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The interpretations of 156 99mtechnetium pyrophosphate myocardial scintigrams by four observers were analyzed in order to determine the reliability and reproducibility of the subjective process of reading scintigrams. The scintigrams were scored on an integral scale from 0 to 4, depending upon the degree of myocardial radionuclide accumulation, and the site and nature of uptake were specified. Exact agreement upon score was generally poor but approximate concurrence of interpretation was good (90.4 and 92.5% inter- and intra-observer agreement, respectively). There was somewhat less agreement on scintigrams with the higher scores of 3 and 4 (83.3 and 78.0%, respectively). A high level of concurrence upon the differentiation between diffuse and localized uptake, and upon the site of uptake, was found. We conclude that only approximate rather than exact agreement of individual readers' interpretations can be expected in this subjective technique, that scintigrams with higher degrees of radionuclide accumulation produce slightly greater observer disagreement, and that variability of interpretation could account for some of the diagnostic inaccuracy of 99mtechnetium pyrophosphate myocardial scintigraphy.

The effects of exercise training on exercise myocardial perfusion and left ventricular (LV) function in the first 6 months after clinically uncomplicated acute myocardial infarction (AMI) were assessed in 53 consecutive men aged 55 +/- 9 years. Symptom-limited treadmill exercise with thallium myocardial perfusion scintigraphy and symptom-limited upright bicycle ergometry with equilibrium gated radionuclide ventriculography were performed 3, 11 and 26 weeks after AMI by 23 men randomized to training and 30 randomized to no training. Peak cycle capacity increased in both groups between 3 and 26 weeks (p less than 0.01), but reached higher levels in trained than in untrained patients (803 +/- 149 vs 648 +/- 182 kg-m/min, p less than 0.01). Reversible thallium perfusion defects were significantly more frequent at 3 than at 26 weeks: 59% and 36% of patients, respectively (p less than 0.05), without significant inter-group differences. Values of LV ejection fraction at rest, submaximal and peak exercise did not change significantly in either group. The increase in functional capacity, i.e., peak treadmill or bicycle workload, that occurred 3 to 26 weeks after infarction was significantly correlated with the increase in peak exercise heart rate (p less than 0.001), but not with changes in myocardial perfusion or LV function determined by radionuclide techniques. Changes in myocardial perfusion or LV function do not appear to account for the improvement in peak functional capacity that occurs within the first 6 months after clinically uncomplicated AMI.

Features extracted from static or dynamic scintigraphic images can be used to produce parametric or functional images. Those images typically map a dynamic parameter (temporal encoding) or a quantitative measure of the tracer distribution. In this report, we consider the cases in which the nature of the extracted feature is well suited for a quantitative normative evaluation, ie, where the values obtained can be directly or indirectly compared with expected normal values. The major difference between this approach and the more common heuristic or synoptic interpretation of "images" lies in the underlying modeling: the model "predicts" a minimal washout rate, a match between ventilation and perfusion rates in the lungs, homogeneous contraction in the left ventricle, an expected angular distribution of thallium in the myocardium, or the absence of an additional kinetic feature. The quantitative aspect of the analysis is based in all cases on an approach that overcomes or is less sensitive to morphological or structural biological variability: in some cases the patient provides the normalizing data, as in ventilation-perfusion ratios. In other cases, the model predicts homogeneous results (as in phase analysis) or a range of normal physiological values (for xenon washout). Less commonly, the analysis requires a transformation of the data, as is the case in the analysis of myocardial perfusion, which follows a polar transformation of the image, and an analysis based on angular coordinates. In a normative approach, pathology is defined as a deviation (in this case a quantitative deviation) from the norm. The next step is to model specific abnormalities: early right-sided reappearance of the bolus in a right-to-left shunt, the appearance of "abnormal" kinetic factors, or a comparison with the expected distribution of bloodflow (or location of defects) in certain coronary lesions. However, in all cases, one should note that the analysis does not compromise the major feature of "imaging," that is to recognize regional, rather than exclusively global malfunction.

