The effects of reperfusion on the myocardial accumulation of neutrophils and their role in the extent of injury were investigated in a canine preparation with a 3 hr coronary occlusion followed by 21 hr of reperfusion. The left anterior descending coronary artery (LAD) was permanently occluded in group 1 and reperfused after 3 hr in four others (groups 2 to 5). All but group 5 received lidocaine (1 mg/min over 8 hr). A critical stenosis was produced and left in place at reperfusion only in group 2. In groups 1 and 2, 11 In-labeled autologous neutrophils were injected at the time of coronary occlusion. Group 4 animals were rendered leukopenic 2 hr before the coronary ligature and throughout the experiment by injection of an antineutrophil rabbit serum. Quantification of the radioactivity by digitized scintigraphy of the heart slices revealed an 80% (p < .05) increase in neutrophil accumulation in the infarct region after reperfusion (group 2) as compared with permanent occlusion (group 1). Gamma counting of myocardial tissue samples showed that the neutrophil accumulation ratio in the subendocardial central zone of the infarct was increased five times (p < .05) by reperfusion, whereas no difference was evident in the subepicardium. Infarct size and myocardial area at risk were not statistically different among the five groups. However LAD flow in the leukopenic group (group 4) was significantly higher (p < .05) 30 min after reperfusion (40.0 ± 5 ml/min) when compared with the preocclusion value (21.7 ± 4 ml/min). In contrast, in a parallel experiment without leukopenia (group 3), LAD flow after reperfusion did not differ from the preocclusion value. We conclude that after a 3 hr occlusion, reperfusion enhances the myocardial accumulation of neutrophils and modifies their distribution in the necrotic area. Neutrophil accumulation appears not to be responsible for the lack of beneficial effect of reperfusion on infarct size in this preparation, since leukopenia failed to limit the extent of injury not otherwise modified by lidocaine. However, neutrophils may adversely affect restoration of flow by the formation of leukocyte plugs. Circulation 75, No. 5, 1083-1090, 1987. CORONARY REPERFUSION is the most promising treatment to limit the size of necrosis and to improve prognosis in patients with acute transmural myocardial infarction. 1' 2 The duration of ischemia before reperfusion is certainly one of the most critical factors that determine myocardial salvage.3 Another factor potentially influencing ultimate infarct size is the extent of the acute inflammatory reaction in the early course of myocardial infarction.48 Neutrophils are suspected to From the Laboratory of Experimental Pathology, Montreal Heart Institute, Montreal, Quebec, Canada Supported by grant MT-4478 of the Medical Research Council of Canada. Dr. Chatelain is a Fellow of the Swiss National Research Foundation. Dr. Latour is a Career Investigator of the Conseil de la Recherche en Sant6 du Qu6bec. Address for correspondence: Jean-Gilles Latour, Ph.D., Laboratory of Experimental Pathology, Montreal Heart Institute, 5000 East Belanger St., Montreal, Quebec, Canada HIT 1C8 Received Oct. 17, 1985; revision accepted Jan. 29, 1987. be mediators of this phenomenon because of their ability to release proteolytic lysosomal enzymes,9 freeradicals ,10. 11 and active metabolites of arachidonic acid,12 all being potentially detrimental for ischemic and normal myocardium. Reduction of the extent of ischemic myocardial injury has been reported in experimental preparations using anti-inflammatory13-18 as well as leukopenic19' 20 and anticomplementary agents.21 On the other hand, some observations have suggested an increase or an acceleration of the inflammatory processes by reperfusion.'12 22 Therefore reperfusion represents a paradoxical situation with both potentially beneficial and detrimental effects on the myocardium. In other words, if reperfusion enhances neutrophil accumulation, which can be detrimental for the myocardium, the beneficial effects of flow restitution may be attenuated. Vol. 75, No. 5, May 1987 1083

