Longitudinal Diffusion Tensor Imaging Detects Recovery of Fractional Anisotropy Within Traumatic Axonal Injury Lesions

Abstract

Background: Traumatic axonal injury (TAI) may be reversible, yet there are currently no clinical imaging tools to detect axonal recovery in patients with traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to characterize serial changes in fractional anisotropy (FA) within TAI lesions of the corpus callosum (CC). We hypothesized that recovery of FA within a TAI lesion correlates with better functional outcome.

Methods: Patients who underwent both an acute DTI scan (≤day 7) and a subacute DTI scan (day 14 to inpatient rehabilitation discharge) at a single institution were retrospectively analyzed. TAI lesions were manually traced on the acute diffusion-weighted images. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured within the TAI lesions at each time point. FA recovery was defined by a longitudinal increase in CC FA that exceeded the coefficient of variation for FA based on values from healthy controls. Acute FA, ADC, AD, and RD were compared in lesions with and without FA recovery, and correlations were tested between lesional FA recovery and functional recovery, as determined by disability rating scale score at discharge from inpatient rehabilitation.

Results: Eleven TAI lesions were identified in 7 patients. DTI detected FA recovery within 2 of 11 TAI lesions. Acute FA, ADC, AD, and RD did not differ between lesions with and without FA recovery. Lesional FA recovery did not correlate with disability rating scale scores.

Conclusions: In this retrospective longitudinal study, we provide initial evidence that FA can recover within TAI lesions. However, FA recovery did not correlate with improved functional outcomes. Prospective histopathological and clinical studies are needed to further elucidate whether lesional FA recovery indicates axonal healing and has prognostic significance.

Keywords: Apparent diffusion coefficient; Diffusion tensor imaging; Fractional anisotropy; Traumatic axonal injury; Traumatic brain injury.

Figure 1. Longitudinal Imaging Changes within a Splenium Lesion with FA Recovery

A traumatic axonal injury lesion in the splenium of the corpus callosum is outlined in red for patient 5. Acutely (day 7), the lesion is hyperintense on diffusion-weighted imaging (DWI) and T2-weighted fluid-attenuated inversion recovery (FLAIR). Subacutely (day 15), the DWI hyperintensity has diminished, the FLAIR hyperintensity has diminished (red arrows), the apparent diffusion coefficient (ADC) has normalized (inset, units = 10⁻³ mm/s²), and the fractional anisotropy (FA) has increased (inset) by a magnitude that exceeded intersubject and intrasubject FA variability in healthy controls. Abbreviations: “+” indicates that a lesion was visible; “−“ indicates that a lesion was not visible.

Figure 2. Longitudinal Fractional Anisotropy Changes within White Matter Tracts Affected by Traumatic Axonal Injury

A traumatic axonal injury (TAI) lesion in the splenium of the corpus callosum of patient 6 (top row) demonstrates FA recovery, as defined by a longitudinal increase in FA that exceeds the coefficient of variation for FA within the splenium of the corpus callosum in the two control datasets. A splenium TAI lesion for patient 7 undergoes a longitudinal decline in FA (bottom row). Each TAI lesion is rendered in 3-dimensions as a semi-transparent white region of interest so that tracts can be visualized passing through the lesions. Fiber tracts were generated using the lesions as seeds. Tracts are color-coded using mean tract FA as a scalar (right panels). All tracts were reconstructed using Diffusion Toolkit version 0.6.2 and TrackVis version 5.2 (Wang & Wedeen, Athinoula A. Martinos Center for Biomedical Imaging, www.trackvis.org).

Figure 3. Fractional Anisotropy Correlations with Apparent Diffusion Coefficient, Axial Diffusivity, and Radial Diffusivity

Scatter plots and linear regression lines are displayed for all diffusion tensor imaging lesional measurements during both the acute and subacute stages of traumatic axonal injury (TAI). Individual data points are shown for each lesion at each time point, and regression lines are shown with 95% confidence intervals (dotted lines). Fractional anisotropy (FA) correlates strongly with radial diffusivity (RD), moderately with apparently diffusion coefficient (ADC), and not with axial diffusivity (AD). The strong correlation between FA and RD suggests that longitudinal changes in RD play a primary role in driving changes in FA within TAI lesions.