Three cases with photopenic lesions on bone scintigraphy due to metastases from osteogenic sarcoma are presented.

The mechanisms responsible for the decrease in exercise capacity after bed rest were assessed in 12 apparently healthy men aged 50 +/- 4 years who underwent equilibrium gated blood pool scintigraphy during supine and upright multistage bicycle ergometry before and after 10 days of bed rest. After bed rest, echocardiographically measured supine resting left ventricular end-diastolic volume decreased by 16% (p less than 0.05). Peak oxygen uptake during supine effort after bed rest was diminished by 6% (p = not significant [NS]), whereas peak oxygen uptake during upright effort declined by 15% (p less than 0.05). After bed rest, increases in heart rate were also greater during exercise in the upright than in the supine position (p less than 0.05). Values of left ventricular ejection fraction increased normally during both supine and upright effort after bed rest and were higher than corresponding values before bed rest (p less than 0.05). After bed rest, increased left ventricular ejection fraction and heart rate largely compensated for the reduced cardiac volume during supine effort, but these mechanisms were insufficient to maintain oxygen transport capacity at levels during upright effort before bed rest. These results indicate that orthostatically induced cardiac underfilling, not physical deconditioning or left ventricular dysfunction, is the major cause of reduced effort tolerance after 10 days of bed rest in normal middle-aged men.

Selection of a nuclear medicine computer system is a process that should be approached with care and forethought. The general scheme should be to define your needs and constraints, determine what is available, investigate the leading candidates, make a site visit, and, finally, submit an order. Through a series of discussions between members of the Computer Council of the Society of Nuclear Medicine and representatives from the manufacturers of computer systems, a set of important considerations emerged, which are reported in this paper. This paper is not intended to be a step-by-step guideline to the purchase of a computer system. Rather, it is a set of concepts and considerations with which the prospective purchaser should be familiar before undertaking such a purchase.

The in vivo distribution of vesicles containing radiopharmaceuticals in their cavities has been studied using three routes of administration: intravenous, subcutaneous, and intraperitoneal. The in vivo distribution in mice was determined by dissection of the animals and calculation of radioactivity in the organs. In rats the in vivo distribution was assessed by scintigraphy using a scintillation camera-digital computer unit. After intravenous injection of vesicles, radioactivity is concentrated to some extent in the liver and spleen but the pattern of distribution is different from that of the corresponding free radiopharmaceutical or radiocolloid made of the corresponding radionuclide. The permeability of the vesicular membrane to contained radiopharmaceutical has been shown to vary according to the chemical composition of the vesicles. Vesicles can be used to introduce materials in vivo and the potential exists for their specific targeting by coupling other molecules to their surfaces.

We examined radionuclide-determined left ventricular ejection fractions (LVEF) at rest and during graded exercise in 37 patients receiving doxorubicin (Adriamycin) therapy in whom the risk of developing congestive heart failure (CHF) was precisely defined by endomyocardial biopsy and right heart catheterization. Echocardiographic (Echo %FS) and phonocardiographic (PEP/LVET) measurements of LV function were also determined. An abnormal LVEF at rest (less than or equal to 45%) had a sensitivity of 53% and a specificity of 75% for detecting patients at moderate or high risk of developing CHF. The addition of exercise LVEF increased the sensitivity of detection of moderate or high-risk patients to 89% but lowered the specificity to 41%. Exercise LVEF improved the sensitivity of detection of high-risk patients from 58% to 100%. Echo %FS and PEP/LVET yielded lower sensitivities than rest or exercise LVEF. As a single test, exercise LVEF possesses the sensitivity for use as a screening method for anthracycline cardiotoxicity, but the lack of specificity prevents the use of single values as a definitive test. Single rest LVEF determinations, although more specific than exercise LVEF, do not possess the sensitivity for use as screening or definitive tests.

