Novel diffusion tensor imaging methodology to detect and quantify injured regions and affected brain pathways in traumatic brain injury

Abstract

Purpose: To develop and apply diffusion tensor imaging (DTI)-based normalization methodology for the detection and quantification of sites of traumatic brain injury (TBI) and the impact of injury along specific brain pathways in (a) individual TBI subjects and (b) a TBI group.

Materials and methods: Normalized DTI tractography was conducted in the native space of 12 TBI and 10 age-matched control subjects using the same number of seeds in each subject, distributed at anatomically equivalent locations. Whole-brain tracts from the control group were mapped onto the head of each TBI subject. Differences in the fractional anisotropy (FA) maps between each TBI subject and the control group were computed in a common space using a t test, transformed back to the individual TBI subject's head space, and thresholded to form regions of interest (ROIs) that were used to sort tracts from the control group and the individual TBI subject. Tract counts for a given ROI in each TBI subject were compared to group mean for the same ROI to quantify the impact of injury along affected pathways. The same procedure was used to compare the TBI group to the control group in a common space.

Results: Sites of injury within individual TBI subjects and affected pathways included hippocampal/fornix, inferior fronto-occipital, inferior longitudinal fasciculus, corpus callosum (genu and splenium), cortico-spinal tracts and the uncinate fasciculus. Most of these regions were also detected in the group study.

Conclusions: The DTI normalization methodology presented here enables automatic delineation of ROIs within the heads of individual subjects (or in a group). These ROIs not only localize and quantify the extent of injury, but also quantify the impact of injury on affected pathways in an individual or in a group of TBI subjects.

Fig. 1

Block diagram of the procedure to detect FA changes between an individual TBI subject and a group of controls following normalization of all FA images to a FA template in MNI space. The t-map of the FA differences in MNI space was inverse mapped to the TBI subject's space and thresholded to generate regions of interest (ROIs) showing significant FA changes due to injury.

Fig. 2

Superposition of fronto-occipital tracts from 10 control subjects, obtained after mapping whole-brain tracts from all control subjects onto the head of a TBI subject and sorting in the TBI subject's head-space using a common set of frontal and occipital regions as filters. (left) Axial view, (right) Sagittal view.

Fig. 3

The procedure used to normalize and sort tracts in each TBI subject's space. (top row) Seeds from the standard MNI space were first distributed within each control and TBI subject's head using inverse normalization to maintain the same number of seeds and anatomical equivalency of seed-distribution in each subject. (left to right blocks) Whole-brain tractography was conducted in each subject and all tracts from all control subjects were first mapped to MNI space and then mapped onto the head space of individual TBI subjects. ROIs were identified in the TBI subject's head using the procedure outlined in Fig. 1. Individual ROIs were then extracted one-by-one from the FA-difference map between the TBI subject and controls, and used to sort tracts. An example of a particular ROI (green) is shown at the bottom of the second column. Tracts were sorted in the TBI subject's space using this ROI from all control subjects and the TBI subject, and the mean number of tracts from the control subjects were compared to those from the TBI subject to generate the tract-count metric for this ROI. The sorted and superimposed tracts for this ROI from two normal subjects (in red and purple respectively) and the TBI subject (blue) are shown at the bottom of the third column.

Fig. 4

Comparison of previous tensor reorientation-based normalized tractography (left, in blue) to our normalized approach where all subject space tracts are individually mapped to normalized (MNI-space) using point-to-point transformation (right, in red). Sorting of both sets of normalized tractography was conducted with identical ROIs, located in the frontal and occipital areas (shown in green) in template space. The tracts generated with the previous voxel-based normalization and reoriented tensor method tend to suffer from discontinuity toward the ends. Compared to our approach, the previous method also appears to increase the confounds of partial volume effects (arrows indicate areas of tract discontinuity and redirection around the posterior right corner of the ventricle) due to the interpolation inherent to voxel based normalization.

Fig. 5

FA reduced regions corresponding to t ≥ 3.0 (see color bar) subject 1. An extent threshold k ≥12 was also used to identify clusters. Some FA-reduced identify regions overlap completely, others partially and some do not overlap with the FLAIR spots. (In this montage, the left hemisphere L appears at the right in each image).

Fig. 6

Three pathways, hippocampal/fornix (HC/FX), inferior fronto-occipital (IFO) and inferior longitudinal fasciculus (ILF) identified as crossing the voxels of the highest t-score ROI in a TBI subject (subject 1). (top panel) Coronal, sagittal and axial views of the ROI with color-coding of the t-score as indicated in the color bar. (middle row) The three pathways (HC/FX-red, IFO-magenta, ILF-black) in a normal subject shown in axial and sagittal views. (bottom row) The same three pathways (HC/FX-blue, IFO-magenta, ILF-black) in a TBI subject. (The yellow and green colors in the middle and bottom row pictures were used to identify sub-ROIs within the ROI as described in the text).

Fig. 7

Tract count-based sensitivity (effect size) to differentiate TBI subjects from controls as a function of FA.

Fig. 8

Similar to Fig. 6, pathways associated with two other ROIs within TBI subject 1 are shown in (a) and (b) respectively. Coronal, sagittal and axial views of the two ROIs with color-coding of the t-score as indicated in the color bar are shown in the top row. The ROI in (a) identified tracts through the posterior portion of the corpus callosum, whereas (b) identified the right HC/FX tracts. Like Fig. 6, tracts for a normal subject are shown in red and those in the TBI subject are shown in blue. The reduction of tract-counts in the TBI subject with respect to the control subject is obvious for these ROIs.

Fig. 9

Similar to Fig. 5, the FA reduced regions for TBI subject 2 superimposed on the FLAIR images of the subject. (In this montage, the left hemisphere L appears at the right in each image).

Fig. 10

Similar to Fig. 6, pathways associated with two ROIs in TBI subject 2 are shown in (a) and (b) respectively. The ROI in (a) identified the left HC/FX tracts, whereas (b) identified the right HC/FX tracts. Like Fig. 6, tracts for a normal subject are shown in red and those in the TBI subject are shown in blue. The reduction of tract-counts in the TBI subject with respect to the control subject is obvious in these ROIs.

Fig. 11

A superposition of the FA reduced regions (in color) detected by a SPM based statistical comparison of the TBI group (n=12) to the normal group (n=10) at p_FDR ≤0.05, k ≥ 12 on the FA template in MNI space. Arrows point to the three ROIs (genu of the corpus callosum, hippocampal region, splenium of the corpus callosum) used in Fig. 12

Fig. 12

Similar to Fig. 6, pathways associated with three ROIs identified as FA-reduced regions in the group study between 10 controls and 12 TBI subjects are shown in (a) , (b), and (c) respectively. The ROI in the middle row of (a) identified the left IFO, HC/FX and a portion of the ILF for a normal control subject (IFO: purple, ILF: black, HC/FX: red), (b) identified the anterior portion of the corpus callosum (red) , and (c) identified the posterior portion of the corpus callosum (red). The bottom row shows corresponding tracts identified by the same ROIs in a TBI subject. (bottom row, a) IFO: purple, ILF: black, HC/FX: blue. (bottom row, b) anterior corpus callosum: blue. (bottom row, c) posterior corpus callosum: blue. The reduction of tract-counts in the TBI subject with respect to the control subject is obvious in these ROIs.