Because neurotrauma often exhibits multiple, overlapping forms of focal and/or diffuse injury, insight from TBI imaging can be enhanced through the use of multimodal techniques. In what follows, the results of each segmentation and 3D model generation are reviewed and the procedures used to perform tissue classification are illustrated. For each patient, we provide six canonical views of ventricles and non-hemorrhagic and hemorrhagic lesions, thus allowing the reader to fully appreciate the 3D nature of TBI as well as the abilities of 3D Slicer to dynamically render and capture the complexities of severe brain pathology.
As reveals, Patient 1 exhibits a large deep-brain injury that is hyperintense in the FLAIR image () because of perfusion by CSF from the ventricular system. Contralaterally with respect to this injury, a smaller insult in the deep WM is also apparent in T1-weighted, FLAIR and GRE images (, respectively). The posterior portion of the left ventricle seems larger than the corresponding part of the right ventricle, possibly because of local WM inflammation. Additionally, FLAIR seems to reveal some DAI in the area surrounding the primary injury (yellow arrows), whereas GRE demonstrates the presence of hemorrhage both adjacent to and remote from the primary insult (, green arrows). Therefore, the inclusion of a GRE sequence is particularly useful in this case because DAI can be visualized indirectly through shear hemorrhages caused by blood vessel lesions (Scheid et al., 2003
). suggests that the ability to characterize TBI is greatly enhanced by the use of SWI. As already quantified in detail by other authors (Tong et al., 2003
) and illustrated in , this technique is very sensitive in the detection of extravascular blood products, which is illustrated by SWI's identification of significant hemorrhage surrounding the primary injury, as well as diffusely throughout the brain (). A 3D animation of the segmentation for this patient is available in the Supplementary Material
(see online supplementary material at http://www.liebertonline.com
FIG. 1. Sample MR images acquired from Patient 1 using the standard protocol. The first and second columns contain images acquired at acute baseline and chronic follow-up, respectively. Shown from top to bottom are T1-weighted MP-RAGE images (A), T2-weighted (more ...)
In , the results of the TBI segmentation for Patient 1 are shown. Each row displays one of six canonical views (left, right, dorsal, ventral, anterior, and posterior) of the MR-segmented brain, with every column corresponding to one particular structure type (ventricles, non-hemorrhagic lesions, hemorrhagic lesions, and the full model). In each image, extracortical lesions, GM, and WM are transparent, whereas the ventricular system is additionally transparent in rows 2–5 to facilitate visualizing the relative position of each structure type with respect to other cortical landmarks. shows 3D views of the ventricular system, with arrows drawing attention to anatomical changes caused by pathology. As previously posited based on , this volumetric analysis reflects the large extent of the primary injury, as well as the significant amount of bleeding present in the WM. The posterior part of the left ventricle is found to have been slightly enlarged as a consequence of the lesion compressing its anterior portion (). By comparison, the posterior part of the right ventricle appears thinner, although its anterior portion is larger because of the primary insult being located contralaterally with respect to the latter (). also illustrate the large volume of the primary injury, which covers a large spatial extent mainly in the left hemisphere and extends from the inferior to the superior extremity of the brain. In , standard views of the full 3D segmentation model are shown in which all structures are visible, with the exception of the WM and GM models, which are omitted for visual clarity. The 3D model of subdural edema is shown as transparent (green color) so as not to obstruct the view of the brain. The full model perspective has the advantage of allowing one to visualize and summarize all forms of TBI-related pathology as displayed in the other columns.
FIG. 2. Three-dimensional models of TBI anatomy for Patient 1 (acute baseline time point), as generated in 3D Slicer. Each row displays one of six canonical views of the brain, whereas each column corresponds to a structure type (ventricles, non-hemorrhagic lesions, (more ...)
displays the segmentations of volumes acquired from Patient 1 during the chronic follow-up session. Although the ventricular system appears to exhibit improved bilateral symmetry () and the combined volume of bleeds as extracted from GRE and SWI imaging appears to be much smaller than in the acute scan (), the latter cannot be stated regarding the volume of the scar caused by the primary injury (). In fact, the volume of the lesion does not appear to have decreased appreciably at follow-up. This is confirmed in , in which a visual time point analysis of the volumes associated with each structure is performed. For the purpose of the latter, all lesions in the acute baseline volume (whether hemorrhagic or non-hemorrhagic) are displayed jointly in red, whereas the lesions and bleeds at follow-up are shown in green. This avoids the highly problematic task of differentiating lesions in the follow-up model according to their provenience (i.e., from hemorrhagic or non-hemorrhagic regions in the acute baseline model), while still allowing one to perform a visual and quantitative comparison of the two time points.
FIG. 4. Time point comparison of TBI in Patient 1 using 3D Slicer-generated volumes displayed in red (for the acute baseline time point), or green (for the chronic follow-up time point). As in and , each row displays one of six canonical (more ...)
