Technical aspects of myocardial planar imaging with technetium-99m sestamibi

Fundamental quantitative planar imaging techniques, evolved over the years, have been adapted to maximize the efficiency and clinical effectiveness of technetium-99m (Tc-99m) sestamibi imaging. To ensure reproducible image interpretation, the Society for Motion Picture and Television Engineers test pattern is used to obtain the necessary standardization of video and hard copy images. A standardized intensity scale intuitively relates count density to perceived brightness. Data are accumulated via standard 16-frame multiple gated acquisition and can be viewed in cine mode to assess wall motion. The images are then automatically summed for quantitative analysis of myocardial perfusion. Excessive extracardiac Tc-99m activity is automatically suppressed by the computer program to prevent suboptimal display of the heart. Due to the difference in heart background ratio and shape of the extracardiac background between resting and exercise Tc-99m sestamibi images, a modified interpolative background subtraction algorithm was developed. Image registration is necessary for accurate comparison of the rest and exercise images to detect redistribution. This is automatically accomplished by adjusting the position of the background-subtracted and centered images so as to maximize the cross-correlation coefficient. Profiles are generated to sample the myocardial count distribution and can be compared to a normal database, subject to confirmation by a competent interpreter. Rest redistribution is defined by a change in the myocardial distribution of Tc-99m sestamibi between exercise and rest images. Flashback display is used to identify subtle regions of redistribution that often signify residual viability within an infarct zone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Technical aspects of myocardial SPECT imaging with technetium-99m sestamibi

Most reports to date using single photon emission computed tomography (SPECT) with technetium-99m (Tc-99m) sestamibi have used acquisition parameters that were optimized for thallium-201. To fully utilize the superior imaging characteristics of Tc-99m sestamibi, there is a need to optimize the technical aspects of SPECT imaging for this agent. Performance can be enhanced through the careful selection of optimal radiopharmaceutical doses, imaging sequences, acquisition parameters, reconstruction filters, perfusion quantification methods and multidimensional methods for visualizing perfusion distribution. The current report describes theoretical considerations, phantom studies and preliminary patient results that have led to optimized protocols, developed at Emory University and Cedars-Sinai Medical Center, for same-day rest-stress studies, given existing instrumentation and recommended dose limits. The optimizations were designed to fit a low-dose-high-dose rest-stress same-day imaging protocol. A principal change in the acquisition parameters compared with previous Tc-99m sestamibi protocols is the use of a high-resolution collimator. The approach is being developed in both prone and supine positions. A new method for extracting a 3-dimensional myocardial count distribution has been developed that uses spherical coordinates to sample the apical region and cylindrical coordinates to sample the rest of the myocardium. New methods for visualizing the myocardial distribution in multiple dimensions are also described, with improved 2-dimensional, as well as 3- and 4-dimensional (3 dimensions plus time) displays. In the improved 2-dimensional display, distance-weighted and volume-weighted polar maps are used that appear to significantly improve the representation of defect location and defect extent, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Detection and location of myocardial infarction using technetium-99m sestamibi imaging at rest

Technetium-99m (Tc-99m) sestamibi imaging at rest has been used to detect and localize myocardial infarction. The largest study to date is a cooperative study of 146 patients in 17 institutions. There were 24 normal subjects and 122 patients with documented myocardial infarction based on clinical, enzymatic or electrocardiographic criteria. The presence of segmental myocardial perfusion defects was compared to the presence of a Q wave on the electrocardiogram or wall motion abnormality on gated blood pool scans, performed within 48 hours of the Tc-99m sestamibi study. Of the 122 infarct patients, 118 (97%) showed perfusion abnormalities by Tc-99m sestamibi imaging. A perfusion defect was found in 110 (99%) of 111 patients with a Q wave and a wall motion abnormality, 113 (99%) of 114 patients with a wall motion abnormality and 113 (98%) of 115 patients with a Q wave. Of the 24 normal subjects, 22 (92%) had normal Tc-99m sestamibi images. In 75% of 1,986 segments, both a Tc-99m sestamibi defect and a regional wall motion abnormality on gated blood scans were present. In 11% of segments, wall motion was normal but Tc-99m sestamibi imaging was abnormal; in 14% of segments, wall motion was abnormal and Tc-99m sestamibi images were normal. In the 24 control subjects, 99% of the segments were normal. Thirty-eight patients had coronary angiography. A close relation existed between the coronary anatomy and myocardial Tc-99m sestamibi uptake. All 9 territories supplied by an occluded vessel and poor collaterals had grade 0 uptake (scale 0 to 2: 0 = markedly reduced; 2 = normal).(ABSTRACT TRUNCATED AT 250 WORDS)     

