Myocardial Perfusion ImagingA Technologist’s Guide

European Association of Nuclear Medicine

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Contributors

Wim van den Broek

Chairman EANM TC; Chief TechnologistDept of Nuclear Medicine, University Medical CentreNijmegen, The Netherlands

Alberto Cuocolo

MDDept of Biomorphological and Functional SciencesFederico II University, Naples, Italy

Adriana Ghilardi

Chief TechnologistDept of Nuclear Medicine, Ospedali Riuniti, Bergamo, Italy

Sue Huggett

Member of EANM TC Education Sub-CommitteeProgramme Coordinator for Nuclear Medicine TechnologyDept of Radiography, City University, London, United Kingdom

Régis Lecoultre

Technologists EducatorHECVSanté - filière TRM, Lausanne, Switzerland

Julie Martin

Director of Nuclear MedicineDept of Nuclear Medicine, Guy’s and St Thomas’ HospitalsLondon, United Kingdom

Giuseppe Medolago

MDDept of Nuclear Medicine, Ospedali Riuniti, Bergamo, Italy

José Pires Jorge

Member of EANM TC Education Sub-Committee; Technologists EducatorHECVSanté - filière TRM, Lausanne, Switzerland

Audrey Taylor

Chief TechnologistDept of Nuclear Medicine, Guy’s and St Thomas’ HospitalsLondon, United Kingdom

Under the auspices of the European Association of Nuclear MedicineTechnologist Committee Education Sub-Committee

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Contents

Foreword 4

Wim van den Broek

Introduction 5

Sue Huggett

Chapter 1 – Applications and Rationale of Myocardial Perfusion Imaging 7–13

Alberto Cuocolo

Chapter 2 – Patient Preparation 14–16

Julie Martin and Audrey Taylor

Chapter 3 – Stress Protocols 17–28

Adriana Ghilardi and Giuseppe Medolago

Chapter 4 – Preparation and Use of Imaging Equipment 29–35

Régis Lecoultre and José Pires Jorge

Chapter 5 – Imaging and Processing 36–43

Julie Martin and Audrey Taylor

References 44

This booklet was sponsored by an educational grant from Bristol-Myers Squibb Medical Imaging.The views expressed are those of the authors and not necessarily of Bristol-Myers Squibb Medical Imaging.

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Technologists have become an important group within the EANM. Since its inception, the Technologist Committee of the EANM has been working to improve the professional expertise of nuclear medicine technologists (NMTs) in Europe.

Expertise is the keyword; NMTs’ professional and practical expertise is essential to ensur-ing an expert nuclear medicine examination. The NMT must safeguard patients’ wellbeing, ensure each examination is performed cor-rectly, and maintain an operating procedure that guarantees the quality of the results.

In 1998, a start was made with the publica-tion of ‘Competencies for the European NMT’, which was followed by ‘Advanced Skills and Responsibility Guidelines for the Senior NMT’ and other publications, all promoting good practice for NMTs.

ForewordWim van den Broek

In early 2004, the idea of providing a series of booklets on imaging for technologists was born. By September 2004, thanks to the hard work of the EANM Technologist Sub-Commit-tee on Education, it was possible to achieve the first goal in this series: this booklet on myocardial perfusion scintigraphy (MPS) for technologists.

I hope this booklet will find its way into the pockets of technologists across Europe, and prove a valuable aid in the daily work of NMTs performing MPS scans.

Many thanks to all who have contributed to this project, in particular the members of the EANM Technologist Sub-Committee on Edu-cation, and to Bristol-Myers Squibb Medical Imaging for the sponsorship that made this project possible.

Wim van den Broek Chairman EANM Technologist Committee

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IntroductionSue Huggett

In early 2004, the EANM Technologist Commit-tee considered producing a booklet on myo-cardial perfusion scintigraphy (MPS) for tech-nologists. This was an exciting opportunity to involve technologists from many European countries in a collaborative effort to produce a piece of work for and mainly by our own profession. We wanted to provide informa-tion for reference in a handy form that could be kept nearby or even in the technologist’s pocket when scanning.

Owing to the timescale, we decided that this booklet should focus on traditional tomo-graphic MPS and gated tomographic MPS methods, with the possibility of further work on PET methodologies to follow. Members of the Education Sub-Committee drafted a framework and set about finding contribu-tors for the various sections. It was gratifying that everyone we approached was happy to help.

Of course, all nuclear medicine studies need to be performed well to obtain optimal diagnos-tic information. MPS in particular encompass-es many areas of technologist practice, from stressing and setting up ECG traces to analysis and display. As a result, the opportunities to maintain and improve quality are sizeable.

We hope this booklet will prove useful in all areas.

Knowledge of imaging theory can provide the technologist with a deeper and more satis-fying understanding of practical techniques, improve decision-making, and allow the tech-nologist to pass on accurate information to patients, their carers, and other staff. Patient care is always paramount, and being able to explain why certain foods must be avoided or why it is necessary to lie in awkward posi-tions improves compliance and is satisfying in its own right.

Protocols vary between departments, even within the broader terms of the EANM Guide-lines, and this booklet is not meant to supplant these protocols but hopefully to supplement and explain the rationales behind them. This will hopefully lead to more thoughtful work-ing practices. For example, both checking for suitability and proper preparation before a study can save time and reduce radiation doses. Information from and about patients can be incomplete or misleading, so under-standing the importance of what they say on arrival is vital if the technologist is to spot potential problems early on.

In order to know when and how to apply variations in the protocol for acquisition or analysis, we must be aware of the rationales behind certain strategies. For example, obese patients attenuate more photons, so in such cases it could be advisable to linger longer at each angle or to use a different order filter if total counts are low.

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The same philosophy applies to equipment; if you understand the consequences of any suspicious QC results, you will know when to pay closer attention to certain parameters. We hope that this booklet can provide informa-tion as and when it is needed so that the in-tegration of theory and practice is facilitated and encouraged.

The authors are indebted to a number of infor-mation sources, not least local protocols, and references have been given where original authors were identifiable.

We apologise if we have inadvertently made uncredited use of material for which credit should have been given.

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Applications and Rationale of Myocardial Perfusion ImagingAlberto Cuocolo

During the past two decades, the clinical role of nuclear medicine procedures in cardiology has evolved significantly. Initially, the diagnos-tic role of nuclear medicine in detecting myo-cardial ischaemia in patients with suspected coronary artery disease was emphasised. Sub-sequently, myocardial perfusion imaging has made significant advances in the determina-tion of prognosis in patients with ischaemic heart disease, preoperative risk assessment for patients undergoing non-cardiac surgery, and assessment of the efficacy of revasculari-sation in patients undergoing coronary artery bypass surgery or interventional procedures. More recently, particular attention has been focused on the ability of nuclear cardiology to characterise myocardial tissue and to assess myocardial viability in patients with ischaemic left ventricular (LV) dysfunction.

Common clinical indications for an MPS study1. Diagnosis of coronary artery disease: pres-ence, location (coronary territory), and extent (number of vascular territories involved)

2. Risk assessment (prognosis) in patients: both after myocardial infarction and preoperatively for major surgery that may be a risk for coro-nary events

3. Assessment of myocardial viability: differen-tiating ischaemia from scar, and predicting im-provement of LV function after interventions

4. Monitoring of treatment effect after coro-nary revascularisation procedures

1. Diagnosis of coronary artery diseaseMyocardial perfusion imaging with exercise or pharmacological stress testing is an accepted technique for the detection and localisation of coronary artery disease (1,2).

During exercise or pharmacological stress, the vasodilating capacity of microcirculation is lim-ited and obstruction in the epicardial coronary arteries becomes physiologically important, providing a mechanism for the non-invasive di-agnosis of obstructive coronary artery disease. Myocardial perfusion abnormalities detected during either exercise or pharmacological stress are due to differential blood flow be-tween normal and stenotic arteries.

The determination of these disparities is de-pendent on the ability of different tracers to reflect the changes in increased blood flow produced by the stressors.

All myocardial perfusion imaging agents avail-able for clinical use have shown a linear rela-tionship up to approximately twofold higher than baseline. Beyond this level, there appears to be a decrease in the uptake of most agents in relation to blood flow. The plateau effect dif-fers demonstrably between tracers. Compared to resting blood flow, it should be assumed that exercise will typically cause a two- to threefold increase in myocardial blood flow,

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while stress in response to pharmacological agents will typically be accompanied by a three- to eightfold increase.

