Effect of Transcranial Low-Level Light Therapy vs Sham Therapy Among Patients With Moderate Traumatic Brain Injury: A Randomized Clinical Trial.

Importance: Preclinical studies have shown that transcranial near-infrared low-level light therapy (LLLT) administered after traumatic brain injury (TBI) confers a neuroprotective response. Objectives: To assess the feasibility and safety of LLLT administered acutely after a moderate TBI and the neuroreactivity to LLLT through quantitative magnetic resonance imaging metrics and neurocognitive assessment. Design, Setting, and Participants: A randomized, single-center, prospective, double-blind, placebo-controlled parallel-group trial was conducted from November 27, 2015, through July 11, 2019. Participants included 68 men and women with acute, nonpenetrating, moderate TBI who were randomized to LLLT or sham treatment. Analysis of the response-evaluable population was conducted. Interventions: Transcranial LLLT was administered using a custom-built helmet starting within 72 hours after the trauma. Magnetic resonance imaging was performed in the acute (within 72 hours), early subacute (2-3 weeks), and late subacute (approximately 3 months) stages of recovery. Clinical assessments were performed concomitantly and at 6 months via the Rivermead Post-Concussion Questionnaire (RPQ), a 16-item questionnaire with each item assessed on a 5-point scale ranging from 0 (no problem) to 4 (severe problem). Main Outcomes and Measures: The number of participants to successfully and safely complete LLLT without any adverse events within the first 7 days after the therapy was the primary outcome measure. Secondary outcomes were the differential effect of LLLT on MR brain diffusion parameters and RPQ scores compared with the sham group. Results: Of the 68 patients who were randomized (33 to LLLT and 35 to sham therapy), 28 completed at least 1 LLLT session. No adverse events referable to LLLT were reported. Forty-three patients (22 men [51.2%]; mean [SD] age, 50.49 [17.44] years]) completed the study with at least 1 magnetic resonance imaging scan: 19 individuals in the LLLT group and 24 in the sham treatment group. Radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA) showed significant time and treatment interaction at 3-month time point (RD: 0.013; 95% CI, 0.006 to 0.019; P < .001; MD: 0.008; 95% CI, 0.001 to 0.015; P = .03; FA: -0.018; 95% CI, -0.026 to -0.010; P < .001).The LLLT group had lower RPQ scores, but this effect did not reach statistical significance (time effect P = .39, treatment effect P = .61, and time × treatment effect P = .91). Conclusions and Relevance: In this randomized clinical trial, LLLT was feasible in all patients and did not exhibit any adverse events. Light therapy altered multiple diffusion tensor parameters in a statistically significant manner in the late subacute stage. This study provides the first human evidence to date that light therapy engages neural substrates that play a role in the pathophysiologic factors of moderate TBI and also suggests diffusion imaging as the biomarker of therapeutic response. Trial Registration: ClinicalTrials.gov Identifier: NCT02233413.

Spot and Diffuse Signs: Quantitative Markers of Intracranial Hematoma Expansion at Dual-Energy CT.

Purpose To compare dual-energy CT with iodine quantification to single-energy CT for evaluation of the spot sign for intracranial hematoma expansion. Materials and Methods In this retrospective study, 42 patients (mean age, 66 years ± 15 [standard deviation]; 19 women) were referred for dual-energy CT assessment of intracranial hemorrhage from October 2014 to January 2017. A machine learning approach (naive Bayes classifier) was used to identify iodine markers of extravasation for risk of hematoma expansion. Specificity and sensitivity of these markers were then independently validated in 65 new patients from February 2017 to February 2018. Results Analysis of dual-energy CT images identified two features of iodine extravasation: total iodine concentration within the hematoma (Ih) and focal iodine concentration in the brightest spot in the hematoma (Ibs) as predictors of expansion. The I2 score derived from these features provided a measure of expansion probability. Optimal classification threshold was an I2 score of 20 (95% confidence interval [CI]: 18, 23), leading to correct identification of 39 of 46 (85%; 95% CI: 71%, 94%) of the hematomas on the training set (sensitivity of 79% [11 of 14; 95% CI: 57%, 100%] and specificity of 88% [28 of 32; 95% CI: 76%, 99%]), and 62 of 70 (89%; 95% CI: 79%, 95%) of the hematomas on the validation set (sensitivity of 71% [10 of 14; 95% CI: 48%, 95%] and specificity of 93% [52 of 56; 95% CI: 86%, 100%]). Sensitivity, specificity, and accuracy of conventional spot sign were, respectively, 57% (eight of 14), 90% (29 of 32), and 80% (37 of 46) on the training set and 57% (eight of 14), 83% (47 of 56), and 75% (53 of 70) on the validation set. Conclusion This study identified two quantitative markers of intracranial hemorrhage expansion at dual-energy CT of the brain. The I2 score derived from these markers highlights the utility of dual-energy CT measurements of iodine content for high sensitivity risk assessment. © RSNA, 2018 Online supplemental material is available for this article.

Dual-Energy Head CT Enables Accurate Distinction of Intraparenchymal Hemorrhage from Calcification in Emergency Department Patients.

Purpose To evaluate the ability of dual-energy (DE) computed tomography (CT) to differentiate calcification from acute hemorrhage in the emergency department setting. Materials and Methods In this institutional review board-approved study, all unenhanced DE head CT examinations that were performed in the emergency department in November and December 2014 were retrospectively reviewed. Simulated 120-kVp single-energy CT images were derived from the DE CT acquisition via postprocessing. Patients with at least one focus of intraparenchymal hyperattenuation on single-energy CT images were included, and DE material decomposition postprocessing was performed. Each focal hyperattenuation was analyzed on the basis of the virtual noncalcium and calcium overlay images and classified as calcification or hemorrhage. Sensitivity, specificity, and accuracy were calculated for single-energy and DE CT by using a common reference standard established by relevant prior and follow-up imaging and clinical information. Results Sixty-two cases with 68 distinct intraparenchymal hyperattenuating lesions in which the reference standards were available were included in the study, of which 41 (60%) were confirmed as calcification and 27 (40%) were confirmed as hemorrhage. Sensitivity, specificity, and accuracy of DE CT for the detection of hemorrhage were 96% (95% confidence interval [CI]: 81%, 100%), 100% (95% CI: 91%, 100%), and 99% (95% CI: 92%, 100%) and those of single-energy CT were 74% (95% CI: 54%, 89%), 95% (95% CI: 83%, 99%), and 87% (95% CI: 76%, 94%), respectively. Six of 68 (9%) lesions were classified as indeterminate and three (4%) were misinterpreted with single-energy CT alone and were correctly classified with DE CT. Conclusion DE CT by using material decomposition enables accurate differentiation between calcification and hemorrhage in patients presenting for emergency head imaging and can be especially useful in problem-solving complex cases that are difficult to determine based on conventional CT appearance alone. (©) RSNA, 2016 Online supplemental material is available for this article.