Simultaneous determination of labile proton concentration and exchange rate utilizing optimal RF power: Radio frequency power (RFP) dependence of chemical exchange saturation transfer (CEST) MRI

Abstract

Chemical exchange saturation transfer (CEST) MRI is increasingly used to probe mobile proteins and microenvironment properties, and shows great promise for tumor and stroke diagnosis. However, CEST MRI contrast mechanism is complex, depending not only on the CEST agent concentration, exchange and relaxation properties, but also varying with experimental conditions such as magnetic field strength and RF power. Hence, it remains somewhat difficult to quantify apparent CEST MRI contrast for properties such as pH, temperature and protein content. In particular, CEST MRI is susceptible to RF spillover effects in that RF irradiation may directly saturate the bulk water MR signal, leading to an optimal RF power at which the CEST contrast is maximal. Whereas RF spillover is generally considered an adverse effect, it is noted here that the optimal RF power strongly varies with exchange rate, although with negligible dependence on labile proton concentration. An empirical solution suggested that optimal RF power may serve as a sensitive parameter for simultaneously determining the labile proton content and exchange rate, hence, allowing improved characterization of the CEST system. The empirical solution was confirmed by numerical simulation, and experimental validation is needed to further evaluate the proposed technique.

Fig. 1

Illustration of two representative CEST systems, a) 2-pool exchange model that depicts relatively concentrated CEST agents undergoing slow chemical exchange, b) shows the case of dilute CEST agents undergoing faster interaction with bulk water.

Fig. 2

a) CEST MRI contrast was simulated as a function RF power for three exchange rates, 30, 75 and 150 s⁻¹ at a labile proton content of 1:1000. The up triangle, down triangle and square markers denote numerical simulation, while the line represent empirical solution results using Eq. 1, which agreed well. The optimal RF power for each exchange rate is shown in dashed line, b) The Optimal RF power was plotted as a function of exchange rate, with circles, sold line and dashed line represent numerically simulated results, analytical estimates from Eq. 1 and Eq. 2, respectively. In addition, CEST MRI was also simulated for labile proton concentration effect, in which concentration was varied from 1:2000 (up triangle), 1:1000(down triangle) to 1:500 (square) for a representative exchange rate of 75 s⁻¹ in (c), with the optimal RF power shown in the dashed line, d) The optimal RF power estimated from empirical solution of Eq. 1 and Eq. 2 agrees well with the numerical simulation (circle).

Fig. 3

evaluation of the dependence of optimal RF power upon chemical offset and relaxation rates for the case of dominant change in exchange rate (Figs 3a, c and d) and the case of labile proton concentration effect (Figs 3b, d and f). Specifically, Figs 3a and b compared optimal RF power as a function of exchange rate and labile proton concentration for amide proton at field strength of 3,4.7 and 7T, respectively. It showed although optimal RF power increases with chemical offset, the optimal RF power remains constant for the range of investigated labile proton concentration, while it increases with exchange rate. In addition, Figs 3c and d evaluated optimal RF power when T_1w was varied from 1,1.5 to 2 s, while Figs. 3e and f studied bulk water T_2w dependence from 40, 60 to 100 ms. All simulation showed that for a given set parameters of chemical offset and relaxation rates, the optimal RF power depends on exchange rate, with negligible dependence on the labile proton concentration, in reasonable agreement with theoretical prediction.

Fig. 4

a flow chart that describes the proposed quantitative RFP-CEST MRI technique. Step 1) CEST MRI contrast is simulated or experimentally measured for a range of RF power. 2) Optimal RF power is identified by finding the RF power that maximizes CEST MRI contrast. 3) Exchange rate is estimated from optimal RF power using Eq. 2, provided that relaxation parameters and chemical offsets are known. 4) Labile proton concentration is derived from Eq. 1, provided that relaxation rates, RF offsets are known.

Fig. 5

Evaluation of the inverse problem that whether exchange rate and labile proton concentration effect can be simultaneously determined from the optimal RF power. For the first case, exchange rate was varied between 1 and 150 s⁻¹, while the labile proton concentration was 1:1000. The estimated exchange rate correlated well with simulated values (a), and can be described by a linear function. In addition, the derived labile proton concentration had a narrow distribution from the simulated value of 1:1000 (b). For the second case, labile proton concentration was varied from 1:2000 to 1:500, for a representative exchange rate of 75 s⁻¹. The exchange rate was found to be 98 s⁻¹ from Eq. 2, in contrast to simulated value of 75 s⁻¹(c). Moreover, the estimated labile proton concentration vs. simulated value can be described by a linear function.