Pathophysiology of technetium-99m stannous pyrophosphate and thallium-201 scintigraphy of acute anterior myocardial infarcts in dogs.

In 17 dogs with acute myocardial infarcts produced by ligation of the proximal left anterior descending coronary artery, a comparative study was made of myocardial scintigrams obtained with technetium-99m stannous pyrophosphate (99mTc-PYP) and thallium-201 (201T1), tissue levels of 99mTc-PYP and 201T1 uptake, histopathologic alterations, and regional myocardial perfusion measured with radioactive microspheres. 9 of the 10 hearts examined histologically had transmural infarcts with outer peripheral, inner peripheral, and central zones characterized by distinctive histopathologic features. A progressive reduction in myocardial blood flow was demonstrated between normal myocardium and the centers of the infarcts, and correlated well with progressive reduction in 201T1 upatke in the same regions. Marked 99mTc-PYP concentration occurred in areas with partial to homogeneous myocardial necrosis and residual perfusion located in the outer peripheral regions of the infarcts. The latter areas also were characterized by the presence of muscle cell calcification. The patterns of distribution of 99mTc-PYP and 201T1 explained the filling defects on 201T1 myocardial scintigrams and the doughnut patterns on 99mTc-PYP myocardial scintigrams in dogs with transmural infarcts. One dog with a subendocardial infarct had a small homogeneous area of activity on the 99mTc-PYP myocardial scintigram, and showed marked uptake of 99mTc-PYP in subendocardial areas of extensive necrosis and calcification still receiving some coronary perfusion. Thus, the data indicate that the status of regional myocardial perfusion is a key determinant for the occurrence of distinctive patterns of myocardial necrosis and for the scintigraphic detection of acute myocardial infarcts with 99mTc-PYP and 201T1.

Infarct sizing with technetium-99m stannous pyrophosphate scintigraphy in dogs and man; relationship between scintigraphic and praecordial mapping estimates of infarct size in patients.

The present study was performed in order to evaluate the ability of technetium-99m stannous pyrophosphate (99mTc-PYP) myocardial scintigrams to size infarcts in experimental animals and man. In 10 dogs with proximal left anterior descending coronary artery occlusion and acute anterior myocardial infarcts, there was a significant correlation between scintigraphic infarct size and histological infarct weight (P less than 0.01). In 25 patients with acute anterior or anterolateral myocardial infarcts, there was a significant correlation between relatively large infarct size determined scintigraphically and the acute development of left ventricular failure. There was some overlap, however, in 99mTc-PYP scintigraphic infarct size between patients who did and did not develop left ventricular failure with infarction. Presumably this is explained by some patients having had earlier myocardial damage and thus developing left ventricular failure with relatively small new infarcts. There was also a statistically significant, but weak, correlation in patients between scintigraphic infarct size and precordial ST segment mapping including peak ST segment elevation (P less than 0.05) and the number of praecordial sites with ST segment elevation equal to or greater than 2 mm (P less than 0.01). The data suggest that 99mTc-PYP scintigrams and praecordial mapping measure some similar but some dissimilar aspects of infarct size in patients, and that 99mTc-PYP scintigraphy does size acute anterior and anterolateral infarcts in experimental animals and patients.

Regional multiparameter estimation from tomographic diffusible tracer clearance curves: modification of the double-integral method.

Measurement of regional CBF in transverse section using inert, diffusible tracers can be carried out using a double-integral form of the Kety-Schmidt equation. An implementation of this form proposed by Kanno and Lassen (the K-L estimator) is utilized by the Tomomatic 64, a dynamic single-photon computed tomography system that records washin-washout data during and following inhalation of 133Xe gas. Advantages of the algorithm include noninvasive calibration of the input function and excellent depiction of ischemia: disadvantages are sensitivity to errors in input function delay (delta), the inability to estimate the partition coefficient (lambda) (hence, only the clearance index, k, is estimated), and a noise sensitivity proportional to k. A modification of the method is proposed that not only accounts for delta variations, but also provides an estimate of relative lambda (hence, the perfusion, f, is estimated). The proposed estimator is shown to be robust in the presence of noise with error variances equal to or better than those with the K-L estimator, yet estimates of both relative f and lambda are provided by the modification. New simulation results implicate the Compton scatter fraction as a major contributor in the overestimation of white matter perfusion values using both the K-L and proposed estimators, and illustrate the need for hardware and software scatter fraction reduction and control.