Thrombolytic therapy for myocardial infarction: Assessment of efficacy by myocardial perfusion imaging with technetium-99m sestamibi

Technetium-99m (Tc-99m) sestamibi has been used to evaluate the efficacy of thrombolytic therapy. Improved image quality due to the higher photon energy of Tc-99m and the increased allowable doses of this radiopharmaceutical along with its lack of redistribution makes Tc-99m sestamibi an acceptable imaging agent for such studies. This imaging agent was used for serial quantitative planar and tomographic imaging to assess the initial risk area of infarction, its change over time and the relation to infarct-related artery patency in patients with a first acute myocardial infarction. Twenty-three of 30 patients were treated with recombinant tissue-type plasminogen activator (rt-PA) within 4 hours after onset of acute chest pain. Seven patients were treated in the conventional manner and did not receive thrombolytic therapy. The initial area at risk varied greatly both in patients treated with rt-PA and in those who received conventional therapy. Patients with successful thrombolysis and patent infarct arteries had a significantly greater reduction of Tc-99m sestamibi defect size than patients who had persistent coronary occlusion. Serial imaging with Tc-99m sestamibi could find important application in future clinical research evaluating the efficacy of new thrombolytic agents. Direct measurements of the amount of hypoperfused myocardium before and after thrombolysis could provide rapid and unequivocal results using fewer patients and avoiding the use of “mortality” as an end point. This approach has not yet been widely tested in the clinical arena.     

Myocardial perfusion imaging with technetium-99m sestamibi in patients with cocaine-associated chest Pain

STUDY OBJECTIVE: To describe the characteristics and outcome in patients presenting to the emergency department with chest pain associated with cocaine use, the majority of whom underwent early rest perfusion imaging. METHODS: From January 1994 to June 1996, 218 patients had 241 ED visits for evaluation of symptoms consistent with myocardial ischemia after cocaine use. High-risk patients (N=25) were admitted directly to the CCU for exclusion of myocardial infarction (MI). Moderate- to low-risk patients (N=216) were promptly injected with technetium-99m sestamibi in the ED and underwent gated myocardial perfusion imaging 60 to 90 minutes later. Moderate-risk patients were observed in the CCU, whereas low-risk patients with negative perfusion imaging results were discharged home directly from the ED. RESULTS: A diagnosis of MI was made in 6 patients, 4 of whom had ECG findings consistent with MI. Of the 216 patients who underwent perfusion imaging, 5 had positive study results, including 2 with MI. None of the 38 patients with negative results after perfusion imaging who were admitted to the CCU had a diagnosis of MI. Only 6 of the 67 patients undergoing stress perfusion imaging had reversible perfusion defects. At 30-day follow-up, there were no cardiac events in patients with negative results after rest perfusion imaging. CONCLUSION: Acute MI is infrequent in patients presenting with cocaine-associated chest pain. Positive results after rest perfusion imaging are uncommon, suggesting that myocardial ischemia is infrequently the cause of cocaine-associated chest pain. Early perfusion imaging may offer an effective alternative to routine CCU admission of patients with cocaine-related cardiac symptoms.     

Risk assessment using single-photon emission computed tomographic technetium-99m sestamibi imaging

