Case 10 cont'd
Image findings: - This exercise stress test was done using Tc-99m sestamibi. Myocardial perfusion SPECT imaging showed ischemia in the anteroapical and mid to basal portions of the lateral and inferolateral walls.
A. LBBB is a conduction abnormality which causes the current to not be able to pass through the left bundle branch. This causes the conduction signal to come to the left ventricle from the right, which delays its arrival. This causes paradoxical septal motion toward the right on gated studies. The most important consequence of this artifact is that it may be interpreted as a septal defect on perfusion imaging. Although LBBB is readily visible on ECG, the diagnostic dilemma arises when a septal defect is apparent in a patient undergoing perfusion imaging, as the defect may be due to an actual coronary artery disease rather than the LBBB.
B. Hypertrophic cardiomyopathies involve myocardium hypertrophy in the septum. This causes radiotracer to be taken up more readily in this area, thus septal wall activity appears increased. This causes the activity in other walls to appear decreased by comparison, which can lead to a false diagnosis of widespread perfusion anomalies.
C. Balanced ischemia raises one of the limitations of SPECT myocardial perfusion imaging, which measures relative activity and not absolute activity. In balanced ischemia, there is decreased perfusion to all walls of the heart. If the decrease is of similar magnitude, tracer activity is decreased quasi-homogeneously across the heart. This may lead to underrecognized multi-vessel disease. Although multi-vessel disease may not be easily diagnosed in such settings, the activity decreased may still be of different magnitudes across h=the 3 main heart vessels such that identification of some degree of coronary artery disease is still feasible (95-98%).
D. If a patient presents for MPI with dextrocardia, the technologist will need to conduct the 180 degree SPECT acquisition from -135 to +45. The issue arises if dextrocardia is unknown by the patient and/or technologist at the time of imaging, as image processing is also dependent on knowing the position of the heart within the thorax.
E. All of the above are potential artifacts due to heart-related issues in myocardial perfusion imaging.
Q1. Answer: C.
Cardiac perfusion imaging is also known as nuclear stress testing. Stress may be exercise-induced or pharmacologically induced.
Q3. i. What are some medications that may interfere with exercise stress testing? Medications that interfere with exercise stress testing are beta-blockers, calcium channel blockers and long acting nitrates. Beta blockers can prevent achievement of peak heart rate, while nitrates and calcium channel blockers may prevent or mask cardiac ischemia.
Q3. ii. What are some medications that may interfere with pharmacologic stress testing? Methylxanthines and caffeine. Pharmacological stress may be induced by dobutamine, adenosine or dipyridamole (persantine). Dobutamine is a synthetic catecholamine that acts on alpha- and beta-adrenergic receptors. It increases cardiac workload and has both inotropic and chronotropic effects on the heart. Due to its side effects (e.g. chest pain), dipyridamole and adenosine are preferred pharmaceuticals in pharmacological stress testing. Both dipyridamole and adenosine are coronary vasodilators and can cause threefold to fourfold increase in blood flow to the heart. If side effects develop due to the use of adenosine, nothing needs to be done as it has a very short plasma half-life. If side effects occur with the use of persantine, the antidote is an IV injection of aminophylline (a methylxanthine). Since persantine and adenosine work in similar ways to induce coronary artery dilation, methylxanthines such as aminophylline and theophylline (bronchodilators that may be used in patients with COPD) antagonize both drugs. Additionally, caffeine is also an antagonist of these drugs. Therefore, in pharmacologically induced stress imaging, these drugs may interfere with the results.
The correct vascular distribution patterns according to coronary artery territory are indicated below:
Left anterior descending artery (LAD) – Defects in septum, anterior wall, apex
Left circumflex artery (LCx) – Defects in the lateral wall, posterior wall, posterior inferior wall and apex
Right coronary artery (RCA) – Defects in inferior wall, posterior inferior wall, right ventricular wall
Left main coronary artery (LCA) – Defects in anterior wall, septum and posterolateral wall
Multivessel disease is characterized by defects in several vascular distributions and ventricular enlargement in response to stress (either pharmacological or exercise-induced).
