Evaluation of simultaneous 201Tl/99mTc dual-isotope cardiac SPECT imaging with model-based crosstalk compensation using canine studies.

BACKGROUND: Simultaneous (201)Tl/(99m)Tc-sestamibi dual-isotope myocardial perfusion SPECT imaging can reduce imaging time and produce perfectly registered rest/stress images. However, crosstalk from (99m)Tc into (201)Tl images can significantly reduce (201)Tl image quality. We have developed a model-based compensation (MBC) method to compensate for this crosstalk. The method has previously been validated with phantom and simulation studies. In this study, we evaluated the MBC method using a canine model. METHODS: Left anterior descending or left circumflex coronary artery stenoses were created in 50 adult mongrel dogs weighing 20-30 kg. The dogs were injected with 111 MBq (3 mCi) of (201)Tl at rest, and a SPECT study acquired. Stress was induced by administering adenosine to the dog, followed by injection of 740 MBq (20 mCi) of (99m)Tc-sestamibi at peak stress. A second SPECT study was performed with data acquired in both (201)Tl and (99m)Tc energy windows to provide simultaneous dual-isotope projection data. The images were reconstructed using the ordered-subsets expectation-maximization reconstruction algorithm with compensation for attenuation, scatter, and detector response. For simultaneously acquired (201)Tl data, we also applied the MBC method to compensate for crosstalk contamination from (99m)Tc. RESULTS: Without compensation, (99m)Tc crosstalk increased the estimated (201)Tl activity concentration in the rest images and reduced defect contrast. After MBC, the (201)Tl images were in good agreement with the registered single-isotope images and ex vivo count data. The ischemic (IS) to non-ischemic (NIS) region (201)Tl activity concentration ratios were computed for single-isotope and dual-isotope studies. The correlation with ex vivo IS-NIS ratios was 0.815 after MBC, compared to the 0.495 from data without compensation. In addition, the regression line for the IS-NIS ratios with MBC was almost parallel to the line of identity with a slope of 0.93, compared to a slope of 0.45 without compensation. CONCLUSIONS: These results demonstrate that model-based crosstalk compensation can provide substantial reduction of crosstalk effects in simultaneously acquired myocardial perfusion SPECT images in living biological systems.

Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain.

D2 dopamine and S2 serotonin receptors were imaged and measured in healthy human subjects by positron emission tomography after intravenous injection of 11C-labeled 3-N-methylspiperone. Levels of receptor in the caudate nucleus, putamen, and frontal cerebral cortex declined over the age span studied (19 to 73 years). The decline in D2 receptor in males was different from that in females.

Imaging dopamine receptors in the human brain by positron tomography.

Neurotransmitter receptors may be involved in a number of neuropsychiatric disease states. The ligand 3-N-[11C]methylspiperone, which preferentially binds to dopamine receptors in vivo, was used to image the receptors by positron emission tomography scanning in baboons and in humans. This technique holds promise for noninvasive clinical studies of dopamine receptors in humans.

Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics.

In postmortem studies of patients with schizophrenia, D2 dopamine receptors in the basal ganglia have been observed to be more numerous than in patients with no history of neurological or psychiatric disease. Because most patients with schizophrenia are treated with neuroleptic drugs that block D2 dopamine receptors in the caudate nucleus, it has been suggested that this increase in the number of receptors is a result of adaptation to these drugs rather than a biochemical abnormality intrinsic to schizophrenia. With positron emission tomography (PET), the D2 dopamine receptor density in the caudate nucleus of living human beings was measured in normal volunteers and in two groups of patients with schizophrenia--one group that had never been treated with neuroleptics and another group that had been treated with these drugs. D2 dopamine receptor densities in the caudate nucleus were higher in both groups of patients than in the normal volunteers. Thus, schizophrenia itself is associated with an increase in brain D2 dopamine receptor density.

Progressive failure of coronary flow during reperfusion of myocardial infarction: documentation of the no reflow phenomenon with positron emission tomography.

