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.

Monitoring Functional Impairment and Recovery after Traumatic Brain Injury in Rats by fMRI

“…[2][3][4][5] The molecular and cellular reorganization patterns that follow TBI are accompanied by hemodynamic alterations. [6][7][8][9][10] Depending upon severity, TBI can lead to long-lasting disabilities, such as motor and cognitive impairment, psychiatric comorbidities, and post-traumatic epilepsy. 3,11,12 The therapeutic window for recovery-enhancing treatments and antiepileptogenesis includes the time period of secondary damage and consequent repair.…”

“…This relates to recent observations that demonstrate how neuronal networks that appear structurally undamaged can still contribute to functional impairment because of their aberrant intracellular or intercellular signaling. 13,14 Several neuroimaging methods have been applied to study brain function in patients with TBI, including positron emission tomography (PET), 15 cerebral blood flow (CBF), 9 cerebral blood volume (CBV), 16 and functional magnetic resonance imaging (fMRI). [17][18][19] The major limitation in patient studies relates to the lack of histological verification of imaging findings.…”

Chronology and Chronicity of Altered Resting-State Functional Connectivity after Traumatic Brain Injury

“…To date, most rs-fMRI studies in this population have taken a whole-brain a priori approach to investigating the DMN. 12,13 However, recent work has suggested that pathology in specific nodes, such as the posterior cingulate cortex (PCC), may have important implications for neurorecovery after trauma. Studies of TBI have reported increased within-DMN functional connectivity during task performance, featuring prominently the PCC and precuneus regions.…”

“…20 In moderate-to-severe TBI, it has been proposed that altered connectivity patterns involving the PCC may be related to neurocognitive impairment. 12,14,15 Therefore, delineation of this region's unique connectivity profile may provide insight into neural mechanisms underlying cognitive sequelae after trauma.…”

A Review of the Effectiveness of Neuroimaging Modalities for the Detection of Traumatic Brain Injury

“…Arterial spin labeling studies have uncovered decreased thalamic perfusion in mild, moderate, and severe TBI patients in group analysis versus controls, with additional findings in posterior cingulate and frontal cortices for moderate-to-severe TBI. 122,123 Dynamic contrast enhanced T1-weighted images can be used to assess vascular permeability and blood brain barrier integrity. Dynamic contrast enhanced studies in rabbit models have found a correlation between increased vascular permeability as quantified by the volume transfer coefficient (Ktrans) and the severity of the experimental TBI, as well as functional outcome at 30 days.…”