Technetium-99m Labeled Radiopharmaceuticals

The development of several classes of ^99m Tc-labeled radiopharmaceuticals that overcome some of the technical limitations of ²⁰¹ Tl has led to their widespread use in MPI. These include principally isonitriles and diphosphines. Compared with ²⁰¹ Tl, the technetium label confers the favorable characteristics of ready availability; larger administered activity for better statistics, with reduced patient radiation doses per unit administered activity; and advantageous photon energy of 140 keV, producing higher-resolution SPECT images. The larger administered activity leading to higher myocardial count rates allows shorter acquisition times, with resultant decrease in patient motion and improved patient tolerance for the examination. The higher 140-keV photon of ^99m Tc also helps minimize attenuation artifacts from the breast or diaphragm. In addition, good statistics and reasonably long retention in the myocardium of ^99m Tc-labeled radiopharmaceuticals optimize G-SPECT acquisition for evaluation of LV function and wall motion. Thus, myocardial perfusion and function can be assessed by using a single tracer. Whichever ^99m Tc agent is used, the overall sensitivity for the detection of CAD is comparable to thallium but the specificity is improved, resulting in part from fewer attenuation artifacts.

In addition to the technetium label, a major distinction between the most commonly used ^99m Tc agents and ²⁰¹ Tl is their behavior once taken up by the myocardium. After entering the myocardial cells, thallium does not remain static but undergoes significant washout from the myocardium back into the blood with reuptake into myocardium over time. This dynamic process, called redistribution, means that a single dose of thallium injected at stress may be immediately imaged to reflect perfusion at stress, but also imaged later when the redistribution of thallium presents an image ultimately reflective of a resting state. In contrast, the technetium agents remain in an essentially fixed myocardial distribution reflecting regional perfusion at the time of injection. There is no significant redistribution over time. Thus, when using the technetium agents, imaging at rest and after stress requires two separate injections, one at rest and one at peak stress. Because both the rest and stress images are obtained with the same 140 keV ^99m Tc radiopharmaceutical, the activities of the injections must be adjusted so that a lower activity is administered for the first study and a higher activity for the second so that differences in perfusion at rest and stress can be distinguished.

Although thallium localizes in the myocardium by active transport through the cell membrane and the lipophilic technetium agents enter the cells by passive diffusion, their deposition in the myocardium is proportional to regional blood flow, with regions of lower blood flow accumulating less of the radiopharmaceutical and thus presenting as areas of decreased activity (defects) compared with adjacent normal areas of relatively higher flow. Thus, the diagnostic information obtained is the same.

Technetium-99m Sestamibi

Technetium-99m sestamibi (Cardiolite) is the most commonly used radiopharmaceutical for MPI. It is a lipophilic cationic isonitrile that is extracted by the myocardium with a first-pass efficiency of 65% and with lengthy myocardial retention primarily through binding to cytoplasmic mitochondria. Unlike thallium, there is minimal redistribution (< 20%) over time in the myocardium. Advantages to this fixed distribution include the convenience of delaying imaging when necessary, without loss of sensitivity, and the ability to reimage in case of equipment malfunction, positioning error, or patient motion. However, lack of significant redistribution also means that imaging of myocardial perfusion under stress and rest conditions requires two separate injections of radiopharmaceutical.

After intravenous (IV) injection, initial concentration of sestamibi is highest in the heart and liver. Approximately 1% to 2% of the activity localizes in the heart at rest. Accumulation of sestamibi in the myocardium is directly proportional to blood flow at physiologic levels. However, at high flow rates (greater than about two to three times baseline flow), such as those achieved during pharmacologic stress, blood flow may be underestimated. Although there is minimal change in concentration in the heart over time, there is progressive clearance of liver activity through biliary excretion (~35%) into the bowel and ultimately into the colon, which receives the highest absorbed dose. There is also some (~25%) renal excretion ( Fig. 5.4 ). Because adjacent or overlapping liver activity may interfere with cardiac imaging, enhanced clearance of activity from the liver and gallbladder may be facilitated by having the patient drink 8 ounces of milk or eat a fatty meal about 15 minutes after sestamibi injection. However, this may result in an increase in interfering bowel activity, especially when imaging is sufficiently delayed to allow passage of the radiopharmaceutical into the transverse colon and splenic flexure. When sestamibi is administered with the patient at rest, hepatobiliary clearance is slower but usually sufficient to permit imaging about 30 to 60 minutes after injection. Accumulation of sestamibi in the liver and gallbladder is relatively lower with maximal exercise than at rest, so postexercise imaging may generally be obtained 15 to 60 minutes after injection.