During reperfusion of a myocardial infarct, development of microvascular occlusion may result in regional hypoperfusion ("no reflow") despite a patent infarct-related artery. This study examined the extent and time course of no reflow with use of rubidium-82 positron emission tomography. In 12 anesthetized dogs, the left anterior descending coronary artery was occluded for 90 min and then freely reperfused. Regional myocardial perfusion was imaged by serial rubidium-82 positron emission tomography during coronary occlusion and every 30 min during reperfusion. After 4 h of reperfusion, infarct size and no reflow zone were measured postmortem by triphenyltetrazolium and thioflavin staining, respectively. Perfusion defects evident on rubidium-82 images during coronary occlusion rapidly resolved during the early reflow period. However, a recurrent perfusion defect appeared after 1 to 2 h of reflow in all dogs. The severity of recurrent perfusion defects progressed with time; after 5 min of reflow, relative perfusion in the left anterior descending artery territory was 97 +/- 6% of that in the normal circumflex artery region, but perfusion decreased progressively to 68 +/- 5% after 2 h (p less than 0.05) and to 55 +/- 4% after 4 h of reperfusion (p less than 0.05 versus 2 h). As measured by radioactive tracer microspheres, endocardial blood flow decreased similarly in the postischemic left anterior descending artery region from 1.2 +/- 0.2 ml/min per g after 5 min of reflow to 0.4 +/- 0.1 ml/min per g after 3 h of reflow (p less than 0.01). Residual infarct perfusion, measured by rubidium-82 after 4 h of reflow, was related to both infarct size (r = -0.88) and the extent of the no reflow zone (r = -0.84) in the postmortem left ventricular sections. Thus, serial positron emission tomography with rubidium-82 demonstrates a progressive loss of infarct perfusion, beginning 1 to 2 h after initial restoration of blood flow despite patency of the infarct-related artery. This phenomenon is probably a manifestation of progressive microvascular occlusion within the reperfused myocardium.

Limitations of regional myocardial thallium clearance for identification of disease in individual coronary arteries.

The purpose of this study was to critically evaluate the usefulness of postexercise regional myocardial thallium-201 clearance for identifying disease in individual coronary arteries. Exercise and redistribution planar imaging studies were performed in 114 subjects, including 19 normal volunteers and 95 patients undergoing cardiac catheterization (70 with and 25 without greater than or equal to 50% narrowing in one or more coronary arteries). Thallium clearance was measured from predefined myocardial regions corresponding to the left anterior descending, left circumflex and right coronary arteries and was expressed as the percent decrease in activity at 4 h, assuming monoexponential clearance. In regions perfused by a normal or insignificantly diseased coronary artery, mean 4 h clearance was 58.9 +/- 9.4% for normal volunteers, 43.1 +/- 15.5% for catheterized patients without coronary artery disease and 36.3 +/- 24.9% for catheterized patients with coronary artery disease (p less than 0.001 patients with coronary artery disease versus normal volunteers). Clearance from normal regions was significantly associated with two measures of exercise performance: percent of predicted maximal heart rate achieved (r = 0.49) and exercise duration (r = 0.35). In regions perfused by a stenotic coronary artery, mean clearance was lower (31.1 +/- 19.8%) but was not significantly different from that in normal regions in the same patients. Clearance from diseased regions was also associated with maximal exercise heart rate (r = 0.28) and exercise duration (r = 0.41), but not with percent coronary artery stenosis (r = 0.02). After taking exercise performance into account, the number of diseased vessels or the presence or absence of disease in a given vessel had little influence on regional thallium clearance. Although measurement of regional post-exercise thallium clearance may help to identify stenotic coronary arteries in selected patients, variability related to exercise performance and other physiologic and technical factors greatly limits the clinical usefulness of absolute thallium clearance measurements.

Improved diagnostic performance of exercise thallium-201 single photon emission computed tomography over planar imaging in the diagnosis of coronary artery disease: a receiver operating characteristic analysis.

Qualitative interpretation of tomographic and planar scintigrams, a five point rating scale and receiver operating characteristic analysis were utilized to compare single photon emission computed tomography and conventional planar imaging of myocardial thallium-201 uptake in the accuracy of the diagnosis of coronary artery disease and individual vessel involvement. One hundred twelve patients undergoing cardiac catheterization and 23 normal volunteers performed symptom-limited treadmill exercise, followed by stress and redistribution imaging by both tomographic and planar techniques, with the order determined randomly. Paired receiver operating characteristic curves revealed that single photon emission computed tomography was more accurate than planar imaging over the entire range of decision thresholds for the overall detection and exclusion of coronary artery disease and involvement of the left anterior descending and left circumflex coronary arteries. Tomography offered relatively greater advantages in male patients and in patients with milder forms of coronary artery disease, who had no prior myocardial infarction, only single vessel involvement or no lesion greater than or equal to 50 to 69%. Tomography did not appear to provide improved diagnosis in women or in detection of disease in the right coronary artery. Although overall detection of coronary artery disease was not improved in patients with prior myocardial infarction, tomography provided improved identification of normal and abnormal vascular regions, particularly of the left anterior descending and circumflex artery regions. These results indicate that single photon emission computed tomography provides improved diagnostic performance compared with planar imaging in many clinical subgroups, and suggest that it represents the diagnostic imaging procedure of choice in exercise thallium-201 perfusion studies.