Objectives. This review summarizes the results of single-photon emission computed tomographic (SPECT) technetium-99m (Tc-99m) tracer imaging in patients with stable symptoms, patients with acute coronary syndromes, patients undergoing major noncardiac surgery and patients with chest pain in the emergency department.Background. Previous studies have examined the prognostic value of stress thallium imaging in several subsets of patients with ischemic heart disease. At present, >50% of myocardial perfusion studies are performed with technetium-labeled tracers in the United States. Furthermore, there is a shift from diagnostic to the prognostic utility of stress testing. There are important differences between technetium-labeled tracers and thallium-201. It is therefore important to review the prognostic value of technetium-labeled tracers.Methods. We analyzed published reports in English on risk assessment using Tc-99m perfusion tracers.Results. The largest experience is in patients with stable symptoms, comprising >12,000 patients in 14 studies. In these patients, normal stress SPECT sestamibi images were associated with an average annual hard event rate of 0.6% (death or nonfatal myocardial infarction [MI]). In contrast, patients with abnormal images had a 12-fold higher event rate (7.4% annually). Both fixed and reversible defects are prognostically important, and quantitative analysis shows increased risk in relation to the severity of the abnormality. These results are similar to those obtained with thallium-201.Conclusions. Patients with stable chest pain syndromes and normal stress SPECT sestamibi images have a very low risk of death or nonfatal MI. It is highly unlikely that coronary revascularization can improve survival in such patients. Patients with abnormal images have an intermediate to high risk for future cardiac events, depending on the degree of the abnormality. Further prospective studies comparing aggressive medical therapy with coronary revascularization in these patients are warranted.     

Differential prognostic significance of peri-infarction versus remote myocardial ischemia on stress technetium-99m sestamibi tomography in patients with healed myocardial infarction

Peri-infarction and remote myocardial ischemia involve different myocardial substrates, but their differential clinical implications have not been previously studied. We assessed the differential prognostic significance of peri-infarction and remote ischemia during long-term follow-up in patients with healed myocardial infarction. We studied 345 patients (59 +/- 12 years old; 282 men) with previous myocardial infarction who demonstrated reversible perfusion abnormalities on exercise or dobutamine stress technetium-99m sestamibi tomography. Follow-up events for 5.5 +/- 2.6 years were 60 deaths (17%; 40 cardiac deaths) and 25 reinfarctions (7%). Reversible perfusion abnormalities were detected in the remote region in 129 patients (37%), the peri-infarction region in 142 patients (41%), and in both regions in 74 patients (21%). The annual rates of cardiac death in these groups were 1.2%, 2.8%, and 2.9%, respectively (p <0.01). The annual rates of reinfarction were 1%, 1.5%, and 0.9%, respectively (p = NS). In a multivariate analysis model, independent predictors of cardiac death were history of heart failure (risk ratio [RR] 2.8, 95% confidence interval [95% CI] 1.2 to 7), diabetes mellitus (RR 4.1, 95% CI 1.9 to 8.9), summed score at rest (RR 1.4, 95% CI 1.1 to 3.1), and peri-infarction ischemia (RR 2.6, 95% CI 1.1 to 6.1). Predictors of reinfarction were age (RR 1.03, 95% CI 1.01 to 1.07) and diabetes mellitus (RR 3.3, 95% CI 1.2 to 9.1). Peri-infarction ischemia assessed by stress technetium-99m sestamibi tomography is associated with a greater risk of cardiac death than is remote ischemia. The risk of reinfarction is not related to the location of ischemia.     

Clinical experience with technetium-99m stannous polyphosphate for myocardial imaging.

Myocardial imaging with technetium-99m stannous polyphosphate was performed on 46 patients. Eleven patients had no cardiac disease, 22 had acute myocardial infarction, and 13 had stable arteriosclerotic heart disease. Distinct patterns of myocardial activity were noted: (1) the patients with no obvious cardiac disease showed no cardiac activity; (2) stable arteriosclerotic heart disease showed faint, ill-defined cardiac activity, primarily in the anterior or inferior aspect of the left ventricle; (3) acute myocardial infarction showed intense, focal, well-defined activity, with a shape that characterized the location of the infarct.     

Myocardial perfusion imaging with technetium-99m sestamibi SPECT in the evaluation of coronary artery disease

