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Abstract
Chemical Exchange Saturation Transfer (CEST) imaging is a method to detect solutes based on the chemical exchange of mobile protons with water. The solute protons exchange with three different patterns, which are fast, slow, and intermediate rates. The CEST contrast can be obtained from the exchangeable protons, which are hydroxyl protons, amine protons, and amide protons. The CEST MR imaging is useful to evaluate tumors, strokes, and other diseases. The purpose of this study is to review the mathematical model for CEST imaging and for measurement of the chemical exchange rate, and to measure the chemical exchange rate using a 3T MRI system on several amino acids. We reviewed the mathematical models for the proton exchange. Several physical models are proposed to demonstrate a two-pool, three-pool, and four-pool models. The CEST signals are also evaluated by taking account of the exchange rate, pH and the saturation efficiency. Although researchers have used most commonly in the calculation of CEST asymmetry, a quantitative analysis is also developed by using Lorentzian fitting. The chemical exchange rate was measured in the phantoms made of asparagine (Asn), glutamate (Glu), γ-aminobutyric acid (GABA), glycine (Gly), and myoinositol (MI). The experiment was performed at a 3T human MRI system with three different acidity conditions (pH 5.6, 6.2, and 7.4) at a concentration of 50 mM. To identify the chemical exchange rate, the “lsqcurvefit” built-in function in MATLAB was used to fit the pseudo-first exchange rate model. The pseudo-first exchange rate of Asn and Gly was increased with decreasing acidity. In the case of GABA, the largest result was observed at pH 6.2. For Glu, the results at pH 5.6 and 6.2 did not show a significant difference, and the results at pH 7.4 were almost zero. For MI, there was no significant difference at pH 5.6 or 7.4, however, the results at pH 6.2 were smaller than at the other pH values. For the experiment at 3T, we were only able to apply 1 s as the maximum saturation duration due to the limitations of the MRI system. The measurement of the chemical exchange rate was limited in a clinical 3T MRI system because of a hardware limitation.
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Fig. 1
Results of the exchange rate experiments with different pH values for asparagine (a), glutamate (b), GABA (c), glycine (d), and myoinositol (e) at 3T. The B1 amplitude was 3 μT and the concentration was 50 mM. Data points with different saturation durations are shown with a circle (pH 5.6), a cross (pH 6.2), and a triangle (pH 7.4). Results were plotted with a solid line at pH 5.6, a dashed line at pH 6.2, and a dotted line at pH 7.4.
Table 1.
Initial values, the lower limit, and the upper limit of the amplitude, the full width of half maximum (FWHM), and the center frequency of the six pools for Lorentzian curve fitting.
The amplitude is no unit because of the normalization of the full Z spectrum signals by the reference signal. The frequency (ppm) is the center frequency of the exchangeable protons. The six pool protons were defined in the initial offset frequency values as water at 0 ppm, amide at 3.5 ppm, amine at 3.0 ppm, hydroxyl at 0.9 ppm, the nuclear overhauser effect (NOE) at −3.5 ppm, and the magnetization transfer (MT) at −1.5ppm.
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