The z-spectrum from human blood at 7T

Simon M Shah,Olivier E Mougin,Andrew J Carradus,Nicolas Geades,Richard Dury,William Morley,Penny A Gowland

doi:10.1016/j.neuroimage.2017.10.053

Abstract

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.

Highlights

Z-spectrum features, in particular chemical exchange saturation transfer (CEST) have recently been used to study both healthy and pathological tissues in vivo (van Zijl and Yadav, 2011; Zaiss and Bachert, 2013; Liu et al, 2013), but so far there has only been one study of the zspectrum of blood (Zheng et al, 2014)
Both spectra suggest high Amide proton transfer (APT) and amine signals and low nuclear Overhauser enhancement (NOE) signals in the sagittal sinus compared to white matter and grey matter
The SO2 of the deoxygenated and control blood was approximately 40% and 80% respectively. Both samples’ oxygenation levels changed during the experiment because the gas in the space above the blood in the vials continued to exchange with the red blood cells

Summary

Introduction

Z-spectrum features, in particular chemical exchange saturation transfer (CEST) have recently been used to study both healthy and pathological tissues in vivo (van Zijl and Yadav, 2011; Zaiss and Bachert, 2013; Liu et al, 2013), but so far there has only been one study of the zspectrum of blood (Zheng et al, 2014). CEST (Zaiss and Bachert, 2013; Ward et al, 2000; Zhou and van Zijl, 2006) uses the principles of magnetisation transfer (MT) to investigate moieties containing labile protons by applying saturation at their resonant frequency and detecting the subsequent transfer of the saturation to the water pool via chemical exchange. Jones et al investigated multiple NOE peaks associated with the macromolecule MRS spectrum (Jones et al, 2013), and Zhang et al observed a ‘new NOE peak around -1.6 ppm’ and showed it was reduced in ischemic stroke (Zhang et al, 2016)

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