Myocardial perfusion tracers available for clinical use include thallium (Tl-201) and technetium-99m (Tc-99m) labelled agents (e.g. sestamibi and tetrofosmin). The relation-ship between blood flow and the activities of these tracers has been widely studied. Blood flow and thallium activity show a lin-ear relationship up to at least 3 ml/min/gm. However, at approximately 3 ml/min/gm there appears to be a plateau effect such that further increases in blood flow do not change thallium activity. The extraction frac-tion of sestamibi is less than thallium. Data from animal studies demonstrate a linear re-lationship between blood flow and sestamibi uptake, up to approximately 2 ml/min/gm. Above this level, uptake is not linked to in-creasing flow in a linear fashion. Similar data are emerging for tetrofosmin, though this tracer demonstrates a plateau during stress at a lower blood flow level than does sestamibi. Thus, thallium, sestamibi, and tetrofosmin all exhibit a plateau effect that occurs above the typical blood flow range for exercise or most pharmacological stress. The Tc-99m la-belled tracer with the best extraction fraction (higher than thallium) is teboroxime, which shows a linear correlation within the range of pharmacological stress. However, the rapid clearance of this tracer from the myocardium has made this agent difficult to use clinically.

All these tracers have different kinetic char-acteristics, which must be considered when attempting to maximise their clinical applica-tion in stress imaging. Moreover, it must be remembered that in clinical imaging ideal conditions do not always exist.

Despite the differences in tracer kinetics, comparative studies involving thallium and Tc-99m labelled agents have failed to show significant differences. Several clinical stud-ies have documented the clinical impact of thallium imaging in the detection of coronary artery disease. In particular, the sensitivity of single-photon emission computed tomog-raphy (SPECT) thallium imaging has been reported to be approximately 90%, with a relatively low specificity of 60% to 70%. Since their introduction, sestamibi and tetrofosmin have been compared to thallium as the gold standard in the identification of patients with coronary artery disease. The reported respec-tive average sensitivities and specificities of sestamibi and tetrofosmin in the identifica-tion of coronary artery disease have been very similar to those obtained with thallium imaging. However, some studies have re-ported that sestamibi and tetrofosmin might underestimate the total extent of myocardial ischaemia, relative to thallium imaging, in pa-tients with coronary artery disease (3). On the other hand, significant differences regarding the image quality have been reported in all comparative studies performed. In particular, images obtained using sestamibi or tetrofos-

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Chapter 1: Applications and Rationale of Myocardial Perfusion Imaging – Alberto Cuocolo

min are of superior quality to those obtained with thallium and tend to show fewer soft tis-sue attenuation artefacts. Better definition of the myocardium, endocardial and epicardial borders, and perfusion defects has been ob-served. In general, there is much less statistical noise when using sestamibi and tetrofosmin, and the myocardial-to-background ratios are reportedly similar to those obtained with thallium imaging. Moreover, the permissible administered dose for Tc-99m labelled agents is much larger than for thallium. This results in an increased pixel count density for Tc-99m labelled tomographic projection images and permits the use of higher resolution filters dur-ing reconstruction.

Modern nuclear cardiology imaging tech-niques coupled with the development of Tc-99m labelled perfusion tracers now permit simultaneous myocardial perfusion and LV function studies in a single test. The potential advantages of simultaneous assessment of myocardial perfusion and LV function have recently been outlined (4). Gated imaging of the perfused myocardium is a well-established technique for this purpose, using a single in-jection of a Tc-99m labelled perfusion tracer. Recent data has demonstrated the impact and clinical role of these studies in the diagnosis of patients with suspected or known coronary artery disease; the addition of functional in-formation to perfusion data has been shown to improve the detection of multivessel dis-ease.

2. Risk assessment (prognosis) in patients with coronary artery diseaseAnother key role of myocardial perfusion im-aging is its ability to provide prognostic infor-mation in patients following acute myocardial infarction, in patients with chronic coronary artery disease, and in patients scheduled for major surgery (5). The utility of thallium scin-tigraphy associated with exercise pharmaco-logical stress testing for this purpose has been widely documented. In particular, it has been demonstrated that in patients without prior myocardial infarction the number of reversible thallium defects is the most important statis-tically significant predictor of future cardiac events. Moreover, the extent and severity of thallium defects correlate with the occurrence of cardiac events. Several studies have report-ed similar results for the prognostic value of thallium stress imaging, both after myocardial infarction and in patients with suspected or known coronary artery disease. The data from these studies demonstrate that the extent of perfusion abnormality found through SPECT imaging is the single most important prog-nostic predictor.

More recently, the prognostic value of Tc-99m labelled myocardial perfusion agents has been demonstrated with data comparable to that of thallium imaging. In particular, the extent of hypoperfusion in post-stress sestamibi im-ages can be factored into the decision-mak-ing process when deciding whether to select medical therapy or revascularisation. Patients

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with mild reversible perfusion defects who are judged to be at low or intermediate risk can usually be treated medically, whereas pa-tients with high risk SPECT reversibility results are candidates for further invasive strategies. Moreover, a strategy incorporating stress MPS is also cost-effective. A large study in stable angina patients referred for stress myocardial perfusion SPECT imaging or direct catheterisa-tion revealed that costs were higher for the initial invasive strategy in clinical subsets with low, intermediate, or high pre-test likelihoods of disease. Diagnostic follow-up costs of care were 30-41% higher for patients undergoing direct catheterisation, without any reduction in mortality or infarction compared with patients having stress perfusion imaging as the initial test for coronary artery disease detection.

3. Assessment of myocardial viabilityIt has been demonstrated that a third of pa-tients with chronic coronary artery disease and LV dysfunction have the potential for significant improvement in ventricular func-tion after myocardial revascularisation. These findings have several implications. Firstly, there is the important relationship between LV function and patients’ survival. In recent years, numerous studies have demonstrated that nuclear cardiology techniques involving SPECT provide important viability information in patients with coronary artery disease and impaired ventricular function (6-12). Although positron emission tomography (PET) remains the most accurate technique for the detec-

tion of viable myocardium, different thallium protocols have been used in previous studies to assess myocardial viability in patients with previous myocardial infarction and chronic LV dysfunction. In particular, if the clinical issue to be addressed is the viability of one or more ventricular regions with systolic dysfunction and not whether there is also inducible isch-aemia, rest-redistribution thallium imaging can yield useful viability data. In particular, it has been demonstrated that quantitative analysis of rest-redistribution images predicts recovery of regional LV function and compares favourably to the results of both thallium re-injection imaging and metabolic PET imaging (7). Optimal interpretation of thallium imaging for the detection of myocardial viability can be accomplished by measuring regional tracer uptake and by selecting the most appropri-ate cut-off to differentiate reversible from ir-reversible LV dysfunction (8-10). Furthermore, sestamibi and tetrofosmin showed similar re-sults to those of thallium scintigraphy in the identification of viable myocardium (8).

A quantitative analysis of tracer content as well as the administration of nitroglycerin prior to tracer injection increases the overall accuracy of Tc-99m labelled agents for identifying vi-able myocardium. Recent data indicate that in patients with chronic myocardial infarction and impaired LV function on nitrate treatment, quantitative analysis of resting thallium and sestamibi regional activities comparably pre-dict recovery of regional and global ventricular

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Chapter 1: Applications and Rationale of Myocardial Perfusion Imaging – Alberto Cuocolo

function following revascularisation proce-dures (11). Nitroglycerin most likely enhances myocardial viability detection by increasing coronary collateral flow, decreasing pre-load and after-load, and direct vasodilatation of stenotic segments in coronary arteries (12-14). These physiological effects in combina-tion may enhance the delivery of myocardial perfusion agents to regions of myocardium supplied by severely stenotic vessels.

In the assessment of myocardial viability, phar-macological stress testing in combination with wall motion analysis via gated images of the perfused myocardium has been used (15). Al-though the recovery of regional function after revascularisation has generally been regarded as the gold standard for detecting myocardial viability, the clinical outcome after revasculari-sation is a better and more valuable end-point. The criteria for viability determination with re-spect to its true clinical impact should be the prediction of short- and long-term outcomes such as cardiovascular mortality and recurrent myocardial infarction (16). It should be kept in mind that preserved myocardial perfusion tracer uptake in zones of asynergy may have a sub-optimal value for positive prediction of improved segmental function after revascu-larisation. However, it appears to predict a high cardiac death and infarction rate with medi-cal therapy and identifies a group of patients with hibernating myocardium who would be predicted to have an excellent outcome after revascularisation. It has been demonstrated

that the amount of dysfunctional myocardi-um with preserved thallium uptake provides independent prognostic information that is incremental to that obtained from clinical, functional, and angiographic data in patients with chronic ischaemic LV dysfunction. In particular, patients with a substantial amount (>30% of the total left ventricle) of dysfunc-tional myocardium with preserved tracer activity exhibited the greatest LV functional benefit after successful revascularisation (17). Moreover, patients with more than 50% viable myocardium represented a subgroup at high-risk of cardiac death in whom successful revas-cularisation improved survival (17). Altogether these observations seem to lend further sup-port to the choice of coronary revascularisa-tion in patients with evidence of a substantial amount of dysfunctional myocardium with preserved myocardial perfusion tracer activ-ity. Thus, it appears that the assessment of myocardial viability should be a mandatory step in clinical decision-making for patients with reduced global and regional LV systolic function, to better predict the potential value of revascularisation in improving functional status and survival.