The diagnostic value of exercise electrocardiography using 14 leads and thallium-201 scintigraphy were evaluated in 54 of 70 patients who underwent percutaneous transluminal coronary angioplasty (PTCA), both in the initial assessment and serial follow-up of patients after PTCA. Of the 45 patients who had successful PTCA, 36 had complete noninvasive studies performed before and 1 month after PTCA. Thirty-three of these 36 were asymptomatic 1 month after PTCA; the number of patients with an abnormal exercise ECG decreased from 20 to seven (p < 0.01) and with an abnormal thallium-201 scintigram from 21 to six (p < 0.001); the number of patients who had at least one of the two tests positive decreased from 26 to 10. The average treadmill time increased from 448 + 183 to 618 119 seconds (i < 0.001), and the average rate-pressure product increased from 19.81 ± 6.4 to 31.35 4.6 units x 10 (p < 0.001). Of the 10 patients with a positive test, two had a partial restenosis 50% but < 70% on the 6-month control angiogram; two had a residual stenosis ¢ 50% in a vessel that was not dilated and three had an abnormal scintigram before and 1 month after PTCA that subsequently became negative at 6 months. Six months after PTCA, a control angiogram was performed in 20 asymptomatic patients; 18 had an excellent PTCA result and two had a partial restenosis ¢ 50% but < 70%. The stress test results were normal in patients with a successful 6-month PTCA and abnormal in the two patients with a partial restenosis. Ten patients redeveloped angina within 3 months of PTCA; nine developed a restenosis ¢ 60% and one had a 90% left circumflex stenosis that could not be dilated or grafted. Six of the 10 patients had a normal exercise ECG and scintigram at 1 month that became abnormal when symptoms reappeared. The ratepressure product before PTCA and when angina symptoms recurred was similar (18.00 ± 2.20 vs 23.58 + 6.7 units x 103) (NS). In conclusion, the use of clinical symptoms in conjunction with the physiologic data, ECG and myocardial scintigram acquired during exercise provide important short-term data on the angiographic evolution of PTCA results. The noninvasive tests may be useful in determining guidelines for repeat angiography in patients who have had PTCA.

The ability of technetium (Tc)-99m sestamibi myocardial perfusion imaging at rest to evaluate myocardial infarction and first-pass ejection fraction was studied in a trial involving 18 institutions. Protocol I compared regional perfusion with occurrence of infarction by Q wave or by gated blood pool scan wall motion abnormality in 146 patients. Protocol II assessed first-pass right and left ventricular ejection fraction in 85 patients. In protocol I, Tc-99m sestamibi images were abnormal in 104 of 111 patients (94%) with both a Q wave and a gated scan wall motion abnormality and was normal in 23 of 25 patients (92%) in whom both were normal. Therefore, concordance existed in 105 (94%) patients. Of 115 patients with a Q wave, 107 (93%) had an abnormal Tc-99m sestamibi study. Of 115 patients with a gated scan wall motion abnormality, 108 (94%) had an abnormal Tc-99m sestamibi study. Tc-99m sestamibi imaging showed corresponding perfusion abnormalities in 81% of 69 anterior Q-wave infarcts, 73% of 55 inferior Q-wave infarcts and 88% of 8 posterior infarcts. Specificity in normal regions on electrocardiography and wall motion was 91, 100 and 100%, respectively, for anterior, inferior and posterior regions, respectively, between wall motion and perfusion. Of 17 myocardial segments per patient, there was concordance in 74% of patients. First pass Tc-99m sestamibi imaging of ejection fraction agreed well with conventional first-pass imaging for the right and left ventricle. It is concluded that Tc-99m sestamibi myocardial imaging at rest reliably diagnoses and localizes infarction and assesses ejection fraction by first-pass imaging.

Conventional gamma cameras are designed for optimal performance only within a narrow energy window. To ensure adequate image quality, techniques using a wide energy spectrum, such as holospectral imaging (HI), require additional correction. A two-step post acquisition linearity correction algorithm has been developed for that purpose. First, the correction coefficients are evaluated based on the a...