Cocaine-induced reduction of glucose utilization in human brain. A study using positron emission tomography and [fluorine 18]-fluorodeoxyglucose.

We examined the effects of cocaine hydrochloride (40 mg intravenously) on regional cerebral metabolic rates for glucose and on subjective self-reports of eight polydrug abusers in a double-blind, placebo-controlled, crossover study. The regional cerebral metabolic rate for glucose was measured by the [fluorine 18]-fluorodeoxyglucose method, using positron emission tomography. With eyes covered, subjects listened to a tape that presented white noise, "beep" prompts, and questions about subjective effects of cocaine or saline. Cocaine produced euphoria and reduced glucose utilization globally (mean reduction, 14%). Twenty-six of 29 brain regions (all neocortical areas, basal ganglia, portions of the hippocampal formation, thalamus, and midbrain) showed significant decrements (5% to 26%) in the regional cerebral metabolic rate for glucose. No significant effects of cocaine were observed in the pons, the cerebellar cortex, or the vermis. Right-greater-than-left hemispheric asymmetry of regional cerebral metabolic rates for glucose occurred in the lateral thalamus. The findings demonstrate that reduced cerebral metabolism is associated with cocaine-induced euphoria.

Morphine-induced metabolic changes in human brain. Studies with positron emission tomography and [fluorine 18]fluorodeoxyglucose.

Morphine sulfate effects (30 mg, intramuscularly) on cerebral glucose utilization and subjective self-reports were examined in 12 polydrug abusers by positron emission tomography and [fluorine 18]fluorodeoxyglucose in a double-blind placebo-controlled crossover study. During testing, subjects sat with eyes covered, listening to white noise and "beep" prompts. Morphine significantly reduced glucose utilization by 10% in whole brain and by about 5% to 15% in telencephalic areas and the cerebellar cortex, assuming no contribution of hypercapnia. When the contribution of PaCO2 (45 minutes after morphine was administered) was partialled out, significant morphine-induced reductions persisted in whole brain and six cortical areas. Irrespective of morphine, left-greater-than-right asymmetry occurred in the temporal cortex, and an interaction between hemisphere and drug was noted in the postcentral gyrus. In most cases, effects on glucose utilization were not significantly related to measures of euphoria.

In vivo D2 dopamine receptor density in psychotic and nonpsychotic patients with bipolar disorder.

BACKGROUND: A prior positron emission tomographic study from The Johns Hopkins University, Baltimore, Md, using N-methylspiperone labeled with carbon 11 reported elevated basal ganglia D2 dopamine receptor density (Bmax) values in neuroleptic-naive schizophrenic patients compared with controls. We have now extended these studies to include patients with bipolar disorder. METHODS: Patients with bipolar disorder (n = 14) either had never received neuroleptic medication or had been neuroleptic-free for more than 6 months, and they met DSM-III criteria for currently symptomatic affective disorder. Patients with bipolar disorder were compared with matched schizophrenic patients and normal controls. All received two positron emission tomographic scans, the second of which was preceded by oral administration of haloperidol lactate, to permit the calculation of D2 dopamine receptor Bmax. RESULTS: Diagnostic groups differed in Bmax by analysis of variance (P < .0001); post hoc tests showed higher Bmax values for psychotic patients with bipolar disorder and schizophrenic patients compared with normal controls and for schizophrenic patients and psychotic patients with bipolar disorder compared with nonpsychotic patients with bipolar disorder. Among patients with bipolar disorder, Bmax values correlated significantly with the severity of psychotic symptoms (r = .63) on the Present State Examination but not with the severity of nonpsychotic mood symptoms. CONCLUSIONS: We conclude that, like schizophrenic patients, patients with psychotic bipolar disorder have elevations of D2 dopamine receptor Bmax values and that such elevations in affective disorder are more closely associated with the presence of psychosis than with mood abnormality. Elevations in dopamine receptor values thus may occur in psychiatric states that are characterized by psychotic symptoms rather than being specific to schizophrenia.

