Two-dimensional magnetization-transfer - CPMG MRI reveals tract-specific signatures in fixed rat spinal cord

Multiexponential T₂ (MET₂) Relaxometry and Magnetization Transfer (MT) are among the most promising MRI-derived techniques for white matter (WM) characterization. Both techniques are shown to have histologically correlated sensitivity to myelin, but these correlations are not fully understood. Furthermore, MET₂ and MT report on different WM features, thus they can be considered specific to different (patho)physiological states. Two-dimensional studies potentially resolving interactions, such as those commonly used in NMR, have been rarely performed in this context. Here, we investigated how off-resonance irradiation affects different MET₂ components in fixed rat spinal cord white matter at 16.4 T. These 2D MT-MET₂ experiments reveal that MT affects both short and long T₂ components in a tract-specific fashion. The spatially distinct signal modulations enhanced contrast between microstructurally-distinct spinal cord tracts. Two hypotheses to explain these findings were proposed: either selective elimination of a short T₂ component through pre-saturation combines with intercompartmental water exchange effects occurring on the irradiation timescale; or, other macromolecular species that exist within the tissue - other than myelin - such as neurofilaments, may be involved in the apparent microstructural segregation of the spinal cord (SC) from MET₂. Though further investigation is required to elucidate the underlying mechanism, this phenomenon adds a new dimension for WM characterization.