Technetium-99m (Tc-99m) sestamibi is a new myocardial perfusion imaging agent that offers significant advantages over thallium-201 (Tl-201) for myocardial perfusion imaging. The results of the current clinical trials using acquisition and processing parameters similar to those for Tl-201 and a separate (2-day) injection protocol suggest that Tc-99m sestamibi and Tl-201 single photon emission computed tomography (SPECT) provide similar information with respect to detection of myocardial perfusion defects, assessment of the pattern of defect reversibility, overall detection of coronary artery disease (CAD) and detection of disease in individual coronary arteries. Tc-99m sestamibi SPECT appears to be superior to Tc-99m sestamibi planar imaging because the former provides a higher defect contrast and is more accurate for detection of disease in individual coronary arteries. Research is currently under way addressing optimization of acquisition and processing of Tc-99m sestamibi studies and development of quantitative algorithms for detection and localization of CAD and sizing of transmural and nontransmural myocardial perfusion defects. It is expected that with the implementation of the final results of these new developments, further significant improvement in image quality will be attained, which in turn will further increase the confidence in image interpretation. Development of algorithms for analysis of end-diastolic myocardial images may allow better evaluation of small and nontransmural myocardial defects. Furthermore, gated studies may provide valuable information with respect to regional myocardial wall motion and wall thickening. With the implementation of algorithms for attenuation and scatter correction, the overall specificity of Tc-99m sestamibi SPECT should improve significantly because of a substantial decrease in the occurrence of attenuation-related image artifacts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Technetium-99m sestamibi myocardial imaging: same-day rest-stress studies and dipyridamole

Unlike thallium-201, technetium-99m (Tc-99m) sestamibi does not redistribute in the myocardium after injection. Thus, 2 separate injections, 1 at rest and the other at stress (or after dipyridamole), are required to differentiate ischemia from scar. From a physical viewpoint, a 24-hour interval between the 2 injections is preferable for detection of coronary artery disease (CAD) with Tc-99m sestamibi imaging. However, same-day studies are more convenient in clinical practice. Results of studies using different Tc-99m sestamibi injection protocols are presented with emphasis on the advantages of a rest-stress injection sequence with a low dose at rest (7 mCi) followed 2 hours later by a higher dose at stress (25 mCi). A prospective study was conducted in a patient population with proven CAD using same-day studies to compare a rest-stress (7 and 25 mCi, respectively) to a stress-rest (7 and 25 mCi) Tc-99m sestamibi injection sequence. There was an agreement in 87.3% of the analyzed segments between the 2 protocols. However, the largest discordance for type of defect applied to 7.4% of the segments judged ischemic in the rest-stress protocol, which were called scars on stress-rest. This study showed that a rest-stress sequence is preferable when using a same-day protocol with a short time interval (less than 2 hours) between the 2 Tc-99m sestamibi injections because the rest image performed initially represents a "true" rest study, which is not necessarily the case with the stress-rest sequence. Preliminary studies were performed to evaluate dipyridamole with Tc-99m sestamibi imaging in normal subjects and in patients with CAD. These studies showed that treadmill and dipyridamole Tc-99m sestamibi imaging are comparable and the results are similar to those obtained with thallium-201.     

Comparison of single-photon emission computed tomographic (SPECT) myocardial perfusion imaging with thallium-201 and technetium-99m sestamibi in dogs.

OBJECTIVES. The purpose of the present study was to compare single-photon emission computed tomographic (SPECT) myocardial images of technetium-99m (Tc-99m) sestamibi and thallium-201 (Tl-201) isotopes in the same dog undergoing partial coronary occlusion during pharmacologic vasodilation. BACKGROUND. To date, no controlled study has been reported comparing SPECT Tc-99m sestamibi with SPECT Tl-201 imaging during stress with anatomic and physiologic standards. METHODS. Mongrel dogs were anesthetized with chloralose and instrumented to record left anterior descending coronary blood flow and aortic pressure. Partial coronary occlusion with a hydraulic cuff reduced coronary vascular conductance, which is equal to the coronary blood flow normalized to aortic pressure during peak vasodilation with intravenous adenosine. Each dog received 5 mCi of Tl-201, then 30 mCi of Tc-99m sestamibi during partial coronary occlusion at peak vasodilation. Tomographic myocardial imaging was performed in a 180 degrees anterior arc scan for 33.5 min, first with Tl-201, and later, without moving the dog, for 33.5 min with Tc-99m sestamibi. Postmortem staining defined the region underperfused because of its dependence on the artery that was partially occluded. RESULTS. In seven dogs with moderate reduction in coronary blood flow, coronary vascular conductance decreased with partial coronary occlusion (47 +/- 12%) during Tl-201 imaging and (47 +/- 8%, p = NS) during Tc-99m sestamibi imaging. The underperfused region was 23.9 +/- 6.4% of total left ventricular mass. Counts in the defects were 39% higher (0.86 +/- 0.08 of normal counts) for Tc-99m sestamibi than for Tl-201 (0.64 +/- 0.09 of normal counts, p < 0.001), and the defect on SPECT Tc-99m sestamibi images occupied only a fraction (0.37 +/- 0.30) of the area of the defect on the Tl-201 images of the same dog. Bull's-eye displays constructed from the pathologic slices showed that the Tl-201 defect size was closer to the underperfused region of the left ventricular mass determined pathologically than was the Tc-99m sestamibi defect size. In four additional dogs a severe, near total coronary occlusion was created during Tl-201 and Tc-99m sestamibi administration. In these dogs, similar defect contrast (0.55 +/- 0.12 vs. 0.62 +/- 0.09, p = NS) and areas (0.18 +/- 0.07 vs. 0.18 +/- 0.11, p = NS) were observed with Tl-201 and Tc-99m sestamibi, respectively. CONCLUSIONS. Tomographic myocardial imaging with Tc-99m sestamibi during moderately severe partial coronary occlusion underestimated the area of the defect relative to Tl-201 or to the pathologic reference standard in dogs. Defect contrast was sharper with tomographic myocardial Tl-201 than with tomographic myocardial Tc-99m sestamibi during moderately severe partial coronary occlusion.     