In , results of the time point comparison for Patient 1 are displayed. The left view of the GM volume reveals important decrease in inflammation at the follow-up time point, particularly over dorsolateral frontal, prefrontal, parietal, and superior temporal cortex. Comparison of the acute and chronic WM volumes, on the other hand, suggests substantial decrease in inflammation over the entire frontal and prefrontal cortex, as well as more diffusely over the other cortical lobes. In this subject, comparison of the volumes associated with lesions portrays the acute baseline lesions as encasing those imaged at the chronic follow-up time point, which again suggests substantial decrease in injury extent. The longitudinal analysis in suggests that Patient 1 exhibits only a small longitudinal change in the volume of the ventricular system. This is confirmed by the quantitative analysis reported in , where it is seen that there is only a 1.3% increase in ventricular volume between the acute and chronic time points. By contrast, in agreement with , both hemorrhagic and non-hemorrhagic lesions are found to decrease in volume substantially, that is, by over 76%. Among the metrics used for quantification of atrophy, Evan's index registers the largest percentage change (11.42%) from the acute to the chronic time point. (See for numerical values of this and other measures in each subject.)
Longitudinal Analysis of Three Selected Volumetric Structures (Ventricular System, Non-Hemorrhagic Lesions, and Hemorrhagic Lesions) in Three TBI Patients
Indices of Atrophy Computed for Three Sample Subjects
Whereas Patient 1 illustrates the effects of a large WM lesion caused by a blunt, closed-head trauma, the imaging of Patient 2 illustrates the damage to the brain caused by a gunshot wound. In this latter case, all imaging modalities reveal extensive—both focal and diffuse—injuries in the left hemisphere, with particularly obvious damage to the temporal lobe, both laterally and medially (). In addition, all modalities reveal injuries to the cerebellum and brainstem, with FLAIR showing large portions of these structures being perfused by CSF (). The medial aspect of the right temporal lobe as imaged using FLAIR and GRE T2 suggests the existence of an insult in this structure as well. In the acute scan slices displayed, the size and extent of the primary injury make the left ventricle essentially indiscernible. All modalities hint at the presence of extensive extracortical insults, whereas GRE T2-weighted and SWI images demonstrate the presence of significant hemorrhage (). The images acquired during the chronic scan session illustrate significant left ventricular hypertrophy, presumably because of WM loss, whereas GM loss is also obvious, especially as seen on the lateral aspect of the left temporal lobe. A 3D animation of the segmentation for this patient is available in the Supplementary Material
(see online supplementary material at http://www.liebertonline.com
In Patient 2, the segmentations of the MR volumes acquired during the acute TBI scan () reveal the presence of substantial loss of volume in the left ventricle as well as notable extracortical insults. Both hemorrhagic and non-hemorrhagic cerebral lesions are found to cover large portions of the temporal lobe, with some injuries also being present dorsofrontally in the left hemisphere as well as in the periventricular region of the anteromedial right hemisphere. The segmentation of the MR data set acquired at follow-up () confirms that Patient 2 exhibits significant enlargement of the lateral ventricle ipsilateral to the primary insult, with large portions of the ventrolateral temporal lobe exhibiting low-density, CSF-perfused tissue ().
Time point comparison of the GM volume in this subject hints to significant lateral shift of the longitudinal fissure (, dorsal view), substantial decrease in frontal lobe GM volume as a consequence of decreased inflammation (, right and left views), and large decrease in left temporal lobe lesion size (, ventral view) amounting to a non-hemorrhagic lesion volume that is 63.6% smaller than that at the acute baseline time point (). Comparison of the ventricular system between acute baseline and chronic follow-up () confirms the significant increase in volume of the left ventricle and decrease in volume of the right ventricle. Whereas the former is probably the result of the replacement of injured WM by CSF, the latter is possibly caused at least in part, by the decrease in intracranial pressure between the two time points. As summarized in , the increase is over 50
, which amounts to a 107% increase with respect to the ventricular volume at the acute time point. The obvious lateral shift in the position of the fourth ventricle (, anterior and posterior views) appears to confirm the noteworthy finding that the midline has been shifted to the left during the chronic period. This impression is strengthened by the fact that lesion volume is smaller at follow-up compared to baseline (). In Patient 2, the bicaudate and ventricular indices have the largest percentage changes at follow-up compared to baseline (26.89% and 15.15%, respectively).
