in six dogs, and four regions of interest on renal cortex were selected on each PET image. RBF derived from dynamic PET imaging with N-13 ammonia was linearly related to microsphere (MS) values (rRBF = 1.06 x MS - 0.17; r = 0.91). Mean rRBF in the canine experiments was 4.0 mL/min/g. The results indicate that dynamic N-13 ammonia renal PET can provide noninvasively quantitative rRBF.

Ammonia↗
PubMed1992

Semiquantitative assessment of myocardial blood flow and viability using polar map displays of cardiac PET images.

Preserved glucose metabolism in ischemically injured, dysfunctional myocardial tissue as demonstrated on PET imaging predicts functional improvement after revascularization. To characterize more precisely the relationship between regional myocardial blood flow, viability and extent and severity of flow and metabolism abnormalities, we developed a PC-based semiquantitative analysis technique using 13N-ammonia and 18F-deoxyglucose polar map displays. A data base for mean values (m) and standard deviations (s.d.) for relative 13N activities reflecting regional myocardial blood flow, relative 18F activities normalized to normal flow regions reflecting regional glucose utilization and the difference of normalized 18F and 13N activities as an index of a flow-metabolism mismatch was established in 11 normals. Parametric polar maps were derived by comparing patient data to a normal range defined as greater than m - 2 s.d. for relative myocardial blood flow and less than m + 2 s.d. for both relative glucose utilization and the difference between normalized 18F and 13N activities. Semiquantitative indices of extent and severity of blood flow defects, of relative increases in glucose utilization and of flow-metabolism mismatch areas are generated for the entire myocardium and the three coronary territories. The approach promises to be clinically useful to confirm presence and absence of flow and metabolic abnormalities and to assess their extent as a potential predictor of functional outcome after therapy.

Adult↗
PubMed1992

Issues in the quantitation of reoriented cardiac PET images.

Reorientation of transaxial cardiac PET images into short-axis images has been shown by other investigators to improve visual identifiability of defects in myocardial tracer uptake. However, quantification of physiologic processes from such reoriented images may be complicated by errors introduced during the reorientation process. Therefore, a quantitative characterization of these errors is necessary. An annular phantom of human cardiac dimensions was imaged in a 15-plane positron emission tomograph at six angles (0 degrees, 5 degrees, 25 degrees, 45 degrees, 65 degrees, 85 degrees) and at two different axial sampling densities. In addition, two different reorientation interpolators were employed, one using three-dimensional linear interpolation and the other using a "hybrid" interpolation algorithm. Distortion of linear distances was variable but was minimized with denser axial sampling and the use of hybrid interpolation. Circumferential profile analysis, corrected for inhomogeneities in reoriented image spatial resolution, revealed a maximal loss of region of interest counts at 65 degrees of at least 14.4%. Reorientation errors were minimized by use of dense axial sampling, low angles of reorientation and use of the hybrid interpolation algorithm.

Deoxyglucose↗
PubMed1992

[The integration of positron emission tomography into noninvasive cardiovascular diagnosis].

Cardiac positron emission tomography is a noninvasive imaging modality that can be used to assess regional myocardial blood flow and metabolism. This combined noninvasive approach to the evaluation of acute or chronic injury to the myocardium is superior to all other imaging modalities. With increasingly widespread use of positron emission tomography it is becoming evident that patients with impaired left ventricular ejection fraction (less than or equal to 35%) resulting from congestive heart failure and patients soon (72-96 h) after acute myocardial infarction in particular may benefit from definition of metabolically active myocardium to stratify therapeutic assessment.

Ammonia↗
PubMed1991

Noninvasive detection of functionally significant coronary artery stenoses with exercise and positron emission tomography.

Positron emission tomography has been employed in vivo to assess flow using N-13 (nitrogen-13) ammonia and glucose metabolism, with the glucose analog F-18 (fluorine-18) fluorodeoxyglucose. Flow metabolism mismatches in which glucose metabolism is increased with respect to flow have been used to define ischemic, but viable myocardium. The feasibility of detecting exercise-induced ischemia using this technique was explored. Eleven normal volunteers and 16 patients who had undergone coronary arteriography were studied with N-13 ammonia at rest and with bicycle exercise, and with F-18 fluorodeoxyglucose in the postexercise period. Each image was divided into 16 sectors. Comparison of absolute net extractions of N-13 ammonia at rest and with exercise was not sensitive in detecting functionally significant coronary artery lesions. Myocardial uptakes of F-18 fluorodeoxyglucose and exercise N-13 ammonia were normalized to the sector with the highest N-13 ammonia uptake (corresponding to the highest flow rate). The differences and ratios of these normalized uptakes were successfully used to objectively define flow metabolism mismatches and to identify functionally significant coronary artery disease. Our data suggest that exercise flow and metabolic imaging are superior to rest and exercise flow imaging, particularly in patients with prior myocardial infarctions.