Functional assessment with electrocardiographic gated single-photon emission computed tomography improves the ability of technetium-99m sestamibi myocardial perfusion imaging to predict myocardial viability in patients undergoing revascularization

This study evaluates the use of electrocardiographic (ECG) gated single-photon emission computed tomographic (SPECT) myocardial perfusion imaging for the prediction of viability in patients undergoing revascularization, who have coronary disease and left ventricular dysfunction. Fifty patients underwent technectium-99m (Tc-99m) sestamibi ECG gated SPECT imaging preoperatively at rest and 1 week after revascularization, whereas 36 (72%) also underwent imaging 6 weeks after revascularization. Images were interpreted by the consensus of 3 experienced readers without knowledge of patient identity or time of imaging (pre- or postrevascularization) for perfusion and wall motion using a 17-segment model. Results of perfusion alone were compared with perfusion and wall motion combined. One hundred five coronary artery territories were revascularized, 96 of which were viable and 9 nonviable. Perfusion alone predicted 87 to be viable and 18 nonviable (sensitivity 86%, specificity 55%, positive predictive value 95%, negative predictive value 28%, and overall accuracy 85%). Perfusion and wall motion combined identified 95 territories to be viable (sensitivity 95%; p <0.025; specificity 55%, positive predictive value 96%, negative predictive value 50%, and overall accuracy 91%; p <0.05). Thus, Tc-99m sestamibi ECG gated SPECT myocardial perfusion imaging at rest allows assessment of both perfusion and wall motion, which significantly improves the sensitivity and overall accuracy for determination of viability in comparison with perfusion alone.     

Technetium-99 m sestamibi imaging in patients with subacute thyroiditis

To determine if subacute thyroiditis (SAT) is associated with changes in the regional perfusion of the thyroid gland, we performed Tc-99 m sestamibi scans on eleven patients with SAT who had painful goiter and clinical thyrotoxicosis. Eleven patients had Tc-99 m pertechnetate and Tc-99 m sestamibi scintigraphy during the acute stage of SAT. The thyroid uptake ratio of sestamibi was compared with the laboratory data and color Doppler ultrasonography. Tc-99 m pertechnetate scintigraphy in the thyroid was markedly reduced during the acute stage of SAT. Conversely, Tc-99 m sestamibi showed diffuse increased uptake in the thyroid region, suggesting increased perfusion. On the other hand, there was near absence of vascularization in the acute phase and slight increase in the recovery phase by color Doppler ultrasonography. The clearance rate of Tc-99 m sestamibi during the early phase (from 10 min to 1 h) was decreased in the acute stage of SAT. The sestamibi uptake ratio correlated with serum immunosuppressive acidic protein (IAP) in the acute stage of SAT and the sestamibi uptake ratio in the recovery stage of SAT was correlated with serum thyrotropin levels. Tc-99 m sestamibi uptake in the early phase in the acute stage of SAT may reflect the inflammatory process associated with SAT.     