Normal distribution of regional cerebral blood flow measured by dynamic single-photon emission tomography.

Regional CBF (rCBF) was measured quantitatively using the inert-gas washout technique with xenon-133 and single-photon emission computed tomography. Tomographic data were reconstructed by filtered back projection, and flow was calculated according to the double-integral method. Ninety-seven subjects ranging in age from 20 to 59 years received a single examination; eight of these received a second examination within 1 h of the first; seven others received a second examination separated from the first by 1-10 days. Transverse-section images were obtained at 2, 6, and 10 cm above and parallel to the canthomeatal line (CML). Cortical gray matter flows were obtained from 12 brain regions in the slice 6 cm above the CML, and cerebellar and inferior cerebral gray matter flows were obtained from 4 regions in the slice 2 cm above the CML. Mean gray matter flow was 72 +/- 12 ml/min/100 g, with highest flows in the parietal lobes and visual cortex. No significant differences in rCBF occurred when a second study followed the first by 30 min to 10 days. Right-sided rCBF was slightly higher than left in all regions except frontal and parietal lobes where there was no difference. Flow was higher in women than in men and declined mildly with age for both sexes (slope = -0.33 ml/min/100 g/year; p less than 0.05).

Error analysis of the double-integral method for calculating brain blood perfusion from inert gas clearance data.

A single-photon dynamic computer-assisted tomograph (DSPECT) has been built and is currently being used to evaluate regional cerebral blood perfusion in patients and volunteers. A computer simulation of the system was created to analyze the effects of data collection, Poisson noise, attenuation compensation, and the reconstruction technique now employed in the DSPECT. Several methods of attenuation compensation were used to generate perfusion images from both ideal and noisy data. The results indicate that the mean perfusion is calculated to within 10.4% accuracy for all perfusion rates in a region of interest if attenuation correction is used. Without attenuation correction, perfusions are underestimated by as much as 27%. The three correctors tested have different effects on the calculated perfusion value, depending on the location of the region of interest in the picture. The algorithm introduces random noise that is proportional to both the random error in the input data and the perfusion rate. Air-curve delay errors result in inaccuracies in the final perfusion picture that are proportional to perfusion rate. Physiological values (0.8-1.5) of the partition coefficient cause overestimation of both gray (0-34%) and white (7-67%) matter perfusion values. Compton scatter and collimator effects were not addressed in this study.

Quantification of intracerebral steal in patients with arteriovenous malformation.

Eleven patients with angiographically and/or pathologically proved arteriovenous malformations (AVMs) were studied using dynamic, single-photon-emission computed tomography (DSPECT). Quantification of regional cerebral blood flow in structurally normal areas remote from the AVM disclosed areas of decreased flow compared with normal controls in eight of 11 patients examined. Areas of hypoperfusion correlated with altered function as manifested by epileptogenic foci and impaired cognitive function. Dynamic, single-photon-emission computed tomography provides a noninvasive technique to monitor quantitatively hemodynamic changes associated with AVMs. Our findings suggest that such changes are present in the majority of patients with AVMs and that they may be clinically significant. The potential application of regional cerebral blood flow imaging by DSPECT in the management of patients with AVMs is discussed.

Single-proton tomographic study of regional cerebral blood flow in epilepsy. A preliminary report.

Regional cerebral blood flow (rCBF) may be measured with a single-photon-emission computed tomograph (SPECT) after inhalation of xenon 133. Our SPECT studies of rCBF in a group of 18 patients with seizure disorders, when compared with studies in 32 normal control subjects, have shown enhanced flow to an active seizure focus and ischemia of brain areas in certain subjects between seizures. Thus, SPECT determination of rCBF has demonstrated a number of findings recently observed with positron-emission tomography and may become a useful modality in the study of patients who have epilepsy.

A contiguous-slice design for single-photon emission tomography (SPECT).