Ammonia↗
PubMed1991

Quantification of absolute myocardial perfusion at rest and during exercise with positron emission tomography after human cardiac transplantation.

The maximal exercise capacity of cardiac transplant recipients is reduced compared with that of normal subjects. To determine if this reduced exercise capacity is related to inadequate myocardial perfusion during exercise, myocardial perfusion was measured noninvasively with use of positron emission tomography and nitrogen (N)-13 ammonia. Twelve transplant recipients with no angiographic evidence of accelerated coronary atherosclerosis were studied. Serial N-13 ammonia imaging was performed at rest and during supine bicycle exercise. The results were compared with those from 10 normal volunteers with a low probability of having cardiac disease. A two-compartment kinetic model for estimating myocardial perfusion was applied to the data. Transplant recipients achieved a significant lower exercise work load than did the volunteers (42 +/- 16 vs. 128 +/- 22 W), but a higher venous lactate concentration (31.3 +/- 14.9 vs. 13.7 +/- 4.1 mg/100 ml). Despite the difference in exercise work load, there was no significant difference in the cardiac work achieved by transplant recipients and normal subjects as evidenced by similar rate-pressure products of 24,000 +/- 3,400 versus 21,300 +/- 2,800 betas/min per mm Hg, respectively. In addition, myocardial blood flow during exercise was not significantly different between the two groups (1.70 +/- 0.60 vs. 1.56 +/- 0.71 ml/min per g, respectively). This study demonstrates that the myocardial flow response to the physiologic stress of exercise is appropriate in transplant recipients and does not appear to explain the decreased exercise capacity in these patients.

Ammonia↗
PubMed1991

A quantitative index of regional blood flow in canine myocardium derived noninvasively with N-13 ammonia and dynamic positron emission tomography.

To derive a quantitative index of regional myocardial blood flow, the arterial input function of the flow tracer N-13 ammonia and the regional myocardial N-13 activity concentrations were noninvasively determined in 29 experiments in eight dogs. N-13 ammonia was administered intravenously and cross-sectional images were acquired dynamically using an ECAT III positron emission tomograph with an effective in-plane resolution of 13.46 mm full-width half-maximum. Time-activity curves were derived from the serial images by assigning regions of interest to the left ventricular myocardium and left ventricular blood pool. Tracer net extractions were estimated from the myocardial time-activity concentrations at various times after tracer injection and the integral of the arterial input function. Myocardial blood flow was altered by intravenous dipyridamole, morphine, propranolol and partial or complete occlusion of the left anterior descending coronary artery, and ranged from 9 to 860 ml/min per 100 g. Estimates of tracer net extractions were most accurate when determined from the myocardial N-13 activity concentrations at 60 s divided by the integral of the arterial input function to that time. These estimates correlated with regional myocardial blood flows determined independently by the microsphere technique by y = x (1 - 0.64(e-114/x); SEE = 22.9; r = 0.94). First pass extraction fractions of N-13 ammonia determined noninvasively with this approach declined with higher flows in a nonlinear fashion and were similar to those determined invasively by direct intracoronary N-13 ammonia injections. The findings indicate that an accurate index of regional myocardial blood flow can be obtained noninvasively by high temporal sampling of arterial and myocardial tracer activity concentrations with positron emission tomography. They also provide a basis for the in vivo application of tracer kinetic principles to derive quantitatively and noninvasively regional rates of functional processes in human myocardium.

Ammonia↗
PubMed1991

Differentiating cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy utilizing positron emission tomography.

