Elsevier

Journal of Magnetic Resonance

Volume 292, July 2018, Pages 137-148
Journal of Magnetic Resonance

Diffusion MRI in acute nervous system injury

https://doi.org/10.1016/j.jmr.2018.04.016Get rights and content

Highlights

  • Diffusion weighted imaging reliably detects acute neurological injury.

  • Decreased diffusion relates to focal swelling of axons and dendrites, termed neurite beading.

  • Novel DWI contrasts may improve the sensitivity to axonal injury.

Abstract

Diffusion weighted magnetic resonance imaging (DWI) and related techniques such as diffusion tensor imaging (DTI) are uniquely sensitive to the microstructure of the brain and spinal cord. In the acute aftermath of nervous system injury, for example, DWI reveals changes caused by injury that remains invisible on other MRI contrasts such as T2-weighted imaging. This ability has led to a demonstrated clinical utility in cerebral ischemia. However, despite strong promise in preclinical models and research settings, DWI has not been as readily adopted for other acute injuries such as traumatic spinal cord, brain, or peripheral nerve injury. Furthermore, the precise biophysical mechanisms that underlie DWI and DTI changes are not fully understood. In this report, we review the DWI and DTI changes that occur in acute neurological injury of cerebral ischemia, spinal cord injury, traumatic brain injury, and peripheral nerve injury. Their associations with the underlying biology are examined with an emphasis on the role of acute axon and dendrite beading. Lastly, emerging DWI techniques to overcome the limitations of DTI are discussed as these may offer the needed improvements to translate to clinical settings.

Introduction

Diffusion weighted MRI (DWI) has demonstrated a tremendous ability to probe the microstructure of the nervous system noninvasively that is not afforded through other methods. DWI is highly sensitive to certain neurological injuries where conventional MRI contrasts such as T1, T2, or T2 either fail to detect the injury or are otherwise non-specific. Most notably this occurs in acute ischemic stroke, but is similarly observed in other acute neurological injuries of the brain, spinal cord, and peripheral nervous system. In this capacity, DWI is a proven diagnostic tool that has gained widespread acceptance. However, while it is sensitive to microscopic changes, DWI is not inherently specific for any single pathological feature. Thus, the microstructural pathophysiology underlying DWI changes have been difficult to isolate even in a prominent change such as stroke. Quantitative metrics of the diffusion weighted signal, such as diffusion tensor imaging (DTI) have further enabled the ability to extract microstructural features from the diffusion weighted images and relate them to the underlying biological substrates. This is an active area of study that has seen strong growth in the last several decades. In this review, we focus on the role of DWI in the detection of acute nervous system injury with a major emphasis on the period of injury within the first 3 days following the onset of injury. Cerebral ischemia, spinal cord injury (SCI), traumatic brain injury (TBI), and acute peripheral nerve injury will be discussed in detail as these reflect rapid or sudden changes in which DWI is particularly sensitive. This review is principally targeted at relating the DWI changes in these injuries to the underlying pathophysiology, and advocates for the role of axonal and dendrite injury as a prominent factor in the sensitivity of DWI to acute neurological injury.

The majority of diffusion studies in acute injury use DWI or diffusion tensor imaging (DTI). This review presumes the reader is familiar with DWI and DTI principles, and several reviews are available [1]. We remind the reader of the parameters derived from DWI methods and briefly reiterate their interpretations. The apparent diffusion coefficient (ADC), or mean diffusivity (MD) describes the per-voxel averaged diffusivity and is invariant to direction of the diffusion weighting relative to the underlying tissues. Fractional anisotropy (FA) reflects the coherence of white matter fibers in the normal brain and is also orientationally invariant. On the other hand, DTI-derived parameters axial and radial diffusivity reflect directionally-dependent diffusion properties. Axial diffusivity (AD), also commonly called longitudinal diffusivity, represents the diffusivity along the fastest diffusion direction within each voxel. Radial diffusivity (RD), also commonly called transverse diffusivity, represents the diffusivity averaged perpendicular to axial diffusivity. It is important to note that in coherent white matter fibers, such as the corpus callosum or in the spinal cord, these parameters reliably reflect the fiber organization, with AD coinciding parallel to the axonal fiber tracts. However, it is also noted that in voxels with high degrees of dispersion or multiple intersecting fiber bundles, AD and RD no longer coincide with the underlying axons, and their interpretation in ambiguous. Moreover, while DTI is unable to resolve intra- and extra-cellular biological water “compartments”, its role in interpreting intra-axonal and extra-axonal diffusion properties are discussed throughout, since these have implications for understanding the relationship between DWI and DTI measurements and the pathophysiology in acute neurological injury.

