Assessment of myocardial blood volume and water exchange: Theoretical considerations and in vivo results

Abstract

The measured signal response in contrast-enhanced myocardial perfusion imaging has been shown to be affected by the rate of water exchange between the intravascular and extravascular compartments, the effect being particularly significant when intravascular contrast agents are used. In the present study, the T 1 relaxation rates were measured in eight pigs in blood and myocardium using a Look-Locker sequence after repeated injections of the intravascular contrast agent NC100150. The selection of myocardial region of interest was automated based on a minimum chi-square method. The intraand extravascular water exchange rates and the myocardial blood volume were calculated from the measured relaxation rates by applying a two-compartment water exchange limited model that accounts for biexponential longitudinal relaxation. Key words: cardiac imaging; T 1 quantification; iron oxide nanoparticle; water exchange dependent relaxation; myocardial water exchange; NC100150 Injection; Clariscan™The influence of water exchange between the different tissue compartments of the MR signal response following administration of a T 1 -shortening contrast agent is well known (1-7). Water exchange effects are of particular importance when the MR signal needs to be related to the contrast agent concentration in tissue, as is the case in T 1 -based contrast-enhanced perfusion imaging. The effect of water exchange on the signal response depends on the peak difference in 1/T 1 relaxation rate between the different tissue compartments relative to the rate of water exchange between the compartments. As long as the difference in 1/T 1 between the compartments in the presence of the contrast agent is significantly less than the rate of water exchange between the compartments, the measured tissue signal response is unaffected by water exchange. This condition is referred to as fast exchange. When the difference in 1/T 1 is comparable to or larger than the water exchange rate the signal response is significantly affected by water exchange and a linear relationship between 1/T 1 and contrast agent concentration can no longer be assumed (3). There is a consensus in the literature that water exchange between the intravascular and extravascular compartments is the rate-limiting factor determining maximum achievable tissue enhancement following injection of a T 1 -enhancing agent. This is because the intra-and extracellular water exchange rate is at least an order of magnitude higher than the intra-and extravascular rate (2,4,8).Contrast-enhanced myocardial perfusion imaging is possibly the one method where water exchange effects have been most comprehensively addressed (4,5,7,9,10). In a recent study, Larsson et al. (5) concluded, based on comprehensive simulations as well as clinical data, that water exchange effects do not introduce significant errors in the estimation of myocardial perfusion-related parameters when extracellular fluid (ECF) agents are used. However, when intravascular agents are used they concluded that water exchange limitation...

Importance of perfusion in myocardial viability studies using delayed contrast‐enhanced magnetic resonance imaging

“…The R 1 measurements in perfused myocardium before CA administration (R 1 ϭ 912 Ϯ 55 msec -1 ) are consistent with previous studies in which R 1 was found to be 860 msec -1 and 930 msec -1 in pigs (25,27), and 840 msec -1 in humans (28).…”

“…Parametric R 1 maps and corresponding 2 error maps (25) (Fig. 1) were calculated from a nonlinear least-squares fit of the Look-Locker data to the equation SI(TI) ϭ ␤ ϫ |(1 -2e -R1ϫTI )| ϩ K, where || denotes the modulus, ␤ and K are fitting constants, and R 1 ϭ 1/T 1 is the model parameter to be determined (26).…”

Measurement of kinetic parameters in skeletal muscle by magnetic resonance imaging with an intravascular agent

“…Similarly, transendothelial exchange rates have been estimated to be 1-6 s -1 in myocardium (18,35). Several approaches have been proposed to account for the effect of water exchange on the relaxation kinetics (34,36,37), although a consensus has yet to emerge on how to best account for these effects and how to balance the need for additional model parameters and the limited precision of the measurements. In the worstcase scenario, the consequence of assuming fast exchange where it does not exist is the underestimation of v p and the overestimation of K trans (17,38).…”

Quantification of Myocardial Blood Volume During Dipyridamole and Doubtamine Stress: A Perfusion CMR Study

“…Our 99m Tc vs. CMR values are fairly consistent, however, this would explain any slight overestimation for epicardial MBV with our CMR method. Thirdly, the water exchange effect was not accounted for in our deconvolution model calculation of MBV (32). This is particularly important when an intravascular contrast agent is used.…”