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Perfusion Measurements of the Myocardium: Radionuclide Methods and Related Techniques

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PanVascular Medicine

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Abstract

Cardiovascular disease is the leading cause of mortality in the USA, with coronary artery disease (CAD) accounting for about half of these deaths. While invasive coronary angiography (ICA) is considered by most people to be the gold standard for the diagnosis of CAD, noninvasive testing is often the initial approach. In many cases an examination to detect physiologic evidence of coronary ischemia is chosen as such tests, having less risk of morbidity and mortality than ICA, more accurately depict the functional significance of any CAD that might be present. Among the common tests chosen is stress radionuclide myocardial perfusion imaging (MPI) , using either single photon emission computed tomography with a 201Tl- or a 99mTc-based (sestamibi or tetrofosmin) radiopharmaceutical or positron emission tomography (PET) that uses either 82Rb or 13N-ammonia. The basic principle by which MPI assesses CAD is by evaluating heterogeneity and homogeneity of coronary flow reserve. Through complex mechanisms involving physical forces, autonomic neural tone, circulating catecholamines, chemical mediators, myocardial metabolites, and other factors, there is tight autoregulation of coronary blood flow that matches blood supply to myocardial oxygen demand, with the normal autoregulation impaired in the setting of atherosclerotic disease. While arterial narrowing can often be compensated for at rest through these autoregulatory mechanisms, with application of “stress” through exercise, positive inotropic agents, or coronary arterial vasodilating agents, the ability to augment coronary blood flow is measured. As myocardial perfusion tracers are identified from nature or artificially designed to be taken up by myocytes in proportion to coronary blood flow, distribution of nuclear gamma or PET camera detected radiotracer counts in the different myocardial walls represents the homogeneity or heterogeneity of coronary blood flow to myocytes that have sufficient structural integrity and metabolic activity to take up and retain tracer. The diagnostic accuracy of radionuclide MPI in relation to ICA detected anatomic stenoses is high, with a sensitivity of 87–89 %, a specificity of 73–75 % (ranges related to mode of stress), and a normalcy rate of 91 %. Accuracy is further improving with increased use of PET and with techniques that can overcome artifacts such as attenuation correction. The introduction of new tracers, such as 18F-flurpiridaz – a PET tracer under phase III investigation – promises even better images and accuracy. Recent developments to assess quantitative blood flow – coronary flow reserve and absolute blood flow in ml/min/g – will further improve the diagnostic accuracy and clinical utility of MPI, including the ability to overcome false-negative MPI images in the setting of balanced ischemia and by identifying earlier disease. Perhaps more important has been the consistently shown robust ability of radionuclide MPI to risk stratify patients such that lower risk patients who require only medical therapy and risk factor reduction can be distinguished from those who might benefit from an invasive evaluation with revascularization. Ancillary data such as left ventricular (LV) function from ECG-gated SPECT further enhance diagnostic and prognostic capabilities. At the same time, it is recognized that complementary noninvasive imaging modalities can enhance radionuclide MPI. Cardiac MRI is a developing alternative imaging modality to assess coronary blood flow. The superior anatomic detail with MRI, including the potential to distinguish subendocardial versus subepicardial blood flow may, with hybrid PET/MRI cameras under development, complement radionuclide MPI and provide a more comprehensive evaluation of coronary blood flow in health and disease. Complementary multidetector CT technology can add further by providing assessment of plaque morphology. New nuclear camera technology promises to not only improve image quality but also to increase efficiency through markedly decreased procedure times that improve patient comfort and allow lower radiation exposure. Improving our ability to assess coronary perfusion with imaging should make a significant contribution to improving cardiovascular diagnostics by noninvasive means.

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Abbreviations

Agatston score:

A measure of the amount of coronary calcium incorporating both the extent and density (based on Hounsfield units) of the calcium, derived from the work of Drs. Arthur Agatston and Warren Janowitz.

Anger gamma camera:

A device developed by Hal Anger to image gamma radiation emitting radioisotopes. The device is organized around one or more solid crystal planes that absorb gamma photons and convert the energy to light scintillations that are detected by optically coupled photomultiplier tubes which use “Anger logic” to locate photons and determine their energies. A lead sheet with holes, i.e., a collimator, mounted on the crystal towards the energy emission source allows focusing of the photons, helping to determine the origin of the emission in the source organ or tissue.

Balanced ischemia:

Equivalent decrease in myocardial perfusion in all vascular territories of the myocardium, resulting in images that underestimate the extent/severity of coronary artery disease and/or ischemia. Occurs typically in the setting of multivessel or left main (with right coronary artery) epicardial disease, but can also be the result of diffuse microvascular disease.

Coincidence detection:

Method of detection of PET tracers. Positrons emitted by the isotope encounter electrons resulting in annihilations that each produce two 511 keV energy photons traveling at approximately 180 degrees opposite each other along a line of response (LOR). Camera detection of the coincident photons within a set time interval on the LOC is registered as an event, with the position of origin determined.

Collimator:

A thin sheet of lead with thousands of holes through it that is placed over a nuclear gamma camera crystal so as to allow only perpendicular energy photons emitted from the radiation source, e.g., the myocardium, to strike the crystal. Collimators come in various forms including different lead thicknesses and with holes of differing length, width, and orientation. Most routine imaging is performed with parallel-hole collimators, but a variation such as a pinhole collimator magnifies a small field of view allowing better visualization of small organs and small animals.

Coronary autoregulation:

Regulation of blood flow through coronary arteries in order to meet myocardial oxygen demands.