Recent multislice, single-photon emission tomographic systems produce nonoverlapping transverse-section images, requiring repositioning of the patient and repeated studies to obtain a complete set of cross-sectional data. A complete, overlapping set of transverse-section images can be obtained by designing a collimator with alternating, staggered centerlines that are offset in the slice dimension.

Effects of noise on the determination of ejection fraction from left ventricular time-activity curves.

The effects of Poisson noise on three estimates of ejection fraction made from left-ventricular time-activity curves have been investigated. All three methods are based on a sinusoidal model of left-ventricular volume changes. The first, developed by Schelbert et al., overestimates the ejection fraction for low-activity levels and low ejection fractions. The second estimate, which is merely a first-order correction for the contribution of Poisson noise to the first estimate, appears to be more accurate when both estimators are applied to simulated time-activity curves, and the resulting ejection fractions are compared. A third, "maximum likelihood" estimator, when applied to the same data, is apparently more accurate than the first two.

Quantitation of experimental canine infarct size using multipinhole single-photon tomography.

A four-pinhole longitudinal tomographic system, with collimator and software, was developed for a standard-field portable scintillation camera. This system was used with technetium--99m pyrophosphate (Tc-PPi) to quantify the volume of infarcted myocardium in 27 dogs with experimental myocardial infarcts. These were induced by ligation of the left anterior descending (LAD) or the circumflex coronary artery. Tomographic estimations of scintigraphic infarct size agreed well with postmortem findings when the circumflex group (r = 0.87) and LAD group (r = 0.83) were considered separately, but the correlation fell when the groups were pooled (r = 0.73). Whereas multipinhole tomography extends Tc-PPi infarct sizing capability in animals to include posterior and subendocardial infarcts as well as anterior lesions, the tomographic sections contain enough blur artifacts to lower the sizing accuracy of the method. The main advantage of the technique may well be its ability to aid in detection and location of small myocardial infarcts.

Quantitation of experimental canine infarct size with multipinhole and rotating-slanthole tomography.

Myocardial infarct size was estimated by three methods in a canine model, using Tc-99m pyrophosphate at 24 and 48 hr after coronary ligation. A gamma camera provided anterior, LAO, and lateral views, and was then fitted with multipinhole (MPH) and rotating-slanthole (RSH) collimators for tomographic studies, processed by computer to display frontal sections of the chest. Infarct weight was measured postmortem for comparison. All transmural infarcts were detected by all three imaging techniques. RSH tomography was superior to both MPH tomography and planar imaging for the detection of nontransmural infarction. Infarcts as small as 1.0 g were detected. Estimates of infarct volume measured from RSH slices showed an excellent correlation with infarct weight (r = 0.89) and were reproducible within acceptable limits. Estimates on infarct volume measured from MPH slices demonstrated a significantly poorer correlation with infarct weight (r = 0.48, p less than 0.01). Both tomographic techniques may improve infarct visualization by suppressing overlying activity and increasing contrast between infarct and background, but both produce significant blur artifacts that hamper their utilization by inexperienced observers.

Attenuation compensation in single-photon emission tomography: a comparative evaluation.

Attenuation of photons in single-photon emission tomography (SPECT) makes three-dimensional reconstruction of unknown radioactivity distributions a mathematically intractable problem. Approaches to approximate SPECT reconstruction range from ignoring the effect of photon attenuation to incorporating assumed attenuation coefficients into an iterative reconstruction procedure. We have developed a computer-based simulation method to assess the relative effectiveness of attenuation compensation procedures. The method was used to study four procedures for myocardial SPECT using an infarct-avid radiopharmaceutical, Tc-99m stannous pyrophosphate. Reconstructions were evaluated by two criteria: overall (sum-of-squares) accuracy, and accuracy of lesion sizing. For moderate- to high-contrast studies there were no significant differences among the reconstructions by either evaluation criterion; for low contrast ratios the iterative method produced lower sum-of-squares criterion; for low contrast ratios the iterative method produced lower sum-of-squares error. We conclude that the additional expense of the iterative method is not justified under the conditions of this study. The approach used here is a convenient tool for evaluating specific SPECT reconstruction alternatives.

