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. May-Jun 2014;9(3):252-8.
doi: 10.1002/cmmi.1566.

The Reciprocal Linear QUEST Analysis Method Facilitates the Measurements of Chemical Exchange Rates With CEST MRI

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The Reciprocal Linear QUEST Analysis Method Facilitates the Measurements of Chemical Exchange Rates With CEST MRI

Edward A Randtke et al. Contrast Media Mol Imaging. .
Free PMC article

Abstract

Magnetic resonance imaging (MRI) contrast media that are detected via chemical exchange saturation transfer (CEST) often require an accurate estimation of their chemical exchange rate, kex . A variety of analysis methods have been proposed to estimate kex , including the nonlinear QUEST analysis method that evaluates the CEST amplitude as a function of saturation time. We have derived a linear version of QUEST, termed the Reciprocal Linear QUEST (RL-QUEST) method. Our simulations and experimental results show that RL-QUEST performs as well as QUEST, while providing a more simplistic fitting procedure. Although CEST results should be acquired with saturation power that has a nutation rate that is faster than kex of the CEST agent, an exact determination of the saturation power is not required to accurately estimate kex with RL-QUEST. This new analysis method requires a determination of the CEST agent's concentration, which is straightforward for the analysis of CEST agents in chemical solutions, but may be a limitation during in vivo CEST MRI studies. Based on the results of this study and previous studies, we provide recommendations for the linear analysis method that should be employed for each type of CEST MRI study.

Keywords: CEST; MRI; QUEST; chemical exchange rates.

Figures

Figure 1
Figure 1
CEST spectra of iopromide. A) A simulated CEST spectrum of iopromide at 4 μT saturation power and 0.5secsaturation time. The chemical structure of iopromide is shown in the inset. B) A simulated CEST spectrum of iopromide at 9 μT saturation power and 0.25secsaturation time (dots). Bloch fitting without a Gaussian point spread function showed a poor fit to the simulated spectrum (gray line), while Bloch fitting with a Gaussian point spread function using a sigma of 56Hz showed a good fit to the simulated spectrum (black line).
Figure 2
Figure 2
Analyses of chemical exchange rates using A) the QUEST method, B) the L-QUEST method, C) the RL-QUEST method, and D) the UL-QUEST method. The slope of the L-QUEST plot or the RL-QUEST plot can be used to measure the chemical exchange rate, kex Each data point of the UL-QUEST plot can be used to determine kex, and the average of these determinations of kex can be used as the estimate of the chemical exchange rate.
Figure 3
Figure 3
The dependence of QUEST and RL-QUEST on saturation power. The chemical exchange rate, kex, estimated with QUEST (dashed lines) and RL-QUEST (solid lines) from simulated CEST spectra showed accurate estimations of slow exchange rates at all saturation powers, but underestimated fast exchange rates especially at low saturation powers. The underestimations were comparable for QUEST and RL-QUEST. A dotted line with slope=1 is shown to aid visualization of the results.
Figure 4
Figure 4
The dependence of estimated kex on CESTtsat=∞ when using RL-QUEST. A) Short saturation times for CESTtsat=∞ caused lower CEST. B) An underdetermined CESTtsat=∞ causedkex to be overestimated. C) kex was only overestimated by 4% when CESTtsat=∞ was underdetermined by 50%, demonstrating that estimates of kex are insensitive to underdetermined CESTtsat=∞ values when using RL-QUEST.
Figure 5
Figure 5
The estimation of experimental kex. A) A CEST spectrum of iopromide was acquired with 4.45 uT saturation power and 4 second saturation time. The kex of the proton resonating at 4.2 ppm was estimated with B) The QUEST method and C) the RL-QUEST method. The kex of the proton resonating at 5.6 ppm was also estimated with D) The QUEST method and E) the RL-QUEST method. Experimental data points are shown as circles, the fitted result is shown as a black line, and the 95% confidence intervals are shown as gray lines.
Figure 6
Figure 6
The estimated experimental chemical exchange rates depend on saturation power. A) The estimated kex of the slowly-exchanging proton resonating at 4.2 ppm showed similar estimates with RL-QUEST (squares) and QUEST (circles). Low saturation powers improved the Lorentzian line shape fitting of experimental CEST spectra, which led to accurate estimations of kex relative to the kex estimated with Bloch fitting (dashed line). However, very low saturation powers led to inaccurate estimations of kex due to low CEST effects. B) The estimated kex of the rapidly-exchanging proton resonating at 5.6 ppm showed similar estimates with RL-QUEST (circles) and QUEST (squares), but these estimates were underestimated relative to the kex estimated with Bloch fitting (dashed line), especially with low saturation powers.

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