Each patient and/or their attendants should be informed in writing about the purpose of the examination, duration, possible side effects that may occur during the process, and the radiation exposure of the examination. The patient should be informed by the cardiologist for possible discontinuation of his medication and refrain from foods and beverages that may contain caffeine.⁷

Thallium 201 (²⁰¹Tl) has been used for more than 40 years for MPI. It is administered by intravenous injection (usual dose of 80 to 110 MBq). The myocardial uptake is proportional to perfusion and in absolute terms amounts to 4% of the injected dose.⁸ After intravenous administration, approximately 88% is cleared from the blood after the first circulation.^{9 201 201}Tl is a monovalent cation, similar in size to the hydrated potassium ion (K⁺). Approximately 60% enters the cardiac myocytes using the sodium-potassium ATPase-dependent exchange mechanism, and the remainder enters passively along an electropotential gradient. The extraction efficiency is maintained under conditions of acidosis and hypoxemia and only when myocytes are irreversibly damaged is extraction reduced.¹⁰ The biologic half-life during extraction of the myocardium is 60 to 90 minutes, when it is injected directly into the coronary arteries, but it is much higher (4 to 5 hours) in the case of intravenous administration, because of the balance that develops between ²⁰¹Tl located intracellularly and ²⁰¹Tl present in the intravascular space.

Although significant experience has been gained over time with this tracer, it has some limitations. First, it has a relatively long physical half-life (72 hours), which results in a high radiation burden for the patient. Eighty MBq deliver an effective dose of 11 mSv.¹¹ This is greater than the average dose received by the patient during angiography (8 to 10 mSv). Second, the relatively low injected dose of 80 to 110 MBq results in a low signal-to-noise ratio and images can be suboptimal, especially in obese patients. Third, the relatively low-energy emission leads to low-resolution images and significant attenuation by soft tissue. Electrocardiographic (ECG)-gated imaging is possible, but the low count statistics may be a cause for concern. For these reasons, ²⁰¹Tl has mainly been superseded by technetium-based radiopharmaceuticals except for viability studies. With the use of novel CZT detector technology, smaller doses of tracer can be used to minimize radiation exposure, and this can be achieved without prolonging image acquisition and without loss of image quality, while technetium dose could be substantially lower than the standard dose (see below).

Two technetium (^99mTc)-labeled perfusion tracers are commercially available: Tc-99m-2-methoxy-isobutyl-isonitrile (MIBI) or sestamibi and Tc-99m-1,2-bis[bis(2-ethoxyethyl) phosphino] ethane (tetrofosmin). MIBI is a cationic complex that diffuses passively through the capillary and cell membrane. Roughly 2.8% of MIBI injected at rest and 3.2% of the dose during dynamic exercise are concentrated in the myocardium, which is smaller than that of ²⁰¹Tl (4%). MIBI is mainly trapped in mitochondria and shows no significant redistribution for at least 2 to 3 hours after administration. Its elimination from the circulation is rapid, and its clearance occurs through the liver and kidneys.¹² Tetrofosmin is rapidly cleared from the blood, and the ultimate myocardial uptake is slightly less than that of MIBI.¹³ The retention of the myocardium is satisfactory and in combination with rapid hepatic clearance makes it possible to obtain an image 20 minutes after the injection. The myocardial uptake mechanism is similar to that of MIBI (Table 23.1).

