Diffusion MRI: Pitfalls, literature review and future directions of research in mild traumatic brain injury
Introduction
Traumatic brain injury (TBI) is a major cause of disability and death in adults aged between 15 and 45 years and thus represents a significant public health burden with high socio-economic impact. Patients are classified using the Glasgow coma scale (GCS) as being mildly (GCS 13–15), moderately (GCS 9–12) or severely injured (GCS < 8). Seventy to ninety percent of all treated brain injuries are mild (mTBI), corresponding to an estimated incidence of 100-300/100,000 according to the WHO Task Force [1]. Nevertheless, after the mTBI, a significant proportion of patients report suffering a distressing combination of physical, emotional and cognitive symptoms, collectively known as post-concussion disorder [2], that persist well after the injury event and thus hinder their return to work or cause resumption of social activities. Depression [3] and vestibular complaints [4] are also frequently reported.
Computed tomography offers only a limited view of the subtle intracranial abnormalities that occur in acute brain injury. Magnetic resonance imaging (MRI) on the other hand has become a major tool for use in diagnosing neurological impairment. Indeed, recent morphological MRI sequences such as susceptibility-weighted imaging (SWI) [5] or contrast-enhanced fluid-attenuated inversion recovery (FLAIR) [6], have considerably improved the assessment of macroscopic lesions. However, diffusion-weighted imaging (DWI) is the only tool capable of mapping the complex fiber architecture of tissues at a submillimetric level [7], [8]. This tool was mainly used to diagnose ischemic brain tissue at early stages after TBI [9]. Today, the development of diffusion tensor imaging (DTI) techniques now enables brain voxel-based quantitative analysis through the measurement of fractional anisotropy (FA) or mean diffusivity (MD) [10]. Diffusion imaging and consecutive fiber tractography in post-processing have also been used inside the brain to highlight white matter (WM) bundles, providing new insight into post-traumatic structural connectivity [11]. The main advantage of tractography, from a clinical research perspective, is the possibility to evaluate the whole fiber bundle, as opposed to just one of its segments. Many methods have been proposed for tractography, and the results vary depending on the chosen method. Recently, other techniques derived from diffusion imaging, including diffusion kurtosis imaging (DKI), multi-shell diffusion [12], [13] and high-order tractography models with super-resolution properties were assessed in terms of their capacity to better detect diagnostic and prognostic biomarkers [14], [15].
In this review, we will briefly outline the physical basis of these techniques including their pitfalls for use in brain trauma, before discussing findings from their use in diagnostic trials assessing brain structural changes in patients with mTBI. To conclude, we will discuss the future direction of research with advanced diffusion acquisition.
Section snippets
Search criteria
A structured search using PubMed was performed on the 15th of March 2015, and included all relevant articles published in and after 2005. The search used the following key word combinations: “DTI” AND “mild traumatic brain injury” (n = 319); “Tractography” AND “mild traumatic brain injury” (n = 104); “Kurtosis diffusion imaging” AND “mild traumatic brain injury” (n = 9). The search resulted in 330 individual articles from which additional relevant articles were identified upon examination of the
DTI physical basis
In WM fibers, the diffusion parallel to the direction of the axons is assumed to be unrestricted while that occurring perpendicularly to this is constrained by membranes. This anisotropic behavior is described by the diffusion tensor model [16] that is based on a Gaussian distribution of the water molecule motion in tissue. DTI is now a well-documented technique for assessing WM integrity, either on a regional or a whole-brain level, via the measurement of FA, a scalar value that describes the
Altered areas
Pathophysiological modifications after mTBI are time-dependent, and thus render chronology a crucial factor in the interpretation of diffusion imaging findings [11].
When focusing on acute stages, results from voxel-based diffusion analyses appear conflicting: mTBI was recently found not to be associated with white matter changes in a rigorous and large controlled study [22] while previous studies showed significant differences in the mean FA for the CC and internal and external capsules [27],
High-order tractography
Beyond the DTI-tractography model, two principal methods exist to describe the orientation dependence of the diffusion-weighted MR signal: the diffusion orientation distribution function (ODF) and the estimation of fiber ODF. The former essentially describes the diffusion within a voxel, as for instance in the composite hindered and restricted model of diffusion (CHARMED) [13]. This model consists of two parts: one accounting for hindered diffusion in the extracellular space and the other for
Conflict of interest
None.
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