assessed at the time of discharge from the rehabilitation unit after TBI (the modal patient had a moderate TBI with GCS score of approximately 8) compared to the late MR imaging findings. As can be seen from this figure, increasing cerebral atrophy, meaning increased nonspe-cific effects of the brain injury, was associated with greater disability at the time of discharge from the rehabilitation unit.
As for an even more long-term outcome, research suggests that the more prevalent the structural abnormal-ities, the greater the neuropsychiatric disability (Bigler 2001a; Jorge et al. 2004; Vasa et al. 2004). There is an-other factor that must be mentioned when discussing out-come: the relationship between significant head injury and the aging process. If brain injury results in atrophy and if brain volume loss also occurs with aging, then age effects in the injured brain may start from different base-lines depending on the age of the patient. This combina-tion may result in less-than-optimal aging (i.e., increased cognitive deficits with aging), increasing the likelihood of neurobehavioral sequelae, including affective disorder (Holsinger et al. 2002) and an earlier age of dementia on-set (Guo et al. 2000; Plassman et al. 2000). Because the hippocampus is one of the structures more vulnerable to injury and is the limbic structure most often implicated in degenerative diseases, it seems reasonable that there is likely a connection.
Many of the studies listed in Appendix 5–1 exam-ined the relationship of quantitative imaging to long-term outcome. Because one of the most frequent cog-nitive sequela to be associated with TBI is impaired memory, various quantitative studies (see Appendix 5–
1) have examined temporal lobe structures and mem-ory in TBI patients. In a detailed analysis of the tempo-ral lobe, Bigler et al. (2002a) demonstrated that changes in WM integrity and volume loss of the hippocampus were the sequelae most related to memory deficits after TBI.
Small but Critical Lesions
There are dedicated pathways in the brain, such as the cor-ticospinal pathway, that have little capacity for adaptation, rerouting, or functional reorganization after significant injury. Accordingly, a small but strategically placed lesion in the internal capsule may produce hemiplegia due to direct injury to the corticospinal tract. For example, the child shown in Figure 5–3 with a right internal capsule–
basal ganglia hemorrhagic shear lesion had a dense hemi-plegia, whereas the patient shown in Figure 5–10, who had massive hemorrhagic lesions bifrontally with concomitant focal frontal atrophy, did not have paralysis. Small but dev-astating lesions may also disrupt the integrity of the limbic
system, where a small lesion of the fornix or fornical atro-phy may be responsible for significant memory deficits (Blumbergs et al. 1994; Tate and Bigler 2000). This situa-tion is shown in Figure 5–7, in which it is clearly visible that the fornix progresses through various degenerative stages postinjury. The hippocampus––another relatively small structure and the origin of the majority of WM pathways that make up the fornix—is also particularly vulnerable to injury that also leads to memory impairment (Tate and Bigler 2000). Small temporal lobe lesions, including those of the hippocampus, may be the source of posttraumatic epilepsy (Diaz-Arrastia et al. 2000). It may also be that small, nonspecific lesions detected by MR imaging are the basis of the relationship between head injury and dementia, as even mild injury increases the risk ratio for dementia (Guo et al. 2000; Plassman et al. 2000).
Functional Lesion Likely Larger Than Structural Lesion
Figure 5–12 depicts the structural injuries sustained by a construction worker in a fall. Acute CT imaging demon-strated the presence of hemorrhagic lesions and midline shift that ultimately resulted in focal right frontal and tem-poral atrophy that was quite extensive (shown in red).
However, when the structural MR imaging was integrated with single-photon emission computed tomography (SPECT), the physiological abnormality could be seen to extend far beyond the boundaries of the focal structural lesions observed on the MR scan; the MR-SPECT scan actually shows a left frontal defect with no concomitant structural abnormality (see Umile et al. 2002).
New Structural Imaging Techniques
F I G U R E 5 – 1 2 . Use of day-of-injury (DOI) computed tomography (CT).
DOI scan (A) showing right subdural hemorrhage, subarachnoid hemorrhage in peri-Sylvian fissure on the right, and significant (white arrow) right-to-left midline shift (B) (gray arrows in frontal region, dark arrows in temporal region). Magnetic resonance (MR) imaging performed 2.5 years later, demonstrating focal frontal and frontotemporal encephalomalacia as permanent sequelae to the DOI lesions observed in A. Single-photon emission computed tomography (SPECT) scan (C) demonstrating significant perfusion abnormalities, particularly in the frontal regions bilaterally and right frontotemporal areas. This can be best viewed in the MR-SPECT fused image (F). A three-dimensional image of the brain (D) outlines the extensive frontotemporal pathology from the right frontal oblique. The pathology from a dorsal perspective is illustrated in E. This figure demonstrates how using the DOI CT as a baseline permits the tracking of subsequent atrophy, how physiological abnormalities often exceed the focal structural pathology, and how all of this can be demonstrated in three dimensions.
