Nuclear Medicine Resources Manual

Подождите немного. Документ загружается.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

190

Some studies have shown decreased accuracy in predicting future cardiac

events in patients who have undergone thrombolytic therapy for acute

myocardial infarction.

One of the more important factors in deciding whether to refer a patient

with left ventricular dysfunction due to coronary artery disease for revasculari

zation (whether coronary bypass or angioplasty) is the presence or absence of

viable myocardium. The term ‘viable myocardium’, in its broadest sense,

denotes any myocardium that is not infarcted. This includes normal, stunned or

hibernating myocardium. For the cardiologist, however, the search for

myocardial viability is primarily a quest for myocardial hibernation.

Myocardial hibernation is classically defined as chronic hypoperfusion and

dysfunction that reverses after revascularization. It can be distinguished from

myocardial stunning, which denotes acute but transient hypoperfusion and

dysfunction, typically after a myocardial infarction in adjacent tissue that does

not require intervention because it recovers spontaneously. It is now accepted,

however, that the line separating hibernation from stunning is not as clear as

was once thought.

Various modifications to basic myocardial perfusion imaging protocols

have been devised in order to distinguish hibernating, viable myocardium from

non-viable, infarcted myocardium. These include late redistribution, re-

injection imaging (both protocols using

201

Tl) and nitrate augmented rest

imaging (using either

201

Tl or

99m

Tc labelled agents).

The current best non-invasive method of detecting myocardial viability is

the comparison of perfusion and metabolism using PET tracers, although this still

underestimates the presence of viable myocardium in roughly 10% of patients.

(d) Assessment of ventricular function

Combining myocardial perfusion imaging with the ECG gating technique

(synchronization of acquisition to the ECG signal) allows the investigation of

ventricular wall motion and thickening throughout a typical cardiac cycle. This

may then be evaluated qualitatively by viewing the images in an endless loop

cine-display, or quantitatively using commercially available software. By

drawing ROIs around the endocardial boundaries of the ventricle, either

manually or through automatic edge detection algorithms, a volume curve can

also be generated for the entire cardiac cycle, from which quantitative

parameters such as end-systolic and end-diastolic volumes as well as ejection

fraction can be derived.

5.2. NUCLEAR CARDIOLOGY

191

Ventricular function may be also assessed by performing a first pass

acquisition of the injection of the perfusion tracer, either at rest or during

stress. This is feasible only using

99m

Tc labelled perfusion tracers.

Finally, ventricular function may be indirectly evaluated from non-gated

images. The presence of global dilatation, thinned out walls, ventricular

aneurysms and increased lung uptake are all suggestive of left ventricular failure.

5.2.4.3. Radiopharmaceuticals

A number of single photon emitting radiopharmaceuticals may be used

for imaging myocardial perfusion. The three most commonly used at present

are

201

Tl and the

99m

Tc labelled tracers sestamibi and tetrofosmin. Some of their

most important properties are summarized in Table 5.10.

(a) Thallium-201

This radionuclide is used in the chemical form of thallous chloride. The

photons of interest are mostly mercury X rays of 68–80 keV. Thallium-201 also has

gamma rays of 135 and 167 keV, which contribute little to the total image counts.

Thallium-201 has a very high single pass extraction fraction in the

myocardium, for which the major mechanism is active transport through the

Na-K ATPase pump. Uptake of this tracer therefore denotes intact

sarcolemmal membranes. The extraction fraction is linearly proportional to

blood flow over a wide range of physiological flow levels, plateauing only at

very high flow rates and logarithmically decreasing towards the very low flow

range. Relative accumulation in the myocardium thus reflects relative regional

perfusion.

This radiotracer is characterized by redistribution in the myocardium,

settling in equilibrium between the myocardial and blood pool concentrations.

This makes

201

Tl a marker of myocardial viability, which is perhaps its greatest

advantage.

(b) Technetium-99m labelled perfusion agents

There are two

99m

Tc labelled myocardial perfusion agents in common use

today. A third agent,

99m

Tc-teboroxime, characterized by extremely avid

myocardial uptake but rapid myocardial washout, is no longer commercially

available, while some others such as

99m

Tc-NOET are under investigation.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

192

(1) Technetium-99m-sestamibi

Sestamibi (sometimes called hexamibi or simply MIBI) is an isonitrile

lipophilic complex. Uptake of this tracer requires sarcolemmal and mitrochon

drial integrity. The major route of excretion is through the hepatobiliary

TABLE 5.10. PROPERTIES OF SINGLE PHOTON MYOCARDIAL

PERFUSION TRACERS

Property Tl-201 Tc-99m-sestamibi Tc-99m-tetrofosmin

Chemical type Electrolyte Isonitrile Diphosphine

Myocite localization Cytosol Mitochondria Mitochondria

Physical half-life (h) 73 6 6

Mode of decay Electron capture Isomeric transition Isomeric transition

Photon energy (keV) 68–80 140 140

Usual activity at single dose

(MBq/mCi)