Normal Whole-Body Distribution of Technetium-99m Sestamibi.

Postexercise anterior (Ant) and posterior (Post) planar images demonstrate left ventricular (arrow) and skeletal muscle activity. There is also a large amount of activity in the liver, gallbladder, and bowel, as well as in the kidneys and bladder because of hepatobiliary and renal excretion routes.

Technetium-99m Tetrofosmin

Technetium-99m tetrofosmin (Myoview) is a cationic diphosphine with good myocardial uptake (1% to 2% of the injected dose with a first-pass extraction efficiency of ~50%) and retention with little redistribution from the myocardium over time. Tetrofosmin underestimates myocardial blood flow at high flow rates (about two times baseline flow). There is rapid clearance of background activity from the blood pool. Similar to sestamibi, its cellular localization involves binding to cytoplasmic mitochondria. Its biokinetics are also in many ways similar to those of ^99m Tc-sestamibi. However, less hepatic uptake and more rapid clearance from the liver after exercise make imaging possible within 30 minutes of IV injection and minimize the likelihood of artifacts associated with overlapping hepatic activity.

Thallium-201 Chloride

Although less commonly used for MPI than the Tc-labeled radiopharmaceuticals, the use of ²⁰¹ Tl can play an important role as an alternative imaging agent at times when shortages of ⁹⁹ Mo and thus ^99m Tc limit or interrupt MPI using Tc-based agents. Further, ²⁰¹ Tl also has properties that make it valuable in assessing myocardial viability and in distinguishing postinfarction scarring from chronically ischemic myocardium.

Thallium-201 is a cyclotron-produced radionuclide that decays by electron capture, with a half-life of about 73 hours. On decay, the major emissions are characteristic x-rays of the daughter product, mercury-201 ( ²⁰¹ Hg), with an energy range of 69 to 81 keV. These are the primary photons used in myocardial imaging. Thallium-201 also emits smaller numbers of gamma rays at energies of 135 keV and 167 keV. The relatively long physical half-life of ²⁰¹ Tl is advantageous, providing convenient shelf storage and successful imaging over a period of hours. The long half-life, however, also increases absorbed dose to the patient and limits the amount that can be administered. The relatively low administered activity requires longer imaging acquisition times and results in lower-count densities with inferior contrast resolution compared to ^99m Tc-labeled radiopharmaceuticals. Further, soft-tissue absorption of the low-energy emissions of ²⁰¹ Tl increases the likelihood of attenuation artifacts from overlying breasts and diaphragm, producing spurious defects that decrease the specificity of the study.

Thallium has biokinetic properties similar, but not identical, to potassium. Like potassium, thallium crosses the cell membrane by active transport mechanisms, especially the adenosine triphosphate–dependent Na ⁺ -K ⁺ pump. After IV administration, it ultimately has a mainly intracellular distribution. Thallium localizes in the myocardium in two phases: (1) initial distribution based on blood flow and cellular extraction by viable myocardium, and (2) delayed redistribution in the myocardium mediated by a dynamic equilibrium based on the continued extraction of thallium from the blood and ongoing washout of previously extracted thallium from the cells.

The extraction of thallium from the blood by viable myocardial cells is rapid, approaching 90% extraction efficiency. However, the total amount of thallium ultimately accumulating in the normal heart is limited by the concentration of thallium circulating through the coronary blood supply. Therefore, only about 3% to 5% of the total injected dose is localized in the heart.

Under resting and normal stress conditions, regional myocardial uptake of ²⁰¹ Tl is linearly related to the regional coronary perfusion. Decreased perfusion to an area of myocardium results in a decrease in thallium accumulation in that region, compared with adjacent areas of relatively normal activity. A flow differential between normally perfused and poststenotic ischemic myocardium of about 2 : 1 is required before a definite defect is noted on thallium imaging.