The influence of biological and technical factors on the variability of global and regional brain metabolism of 2-[18F]fluoro-2-deoxy-D-glucose.

This study investigated the influence of biological and technical factors on variations of global and regional cerebral metabolic rate of glucose (CMRglc) measured with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG). Twelve male volunteers (22-40 years) were investigated on three or four occasions for a total of 42 studies. We calculated the variance/covariance of the following parameters: CMRglc, six parameters of the blood clearance of [18F]FDG, hour of injection, peak time of blood radioactivity, and six components of the operational equation (nonradioactive blood glucose concentration, brain radioactivity, two integrals, numerator, and denominator). There was correlation among these six components, except for nonradioactive blood glucose. However, the correlation between the CMRglc and the individual components of the operational equation was poor. The inter- and intrapersonal CMRglc coefficients of variations were 13.8 and 7.1%, respectively. In contrast, coefficients of variations of the numerator and denominator of the operational equation were 34.6 and 32.6%, respectively, and were always in the same direction. No correlation was found between CMRglc and the technical factors in the numerator and denominator of the operational equation. Factor analysis disclosed that a single factor was responsible for 70% of the variance. This factor included caudate, putamen, thalamus, frontal cortex, temporal cortex, and cingulate gyrus. These structures are involved with multiple complex functions, from autonomic motor control to behavior and emotions. The intrinsic metabolic variability of these structures, along with the basal metabolic processes that are continuously going on in the brain, may be the best explanation for the variance encountered in our investigation.

Comparison of [11C]diprenorphine and [11C]carfentanil binding to opiate receptors in humans by positron emission tomography.

The kinetics and regional distribution of [11C]carfentanil, a mu-selective opiate receptor agonist, and [11C]diprenorphine, a nonselective opiate receptor antagonist, were compared using paired positron emission tomography studies in two normal volunteers. Kinetics of total radioactivity (counts/mCi/pixel) was greater for [11C]diprenorphine than [11C]carfentanil in all regions. [11C]Carfentanil binding (expressed as the total/nonspecific ratio) reached near equilibrium at approximately 40 min, whereas [11C]diprenorphine showed a linear increase until approximately 60 min. Kinetics of specific binding demonstrated significant dissociation of [11C]carfentanil from opiate receptors, whereas little dissociation of [11C]diprenorphine was observed during the 90-min scan session. Regional distributions of [11C]carfentanil and [11C]diprenorphine were qualitatively and quantitatively different: Relative to the thalamus (a region with known predominance of mu-receptors), [11C]diprenorphine displayed greater binding in the striatum and cingulate and frontal cortex compared to [11C]carfentanil, consistent with labeling of additional, non-mu sites by [11C]diprenorphine. We conclude from these studies that [11C]diprenorphine labels other opiate receptor subtypes in addition to the mu sites selectively labeled by [11C]carfentanil. The nonselective nature of diprenorphine potentially limits its usefulness in defining abnormalities of specific opiate receptor subtypes in various diseases. Development of selective tracers for the delta- and kappa-opiate receptor sites, or alternatively use of unlabeled inhibitors to differentially displace mu, delta, and kappa subtypes, will help offset these limitations.

Quantification of Neuroreceptors in the living human brain. II. Inhibition studies of receptor density and affinity.

A method for estimating receptor density (Bmax) in the living human brain by positron emission tomography was exemplified by a ligand, 3-N-[11C]methylspiperone ([11C]NMSP), that binds to D2 dopamine receptors with high affinity. The ligand binds essentially irreversibly (i.e., with very little dissociation) to the receptors during the 2-h scanning period. Transfer constants were estimated at steady state. In a previous article, we presented a method for the determination of k3, the rate of binding of the labeled ligand. In the present work, we varied k3 by reducing the number of available receptors with a previously administered receptor blocking agent, haloperidol. We calculated a receptor density of 9.2 pmol g-1 in the caudate nucleus of four normal volunteers, and an inhibitory constant of haloperidol of 1.4 nM by comparing tracer accumulation in the absence and the presence of the blocking agent. The values agreed with measurements of NMSP receptor density and haloperidol inhibitory potency in vitro in brain homogenates from human autopsy material.

