Quantitative cardiac perfusion MRI is a non-invasive
radiation-free technique that can estimate absolute myocardial blood flow (MBF)
and myocardial perfusion reserve (MPR), which are known to be good indicators
of ischemic burden in CAD patients, as well as of hemodynamic significance of
stenotic lesions. Further, there is
growing evidence that MBF and MPR may be sensitive biomarkers of microvascular ischemia. A typical perfusion MRI experiment involves
the administration of contrast agents to capture the wash-in wash-out
characteristics of the arterial input function and the tissue output function
at rest and during pharmacologically induced stress. The functions are then modeled using either
compartmental modeling approaches or deconvolution approaches to extract myocardial
blood flow at the two experimental states from which myocardial perfusion
reserve is quantitated. This module will
focus on presenting contrast agents and mechanisms involved, typical protocols,
sequences and stress agents used, as well as discuss in detail the perfusion
models used for quantitative data analysis.
Upon completion of this course, participants should be able to:
The aim of this module on tissue perfusion is to:
Contrast agents and contrast mechanisms: There are two major classes of contrast agents (extravascular extracellular, intravascular) used for first pass perfusion imaging [1,2]. While intravascular agents present with some advantages, Gd-based extravascular extracellular contrast agents are the most commonly used agents in the clinic. These paramagnetic agents results in enhanced signal intensity in T1-weighted images in the tissue that it perfuses through [3]. A brief overview of the contrast agents and mechanisms will be presented.
Imaging Sequences and Protocols: To capture the wash-in and wash-out characteristics of the contrast agent as it perfuses through the tissue, a saturation recovery imaging pulse sequence has emerged as the current standard. The pulse sequence is specially designed to generate strong T1 contrast while covering as much of the myocardium as possible maintaining a high temporal resolution and providing adequate spatial resolution [4]. Specially designed RF pulses are sometimes used to achieve less sensitivity to variations in the transmitted RF field [5].
For quantitative measurement of MBF, mapping of the arterial input function is essential. This calls for a dual bolus [6] or a dual sequence [7] approach to avoid the saturation and T2* effects that the AIF will encounter at higher concentration of the contrast agents. These methods will be introduced in the talk.
For quantification of MPR, specialized stress protocols are designed to allow quantitation of MBF at rest and during pharmacological stress. Different pharmacological agents (e.g. adenosine, dobutamine) can be used to induce stress [8, 9]. These will be discussed briefly.
Perfusion Modeling Approaches: Two classes of approaches have typically been used to quantitate myocardial blood flow from first pass perfusion MR images 1) compartmental models, 2) model-based/model-independent deconvolution [10].
Lumped compartmental models [11], especially two compartmental models [12, 13] have been used where the vessels are lumped into a vascular compartment and the interstitial space into a secondary compartment, with exchange of contrast agent through the capillary barriers between the two spaces. These models will be discussed in detail and the main equations will be reviewed.
Next, the central volume principal will be first introduced. Within the framework of the central volume principal, the discussion will focus in detail on two different types of deconvolution approaches: Fermi function model [14], and model-independent deconvolution [15]. Once again, the main equations will be reviewed.
Regional quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) using MRI will provide a radiation-free and non-invasive approach to evaluate:
Conclusions
1 Weinmann H, et. al. Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent. American Journal of Radiology 142, 619-624, (1984).
2 Jerosch-Herold M, et. al. Magnetic resonance imaging of myocardial contrast enhancement with MS-325 and its relation to myocardial blood flow and the perfusion reserve. Journal of Magnetic Resonance Imaging 18, 544-554, (2003).
3 Moriarty JM, et. al. Contrast agents used in cardiovascular magnetic resonance imaging. American Journal of Cardiovascular Drugs 10(4), 227-237, (2010).
4 Kellman P, et. al. Imaging sequences for first pass perfusion – a review. Journal of Cardiovascular Magnetic Resonance 9(3), 525-537, (2007).
5 Kim D et. al. B(0) and B(1)- insensitive uniform T(1)-weighting for quantitative, first-pass myocardial perfusion magnetic resonance imaging. Magnetic Resonance in Medicine 54(6), I423-I429, (2005).
6 Hsu LY, et. al. Quantitative myocardial perfusion analysis with a dual-bolus contrast-enhanced first-pass MRI technique in humans. Journal of Magnetic Resonance Imaging 23(3), 315-322, (2006).
7 Gatehouse PD, et. al. Accurate assessment of the arterial input function during high-dose myocardial perfusion cardiovascular magnetic resonance. Journal of Magnetic Resonance Imaging 20(1), 39-45, (2004).
8 Hamirani YS, et. al. Cardiac MRI assessment of myocardial perfusion. Future Cardiology 10(3), 349-358, (2014).
9 Sampath S, et. al. Quantitative MRI biomarkers to characterize regional left ventricular perfusion and function in nonhuman primates during dobutamine‐induced stress: A reproducibility and reliability study. Journal of Magnetic Resonance Imaging 45(2), 556-569, (2017).
10 Pack NA, et. al. Comparison of myocardial perfusion estimates from dynamic contrast-enhanced magnetic resonance imaging with four quantitative analysis methods. Magnetic Resonance in Medicine 64(1), 125-137, (2010).
11 Cullen JHS, et. al. A myocardial perfusion reserve index in humans using first-pass contrast-enhanced magnetic resonance imaging. Journal of the American College of Cardiology 33(5), 1386-1394, (1999).
12 Larsson HBW, et. al. Myocardial perfusion modeling using MRI. Magnetic Resonance in Medicine 35, 716-726, (1996).
13 Vallee J-PM, et. al. Quantification of myocardial perfusion by MRI after coronary occlusion. Magnetic Resonance in Medicine 40, 287-297, (1998).
14 Jerosch-Herold M et. al. Analysis of myocardial perfusion MRI. Journal of Magnetic Resonance Imaging 19, 758-770, (2004).
15 Jerosch-Herold M et. al. Myocardial blood flow quantification with MRi by model-independent deconvolution. Medical Physics 29(5), 886-897, (2002).
16 Thomson LEJ et. al. Cardiac Magnetic Resonance Myocardial Perfusion Reserve Index Is Reduced in Women With Coronary Microvascular Dysfunction: A National Heart, Lung and Blood Institute-Sponsored Study From the Women's Ischemia Syndrome Evaluation (WISE). Circulation Cardiovascular Imaging 8(4), 1-20, (2015).