Measurement of acute myocardial infarcts in dogs with 99mTc-stannous pyrophosphate scintigrams.

Myocardial scintigrams using 99mTc-stannous pyrophosphate (99mTc-PYP) can be used to measure myocardial infarcts produced in dogs by proximal ligation of the left anterior descending coronary artery. Seven dogs had 99mTc-PYP myocardial scintigraphy performed 24--32 hr after ligation of the proximal left anterior artery. In each dog the scintigrams showed increased 99mTc-PYP uptake in the distribution of the artery. The scintigraphically visible areas of infarction, measured using interactive computer-aided techniques, were compared subsequently with independent histologic measurements of myocardial infarct size. Several methods for using the area measurements to estimate infarct size were tested. The most successful method (r = 0.92, p less than 0.01) assumed a linear relationship between the largest scintigraphic infarct area and the histologically determined infarct weight. The results suggest that 99mTc-PYP myocardial scintigrams provide a useful noninvasive method for measuring infarct size in dogs with proximal ligation of the left anterior descending coronary artery.

Acute myocardial infarction imaged with 99mTc-stannous pyrophosphate and 201Tl: a clinical evaluation.

Twenty-six patients suspected of having acute myocardial infarction (AMI) underwent myocardial scintigraphy sequentially with 201Tl and 99mTc-stannous pyrophosphate (99mTc-PPi). Of the 26 patients, 24 had AMI documented by enzyme and electrocardiographic changes. Nineteen had transmural and five had subendocardial myocardial infarctions. The remaining two patients had "unstable angina pectoris." The mean time from onset to imaging was 4 days. Of the 24 patients with AMI, 22 had positive 99mTc-PPi scintigrams. In 20 the area of acute myocardial damage appeared to be the same by 99mTc-PPi scintigram as by ECG; in two, the location could not be precisely determined. The two patients with negative 99mTc-PPi scintigrams at the time of combined myocardial imaging had had positive 99mTc-PPi images previously. In all 24 patients, the 201Tl images were abnormal in at least the location suggested by the electrocardiogram. In seven patients, the area of decreased 201Tl activity was grossly equal to the positive area on the 99mTc-PPi images; in 15, the 201Tl defect was definitely larger; and in two, the 201Tl defect appeared slightly smaller. Although the 99mTc-PPi and 201Tl myocardial images provide different information, both are valuable in determining the overall integrity of the myocardium in patients with ischemic heart disease.

Quantification of three-dimensional left ventricular segmental wall motion and volumes from gated tomographic radionuclide ventriculograms.

Tomographic radionuclide ventriculograms may be used for three-dimensional wall motion analysis. We propose that automatic quantification of these images is possible, and here we describe the implementation and validation of a method to perform this task. Automatic computer methods were developed to locate the left ventricular (LV) endocardial surfaces in all time frames of the cardiac cycle. Global, regional, and local motion and volume were computed. Results were displayed using three-dimensional graphics. The methods were validated using phantom, canine, and human studies. Actual phantom values correlated well with experimentally determined volumes, y = 1.01x + 1.29ml, r = 0.99. In the canine model, the LV endocardial surfaces were located to within an average of 1.9 mm and 3.7 mm at end-diastole and end-systole, respectively. Areas of obvious wall motion abnormalities in automatically processed patient studies corresponded well with angiographically documented coronary artery disease. End-diastolic and end-systolic volumes computed automatically from single photon emission computed tomography averaged errors of 9% and 38%, respectively, when compared with contrast ventriculographic volumes. These results indicate that it is possible to automatically identify the left ventricular endocardial surface in gated tomographic radionuclide ventriculograms. The location of these surfaces corresponds well with the location of implanted endocardial markers, and global volume computed from these surfaces corresponds well with known volumes.

Comparison of different noninvasive methods of infarct sizing during experimental myocardial infarction.

