Abstract
Many pathological conditions lead to altered intracellular pH (pHi) disrupting normal cellular functions. The chemical exchange saturation transfer (CEST) method, known as Amine and Amide Concentration Independent Detection (AACID), can produce image contrast that is predominantly dependent on tissue intracellular pHi. The AACID value is linearly related to the ratio of the 3.5 ppm amide CEST effect and the 2.75 ppm amine CEST effect in the physiological range. However, the amine CEST effect at 2 ppm is often more clearly defined in vivo, and may provide greater sensitivity to pH changes. The purpose of the current study was to compare AACID measurement precision utilizing the 2.0 and 2.75 ppm amine CEST effects. We hypothesized that the 2.0 ppm amine CEST resonance would produce measurements with greater sensitivity to pH changes. In the current study, we compare the range of the AACID values obtained in 24 mice with brain tumors and in normal tissue using the 2 ppm and 2.75 ppm amine resonances. All CEST data were acquired on a 9.4T MRI scanner. The AACID measurement range increased by 39% when using the 2 ppm amine resonance compared to the 2.75 ppm resonance, with decreased measurement variability across the brain. These data indicate that in vivo pH measurements made using AACID CEST can be enhanced by incorporating the 2 ppm amine resonance. This approach should be considered for pH measurements made over short intervals when no changes are expected in the concentration of metabolites that contribute to the 2 ppm amine resonance.
Highlights
Intracellular pH plays an important role in many physiological processes, including apoptosis, cell proliferation, and protein interactions, and it is altered in several disease states
In previous work [18] using 9.4T MRI, we have demonstrated that the ratio of the 3.5 ppm amide Chemical exchange saturation transfer (CEST) effect to the 2.75 ppm amine CEST effect varies linearly with pH in the physiological range, and is largely independent of protein concentration and temperature [18]
The purpose of the current study was to investigate whether AACID CEST measurements incorporating the 2 ppm amine resonance would have greater sensitivity compared to measurements made using the 2.75 ppm resonance in brain tumors and contralateral tissue
Summary
Intracellular pH plays an important role in many physiological processes, including apoptosis, cell proliferation, and protein interactions, and it is altered in several disease states. The measurement of the APT CEST effect depends on several factors including the amide proton concentration, water concentration, and the relaxivity (R1) of bulk water [6], this contrast has been successfully used to identify ischemic tissue following acute stroke [7–12] and to study cancer [13–17]. In previous work [18] using 9.4T MRI, we have demonstrated that the ratio of the 3.5 ppm amide CEST effect to the 2.75 ppm amine CEST effect varies linearly with pH in the physiological range, and is largely independent of protein concentration and temperature [18]. This ratiometric CEST method called Amine and Amide Concentration
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