Q3. Answer: D.
Discussion:
Myocardial perfusion imaging (MPI) is usually indicated for assessment of coronary artery disease (CAD), acute myocardial infarction (MI), risk stratification post-MI, assessment of coronary artery bypass surgery and angioplasty, evaluation of thrombolytic therapy and myocardium viability studies in patients with chronic CAD. MPI may be done using planar imaging, SPECT or PET. In SPECT and PET, views of the heart are acquired in three axes : short axis, vertical long axis and horizontal long axis (see Figure 1).
https://www.digirad.com/understanding-your-nuclear-medicine-stress-test/
Figure 1 – Views of the heart on SPECT and PET imaging
Spect
In SPECT imaging and planar studies, the following Tc-99m radiopharmaceuticals may be used; Tc-99m sestamibi, Tc-99m tetrofosmin and Tc-99m teboroxime. Additionally, thallium-201 chloride (TI-201) may also be used as a radiotracer, as it is distributed in vivo similarly to potassium. All radiopharmaceuticals are injected intravenously, but dose varies (2-3.5 mCi for TI-201 vs 10-30 mCi for Tc-99m tracers). If TI-201 is used, patient should fast 4 hours before the imaging study to reduce uptake by the abdomen and both stress and rest imaging may begin 10 minutes after injection. With Tc-99m tracers, imaging should begin 60-90 minutes after injection in rest studies and 15-30 minutes after injection for stress studies. In SPECT imaging, views are acquired with the patient supine and their left arm raised. Images are acquired in 180° (45° right anterior oblique, 135° left posterior oblique).
A coronary stenosis may produce no symptoms at rest even if it the artery is 90% obstructed. Therefore, the core principle behind stress testing is the following: unveil hidden CAD by increasing cardiac workload, blood demand and oxygen demand. This can be achieved by exercise (treadmill) or pharmacologically with the use of certain drugs.
There exists a few absolute contraindications to exercise-induced stress, for example in patients who have had an MI within the last 3 months prior to the test. Severe arrythmias, acute inflammatory diseases of the heart (e.g. valvulitis), critical aortic stenosis and PE are a few other examples of contraindications to exercise stress testing. In such patients, drug-induced stress is preferred. The extent of stress must also be sufficient to unveil underlying abnormalities. This is calculated as being >85% of the patient’s age-predicted maximal heart rate. Another measure to reveal whether adequate exercise was achieved is the double product (heart rate x systolic bp). A double product over 25 000 is another indicator that exercise was adequate unmask potential anomalies. In some patients, no contraindications exist but failure to achieve adequate exercise level occurs. Early exercise termination may also play a role in inadequate stress test results. This may be due to observed ST segment depression (> 3mm) on the 12-lead ECG monitoring the patient, poor patient compliance, atrial fibrillation, claudication or other causes.
In exercise stress testing, once peak tolerance or adequate exercise has been achieved, the tracer is intravenously injected and the patient is instructed to keep exercising for another 30-90 seconds, if possible, to ensure that initial myocardial tracer uptake is an accurate reflection at peak stress. Depending on the radiotracer injected (TI-201 or Tc-99m), imaging starts either 10 minutes or 15-30 minutes after injection, respectively.
PET
In PET imaging, two radiopharmaceuticals are most commonly used: rubidium-82 chloride (Rb-82) and nitrogen-13 ammonia (N-13). Studies with these tracers are conducted both at baseline conditions (rest) and after pharmacological stress. Exercise stress is not typically used in PET imaging as the time from injection to imaging is brief for these two radiopharmaceuticals and tomographic imaging is sensitive to motion artifacts. Protocol for imaging is the same as described for SPECT. The preferred modality of myocardial perfusion imaging is PET, as it offers better spatial resolution (see Figure 2). However, due to PET not being readily available in all centers, SPECT may still be used.