74–111/2–3 <1110/30 <1110/30

Effective dose equivalent

(mSv/MBq)

26/74 18/1110 8/1110

Critical organ Kidneys

(1.2 cGy/mCi)

Upper colon

(0.18 cGy/mCi)

Gall bladder wall

(48.6 mGy/MBq)

Adverse effects at

recommended dose ranges

No serious

reported

No serious

reported

No serious

reported

Advantages Redistribution

property ideally

suited for

assessment of

myocardial

viability.

Short half-life allows

larger doses for

increased photon

flux.

Lack of significant

redistribution allows

early injection with

delayed acquisition

(e.g. in an

emergency room).

More easily

prepared compared

with sestamibi.

More rapid

hepatobiliary

clearance compared

with sestamibi.

Same advantages as

Tc-99m-sestamibi

over Tl-201.

Disadvantages Relatively long

half-life limits

allowable dose.

High incidence

of attenuation

artefacts.

High hepatobiliary

activity needs delay

in acquisition.

—

5.2. NUCLEAR CARDIOLOGY

193

system, and intense liver and intestinal activity occasionally causes significant

interference with image quality. Protocols employing

99m

Tc-sestamibi involve

post-injection waiting times of 45–90 min, to allow for adequate clearance of

subdiaphragmatic activity.

Technetium-99m-sestamibi is characterized by a minimal yet discernible

amount of redistribution, which may sometimes be used as a marker of

recoverable myocardium.

(2) Tc-99m-tetrofosmin

Tetrofosmin is a diphosphine compound whose pharmacokinetics largely

parallel that of Tc-99m-sestamibi. Its main advantages are ease of preparation

and faster hepatic clearance, allowing shorter post-injection waiting times of

20–30 min.

5.2.4.4. Equipment

(a) Cameras

A single-crystal gamma camera is the basic piece of equipment required

for myocardial perfusion imaging using both

201

Tl and

99m

Tc agents. Most

commercial models are equipped with a rotating gantry for SPECT imaging.

Planar imaging is no longer recommended for myocardial perfusion imaging.

Planar imaging is not considered optimal for myocardial perfusion due to its

lower sensitivity.

Acquiring images in a single, symmetric energy window is adequate,

although an asymmetric window as well as multiple window capability allow

minimization and correction of scattered radiation. A single-detector camera is

adequate for heavy patient workloads; however, a dual-detector camera, with

the heads oriented at 90° to each other, would reduce the acquisition time for a

typical 180° SPECT orbit. A small FOV camera, which only admits counts from

the heart and some adjacent part of the lungs, allows closer positioning of the

detector to the patient compared with a large FOV camera and is ideal for

departments with high patient throughputs.

Many current gamma cameras provide an option for non-uniform

attenuation correction using an attenuation map acquired with a transmission

source. By reducing or eliminating the incidence of attenuation artefacts on

SPECT, the specificity of the study is potentially enhanced. It is probable that

transmission attenuation correction will become the standard technique in the

future. With caution and experience, however, most attenuation artefacts can

be identified even without special techniques or manoeuvres.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

194

(b) Collimators

Two low energy collimators should be sufficient for imaging with

201

Tl and

99m

Tc agents: a general purpose collimator to obtain adequate count statistics in

201

Tl imaging and a high resolution collimator to take advantage of better

tolerance of patient-to-detector distance with

99m

Tc myocardial agents.

General purpose collimators may also be used for

99m

Tc imaging;

however, high resolution collimators may yield inadequate count statistics

using

201

Tl.

An ECG synchronizer or gating device is required for gated cardiac

SPECT if one is not already included with the camera. The ideal is gated

acquisition software that automatically adjusts RR interval windows to

changing heart rates (for a more equal distribution of counts across the cardiac

cycle) coupled with premature beat rejection.

(d) Processing computers

An automated reconstruction and reorientation program is not a

requirement. For accuracy, there is still no substitute for a trained and

experienced human operator. Most manufacturers, however, provide for

automated endocardial border ROI placement for quantitation of ventricular

function, a feature that may provide greater consistency. Nonetheless,

automated drawings always require human verification, especially in cases of

ventricles with extensive and severe perfusion defects.

An effective quality control program should be strictly observed for

myocardial perfusion imaging. Any error in the acquired image resulting from

a failure of quality control will be magnified many times upon tomographic

reconstruction.

(e) Exercise stress

A programmable motorized treadmill and ECG machine is preferred for

exercise testing, although a bicycle ergometer is an acceptable alternative.

