Structure or Exchange?
We analyze the feasibility of chemical exchange detection with balanced steady-state free precession experiments in brain tissues at high to ultra-high fields – an in vitro study.

(A) Postmortem imaging of a fresh pig brain hemisphere at 3 T: anatomical MPRAGE (left), color-coded principal diffusion direction map weighted by the fractional anisotropy (middle; anterior-posterior ≡ green, superior-inferior ≡ blue, right-left ≡ red), asymmetry index (AI) map of bSSFPX (right). To analyze the dependency of the bSSFP profile asymmetry on the orientation of the white matter fiber tracts with respect to B0 (≡ superior-inferior axis, blue), the phantom was rotated by about 90° around the anterior-posterior axis as displayed in the second row. The bSSFP frequency profile was assessed in corpus callosum (1) and corticospinal tract (2). (B) The measured 3 T bSSFP frequency response (solid curves) and corresponding non-normalized asymmetries (dashed curves) in corpus callosum (left) and corticospinal tract (right) as defined in (A) along with the calculated normalized AI values. Two different angles with respect to B0 ( ) are analyzed: initial position (blue curves) and ≈ 90° rotation about the anterior-posterior axis relative to the initial position (red curves). (C) Left: Z-spectra reconstructed at an actual irradiation amplitude of B1,mean = 0.5 μT from standard CEST experiments at 9.4 T. Mean Z-values are plotted for a tissue homogenate (tissue volume fraction: 17/20, yellow curves) and the corticospinal tract measured at two different angles relative to B0 (cf. A). Right: Corresponding relaxation-compensated AREX spectra.
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 MnCl2 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 B0.
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 B0. In tracts perpendicular to B0, 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.