Myocardial Perfusion

Assessing Perfusion Defects

This discussion focuses on the detection of reversible ischemia noninvasively via stress testing and myocardial perfusion imaging during a cardiac magnetic resonance imaging (MRI) exam.

Under normal conditions, oxygen supply to the myocardium is balanced with its changing oxygen demands. Oxygen demand is affected by heart rate, contractility, and systolic pressure (myocardial wall stress), whereas oxygen supply is determined by oxygen extraction and coronary blood flow. Imbalances between supply and demand may cause ischemia—a pathological state in which the demand for oxygen by the tissue (the myocardium) exceeds oxygen availability. Ischemia often arises from atheromatous plaque forming in one or more of the coronary arteries and/or the disruption of microvascular circulation. Depending on its severity, ischemia may cause compromised myocyte function and/or cell death. (For a more detailed examination of this topic, see Ischemia and Coronary Artery Disease under Disease Guide.)

Stress testing is critical for evaluating the hemodynamic impact of a coronary artery stenosis(es) and may induce detectable ischemia in individuals with little or no evidence of it at rest. The general logic underlying stress testing is as follows:  Under stress conditions—whether they are induced through bodily movement during exercise or by a pharmacologic modality— tissues demand more oxygen (blood) than under rest conditions to meet the metabolic needs that are imposed by a stressor(s). In these circumstances, coronaries may dilate to 5 times their resting (non-stressed) size, thereby increasing blood flow. The capacity to increase blood flow above resting volumes in response to stimuli is known as coronary flow reserve. (See Ischemia and Coronary Artery Disease under Disease Guide for more information.) In normal (unaffected, non-ischemic) tissue, this compensatory mechanism is sufficient to meet the myocardial metabolic changes resulting from a stressor. In abnormal (affected, ischemic) tissue, myocardial perfusion also may not be altered under rest conditions, due to coronary flow reserve. Arteriolar vasodilation compensates to increase the blood flow despite the blockage, enabling the tissue to receive an adequate supply of oxygen. (It is important to note, however, that this compensatory property functions effectively in rest conditions until a given coronary artery has a stenosis whose diameter is nearly 85%. Beyond this percentage, ischemia arises regardless, because the vessel cannot provide a sufficient blood supply.) Under stress conditions, nonetheless, this compensatory mechanism may become partially or completely exhausted. Consequently, myocardium surrounding even smaller stenosis(es) may become ischemic—even if resting perfusion is preserved.

Ischemic left ventricular (LV) myocardium is detected as one or more perfusion defects arising during a stress test in a cardiac MRI examination. This analysis proceeds accordingly: First, gated, short-axis, ultra-fast gradient echo series are acquired. Images must be taken with enough time available to see the contrast agent pass through the LV myocardium— a time interval of approximately 30 seconds (F1). Second, stress may be induced through exercise (e.g., by using a magnetic-resonance-compatible bike) or via a pharmacological agent (e.g., dipyridamole, dobutamine/atropine, or adenosine). Limitations of using exercise to induce stress include inducing a very high heart rate as well as cardiac and bodily motion. These factors may compromise image quality and gating. Pharmacological agents, by contrast, are well tolerated, safe, and they reliably induce myocardial ischemia. After stress-induction is confirmed, a contrast agent is injected. While a variety of contrast agents may be employed, the use of a gadolinium-based contrast agent is assumed here. (For additional information about pharmacological stress and contrast agents, see Stress Imaging Pharmacology and Contrast Agents, respectively, under Technical Guide.) Third, the progression of the contrast agent through the heart must be imaged carefully such that its passage throughout the cardiac cycle is captured entirely (F1). Fourth, myocardial perfusion defects (F2, F3)—regions in the LV myocardium in which blood flow has been obstructed—are detected qualitatively and semiquantitatively.

Perfusion defects are apparent qualitatively as gray-black blotches pervading the LV myocardium (F2, F3). To positively identify a perfusion(s) defect the image usually must satisfy all of the following conditions: 1) It displays consistent, localized gray-black areas of enhancement persisting throughout several phases of the cardiac cycle; 2) The dark areas of enhancement roughly align with where the coronary arteries feed the LV myocardium (F5); that is, the areas of enhancement often span the base, mid ventricle, and apical regions in a way that is characteristic of the coronary arteries; and 3) The regions of enhancement are lighter than the tone of the initial contrast bolus. If such enhancement is the same tone as, or is darker than, the initial contrast bolus, then there is a reasonable chance that the enhancement represents artifact, not true ischemia (F6).It is important to note that, when using a gadolinium-based contrast agent, it is the magnetic effects of the agent on the tissue—not the contrast agent’s concentration—that is detected. This implies that signal intensities are not necessarily proportional to the concentration of the agent.