Interpretation of results
The rationale behind nuclear stress testing is that increasing cardiac workload by increasing oxygen demand will unmask hidden CAD, as normal arteries will dilate to increase blood and accommodate for the larger demand, while coronary stenoses will not be able to dilate and myocardial ischemia ensues. On MPI (whether SPECT or PET), this induced ischemia will appear as “cold defects”, i.e. areas of low photon uptake as the IV radiotracer is not able to flow through the obstructed arteries due to lack of blood flow. Relative decrease of regional reduced blood flow therefore show up as photon-deficient (less uptake/activity/signal) areas on scintigraphy.
Stress studies are compared to images acquired during rest studies (baseline conditions) and differences observed (such as areas appearing well perfused at rest but presenting a cold defect at stress) are interpreted. Possible findings and outcomes are indicated below:
Table 1 – Probable diagnoses according to combined findings on rest and stress studies
A visual list of possible findings is indicated below (see Figure 3).
https://thoracickey.com/nuclear-cardiology-3/
Figure 3 – Comprehensive list of possible findings on nuclear stress testing and their interpretation
Scarring due to previous MI may also be distinguished from transient ischemia (see Figure 4).
Figure 4 – Inducible ischemia vs prior MI
Another important concept to note is the vascular distribution of the defects observed. Depending on distribution, the specific obstructed artery/arteries may be identified, which aids in pursuing further re-perfusion therapies (e.g. angioplasty) if need be. Alternatively, if a defect distribution does not align with an expected pattern of one of the main coronary arteries, it may be a clue that a defect is due to an artifact. The patterns of distribution associated with each coronary artery are indicated below (see Figure 5).
Figure 5 – Vascular distribution patterns of coronary artery territories
Coronary artery territories are further divided into 17 segments (see Figures 6, 7 & 8).
https://www.researchgate.net/figure/17-segment-model-of-the-left-ventricle_fig2_320788702
Figure 6 – 17 coronary segments
Figure 7 – Coronary vascularization of the 17 heart segments
https://epos.myesr.org/posterimage/esr/ecr2017/138182/mediagallery/714292?deliveroriginal=1
Figure 8 – Coronary vascularization of the 17 heart segments
There is a set of terminology used to characterize the myocardium. These terms and their definitions are indicated below:
Myocardial ischemia: ischemic myocardium cannot keep up with increasing oxygen demand (stress) due to CAD. Blood flow is reduced and therefore appearance on scan is photon deficiency (i.e. less radiotracer activity on post-stress set of images when compared to rest images).
Myocardial infarction: Due to prior MI, tissue necrosis causes scarring of the myocardium. Non-viable myocardium/myocardial scars appear on scintigraphy as photon deficient (relative diminished radiotracer signal). Transmural infarction (involving all layers of the heart) is more sensitively detected than sub-endocardial infarction.
Hibernating myocardium: Hibernating myocardium is comprised of viable but chronically ischemic tissue with reduced contractility. This may be reversed with adequate blood flow restoration. Appears photon deficient on MPI scintigraphy but is metabolically active.
Stunned myocardium: Metabolically active myocardium with persistent abnormal contractility despite adequate reperfusion post-ischemic episode. Appears either as reduced photon uptake or normal on scintigraphy.
Reverse distribution is a term used to describe paradoxical finding, whereby radiotracer uptake is relatively decreased (perfusion defect) at rest but normal perfusion at stress. Reverse distribution may also be on TI-201 redistribution images when immediate post-stress images appear normal. As this tracer is metabolized by the body similarly to potassium, the tracer taken up by the myocardium after initial injection gets replaced by TI-201 in the systemic blood pool, which constantly undergoes redistribution. After a few hours, the images acquired (delayed imaging) show an equilibrated pattern. Therefore, the use of this tracer may help determine viable vs non-viable myocardium. Early images with cold defects may represent either ischemic tissue or non-viable myocardium. Delayed (24 hours later) images of the same tissue at equilibrium may show either perfusion defects – consistent with non-viable myocardium – or may show equilibration/ fill-in of the perfusion defect, thus demonstrating that the tissue underwent ischemia during exercise but is viable. The paradoxical presence of cold defects on redistribution (delayed) images when early post-stress images appeared normal may be seen in patients with extensive CAD, presumably due to differential washout of the tracer. This can also be observed in patients post-MI, due to inability of stunned myocardium to retain tracer. However, this sign may also be seen in patients with other conditions, such as Kawasaki disease, Wolff-Parkinson-White syndrome or sarcoidosis.
