Spin-locking versus chemical exchange saturation transfer MRI for investigating chemical exchange process between water and labile metabolite protons

Abstract

Chemical exchange saturation transfer (CEST) and spin-locking (SL) experiments were both able to probe the exchange process between protons of nonequivalent chemical environments. To compare the characteristics of the CEST and SL approaches in the study of chemical exchange effects, we performed CEST and SL experiments at varied pH and concentrated metabolite phantoms with exchangeable amide, amine, and hydroxyl protons at 9.4 T. Our results show that: (i) on-resonance SL is most sensitive to chemical exchanges in the intermediate-exchange regime and is able to detect hydroxyl and amine protons on a millimolar concentration scale. Off-resonance SL and CEST approaches are sensitive to slow-exchanging protons when an optimal SL or saturation pulse power matches the exchanging rate, respectively. Recently, there has been an increasing number of in vivo studies that have used the chemical exchange (CE) effect to probe the tissue microenvironment and provide novel imaging contrasts that are not available from conventional MRI techniques. Most of these studies adopted either a chemical exchange saturation transfer (CEST) or a spinlocking (SL) approach to detect contrast in tissue pH or the population of labile protons, which have a Larmor frequency different from water. Ideally, a CE-sensitive imaging contrast should have good sensitivity and vary monotonically with pH and linearly with labile proton concentration. The CE contrast is determined by many parameters, such as the exchange rate between water and labile protons (k ex ), the difference in their Larmor frequencies (d), the populations of the exchangeable protons, water T 1 , and the magnetic field strength (B 0 ). The CE effect in MRI is also highly sensitive to a ratio of k ex to d. k ex /d, which indicates the CE kinetics, is usually divided into three regimes: slow (k ex /d ( 1), intermediate (k ex /d $ 1), and fast exchange (k ex /d ) 1). CEST techniques are mostly applied at the slow-or slow-to intermediate-exchange regime (1,2), whilereas the CE is often assumed to occur at the fast-exchange regime for SL applications (3,4).In CEST studies that are based upon endogenous contrast, selective off-resonance irradiation of labile protons of protein or peptide side chains attenuates the water signal via exchange between these labile protons and bulk water. The signal intensity as a function of irradiation frequency, often referred to as the Z-spectrum, can be expressed by the magnetization transfer ratio (MTR):where V is the frequency offset with respect to water. In practice, the conventional non-CE magnetization transfer effect and direct water saturation (or the so-called spillover effect) also affect the Z-spectrum, and these effects are assumed to be symmetrical around the water resonance frequency. To minimize these non-CE contributions, CEST contrast in MRI is usually extracted from two images-one acquired with off-resonance irradiation on the targeted labile proton and the other as a control with opposite offset frequency from the water (5). The norma...

Proton Chemical Exchange Saturation Transfer (CEST) MRS and MRI

“…21 This is the reverse of the exchange-relayed NOEs measured in the WEX spectra ( Figure 3). rNOE effects on mobile molecules have further been detected in the brain in animals 70 and humans. 71 However, they are difficult to detect without interference with the MTC effect, which is of course also NOE based.…”

Basics of Chemical Exchange Saturation Transfer (CEST) Magnetic Resonance Imaging

“…As pointed out by Jin et al [27], the SL approach is useful for improving the signal-to-noise ratio (SNR) in CEST MRI. Furthermore, Kogan et al [28] demonstrated that a combination of the CEST and SL approaches is useful for detecting proton exchange in the slow-to intermediate-exchange regimes.…”

“…M a zss in Eq. (27) is approximated by [27]. Figure 11 shows an example of the three-dimensional plots of the magnetization vector in pool A in the two-pool chemical exchange model (Figure 1).…”

Relationship altered between functional T1ρ and BOLD signals in bipolar disorder

“…This technique aims to quantitatively map the spin‐lock–based T1ρ relaxation time temporally and is sensitive to chemical exchange of protons between water and amide, hydroxyl, and/or amine groups (Jin, Autio, Obata, & Kim, 2011). This chemical exchange is influenced by pH and metabolite concentration (e.g., glucose and glutamate) (Jin et al., 2011; Kettunen, Gröhn, Silvennoinen, Penttonen, & Kauppinen, 2002), which have been shown to change in response to neural activation prior to changes in blood flow (Belanger, Allaman, & Magistretti, 2011). T1ρ relaxation is also sensitive to stimulus‐induced rotary saturation (SIRS), which may directly measure neuronal currents (Witzel, Lin, Rosen, & Wald, 2008).…”