Myocardial flow reserve (MFR) with positron emission tomography (PET)/computed tomography (CT): clinical impact in diagnosis and prognosis

Abstract

In recent years, radionuclide myocardial perfusion imaging (MPI) using positron emission tomography/computed tomography (PET/CT) has emerged as a robust tool for the diagnosis, risk stratification and management of patients with known or established coronary artery disease (CAD). Cardiac PET/CT imaging affords key advantages compared to single photon emission computed tomography (SPECT) that encompass: (I) improved diagnostic accuracy; (II) decreased radiation exposure due to the utilization of short-lived radiopharmaceuticals, and importantly; (III) the ability to quantify noninvasively myocardial blood flow (MBF) in absolute terms, that is in ml per minute per gram of tissue. Quantitative approaches that measure MBF with PET can facilitate the diagnosis of multivessel CAD and offer the opportunity to monitor responses to lifestyle and/or risk factor modification and to therapeutic interventions. The aim of this review is to focus on the potential clinical utility of MBF and will discuss: (I) basics aspects of PET clinical perfusion tracers and flow quantification parameters; (II) limitations of relative MPI, (III) summarize a classification of diseases where flow quantification may be of use; (IV) specifically, review data on the diagnosis and prognostic value of flow quantification.

Keywords: Positron emission tomography/computed tomography (PET/CT); clinical value; myocardial flow reserve.

Figure 1

Tracer uptake rate K₁ vs. FLOW from a one-tissue-compartment model of tracer kinetics. K₁ is equal to the product of FLOW times the unidirectional extraction fraction. In all tracers except ¹⁵O-water, the tracer extraction is reduced when perfusion is increased leading to underestimation of perfusion if only tracer uptake is used.

Figure 2

Hybrid PET/CT allows non-invasive evaluation of the coronary anatomy and functional information in one setting. (A) CT angiography (step and-shoot mode) shows multi-vessel disease with massive coronary calcifications and severe stenosis in all major coronary arteries. (B) Hybrid display during adenosine stress demonstrates quite preserved perfusion in anterolateral wall but moderate reduction in septal wall (anterior view). In RCA related region the perfusion was the most severely reduced (posterior view) indicating culprit stenosis in this vessel. Perfusion was colour scaled so that red colour denotes to 3.5 mL/min/g. Resting perfusion was normal (not shown). Total radiation dose of the hybrid study was 11.3 mSv. Reproduced with permission of (21).

Figure 3

Schematic diagram of Time-Activity curves of tracer radioactivity in Blood and in the myocardium. Flow quantification with PET requires IV injection of a PET perfusion tracer and dynamic acquisition of images. Tracer-kinetic models (1 to 3 compartments) and operational equations are then applied to correct for physical decay of the radioisotope, partial volume-related underestimation of the true myocardial tissue concentrations (by assuming a uniform myocardial wall thickness of 1 cm), and spillover of radioactivity between the left ventricular blood pool and myocardium. Time activity curves, in red in the blood and in light blue the pure tracer concentration after we correct for partial volume and spillover of blood in the myocardium.

Figure 4

Unadjusted predicted probability (red line) and 95% Confidence Interval (blue lines) of severe 3 vessel CAD at various levels of ⁸²Rb PET MFR based on the analysis model. When MFR is preserved, the likelihood of multivessel CAD is low, whereas with reducing MFR the likelihood of 3-vessel CAD increases. MFR, myocardial flow reserve. Reproduced with permission of (47).

Figure 5

Clinical example in which flow quantification with PET may improve diagnosis of CAD. (A) Dypiridamole ⁸²Rb PET MPI static images demonstrate normal relative perfusion at rest and during peak stress; (B) 17-segment model polar maps of rest MBF (lower left; color display scale 0 to 1.5 mL/min/g), stress MBF (upper left; scale: 0–3.0 mL/min/g), MFR (upper right; scale: 0–3.0) and MFD (lower right; scale: 0–2.0) which demonstrate global impairments, absolute values displayed in the table below; (C) Coronary Angiogram reveals significant obstructive 3-vessel CAD, relative perfusion underestimated the presence of disease (arrows point out significant stenosis). HLA, horizontal long axis; SA, short axis; VLA, vertical long axis; MBF, myocardial blood flow; MFR, myocardial flow reserve; MFD, myocardial flow difference; LAD, left anterior descending artery; LCX, left circumflex; RCA, right coronary artery; RPLS, right posterolateral branch.

Figure 6

A 70-year-old male with hypertension, PVD, renal insufficiency, worsening angina with exertion. (A) dipyridamole ⁸²Rb PET MPI static images demonstrate moderate ischemia in the RCA territory (red arrows); (B) 17-segment model polar maps of rest flow (lower left; color display scale 0–1.5 mL/min/g), stress flow (upper left; scale: 0–3.0 mL/min/g), MFR (upper right; scale: 0–3.0) and MFD (lower right; scale: 0–2.0) with several global reduction in MFR; (C) coronary anatomy showed severe LM stenosis and critical ostial RCA with diffuse CAD in LAD and LCX (arrows point out significant stenosis). Relative MPI underestimated CAD in LM territory. HLA, horizontal long axis; SA, short axis, VLA, vertical long axis; MBF, myocardial blood flow; MFR, myocardial flow reserve; MFD, myocardial flow difference. Reproduced with permission of (47).

Figure 7

MACE within subgroups of SSS for different levels of MFR. At any level of SSS, the prevalence of MACE is higher in patients with the lowest MFR (<1.5), and statistically significant different compared to MFR ≥2 among patients with overt ischemia. (*P=0.028 for SSS ≥4–7 and MFR <1.5 vs. MFR ≥2 and **P=0.002 for SSS ≥8 and MFR <1.5 vs. MFR ≥2). SSS, summed stress score; MACE, major adverse cardiac events; MFR, myocardial flow reserve. Reproduced with permission of (55).