The response to the stress has a central role in assessing the function of the cardiovascular system. This is especially important in case of CAD, because flow at rest is normal until a diameter stenosis of around 80% of the lumen occurs. Most of these techniques use some type of stress of the cardiovascular system seeking to reveal differences in coronary flow reserve (CFR) between different arteries. Some of them cause myocardial ischemia due to the increased oxygen consumption by the myocardium, while others, such as, for example, the pharmacologic test with adenosine, alter blood flow levels without necessarily leading to ischemia. The most frequently used method is dynamic exercise, but in many patients, it is not feasible usually due to peripheral vascular disease and musculoskeletal diseases. Dynamic exercise is the method of choice and is applicable to patients who are able to achieve satisfactory load (at least 85% of their maximum heart rate appropriate to the age and sex of the patient). If the test is performed for diagnostic purposes, preparation of patients includes discontinuation of medications with anti-ischemic effect, ideally for five half-lives, provided that this is approved by the referring physician (the same applies also for pharmacologic stress with vasodilators). In addition, patients should avoid foods, liquids, and medicines that contain caffeine, while specific diet is not necessary. The aim is to perform a symptom-limited exercise test (see Table 23.2). However, there are patients who are unable to undergo dynamic exercise, absolute contraindications of which are the following: a recent acute coronary syndrome (ACS) (the patient should be hemodynamically stable for at least 24 to 72 hours, after chest pain depending upon clinically assessed risk), left main stem stenosis that is likely to be hemodynamically significant, symptoms of heart failure (HF) at rest, a recent history of severe arrhythmia, aortic stenosis, hypertrophic cardiomyopathy (HCM), severe hypertension (systolic blood pressure >220 mm Hg or diastolic blood pressure >120 mm Hg), recent pulmonary embolism or infarction, thrombophlebitis or active deep vein thrombosis, active endocarditis, myocarditis, or pericarditis. Relative contraindications to the dynamic stress are left bundle branch block (LBBB), paced rhythm, movement disorders, and inability to complete a recent exercise test.¹⁴ In these cases, administration of drugs that alter the coronary flow or myocardial oxygen consumption is the only option. There are currently four pharmacologic stressors: dipyridamole, adenosine, regadenoson, and dobutamine.

Dipyridamole dilates arteriolar coronary circulation by increasing adenosine levels in the plasma, which is a strong vasodilator substance, acting via the purinergic receptors. The increase of flow in the coronary circulation in normal subjects is about 250% to 600% of flow at rest. In patients with CAD, the administration of dipyridamole causes uneven increase in the flow and deficits in SPECT MPI. Dipyridamole is administered intravenously at a dose of 140 µg/kg/min for 4 minutes. The time required to achieve maximal vasodilation is about 4 minutes, and therefore, the radiopharmaceutical should be injected in the 8th minute of the test. The maximum increase of flow in the coronary circulation is maintained for 10 min and then returns to baseline levels within half and hour. The administration of dipyridamole is indicated as stress test to patients who cannot exercise to an adequate level as well as for those with LBBB or paced rhythm. Chest pain (not necessarily ischemic) appears in 20% of patients and significant arrhythmias in less than 2% of patients. Extracardiac effects (headache, dizziness, nausea, epigastric pain, flushing) are observed in 30% to 40% of patients treated by slow intravenous aminophylline (up to 250 mg), which is a specific antagonist.¹⁵

Adenosine dilates coronary vessels, and the main advantage is the very short half-life time in plasma, which is estimated at less than 10 seconds. This has the effect of reducing the duration of side effects, and this is the main reason why, while it is more expensive than is dipyridamole, many nuclear medicine laboratories prefer to use adenosine. It causes arterial vasodilation in most networks by acting on A2a receptors and increasing the level of intracellular cyclic adenosine monophosphate. This results in relaxation of smooth muscle fibers of small vessels and consequently vasodilation. Adenosine has negative chronotropic and inotropic effect by its action on the A1 receptors. Intravenous administration at a rate of 140 µg/kg/min results in maximal or near-maximal hyperemia in 92% of patients, with an average increase of the flow in normal coronary vessels by 4.4 times compared to the resting value. The time required to achieve maximum vasodilatation is about 2 minutes,

and therefore, the radiopharmaceutical may be given in the second to third minute of the test, and the test may be finished over 2.5 to 3 minutes later. Like dipyridamole, adenosine can be coupled with submaximal dynamic exercise when tolerated to reduce the frequency and severity of adverse effects associated with vasodilator infusion.¹⁴ A bicycle ergometer, allowing a semirecumbent patient’s position, may be preferable to a treadmill, because intravenous infusions are easily managed when the patient is relatively steady. Heart rate, blood pressure, and ECG should be measured and recorded at baseline and every 2 minutes during the infusion. The tracer is injected between the 3rd and 4th minutes of the adenosine infusion or sooner if symptoms or other complications require.