Filtered back projection:

A method of processing, i.e., reconstructing tomographic images based on the concept that a 3-dimensional image can be reconstituted from a series of 2-dimensional image acquisitions from a sufficient number of positions around an object. In the process, changes in pixel values across physical space are converted to mathematical frequency component representations, i.e., a Fourier transform. Mathematical “filters” are then applied to remove high frequency noise components and low frequency background components, by which reconversion back to spatial displays yields transverse image slices that maximize detail and edges, with sufficient contrast such that defects can be detected. Mathematical filters are selected that give the best balance between image smoothness and detail and vary depending on type of tracer and dose administered, as well as camera system characteristics. An alternative method of SPECT processing is iterative reconstruction.

Fractional flow reserve (FFR):

A technique used during invasive coronary angiography (cardiac catheterization) to assess the physiologic significance of a visualized anatomic stenosis. FFR is defined as the pressure distal to the stenosis in relation to the pressure proximal to the stenosis and is assessed during maximal coronary vasodilation during infusion of a vasodilator such as adenosine. A value less than 0.75–0.80 is considered to represent a flow limiting stenosis.

FWHM:

Full width at half maximum, that is, a measure of spatial resolution for nuclear images. Indicates the closest that two separate objects can be to each other and still be distinguished.

Gibbs ringing:

An MRI artifact that is a series of lines parallel to abrupt and intense changes at the boundaries of different tissues.

Hormesis (radiation hormesis):

Concept that low dose of ionizing radiation can upgrade protective cellular defense mechanisms and prevent cancers.

Invasive coronary angiography (ICA):

Assessment of coronary anatomy with IV contrast by an invasive method, i.e., cardiac catheterization, as opposed to noninvasive coronary angiography with a technique such as computed tomography (CT). Both techniques use x-rays.

Iterative reconstruction:

A method of reconstructing tomographic images using algebraic techniques in order to find an exact mathematical solution to tracer activity distribution. The value of each pixel is initially guessed using filtered back projection, and then each value is altered repeatedly, termed “iterations” such that the subsequently calculated 2-dimensional activity distributions converge towards the true count profiles derived from the multiple image acquisition angles. Iterative reconstruction is slower and therefore requires more computer power than filtered back projection. An earlier method of iterative reconstruction was MLEM, i.e., maximum likelihood expectation maximization, but the current technique is a variant known as OSEM, i.e., ordered subset expectation maximization, that is faster than MLEM.

LEHR:

Low-energy high-resolution collimators, ideal for conventional radiotracers such as 201Tl and 99mTc compounds.

Line of response (LOR):

See coincidence detection.

Linear no-threshold (LNT) model:

The assumption that the relationship between the relative risk of cancer and high-dose radiation exposure, such as was received by Japanese atomic bomb survivors, extends linearly and without threshold to people receiving lower radiation exposures such as medical imaging procedures.

Maximum likelihood expectation maximization (MLEM):

See iterative reconstruction.

Myocardial perfusion imaging (MPI):

Assessment by imaging of blood flow to the myocardium that can be done with various methodologies including radionuclide techniques, echocardiographic contrast techniques, and cardiac magnetic resonance techniques. Can be performed at rest, with some form of stress (e.g., exercise, pharmacologic, or during pacing) or during a clinical episode (e.g., acute chest pain).

Ordered subset expectation maximization (OSEM):

See iterative reconstruction.

PET:

Positron emission tomography. Tomographic imaging of organ or tissue uptake of radioactive nuclear tracers that decay by emission of positrons (i.e., the antimatter counterparts of electrons).

Redistribution:

Refers to radioactive tracer washing out of a normal perfused area after initial uptake, while at the same time washing into hypoperfused areas, basically proceeding towards an equilibrium distribution. This phenomenon typically occurs with 201Tl, with initial distribution of tracer reflecting blood flow and the redistribution reflecting the equilibrium potassium pool distribution.

SPECT:

Single photon emission computed tomography. Tomographic imaging of organ or tissue uptake of radioactive nuclear tracers that decay by emission of single photons.

TID (transient ischemic dilation):

Image finding in which the stress images appear larger than the rest images. For SPECT it is the inner cavity dimension that is considered. The etiology is unclear, ascribed both to stress-induced subendocardial and stress-induced LV contractile dysfunction.

Wide beam reconstruction:

A noise compensation processing technique that suppresses noise thereby enhancing the signal to noise ratio of an image. This technique, as well as other resolution recovery methods developed by various vendors, allows high-quality images to be produced with shorter imaging times and/or lower administered tracer doses.

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Authors and Affiliations

  1. Division of Nuclear Medicine/Department of Radiology, Albert Einstein College of Medicine, Montefiore Medical Center, 111. East 210th Street, Bronx, NY, 10467-2490, USA

    Dr. Mark I. Travin

  2. Westchester Medical Center, New York Medical College, Valhalla, NY, USA

    Dr. Diwakar Jain

  3. Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Prof. Vishal C. Mehra & Prof. Dr. Katherine C. Wu

Authors
  1. Dr. Mark I. Travin
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  2. Dr. Diwakar Jain
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  3. Prof. Vishal C. Mehra
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  4. Prof. Dr. Katherine C. Wu
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Corresponding author

Correspondence to Mark I. Travin .

Editor information

Editors and Affiliations

  1. Akademisches Lehrkrankenhaus MLU, Bitterfeld-Wolfen, Germany

    Peter Lanzer

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Travin, M.I., Jain, D., Mehra, V.C., Wu, K.C. (2014). Perfusion Measurements of the Myocardium: Radionuclide Methods and Related Techniques. In: Lanzer, P. (eds) PanVascular Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-37393-0_45-2

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  • DOI: https://doi.org/10.1007/978-3-642-37393-0_45-2

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  • Online ISBN: 978-3-642-37393-0

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