Holospectral Imaging (HI), unlike the conventional technique, acquires data over a wide energy range. The new data is then used to form a series of frames corresponding to the object's spatial distribution at different energies. The multidimensional information is examined using the principal component analysis in order to characterize the different energy-dependent processes, namely: the primary photon information, the Compton scattering, the camera distorsions and the quantum noise. Each one of these factors has a typical location in the energy space RN (N is the number of energy frames). The primary photon is the main source of variance and has the most important contribution to the "principal" axis. In theory, without interference from other processes, the primaiy photon distribution defines a straight line in RN. Quantum noise will be distributed "around" this principal axis. However, scattering and camera distorsions will tend to pull the distribution toward a definite direction in the energy space. HI then finds, for each set of data, a transformation optimizing the "principal" information, the quality of this information being limited by the level of the statistical noise. Resulting images show an improvement in contrast to noise ratio and in quantitative analysis. We conclude that HI is a useful tool to describe the different contributions of scatter, camera non-uniformity and quantum noise to image variance. Therefore, energy variable should be included in the generalized transfer function of future nuclear medicine imaging systems.

Technetium-99m-hexamibi (methoxy isobutyl isonitrile) is a Tc-99m-hexakis analog that can be used as a myocardial perfusion imaging agent. This is a report of an initial study that was performed in four institutions to assess the feasibility of Tc-99m-hexamibi myocardial imaging for the detection of coronary artery disease in patients undergoing treadmill stress test. Thirty-three patients referred for evaluation of chest pain had two exercise stress tests, one with Tl-201 and at least 24 hours after, and a second one with Tc-99m-hexamibi. Myocardial planar imaging started 60 minutes after injection at stress of 10-20 mCi of Tc-99m-hexamibi. Because this agent does not redistribute in myocardium after a stress injection, a second injection of 10-20 mCi of Tc-99m-hexamibi was performed with the patient at rest a few days later. Qualitative assessment of both Tl-201 and Tc-99m-hexamibi myocardial distribution was performed in 297 left ventricle segments (three segments of each of three views). There was a good correlation for the presence of normality, scar, or ischemia with the two radiopharmaceuticals, both on a segment by segment (259/297, or 87.2%) and patient-by-patient basis (29/33, or 87.9%). The number of segments found ischemic with Tl-201 and with Tc-99m-hexamibi were nearly equal, as were the number that were normal with one radiopharmaceutical and ischemic by the other. This initial study demonstrates that it is possible to detect stress-induced abnormalities of myocardial perfusion with Tc-99m-hexamibi similar to Tl-201 imaging.

99mTc-hexamibi (methoxy isobutyl isonitrile) is a new 99mTc-hexakis analog that can be used as a myocardial perfusion imaging agent. The purposes of this study were to compare 99mTc-hexamibi to 201Tl-thallous chloride myocardial stress scintigraphy in patients referred for investigation of chest pain and to evaluate the sensitivity of 99mTc-hexamibi in detection of coronary artery disease. One hundred patients were prospectively studied with both 201Tl and 99mTc-hexamibi planar imaging. Sixty five patients had a current coronary angiography. There was a total of 97 significantly (≤70%) stenosed major coronary arteries. 99mTc-hexamibi (25 mCi) study was done within a week of the 201Tl scan with similar double products upon standard treadmil stress testing. Rest studies with 99mTc-hexamibi were obtained 24–48 h after the stress test using the same acquisition parameters and dose. Analysis was performed blind by three observers. The left ventricle was divided into five segments in each image. Analysis of 201Tl and 99mTc-hexamibi results in 1500 left ventricle segments showed an overall agreement in 1326/1500 (88.4%) segments. Correlation between the patient diagnosis on the 201Tl and 99mTc-hexamibi studies showed an agreement in 89 patients (89%). 201Tl revealed myocardial uptake defects in 526 segments, detecting 72 out of 97 (74.2%) significantly stenosed coronary arteries and 99mTc-hexamibi detected 513 segments corresponding to 68 (70.1%) stenosed arteries (no significant statistical difference). In conclusion, these results show a good correlation between 201Tl and 99mTc-hexamibi myocardial imaging in the detection of significant coronary artery disease.

An approach to image analysis and processing, called holospectral imaging, is proposed for dealing with Compton scattering contamination in nuclear medicine imaging. The method requires that energy information be available for all detected photons. A set of frames (typically 16) representing the spatial distribution at different energies is then formed. The relationship between these energy frames is analyzed, and the original data is transformed into a series of eigenimages and eigenvalues. In this space it is possible to distinguish the specific contribution to the image of both primary and scattered photons and, in addition, noise. Under the hypothesis that the contribution of the primary photons dominates the image structure, a filtering process can be performed to reduce the scattered contamination. The proportion of scattered information removed by the filtering process is evaluated for all images and depends on the level of residual quantum noise, which is estimated from the size of the smaller eigenvalues. Results indicate a slight increase in the statistical noise but also an increase in contrast and greatly improved ability to quantitate the image.

