Biophysical mechanisms of phase contrast in gradient echo MRI

Abstract

Recently reported contrast in phase images of human and animal brains obtained with gradient-recalled echo MRI holds great promise for the in vivo study of biological tissue structure with substantially improved resolution. Herein we investigate the origins of this contrast and demonstrate that it depends on the tissue ''magnetic architecture'' at the subcellular and cellular levels. This architecture is mostly determined by the structural arrangements of proteins, lipids, non-heme tissue iron, deoxyhemoglobin, and their magnetic susceptibilities. Such magnetic environment affects/shifts magnetic resonance (MR) frequencies of the water molecules moving/diffusing in the tissue. A theoretical framework allowing quantitative evaluation of the corresponding frequency shifts is developed based on the introduced concept of a generalized Lorentzian approximation. It takes into account both tissue architecture and its orientation with respect to the external magnetic field. Theoretical results quantitatively explain frequency contrast between GM, WM, and CSF previously reported in motor cortex area, including the absence of the contrast between WM and CSF. Comparison of theory and experiment also suggests that in a normal human brain, proteins, lipids, and non-heme iron provide comparable contributions to tissue phase contrast; however, the sign of iron and lipid contributions is opposite to the sign of contribution from proteins. These effects of cellular composition and architecture are important for quantification of tissue microstructure based on MRI phase measurements. Also theory predicts the dependence of the signal phase on the orientation of WM fibers, holding promise as additional information for fiber tracking applications. cellular architecture ͉ contrast mechanisms ͉ grey matter ͉ white matter

In vivo assessment of myelination by phase imaging at high magnetic field

“…Against this hypothesis is the observation that the offset is greater in magnitude in the corpus callosum (which is perpendicular to the main magnetic field) than in the anterior commissure (which is close to parallel to the magnetic field~10-20°). Such a modulation is inconsistent with a recently proposed local microstructure contribution (He and Yablonskiy, 2009) that would be characterized by a term proportional to cos 2 (θ)-1/3 if it was assumed that the underlying microstructure of the AC and the CC fiber bundles would be exactly the same. The second mechanism that could explain the variation of polarity of the white gray matter contrast in the absence of myelin would be a variation of the local bulk susceptibility of the surrounding gray matter or of the white matter itself.…”

“…Phase imaging is known to depend not only on the shape of the different structures with different susceptibilities (Marques and Bowtell, 2005;Salomir et al, 2003;Schafer et al, 2009) but also on local microstructure (He and Yablonskiy, 2009), on local anisotropy of the magnetic susceptibility (Lee et al, 2010b;Liu, 2010) and even on nonsusceptibility mechanisms such as water exchange mechanisms (Luo et al, 2010;Shmueli et al, 2011;Zhong et al, 2011). In this study the phase shift observed locally between adjacent structures that remain geometrically unchanged during development was used to estimate myelination.…”

“…One conclusion that can be therefore drawn is that only structures associated with myelin are likely to impact the phase contrast observed between white and gray matter. Other contributions such as the axonal microstructure (He and Yablonskiy, 2009) per se are expected to have a smaller (but not negligible) impact in the contrast. The upper limit of these other contributions towards the final contrast could be estimated from the y axis crossing point in Figs.…”

“…The analysis of the CC is more complex due to the presence of neighboring white matter structures that have different maturation timelines and could affect the phase shift observed between the CC and gray matter. One possible mechanism that could explain the different polarities of the offsets observed in the ac and the cc in the absence of myelin would be an axonal microstructure contribution to the contrast (He and Yablonskiy, 2009). Against this hypothesis is the observation that the offset is greater in magnitude in the corpus callosum (which is perpendicular to the main magnetic field) than in the anterior commissure (which is close to parallel to the magnetic field~10-20°).…”

“…Phase contrast was shown to be affected by tissue lipid and iron content (Duyn et al, 2007;Fukunaga et al, 2010) and the local microstructure (He and Yablonskiy, 2009). The effect of cerebral blood volume has been demonstrated to have a minor, if any, impact on the phase contrast observed between white and gray matter (Lee et al, 2010a;Marques et al, 2009).…”