Low-Level Light Therapy Effect on Metabolites measured by Magnetic Resonance Spectroscopy in Patients with Moderate Traumatic Brain Injury: A Double-blind, Randomized, Placebo-controlled Clinical Trial

Low-level light therapy (LLLT) has been shown to modulate recovery in patients with traumatic brain injury (TBI). However, the longitudinal impact of LLLT on brain metabolites has not been studied. The purpose of this study was to use magnetic resonance spectroscopic imaging (MRSI) to assess the metabolic response of LLLT in patients with moderate TBI at acute (within 1 week), subacute (2-3 weeks), and late-subacute (3 months) recovery phases. This is a secondary analysis of a prospective single-site double-blinded sham-controlled study conducted in patients with moderate TBI. Participants were randomized for LLLT and sham treatment. Three Tesla two-dimensional MRSI was acquired. Our focus of investigation was the metabolic change in the corpus callosum (CC) and the changes in myo-inositol/N-acetyl aspartate (mI/NAA), representing the combined effect of elevated neuroinflammation (mI) and decreased neuronal/axonal health (NAA). A linear mixed-effects model was constructed to quantify the association between mI/NAA and treatment, scan, and the interaction between treatment and scan. Thirty-four participants (18 male, age 49±17 (20 to 79); 15 LLLT, 19 sham) were included in the final data set and were scanned at the following timepoints: acute (N=24), subacute (N=27) and late subacute (N=23). The mI/NAA ratio in the CC of the sham-treated participants increased over time. Sham-treated participants revealed a significant increase in mI/NAA from the acute to the late subacute phases (0.19, 95%CI: 0.09, 0.29; pHolm=0.005). mI/NAA stayed relatively stable in participants undergoing LLLT treatment (all pHolm>0.64). Consequently, mI/NAA was significantly higher in the sham-treated participants compared to the LLLT-treated participants during the late subacute phase of recovery (-0.31, 95%CI: -0.50, -0.12; pHolm=0.019). Despite the small sample size, MRSI indicates a metabolic response in participants treated with LLLT compared to those receiving sham treatment. This potentially suggests a neuroprotective and anti-inflammatory effect from the acute administration of LLLT in individuals with moderate TBI. LLLT＝Low-level light therapy; TBI＝traumatic brain injury; MRSI = magnetic resonance spectroscopic imaging; CC = corpus callosum; mI = in myo-inositol; NAA = N-acetyl aspartate; ATP = adenosine triphosphate; GCS = Glasgow Coma Scale; LASER = Localization by Adiabatic SElective Refocusing.