Use of technetium-99m sestamibi to determine the size of the myocardial area perfused by a coronary artery

The value of the new radionuclide tracer, technetium-99m (Tc-99m) sestamibi, to demonstrate myocardial perfusion in areas supplied by specific coronary arteries was evaluated in patients injected with the agent during cardiac catheterization. Tc-99m sestamibi differs from thallium-201 in its physical characteristics (photon energy 140 keV), half-life (6 hours) and lack of significant redistribution, allowing its administration during an episode of chest pain or ischemia occurring outside the nuclear medicine laboratory with later imaging to visualize the distribution. In 13 patients Tc-99m sestamibi was administered intravenously during balloon-occlusion angioplasty. In 11 of 13 patients, defects of the single photon emission computed tomography images corresponded to the area made ischemic during angioplasty. In the remaining 2 patients, abundant collateral flow was present and no defects were seen. In a second study, 15 patients had Tc-99m sestamibi selectively injected into a coronary artery during angiography. Later imaging identified the area supplied by the artery injected. Tc-99m sestamibi imaging can detect perfusion defects associated with short episodes of ischemia, and the area supplied by the different coronary arteries.     

Comparison of electrocardiographic-gated technetium-99m sestamibi single-photon emission computed tomographic imaging and rest-redistribution thallium-201 in the prediction of myocardial viability

Although the combined assessment of perfusion and function using rest electrocardiographic (ECG)-gated technetium-99m (Tc-99m) sestamibi single-photon emission computed tomographic (SPECT) imaging has been shown to improve sensitivity and accuracy over perfusion alone in the prediction of myocardial viability, no data are available comparing this technique with rest-redistribution thallium-201. Thirty patients with coronary artery disease and left ventricular dysfunction (ejection fraction < or = 40%) underwent rest-redistribution thallium-201 and rest ECG-gated Tc-99m sestamibi SPECT imaging before revascularization and rest ECG-gated Tc-99m sestamibi SPECT imaging at 1 or 6 weeks after revascularization. All thallium-201 and Tc-99m sestamibi images were interpreted by a consensus agreement of 3 experienced readers without knowledge of patient identity or time of imaging with Tc-99m sestamibi (before or after revascularization) using a 17-segment model. Concordance between techniques for the prediction of viability was 89% (kappa 0.556 +/- 0.109). With rest-redistribution thallium-201, sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy were 95%, 59%, 88%, 78%, and 86%, respectively. With rest ECG-gated Tc-99m sestamibi SPECT imaging, sensitivity, specificity, positive predictive value, negative predictive value, and predictive accuracy were 96%, 55%, 87%, 80%, and 86%, respectively (p = NS vs rest-redistribution thallium-201). Although both techniques are comparable for detecting viable myocardium, rest ECG-gated Tc-99m sestamibi SPECT imaging allows direct assessment of both myocardial perfusion and ventricular function, which may be clinically useful in patients who require assessment of myocardial viability.     

Detection and assessment of unstable angina using myocardial perfusion imaging: comparison between technetium-99m sestamibi SPECT and 12-lead electrocardiogram

Forty-five studies using technetium-99m (Tc-99m) sestamibi single photon emission computed tomography (SPECT) were performed on patients hospitalized for spontaneous chest pain suggestive of myocardial ischemia. The studies were done after an injection during an episode of chest pain and a repeated injection when the patients were free of pain. All patients were hospitalized with a presumed diagnosis of unstable angina, and none had evidence of a previous myocardial infarction. The presence of a perfusion defect observed with Tc-99m sestamibi injected during chest pain had a 96% sensitivity and a 79% specificity for the detection of significant coronary artery disease (stenosis greater than or equal to 50%) on subsequent angiography. When the criterion of a larger perfusion defect during pain compared to absence of pain was used, the sensitivity was 81% and the specificity was 84%. In contrast, transient electrocardiographic ischemic changes during pain had a sensitivity of 35% and a specificity of 68%; electrocardiographic changes during or outside episodes of chest pain had a sensitivity of 65% and a specificity of 63% for the diagnosis. Tc-99m sestamibi SPECT represents a reliable noninvasive diagnostic tool that could aid in the diagnosis of myocardial ischemia in patients with spontaneous chest pain and provide additional information to that provided by the electrocardiogram.