As with dipyridamole, most of the perfusion defects are created by flow heterogeneity between normal arteries and arteries with stenotic lesions. Ischemia is uncommon but may be caused by coronary steal, when collateral circulation is present. ST segment depression is observed in 15% of patients being investigated for CAD and in 25% of patients with known CAD, which is less than that observed during dynamic stress. Side effects are present in 80% of patients. Chest pain (not necessarily ischemic) is common seen in up to 40% of patients.¹⁴,¹⁶ Other side effects are headache, facial redness, and atrioventricular (AV) block. Because the half-life of the drug in plasma is very short (10 seconds), side effects disappear rapidly. Contraindications and preparation for testing with adenosine are similar to those of dipyridamole and regadenoson.

To avoid the side effects of vasodilator stress, agonists with a high selectivity for the adenosine A_2A receptor responsible for the coronary vasodilator effect of adenosine have been developed. Of all compounds, regadenoson (Rapiscan, United Kingdom, or Lexiscan, United States) is the most commonly available for use in Europe and United States. Regadenoson has a rapid onset of action with peak coronary vasodilation by 30 seconds after administration and a short-lasting vasodilator effect of 2.30 minutes that is sufficient for adequate myocardial tracer extraction. Regadenoson was tested in two randomized double-blind studies of over 2,000 patients, and the results demonstrated that beyond its appealing features for clinical use, such as ease of administration as a rapid injection over 10 seconds and single non-weight-adjusted dose of 400 µg, regadenoson has comparable efficacy to adenosine and a similar side effect profile but better tolerability compared to the latter.¹⁷,¹⁸ Moreover, regadenoson can be used safely in patients with mild-to-moderate reactive airway disease and obstructive lung disease.¹⁹,²⁰ Like adenosine and dipyridamole, regadenoson can also be combined with submaximal exercise when tolerated. Regadenoson has also been used during dynamic exercise when maximal exercise is not achieved, but there is little evidence for the effectiveness and safety of this approach.

Absolute contraindications for the administration of the above vasodilators are known bronchospasm requiring treatment with steroids, second- and third-degree AV block in the absence of functioning pacemaker, hypotension (systolic pressure <90 mm Hg), taking xanthine or dipyridamole during the last 24 hours, known or suspected sinoatrial disease, and any other cases in which a stress test is contraindicated (e.g., acute HF, hemodynamic instability). Relative contraindications are recent cerebral ischemia or infarction.¹⁴ Patients with well-controlled or mild asthma or chronic obstructive pulmonary disease (COPD) can be stressed with adenosine. The latter can be given as a titrated protocol starting at a low dose of 70 or 100 µg/kg/min for a minute and increasing if tolerated up to 140 µg/kg/min with tracer injection two minutes after the maximal dose of 140 µg/kg/min. Patients who are already on a β₂-adrenergic agonist such as salbutamol can be given two puffs of the inhaler prior to starting the adenosine infusion.

In patients stressed with the vasodilators, dipyridamole should be withheld for at least 24 hours prior to adenosine or 48 hours before regadenoson administration. Patients must also avoid aminophylline and theophylline as well as consumption of any foods and drinks containing caffeine (coffee, tea, chocolate) or caffeine-containing medications, for a minimum of 24 hours prior to the test.⁷ Caffeine ingestion may attenuate the normal vasodilator response to adenosine, dipyridamole, and regadenoson. Attenuation of adenosine-induced perfusion abnormality by caffeine (in patients who have consumed caffeine within 12 hours prior to the test) can be overcome by increasing the adenosine dose to 210 µg/kg/min.