Successful heterotopic cardiac transplantation in a 24 year old man with end stage cardiomyopathy provided an opportunity to study cardiovascular physiology. The donor and native hearts, functioning independently in parallel, were studied by serial physical examination, electrocardiography, echocardiography, nuclear angiography and cardiac catheterization. Results indicated that the donor left heart assumed the predominant role in supplying systemic output, possibly contributing to decreasing function of the patient's own (native) heart. Analysis of serial nuclear angiograms revealed an initial postoperative ejection fraction of 52 and 21 percent in the donor and the native left ventricle, respectively; repeat studies 3 months postoperatively showed values of 50 and 9 percent, respectively, indicating significant deterioration in native left ventricular cardiac function. Observation of valve motion of the native heart showed major irregularities of the aortic valve in contrast to seemingly normal, regular mitral valve motion. These data rise interesting questions regarding interpretation of valve motion as an indicator of ventricular function.

In 3 patients, each of whom had previously had part of one kidney included within the field during radiation therapy, whole-body bone imaging using 99mTc-pyrophosphate showed increased activity in the irradiated renal segment. Possible mechanisms of such renal uptake are discussed.

Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentration was studied in 23 runners before and after a marathon race. Blood samples were drawn from an antecubital vein the morning before the race (baseline), at 3 p.m. 2 h before the start, on finishing, and 12 and 36 h later. Compared to the baseline values, erythrocyte 2,3-DPG concentration was increased (p less than 0.001) immediately after the marathon from 4.62 +/- 0.14 to 5.56 +/- 0.13 mumol.ml-1 RBC and remained elevated 12 h later (5.45 +/- 0.14 mumol.ml-1 RBC): it returned to prerace values 36 h after completion of the marathon.

The value of ventilation studies in conjunction with pulmonary perfusion scintigraphies for the diagnosis of pulmonary emboli is reviewed. A retrospective study of 273 consecutive cases and comparison with 42 angiographic results provides the data base. The data are compared with previously reported results and confirm the diagnostic gain obtained by ventilation studies. Possible advantages of the use of krypton-81m for the ventilation study are suggested. Finally, with the observed prevalence of six possible scintigraphic outcomes and assuming that two outcomes are diagnostic, it can be shown that the addition of a ventilation study in the diagnostic work-up decreases the average cost of the diagnosis.

The purpose of single photon emission computed tomography (SPECT) data is to map the tracer concentration from the three-dimensional object into a three-dimensional image array. The conventional interrogation of the data is through slice interrogation. In this paper we explore display methods in which the data are directly interrogated and processed as three-dimensional data. This includes direct addressing of sagittal, transverse, and frontal slices, around a targeted subvolume, and direct addressing of nonorthogonal slices. The three-dimensional aspect of the data is further accommodated by thresholding and edge definition in space. Finally, morphological information, which is sparse in scintigraphic slices, is recaptured by the generation of planar data derived from data processed in the three-dimensional space.

Plasma indicators of muscle cell leakage and of hemolysis were studied in 23 runners before and after a marathon race. Blood samples were drawn from an antecubital vein the morning before the race (baseline), at 3 p.m., i.e., 2 h before the start, on arrival, 12 and 36 h, and 7 days later. Compared with the baseline values, the plasma creatinine phosphokinase MM and MB subfractions, aldolase and glutamicoxaloacetic transaminase activity were increased immediately after the race, rose further 12 h after the marathon, and remained elevated the race, rose further 12 h after the marathon, and remained elevated 36 h and 7 days later. The plasma lactate dehydrogenase activity and myoglobin concentration were increased on arrival and returned to the pre-race activity 7 days after the marathon. Compared with the pre-race values, the plasma haptoglobin concentration was decreased immediately and 12 h after the marathon. Our data show that indicators of muscle cell leakage and of hemolysis in plasma, withdrawn after a marathon race, remained elevated for up to 7 days after the race.