F I G U R E 5 – 1 3 . The superiority of magnetic resonance (MR) techniques in detecting pathology.
The computed tomography (CT) scan (A) provides a faint hint of a density change in the corpus callosum. However, both MR images (B, a fluid-attenuated inversion recovery [FLAIR] image; C, a diffusion-weighted [DW] image) clearly demonstrate the abnormality.
This figure shows the superiority of MR techniques in detecting pathology.
D–F A–C
B C
A
Diffusion-tensor imaging (DTI) is another technique that may provide refined detail concerning the integrity of WM in the brain and permit the tracking of aggregate groups of axons and their projection within the brain (Arfa-nakis et al. 2002; Jellison et al. 2004; Lazar et al. 2003; Wa-kana et al. 2004). Two examples of DTI technology are given in Figures 5–14 and 5–15. Figure 5–14 shows how DTI technology capitalizes on two simple biological prin-ciples of brain organization: 1) WM projections in the brain follow orderly projection routes, namely anterior-posterior, lateral, and inferior-superior projections; and 2) WM integrity can be assessed by applying the principle of anisotropy: the diffusion rates of water molecules are de-pendent on the direction of the WM pathway, which can
be determined by the physics and mathematics of vectors, or tensors (hence the name diffusion-tensor imaging). Using DTI, these dispersion differences define the orientation of pathways and can be easily color-coded using the red-green-blue color base (see Figure 5–14).
Such a color map provides in two dimensions what is ac-tually occurring in the three-dimensional space of the brain.
For example, as shown in Figure 5–14, green represents anterior-posterior pathways and red the lateral pathways across the CC; however, just outside the midpoint of the CC, the color turns yellow because the pathways there are coursing in a different direction, resulting in a different color combination. Some pathways, such as the corticospinal pathway, can be easily delineated and highlighted, as shown F I G U R E 5 – 1 4 . RGB (red-green-blue) color diffusion-tensor imaging (DTI).
RGB color DTI images depict the major eigenvector of the diffusion tensor weighted by anisotropy degree. The fibers running from side to side (x-direction) appear red, the fibers running anteriorly to posteriorly appear green (y-direction), and the fibers running superiorly to inferiorly appear blue (z-direction). The fibers running in other directions than x, y, and z appear as a combination of the RGB colors. For example, in the axial image, the corpus callosum appears red at the midline and turns yellow (red plus green) when oriented in xy direction.
In the sagittal image, the cingulum appears mostly green (running in the y-plane) and the corticospinal tract appears blue. Diffusion tensor approximates the diffusion profile of the water molecules existent in the tissue at each sampling point. The diffusion pattern is related to the microstructural properties of the tissue. One important observation is that in white matter fibers (or other fibrous tissues such as muscle), the water diffuses preferentially along the fiber direction. The image in the lower left shows the separation of the corticospinal tract, with an anterior-oblique-axial magnetic resonance view at the level of the temporal-occipital lobes showing the corticospinal tract descending through the cerebral peduncles. This technology will likely be used in studying traumatic brain injury to demonstrate pathway abnormalities produced by shearing and other pathological consequences of injury (see Jellison et al. 2004; Lazar et al. 2003).
Source. Figure courtesy of Mariana Lazar, Ph.D., and Andrew Alexander, Ph.D., University of Wisconsin, Madison.
in Figure 5–14. The implications of such refined image anal-yses are obvious in studying the integrity and effects of TBI on motor, sensory, and language systems that have a known anatomical basis. It is likely that the use of such technology will make possible more refined image analysis of subtle per-turbations associated with TBI. Although these applications are a bit futuristic, DTI has current application in TBI, as il-lustrated in Figure 5–15, which depicts a patient who sus-tained TBI 20 years before DTI. Using what is called frac-tional anisotropy (FA), FA maps of the brain can be created in which brighter voxels represent greater anisotropy and thus greater integrity, directionality, or coherence. As clearly seen in Figure 5–15, through the use of the DTI technique there is a general loss of integrity throughout the brain in severe TBI, particularly in frontal regions.
Last, there is a host of functional imaging methods, dis-cussed in Chapter 6, Functional Imaging, that will be inte-grated with structural imaging in the future for the detec-tion of objective abnormalities that can be related to the neuropsychiatric state of the patient after a brain injury.