Dobutamine is used in patients with asthma or COPD, where vasodilators cannot be administered and a dynamic stress test is not feasible. Dobutamine increases myocardial perfusion in two ways: (a) causing vasodilatation through direct action into β₂ receptors and (b) increasing the oxygen consumption due to an increase in heart rate and myocardial contractility. The increase of coronary flow due to dobutamine is greater than that induced by dynamic exercise, but lower than that with dipyridamole or adenosine.²¹ The half-life in the plasma is approximately 90 seconds. Dobutamine is administered intravenously by a peripheral vein (initial dose of 5 to 10 µg/kg/min and then the dose is increased to 15, 20, 30, and 40 µg/kg/min every 3 to 5 minutes). The preparation of patients includes discontinuation of β-adrenergic antagonists for five halflives, if possible, or at least for 24 hours. When dobutamine is used in echocardiography stress studies (stress echo), the additional intravenous atropine administration is useful (if there are no contraindications) when there is no satisfactory increase in heart rate. However, the use of atropine is less frequent in scintigraphic imaging, for the reason that the main mechanism of action of dobutamine is vasodilation, and therefore, the creation of perfusion deficits in patients with CAD is the result of inhomogeneous flow increase in coronary vessels. Intravenous administration of dobutamine in patients with CAD is safe, and serious complications occur rarely. Chest pain occurs in one-third of the patients, palpitation in 10%, and transient ventricular tachycardia, causing no hemodynamic changes, in 4% of patients. The effects of dobutamine are resolved by the administration of β-blockers. Given the positive chronotropic and inotropic action, dobutamine should not be used as a stress test in patients with contraindications to dynamic exercise as well as known hypokalemia. Relative contraindications are LBBB and paced rhythm, because dobutamine, like dynamic exercise, can cause septal perfusion defects even in the absence of epicardial CAD.

²⁰¹Tl is usually administered at peak stress test, which is continued for about 2 minutes after the injection in order to maintain constant conditions during the uptake of the tracer from the myocardium. Imaging begins 5 to 10 minutes after injection and must be completed within 30 minutes. During this period, the distribution of the radiotracer in the myocardium is relatively stable, and the obtained images correspond to myocardial perfusion at the time of maximum stress. In areas with reduced perfusion, the concentration of ²⁰¹Tl is reduced, resulting in the creation of perfusion defects. Then, ²⁰¹Tl exits the myocardium with a washout rate that differs in regions with normal compared to those with reduced perfusion. The result of the different washout rates is the relative increase in uptake of ²⁰¹Tl after 2 to 4 hours in areas that initially showed reduced intake. The effect of improving or “filling” of a perfusion deficit over time is called redistribution. Comparison of images of stress with those of redistribution allows differentiation of inducible ischemia from permanent necrosis (partial or transmural). In some cases, it is likely that redistribution is incomplete at 4 hours. Therefore, for a more complete imaging, ²⁰¹Tl (40 MBq) is reinjected (ideally after sublingual nitrates) followed by a third set of images obtained at 45 to 60 minutes after injection.²²

For stress and rest imaging with ^99mTc-labeled tracers, two separate injections are necessary, and these can be given on the same or different days. Different imaging protocols can be followed, depending on clinical indication and local practices: (a) 1-day stress-rest, (b) 1-day rest-stress, and (c) 2-day protocol. The latter is recommended on the grounds of image quality (it is ideal for obese patients), but it may be less convenient for the patient. In the United States, the 2-day protocol includes an initial study in which 888 to 1,332 MBq (this is lower in Europe, for instance, 800 MBq per study is used in the United Kingdom, www.arsac.org.uk) of the tracer are administered during stress followed by a resting study performed on a different day after administering the same tracer activity.²³ Imaging begins 30 to 60 minutes after injection to allow for hepatobiliary clearance with longer delays required for resting images and for stress with vasodilators alone because of the higher liver uptake. The two studies can also be performed on the same day if the second study is obtained after administration of a higher (usually three times compared with the first) tracer activity, in order to reduce significantly the influence of the residual activity of the first injection.²⁴ A count density of 1:3 or 4 between the two studies is recommended. The 1-day protocol of tetrofosmin or MIBI involves administration of 296 to 444 MBq (in the USA) at stress and, 3 hours later, injection of 888 to 1,332 MBq at rest.²³ Higher doses can be considered on an individual basis by the practitioner, for instance, in obese patients. The levels of activity can be reduced considerably when using modern imaging systems (see below). If a 1-day protocol is performed, a rest-first study has advantages including better contrast between normal and ischemic segments and lesser time interval between the two studies. However, in patients with low pretest likelihood of obstructive coronary disease, one could consider a stress-first study, especially with ECG gating and attenuation correction (AC) to obviate the need for a rest study.