After the rapid initial uptake of ²⁰¹ Tl by the normal myocardium, there begins a slower process of washout of the thallous ion from the myocardial intracellular compartment back into the vascular compartment. At the same time, however, there is representation of additional bloodborne thallium to the myocardial cells for reextraction provided by the large pool of the injected radioisotope that was initially held by other organs of the body. These simultaneous processes of thallium washout and reextraction across the cell membrane provide a means for a dynamic equilibrium between intracellular and extracellular thallium, which defines the phenomenon known as redistribution. The washout component of redistribution depends strongly on coronary perfusion, with ischemic areas demonstrating much slower washout than normal regions.

Because of the more rapid washout of thallium from normally perfused tissue and the slower washout from myocardium that became ischemic at stress, the delayed redistribution images show an ultimate equalization of activity between the normal and ischemic tissue under most circumstances. Thus, on postexercise thallium images, a defect indicative of relatively decreased perfusion should disappear on later redistribution images if the initial defect was caused by transient reversible stress-induced ischemia. Because this redistribution may occur rapidly in some patients, post-stress images should be obtained early (usually in 15 to 20 minutes) to ensure a snapshot of myocardial perfusion at peak stress and so that an ischemic defect will not be missed. A nonreversible (“fixed”) defect carries other implications and frequently indicates an area of scarring.

Technetium-99m Radiopharmaceutical SPECT Rest and Stress Imaging Protocols

In patients with a moderate- to high-risk of CAD, known coronary artery disease, or a history of myocardial infarction, both rest and stress images are usually obtained to distinguish myocardial scars from salvageable ischemic myocardium. The requirement of separate stress and rest injections of ^99m Tc-sestamibi or ^99m Tc-tetrofosmin to differentiate fixed from reversible defects has given rise to several different imaging protocols. These may be summarized as 1- and 2-day protocols ( Fig. 5.5 ).

Schematic Representation of 1- and 2-day ^99m Tc-Sestamibi Myocardial Exercise Protocols.

The protocol using ^99m Tc-tetrofosmin is similar, except that rest images may be obtained as early as 30 minutes after injection of the radiopharmaceutical.

Thallium SPECT Stress–Rest Imaging Protocol

The use of ²⁰¹ Tl for MPI has decreased over the years in favor of ^99m Tc agents, largely due to the less than ideal imaging characteristics and greater absorbed doses. However, in certain instances, it can be very useful. These include (1) clinical situations in which myocardial viability assessment is needed, (2) when used in combination with ⁹⁹ Tc radiopharmaceuticals for so-called “dual isotope” studies, allowing for shorter study times since the relative isotope energies do not interfere with each other and waiting time between rest and stress studies can be considerably shortened, and (3) in times of shortage of ⁹⁹ Mo, limiting availability of ^99m Tc radiopharmaceuticals for MPI.

The SPECT thallium exercise test consists of an initial post-stress set of myocardial images and an identical set of delayed redistribution images. An outline of the procedure is presented in Fig. 5.6 .

Schematic Representation of Thallium Stress–Redistribution (Rest) Imaging Protocol.

Dual Isotope Imaging: ²⁰¹ Tl- ^99m Tc Sestamibi/Tetrofosmin Protocol

A dual isotope protocol using ²⁰¹ Tl at rest and ^99m Tc perfusion tracers during stress has been used as a variant of the 1-day, rest–stress all- ^99m Tc protocol. In this protocol ( Fig. 5.7 ), a rest study using about 3 mCi (111 MBq) of ²⁰¹ Tl is first obtained, followed shortly by a stress ^99m Tc sestamibi or tetrofosmin study (24 to 36 mCi [888 MBq to 1.33 GBq]), so that the entire examination can be completed within 90 minutes, although at a higher patient absorbed dose. The rest study is performed first with the lower-energy ²⁰¹ Tl (68 to 80 keV) so that there is no interference with the higher-energy ^99m Tc (140 keV) acquisition. Because attenuation defects are generally more prominent on thallium imaging than with technetium agents, stress imaging is subsequently performed with ^99m Tc sestamibi or tetrofosmin to minimize false-positive stress examinations caused by such artifacts. Further, post-stress G-SPECT using ^99m Tc radiopharmaceuticals may increase the specificity of any perfusion defects. Extra care should be taken in processing the two different sets of images because different parameters need to be used to optimize the image quality of each data set.

Schematic Representation of 1-day Thallium-201-technetium-99m ( ^99m Tc) Sestamibi Exercise Imaging Protocol.

A similar protocol may be followed using ^99m Tc tetrofosmin.