Measurement of radiotracer concentration in brain gray matter using positron emission tomography: MRI-based correction for partial volume effects.

Accuracy in in vivo quantitation of brain function with positron emission tomography (PET) has often been limited by partial volume effects. This limitation becomes prominent in studies of aging and degenerative brain diseases where partial volume effects vary with different degrees of atrophy. The present study describes how the actual gray matter (GM) tracer concentration can be estimated using an algorithm that relates the regional fraction of GM to partial volume effects. The regional fraction of GM was determined by magnetic resonance imaging (MRI). The procedure is designated as GM PET. In computer simulations and phantom studies, the GM PET algorithm permitted a 100% recovery of the actual tracer concentration in neocortical GM and hippocampus, irrespective of the GM volume. GM PET was applied in a test case of temporal lobe epilepsy revealing an increase in radiotracer activity in GM that was undetected in the PET image before correction for partial volume effects. In computer simulations, errors in the segmentation of GM and errors in registration of PET and MRI images resulted in less than 15% inaccuracy in the GM PET image. In conclusion, GM PET permits accurate determination of the actual radiotracer concentration in human brain GM in vivo. The method differentiates whether a change in the apparent radiotracer concentration reflects solely an alteration in GM volume or rather a change in radiotracer concentration per unit volume of GM.

MR-based correction of brain PET measurements for heterogeneous gray matter radioactivity distribution.

Partial volume and mixed tissue sampling errors can cause significant inaccuracy in quantitative positron emission tomographic (PET) measurements. We previously described a method of correcting PET data for the effects of partial volume averaging on gray matter (GM) quantitation; however, this method may incompletely correct GM structures when local tissue concentrations are highly heterogeneous. We have extended this three-compartment algorithm to include a fourth compartment: a GM volume of interest (VOI) that can be delineated on magnetic resonance (MR) imaging. Computer simulations of PET images created from human MR data demonstrated errors of up to 120% in assigned activity values in small brain structures in uncorrected data. Four-compartment correction achieved full recovery of a wide range of coded activity in GM VOIs such as the amygdala, caudate, and thalamus. Further validation was performed in an agarose brain phantom in actual PET acquisitions. Implementation of this partial volume correction approach in [18F]fluorodeoxyglucose and [11C]-carfentanil PET data acquired in a healthy elderly human subject was also performed. This newly developed MR-based partial volume correction algorithm permits the accurate determination of the true radioactivity concentration in specific structures that can be defined by MR by accounting for the influence of heterogeneity of GM radioactivity.

Multicompartmental analysis of [11C]-carfentanil binding to opiate receptors in humans measured by positron emission tomography.

[11C]-Carfentanil is a high affinity opiate agonist that can be used to localize mu opiate receptors in humans by positron emission tomography (PET). A four-compartment model was used to obtain quantitative estimates of rate constants for receptor association and dissociation. PET studies were performed in five normal subjects in the absence and presence of 1 mg/kg naloxone. Arterial plasma concentration of [11C]-carfentanil and its labeled metabolites were determined during each PET study. The value of k3/k4 = Bmax/kD was determined for each subject in the presence and absence of naloxone. There was a significant reduction in the value of k3/k4 from 3.4 +/- 0.92 to 0.26 +/- 0.13 in the thalamus (p less than 0.01) and from 1.8 +/- 0.33 to 0.16 +/- 0.065 in the frontal cortex (p less than 0.001). Mean values of frontal cortex/occipital cortex and thalamus/occipital cortex ratios were determined for the interval 35-70 min after injection when receptor binding is high relative to nonspecific binding. The relationship between the measured region/occipital cortex values and the corresponding values of k3/k4 in the presence and absence of naloxone was: regions/occipital cortex = 0.95 + 0.74 (k3/k4) with r = 0.98 (n = 20). Simulation studies also demonstrated a linear relationship between the thalamus/occipital cortex or frontal cortex/occipital cortex ratio and k3/k4 for less than twofold increases or decreases in k3/k4. Simulation studies in which thalamic blood flow was varied demonstrated no significant effect on the region/occipital cortex ratio at 35-70 min for a twofold increase or fourfold decrease in blood flow. Therefore, the region/occipital cortex ratio can be used to quantitate changes in k3/k4 when tracer kinetic modeling is not feasible.

