The balanced steady-state free precession (bSSFP) profile is known to carry information about the tissue-dependent frequency content in a voxel. There has been strong evidence that the observed asymmetries in the bSSFP profile of white matter depend on the tract orientation with the largest asymmetries occurring in tracts perpendicular to B0. Recently, it was demonstrated that the bSSFP sequence can be used for chemical exchange detection based on profile asymmetries arising in isotropic probes of two exchanging pools. In this work, we explore the question whether exchanging species might contribute to the bSSFP profile asymmetry observed in white matter.
The pronounced asymmetries found in the balanced steady-state free precession (bSSFP) frequency profile of white matter (WM) 1 exhibit a strong sensitivity to the orientation of the fiber tracts with respect to B0 2,3. These results suggest a relation to anisotropies in the tissue microenvironment 4. On the other hand, bSSFP imaging was reported to be intrinsically sensitive to chemical exchange processes leading to asymmetric profiles in isotropic probes of exchanging moieties 5. Here, we investigate the bSSFP profile as well as chemical exchange saturation transfer (CEST) experiments in homogenized pig brain tissue to eliminate structural effects.
Pig brain tissue preparation.
A homogenate (probe 1, cf. Fig. 1) was prepared from the brainstem of pig brains using a tissue grinder (capacity: 40ml, tube length: 215mm, pestle clearance: ~45µm). The obtained homogenized tissue was filled into a 25ml tube. For comparison, a second 25ml tube (probe 2, cf. Fig. 1) was filled with intact brainstem (i.e., intact white matter tracts). It was not ensured to maintain a predominant WM tract orientation in probe 2.
MR acquisition protocol.
The measurements were performed at 9.4T using a custom-built head coil (16 transmit/31 receive channels) 6. 3D bSSFP data were acquired with an in-plane resolution of 1.2x1.2mm2 and a slice thickness of 2mm (TR=3.80ms, matrix size: 130x126x24). The frequency profile was sampled at 60 measurement points using RF phase-cycles which covered a range of 400° in steps of 6.66°, thus ensuring to acquire the entire bandwidth in the presence of frequency drifts. Each phase-cycle acquisition was preceded by 256 dummy pulses. A set of three flip angles (αnom=[7, 9, 11]°) were acquired (scan time/αnom: 16min 11s). The αnom=11°-scan was repeated with negative frequency sweep to exclude transient effects that were seen to cause profile asymmetries 1. CEST imaging was performed with a spectrally but not spatially selective saturation period of 5s (B1,mean=[0.6, 0.9, 1.2]µT) and a subsequent single-shot centric-spiral reordered 3D gradient-echo readout (TR=3.82ms, αnom=5°, in-plane resolution: 1.4x1.4mm2, slice thickness: 2mm, matrix size: 112x112x18, scan time/B1,mean: 5min 32s) 7. B0 and B1 field maps were acquired using the WASABI method 8 and used for B0-/B1-correction 9; T1 maps were derived from adiabatic saturation recovery images.
Assessment of asymmetries.
The acquired raw bSSFP profiles were centered (B0-corrected) on a voxel-wise basis 2. Profile asymmetry was defined by the anisotropy index (AI):
$$AI = \frac{h_{p}-h_{n}}{h_{p}+h_{n}}$$
(hp,n: signal peaks at positive (p) and negative (n) frequency offsets relative to the banding 2). To investigate the effect of B1 variations on profile asymmetries, the AI values derived from three scans with varying flip angles were binned according to their actual flip angle αact=cB1·αnom (cB1: B1 scaling factor) and averaged. CEST asymmetry maps (MTRasym) were calculated at -3.5ppm since the Z-spectra are dominated by nuclear Overhauser enhancement (NOE) effects at the used low power (B1,mean=0.6µT).
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