Patient Absorbed Dose Considerations

Imaging physicians should be aware that MPI studies impose a relatively high radiation dose. This places an added responsibility for them to be used in accordance with established appropriateness criteria. Patient doses from MPI may be lowered by selection of the protocol used. The patient effective doses for the commonly used protocols are given in Table 5.2 . Dual-isotope rest–stress imaging using ²⁰¹ Tl and ^99m Tc-sestamibi may increase patient throughput, but they are associated with notably greater radiation doses than other protocols. Protocols using only ^99m Tc radiopharmaceuticals typically reduce doses to half that of dual isotope imaging. Further, protocols limited to stress-only acquisitions, such as foregoing the rest study if the stress images are normal, offer a significant dose reduction, as may lowering the administered doses used in standard rest–stress protocols. Performance of MPI using newer SPECT instrumentation incorporating innovations in acquisition and image reconstruction technologies offer even lower dose alternatives without loss of image quality.

Strategies for reducing patient doses from MPI include use of:

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  ^99m Tc radiopharmaceuticals.

  
  
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  Lower administered activity protocols, especially in smaller patients.

  
  
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  Stress-only protocols in low-risk patients with normal post-stress images.

  
  
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  Lower x-ray tube current in SPECT/CT and PET/CT protocols.

  
  
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  Adequate patient hydration and encouragement of frequent bladder emptying.

  
  
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  Advanced, dedicated cardiac camera and image reconstruction technologies.

Image Processing

After acquisition, the post-stress and rest (redistribution) images are reformatted in oblique planes. For structures with an oblique axis of symmetry in the body, such as the heart, the standard reconstructed cross-sectional views referencing the body are inadequate. Thus image reconstruction of cardiac tomograms is performed in three planes that are perpendicular to or parallel with the long-axis of the heart and oblique to the axis of the body; these include (1) short-axis, (2) vertical long-axis (VLA), and (3) horizontal long-axis (HLA) images ( Figs. 5.8 to 5.10 ). Generally, the primary operator input required for reconstruction is the identification of the long axis of the heart and rough delineation of the myocardial limits. This allows the appropriate reconstruction of tomographic images in three orthogonal planes relative to the orientation of the heart in the chest. The displayed reconstructed myocardial images are typically ~ 3 to 6 mm in thickness when 64 × 64 (pixel size ~ 6 mm) or 128 × 128 (pixel size ~ 8–9 mm) matrices are used.

Short-Axis Anatomy and Images.

Short-axis sections through the left ventricle from the base of the heart to the apex are shown with corresponding single-photon emission computed tomography slices of the myocardium. Note the considerable thinning of the proximal septal wall in plane A (the base of the heart) as a result of the membranous septum.

Vertical Long-Axis Anatomy and Images.

Vertical long-axis sections through the left ventricle from septum to free (lateral) wall are shown with corresponding single-photon emission computed tomography slices of the myocardium.

Horizontal Long-Axis Anatomy and Images.

Horizontal long-axis sections through the left ventricle from the anterior to the inferior wall are shown with corresponding single-photon emission computed tomography slices of the myocardium.

The quality of SPECT images is greatly enhanced by computer processing and display. The most frequent maneuvers applied to the raw data are background subtraction, contrast enhancement, and image filtering. These processes are meant to make the images more pleasing to the eye and to improve contrast by removing distracting, unwanted activity and statistical noise. A wide choice of image filters is available for image manipulation, commonly including Butterworth, Hamming, and Hanning filters. The specific filtering processes used vary greatly among laboratories and depend on the preferences of individual interpreters. Care must be taken not to overprocess images such that the data are distorted and artifacts are induced ( Fig. 5.11 ).

Effect of the Cutoff Value of a Filter Applied to a Single Short-Axis Image of the Left Ventricle.

Sharpness of the image is improved with an increasing cutoff value, but artifactual defects may be created. The image becomes fuzzy with a low cutoff value, which may mask true defects. Obviously, the choice of filter may have great effect on the quality of the images and, if not properly chosen, can produce false-positive or false-negative interpretation.

SPECT Image Display

After processing is completed, the myocardial slices must be displayed in a fashion that facilitates comparison of the stress and redistribution/rest image sets. It is attendant on the interpreter to ensure that corresponding slices between the two sets of images are displayed so that an accurate comparison is made. The orientation of the images obtained in each reconstruction plane is standardized to the generally accepted convention ( Fig. 5.12 ). This is usually automatically performed by using the user software supplied by the equipment manufacturer. Generally, only tomographic sections that represent slices through both the myocardium and the cavity of the heart are used, to avoid partial-volume artifacts. Subsequent interpretation is best performed by manipulation of the image intensity and contrast on the computer screen or the viewing station of a picture archiving system.