The effective dose of SPECT MPI for the 2-day protocol with MIBI and tetrofosmin is 8.1 and 7.2 mSv, respectively, while for ²⁰¹Tl, it is 11 mSv. The effective dose is increased when the 1-day protocol with ^99mTc is performed as the dose in the second study is usually three times higher than the first. The effective dose is also increased in ²⁰¹Tl studies when it is reinjected for viability assessment. When SPECT MPI with MIBI or tetrofosmin is performed for diagnostic purposes and the stress scan is normal, the effective dose is significantly reduced.⁷

An important consequence of the lack of redistribution of the ^99mTc-labeled tracers is that stress imaging can be delayed for sometime after injection, and there is no need to inject close to the γ camera. Injections can be given during treadmill exercise testing, in the catheter laboratory, or in the coronary care unit immediately before thrombolysis. In addition, because of the higher activity that can be used with ^99mTc, ventricular function can be assessed either by first-pass imaging of the tracer as it passes through the central circulation or by ECG-gated acquisition of the myocardial perfusion images (see below).

This is designed to overcome the disadvantages of the time-consuming imaging protocol, which uses two injections of MIBI or tetrofosmin. However, it has the disadvantage of increasing the total radiation dose received by the patient. ²⁰¹Tl is initially administered at rest, and images are obtained 30 to 120 minutes after tracer injection. Following completion of the rest scans, stress images following a tracer injection of MIBI or tetrofosmin are obtained. The interval between injection and image acquisition for ²⁰¹Tl depends on the clinical indication for carrying out the study. Thus, if the study is performed in patients with significant CAD and impaired ventricular function wherein detection of viable myocardium is important, late imaging (120 minutes after injection) is recommended, whereas if the examination is performed for diagnostic purposes, imaging can begin much earlier.²⁵ The advent of the solid-state detector (such as CZT)-based technology enables the execution of such studies with a total radiation exposure comparable to that of high-dose 1-day stress/rest technetium-99m-MIBI SPECT MPI but lower than dual thallium-201/technetium-99m imaging using a conventional camera. With such scanners, a strong correlation for several variables including image quality and the extent and depth of perfusion abnormality was found between simultaneous acquisition of thallium-201 and technetium-99m images and sequential acquisition with conventional SPECT (see immediately below).

Single photon emission computed tomography. This technique uses γ camera with a rotating head for the collection of data. Nowadays, in many nuclear cardiology departments, dual head tomographic imaging is performed over a 180-degree rotation from right anterior oblique (RAO) 45 degrees to left posterior oblique (LPO) 45 degrees. For ²⁰¹Tl, imaging general purpose collimators are used, while for ^99mTc, high-resolution collimators are used, unless resolution recovery software is available, in which case, the use of low-energy general purpose should also be considered in order to reduce either the acquisition time or the administered dose. A 15% to 20% energy window at 72 and 167 keV for thallium-201 and 140 keV for technetium-99m-labeled radiopharmaceuticals should be selected. The acquired pixel size should be in the region of 6 mm. A step-and-shoot acquisition with 32 or 64 stops separated by 3 to 6 degrees or a continuous acquisition can be used. The duration of acquisition at each stop depends partly on the equipment, protocol, dose of radiopharmaceutical, patient size, and reconstruction algorithm. Total acquisition times of longer than 20 to 30 minutes can be counterproductive as they increase the likelihood of patient motion. ECG gating can be performed, particularly with technetium-99m-labeled radiopharmaceuticals.²⁶

In recent years, there have been significant developments in terms of the image reconstruction algorithms, which, in combination with improvements in collimators, have resulted in resolution and signal-to-noise ratio improvement. The result is a reduction of the acquisition time to half the standard, or alternatively, administration of half the dose in standard time.²⁷,²⁸ and ²⁹ Reconstruction with the resolution recovery approach is the recommended option, but if resolution recovery is not available, then reconstruction is performed with iterative reconstruction. With the evolution of imaging systems (CZT camera), the administered radioactivity can be greatly reduced (e.g., 185 MBq at rest and 555 MBq at stress for ^99mTc tracers), thereby reducing the effective dose to the patient by 50% to 70% compared with the conventional protocols. Reduction of imaging time is also feasible to 2 and 4 minutes, respectively, for stress and rest compared to 16 and 12 minutes, respectively, for a standard stress/rest SPECT study in a technetium-99m protocol. This shorter acquisition time has multiple benefits including a better tolerated examination by the patients, reduction of motion artifacts, and the ability to scan a higher number of patients without compromising the diagnostic accuracy or the predictive value of SPECT MPI.¹,²⁵,³⁰,³¹,³²,³³,³⁴ and ³⁵

