The z-spectrum from human blood at 7T.

Chemical Exchange Saturation Transfer (CEST) has been used to assess healthy and pathological tissue in both animals and humans. However, the CEST signal from blood has not been fully assessed. This paper presents the CEST and nuclear Overhauser enhancement (NOE) signals detected in human blood measured via z-spectrum analysis. We assessed the effects of blood oxygenation levels, haematocrit, cell structure and pH upon the z-spectrum in ex vivo human blood for different saturation powers at 7T. The data were analysed using Lorentzian difference (LD) model fitting and AREX (to compensate for changes in T1), which have been successfully used to study CEST effects in vivo. Full Bloch-McConnell fitting was also performed to provide an initial estimate of exchange rates and transverse relaxation rates of the various pools. CEST and NOE signals were observed at 3.5 ppm, -1.7 ppm and -3.5 ppm and were found to originate primarily from the red blood cells (RBCs), although the amide proton transfer (APT) CEST effect, and NOEs showed no dependence upon oxygenation levels. Upon lysing, the APT and NOE signals fell significantly. Different pH levels in blood resulted in changes in both the APT and NOE (at -3.5 ppm), which suggests that this NOE signal is in part an exchange relayed process. These results will be important for assessing in vivo z-spectra.

Quantitative analysis of the z-spectrum using a numerically simulated look-up table: Application to the healthy human brain at 7T.

PURPOSE: To develop a method that fits a multipool model to z-spectra acquired from non-steady state sequences, taking into account the effects of variations in T1 or B1 amplitude and the results estimating the parameters for a four-pool model to describe the z-spectrum from the healthy brain. METHODS: We compared measured spectra with a look-up table (LUT) of possible spectra and investigated the potential advantages of simultaneously considering spectra acquired at different saturation powers (coupled spectra) to provide sensitivity to a range of different physicochemical phenomena. RESULTS: The LUT method provided reproducible results in healthy controls. The average values of the macromolecular pool sizes measured in white matter (WM) and gray matter (GM) of 10 healthy volunteers were 8.9% ± 0.3% (intersubject standard deviation) and 4.4% ± 0.4%, respectively, whereas the average nuclear Overhauser effect pool sizes in WM and GM were 5% ± 0.1% and 3% ± 0.1%, respectively, and average amide proton transfer pool sizes in WM and GM were 0.21% ± 0.03% and 0.20% ± 0.02%, respectively. CONCLUSIONS: The proposed method demonstrated increased robustness when compared with existing methods (such as Lorentzian fitting and asymmetry analysis) while yielding fully quantitative results. The method can be adjusted to measure other parameters relevant to the z-spectrum. Magn Reson Med 78:645-655, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.