Pharmacological stress modalities should be selected for patients who are

unable to perform upright leg exercise. A common protocol for treadmill

exercise is the Bruce protocol with symptom limited stress. The exercise is

terminated if there are significant ECG changes, drop in blood pressure, severe

chest pain, severe arrhythmia or exhaustion of the patient.

5.2. NUCLEAR CARDIOLOGY

195

(f) Pharmacological stress

No special equipment is required for dipyridamole infusion, other than a

syringe and an intravenous line. An infusion pump is essential with

dobutamine, because of the tight control required of the infusion rate.

Adenosine may be manually infused, but its extremely short duration of action

requires special attention to be paid to the timing in order to maintain an

adequate vasodilatory effect during tracer uptake, so an infusion pump is

preferable.

(g) Intravenous administration of dipyridamole

The standard protocol consists of a slow intravenous injection of the drug

(0.142 mg · kg

–1

· min

–1

) for 4 min, followed 3 min later by intravenous

administration of the tracer. This is necessary because the peak effect of

dipyridamole on coronary blood flow occurs 2–2.5 min after injection and then

declines exponentially with a half-life of 33 min. ECG, heart rate and blood

pressure should be monitored every minute for ten minutes and longer if

necessary. There is usually a mild reduction in systemic blood pressure, an

increase in heart rate and cardiac output and a significant increase in coronary

blood flow up to five times the resting values.

The common side effects of dipyridamole are angina, nausea, ST

depression, headache, dizziness, facial flush, vomiting and ventricular

arrhythmia.

5.2.4.5. Patient preparation

In order to obtain optimal image quality and maximal diagnostic benefit

from myocardial perfusion imaging, certain steps must be strictly observed for

patient preparation.

(a) Clinical examination

Ascertaining the reason for the request for myocardial perfusion imaging,

i.e. the precise information desired from the study, is the first step in

preparation for the test. This may be indicated on the attending physician’s

request. If not, a discussion with the referring physician is advisable.

It is essential to obtain an adequate history and conduct a physical

examination in order to interpret the images properly. What is the patient’s risk

profile for ischaemic heart disease? Are there any predisposing conditions for

small vessel disease, such as diabetes mellitus? Any complaints of chest pain

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

196

must be characterized, as well as any symptoms of congestive heart failure. A

history of eventual hospitalization for chest pain, shortness of breath or

syncope should be taken, as well as therapeutic measures adopted. Awareness

of previous operations, especially those involving implants such as breast

implants, pacemakers or valve prostheses, is important. A description of any

previous revascularization procedure should be available. It is also important

to know the results of recent cardiac diagnostic studies, especially catheteri

zation as well as imaging studies, provided this will not bias the interpretation

of the myocardial perfusion images. Obtaining a current and recent drug

history is always necessary.

A physical examination should include a description of the patient’s body

habitus, as well as breast size; note should be taken of any thoracic deformities

that could affect the orientation of the heart within the thorax and/or the

positioning of the patient under the camera.

(b) Diet and medication

A fasting state is required for both

201

Tl and

99m

Tc imaging at rest, except

for diabetic patients on insulin or oral hypoglycemic agents.

Patients undergoing exercise or vasodilator testing should discontinue

medications and foods that could interfere with the test. For exercise testing,

these include drugs that limit the tachycardic response to exercise, such as beta

blockers and calcium antagonists and drugs that increase flow to segments

subtended by coronary stenoses, such as nitrates. For dipyridamole or

adenosine testing, drugs and foods that antagonize the effects of adenosine

should be withheld, especially caffeine and other methylxanthine containing

drugs and beverages. For purely resting (viability) studies, no medication needs

to be withheld; the intake of nitrates may in fact optimize the sensitivity for

detecting viable myocardium.

Radiopaque objects should be removed from the area of the thorax. Note

should be taken of any implanted radiopaque devices (e.g. pacemakers and

silicone breast implants).

5.2.4.6. Procedure

(a) Viability studies

When the clinical situation simply requires an assessment of the distri-

bution and extent of viable myocardium, no cardiac stress is required. A rest

redistribution

201

Tl protocol will detect resting ischaemia as well as myocardial

5.2. NUCLEAR CARDIOLOGY

197

viability with satisfactory accuracy. This is done by simply injecting the patient

with 2–3 mCi of

201

Tl and commencing imaging 15 min later.

Alternatively, a single injection of a

99m

Tc agent at rest after administering

a short acting nitrate will yield an image from which myocardial viability may

be inferred by uptake alone; however, it sometimes may not differentiate

hibernating myocardium from a mixture of normal myocardium and scar tissue.