4. Monitoring of treatment effect after coronary revascularisation proceduresThe use of exercise or pharmacological myo-cardial perfusion imaging in the assessment of interventions in chronic ischaemic heart dis-ease is indicated for the evaluation of resteno-sis after percutaneous transluminal coronary

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angioplasty (PTCA) in symptomatic patients, and in the assessment of ischaemia in symp-tomatic patients after coronary artery bypass grafting (CABG). Radionuclide techniques are also indicated in the assessment of selected asymptomatic patients after PTCA or CABG, such as those with an abnormal electrocardio-graphic response to exercise and those with rest electrocardiographic changes precluding identification of ischaemia during exercise.

SPECT exercise imaging is an excellent tool for the detection of restenosis and disease progression after PTCA after both one and multivessel angioplasty, and in complete and partial revascularisation. Hecht et al (18), study-ing exercise tomographic thallium imaging in the detection of restenosis after PTCA, showed sensitivity of 93% for scintigraphic studies and 52% for exercise electrocardiographic studies, specificity of 77% vs 64%, and accuracy of 86% vs 57%, respectively. Moreover, it has been demonstrated that, after PTCA, sensitivity and accuracy of exercise electrocardiography in the detection of restenosis were significantly less than those of SPECT imaging for patients with silent or symptomatic ischaemia (19). Patients with less typical symptoms and in-termediate probability of restenosis can be accurately assessed for this PTCA complication by myocardial perfusion imaging studies. In the patients with recurrent atypical symptoms, stress perfusion imaging should be performed soon after the onset of symptoms in order to determine whether persistent myocardial

ischaemia is the cause of chest pain. Myocar-dial imaging studies offer several advantages over stress electrocardiography, particularly in patients with an abnormal resting electro-cardiogram, multivessel coronary disease, or a limitation to exercise stress testing. After PTCA, nuclear cardiac imaging procedures are not generally recommended in the absence of recurrent symptoms, particularly since im-aging abnormalities would not likely result in either a changed therapeutic regimen or repeat revascularisation. However, recent data demonstrate that extent and severity of myocardial ischaemia found via exercise SPECT performed between 12 and 18 months after percutaneous coronary intervention (PCI) predict cardiac events during long-term fol-low-up in both symptomatic and symptom-free patients (20).

Exercise scintigraphy after CABG demonstrates improved regional myocardial perfusion in most patients. After CABG, the New York Heart Association’s functional class improved significantly. Early (less than 3 months) post-CABG, myocardial imaging may be useful for the detection of perioperative infarction, or if early graft closure with recurrence of angina symptoms is suspected. Beyond 3 months, and following the recovery of hibernation effects, non-invasive cardiac imaging is use-ful for detecting asymptomatic graft attrition and the recurrence of myocardial ischaemia. However, this approach cannot be routinely recommended in all patients who undergo

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Chapter 1: Applications and Rationale of Myocardial Perfusion Imaging – Alberto Cuocolo

CABG because it would not be cost-effective to screen this large population in the 1 to 2 years following CABG surgery.

ContraindicationsMyocardial perfusion imaging is non-invasive - the complication rate of dynamic exercise and pharmacological stress tests is low and well established (at most 0.01% deaths and 0.02% morbidity) (21-24). Therefore, except in patients with unstable heart disease or other contraindications to stress, the risk is not con-sidered significant.

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Patient PreparationJulie Martin and Audrey Taylor

Patient identificationTo minimise the risk of a misadministration, it is necessary to:

establish the patient’s full name and other relevant details prior to administration of any drug or radiopharmaceutical

corroborate this data with information provided on the diagnostic test referral

If the information on the referral form does not match the information given from the identifi-cation process, then the radiopharmaceutical/drug should not be administered to the pa-tient. This should be explained to the patient and clarification sought as soon as possible by contacting the referral source.

The patient/parent/guardian/escort should be asked the following questions and the in-formation checked against their request form and ward wristband if an inpatient.

“Please can you tell me you/your patient’s…

full name.” - check any spellings as appropriate, e.g. Steven vs Stephen

date of birth.”

address.”

A minimum of TWO corroborative details should be asked and confirmed as correct.

The following information should be checked with the patient/parent/guardian/escort where appropriate.

Referring Clinician/GP/Hospital

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•

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Any relevant clinical details

That the patient has complied with the dietary and drug restrictions

If there are any known allergies or previous reactions to any drug/radio-pharmaceutical/iodine-based contrast media or products such as Microspore/Band-Aids

That the results of correlative imaging (e.g. echo, angiography, etc.) are available prior to the study taking place, and that any recent interventions have been noted

IF IN DOUBT, DO NOT ADMINISTER THE RADIOPHARMACEUTICAL/DRUG, AND SEEK CLARIFICATION

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Patients with communication difficulties

Ideally, patients who for any reason are un-able to identify themselves should wear an identification wristband.

Hearing difficulties - Use written questions and ask the patient to supply the infor-mation verbally or write their responses down.

Speech difficulties - Ask the patient to write down their name, date of birth, address, and other relevant details.

Language difficulties - If an accompany-ing person is unable to interpret the questions, then the study should be rescheduled to a time when a member of staff/relative/interpreter with the appro-priate language skills will be available.

Unconscious patient - Check the patient’s ID wristband for the correct name and date of birth. If no wristband is attached, ask the nurse looking after the patient to positively confirm the patient’s ID.

Confused patient - If an inpatient, check the patient’s ID wristband for the correct name and date of birth. If no wristband is attached, ask the nurse looking after the patient to positively confirm the patient’s ID. If an outpatient, ask the person accom-panying the patient to positively confirm the patient’s ID.

If a relative/friend/interpreter provides information regarding the patient’s name,

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date of birth, etc., it is advisable for them to sign as written evidence of confirmation of the relevant details.

Patient information

Patients can be required to send in a list of medications, approximate height, weight, and asthma status so that stressing drugs can be chosen in advance. They should be advised to contact the department if they are diabetic to ensure that they are given the appropriate guidance regarding eating, medication, and so on.

A full explanation of the procedure should be given, including risks, contraindications and side effects of stress agents used, time taken for scan, the need to remain still, and so on.

Ideally, patients should be phoned before-hand to remind them of their appointment and to give them an opportunity to discuss any concerns they may have.

Pregnancy

Women of child-bearing potential should have their pregnancy status checked using a form similar to that shown on the right.

The operator administering the radiophar-maceutical should advise the patient re-garding minimising contact with pregnant persons and children.

The operator administering the radiophar-maceutical should check that any accom-panying person is not pregnant (e.g. escort nurse).

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Chapter 2: Patient Preparation – Julie Martin and Audrey Taylor

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Exercise stressingThere are two main types of exercise: 1. Dynamic or isotonic exercise (bicycle ergometry) 2. Static or isometric exercise (treadmill protocol)

Exercise is preferred to pharmacological stress for testing a physiological imbalance between oxygen supply and demand due to impaired flow reserve, as it can be graduated in order to identify an ischaemic threshold related to heart workload. This can be easily estimated by the double product or rate-pressure prod-uct, which is the product of heart rate and systolic blood pressure at the peak of exercise. Exercise testing should be undertaken under the supervision of a physician properly trained to perform such a test.

In both cases, the patient is prepared with a standard 10-12 lead ECG set-up. HR, BP, and ECG are registered at rest, at the end of each stage, and also during recovery. ECG monitor-ing is mandatory during the whole test.

1. Bicycle ergometrya) ProtocolBicycle protocols involve incremental work-loads calibrated in watts or kilopond (KPD) metres/minute. 1 watt is equivalent to 6 KPD. Mechanically or electronically braked bicycles can be used. Electronically braked bicycles are more commonly used and preferred because they provide a constant workload regardless

of changes in pedalling rate (usually ranging from 60 to 80 rpm) and are less dependent on patient cooperation.

The principle of the test is to gradually increase the resistance to pedalling via a standardised protocol while keeping the rate of pedalling constant, thereby controlling the workload the patient is performing.

Most protocols begin at a workload of 25 watts and increase in 25 watt increments every 2-3 min. Younger or fitter subjects may start at 50 watts or more, with adequate increments every 2-3 min. It takes about 1-2 min for the cardiovascular system to adjust and stabilise heart rate (HR) and blood pressure (BP) at each new workload.

Exercise is usually completed when the patient reaches 85% of predicted maximum heart rate (max. = (220 – age) x 0.85). The patient is then required to keep on pedalling at a minor work-load (25-50 watts) for a few more minutes in order to recover and return to near resting values of HR and BP.