Shown in are MR images acquired from Patient 3. As in the previous patient, one can note an extensive primary TBI covering a significant portion of the left temporal lobe, including the inferior, middle, and superior temporal gyri and sulci. Smaller insults include lesions to the frontopolar region of both hemispheres, as well as bilateral subdural edema over substantial lateral portions of the frontal, parietal, temporal, and occipital lobes. Insults are visible as hypointensities in T1-weighted MP-RAGE images () and as hyperintensities in T2-weighted TSE images (). FLAIR images () reveal hyperintense, CSF-perfused lesions located bilaterally in the frontal lobe, as well as a primary insult in the left temporal lobe. Focal and hyperintense periventricular lesions are also visible throughout the volume. presents T2-weighted GRE images, with hypointensities present in both the acute baseline and follow-up volumes. In the present case, this type of imaging reveals hypointense, CSF-perfused lesions () as well as some chronic injuries in proximity to the left ventricle. MR volumes available from the extended protocol () provide confirmation of these findings, with additional identification of micro-bleeds being made possible from the mIP angiography volume, which allows one to identify the existence of numerous additional micro-bleeds throughout the brain (). Oxygen extraction factor (OEF) ), DTI images (), and DWI-based apparent diffusion coefficient (ADC) maps () additionally confirm the existence and extent of lesions. Because ADC represents the algebraic sum of vasogenic (increased ADC) and cellular (decreased ADC) brain edema, the ADC maps () can be used to confirm the presence of edemic regions as identified using FLAIR, as well as T1 and T2 images. Whereas mIP () and DWI () are both useful for the identification of hemorrhage, demonstrates the improved ability of SWI to localize hemorrhages and micro-bleeds, some of which are not visible using the former two techniques. In addition, SWI is capable of identifying micro-bleeds present in the follow-up scans (, left).
Inspection of the left and right views of the brain as reconstructed in reveals left–right asymmetry of the lateral ventricles, possibly partly caused by inflammation. The temporal horn of the left ventricle is positioned slightly above the horizontal plane of the right ventricle (left and right views), and its location is also seen to have shifted more medially (dorsal and ventral views). displays non-hemorrhagic cerebral lesions. The primary lesion occupies a significant volumetric extent within the temporal lobe of the left hemisphere, with smaller lesions in the frontopolar areas of both hemispheres as well as smaller, contrecoup lesions in the right temporal lobe. reveals that some portions of these lesions are hemorrhagic, with significant bleeding in the left temporal lobe and in the frontal lobes. A 3D animation of the segmentation for this patient is available in the Supplementary Material
(see online supplementary material at http://www.liebertonline.com
showcases the results of segmenting the MR volumes acquired during the follow-up session. In the case of the ventricular system (), as one might expect as a result of partial recovery, there is considerably more lateral symmetry than in the acute case. Approximately 8 months after acute injury, the lesion in the left temporal lobe is seen to have progressed into a structure () consisting of low-density WM and/or GM perfused by CSF. Diffuse bleeds are identified throughout the brain (), mostly in areas that appear to hemorrhage in the acute baseline volume, although a few also appear in new locations (see arrows). Overall, the full model of the anatomy at follow-up () indicates noteworthy improvement after 8 months of recovery and treatment.
shows the results of the time point comparison for the third patient. In the case of the GM volume, surface displacement is visible in the acute baseline case compared to the follow-up case. For example, the view of the left hemisphere reveals this to be true particularly in occipital, parietal, and dorsofrontal areas, where the segmented GM surface for the acute baseline model (red) lies above the corresponding surface for the follow-up case (green). For the right hemisphere, the dorsal view of the GM models has large portions of the acute baseline volume lying atop the follow-up volume, and vice versa for the left hemisphere. This obviates a clear rightward shift of the GM in the acute baseline case, presumably as a result of inflammation in the left temporal lobe. Confirmation of this impression is suggested by the ventral view of the brain, where it is seen that the temporal lobe and frontopolar regions are both larger in the acute baseline.
The time point comparison of the WM volumes also indicates the presence of large differences between the two time points. The right and left views reveal a striped appearance of the two superposed models, with the crowns of gyri in the baseline volume consistently atop the corresponding gyral crowns in the follow-up volume, and vice versa for the troughs of gyri. This relative positioning of the two surfaces is consistent with the scenario of diffuse inflammation throughout the acute baseline WM volume, and possibly with the presence of DAI at the GM–WM boundary. In addition to these findings, the time point comparison of WM confirms the impressions formed from inspecting the GM volumes, where a general rightward shift of the brain had been found. This scenario is confirmed by exploring the time point comparison of the ventricular system where, in the acute baseline model, the left ventricle (ipsilateral to the primary insult) is positioned above the level corresponding to the follow-up model. This situation is reversed for the contralateral (right) hemisphere, suggesting a shearing transformation between the two models wherein the acute baseline brain mass is rotated counterclockwise about the anteroposterior axis as a result of the primary injury. This scenario is confirmed by the clear shift of the fourth ventricle in the acute baseline model (red) toward the left hemisphere, compared to the position of this ventricle in the follow-up model. Similar shifts are observed for the ventricular horns in the anterior and posterior views of .
As shown in , the time point comparison of Patient 3 reveals significant decreases in the total volume of injured brain regions, especially with regard to frontal lobe lesions as well as micro-bleeds located diffusely throughout the brain. As outlined in , the former are found to have a combined volume that is significantly smaller at chronic follow-up (0.9
) than at acute baseline (54.7
). A similar impression emerges for hemorrhagic lesions (0.3
at follow-up, 22.5