In this review, the use of DWI to assess the effects of acute neurological injury will be summarized with an emphasis on the relationship between these changes and the underlying pathophysiology. We particularly focus on injuries with relatively sudden onsets, including acute cerebral ischemia, spinal cord injury, traumatic brain injury, and peripheral nerve injury. For each injury, the role of biophysical modelling, animal experiments, and human findings will be reviewed. The scope of the review is aimed at providing the reader with a critical view of the commonalities and differences in the pathophysiology of nervous system injury and how it relates to the detection and interpretation of DWI findings. A section on outlook and future directions will guide efforts to improve the sensitivity and specificity of DWI using advanced modelling and non-traditional diffusion encoding strategies.

Section snippets

DWI in acute cerebral ischemia

In 1990, Mosely et al. first demonstrated that MRI contrast sensitized to diffusion was uniquely reflective of acute stroke [2]. The ischemic lesion appeared hyperintense on diffusion weighted imaging within several minutes of the insult whereas the lesion was invisible with T2-weighted contrast, yielding a decrease in ADC by approximately one-half compared to the surrounding healthy brain tissue. It has become an integral part of the clinical management of stroke and its use in diagnosis of

Biophysical mechanisms

Spinal cord injury is caused by a physical insult most often the consequence of trauma from falls or motor vehicle accidents. Compared to ischemia, in which T2-weighted changes do not typically manifest early after injury, the acutely injured spinal cord exhibits prominent hyperintensity on T2-weighted imaging. Consequently, T2-weighting MRI is the modality of choice for clinical diagnosis. The T2 hyperintensity is due to both cytotoxic and vasogenic edema and may be accompanied by hemorrhage.

DWI in acute traumatic brain injury

TBI is caused by a physical insult to the brain through mechanical forces, causing a wide range of injury to the neuronal and vascular systems. TBI has a broad range of severity and manifestation of clinical symptoms that varies from severe, penetrating TBI to mild TBI or concussion. Despite numerous reports of the utility of DTI to identify individual (Fig. 3) and group differences across the severity spectrum of TBI, DTI has yet to be shown to be robust and useful as a clinical marker of

Biophysical mechanisms

DTI of the peripheral nerves has been explored to investigate the consequences of acute nerve injury or neuropathy (Fig. 4). Compared to central nervous system axons, axons of peripheral nerves exhibit somewhat different pathological time courses after injury. For instance, in an optic nerve injury, which is a part of the central nervous system, formation of axonal varicosities started within 30 min to an hour after the injury, and continued to evolve while the axon continued to disintegrate

Discussion

DWI is an accepted diagnostic tool for cerebral ischemia and it is available in most acute care settings. Its success is, in part, due to its unique sensitivity to detect injured brain tissue that remains invisible on other MRI contrasts. The biophysics underlying the abrupt ADC decreases are intimately related to cell swelling in which neurite beading is compatible with the observational and experimental findings. Further experiments to concretely implicate beading or other features would be

Acknowledgements

MDB acknowledges support from the Craig H. Neilsen Foundation and the U.S. Department of Veterans Affairs. NPS acknowledges support from the National Institutes of Health and the Medical Scientist Training Program. All animal procedures were approved by the Institutional Animal Care and Use Committees at the Medical College of Wisconsin and Clement J Zablocki VA Medical Center and were performed in accordance with the relevant guidelines and regulations.

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