Structure or Exchange? On the Feasibility of Chemical Exchange Detection with Balanced Steady‐State Free Precession in Tissue – An In Vitro Study

Abstract

Balanced steady-state free precession imaging has recently been suggested for chemical exchange detection (bSSFPX). The objective of this work is to investigate the contributions of microstructural, chemical shift and chemical exchange effects to the asymmetry of the bSSFP profile at field strengths of 3 T and 9.4 T. To this end, in vitro bSSFPX experiments are performed for a range of repetition times and flip angles in glucose water solutions with different MnCl 2 concentrations and tissue homogenates obtained from the brainstem of pig brains. The experimental results are compared to multi-pool Bloch-McConnell simulations. Additionally, the influence of white matter tract geometry is analyzed ex vivo in pig brain hemispheres measured at two different angles with respect to B 0 .The detectable bSSFP profile asymmetry in glucose solutions with tissue-like relaxation times and white matter homogenates was consistent with Bloch-McConnell simulations but relatively small. In intact white matter tracts, the asymmetry was dominated by structural effects with a strong dependency on tract orientation relative to B 0 . In tracts perpendicular to B 0 , the asymmetry was ≈ 3-4 times higher than in the homogenates, thus barely affected by chemical exchange effects. In conclusion, chemical exchange-related bSSFP profile asymmetries are detectable in tissue homogenates, however, the observed asymmetry level is generally low and prone to confounding structural effects rendering in vivo chemical exchange detection with bSSFP challenging in the brain. KEYWORDSbSSFP, profile asymmetry, chemical exchange, glucose, white matter, pig brain | INTRODUCTIONThe MR signal acquired with a balanced steady-state free precession (bSSFP) sequence is known to be considerably off-resonance sensitive 1 and thus to carry information about the frequency content in a voxel. Tissues can generally not be described by a single T 1 , T 2 , and resonance Abbreviations: AI, asymmetry index; AREX, apparent exchange-dependent relaxation; APT, amide proton transfer; B 0 /B 1 , static/transmit magnetic field; bSSFP, balanced steady-state free

Intravascular BOLD signal characterization of balanced SSFP experiments in human blood at high to ultrahigh fields

“…This may include simulations and experiments to gain more insights into the possible mechanisms driving the bSSFP profile asymmetry observed in oxygenated blood samples (Figure 4), such as diffusion 14 or chemical exchange effects. 53,54…”

“…Future studies may focus on analyzing the dependence of MIRACLE‐R 2 on TR and flip angle in more detail, to ultimately establish a quantitative model for given blood oxygenation levels and field strengths. This may include simulations and experiments to gain more insights into the possible mechanisms driving the bSSFP profile asymmetry observed in oxygenated blood samples (Figure 4), such as diffusion 14 or chemical exchange effects 53,54 …”

High‐resolution neural network‐driven mapping of multiple diffusion metrics leveraging asymmetries in the balanced steady‐state free precession frequency profile

“…33 The results of a recent study investigating the contribution of chemical exchange effects to asymmetric intravoxel frequency distributions in WM corroborate that the main factor driving bSSFP profile asymmetries in WM is structure-and not exchange-related. 35 This inherent sensitivity to tissue microstructure, combined with a mixed dependence on both T 1 and T 2 , as well as the ability to enable distortion-free motion-robust volumetric imaging with high signal-to-noise ratio efficiency in short scan times, 36,37 makes phase-cycled bSSFP an interesting tool for multiparametric mapping of various MR quantities. [38][39][40] Because off-resonance effects in the bSSFP signal arising from B 0 inhomogeneities are used as an additional encoding dimension for multiparametric mapping, phase-cycled bSSFP is well suited for high-resolution imaging at ultrahigh field strength.…”

Multi‐parametric artificial neural network fitting of phase‐cycled balanced steady‐state free precession data

“…It has been reported that an asymmetric frequency distribution causes asymmetries in the bSSFP frequency profile. [17][18][19] MIRACLE and PLANET fail to account for these anisotropies in the tissue microenvironment, but assume an idealized model for the bSSFP profile, ie, a symmetric frequency response. 15,20 To eliminate this bias, a feedforward artificial neural network (ANN) is trained in this work with phase-cycled bSSFP data acquired at 3T in healthy volunteers as input and a multi-parametric output, ie, T 1 , T 2 , transmit field B + 1 , and off-resonance ∆B 0 , using dedicated reference relaxation time measurements and field maps as targets.…”

“…This bias is especially prominent in white matter (WM) and expected to be caused by an asymmetric intra‐voxel frequency content due to fiber tract geometry, in combination with multi‐component relaxation, eg, due to the presence of myelin. It has been reported that an asymmetric frequency distribution causes asymmetries in the bSSFP frequency profile 17‐19 . MIRACLE and PLANET fail to account for these anisotropies in the tissue microenvironment, but assume an idealized model for the bSSFP profile, ie, a symmetric frequency response 15,20 …”