Artifacts and pitfalls
Other than the pitfalls and artifacts enumerated in Question 1, there are other artifacts resulting from other categories (pre-imaging issues, technical issues and patient-related issues – see Figures 9 & 10).
Figure 9 – Categories of artifacts in MPI
Figure 10 – Artifacts and pitfalls in MPI
For example, attenuation artifact (which are the most common artifact) occurs when photons are attenuated by the patient. This can happen either in a generalized manner or a focal manner. Generalized photon attenuation is usually the result of high corporal mass, which creates a noisier and less diagnostically reliable image. Focal attenuation on the other hand may be due to breast tissue in women and the diaphragm in men. In women, breast tissue may be read as left ventricle anterior wall perfusion defect (see Figures 11, 12 & 13). However, depending on the patient’s body, the defect(s) may be seen in the lateral wall, the septum and the apex of the heart. This can be dismissed if normal motion and thickening is seen on the gated study. In men, larger abdomens result in the attenuation of the inferior wall of the heart. This can be remedied by the addition of prone imaging to supine imaging of the patient (see Figure 14).
https://tech.snmjournals.org/content/34/4/193
Figure 11 – Attenuation artifacts due to breast tissue
(A) MPI shows a fixed defect in the anterior wall (arrowheads). (B) Frame from raw data reveals marked attenuation by left breast (arrowheads), which is causing the apparent perfusion defect.
Figure 12 – Attenuation artifact due to breast tissue
MPI shows a fixed defect (arrowheads) due to breast tissue.
Figure 13 – Attenuation artifacts
(A) MPI demonstrates typical mild fixed inferior wall perfusion abnormality (arrowheads) in a male patient due to diaphragmatic attenuation.
Subdiaphragmatic activity is another cause of artifacts in MPI. Activity may be seen in the liver and the bowel due to hepatobiliary clearance of the radiotracer (see Figures 15 & 16). Signal may also be seen in the stomach due to duodenal reflux. Radiopharmaceutical activity in these adjacent organs interferes with the inferior wall and may cause one of two possible outcomes:
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Activity in the inferior wall may appear increased due to scatter and volume averaging. This can further either hide a perfusion defect in the inferior wall, or cause activity in adjacent walls to appear diminished in comparison to the inferior wall.
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Paradoxically, the adjacent activity from adjacent organs may result in diminished apparent activity in the inferior wall.
The best way to reduce subdiaphragmatic activity remains to wait an appropriate amount of time between injection of the tracer and imaging to allow it to clear.
(A) Perfusion images demonstrate apparent perfusion defect in inferior wall that is much worse at rest than during stress (arrowheads). (B) Anterior frames from raw data reveal liver activity to be much greater than cardiac activity at rest (left frame), which is not the case on the stress study (right frame). (C and D) Trans-axial slices at level of liver and heart (C) and count profiles across the images (D) (left frames rest, right frames stress). Note negative counts adjacent to intense liver activity on rest study, which results in artifactual reduction in counts in adjacent myocardium.
(A) Raw data frame from rest MPI study demonstrates prominent activity in stomach adjacent to LV inferior wall (arrowhead). (B) Raw data from delayed study after gastric activity had cleared.
Clues that an observed defect is due to attenuation and not coronary artery disease is the fact that the defect may not align with any expected coronary artery vascular distribution on imaging. The defect may also be fixed, meaning that it is observed and unchanged in both rest and stress imaging (although fixed defects may also be due to scarring).