Global decrease in brain sodium concentration after mild traumatic brain injury

Abstract

The pathological cascade of tissue damage in mild traumatic brain injury is set forth by a perturbation in ionic homeostasis. However, whether this class of injury can be detected in vivo and serve as a surrogate marker of clinical outcome is unknown. We employ sodium MRI to test the hypotheses that regional and global total sodium concentrations: (i) are higher in patients than in controls; and (ii) correlate with clinical presentation and neuropsychological function. Given the novelty of sodium imaging in traumatic brain injury, effect sizes from (i), and correlation types and strength from (ii), were compared to those obtained using standard diffusion imaging metrics. 27 patients (20 female, age 35.9 ± 12.2 years) within two months after injury and 19 controls were scanned with proton and sodium MRI at 3 Tesla. Total sodium concentration, fractional anisotropy and apparent diffusion coefficient were obtained with voxel averaging across 12 grey and white matter regions. Linear regression was used to obtain global grey and white matter total sodium concentrations. Patient outcome was assessed with global functioning, symptom profiles, and neuropsychological function assessments. In the regional analysis, there were no statistically significant differences between patients and controls in apparent diffusion coefficient, while differences in sodium concentration and fractional anisotropy were found only in single regions. However, for each of the 12 regions, sodium concentration effect sizes were uni-directional, due to lower mean sodium concentration in patients compared to controls. Consequently, linear regression analysis found statistically significant lower global grey and white matter sodium concentrations in patients compared to controls. The strongest correlation with outcome was between global grey matter sodium concentration and the composite z-score from the neuropsychological testing. In conclusion, both sodium concentration and diffusion showed poor utility in differentiating patients from controls, and weak correlations with clinical presentation, when using a region-based approach. In contrast, sodium linear regression, capitalizing on partial volume correction and high sensitivity to global changes, revealed high effect sizes and associations with patient outcome. This suggests that well-recognized sodium imbalances in traumatic brain injury are: (i) detectable non-invasively, (ii) non-focal, (iii) occur even when the antecedent injury is clinically mild. Finally, in contrast to our principle hypothesis, patients’ sodium concentrations were lower than controls, indicating that the biological effect of traumatic brain injury on the sodium homeostasis may differ from that in other neurological disorders.

Quantitative 7T sodium magnetic resonance imaging of the human brain using a 32‐channel phased‐array head coil: Application to patients with secondary progressive multiple sclerosis

“…As the integrated 23 Na 32-channel receive phased-array of the dual-tuned 23 Na/ 1 H head coil prohibits the use of external references due to restricted space around the head, an internal reference had to be used. Besides the vitreous humor in the eyes, 22 CSF can be used as an internal reference for concentration calibration. 21 The determined sodium concentrations are in good agreement with the literature.…”

“…Regarding the signal calibration for quantification, external references with known 23 Na concentrations are mostly used. 18 As dedicated head coils with integrated receive phased arrays to enable improved spatial resolution by increasing SNR 19,20 often prohibit external references due to restricted space, using internal references such as the cerebrospinal fluid (CSF) 21 or vitreous humor 22 for quantification would be desirable. However, currently, these are rarely employed and further validation is necessary.…”

Antioxidant-based neuroprotective effect of dimethylsulfoxide against induced traumatic brain injury in a rats model

“…( Camici et al, 2006 ). reported that DMSO also can block Na + channel activation The Na + channel is activated by the physical impact on the brain tissue in TBI which leads to initiation of action potential and loss of membrane permeability culminating in necrosis and free radical generation ( Huang et al, 2014 ; Gerhalter et al, 2021 ). ( Jacob and Torre, 2009 ) reported a reduction in intracranial pressure, tissue edema, and inflammatory reactions by DMSO following TBI and these could further support its neuroprotective effects.…”

Replicability of proton MR spectroscopic imaging findings in mild traumatic brain injury: Implications for clinical applications

“…The Cohen’s d statistic, defined as the difference between mean metabolite levels divided by the pooled SD, was calculated as a measure of effect size for the differences between patients and controls: where , , , , , and , denote the patients’ (“p”) and controls (“c”) sample sizes, metabolite level means and SDs, following Davitz et al (2019) . A “small” effect was defined as | d | ≤ 0.5, a “medium” effect was defined as 0.5 < | d | < 0.8, and a “large” effect was defined as | d | ≥ 0.8, as done in Gerhalter et al, 2021 .…”