The precise delineation of the left ventricular projection area is an essential part in the quantitative analysis of nuclear angiocardiograms. We have devised an algorithm that permits automation of this step, based on a one-dimensional Laplace operator whose kernel is 2, 2, -2, -4, -2, 2, 2. The operator characteristically enhances "valleys" more than edges and, therefore, favors septal and the valve plane detection. The operator is applied vertically, horizontally, and along both diagonals. Each pass is immediately followed by a local maximum search during which the image resulting from the Laplacian operator is reduced to a binary one, with zeros everywhere except where a local maximum was found along the path of the operator. This resultant image yields a closed "edge" around the left ventricle, even though many structures outside the left ventricle are also delineated. However, the centroid of the ventricle is defined from functional criteria and the region of interest is defined from centroid to first edge. The method has been applied to first-pass and gated studies in anterior and 45 degree left anterior oblique views. In 100 successive cases the ejection fraction obtained automatically was compared to the manual result. The regression equation yielded the relation: automatic method (%) = 1.7 + 1.0 manual method (%) +/-2% (r = 0.995), which is not significantly different from the identity relation. The failure rate was low (13%) but varied from 28% in the first-pass studies in the anterior view, to less than 8% in gated studies in the left ventricular oblique projection.

Eighty-eight patients with maxillary-facial abnormalities were studied with 99mTc-labeled phosphate compounds. Straight and tilted anterior views plus oblique orbital and lateral views were correlated with 201 thallium transmission images of a dried skull. Interpretation of any single view may be hampered by various superimposed structures. Careful patient positioning with multiple views allows for parallactic correlation which is crucial if radiotherapy, biopsy, or corroborative studies are planned.

The contribution of the donor heart to total circulatory performance after heterotopic heart transplantation has been difficult to assess. First-pass nuclear angiocardiography and directional Doppler echocardiography were used to examine separately left and right ventricular function of the donor heart after heterotopic transplantation. A comparison was made between two patients, one with a low initial pulmonary vascular resistance and one with a high, relatively fixed pulmonary vascular resistance. In both cases, currently available noninvasive techniques allowed confirmation of the expectation that the donor left ventricle can function effectively as a left ventricular bypass. In neither case was recovery of the native heart demonstrated. The contribution of the donor right ventricle to total right ventricular output appeared to be dependent on the condition of the donor heart and on the pulmonary vascular resistance. In situations with a high pulmonary vascular resistance and end-stage right ventricular failure, it was concluded that the donor heart may not at first constitute an effective assist for the native right ventricle. Native right ventricular failure may then become a major factor influencing survival after heterotopic heart transplantation.

Thallium-201 myocardial imaging was performed in seven long-term cardiac transplant survivors who were undergoing selective coronary arteriography as a screening test for immune mediated coronary atherosclerosis. The radionuclide studies showed fixed defects in all patients, though none was known to have had a myocardial infarction. Such abnormalities may be due to previous rejection episodes. Reversible ('ischaemic') defects were present in two patients with triple vessel disease, and were also seen in three subjects with minor (less than 50% luminal diameter) stenosis. Ischaemic thallium-201 defects in cardiac transplant recipients indicate the presence of coronary artery disease, though the stenosis may be of a degree which would normally be considered haemodynamically non-significant. The possible role of small vessel disease in producing these defects is discussed.

