On B1 inhomogeneity correction of in vivo human brain glutamate chemical exchange saturation transfer contrast at 7T.

Chemical exchange saturation transfer (CEST) MRI is a novel method for exploring metabolites/macromolecules having exchangeable protons (−OH, −NH2, −NH) (1–4) with high sensitivity. In CEST MRI, the change in the free water magnetization, while selectively saturating the exchangeable protons of the metabolite of interest, is used as a measure of the metabolite content. Recently, a number of in vivo studies have been carried out for exploring the potential of CEST MRI for detecting changes in an array of endogenous metabolites (3,5–9). Notably, there is an extensive literature on the use of amide proton transfer in tumors to assess pH and protein content (3,5,6). The CEST MRI contrast depends on the exchange rate (kex), offset frequency (Δω), concentration, T1 and T2 values of water and the exchanging molecule as well as the saturation pulse power (B1rms) and duration. The Δω values of most of the exchangeable protons of endogenous CEST agents (such as labile groups on macromolecules, glutamate, creatine, glycogen, glucose, and myo-inositol) fall within 5 p.p.m. downfield from the bulk water. In these cases, direct saturation (DS) of bulk water needs to be accounted for. In addition to DS, CEST contrast can be further reduced by magnetization transfer (MT) effect exhibited by tissue with a bound water pool. In general, CEST contrast is computed using asymmetry analysis (3,5) for removing DS and MT contributions and is contaminated by native asymmetry in MT (MTasy) effect. Recently, a magnetization exchange mediated nuclear Overhauser effect (NOE), centered around Δω = −3.5 p.p.m., has also been reported, which, along with MTasy at low saturation power, can result in negative CEST contrast (10). CEST contrast exhibits nonlinear dependence on saturation power because of the contamination from DS, MTasy, and NOE effects. Along with the above-mentioned challenges, CEST contrast is highly sensitive to local B0 and B1 variations. B0 inhomogeneity issues are present at all field strengths, and several correction methods are available in the literature (11–13). B1 inhomogeneity depends on the type of RF-coils and MR scanner field strength. Previously published approach (11) to correct B1 inhomogeneity relies on steady state saturation conditions, prior knowledge of a number of parameters like T1, T2, concentrations and exchange rate and a single CEST pool. As demonstrated in recently published in vivo studies (8,9), CEST contrast obtained at Δω = 3 p.p.m. and with high saturation pulse amplitude (>3.0 μT) predominantly originates from glutamate and was named GluCEST. Under the constraints of specific absorption rate, the optimum GluCEST contrast in human brain at 7T was obtained using a saturation pulse with B1rms of 3.64 μT and duration of 1 s (8). In this study, our objective is to perform B1 inhomogeneity correction for GluCEST contrast maps obtained with nonsteady state saturation conditions at 7T. In this study, we present a new approach to correct B1 inhomogeneity for in vivo GluCEST at 7T. Specifically, experimental dependence of GluCEST contrast on saturation power and tissue type is studied in human brain at 7T and an approach based on polynomial fitting is presented to correct for B1 field inhomogeneity. The method is validated on healthy human subject data obtained from different regions of the brain. It is also shown that a calibration curve derived from data on one normal volunteer could be used to correct B1 inhomogeneity on GluCEST maps obtained from other normal volunteers, without significant errors in the computed GluCEST contrast from the brain. Possible extensions of this approach to study CEST contrast from other metabolites and tissue types are discussed.