There is a crucial need to establish neuroimaging biomarkers in mild traumatic brain injury (MTBI) that can account for its organic origin and identify patients at risk of long-term or permanently disabling cognitive impairment. This paper is part of a larger body of research our group is conducting to address the matter using multiple advanced MRI techniques, some of which we have developed. We are investigating the widely held hypothesis that there exists diffuse axonal injury in white matter that cannot be resolved by standard clinical approaches. In addition, we are exploring the possibility that the thalamus may be another important site of subtle damage, because this structure has reciprocal projections to the entire cerebral cortex and could account for much of the morbidity experienced by patients.

One important factor that made this work possible was our development of diffusional kurtosis imaging (DKI).^1–3 Compared to its older relative, diffusion tensor imaging (DTI), DKI does not assume water diffusion occurs in an unrestricted homogeneous environment and can be estimated using a Gaussian displacement distribution. Instead, DKI is based on the premise that the process is partly impeded by the presence of intricate microstructural barriers, and it determines the degree of displacement from the normal curve that this interference causes. Thus, for example, while DTI is effective at evaluating the magnitude of diffusion, DKI is better suited for assessing intravoxel diffusional heterogeneity, which is an indicator of complexity.

A second important factor was our development of a segmented true fast imaging with steady-state precession (True-FISP) method of arterial spin-labeling (ASL).⁴ Unlike more commonly used echo-planar imaging–based approaches, segmented True-FISP ASL is capable of measuring perfusion in the thalamus and other deep gray matter regions without the problems of magnetic susceptibility and rapid dephasing often caused by local magnetic field inhomogeneities.

In more recent work, we have been examining ways to expand on our previous innovations by developing a white matter tract integrity model suitable for use with DKI and DTI.^5–7 Doing so allows for the quantification

of more sensitive and specific compartmental metrics than is possible with empirical diffusion data, such as intra-axonal diffusivity, extra-axonal axial and radial diffusivity, axonal water fraction, and tortuosity of extra-axonal space.

The findings we have reported move us closer to translating neuroimaging technological advances into clinical tools that can benefit patients with MTBI. With continued research, quantitative MRI could become an important diagnostic measure for determining which individuals would most likely benefit from early medical and rehabilitative interventions that might reduce the risk of developing a chronic condition.

References

1. Jensen JH, Helpern JA. MRI quantification of non-Gaussian water diffusion by kurtosis analysis. NMR Biomed 2010;23:698–710. doi: 10.1002/nbm.1518
2. Jensen JH, Helpern JA, Ramani A, et al. Diffusional kurtosis imaging: the quantification of non-Gaussian water diffusion by means of magnetic resonance imaging. Magn Reson Med 2005;53:1432–40. doi: 10.1002/mrm.20508
3. Lu H, Jensen JH, Ramani A, et al. Three-dimensional characterization of non-Gaussian water diffusion in humans using diffusion kurtosis imaging. NMR Biomed 2006;19:236–47. doi: 10.1002/nbm.1020
4. Grossman EJ, Zhang K, An J, et al. Measurement of deep gray matter perfusion using a segmented true-fast imaging with steady-state precession (true-FISP) arterial spin-labeling (ASL) method at 3T. J Magn Reson Imaging 2009;29:1425–31. doi: 10.1002/jmri.21794
5. Fieremans E, Jensen J H, Helpern JA. White matter characterization with diffusional kurtosis imaging. Neuroimage 2011;58:177–88. doi: 10.1016/j.neuroimage.2011.06.006
6. Fieremans E, Novikov DS, Jensen JH, et al. Monte Carlo study of a two-compartment exchange model of diffusion. NMR Biomed 2010;23:711–24. doi: 10.1002/nbm.1577
7. Grossman EJ, Kirov II, Gonen O, et al. Relationship between diffusion magnetic resonance imaging white matter tract integrity and N-acetylaspartate magnetic resonance spectroscopy in mild traumatic brain injury. Int Soc Magn Reson Med Workshop 2013; Podstrana, Croatia.

 

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