Normal Single-Photon Emission Computed Tomography Technetium-99m Sestamibi Stress–Rest Study.

The upper two rows represent short-axis stress and short-axis rest images. These “slices” progress from the apex on the left to the base of the heart on the right. The next two rows show horizontal long-axis stress and rest images, from the inferior to the anterior left ventricular wall. The lower two rows are the vertical long-axis stress and rest images, from the septum on the left to the lateral wall on the right.

Bull’s Eye (Polar Map Display)

In addition to the conventional display of tomographic slices, the entire three-dimensional perfusion distribution of a set of exercise or rest images may be condensed into one two-dimensional display by using a so-called polar or “bull’s eye” map ( Fig. 5.13 ). This display may be thought of as the heart viewed from its apex and opened up like an umbrella. Semiquantitative methods are applied to this bull’s eye display of the SPECT perfusion data that compare the radiopharmaceutical distribution for each patient to a gender-matched normal database of distribution. Thus regional activity less than that expected in a normal population identifies a perfusion deficit and is displayed as such on the polar map. The actual visual appearance of this deficit based on its severity is determined by the gray or color scale used. When using this display, however, the interpreter should be aware that perfusion defects at the base of the heart (outer circumference of the polar map) tend to be overemphasized, whereas centrally located defects, such as the LV apex, tend to be underrepresented. The bull’s eye representations of stress and rest (redistribution) myocardial perfusion can easily be visually compared in a third bull’s eye display that shows the differences in activity. This defines the reversibility or fixed nature of a perfusion defect. These bull’s eye plots are a convenient tool to be used as an adjunct to standard visual image interpretation and to summarize a patient’s perfusion pattern in a single image.

Normal Polar (Bull’s Eye) Display of Myocardial Perfusion.

(A) Both the stress and rest images demonstrate relatively uniform activity without significant deviation from perfusion in age-matched controls. (B) Approximate coronary artery distribution relative to the polar plot. The unshaded regions are areas of variable arterial supply. Ant, Anterior; Inf, inferior; Lat, lateral; Sept, septum.

Approach to Interpretation

Visual interpretation principles are virtually the same regardless of the myocardial perfusion radiopharmaceutical used. Consistent interpretation of SPECT myocardial perfusion images is best ensured by a systematic approach that includes the following elements:

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  Raw projection SPECT images are reviewed for patient motion, attenuation patterns, extracardiac activity, subdiaphragmatic activity, and position of the arms

  
  
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  Proper alignment (coregistration) of the post-stress and rest tomographic slices

  
  
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  Perusal of the images for obvious patient motion and attenuation artifacts, with review of sinogram or rotating cine images as needed

  
  
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  Evaluation of the LV myocardium for the presence of perfusion defects and classification regarding size, severity, location, and degree reversibility, if any

  
  
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  Estimation of LV cavity size and any transient enlargement

  
  
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  Assessment of lung activity on thallium scans

  
  
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  Assessment of RV activity

  
  
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  Recognition of interfering adjacent splanchnic (liver, spleen, or bowel) activity

  
  
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  Correlation with adequacy of stress and any ECG findings

  
  
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  Correlation of findings with ancillary patient information, including history and clinical findings, prior coronary angiography or revascularization procedures, and previous myocardial perfusion studies

  
  
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  On G-SPECT studies: evaluation of LV ejection fraction (LVEF) and correlation of LV wall motion with any perfusion abnormalities noted on the tomographic slices

Alignment of Images

An initial task of the interpreter is to assess the two series of processed images consisting of reconstructed stress and rest (redistribution) slices to ensure that they are properly aligned. Such coregistration of the slices in all three planes is essential for accurate comparison of perfusion in corresponding regions of the myocardium. Misalignment of the image sets may lead to a false impression of the fixed or reversible nature of areas of relative hypoperfusion and significantly reduce the accuracy of the examination.