Figure 1

50W

100W

150W

200W

250W Injection

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Chapter 3: Stress Protocols – Adriana Ghilardi and Giuseppe Medolago

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b) AdvantagesPatient motion is limited.

c) DisadvantagesPatient might not be used to riding a bicycle.

2. Treadmilla) ProtocolLike any exercise test, the treadmill protocol should be consistent with the patient’s physi-cal capacity and the purpose of the test. Sev-eral standardised treadmill exercise protocols exist; each of them is motor driven, and speed and gradient (steepness) can be varied. Bruce designed the most widely used. The standard Bruce multistage maximal treadmill protocol has 3 min periods (steps) to achieve a steady state before workload is increased. The patient starts at a relatively slow treadmill speed (1.7 mph/2.7 km/h), which is gradually increased until the patient has a good stride. The ramp angle is usually initially 10% grade, and this angle is then progressively increased at fixed 3 min intervals (stages). It takes about 1-2 min for the cardiovascular system to adjust and

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stabilise heart rate (HR) and blood pressure (BP) at each new workload.

The Bruce protocol can be modified to in-clude two 3 min warm-up stages at the same speed (1.7 mph/2.7 km/h) but with no slope (0% grade), followed by a second stage of 1.7 mph and 5% grade. This modified protocol is suitable for elderly patients or patients whose exercise capacity is limited by cardiac disease or any difficulties with physical performance. To avoid overestimation, it is important to en-courage the patient not to grasp the handrails of the treadmill during exercise. There is an increase of as much as 20% in functional ca-pacity when handrail support is permitted.

Exercise is usually completed when the pa-tient reaches 85% of predicted maximum heart rate (max. = (220 – age) x 0.85) (Table 2). The patient is then required to continue walking at a minor ramp angle for a few more minutes to recover and return to near resting values of HR and BP.

Standard Bruce Protocol (Table 2)

Stage Duration (min) Total Time (min) Speed (mph) Grade (%)

1 3 3 1.7 10

2 3 6 2.5 12

3 3 9 3.4 14

4 3 12 4.2 16

5 3 15 5.0 18

6 3 18 6.0 20

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b) AdvantagesMost patients find exercise by walking nat-ural and easy to perform compared with cycling.

c) DisadvantagesBP measurements are often difficult to ob-tain due to patient motion and gripping of the support railing. ECG tracings may have more motion artifacts at high workloads due to patient motion.

Endpoints for exercise stressing1. Reaching 85% of predicted maximum

heart rate2. Typical chest pain (angina) or equivalent

(dyspnoea)3. Ischaemic ECG abnormalities: diagnostic

ST depression of >2-3 mm, horizontal or down sloping

4. Significant ventricular or supraventricular arrhythmia on ECG

5. Progressive reproducible decrease in sys-tolic BP

6. Abnormal elevation of systolic BP7. Maxi-mum stress (fatigue)

Safety and risksThe risk associated with exercise stressing is determined by the clinical characteristics of the patient referred for the procedure. In a non-selected patient population, mortality is less than 1% and morbidity less than 0.05%; thus, the risk of complications is greatest in post-infarction patients and in those being

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evaluated for complex ventricular disease and multivessel disease.

Chapter 3: Stress Protocols – Adriana Ghilardi and Giuseppe Medolago

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Acute myocardial infarction or recent change on resting ECG

Active unstable angina

Serious cardiac arrhythmias

Acute pericarditis

Endocarditis

Severe aortic stenosis

Severe left ventricular dysfunction

Acute pulmonary embolus or pulmonary infarction

Acute or serious noncardiac disorder

Severe physical handicap or disability

Less serious noncardiac disorder

Significant arterial or pulmonary hypertension

Tachyarrhythmias or bradyarrhythmias

Moderate valvular or myocardial heart disease

Drug effect or electrolyte abnormalities

Left main coronary obstruction or its equivalent

Hypertrophic cardiomyopathy

Psychiatric disease

Absolute Relative

Peripheral arteriosclerosis vascular disease

Disabling arthritis

History of stroke

Orthopaedic problems

Chronic pulmonary disease

Extremity amputations (diabetic patients)

Poor motivation to exercise

Poor exercise capacity due to noncardiac endpoints, e.g. fatigue

Beta-blocking drugs limiting heart rate response

Left bundle branch block (false positive exercise perfusion scans)

Early post-MI (<5 days)

Absolute and Relative Contraindications to Exercise Testing

Limitations to Exercise Testing

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Pharmacological stressingPharmacological stress is increasingly being employed as an alternative to exercise testing for detection of physiologically significant cor-onary artery disease and for prognostication. A substantial number of patients referred to the nuclear cardiology laboratory are incapable of exercising either on a treadmill or a bicycle. Patients with orthopaedic, neurological, or peripheral vascular disease can be evaluated for the presence of coronary artery disease using a pharmacological vasodilation (in com-bination with nuclear imaging). In addition, patients on beta-blocking medication who are unable to increase their heart rate adequately by physical exercise can be studied success-fully with pharmacological vasodilation.

The patient is prepared with a standard 10-12 lead ECG set-up in the supine position. HR, BP, and ECG are registered at rest and every min-ute during the whole test and the recovery period. ECG monitoring is mandatory during the whole test.

There are three main types of pharmacologi-cal stressors:

DipyridamoleAdenosineDobutamine

•••

1. Dipyridamole infusion protocolDipyridamole is the pharmacological test of which there is the most extensive clinical experience. It was the first pharmacological stress test agent to be introduced (in the early 1980s); it was initially administered as capsules (with many gastro-intestinal side effects) and later as an i.v. infusion.

Dipyridamole is a synthetic indirect vasodilator. Intravenous infusion of Dipyridamole blocks the normal facilitated cellular uptake (in vas-cular endothelium and red blood cell mem-branes) of the natural vasodilator Adenosine, which regulates coronary blood flow to meet myocardial metabolic demands. Adenosine is synthesised and released by endothelial cells as part of local vaso-regulatory systems. Thus, Dipyridamole increases the extracel-lular interstitial concentration of Adenosine available to react with the specific Adenosine receptors that stimulate the relaxation of vas-cular smooth muscle cells with consequent coronary vasodilatation and increased blood flow.

In a patient without coronary artery disease, Dipyridamole infusion causes vasodilatation and increases coronary blood flow to 3 to 5 times baseline levels. In contrast, in patients with significant coronary artery disease, the vessels distal to the stenosis are already di-lated, sometimes maximally, to maintain nor-mal resting flow. In these patients, infusion of Dipyridamole does not cause any further

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vasodilatation in the stenotic vascular bed. Conversely, in the adjacent myocardium, which is supplied by normal vessels, a sub-stantial increase in blood flow occurs. Thus, heterogeneity of myocardial blood flow is produced; vascular territories supplied by diseased coronary arteries are relatively hy-poperfused compared with normal regions (‘coronary steal’).

a) ProtocolDipyridamole is infused over a 4 min period at a dose of 0.56 mg/kg diluted in normal solu-tion saline (20 ml). Maximal dilatory effect is achieved approximately 4 min after comple-tion of the infusion. This is usually associated with a slight increase in heart rate and de-crease in systolic blood pressure. Radiotracer is injected at the 7th minute of the infusion.

In some laboratories, Dipyridamole infusion is combined with handgrip exercise to reduce background activity of the tracer in the ab-dominal viscera. In some laboratories, at the end of Dipyridamole infusion and after the i.v. administration of the radiotracer, the in-travenous antidote Aminophylline is also ad-ministered to rapidly reverse any undesirable Dipyridamole-associated side effects.

b) Drug interactions (see Table 1)Ongoing treatment with beta blockers does not affect the efficiency of Dipyridamole; in fact, pharmacological dilatation represents the pro-tocol of choice for patients on beta blockers.

Dipyridamole protocol is particularly well suited to patients with left bundle branch block. The false positive rate with this proto-col is only 2-5%, compared with 30-40% for exercise testing.

c) Safety and risksThe side effects of Dipyridamole are often more severe and more difficult to control. The risks associated with this procedure are determined by the clinical characteristics of the patient. It should be undertaken under the supervision of a physician properly trained to perform such a test; any side effects, though often slightly more severe and harder to control than with other stress agents, can be quickly reversed with the intravenous antidote Aminophylline.

d) Absolute and relative contraindications to Dipyridamole testing

bronchospasmdrug intolerance

e) LimitationsLike any other drug, Dipyridamole pharmaco-logical efficacy is slight or moderate in some patients (‘non-responders’), thus reducing the accuracy of the stress testing.

2. Adenosine infusion protocolUnlike Dipyridamole, Adenosine is a natural vasodilator. It is synthesised from ATP in the vascular endothelium, and rapidly metabo-lised through active cellular uptake and en-

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zymatic degradation in myocardial cells and vascular smooth cells (the T1/2 of exogenously infused Adenosine is about 10 sec).