Modern systems also offer motion correction software. This can correct certain forms of motion such as movement in the longitudinal axis and vertically. Patient motion should be corrected only when it is greater than 2 pixels, since less significant motion does not create serious artifacts.⁷ Another parameter that can affect image quality is photon scattering by the patient’s body and the detectors, which can be corrected by the use of additional energy windows or by reducing the width of the selected energy window.⁷ Photon attenuation by the patient’s body is yet another source of artifacts. These are created by an unevenly reduced tracer uptake by
the myocardium, which depends on the type of tissue (soft tissue, bone, or lungs), the activity of the radiopharmaceutical, and the body type of the patient. The most common artifact is the appearance of an inferior defect in men due to attenuation of photons by the diaphragm or an anterior wall defect in women due to photon attenuation from the breast tissue⁷ (Table 23.3).

AC of the tomographic images can be performed either using a radionuclide line source (e.g., gadolinium 153) or more commonly now by using a CT detector integrated into the gamma camera gantry. However, it may itself introduce artifacts of its own. Misalignment between emission and transmission data can risk incomplete correction and create artificial perfusion defects. Misregistration of just 1 pixel can cause a diagnostically significant artifact.⁷ Both European and American guidelines recommend careful use of AC for myocardial perfusion SPECT studies.³⁶ The corrected images (AC) should be considered together with the uncorrected (non-AC) ones, because overcorrection can occasionally occur resulting in reduced sensitivity. CT-AC can improve the specificity of the test, but at the expense of sensitivity. Also, it can underestimate the size and severity of a perfusion defect, particularly in the inferior wall.³⁷

Myocardial perfusion and hence tracer distribution is uniform in normal myocardium (Fig. 23-1). A regional defect indicates reduced perfusion in viable myocardium, a reduced amount of viable myocardium, or a combination of both. If a stress defect returns to normal in the resting images, this indicates an inducible perfusion abnormality that is sometimes referred to as inducible ischemia. Strictly, the term “ischemia” is not always correct, particularly if stress is performed with the vasodilators, in which case, the image indicates heterogeneity of perfusion rather than an absolute reduction. Areas of infarction are depicted as a defect in both stress and rest images, and the depth of the defect indicates the amount of myocardial loss. Ischemia can be superimposed upon partial thickness infarction, and in this case, a stress defect may be only partially reversible at rest (Fig. 23-2). Reverse redistribution is the term used to describe a defect in redistribution thallium images that is less apparent in the stress images. When the phenomenon is seen, it is often the result of artifact or other technical differences between images, and, in this case, it is not strictly speaking reverse redistribution. When true reverse redistribution is seen, it is the result of rapid washout of tracer as might occur in an area of partial thickness infarction supplied by a patent artery after angioplasty or thrombolysis. In addition to regional myocardial uptake, other features of the images are important. Ventricular dilation is best judged from the planar images although it is also apparent in the tomograms. Of particular significance is left ventricular dilatation in stress images that is less marked on the resting ones, since this implies extensive inducible ischemia and is associated with an adverse prognosis. The dilatation may be partly real, but it may also be the result of widespread subendocardial ischemia that simulates cavity enlargement. The normal right ventricular myocardium is much thinner than the left, but it is not unusual to see right ventricular uptake. Hypertrophy in either ventricle can be seen as myocardial thickening and an increase in counts. When a relative defect is seen, care must be taken to distinguish between reduced uptake in an area of reduced perfusion and increased uptake in a neighboring area of hypertrophy. Because the myocardial images are not of high spatial resolution, it is often necessary to make this distinction only after echocardiography or MRI has been used to define myocardial thickness.³⁸,³⁹,⁴⁰ and ⁴¹ Increased ²⁰¹Tl uptake of the lungs is caused by increased pulmonary capillary pressure and is accompanied by an
increased incidence of future cardiac events in patients with CAD. Lung uptake is a marker of impaired left ventricular function at rest or induced by ischemia during exercise. It is expressed as a ratio between uptake in the lungs and the myocardium, even though myocardial uptake depends upon viability and perfusion. The measurements are obtained either from an initial anterior planar image or from the appropriate image of the tomographic acquisition, and a normal lung:heart ratio is less than 0.55 ± 0.11.⁴² In a mechanism similar to that of ²⁰¹Tl, the increased uptake of MIBI or tetrofosmin by the lungs and an LHR more than 0.35 ± 0.08 is associated with LV dysfunction and is a predictor of adverse prognosis in patients with known or suspected CAD.⁴³,⁴⁴ Perfusion defects are not always the result of CAD (see below). Abnormalities can be seen with coronary spasm, anomalous arteries, muscle bridges, small vessel disease as may occur in diabetes or syndrome X, the dilated and hypertrophic cardiomyopathies, hypertrophy caused by outflow obstruction or hypertension, infiltrative disorders such as sarcoidosis and amyloidosis, connective tissue disorders, and conduction defects such as LBBB.