Artifacts

Because tomographic images are composed of highly processed data, the interpreter should ascertain that the acquisition and resulting processed images are artifact free. Artifacts most frequently encountered are related to either the specific technology employed or to the patient. If an artifact is suspected, careful examination of the raw data in a rotating cine display of the sequential planar projections aids in detecting gross patient motion, areas of significant soft-tissue attenuation by overlapping tissue or pacing devices, and any superimposed liver or spleen activity. Other means for detecting patient motion, such as a sinogram (an abrupt break in the otherwise continuous sinogram stripe signifies patient motion), or a summed display of all the projections may be generated and viewed as needed. A thorough knowledge of common SPECT imaging artifacts is critical in SPECT image interpretation ( Table 5.3 ).

Attenuation Artifacts

Significant soft-tissue attenuation by large breasts or breast implants may produce spurious fixed anterior or lateral wall defects ( Fig. 5.14 ), and considerable accumulation of adipose tissue in the lateral chest wall in obese patients may give rise to fixed lateral wall myocardial defects if the patient is imaged identically in the postexercise and subsequent rest (or redistribution) studies. Significant changes in positioning of the patient or of the patient’s breasts in the rest images that make the attenuation defect less apparent than on the postexercise images, however, may give rise to apparent reversible abnormalities.

Single-Photon Emission Computed Tomography (SPECT) Breast Attenuation Artifact.

(A) Both the short-axis stress (SAS) and short-axis rest (SAR) myocardial perfusion images demonstrate an anterior wall defect (large arrow) attributable to breast attenuation. The apparent defect is fixed because the breast position is similar on both the stress and rest images. There is a true defect in the inferior wall (small arrow). (B) Soft-tissue attenuation of breast tissue can easily be appreciated on three-dimensional rotating views of the thorax. Here, selected planar image frames from the SPECT acquisition at different angles show the overlying breast tissue (arrows) having progressively more attenuation of the myocardial (H) activity as the SPECT camera rotates around the patient during acquisition. LAO, Left anterior oblique view.

Patients with left hemidiaphragmatic elevation may have spurious inferior wall defects because of focal attenuation. In addition to attenuation, intense liver, spleen, or bowel activity overlying the inferior wall of the LV may mask areas of decreased perfusion or may paradoxically produce an inferior wall defect ( Fig. 5.15 ). This latter artifact is thought to be related to an inherent effect of filtered back projection on myocardial segments immediately adjacent to such areas of intense activity.

Reconstruction Artifact.

(Top) Consecutive short-axis post-stress images from a technetium-99m tetrofosmin myocardial perfusion study demonstrate a focal defect in the inferolateral wall of the left ventricle (short arrows) adjacent to a focus of intensely increased bowel activity (open arrow) . (Bottom) Repeat images after the bowel activity has passed from the area show the defect to have resolved. Such artifactual myocardial defects adjacent to areas of nearby extracardiac increased activity are a result of filtered back-projection using ramp filtration. SAS, Short-axis stress.

In addition to indirect approaches, such as review of the raw data as a rotating display of frames in a cine loop format, regional and wall motion data available with G-SPECT often allow differentiation of true fixed defects, substantiated by locally diminished wall motion, from attenuation artifacts with regionally preserved wall motion.

Attenuation Correction and SPECT-CT Image Misregistration Issues

Direct attenuation correction methods can greatly improve the specificity of SPECT imaging by eliminating or minimizing soft-tissue attenuation artifacts ( Fig. 5.16 ). Advances in instrumentation, especially SPECT/CT (or PET/CT) hybrid scanners have allowed considerable strides in this maneuver. However, misregistration of the CT and SPECT images during this process is one of the most common causes of artifacts on SPECT/CT or PET/CT images and thus of errors in semiquantitative data displays.

Attenuation Correction.

(Top) Consecutive nonattenuation-corrected, short-axis, post-stress myocardial perfusion images show an inferior wall defect (short arrows) . Review of the rotating display of single-photon emission computed tomography image frames suggested diaphragmatic attenuation. (Bottom) Repeat imaging using an attenuation correction program corrects for the diaphragmatic attenuation and the defect is no longer seen. AC, Attenuation-corrected; Non-AC, non–attenuation corrected.