Unlike 201Tl, 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) does not redistribute in the myocardium after injection. Thus, two separate injections of this new myocardial perfusion agent are required to differentiate ischemia from scar. An injection at stress followed by a 2nd injection at rest performed 24 h later, or the inverse, has been proposed. This protocol is not ideal in clinical practice. It would be preferred if both injections were performed on the same day. Fifteen patients with significant coronary artery disease demonstrated by coronary angiography and with at least one ischemic segment on the myocardial 201Tl study were evaluated within two weeks with the following protocol. On the same day (short time interval protocol), 3 images, each of 10 min duration (anterior, 45° LAO and 70° LAO views) were performed between 30 to 60 min after the injection at rest of 7–10 mCi 99mTc-MIBI. On completion of the rest study, the patient received 25–30 mCi 99mTc-MIBI at stress and images were again obtained 30 to 60 min later. Two days later (long time interval protocol) a stress study alone was repeated using 10 mCi 99mTc-MIBI with the same imaging time. Qualitative and quantitative comparisons between the short and the long time interval studies were performed by four experienced observers. Both protocols showed the same number of ischemic segments (52/225) and fixed defects (19/225). The diagnostic information of images was judged similar in nine patients while the short protocol was judged superior to the long protocol in five patients and inferior in 1. Normal to abnormal wall ratios were 1.33±0.12 for the short and 1.28±0.10 for the long protocol. Comparison of the 201Tl scans with 99mTc-MIBI studies showed agreement in 90% of the myocardial segments. Injection of a low dose of 99mTc-MIBI at rest followed 1 h later by a higher dose at stress is a valuable and useful alternative for myocardial perfusion imaging with 99mTc-MIBI in clinical practice.

The effects of reperfusion on the myocardial accumulation of neutrophils and their role in the extent of injury were investigated in a canine preparation with a 3 hr coronary occlusion followed by 21 hr of reperfusion. The left anterior descending coronary artery (LAD) was permanently occluded in group 1 and reperfused after 3 hr in four others (groups 2 to 5). All but group 5 received lidocaine (1 mg/min over 8 hr). A critical stenosis was produced and left in place at reperfusion only in group 2. In groups 1 and 2, 111In-labeled autologous neutrophils were injected at the time of coronary occlusion. Group 4 animals were rendered leukopenic 2 hr before the coronary ligature and throughout the experiment by injection of an antineutrophil rabbit serum. Quantification of the radioactivity by digitized scintigraphy of the heart slices revealed an 80% (p less than .05) increase in neutrophil accumulation in the infarct region after reperfusion (group 2) as compared with permanent occlusion (group 1). Gamma counting of myocardial tissue samples showed that the neutrophil accumulation ratio in the subendocardial central zone of the infarct was increased five times (p less than .05) by reperfusion, whereas no difference was evident in the subepicardium. Infarct size and myocardial area at risk were not statistically different among the five groups. However LAD flow in the leukopenic group (group 4) was significantly higher (p less than .05) 30 min after reperfusion (40.0 +/- 5 ml/min) when compared with the preocclusion value (21.7 +/- 4 ml/min). In contrast, in a parallel experiment without leukopenia (group 3), LAD flow after reperfusion did not differ from the preocclusion value.(ABSTRACT TRUNCATED AT 250 WORDS)

The frequency content of the ungated radionuclide time-activity curves for left and right ventricles was analyzed using a power spectrum estimation technique. This technique was applied to ten patients. It was observed that 75% of the contraction power of any ventricle was contained in the fundamental and at least 98% contained in the fundamental plus the first harmonic. Patients presenting bigeminy and trigeminy had a completely different spectrum distribution which calls for a different interpretation. Low frequency spectrum lines have been observed at breathing frequency. Up to 62% of the total power may be contained in those spectrum lines.