Understanding quantitative pulsed CEST in the presence of MT

Abstract

Phantom experiments in agar and ammonium chloride were performed to evaluate a three-pool model of magnetization transfer and chemical exchange saturation transfer (CEST) in a pulsed saturation transfer experiment. The utility of the pulsed CEST method was demonstrated by varying the pH of the phantoms and observing the effect upon the CEST spectra both with and without the solid agar (the magnetization transfer pool), while fitting the spectra to the Bloch equation model with exchange. Pulsed CEST could be used to robustly quantify parameters related to CEST, including the exchange rate constant describing proton exchange with free water and the concentration of exchanging protons. Furthermore, the exchange rate constant and the CEST pool offset frequency of the ammonium chloride remained unchanged in the presence of a magnetization transfer pool. The logarithm of the fitted exchange rate constant was linearly related to pH: this relationship was maintained in the presence of magnetization transfer. Magn Reson Med 67:979-990,

Proton Chemical Exchange Saturation Transfer (CEST) MRS and MRI

“…In practice, it is adversely affected by the presence of other asymmetrical or partially symmetrical effects. For instance, in vivo, the conventional MTC caused by the presence of semisolid structures interferes when strong RF fields are used [53][54][55][56] and the endogenous signals of multiple tissue constituents can contribute. The following sections present some methods for addressing such effects.…”

“…Thus, both long and short T 2 spin systems and slow and fast transferring components contribute to the MTR asym , the relative magnitude of which depends on the B 1 field used. 53,69,75 At low B 1 , slow exchanging protons (<100 Hz, mainly amide protons) and rNOEs from mobile MMs dominate. As B 1 is increased, the comparatively faster exchanging amide, amine, imino, and hydroxyl protons and the partially asymmetric conventional MTC effect become dominant.…”

“…Actually, even if MTC effects were symmetric, these two mechanisms generally cannot be added in a zero-order approach but are interdependent, especially at higher B 1 . 53 Recent efforts have therefore focused on trying to separate out MTC and CEST effects using sequences that exploit the different properties mentioned above. In particular, the difference in the R 2 of the protons involved leads to fast incoherent dephasing in the MTC pool but an identifiable resonance in the CEST and rNOE signals from mobile species.…”

“…Subsequently, APT was used to detect pH changes during early ischemia (based on the pH dependence of the amide proton exchange rate) 43,62,88 and increases in the mobile protein/peptide content of brain tumor tissue. 42,165 In these studies, CEST effects were assessed using MTR asym analysis and, due to contamination by other transfer processes, 21,42,43,53,72,102,[125][126][127][128]130,131,166 it is most appropriate to refer to the contrast achieved as APTw. In studies of cancer in the brain, APTw MRI is showing promise for (i) separating high-grade tumors from low-grade tumors and edema; 42,112,167 (ii) distinguishing recurrent tumor from treatment necrosis; 159 and (iii) detecting early response to treatment.…”

CEST Imaging

“…Since the most intuitive approach for obtaining narrowband saturation, i.e. ,continuous-wave (CW) irradiation, is often not possible on clinical MRI scanners because of technical and SAR constraints, a considerable amount of CEST research is focused on optimizing pulsed saturation schemes [34][35][36][37]. Since multiple data sets are acquired for one z-spectrum, it is also mandatory to compensate for patient motion between acquisitions in order to correctly align the data sets with different saturation offsets for proper analysis of z-spectra.…”