Attenuation correction is a recommended but optional procedure performed by using a transmission scan (CT portion of SPECT/CT) to assess relative tissue density differences in the patient to create an “attenuation map,” used to correct for areas of attenuation of the radionuclide (emission) that would otherwise appear as a relative perfusion defect on the images. If performed successfully, a defect due to attenuation on the uncorrected images will “disappear” or be less apparent on the corrected images. In order for the technique to be successful, comparable positioning of the CT and radionuclide images and near exact coregistration of the two is imperative. Because the CT scan is performed in a matter of seconds (8 to 12 seconds) and the cardiac SPECT scan is performed over a period of minutes (5.12 minutes), cardiac motion caused by respiration is averaged over substantially different time intervals, and significant differences between the two regarding the position of the heart may occur, preventing the precise coregistration needed for successful attenuation correction. Further, misregistration of the images introduces artifacts of its own. It is not uncommon for artifactual defects to occur in the anterior and lateral LV walls when the SPECT emission and transmission (attenuation map) images are misregistered. Experience suggests that protocols using shallow tidal breathing (rather than breath-hold) with averaging of respiratory motion for both the CT (or PET) and radionuclide scans is the best technique to increase chances of better cardiac alignment and more accurate attenuation correction. SPECT/CT cameras allowing low-dose CT scans obtained over longer periods may be another option to improve the technique. Further, patient body movement during the longer SPECT scan also presents an opportunity for misregistration. However, because of frequent patient motion between the separately acquired MPI and computer tomography attenuation correction (CTAC) studies, which can be difficult to detect by patient observation, or if the patient is moved between the rest and stress MPI, a separate CTAC for the rest and stress MPI study may be used (optional). For SPECT MPI, separate CT scans for post-stress and rest attenuation mapping are typically necessary for the rest and stress MPI studies. If considerable motion between rest and stress images occurs, display of both corrected and uncorrected images for comparison during interpretation may be advisable. Consideration of various acquisition protocols depending on specific instrumentation used and patient presentations may be necessary to optimize coregistration in a particular clinical laboratory. Additionally, apparent myocardial defects may occur when the transmission and emission images are performed sequentially rather than simultaneously with patient movement between the two image sets. In general, shallow tidal breathing during both CT and SPECT or PET acquisitions is recommended.

Normal Appearance and Variants

In the normal myocardial perfusion study, there is often slightly diminished activity at the LV apex, and in areas of anatomic thinning at the base of the intraventricular septum (membranous portion) and in the base of the inferior wall. Thinning at the base of the septum and inferior walls may be distinguished from true perfusion defects in that they are limited to the base of the heart and do not extend distally to the apex. These anatomic variants should not be mistaken for fixed perfusion defects. Defects that extend from the base toward the apex should be considered abnormal. Furthermore, the lateral myocardium normally demonstrates more activity than do other myocardial territories, especially when compared with the septum in the short-axis slices. This likely results from the lateral wall being closest to the camera during much of the usable acquisition.

Areas of focally increased activity in and at the insertions of the papillary muscles frequently can be seen, especially on the short-axis images at about the 2-o’clock and 7-o’clock positions. These “hot spots” may give a false impression of a defect adjacent to or between them, owing to relative differential in activity, when in actuality the intervening activity is normal. The apparently diminished perfusion is often accentuated by the scaling of relative intensities in the displayed images, based on the most intense pixel in the images (the markedly increased activity in the papillary muscles). This may artificially suppress activity in the normal but relatively less intense regions. These apparent differences in relative activity must be interpreted with caution. Generally, review of these areas in the long-axis slices, in which the papillary muscles are not as well seen, will demonstrate a homogeneous normal distribution in these regions, confirming a scaling artifact rather than a real perfusion deficit. However, significant perfusion defects that are also evident on the long-axis slices and are not attributable to artifact may be viewed as a positive finding.

Abnormal Scans

Visual Analysis of Myocardial Activity

Two distinct patterns of abnormal radiopharmaceutical distribution in the myocardium provide the basis for the detection and differential diagnosis of stress-induced ischemia and permanent myocardial damage. These patterns are referred to as (1) reversible (transient) defects and (2) nonreversible (fixed) defects . Defects may also be partially fixed with a reversible component. A third pattern, called reverse perfusion defects, is well documented but its significance is less well defined.

True defects usually are visible on at least two of the three standard sets of reconstructed slices. In addition to the short-axis views, defects are often best seen on the long-axis image set in which the axis of the slices is perpendicular to the involved wall (i.e., the anterior or inferior wall on VLA images and the septum or posterolateral wall on HLA images).