This study evaluated the accuracy of several noninvasive infarct-sizing techniques in 12 awake, unsedated dogs with multivessel coronary obstructions and acute anterior myocardial infarcts. Estimations of infarct size by scintigraphy with technetium-99m Sn pyrophosphate (Tc-PP), serum creatine phosphokinase (CPK) release, peak serum myoglobin levels by radioimmunoassay, and precordial ECG mapping were compared and correlated with histologic measurements of infarct size. The comparisons indicate that precordial ST segments mapping, serum CPK release measurements and peak serum CPK, peak serum myoglobin, and Tc-PPi myocardial scintigraphy all provide approximate estimates of infarct size in this model. Each technique also has certain important limitations, however, including: (A) precordial mapping is relatively insensitive in the identification of small anterior infarcts, (B) serial serum CPK release measurements when obtained for only 24 hr after infarction tend to underestimate large anterior infarct size, and (C) Tc-PPi myocardial scintigrams may fail to recognize anterior infarcts less than 3 gm in size and may overestimate the size of small predominantly subendocardial infarcts. The findings also show that the closest estimate of histologic infarct size in this model was provided by combining two of the noninvasive techniques (precordial mapping to identify sites with 2 or more millimeters of ST segments elevation and Tc-PPi myocardial scintigrams) rather than by relying exclusively on any one technique alone.

Myocardial infarct imaging with technetium-99m phosphates.

Technetium-99m-phosphate imaging is particularly valuable in detecting (1) small transmural infarcts (3 g and larger in size); (2) new acute transmural infarcts in or near regions of old infarction; (3) acute subendocardial infarcts (larger than 3 g in size); (4) acute infarction in patients with left bundle branch block; and (5) perioperative myocardial infarction. Localization of inferior and posterior myocardial infarction is improved with imaging. Sizing of acute anterior and lateral infarcts has been accurately done in dogs and should prove helpful in patients. Extensive evaluation in both experimental animals and in patients has shown 99mTc-phosphate myocardial imaging to be a useful clinical tool, and it may be one of the most sensitive noninvasive ways presently available to identify acute myocardial necrosis. It is important to understand that 99mTc-phosphate imaging has a different pathophysiology basis from EKG's or serum enzymes. These tests do not compete but instead should complement one another.

Grid versus non-grid techniques for the detection of pulmonary nodules in a chest phantom.

A partial chest phantom was constructed to compare two commonly employed radiographic techniques, 70 kVp without a grid and 120 kVp with a grid, for the detection of pulmonary nodules. The phantom consisted of human ribs embedded in paraffin, the lungs of a dog injected with silicone rubber, a tissue equivalent wax heart and beeswax nodules. The nodules ranged in size from 3-7 mm. A series of 120 films was exposed, half with each technique, and the films were interpreted by three senior residents and seven staff radiologists. More nodules of all sizes except 3 mm were detected with the 120 kVp technique. The 3 mm nodules were rarely detected with either technique. The disadvantages of the 120 kVp technique were an approximate 50 percent increase in patient exposures and almost twice as many false-positive nodule detections.

Single-photon tomographic determination of regional cerebral blood flow in epilepsy.

Using a single-photon emission computed tomographic scanner (SPECT) the authors determined regional cerebral blood flow (rCBF) with inhaled xenon-133, a noninvasive procedure. Studies were performed in 40 normal individuals, and these were compared with rCBF determinations in 51 patients with seizure disorders. Although positive results were obtained in 15 of 16 patients with mass lesions, the group of principal interest comprised 25 patients suffering from "temporal lobe" epilepsy. Only one of these had a positive x-ray computed tomogram, but 16 had positive findings on rCBF study. These findings included increased local blood flow in the ictal state and reduced flow interictally.

Feature detection in 3-d medical images using shape information.

Three methods for identifying the left ventricular apex in 3-D medical images of the heart called gated blood pool tomograms were investigated. The first method assumed a known orientation and positioning of the entire blood pool. The second and third methods used shapes described by quadratic surfaces, which are invariant to position and orientation. The first method performed best when the blood pool was accurately oriented, but as expected, could not handle blood pools in the wrong orientations. The quadratic surface methods performed well whether or not the blood pool was accurately oriented. The best quadratic surface method predicted the x, y, z value of the apex with correlations of 0.97, 0.98, 0.99.