Diltiazem and propranolol alone and in combination as antianginal agents were compared with placebo in 12 patients with stable exertional angina at Stanford University Medical Center. The patients performed symptom-limited, multi-stage upright bicycle ergometric exercise while undergoing radionuclide angiographic studies every two weeks while being treated with 90 mg of diltiazem four times daily, 60 mg of propranolol four times daily, a combination of 90 mg of diltiazem and 60 mg of propranolol four times daily, and placebo. Diltiazem, propranolol and a combination all significantly increased exercise duration compared to placebo (526 +/- 149, 525 +/- 115, and 549 +/- 129 vs 430 +/- 132 sec.). Although rate pressure product and heart rate decreased with diltiazem therapy at submaximal workloads, these values were unchanged at peak exercise in contrast to propranolol or the combination of propranolol or diltiazem. Diltiazem decreased the sub-maximal and maximal degree of exercise-induced ST segment depression by over 50% compared to placebo (P less than 0.01 vs placebo). Diltiazem resulted in a higher exercise left ventricular ejection fraction compared to placebo, propranolol or the combination of diltiazem or propranolol (all less than P less than 0.05). Sinus bradycardia or orthostatic hypertension occurred in four patients on the high-dose combination therapy and required dose reduction. We concluded that high-dose diltiazem, appeared to be even more effective than moderate-dose propranolol or the combination of diltiazem and propranolol in improving exercise tolerance, electrocardiographic evidence of myocardial ischaemia and left ventricular function in patients with stable effort angina due to occlusive coronary artery disease.

A method is presented for the quantitative interpretation of thallium-201 myocardial perfusion studies. The data are planar images collected immediately following the stress injection, and 4 to 6 hours later. Data analysis consists of preprocessing, including thresholding of the original data, and data reduction using a variant of the circumferential profile methods. The profiles are subdivided into segments, and for each segment the difference between the norm and the actual data is computed. This difference is a quantitative symptom, whose size is assumed to be related to the probability of having the disease. The relationship between the size of the symptom in each of nine segments (three segments/view in three views) and the probability of disease is expressed in a table in which for 30 diseases (combinations of vascular lesions) the sensitivity for each of the nine symptoms is described as a Gaussian function whose average and standard deviation are computed from previous validated cases. Using an arbitrary prevalence, the post-testing probability can then be computed using Bayes' formula sequentially. The sensitivities, however, are not expressed as a binary function of the presence or absence of a symptom, but as a distribution function defined by experience. The method is sensitive for the detection of isolated left anterior descending disease (100%) and triple vessel disease (96%). When specific combinations of vascular lesions are recognized the specificity increases from 79% (when unspecified abnormalities are recognized) to 87% when left anterior descending disease or triple vessel disease is recognized.(ABSTRACT TRUNCATED AT 250 WORDS)

This study examined the pathophysiology of the myocaridal damage produced by direct current shock over a dose range of 10 to 90 watt-seconds, applied directly to the heart in 26 dosgs. The extent of injury produced was assessed with creatine kinase depletion and light and electron microscopy, and was correlated with in vivo imaging and tissue distributions of the isotopes technetium-99m pyrophosphate and thallium-201. Changes in intramyocardial temperature and regional myocardial blood flow were also measured. Uptake of technetium-99m pyrophosphate occurred exponentially with graded increases in shocks, and this agent was more sensitive than thallium-201 in detecting injury both on imaging and at tissue level. The threshold for significant injury was approximately 30 watt-seconds, and on electron microscopy a characteristic feature was marked dehiscence of the intercalated disks between the damaged myocytes. The use of different-size paddles did not appear to affect the total number of cells damaged. However, with large paddles the injury was more superficial and spread over a wider area. With short time intervals between successive shocks, a greater amount of injury occurred, in part because of a compounding of the thermal component of the damage. Hypothermia can reduce the degree of injury.

The use of skeletal scintigraphy for the detection of metastatic disease of the bone is reviewed. The review is based on published data for sensitivity, specificity, yield and prognostic value. The analysis, and interpretation of published data is complicated by the variation in criteria. It appears nonetheless, that for a number of tumors the relative (in comparison with other methods) and absolute (based on outcome prediction) sensitivity is high. For certain tumors in early stages, and in asymptomatic patients the yield (of positive studies) is low, even when the prognostic value is high. Those factors should be weighed with the availability of therapeutic options to determine the clinical efficacy of skeletal scintigraphy.

