With the application of DOT techniques becoming more common, across a variety of fields, there is a growing need to develop a method which extracts as much of the spatial information present in DOT as possible, while maintaining the advantages the technique has over other neuroimaging modalities; namely convenience, cost and portability. The atlas-guided DOT approach described here and by Custo et al. (2010)
meets this requirement. As a prerequisite for its extended application we have investigated and quantified the localization error inherent to atlas-guided DOT.
The localization error of atlas-guided DOT has three fundamental sources. The first is the error in registration of the atlas to the subject surface. This error varies from subject to subject and will depend on the accuracy of the measurement of the cranial landmarks and has been estimated by Singh et al., 2005
, to be between 4 and 7 mm. The second is anatomical differences between the subject and the atlas. Even if the affine transformation of the cranial landmarks from the atlas to the subject space is perfectly accurate, there will still be significant differences between the position and folding of the atlas cortex and that of the subject’s cortex. Therefore, the contribution of registration and anatomical differences to the cortical localization is likely to be significantly greater than 4–7 mm, particularly in regions of dense cortical folding.
The third factor contributing to the error of atlas-guided DOT is the inaccuracy of diffuse optical image reconstruction itself, which is dependent on the probe geometry and the sensitivity of that probe in a given subject.
The sensitivity of the simulated probe varies across the cortex and across subjects. Regions which have consistently low sensitivity compared to the subject maximum (such as the pre-frontal cortex, ) clearly yield high localization errors across subjects, ( and ). A comparison of and shows that there are also areas of high localization error in each subject which are not consistent with low probe sensitivity, suggesting that errors in registration and anatomical differences are a significant, if not dominant, source of error in those regions.
The results of our simulation in 32 subject and 32 registered atlas volumes show that the Euclidean error in the localization of brain activations increases two-fold, from 9.1 to 18.0 mm, when an atlas is used in place of the subject’s own MRI. The subject-guided localization error of 9.1 mm should be thought of as the error inherent to diffuse optical image reconstruction in regions of the cortex to which our probe is reasonably sensitive. This figure is in good agreement with previous studies. Boas and Dale (2005)
found the localization error to be between 5 and 10 mm when using a subject’s true anatomy and a similarly dense DOT probe. We can therefore conclude that the additional Euclidean localization error introduced by an atlas-driven approach is on the order of 1 cm.
The significant difference between the Euclidean and geodesic error metrics shown in suggests that in many cases the centroid of brain activation is incorrectly reconstructed on a neighboring gyrus. The largest geodesic errors occur over the frontal poles and around the posterior temporal lobe ( and ), which (due to the limits of the virtual probe) are regions of low sensitivity. Although the geodesic error is smaller in regions of good sensitivity (for example, around the pre-central gyrus, ) it still greatly exceeds the Euclidean error. Our results therefore indicate that those applying atlas-based DOT must be extremely cautious in assigning a region of activation to a particular cortical gyrus, particularly in regions of high dense cortical folding. It is important to note that the geodesic error also significantly exceeds the Euclidean error for subject-specific DOT reconstruction in regions of low sensitivity, though the effect is clearly exacerbated by the errors associated with atlas registration and anatomical variation. It is therefore likely that employing a higher density DOT probe would allow greater confidence in localizing activations to specific gyri for both subject-specific and atlas-based DOT (Dehghani et al., 2009
The Hausdorff distance is a useful metric for quantifying the difference between the shape and size of the reconstructed activations. The fact that the Hausdorff and Euclidean errors are of similar magnitude suggests that the Hausdorff error is generally the result of the shift in position of the peak of activation and that the spatial extent of a simulated activation is, on average, well maintained by DOT.
shows the localization error metrics averaged across all 32 subjects. It is clear from these figures that there is a consistent spatial pattern of localization error, despite there being significant inter-subject variability (). While it is difficult to comment on its significance, this pattern must arise because of a consistent, spatially varying bias. The source of this error could potentially be consistent anatomical differences between the subjects and the atlas. This is a possibility because the Colin27 atlas (which was chosen because of its high resolution) was produced from the repeated MRI scans of a single subject. However, it is also probable that this bias is a manifestation of the cortically varying sensitivity of the virtual DOT probe, which was applied to every subject.
In conclusion, we have performed a validation of a specific anatomical atlas-guided approach to the analysis of DOT data. Although care should be taken in assigning a hemodynamic response to a particular gyrus, atlas-guided DOT can produce reasonably accurate images of cortical activation, and constitutes a suitable functional imaging approach when a spatial resolution of approximately 2 cm is permitted.