Upon initial inspection of the scans, we noted that after the B1-receive field correction a high degree of residual non-uniformity centred in the brain persisted. This was more pronounced in the MP-RAGE compared to the SPGR sequence and is quantitatively shown by Figs. and . Thus it is likely that different pulse sequences are affected to varying degrees by non-uniformity in 3-T scanning.
Visual inspection of the N3-corrected scans indicated the residual non-uniformity was considerably reduced when using accurate masks and smaller smoothing distances, as indicated in Figs. -. The quantitative measures support our assumption that masks with greater clarity in the histogram improves the correction, and also that reducing the smoothing distance encapsulates the form of the non-uniformity field more accurately. For both the white matter and normalized difference images, the variance is significantly reduced as the accuracy of the masks increase and the smoothing distance decreases. These quantitative measurements are consistent with the findings of our visual assessments.
Upon inspection of the masks that were created (), the most notable problem is the number of failures in the thresholded masking technique for the MP-RAGE scans. Overall the mask included a significant amount of non-brain (also the case for the SPGR thresholded masks), with CSF and sometimes brain being excluded. This may explain the poor performance of the non-uniformity correction associated with this mask for both pulse sequences, as not enough distinct tissue classes are made available to N3. The sensitivity of the threshold on the MP-RAGE scans to the non-uniformity is an important problem; clearly a masking technique should be independent of any non-uniformity to be of any practical use. For both masks derived from the 6-dof and 12-dof template registration techniques, we used an entropy-based measure (NMI) as the cost function for the registration, which should be largely independent of any non-uniformity present in the scan (Maes et al., 1997
). Despite this the four masking failures on the single subject when using the 12-dof registration show that the technique is not completely robust, and suggest that the use of a different template (e.g., one created from a group of aged normal controls) may be more appropriate. Although the registration technique has been shown to be highly robust (Smith et al., 2002
), it would be advisable to check the generated masks prior to N3 correction (e.g., range checking of the volume or visual inspection), and any of poor quality interactively edited.
When comparing the correction using the template 12-dof mask to the semi-automated (Manual) correction, it is apparent on both MP-RAGE and SPGR scans that the variance results are more tightly clustered over the different smoothing distances. For the MP-RAGE corrections at the 100- and 50-mm distances there is little to choose between the template 12 dof and Manual masks, while at the 150- and 200-mm distances the template 12-dof mask is inferior. For the SPGR sequence the 50-mm smoothing distance performed better than the 100 mm in both WM and paired difference variance assessments.
We initially expected that including CSF in any mask would improve the performance of N3 as another, distinct tissue class would be included, and the greater volume would encapsulate more of the non-uniformity, leading to higher accuracy. However, this was not the case, as there was no significant difference between the Manual-CSF and Manual+CSF masks at any smoothing distance, indicating that two tissue classes suffice. This finding suggests that the template MNI 152 template mask we created could be altered to include less extra-sulcal CSF, which may reduce the amount of tissue external to the brain cavity included in the incoming scan, further improving the template-based correction.
In determining an ideal smoothing distance, the quantitative results of the MP-RAGE indicate that 50 mm and 100 mm are significantly better than 150 or 200 mm, with a minimal improvement between 50 and 100 mm in our assessment. For the SPGR scans, there is greater benefit in using a smaller smoothing distance of 50 mm, as shown in Figs. and . However, smaller distances will naturally smooth out any variance; the key is that it must smooth only non-uniformity, not noise or anatomical variation. We believe that no slowly varying anatomical variance should occur over a spatial scale of 50 mm, and thus N3 should not be capable of removing any anatomical features in the scans. We checked this by visually inspecting some of the 50 mm corrected scans and found that no naturally occurring variance was eliminated.
One of the parameters of N3 that was not considered in this paper is the FWHM, which is used to describe the assumed distribution of the non-uniformity field. In this paper it was chosen to be 0.05, in order to favor accuracy over speed. Sled noted this and also suggested a varied approach to the FWHM parameter during the correction procedure, leading to faster convergence but reduced accuracy of the estimated non-uniformity field. This idea was not explored and could be in future to obtain more accuracy with less computational cost.
The main finding of this work is that the reliability and robustness of the N3 algorithm for correcting non-uniformity in 3-T head scans for different pulse sequences can be improved by considered selection of brain masks and the smoothing parameter. N3 cannot be assumed to perform well for a wide range of scanners and coils using just the default parameters. We conclude that for 3-T brain imaging using phased array receiver coils a spline distance of 50 mm should be chosen and a brain mask provided which excludes non-brain tissues, as inclusion of CSF spaces does not appear essential. Automated brain masks created using 12-dof registration of a brain template performed well although checking of the masks or anomalous results is recommended. An informed selection of the smoothing distance can be made using visual inspection and knowledge of the sequence, coil and field strength. These factors are likely to be particularly important for other higher field scanners and phased array coils.