Mapping intracellular pH in tumors using amide and guanidyl CEST‐MRI at 9.4 T

Abstract

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Guanidinium and amide CEST mapping of human brain by high spectral resolution CEST at 3 T

“…The high GuanCEST signal at 3 T is consistent with the high field MRI observation, in which the GuanCEST intensity is even higher than the amideCEST intensities with specific B 1 values (GuanCEST 2.9% at 2 μT vs. amideCEST 1.87% at 1 μT). 6,24,25,31,32,61 The GuanCEST has not been well studied on 3 T MRI for 2 reasons, first, most of the previous CEST studies were performed with very few offsets and cannot easily separate the severely overlapped Guan and amideCEST peaks. Second, high saturation power (around 2 μT) was implemented in most APT-weighted studies, 9 which can dramatically decrease the signal at 2.28 ppm.…”

“…33 Because the mixed signal always complicates ArgCEST with creatine and phosphocreatine CEST (CrCEST/PCrCEST) at 2 ppm, 16 the CEST peak at this range is named collectively as GuanCEST. Interestingly, GuanCEST is visible at the high field MRI (>7 T) on both animal [6][7][8]11,32 and human brains. 15,23,34 It has not been observed on 3 T MRI to our best knowledge.…”

“…Those protons can still exchange with water through the relayed process similar to the aliphatic NOE, [28][29][30] named amideNOE. 22 Assisted by those discoveries, amideCEST was extracted from the crowded Z-spectrum and quantified using either a polynomial and Lorentzian line-shape fitting (PLOF) approach or a simplified principle of the 3-point approach at both high magnetic fields 24,25,31,32 and 3 T. 22 In the recent study on the human brain at 3 T with the PLOF method, the amideCEST peak was assumed as a single peak at 3.5 ppm. Nonetheless, more careful inspection suggests that the amideCEST peak may have more sophisticated components.…”

The exchange rate of creatine CEST in mouse brain

“…The CrCEST signal change due to the pH reduction (0.2) was simulated as a function of the CrCEST exchange rate for three B 1 values by fixing the MTC background extracted from the Z‐spectra recorded with 2.0 μT/1 s on WT mice. The exchange rate determination by multiple pH and B 1 values has recently been demonstrated on tissue homogenate 36 . The method can be treated as a simplified version of the same principle using two pH and three B 1 values.…”

“…The method can be treated as a simplified version of the same principle using two pH and three B 1 values. In the simulation, the CrCEST exchange rate is given by 36 $$$$ k={k}_c{10}^{pH} $$$$ with a pH reduction of $$$ \Delta pH $$$ introduced by CO 2 inhalation, the CrCEST exchange rate $$$ {k}_{\mathrm{co}2} $$$ during CO2 inhalation will be reduced to $$$$ {k}_{\mathrm{co}2}=k{10}^{-\Delta pH} $$$$ Then, the CrCEST signal will be alternated due to the exchange rate change (from k to $$$ {k}_{\mathrm{co}2} $$$). The identical two‐step BM fitting was also used to simulate the CrCEST signal at 3T using the human brain Z‐spectrum previously recorded 35 .…”