Researchers interested in characterization of White Matter (WM) and R₂ mapping.In this study we investigate the orientation dependence of transverse relaxivity (R₂) maps in WM. Diffusion MRI has been widely used to map WM fibre orientations yet, it cannot provide information on myelin integrity or volume fraction. Apparent transverse relaxivity (R^*₂) has been shown to vary as a function of fibre orientation [1] due to the susceptibility effects generated by the structurally organized myelin. Such susceptibility effects of microstructure are expected to be present also on R₂ maps in the fast diffusion regime. In this abstract we demonstrate this hypothesis in-vivo and study the level of anisotropy across brain fibre populations.

Data from six subjects was acquired on a 3T scanner (Magnetom Prisma, Siemens Healthcare, Germany) using a 32 channel head coil with a protocol approved by the local ethics committee. The following sequences were used:

1-R₁ mapping MP2RAGE [2]: TR/TI1/TI2/TE=6000/700/2000/2.34msec; FA1/FA2=6^o/5^o; res:1mm isotropic; Taq=7min32sec;

2- DWI EPI: TR/TE=3490/74.6msec; res:1.5mm isotropic; matrix=150x150x90; b-value=1000s/mm²; diffusion encoding directions=137; MBfactor=3; Taq=8min47sec;

3- Model-based accelerated R₂ mapping multi-echo-spin-echo (MESE) prototype sequence [3]: TR/TE1/TE10=4080/9.6/96msec; BW=363Hz/px; res:1.5mm isotropic; MARTINI [4] undersampling=3; GRAPPA=2; slices=80; Taq=2min53sec.

The R₂ mapping protocol was repeated 6-7 times with the subject's head rotated along different orientations with respect to the main magnetic field (B₀). Data was processed using custom-developed Matlab scripts and FSL tools [5]. R₂ maps acquired with different head orientation were co-registed to the diffusion imaging space. The post-processed DWI was used to calculate angle maps (θ) between the main fibres relative to B₀. The R₂ co-registration matrices were used to calculate the θ maps of the different fibres in the different positions. Finally, five WM fibre masks were created using probabilistic tractography (probtrackX from FSL), see Fig.1c. The R₂ values measured in each fibre in different head positions were decomposed into an orientation independent (isotropic component, R_2iso) and an orientation dependent (anisotropic component, R_2aniso) part by applying the model: $$$R_2=R_{2iso}+R_{2aniso}sin^4(\theta)$$$

Figure 1 shows the contrast seen in R₂ maps and its visual correlation with diffusion main orientations. In Figure 2, the fitting model is plotted along with the 10^th, 50^th and 90^th percentiles of the measured R₂ of fibres (as shown on Fig.1c) for one subject as a function of θ. It can be seen that, for both the total WM inside the masks (in agreement with previous reports [6]) and for each fibre mask, the fitting of the R₂ values within each mask closely matches the 50^th percentile curve. Interestingly it can be seen that different fibres have different levels of orientation dependence.

The variations of the mean R₁ over the 6 subjects (Fig.3c) are small (0.05 Hz) when compared to the R₂ isotropic values (Fig. 3a), ruling out contributions of R₁ contamination due to slice profile on the measured R₂.

From the R₂ isotropic bars it is seen that the corticospinal tracts (CST) and forceps major present inferior values than the rest of the fibres which could be attributed to water mobility and axonal size. On the other hand, Fig. 3b shows that the cingulum and forceps major and minor all present significant orientation-dependent R₂ (of similar amplitude on left and right hemispheres), while the inferior long fasciculus (ILF) shows no significant anisotropic effects, suggesting reduced susceptibility effects. The CST have the largest variability of anisotropy which might be related with the smaller range of θ values (see Fig. 3d) observed even after the 6 head rotations. This is due to the combination of the restricted space for head movement inside the head coil (rotation <30^o in all directions) and the fiber orientation with respect to B₀ that lead to a further restriction on sin⁴(θ) values.

Regional WM variations of R₂ were observed; for example, anterior WM had increased relaxivity in respect to posterior WM. It was shown that the orientation of WM fibres influences R₂ contrast. For both the anisotropic and isotropic R₂ of different fibres, coherence between hemispheres was observed. Isotropic values were very similar for most fibres with the exception of the CST and forceps major which could be associated with their different diameter [7, 8]. As for the anisotropic component of R₂, this should be associated with the susceptibility effects from myelin. The lowest effects (0 Hz) were observed in the ILF and the largest effects ranging around 1Hz were found on the cingulum and the CST. Future work should be directed to ex-vivo samples where larger rotations can be achieved allowing a more robust assessment of the orientation dependence of R₂.