If detected, ischemia is characterized as reversible or irreversible (F2, F3). Reversible injury or reversible ischemia consists of affected LV myocardial tissue that may be revived by restoring blood flow to the compromised region(s). To accomplish this, techniques such as surgery, medication, and/or catheterization are employed. By contrast, irreversible injury or irreversible ischemia consists of dead LV myocardial tissue (resulting from oncosis, apoptosis, autophagy, and other processes ending in cell death) which, at the time of this writing, cannot be revived. (For further discussion about this topic, see Viability under Left Ventricle of the Analysis Guide, and Coronary Artery Disease and Myocardial Infarction under Disease Guide.) Therefore, irreversible ischemia is referred to as a fixed perfusion defect(s). Describing perfusion defects as reversible or irreversible ischemia is accomplished by considering the presence of infarct on corresponding delayed-enhancement series (F3): Perfusion defects are classified as reversible ischemia when 1) there is no corresponding infarct on the delayed-enhancement series (F2) or 2) there is infarct on the corresponding delayed enhancement series, but the location(s) of the defect(s) and infarct(s) share no overlap (F3A). In contrast, perfusion defects are classified as irreversible ischemia only when their LV myocardial locations match exactly those of the infarct on corresponding delayed-enhancement series. Put another way, the location of irreversible ischemia on ultra-fast gradient echo sequences will always overlap with infarct (also known as a viability defect(s)) on delayed-enhancement sequences), if the perfusion defect truly constitutes irreversible ischemia (F3B). In summary, reversible ischemia and irreversible ischemia might be present in the same tissue, one type might affect the tissue without the other, or both might be absent (F3).

The location(s) of perfusion defects may be mapped out and reported using the American Heart Association’s 16-segment polar plot system (F4). (The American Heart Association’s 17-segment model is used to map out viability defects. For further details, see Viability under Left Ventricle of the Analysis Guide.) Also, the degree of reversible ischemia may be characterized as absent, small, moderate, or large (F2).

Perfusion defects can be further evaluated with color maps (F7). By employing suiteHeart® software, such maps are obtained on gated, short-axis, ultra-fast gradient echo series. The cardiac phase where the first pass of contrast agent is evident is established, and the Time Course function is selected. On a single slice, epicardial and endocardial borders of the left ventricular myocardium are traced, the right ventricular insertion point is marked, and the software calculates the signal intensity(ies) across the tissue. A signal intensity vs. time graph may be generated (data not shown) to facilitate the identification of perfusion defects semiquantitatively.

References:

  1. Barker P, Golay X, Zaharchuk G. Clinical perfusion MRI techniques and applications. 1st ed. Cambridge: Cambridge University Press; 2013.
  2. Bogaert J, Dymarkowski S, Taylor A, Muthurangu V. Clinical Cardiac MRI. 1st ed. Berlin, Heidelberg: Springer Berlin Heidelberg; 2012.
  3. Braunwald E, Bonow R. Braunwald’s heart disease. 1st ed. Philadelphia: Saunders; 2012.
  4. Buckert D, Rasche V, Rottbauer W, Bernhardt P. Quantitative and qualitative adenosine perfusion magnetic resonance imaging for the detection of coronary artery disease at 3 Tesla. Journal of Cardiovascular Magnetic Resonance. 2014;16(Suppl 1):P180.
  5. Chiong M, Wang Z, Pedrozo Z, Cao D, Troncoso R, Ibacache M et al. Cardiomyocyte death: mechanisms and translational implications. Cell Death and Disease. 2011;2(12):e244.
  6. Coelho-Filho O, Rickers C, Kwong R, Jerosch-Herold M. MR Myocardial Perfusion Imaging. Radiology. 2013;266(3):701-715.
  7. Dilsizian V, Pohost G. Cardiac CT, PET and MR. 1st ed. Somerset: Wiley; 2011.
  8. Gerber B, Raman S, Nayak K, Epstein F, Ferreira P, Axel L et al. Myocardial first-pass perfusion cardiovascular magnetic resonance: history, theory, and current state of the art. Journal of Cardiovascular Magnetic Resonance. 2008;10(1):18.
  9. Jensen C, Van Assche L, Spatz D, Parker M, Rehwald W, Kim R et al. Assessment of semi-quantitative parameters for visual interpretation of stress-perfusion CMR in obstructive coronary artery disease. Journal of Cardiovascular Magnetic Resonance. 2013;15(Suppl 1):P210.
  10. Katritsis D, Camm A, Gersh B. Clinical cardiology. 2nd ed. Oxford: Oxford University Press; 2016.
  11. Konstantinidis K, Whelan R, Kitsis R. Mechanisms of Cell Death in Heart Disease. Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;32(7):1552-1562.
  12. Kostin S. Myocytes Die by Multiple Mechanisms in Failing Human Hearts. Circulation Research. 2003;92(7):715-724.
  13. Lim T. Practical Textbook of Cardiac CT and MRI. 1st ed. Berlin, Heidelberg: Springer Berlin Heidelberg; 2015.
  14. Patel A, Antkowiak P, Nandalur K, West A, Salerno M, Arora V et al. Assessment of Advanced Coronary Artery Disease. Journal of the American College of Cardiology. 2010;56(7):561-569.
  15. Syed M, Raman S, Simonetti O. Basic Principles of Cardiovascular MRI. 1st ed. Cham: Springer International Publishing; 2015.
  16. Xiao-Fang T, Shi-Wei Y, Yu-Jie Z. Autophagy, dysglycemia and myocardial infarction. IJC Metabolic & Endocrine. 2017;14:40-44.