By directly stimulating A2 purine receptors in the heart, endogene and exogene Adenosine has an important role in the natural regulation of coronary flow (vasodilatation) and cardiac demand (lowering BP). By stimulating A1 pu-rine receptors in SA and AV node, it inhibits norepinephrine release from sympathetic nerve endings, reduces AV node conduction velocity, and has negative inotropic and chro-notropic effects.

Although both Dipyridamole and Adenosine exhibit similar physiological effects on coro-nary and systemic circulation, the vasodila-tor effect of Dipyridamole is more prolonged (up to 20-40 min) than that of Adenosine. In contrast, the regional and systemic vascular ef-fects of Adenosine appear earlier (within 20-30 sec) and quickly disappear after discontinua-tion of the infusion (T1/2 in plasma is about 15 sec). Maximal effect has been observed invasively after 60 sec and continues as long as the drug is infused. These metabolic char-acteristics explain the lesser rate of side effects for Adenosine compared to Dipyridamole (see Table 3).

a) ProtocolAdenosine is infused over a 4-6 min period at a dose of 140 μg/kg/min. Radiotracer is injected during the 5th or 6th minute of the infusion.

Many laboratories use the 2 plus 2 Adenosine protocol, which is very convenient, effective, and well tolerated. In this protocol, the radio-tracer is injected after 2 min of infusion, and the infusion then continues for an additional 2 min to clear the tracer from the blood.

In some laboratories, Adenosine infusion is combined with handgrip exercise to reduce background activity of the tracer in the ab-dominal viscera. In some laboratories, at the end of Adenosine infusion and after the i.v. ad-ministration of the radiotracer, the intravenous antidote Aminophylline is also administered in order to rapidly reverse any undesirable Adenosine-associated side effects.

b) Drug interactions (see Table 1)Adenosine testing is the protocol of choice in patients with significant arrhythmias or a psychiatric history. Furthermore, Adenosine testing is safe for stress testing soon after acute MI.

c) Safety and risksThe risks associated with this procedure are de-termined by the clinical characteristics of the patient referred for the procedure. It should be undertaken under the supervision of a physi-cian properly trained to perform such a test; any side effects, though often slightly more severe and harder to control than with other stress agents, can be rapidly reversed with the intravenous antidote Aminophylline.

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d) Absolute and relative contraindications to Adenosine testing

bronchospasmdrug intolerance

••

Reported Side Effects of Intravenous Dipyridamole and Adenosine (% of Patients) (Table 3)

Dipyridamole Ranhosky et al (1)

Adenosine Cerqueira et al (2)

Cardiac % of Patients % of Patients

Fatal MI 0.05 0

Nonfatal MI 0.05 0

Chest pain 19.7 57

ST-T changes on ECG 7.5 12

Ventricular ectopy 5.2 N.R

Tachycardia 3.2 N.R

Hypotension 4.6 N.R

Blood pressure liability 1.6 N.R

Hypertension 1.5 N.R

AV block 0 10

Noncardiac

Headache 12.2 35

Dizziness 11.8 N.R

Nausea 4.6 N.R

Flushing 3.4 29

Pain (nonspecific) 2.6 N.R

Dyspnoea 2.6 15

Paraesthesia 1.3 N.R

Fatigue 1.2 N.R

Dyspepsia 1.0 N.R

Acute bronchospasm 0.15 0

N.R = Not Recorded

e) LimitationsLike any other drug, Adenosine pharmaco-logical efficacy is slight or moderate in some patients (‘nonresponders’), thus reducing the accuracy of the stress testing.

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3. Dobutamine infusion protocolThe Dobutamine stress protocol is a demand-/supply-type protocol simulating a physical stress test.

The rationale for using this pharmacologi-cal approach is that Dobutamine infusion increases heart rate, blood pressure, and myocardial contractility; this increases myo-cardial oxygen demand and, in the presence of a functionally significant coronary stenosis, causes a mismatch between oxygen supply and demand that produces abnormal systolic wall motion.

Dobutamine is a synthetic sympathomimetic α1/β2 and β2 agonist:1. Cardiac β1 adrenergic stimulation results in increased myocardial contractility and heart rate (HR) - the inotropic effect is greater.2. The stimulation of cardiac α1 and β1 tends to offset the β2 effect on the vascular arteriolar smooth muscle cells leading to vasoconstric-tion, i.e. an increase in blood pressure (BP).

a) ProtocolDobutamine is first diluted to a concentra-tion of 1 mg/ml and infused at incremental doses of 5, 10, 20, 30 and 40 μg/kg/min at 3 min intervals, until symptoms or attainment of target HR. If the target HR cannot be reached by Dobutamine infusion alone (most often due to ongoing beta blocker medication), adjunctive small i.v. doses of Atropine (0.25-0.50 mg/push) should be used to reach the

target HR. Radiotracer is injected when target HR is reached.

Dobutamine quickly clears from the blood (T1/2 of about 2 min). It is useful to empha-sise that it is relatively common (in 15-20% of patients) to observe a blood pressure fall at higher doses of Dobutamine, both in patients with or without CAD, due to a mechano-re-ceptor reflex initiated in the left ventricle. This reaction does not carry the same significance as a blood pressure fall during exercise testing. If symptoms occur, simple leg elevation will help; occasionally, in the presence of severe symptoms, small doses of beta blocker anti-dote are needed.

b) Absolute or relative contraindications to Dobutamine testing

severe arrhythmiaspsychiatric disorders

••

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c) Reported Side Effects of Intravenous Dobutamine Infusion (% of Patients) (Table 4)

Cardiac % of Patients

Chest pain 19.3

Arrhythmias (all types) 15.0

Ventricular premature beats 15.0

Atrial premature beats 3.0

Noncardiac

Headache 3.0

Nausea 3.0

Dyspnoea 3.0

All side effects and severe symptoms are usually easily reversible with small doses of antidote beta blockers i.v. (Metropolol). Sometimes, ongoing treatment with beta blockers is a problem when using the Dobutamine protocol as it can be very difficult (or impossible) to reach the target HR, even after addition of Atropine. In this situation, a pharmacological vasodilatation protocol (using Dipyridamole or Adenosine) should be used.

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Preparation and Use of Imaging EquipmentRégis Lecoultre and José Pires Jorge

Quality control procedures that must be performed satisfactorilyThe end goal of any SPECT gamma camera quality control programme is the production of high-quality images for the best possible diagnostic service to the patient.

Prior to initiating a routine quality control programme for a newly purchased gamma camera, it must undergo acceptance test-ing in order to ascertain that its performance corresponds to the manufacturer’s specifica-tions and that it is fit for clinical use.

After acceptance testing, a quality control protocol must be set up in each department and followed in accordance with national guidelines. The following quality control test schedule is typical:a) Daily energy peakingb) Daily flood uniformity testsc) Daily gamma camera sensitivity

measurementd) Weekly linearity and resolution

assessmente) Weekly centre-of-rotation calibrationf ) Quarterly multipurpose SPECT phantom

evaluation

A routine quality control programme for SPECT gamma cameras should include qual-ity control procedures appropriate for planar scintillation cameras [see (a) to (d) below], and specific SPECT quality controls [see (e) to (f ) below].

a) Daily energy peakingThis quality control procedure consists of ‘peaking’ the gamma camera for relevant ener-gies prior to obtaining flood images. In cardiac imaging, technologists are mainly concerned with Tc-99m and Tl-201. For each radionuclide used, energy peaking must be undertaken on a daily basis.

Checking the peaking is necessary to ascer-tain that:

the camera’s automatic peaking circuitry is working properly

the shape of the spectrum is correct

the energy peak appears at the correct energy

there is no accidental contamination of the gamma camera

It is recommended that the spectra obtained during peaking tests are recorded.

b) Daily flood uniformity testsAfter a successful peaking test, it is recom-mended that a uniformity test is performed on a daily basis. Flood fields are acquired and evaluation of camera uniformity can be made via a visual assessment. Quantitative param-eters should also be computed regularly and recorded in order both to demonstrate sud-den variations from the norm and to alert the

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technologist to a progressive deterioration of the equipment.

On cameras that have interchangeable unifor-mity correction maps, it is vital that the one being used is accurate, up-to-date and for the correct nuclide.

c) Daily gamma camera sensitivity measurementA practical means of measuring sensitivity is to record the time needed to acquire the flood field using the known activity. This should not vary by more than a few percent from one day to another.

d) Weekly linearity and resolution assessmentLinearity and resolution should be assessed weekly. This may be done by using transmis-sion phantoms.

e) Weekly centre of rotation calibrationThe centre of rotation (COR) measurement determines the offset between the axis of rotation of the camera and the centre of the matrix used for reconstruction, as these do not automatically correspond.