With

99m

Tc sestamibi, by delayed imaging 2–4 hours later, it may be possible to

detect a slight redistribution and thus infer the presence of myocardial hiber

nation; however, this is currently not widely recommended for evaluation of

viability.

Where there is a question of both inducible ischaemia and viability,

exercise or pharmacological stress imaging should be performed either on a

separate day or as a second procedure in a same day protocol (using

99m

Tc) or

with late redistribution or re-injection imaging (with

201

Tl). Late redistribution

imaging should be done no more than 18–24 hours after injection; later times

often result in images too degraded for interpretation.

(b) Ischaemia studies

In order to detect inducible myocardial ischaemia when the resting

perfusion is normal, a stress study is performed, whether physical or pharmaco

logical.

From an imaging standpoint, a two day protocol is preferable over a one

day protocol for

99m

Tc labelled tracers because a full allowable dose of

99m

may be given for both stress and rest studies. The main advantage of a one day

protocol is convenience for the patient, although a two day protocol could also

spare the patient a return trip for the rest study if the stress study is normal. For

a one day protocol, a rest stress sequence is preferable, not only because of

improved detection of defect reversibility but also because it may avoid the

effect of post-exercise stunning in the rest images.

This may be done in conjunction with either an ischaemia or a viability

study. When a two day protocol is used, both studies should be gated, although

for practical purposes only the rest study can be gated and used to evaluate

function in the true basal state.

CHAPTER 5. GUIDELINES FOR GENERAL IMAGING

198

5.2.4.7. Interpretation

Information useful for the interpretation of patient studies is summarized

in Tables 5.11–5.13.

Anatomical and physiological variations should be kept in mind, such as

low uptake at the apex and the membranous part of the interventricular

septum as well as low activity at the anterior wall (due to breast attenuation)

and the inferior wall (due to diaphragmatic attenuation). Artefacts such as

metallic implants, motion artefacts and bowel tracer should be excluded.

(a) Ischaemia

For

201

Tl, early redistribution in stress defects indicates stress induced

ischaemia. Late redistribution, redistribution after a resting injection or

improvement after re-injection implies hibernation or critical stenosis of the

TABLE 5.11. TYPICAL

PERFUSION ABNORMALITIES IN VARIOUS

CLINICAL CONDITIONS

Condition

Typical regional perfusion findings (assuming no artefacts)

Stress Rest

Late imaging –

re-injection (Tl-201)

Normal Normal Normal —

Stunned Variable Variable No further change

Inducible ischaemia Decreased Normal —

Mixture of ischaemia and

infarcted tissue

Decreased Partially improves No further change

Subendocardial infarction Normal Worsens Partially improves

or no further change

Critical stenosis/

hibernating myocardium

Decreased No change to partial

improvement

Partial

improvement to

normal

Infarction (transmural) Decreased

(moderate to

severe)

No change No change

Dilated idiopathic

cardiomyopathy

Patchy,

decreased

No change No change

Considerable variation may occur, depending on the clinical circumstances.

5.2. NUCLEAR CARDIOLOGY

199

supplying artery. Defects that persist after these latter procedures, especially

after enhancement by nitrates, very likely represent an infarct.

For

99m

Tc-sestamibi or -tetrofosmin, higher relative uptake with rest

imaging compared with stress implies induced ischaemia. Rest defects that

improve after nitrate enhanced rest imaging indicate hibernation with a critical

stenosis of the supplying artery. Defects that persist after such manoeuvres are

probably due to infarction.

(b) Prognosis

The finding of normal stress–rest myocardial perfusion indicates a very

low (<1%) annualized risk for myocardial infarction and cardiac death,

regardless of positive findings on a stress ECG or the findings of a coronary

TABLE 5.12. MARKERS OF HIGH RISK FOR FUTURE CARDIAC

EVENTS WITH POOR PROGNOSIS IF UNTREATED

Without prior infarction Defects in multiple vascular territories

Redistribution in perfusion defects (partial or complete)

Transient ventricular cavity dilatation

Persistent global ventricular dilatation

Elevated pulmonary tracer activity under stress

Left ventricular ejection fraction less than 40%

With prior infarction Any of the above, plus:

Redistribution in infarct zone

Extent of infarct more than 40% of entire ventricular wall

For pre-operative assessment, this means a 10–20% risk of perioperative cardiac

events.

TABLE 5.13. MARKERS OF POTENTIALLY RECOVERABLE

MYOCARDIAL SEGMENTAL DYSFUNCTION

Perfusion Stress or pharmacologically induced (reversible) perfusion defects

Nitrate enhanced Uptake improvement relative to rest

Redistribution Late Tl-201 redistribution or redistribution after resting injection

Re-injection Increased uptake on Tl-201 re-injection

Relative uptake >50% of maximum myocardial uptake

Gated images Significant wall thickening