Several methods have been used to quantify myocardial uptake, and these are all relative rather than absolute techniques in which uptake is expressed relative to the “hottest” voxel (i.e., highest uptake value) within the myocardium. The techniques include linear profiles, circumferential profiles, and analysis of count histograms, but a method that is popular for tomographic imaging is to display the whole myocardium as a polar map or “bull’s-eye” image (Figs. 23-1 and 23-2). Individual polar maps can be compared with a normal database and abnormalities detected automatically as areas with counts less than two standard deviations (or other threshold) from the mean. The normal database should be gender and radionuclide specific and may also be institute specific. The polar mapping is usually visualized with a color scale, where the corresponding pixels below the normal range are displayed with different colors. The extent of myocardial perfusion deficit may be determined as a percentage of the pixels of the polar mapping in which the uptake of the radiopharmaceutical is less than the statistically predetermined threshold. Polar maps with quantification are probably most helpful to assess the depth and extent of defects, but they should not be used as sole basis. However, they can be helpful to assess changes posttreatment. Most experienced nuclear cardiologists prefer to assess the presence of a defect from the tomograms initially and to use quantification to assess depth and extent of an abnormality. The three-dimensional display of LV (3D display) is another option, helping to determine the presence, extent, and location of perfusion defects, while giving information for the size and configuration of LV. Additionally, it can help in correlating SPECT MPI findings with those of other imaging studies, such as those of angiography.⁷ Segmental analysis can be performed by visual analysis or automated using a number of models of the left ventricular myocardium. A 17-segment model is recommended by several professional societies, and in each segment, tracer uptake is classified semiquantitatively on a five-point scale where 0 = normal (uptake >70%), 1 = mild deficit (uptake 50% to 69%), 2 = moderate deficit (uptake 30% to 49%), 3 = severe deficit (uptake 10% to 29%), and 4 = absence of perfusion (uptake <10%). By adding those numbers together, the sum of the stress scores (SSS), the sum of the rest scores (SRS), or the sum of the difference scores (SDS)⁴⁵,⁴⁶ can be calculated (Figs. 23-3 and 23-4).

Because automated analysis has the drawback of being susceptible to artifacts leading sometimes to false-positive results, the findings must not be reported in isolation and without expert review of the images from which the results are derived.⁷,⁴⁷ Caution is also required in relating perfusion findings with coronary artery anatomy (Fig. 23-5). Usually, the right feeds the bulk of the inferior wall of the LV and the adjacent portion of the septum. The left after
a short course is divided into the anterior descending artery (LAD) and the circumflex artery (LCX). The LAD feeds the anterior wall and the upper 2/3 of the septum, while the LCX feeds the lateral LV wall and sometimes also the base of the inferior wall. In 85% of cases, the right is the dominant (right dominance), giving rise to the posterior descending artery (PDA). In the rest of the cases, PDA stems from the circumflex artery (left dominance) and perfuses the inferior wall and the lower part of the intraventricular septum or (rarely) from both the LCX and the RCA (codominance).⁴⁸ Exact matching of anatomical damage and ischemia may be achieved by hybrid imaging, combining CT coronary angiography with SPECT MPI⁴⁹,⁵⁰