The calibration of the centre of rotation is made using a reconstruction of a tomographic acquisition of a point source placed slightly offset from the mechanical centre of the rota-tion of the camera. A sinogram is formed from the projections and used to fit the maximum

count locations to a sine wave. Deviations be-tween the actual and fitted curves should not exceed 0.5 pixels.

f ) Quarterly multipurpose SPECT phantom evaluationMultipurpose plastic phantoms filled with a radioactive solution approximate realistic con-ditions of clinical scattering and attenuation. The multipurpose phantom includes remov-able cold rod sections and spheres simulating cold lesions. The main purpose of imaging this phantom is to determine the SPECT system’s limits of resolution. It is recommended that the phantom be filled with 750-1000 MBq of Tc-99m and the data acquired with an energy setting of 140 keV, a 20% energy window and a 128 x 128 pixel matrix for 128 projections over 360˚.

CollimatorIn myocardial imaging the current tracers are Tl-201 and Tc-99m labelled agents. The choice of a collimator for a given study is determined mainly by tracer activity. This influences the statistical noise content of the projection im-ages and the spatial resolution. The number of counts must be maximised, possibly at the expense of some resolution.

Collimators vary in terms of the relative length and width of the holes. The longer the hole, the better the spatial resolution obtained but the lower the count sensitivity. Conversely, a larger hole gives better count sensitivity but with a loss of spatial resolution.

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When using thallium, owing to the limited dose and the long half-life of this isotope, the count sensitivity will be greatly reduced. Tra-ditionally, a low-energy general purpose col-limator is recommended for use with Tl-201. For Tc-99m imaging, count sensitivity is no longer a major limitation so a high-resolution collimator is recommended.

In myocardial SPECT imaging, however, the major problem is the reduced spatial reso-lution that occurs if the source-to-detector distance is lengthened by the anatomical situation of heart. Nevertheless, the resolu-tion of an HR collimator decreases less with distance from the source than does that of a GP collimator. Although the choice of col-limator is crucial, we should bear in mind that other technical aspects play an important role in determining the optimal spatial resolution; these include the matrix size, the number of angles and the time per view.

Matrix used and zoom factorThe goal of SPECT is to ascertain the distribu-tion of injected activity in the patient’s body, and in particular in the heart. The images (or projections from the angles around the pa-tient) create multiple raw data sets. Each of these is electronically stored so that later on they can be processed and their information extracted. Each matrix contains the repre-sentation of the data in one projection. It is characterised by the number of pixels, each pixel representing part of the object. Pixels

are square and typically organised in arrays of 64 x 64 or 128 x 128.

a) MatrixThe choice of matrix is dependent on four factors:

i. Resolution:The chosen matrix should not degrade the in-trinsic resolution of the object. The commonly accepted rule for SPECT (1) is that the pixel size should be one third of the FWHM resolution of the organ, which will depend on its distance from the camera face. Spatial resolution of a SPECT system is of the order of 18-25 mm at the centre of rotation (2). Thus a pixel size of 6-8 mm is sufficient.

ii. Noise:This is caused by the statistical fluctuations of radioactive decay. Noise decreases with the total number of counts, and if the matrix size is doubled (to 128 instead of 64), the number of counts per pixel is reduced by a factor of four. 128 x 128 matrices produce approximately three times more noise in the image after re-construction than do 64 x 64 matrices (3).

iii. Data size:Of course, if there are four times more pixels in each projection (128 versus 64), four times more computer memory is needed for raw data and approximately eight times more for all processing. The processing time will also increase. All new generation computers have

Chapter 4: Preparation and Use of Imaging Equipment – Régis Lecoultre and José Pires Jorge

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more memory and resources for data calcula-tion, but may take some time to come onto the nuclear medicine market.

iv. Software:Sometimes, set protocols restrict the software options available to the technologist. This re-striction may be needed to ensure that re-sults can be compared with reference studies or databases. It is very important to ensure reproducibility in this way before setting up individual acquisitions. The reconstruction processing cannot replace information lost in the acquisition.

b) ZoomThe pixel size is dependent on the camera FOV (field of view). When a zoom factor of 1.0 is used, the pixel size (mm) is the UFOV (mm) divided by the number of pixels in one line. When a zoom factor is used, the number of pixels per line should first be multiplied by this factor; the FOV should then be divided by the result of this multiplication.

Example:Acquisition with matrix 64, zoom 1.0 and UFOV 400mm:Pixel size (mm) = 400/64 = 6.25 mm

Same acquisition with a zoom factor of 1.4:Pixel size (mm) = 400/(1.4 x 64) = 4.46 mm

c) Preferred orbitsEither circular or elliptical orbits can be used in

Figure 2a Figure 2b

cardiac SPECT imaging (Fig 2). A circular orbit (a) is defined by a fixed distance from the axis of rotation to the centre of the camera sur-face for all angles. Elliptical orbits (b) follow the body outline more closely.

With a circular orbit, the camera is distant from the heart at some angles, causing a reduction of spatial resolution in these projections. This will reduce the resolution of the reconstructed images.

With an elliptical orbit, spatial resolution is improved as the camera passes closer to the heart at all angles. Nevertheless, the distance from the heart to the detector varies more sig-nificantly with an elliptical orbit than a circular orbit. This may generate artifacts that simulate perfusion defects when reconstructing using filtered back projection.

Programmes that allow the camera to learn and closely follow the contours of the body are available and improve resolution, although this is at the expense of computing power to modify the data before reconstruction.

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The loss of spatial resolution with a circular orbit must be offset against the potential ar-tifacts that may be generated by an elliptical or contoured orbit.

When selecting an orbit in cardiac SPECT im-aging, it is most important to choose one that does not truncate or clip the heart. This should be checked after the acquisition while the pa-tient is still available so that the acquisition can be repeated if necessary.

ECG Gatinga) The ECGThe principal of the electrocardiogram is that the electrical activity of the heart is detectable on the body’s surface via electrical potential differences between sites. These differences can be recorded with electrodes coupled to

an electrocardiograph machine.

The ECG sequence:Excitation of the atrium begins in the region of the sino-atrial node (SN). One positively charged electric wave goes through both atria (‘depolarisation’). This is represented by the P wave on the ECG, and causes contractions. The electric stimulation then reaches the atrioven-tricular knot (AV) and, after a short stop whilst the ventricles fill, progresses along the bundle of His and Purkinje fibres. This step in ventricle stimulation is seen in the QRS complex. After a 1 sec pause, the ventricles repolarise (this is visible as the T wave). The repolarisation of the atria occurs at the same time as the QRS waves and is therefore not visible on the ECG.

P Wave

T Wave

RR IntervalR Wave

S WaveQ Wave

Example of an ECG (Figure 3)

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b) AcquisitionFor gating, only the contraction signal is need-ed and the R wave (the biggest signal from the QRS complex) is used (Fig 4).

The three lead ECG is not for medical diagnosis but for acquisition synchronisation. It provides the most distinct R signal when the patient is in the right position for acquisition.

Positive or negative signals can be used equally but, if required, the inversion can be done easily by changing over the two cables. If necessary, the signal can be amplified elec-tronically on the ECG machine.

For a reliable trace, it is best to fix an electrode onto each shoulder (first moving the arm into the acquisition position) and a third one onto the abdomen, right lateral. It’s best to fix this lead on the righthand side as most acquisi-tions are done with a 180˚ rotation over the lefthand side of the patient.

It is possible to define between 8 and 32 im-ages per cardiac cycle, depending on how much information is wanted on ventricular wall motion. Two issues affect this choice:

i. The total counts and hence ‘noise’:When the number of images is increased in order to reach a given number of counts per frame, the total acquisition time is extended.

ii. The data volume:If one acquisition is considered, every division of the cardiac cycle multiplies the data volume (or the number of frames) by the same factor. This is why 8 or 16 images per cycle are usually used for SPECT. Each image of the cycle can be called a bin.

c) ArtifactsThe greatest source of artifacts during gated acquisition is a changing HR. If any cycles differ significantly in length then the information in the total image will not be representative of the same stage of contraction in each cycle, but will instead be a mixture. Each image in one gated cycle is written initially to the buffer. If the length of its cardiac cycle is subsequently found to be more than ± 10% of a preset value based on prior observation of the patient’s heartbeat, this cycle should be rejected from the final sum.It may be impossible to do gated acquisitions on a patient who has a very unstable HR.

HR changes could be due to physical stress; if the patient has come directly from the exer-cise bicycle or has run along the corridor, their HR will decrease after a few minutes, and the window will have been wrongly set. Another explanation of this problem is psychological stress or anxiety. Conversely, if the patient’s HR increases over time, it may be that the patient is either becoming impatient or in an uncom-fortable or painful position.

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In some systems it is possible to exceed the defined time per projection in order to com-plete cardiac cycles that were not in the acceptance window. We speak of an effective acquisition time per projection. This is a good solution but the window definition should be good.