Reversible (Transient) Defects

A reversible defect is virtually synonymous with stress-induced ischemia in patients with CAD. The abnormality is identified on the initial post-stress images as an area of relatively decreased radiopharmaceutical activity that disappears or becomes significantly less apparent on the rest or redistribution views ( Fig. 5.17 ).

Anterior Wall Ischemia (Reversible Myocardial Perfusion Defect).

(Upper row) Single-photon emission computed tomography images in short-axis stress (SAS) , vertical long-axis stress (VLAS) , and horizontal long-axis stress (HLAS) stress images clearly demonstrate a perfusion defect (arrows). (Middle row) Rest images; the perfusion defect has disappeared on the rest (redistribution) views. (Lower row) Bull’s eye images confirm the perfusion defect at stress (arrows) but not at rest. HLAR, Horizontal long-axis rest; SAR, short-axis rest; VLAR, vertical long-axis rest.

Nonreversible (Fixed) Defects

Fixed defects demonstrate no significant change in activity between the post-stress and rest or redistribution studies ( Fig. 5.18 ). They most frequently indicate areas of scarring or fibrosis, usually after myocardial infarction, with loss of contractile function. Some fixed lesions identified on the initial post-stress images may be partially reversible. Ischemia associated with a previous myocardial infarction with scarring (peri-infarct or “flanking” ischemia) commonly presents in this manner.

Left Ventricular Anterior/Apical Infarct (Fixed Perfusion Defect).

(Top row) Decreased perfusion ( arrows ) to the left ventricular anterior wall and apex on short-axis stress ( SAS ), vertical long-axis stress ( VLAS ), and horizontal long-axis stress ( HLAS ) technetium-99m sestamibi SPECT images. (Bottom row) The anterior/apical defect persists on rest images in all three projections. Of note is activity ( open arrow ) on the horizontal long-axis rest ( HLAR ) image owing to sestamibi in the colon after hepatic excretion. SAR, Short-axis rest; VLAR, vertical long-axis rest.

This straightforward approach to myocardial perfusion scan interpretation is complicated by the recognition that some nonreversible, fixed defects may actually represent primarily viable myocardium rather than postinfarction scarring. In patients with severe coronary stenoses, these defects frequently represent chronically ischemic, but viable, “hibernating” myocardium that remains poorly perfused at rest with loss of functional wall motion. Differentiating scar tissue from viable, but hibernating myocardium can be critical as the latter may be reversed by revascularization interventions resulting in restoration of regional contractile function.

To differentiate hibernating myocardium from scar in patients with fixed myocardial perfusion defects, PET imaging with ¹⁸ F-fluorodeoxyglucose ( ¹⁸ F-FDG) is the procedure of choice (described later in this chapter). However, thallium imaging also offers an effective method to confirm myocardial viability in this setting because thallium uptake in myocardial cells serves as an indicator of preserved cell membrane function. Thallium uptake in a fixed perfusion defect with accompanying myocardial dysfunction predicts improvement of function after revascularization. If a stress–redistribution thallium imaging protocol was initially used, additional thallium, additional time for redistribution, or both is required. Reinjections of patients with additional thallium (1 mCi [37 MBq]) before 4-hour redistribution imaging and/or further delayed 18- to 24-hour imaging are common approaches.

If the initial study was performed by using a technetium labeled agent, a thallium rest–redistribution protocol may be used on a separate day (to allow for radioactive decay). In this protocol, the patient is injected with thallium at rest and imaged immediately and again after a variable delay of 4 to 24 hours to image the chronically ischemic myocardium.

Reverse Perfusion Defects (Reverse Redistribution)

Reverse perfusion defects occur when a scan appears normal or with only a slight defect on the post-stress views and shows a new or worsened defect on the rest or redistribution images ( Fig. 5.19 ). Although initially reported on ²⁰¹ Tl imaging, the phenomenon may also be seen when ^99m Tc radiopharmaceuticals are used. The exact mechanisms that produce this pattern and its significance are uncertain. In many instances, the effect is simply related to a worse attenuation artifact on the post-stress images than on the rest images. However, reverse redistribution has been associated with prior myocardial infarction, especially after revascularization or thrombolytic therapy. This is likely to be the result of some residual tissue viability and some postulate that the regional hyperemic response to exercise may mask resting hypoperfusion in these areas. The finding is uncommon and does not indicate stress-induced ischemia.

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