A method is presented by which tomographic myocardial perfusion data are prepared for quantitative analysis. The method is characterized by an interrogation of the original data, which results in a size and shape normalization. The method is analogous to the circumferential profile methods used in planar scintigraphy but requires a polar-to-cartesian transformation from three to two dimensions. As was the case in the planar situation, centering and reorientation are explicit. The degree of data reduction is evaluated by reconstructing "idealized" three-dimensional data from the two-dimensional sampling vectors. The method differs from previously described approaches by the absence in the resulting vector of a coordinate reflecting cartesian coordinate in the original data (slice number).

Using the angiographic findings as the standard, we have examined the sensitivity and specificity of ECG-gated static thallium-201 myocardial images in 54 patients undergoing selective coronary arteriography. Gated and nongated images, each in anterior, 45 degrees LAO, and 65 degrees LAO projections, were processed by interpolative background subtraction. They were then analyzed separately by four independent observers who were unaware of patient identity, the results of coronary arteriography, and which studies were gated or nongated. No significant differences were observed between the gated and nongated images regarding sensitivity or specificity, the detection rate for reversible myocardial ischemia, the accuracy of prediction of arteriographic extent of disease, or the degree of inter- or intraobserver variability. We conclude that ECG-gated acquisition of T1-201 images does not produce any significant advantages, at least when interpolative background subtraction is used.

99m-technetium (Tc) pyrophosphate myocardial scintigrams of 55 patients with stable angina pectoris were compared with those of 13 normal subjects. The mean scintigraphic score, obtained by averaging the blinded interpretations of four readers scoring on an integral scale from 0 to 4, was significantly higher for the patients with angina than for the control subjects (1.36 compared with 0.48, P less than 0.001). Among the patients with angina, those who had a prior myocardial infarction had a higher mean scintigraphic grade than those without a previous infarction (1.73 versus 1.15, P less than 0.005), and the mean grade in both groups was higher than that of control subjects (P less than 0.001). Radionuclide uptake was predominantly diffuse in the patients with angina pectoris (70%), although in those with greater uptake accumulation tended to be localized. Three of the 68 subjects had high levels of radionuclide uptake but no clinical evidence of acute myocardial injury. This study demonstrates that excess myocardial accumulation of 99m-Tc pyrophosphate can occur in patients with stable angina pectoris.

One hundred and two previously treated lymphoma patients were studied with 111Indium bone marrow scans and bone marrow biopsies. The biopsies were considered to represent sampling errors when the cellularity of the biopsy did not reflect the general state of the marrow organ cellularity as demonstrated by the scan. In each instance the accuracy of the scan was confirmed by either another biopsy or the subsequent clinical course of the patient. Sampling errors were infrequent (1/51) in patients with normal peripheral blood counts and whose marrow had never been involved with tumor. Errors were especially likely (17/51) in patients who had had marrow involvement or those who had anemia, leukopenia, or thrombocytopenia. The 111Indium bone marrow scan allows the clinician to avoid selecting a biopsy site with a high risk for sampling error.

Regeneration of bone marrow following radiation only was investigated using 111Indium as a bone scanning agent. Factors which influence local marrow regeneration are dose, age of the patient, and the total amount of the marrow which was irradiated. Time effects are not demonstrated in this study, except to the extent that most regeneration did occur within the first 12 months following irradiation. The most striking finding is the effect of the irradiation volume. Apparent inconsistencies in earlier reports concerning the dose effect could be explained by this effect alone.

In this report we present a method for the quantitative description of the degree of deviation from the norm of 201thallium single photon emission tomographic (SPECT) data. Validation is obtained from the frequency of "positive" outcomes in subgroup of patients in whom the prevalence of coronary artery disease, for the group as a whole, is known, even if individual patient outcomes are not verified. This approach overcomes the bias associated with nonrandomized clinical studies, in which the likelihood that a more invasive but definitive procedure (coronary arteriogram) will be performed is influenced by the result of the outcome of the procedure under study.