Dear Editor,
We appreciate the effort of Santos and colleagues for writing the letter entitled
“Diffuse axonal injury: diffusion tensor imaging and cognitive outcome”[1], about the published article by Grassi et al.[2]. We thank them for all their comments on our paper and we acknowledge the opportunity
to reply to their considerations.
Traumatic brain injury remains a major public health concern, directly affecting millions
of otherwise healthy individuals, as well as, indirectly, their household members,
who usually have to deal with long-term sequelae, including psychiatric symptoms and
cognitive deficits. During the last years, advanced magnetic resonance (MR) techniques
have played an important role in detecting abnormalities that were once under-recognized
when using conventional MR technology. In particular, diffusion tensor imaging represents
an important advanced MR tool in the context of traumatic brain injury and diffuse
axonal injury[3]. There are already extensive compendiums concerning the physics of diffusion tensor
imaging, however, instead, in our work we aimed to briefly review its basic principles
and main analytical methods (region-of-interest, tractography and voxelwise analyses),
along with the main relevant findings in the context of traumatic brain injury and
diffuse axonal injury[2].
Taking into account the advantages of diffusion tensor imaging in the noninvasive
exploration of brain microstructure and networks, one should not be surprised by the
striking number of recent publications using this technique in the evaluation of patients
at different stages after a traumatic episode, ranging from mild to moderate and severe
injuries[2],[3]. However, there is still an urge to associate diffusion tensor imaging findings
with clinical aspects and to correlate the scores with cognitive outcomes, making
it valuable and accessible as a prognostic tool in a daily clinical practice.
Fortunately, new scientific studies are evolving steadily and, soon after our recently-published
paper[2], new evidences have strengthened the relationship between diffusion tensor imaging
abnormalities and diffuse axonal injury outcomes. As pointed out by Santos et al.,
the work conducted by Hellstrøm and colleagues[4] indicated robust associations between self-reported cognitive, somatic and emotional
symptoms, 12 months after mild traumatic brain injury with white matter diffusion
tensor imaging parameters, extracted with a voxelwise analysis, dubbed as tract-based
spatial statistics. This work also reinforced physiologic effects of aging on brain
white matter structures, leaving the older brain more vulnerable to subtle injury-related
processes[3]. This also emphasizes the need to control age as a potential confounding variable
in case-control diffusion tensor imaging studies.
A work by Leon et al.[5] assessed 217 victims with moderate to severe traumatic brain injury 19 days after
the traumatic episode. Twenty-eight white matter fiber bundles were chosen because
of their susceptibility to trauma and were evaluated by region-of-interest analysis.
Diffusion tensor imaging metrics were highly associated with unfavorable clinical
outcomes after six months to one year after the trauma.
Furthermore, a recent meta-analysis of 20 studies investigated correlations between
diffusion tensor imaging measures and seven cognitive domains in mild to severe traumatic
brain injury victims. All studies pointed to a concordance between diffusion tensor
imaging parameters and cognition: increased fractional anisotropy values were associated
with higher cognitive performance, especially regarding memory and attention functions[6].
It is expected that diffusion tensor imaging evaluation will potentially have clinical
application in head injury survivors in the near future. Nevertheless, most findings
heretofore were based on single works and hence upcoming studies are awaited to highlight
the prognostic value of diffusion tensor imaging. There is still much work to be done.
Larger scale, longitudinal analyses with homogeneous traumatic brain injury groups
may play a decisive role in how this technique will prove helpful in predicting a
patient's prognosis and also aiding in selection of patients who might benefit from
targeted therapies.
