Abstract
Registration of subject and control brains to a common anatomical space or template is the basis for quantitatively delineating regions of abnormality in an individual brain. Normally, a brain atlas is chosen as the template. Limitations in the registration process result in persistent differences between individual subject brains and template, which can be a source of error in an analysis. We propose a new approach to the registration process where the subject of interest is the registration template. Through this change, we eliminate errors due to differences between a brain template and a subject’s brain. We applied this method to the analysis of FA values derived from DTI data of 20 individual mTBI patients as compared to 48 healthy controls. Subject-centered analysis resulted in identification of significantly fewer regions of abnormally low FA compared to two separate atlas-centered analyses, with subject-centered abnormalities essentially representing the common subset of abnormal low FA regions detected by the two atlas-centered methods. Whereas each atlas-centered approach demonstrated abnormalities in nearly every subject (19/20 and 20/20), the subject-centered approach demonstrated abnormalities in fewer than half the subjects (9/20). This reduction of diffusion abnormalities observed using the subject-centered approach is due to elimination of misregistration errors that occur when registering the subject of interest to a template. Evaluation of atlas-centered analyses demonstrated that 9.8% to 13.3% of subject GM and CSF was misregistered onto the WM of the brain atlas, resulting in the observation of additional low FA clusters compared to the subject-centered approach. Without careful evaluation, these misregistrations could be misinterpreted as pathology. An additional benefit of the subject-centered approach is that diffusion abnormalities can now be visualized directly in the subject’s anatomical space, rather than interpolating results from the brain atlas space, and can thereby enhance correlation with other components of an imaging protocol.
Highlights
Conventional neuroimaging techniques, such as CT and MRI, readily demonstrate distinct lesions due to many neurological diseases
Locations of these clusters tend to be in regions typical of mTBI injury [22,23]. Both atlas-based registration” (aBR) approaches detected significantly more abnormally low FA clusters than the subject-based registration (sBR) approach, detecting an average of 76.8% fewer abnormally low FA clusters compared to the two aBR methods
The results of the Wilcoxon signed-rank test identified significant differences between the number of abnormally low FA clusters in each of the 20 subjects using the sBR method to those identified in each using the aBR approach (both sBR vs aBR-Johns Hopkins University (JHU) and sBR vs aBR-Montreal Neurological Institute (MNI) had W = 171 (N = 18) one-tailed p-value < 0.0001)
Summary
Conventional neuroimaging techniques, such as CT and MRI, readily demonstrate distinct lesions due to many neurological diseases. These techniques provide a limited window into brain pathology. Advanced MR imaging techniques, such as DTI, reveal additional pathology and offer important additional information that compliments standard imaging. It is increasingly apparent that even small changes in diffusion parameters can indicate clinically significant pathology. The inherent spatial variability of normal MR-derived diffusion measures limits the identification of significant alterations in these parameters by visual inspection. Quantitative methods for detecting regions of abnormal diffusion in a single subject require comparison of diffusion parameter images from the subject to the diffusion parameter images from a normative reference group. In order to ensure that analogous brain regions are compared, one of two basic strategies is followed: a region-of-interest (ROI) based approach or a voxel-based approach [1,2,3,4]
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