Gating via an ECG signal (Figure 4)

Chapter 4: Preparation and Use of Imaging Equipment – Régis Lecoultre and José Pires Jorge

��

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Imaging and ProcessingJulie Martin and Audrey Taylor

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Chapter 5: Imaging and Processing – Julie Martin and Audrey Taylor

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Fraction of Adult Administered Activity

3 kg = 0.1 22 kg = 0.50 42 kg = 0.78

4 kg = 0.14 24 kg = 0.53 44 kg = 0.80

6 kg = 0.19 26 kg = 0.56 46 kg = 0.82

8 kg = 0.23 28 kg = 0.58 48 kg = 0.85

10 kg = 0.27 30 kg = 0.62 50 kg = 0.88

12 kg = 0.32 32 kg = 0.65 52–54 kg = 0.90

14 kg = 0.36 34 kg = 0.68 56–58 kg = 0.92

16 kg = 0.40 36 kg = 0.71 60–62 kg = 0.96

18 kg = 0.44 38 kg = 0.73 64–66 kg = 0.98

20 kg = 0.46 40 kg = 0.76 68 kg = 0.99

Dosage for ChildrenThe following table* from the Paediatric Committee of the EANM may be used (1):

Thallium-201 Adult 15 y-old 10 y-old 5 y-old 1 y-old

Effective dose (μSv/MBq) 231 319 1,265 1,724 2,940

* This table summarizes the views of the Paediatric Committee of the European Association of Nuclear

Medicine. It should be taken in the context of ”good practise“ of nuclear medicine and local regulation.

Thallium Dosimetry by Age of PatientThallium should be avoided for children because of its dosimetry (2).

Drug interactions with radiopharmaceuticalsNone yet known.

Delay between Injection and Imaging - Tc-99m Sestamibi and Tc-99m Tetrofosmin

First study Second study Imaging period between injection rest/

stress and scan (min)

Waiting period bet-ween injections (min)

Rest Stress

Stress Rest

30-60 30-60

100 100-180

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Imaging should begin 30-60 min after injec-tion to allow for hepato-biliary clearance; lon-ger delays are required for resting images and for stress with vasodilators alone due to higher liver uptake.

After the injection, patients are asked to walk around and then eat a fatty meal to aid tracer clearance from the liver and gall bladder. Patients are also asked to drink two or three glasses of water 15 min prior to imaging.

Thallium studiesImaging should begin within 5 min of the stress study injection and be completed within 30 min of injection. This ensures that redistribution has not yet taken place. Redis-tribution imaging should be performed 3-4 hours after stress injection.

If the redistribution images are unsatisfactory, some centres then give a resting injection (ideally after sublingual nitrates) and image again after a further hour.

Dual-isotope protocolSome centres perform a dual-isotope protocol with thallium injected at rest, followed by a Tc-99m labelled agent injected at stress.

Patient positionsThe patient should be supine with both arms above the head and supported in a comfort-able position. Knee support is also helpful and patient comfort is essential to minimise mo-

tion. Prone imaging has been used in some centres to reduce the incidence of inferior attenuation artifacts, but it can produce an-terior artifacts and is not recommended in isolation.

In some centres female patients are imaged without underclothes. A chest band can be used to minimise breast attenuation and to ensure reproducible positioning during later image acquisition. This can however increase attenuation depending on how the band is applied so careful attention must be paid to technique when the breasts are strapped. Chest bands can also be used in males to re-duce motion.

The patient is positioned so that the heart is in the field of view. Immobilisation aids should be used to minimise patient movement and to ensure patient comfort, with arms raised above head. It may be more comfortable for the patient to have their left arm above their head and their right arm either under their bottom or in a pocket, but take care if the in-jection site is in the right arm. However, it is important that the patient is not rotated.

The camera is positioned to minimise patient-camera distance for the complete 180˚ SPECT rotation.

It is extremely important that the same op-erator performs both stress and rest studies whenever possible. It is essential that the

Chapter 5: Imaging and Processing – Julie Martin and Audrey Taylor

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camera/patient positioning is reproduced as closely as possible for rest and stress in order to ensure accurate comparison between the images. Where available, parameters such as bed height and lateral movements can be re-corded for reproducibility.

The study can be performed using an LFOV camera or dedicated cardiac camera (e.g. Optima), with an LEHR collimator when us-ing the Technetium agents, and LEGP when using Thallium and software zoom.

Gated SPECT with or without attenuation cor-rection should be used as appropriate.

Image magnificationA software zoom can be used, depending on the chosen camera.

Suggested Acquisition Parameters

Matrix 64 x 64

Frame time Thallium Tc-99m agents

40 sec/view 30-40 sec/view

No. of projections 32 or 64 depending on camera used (dual or single head)

180˚

Provision of both attenuated corrected and non-attenuated data should be available where possible.

ECG gating can be performed (unless HR is irregular), particularly with Tc-99m labelled ra-diopharmaceuticals. 8/16 frames per cardiac cycle should be acquired for accurate calcula-tion of left ventricular ejection fraction, depen-dent on the camera used.

The technologist should adjust the time per view if the count rate is lowered, e.g. due to patient size, tissued injection or imaging de-lays.

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Processing instructions - reconstructionFiltered back projection using Butterworth and Hanning filters is the most common method of reconstruction. Cut-off frequen-cies as per the manufacturer’s recommenda-tions, e.g. 0.5 cycles per cm (order 5 or 10) and 0.75 cycles per cm respectively can be chosen; these should be the same for each patient and should not be altered to compensate for low-count images in order to maintain consis-tency of appearance. Iterative reconstruction is preferred if attenuation correction has been performed, and can also be used without at-tenuation correction.

The long axis of the left ventricle runs from the apex to the centre of the mitral valve, and defi-

nition of this axis can be manual or automatic. Automatic definitions should be checked and adjusted if necessary. The definition should be consistent in both stress and rest stud-ies, bearing in mind that the orientation of the ventricle may change slightly between acquisitions.

The transverse tomograms are reoriented into three sets of oblique tomograms: (1) short axis (perpendicular to the long axis of the left ven-tricle), (2) vertical long axis (parallel to the long axis of the left ventricle and to the septum), and (3) horizontal long axis (parallel to the long axis of the left ventricle and perpendicular to the septum) (Fig 5).

Display of a Tc-99m Sestamibi SPECT (Figure 5)

Short axis - stress

Short axis - rest

Vertical long axis - stress

Vertical long axis - rest

Horizontal long axis - stress

Horizontal long axis - rest

Chapter 5: Imaging and Processing – Julie Martin and Audrey Taylor

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Image evaluationThe planar projection images and the recon-structed tomograms should be inspected immediately after acquisition by an operator or practitioner in order to identify technical problems that might require repeat acquisi-tion. These might include:

injection site or external objects passing across the heart

patient motion

inaccurate ECG gating

problems related to the detector(s), such as drift in energy window and artifact(s) generated by transition between the two detectors

inappropriate collimation or energy windows

gut activity encroaching into the heart wall

Image displayStress and rest images should be appropri-ately aligned and presented in a format that allows ready comparison of corresponding tomograms, such as interactive displays that triangulate the three planes or display the full set of tomograms. Each tomographic acquisi-tion should be displayed with the top of the colour scale at the maximum within the myo-cardium for each set.

•

•

•

•

•

•

Displays with the top of the colour scale at the maximum of each individual tomogram and those that use the same maximum for stress and rest images should not be used. Care should be taken if the maximum lies outside the myocardium and manual adjust-ment or masking of extracardiac activity may be required. The bottom end of the colour scale should be set to zero and background subtraction should be avoided. Neighbour-ing pairs of tomograms can be summed for display according to local preference.

Check that all images have the correct patient details displayed.

Attenuation correctionA number of techniques have been devel-oped for correcting emission tomograms for attenuation, in an effort to reduce or eliminate attenuation artifacts. Many of these incorpo-rate additional corrections for scatter and for depth-dependent resolution recovery. Al-though initial results are encouraging, each method behaves differently and none over-comes artifacts entirely, some even introduc-ing new forms of artifact through overcorrec-tion. The effectiveness of these techniques in routine clinical practice is currently uncertain. They should be used only in experienced cen-tres and preferably as part of a formal evalu-ation of their value. Corrected images should not be used without reviewing them along-side the uncorrected images.

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AftercareThe operator administering the radiopharma-ceutical should advise the patient with regard to minimising contact with pregnant women and children for 24 hours. After each study, and prior to the patient leaving the depart-ment, it is advisable to check that the data has been correctly acquired on the computer and to view the cine/sinogram to ensure that there is/are no patient movement/artifacts. The patient should be told that the procedure is completed, when the results will be sent and that they can return to taking routine tablets, eating, and drinking.