To determine if imaging of blood flow (using N-13 ammonia) and glucose metabolism (using F-18 2-deoxyglucose) with positron emission tomography can distinguish cardiomyopathy of coronary artery disease from nonischemic dilated cardiomyopathy, 21 patients with severe left ventricular dysfunction who were evaluated for cardiac transplantation were studied. The origin of left ventricular dysfunction had been previously determined by coronary angiography to be ischemic (11 patients) or nonischemic (10 patients). Images were visually analyzed by three observers on a graded scale in seven left ventricular segments and revealed fewer defects in dilated cardiomyopathy compared with ischemic cardiomyopathy for N-13 ammonia (2.7 +/- 1.6 versus 5 +/- 0.6; p less than 0.03) and F-18 deoxyglucose (2.8 +/- 2.1 versus 4.6 +/- 1.1; p less than 0.03). An index incorporating extent and severity of defects revealed more homogeneity with fewer and less severe defects in subjects with nonischemic than in those with ischemic cardiomyopathy as assessed by imaging of flow (2.8 +/- 1.8 versus 9.2 +/- 3; p less than 0.001) and metabolism (3.8 +/- 3.3 versus 8.5 +/- 3.6; p less than 0.005). Diagnostic accuracy for distinguishing the two subgroups by visual image analysis was 85%. Using previously published circumferential count profile criteria, patients with dilated cardiomyopathy had fewer ischemic segments (0.4 +/- 0.8 versus 2.5 +/- 2 per patient; p less than 0.01) and infarcted segments (0.1 +/- 0.3 versus 2.4 +/- 1.4 per patient; p less than 0.001) than did patients with cardiomyopathy of coronary artery disease. The sensitivity for differentiating the two clinical subgroups using circumferential profile analysis was 100% and the specificity 80%. An index incorporating both number and severity of defects derived from circumferential profile analysis was significantly lower in subjects with dilated cardiomyopathy than in ischemic cardiomyopathy (0.3 +/- 0.8 versus 2.7 +/- 2.4; p less than 0.005). Thus, noninvasive positron emission tomographic imaging with N-13 ammonia and F-18 deoxyglucose is helpful in distinguishing patients with severe left ventricular dysfunction secondary to coronary artery disease from those with nonischemic cardiomyopathy, and a semiquantitative index such as circumferential profile analysis is superior to that of visual analysis alone.

Adult↗
PubMed1991

Positron emission tomography demonstrates that coronary sinus retroperfusion can restore regional myocardial perfusion and preserve metabolism.

Positron emission tomography was used to image blood flow and metabolic tracers in risk zone myocardium after left anterior descending coronary artery occlusion during synchronized coronary venous retroperfusion. Six control and seven intervention open chest dogs had occlusion of the mid left anterior descending coronary artery. Synchronized retroperfusion commenced 25 min later. Flow tracers (rubidium-82 and nitrogen-13 ammonia) were injected retrogradely. Three hours after coronary occlusion, fluorine-18 (F-18) deoxyglucose uptake in the control and treatment groups was compared. At 200 min of occlusion, infarct size was assessed. Retrograde flow tracer uptake was observed in the risk zone in the seven intervention dogs. Fluorine-18 deoxyglucose uptake in the risk zone was increased in five of the six intervention dogs but was reduced in five of the six control dogs. The risk zone to normal zone F-18 deoxyglucose count ratio was higher in the intervention than the control group (1.13 +/- 0.39 vs. 0.59 +/- 0.51; p less than 0.05). The endocardial subsegment risk zone to normal zone F-18 deoxyglucose count ratio was also significantly higher in the intervention group. Percent infarction in the risk zone was 70% lower in the group treated with synchronized retroperfusion than in the control group (18.4 +/- 22.6% vs. 61.2 +/- 25.4%; p less than 0.02). Thus, positron emission tomography revealed that retroperfusion could deliver oxygenated blood and maintain metabolism in risk zone myocardium. Infarct size was limited to 30% of that of control. In acute closure of the left anterior descending coronary artery, synchronized retroperfusion might be considered for maintaining viability of the jeopardized myocardium if the artery cannot be reopened rapidly.

Animals↗
PubMed1991

Correlation of myocardial necrosis with kinetics of 111In-labeled myosin-specific antibody in isolated rabbit septum.

Radiolabeled monoclonal antibody fragments to myosin, specifically 111In-labeled antimyosin, have been shown to be effective for imaging areas of myocardial infarct. To determine if 111In-labeled antimyosin can be used to assess the extent of necrosis, we compared the tissue retention fraction of 111In-labeled antimyosin with the amount of creatine kinase (CK) released from the isolated, perfused, interventricular rabbit septum after an intervention to induce tissue necrosis. 111In-labeled antimyosin was injected and tissue radioactivity was monitored for a 60-min period under control conditions. Effluent samples were also collected during this period and assayed for CK content. After a period of Ca2+ depletion followed by Ca2+ repletion, 111In-labeled antimyosin was again injected, and washout and CK data were collected. Comparison of the changes in 111In-labeled antimyosin retention fraction from control to intervention with the corresponding increase in CK released during intervention resulted in a correlation coefficient of 0.83. To corroborate the findings of the Ca2+ depletion followed by repletion experiments, further experiments were conducted in which zero-flow ischemia followed by reperfusion was used as a means of introducing necrosis in the septum. The resulting correlation coefficient between CK release and 111In-labeled antimyosin retention fraction was 0.82. The results of these experiments indicate that 111In-labeled antimyosin can be used to quantitatively estimate the extent of necrosis in the rabbit septum, as determined by CK release, and endorse the potential use of tracer kinetics in humans for quantitation of myocardial necrosis in vivo.

Animals↗