PET imaging of cortical S2 serotonin receptors after stroke: lateralized changes and relationship to depression.

Patients with right-hemisphere strokes (N = 9) more than 1 year after injury had greater cortical binding of (3-N-[11C]methyl)spiperone than a similar group of patients with left-hemisphere strokes (N = 8) or normal control subjects (N = 17). The higher S2 serotonin receptor binding occurred in uninjured regions of the right parietal and temporal cortex. The ratio of binding in the ipsilateral to contralateral cortex showed a significant negative correlation with severity of depression scores in the left temporal cortex. These findings suggest that the biochemical response of the brain may be different depending on which hemisphere is injured and that some depressions may be a consequence of the failure to upregulate serotonin receptors after stroke.

Past adult lead exposure is associated with longitudinal decline in cognitive function.

OBJECTIVE: To determine whether adults with past exposure to neurotoxicants have progressive declines in cognitive function years after exposure has ceased, and whether tibia lead is a predictor of the magnitude of change. METHODS: A total of 535 former organolead manufacturing workers with a mean age of 55.6 years, a mean duration of 16 years since last occupational lead exposure, and low blood lead levels at the first study visit and 118 controls were evaluated with neurobehavioral tests two to four times over 4 years. "Peak" tibia lead levels, estimated from current levels measured by X-ray fluorescence, were used to predict changes in cognitive function over time. RESULTS: In former lead workers, peak tibia lead ranged from -2.2 to 98.7 microg Pb/g bone mineral. Compared to controls, former lead workers performed worse over time for three tests of visuo-constructive ability and verbal memory and learning (p < 0.05). In former lead workers, peak tibia lead predicted declines for six tests of verbal memory and learning, visual memory, executive ability, and manual dexterity (p < 0.05 for four tests and < 0.10 for two additional tests). On average, for these six tests, an increase of 15.7 microg/g of peak tibia lead was equivalent in its effects on annual test decline to 5 more years of age at baseline. CONCLUSIONS: These are the first data to suggest that cognitive function can progressively decline due to past occupational exposures to a neurotoxicant.

Effect of differential tracer washout during SPECT acquisition.

A central assumption in SPECT is that the projection data are "consistent," that is, the camera views an unchanging distribution during acquisition. Several new radiotracers of interest, including 99mTc-teboroxime (Cardiotec), have rapid clearance from the myocardium. Furthermore, the washout is different in normal and ischemic tissues. We used computer simulations to estimate the effect of this differential washout on quantification of the severity of ischemia. We simulated defect-to-normal myocardial activity ratios of 1 (no defect), 0.8, 0.6, 0.4, 0.2, and 0 (complete defect), with single defects placed either in the lateral wall or apex, and SPECT acquisitions of 1, 3, 6, 12, and 24 total minutes. We modeled washout with a monoexponential curve whose clearance half-time was 5.9 min for "normal myocardium" and 9.3 min for "ischemic myocardium." We found that differential washout from normal and ischemic zones produced image artifacts and errors in defect quantification for acquisitions longer than 3 min. With longer acquisitions, the degree of ischemia was significantly underestimated, with increasing error at longer acquisition times. In addition, in the "no defect" situation an apparent small lateral wall defect (relative to the apex) was present. Finally, lateral wall defects produced artifacts (streaks and reduced apparent activity) in the opposite (medial) wall. Differential normal/ischemic zone washout during SPECT acquisition produces artifacts and errors in quantification, whose severity is dependent on acquisition length, actual defect severity, and defect location.

Patterns of ventricular emptying by Fourier analysis of gated blood-pool studies.

Temporal Fourier analysis was applied to the processing of ECG-gated cardiac blood-pool studies on a pixel-by-pixel basis, to yield information about the pattern of ventricular emptying in normal hearts and in others with conduction abnormalities. The transform data at the fundamental frequency (the heart rate) were used to construct two types of display: (a) a distribution histogram of the pixel phase values, and (b) a cinematic display of the wave of emptying as it spread over the cardiac chambers. Preliminary results indicate that temporal Fourier analysis permits visualization of the pattern of ventricular emptying, which may prove useful in the study of motion abnormalities and asynergies, including those resulting from myocardial hypertrophy or conduction abnormalities, and as an aid in the optimum placement of pacemakers.