Resting cerebral blood flow alterations in chronic traumatic brain injury: an arterial spin labeling perfusion FMRI study

Abstract

Non-invasive measurement of resting state cerebral blood flow (CBF) may reflect alterations of brain structure and function after traumatic brain injury (TBI). However, previous imaging studies of resting state brain in chronic TBI have been limited by several factors, including measurement in relative rather than absolute units, use of crude spatial registration methods, exclusion of subjects with substantial focal lesions, and exposure to ionizing radiation, which limits repeated assessments. This study aimed to overcome those obstacles by measuring absolute CBF with an arterial spin labeling perfusion fMRI technique, and using an image preprocessing protocol that is optimized for brains with mixed diffuse and focal injuries characteristic of moderate and severe TBI. Resting state CBF was quantified in 27 individuals with moderate to severe TBI in the chronic stage, and 22 demographically matched healthy controls. In addition to global CBF reductions in the TBI subjects, more prominent regional hypoperfusion was found in the posterior cingulate cortices, the thalami, and multiple locations in the frontal cortices. Diffuse injury, as assessed by tensor-based morphometry, was mainly associated with reduced CBF in the posterior cingulate cortices and the thalami, where the greatest volume losses were detected. Hypoperfusion in superior and middle frontal cortices, in contrast, was associated with focal lesions. These results suggest that structural lesions, both focal and diffuse, are the main contributors to the absolute CBF alterations seen in chronic TBI, and that CBF may serve as a tool to assess functioning neuronal volume. We also speculate that resting reductions in posterior cingulate perfusion may reflect alterations in the default-mode network, and may contribute to the attentional deficits common in TBI.

FIG. 1.

Mean raw cerebral blood flow images in an individual with traumatic brain injury. Total acquisition time was approximately 6 min. The patient had bilateral orbitofrontal lesions extending into the frontal pole superiorly (white arrows). (Color image is available online at www.liebertonline.com/neu)

FIG. 2.

Top panels: Absolute mean cerebral blood flow (CBF) difference map between control (n = 22) and TBI (n = 27) groups (left), and the corresponding voxel-wise statistical map, thresholded with a whole-brain false-discovery rate of less than 5% (right). Bottom panels: Relative mean CBF difference map from the same groups (left), and the corresponding statistical map (right). Radiological convention is used. (Color image is available online at www.liebertonline.com/neu)

FIG. 3.

Top left: Mean cerebral blood flow (CBF) difference map between controls (n = 22) and traumatic brain injury (TBI) survivors with focal lesions (n = 12). Top right: Difference between controls and TBI survivors without focal lesions (diffuse subgroup, n = 15). Bottom left: Mean CBF difference between the diffuse and focal subgroups. Bottom right: Lesion frequency map displaying the 12 TBI survivors with focal lesions. Radiological convention is used. (Color image is available online at www.liebertonline.com/neu)

FIG. 4.

Relationship between gross volume and cerebral blood flow. Each symbol represents one participant. Individuals with traumatic brain injury (TBI) were divided into two subgroups.