Chapter 5: Imaging and Processing – Julie Martin and Audrey Taylor

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References

Chapter 1

References1. Nishimura S, Mahmarian JJ, Boyce TM, Verani MS. Quan-titative thallium-201 single-photon emission computed tomography during maximal pharmacological coronary vasodilation with adenosine for assessing coronary artery disease. J Am Coll Cardiol 1991;18:736-745.

2. Varma SK, Watson DD, Beller GA. Quantitative comparison of thallium-201 scintigraphy after exercise and dipyridamole in coronary artery disease. Am J Cardiol 1989;64:871-877.

3. Dilsizian V, Rocco TP, Strauss HW, Boucher CA. Techne-tium-99m isonitrile myocardial uptake at rest. I. Relation to severity of coronary artery stenosis. J Am Coll Cardiol 1989;14:1673-1677.

4. Borges-Neto S, Shaw LK. The added value of simultane-ous myocardial perfusion and left ventricular function. Curr Opin Cardiol 1999;14:460-463.

5. Iskandrian AS, Chae SC, Heo J, Stanberry CD, Wasserleben V, Cave V. Independent and incremental prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging in coronary artery disease. J Am Coll Cardiol 1993;22:665-670.

6. Bonow RO, Dilsizian V. Thallium-201 for assessing myocar-dial viability. Semin Nucl Med 1991;21:230-241.

7. Holman ML, Moore SC, Shulkin PM, Kirsch CM, English RJ, Hill TC. Quantification of perfused myocardial mass through thallium-201 and emission computed tomography. Invest Radiol 1983;4:322-326.

8. Udelson EJ, Coleman PS, Metheral J, et al. Predicting reco-very of severe regional ventricular dysfunction. Comparison of resting scintigraphy with 201Tl and 99mTc-sestamibi. Circulation 1994;89:2552-2561.

9. Sciagrà R, Santoro GM, Bisi B, Pedenovi P, Fazzini PF, Pupi A. Rest-redistribution thallium-201 SPECT to detect myocardial viability. J Nucl Med 1998;39:385-390.

10. Pace L, Perrone Filardi P, Mainenti PP, et al. Identification of viable myocardium in patients with chronic coronary artery disease using rest-redistribution thallium-201 tomo-graphy: optimal image analysis.J Nucl Med 1998;39:1869-1874.

11. Cuocolo A, Acampa W, Nicolai E, et al. Quantitative thallium-201 and technetium-99m sestamibi tomography at rest in detection of myocardial viability and prediction of improvement in left ventricular function after coronary revascularization in patients with chronic ischaemic left ventricular dysfunction. J Nucl Cardiol 2000;7:8-15.

12. Brown BG, Bolson E, Peterson RB, Pierce CD, Dodge HT. The mechanisms of nitroglycerin action: stenosis vasodilati-on as a major component of the drug response. Circulation 1981;64:1089-1097.

13. Fujita M, Yamanishi K, Hirai T et al. Significance of col-lateral circulation in reversible left ventricular asynergy by nitroglycerin in patients with relatively recent myocardial infarction. Am Heart J 1990;120:521-528.

14. Rafflenbeul W, Urthaler F, O’Russel R,et al. Dilatation of coronary artery stenoses after isosorbide dinitrate in man. Br Heart J 1980;43:546-549.

15. Petretta M, Cuocolo A, Nicolai E, Acampa W, Salvatore M, Bonaduce D. Combined assessment of left ventricular function and rest-redistribution regional myocardial thalli-um-201 activity for prognostic evaluation of patients with chronic coronary artery disease and left ventricular dys-function. J Nucl Cardiol 1998;5:378-386.

16. Beller GA, Ragosta M. Extent of myocardial viability in regions of left ventricular dysfunction by rest-redistribution thallium-201 imaging. A powerful predictor of outcome. J Nucl Cardiol 1998;5:445-448.

17. Cuocolo A, Nicolai E, Petretta M, et al.One-year effect of myocardial revascularization on resting left ventricular function and regional thallium uptake in chronic CAD. J Nucl Med 1997;38:1684-1692.

18. Hecht HS, Shaw RE, Bruce TR, Ryan C, Stertzer SH, Myler RK. Usefulness of tomographic thallium-201 imaging for detection of restenosis after percutaneous transluminal coronary angioplasty.Am J Cardiol 1990;66:1314-1318.

19. Hecht HS, Shaw RE, Chin HL, Ryan C, Stertzer SH, Myler RK. Silent ischaemia after coronary angioplasty: evaluation of restenosis and extent of ischaemia in asymptomatic pa-tients by tomographic thallium-201 exercise imaging and comparison with symptomatic patients.J Am Coll Cardiol 1991;17:670-77.

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20. Acampa W, Petretta M, Florimonte L, Mattera A, Cuo-colo A. Prognostic value of exercise cardiac tomography performed late after percutaneous coronary intervention in symptomatic and symptom-free patients. Am J Cardiol 2003;91:259-263.

21. Rochmis P, Blackburn H. Exercise tests. A survey of pro-cedures, safety and litigation experience in approximately 170,000 tests. JAMA 1971;217:1061-1066.

22. Cerqueira MD, Verani MS, Schwaiger M, et al. Safety profile of adenosine stress perfusion imaging: results from the Adenoscan multicenter trial registry.J Am Coll Cardiol 1994;23:384-389.

23. Lette J, Tatum JL, Fraser S, et al. Safety of dipyridamole testing in 73,806 patients: the multicentre dipyridamole safety study.J Nucl Cardiol 1995;2:3-17.

24. Mertes H, Sawada SG, Ryan T, et al. Symptoms, adverse effects, and complications associated with dobutamine stress echocardiography: experience in 1118 patients. Cir-culation 1993;88:15-19.

Chapter 2

Further ReadingPennell and Prvulovich. Clinicians Guide to Nuclear Medici-ne - Nuclear Cardiology Series Ed.Ell 1995 BNMSProcedure Guidelines for Radionuclide Myocardial Perfu-sion Imaging. Adopted by the British Cardiac Society, the British Nuclear Cardiology Society, and the British Nuclear Medicine Society obtainable fromhttp://www.bncs.org.uk

Chapter 3

References1. RanhoskyA, Kempthorne-Rawson J. The safety of intrave-nous Dipyridamole Thallium myocardial perfusion imaging. Circulation 1990;81:1425-1427.

2. Cerqueira MD, Verani MS, Schwaiger M, Heo J, Iskandrian AS. Safety profile of adenosine stress perfusion imaging: results of the Adenosine multicenter trial registry. J Am Coll Cardiol 1994;23:384-389.

Chapter 4

References1. Groch MW, Erwin WD. SPECT in the Year 2000: Basic Prin-ciples. J Nucl Med Technol 2000;28:233-244.

2. De Puey EG, Garcia EV, Berman D. Cardiac Spect Imaging. Lippincott Williams & Wilkins 2001.

3. Garcia EV, Cooke CD, Van Train KF, Folks R, Peifer J, De Puey EG, Maddahi J, Alazraki N, Galt J, Ezquerra N, et al. Technical Aspect of Myocardial SPECT Imaging with Technetium-99m Sestamibi. Am J Cardiol 1990;66:23E-31E.

Further ReadingNuclear Medicine and PET, Technology and Techniques / Christian / MosbyPrinciples and Practice of Nuclear Medicine / Paul J.Early, D.Bruce Soddee

Chapter 5

References1. Paediatric Task Group European Association Nuclear Medicine Members. A radiopharmaceutical schedule for imaging in paediatrics. Eur J Nucl Med 1990;17:127-129.

2. Adsorbed doses from ICRP publication 80. ICRP publica-tion 80. Radiation dose to patients from radiopharmaceu-ticals. Addendum 2 to ICRP Publication, Pergamon Press, Oxford 1998.

Further ReadingPennell and Prvulovich. Clinicians Guide to Nuclear Medici-ne - Nuclear Cardiology Series Ed.Ell 1995 BNMSProcedure Guidelines for Radionuclide Myocardial Perfusion Imaging. Adopted by the British Cardiac Society, the British Nuclear Cardiology Society, and the British Nuclear Medici-ne Society obtainable from http://www.bncs.org.uk

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Imprint

Publisher:European Association of Nuclear MedicineTechnologist Committee and Technologist Education SubcommitteeHollandstrasse 14, 1020 Vienna, AustriaTel: +43-(0)1-212 80 30, Fax: +43-(0)1-212 80 309E-mail: info@eanm.orgURL: www.eanm.org

Content:This is a reprint of the „Myocardial Perfusion Imaging - Technologist‘s Guide“ of 2004.No responsibility is taken for the correctness of this information.Information as per date of preparation: August 2004

Layout and Design:Grafikstudio SacherHauptstrasse 3/3/10, 3013 Tullnerbach, AustriaTel: +43-(0)2233-64386, Fax: +43-(0)2233-56480E-mail: studio.sacher@aon.at

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European Association of Nuclear Medicine