Transcranial Near-Infrared Laser Transmission (NILT) Profiles (800 nm): Systematic Comparison in Four Common Research Species.

Transcranial near-infrared laser therapy (TLT) is a promising and novel method to promote neuroprotection and clinical improvement in both acute and chronic neurodegenerative diseases such as acute ischemic stroke (AIS), traumatic brain injury (TBI), and Alzheimer's disease (AD) patients based upon efficacy in translational animal models. However, there is limited information in the peer-reviewed literature pertaining to transcranial near-infrared laser transmission (NILT) profiles in various species. Thus, in the present study we systematically evaluated NILT characteristics through the skull of 4 different species: mouse, rat, rabbit and human.Using dehydrated skulls from 3 animal species, using a wavelength of 800nm and a surface power density of 700 mW/cm2, NILT decreased from 40.10% (mouse) to 21.24% (rat) to 11.36% (rabbit) as skull thickness measured at bregma increased from 0.44 mm in mouse to 0.83 mm in rat and then 2.11 mm in rabbit. NILT also significantly increased (p<0.05) when animal skulls were hydrated (i.e. compared to dehydrated); but there was no measurable change in thickness due to hydration. In human calvaria, where mean thickness ranged from 7.19 mm at bregma to 5.91 mm in the parietal skull, only 4.18% and 4.24% of applied near-infrared light was transmitted through the skull. There was a slight (9.2-13.4%), but insignificant effect of hydration state on NILT transmission of human skulls, but there was a significant positive correlation between NILT and thickness at bregma and parietal skull, in both hydrated and dehydrated states.This is the first systematic study to demonstrate differential NILT through the skulls of 4 different species; with an inverse relationship between NILT and skull thickness. With animal skulls, transmission profiles are dependent upon the hydration state of the skull, with significantly greater penetration through hydrated skulls compared to dehydrated skulls. Using human skulls, we demonstrate a significant correlation between thickness and penetration, but there was no correlation with skull density. The results suggest that TLT should be optimized in animals using novel approaches incorporating human skull characteristics, because of significant variance of NILT profiles directly related to skull thickness

Human Skull Characteristics.

<p>Human Skull Characteristics.</p

Dehydrated Human Calvaria #12–325 NILT Penetration.

<p>Ventral surface of the human skull showing NILT transmission (A) and the limited diffusion pattern observed (B).</p

Dehydrated Rabbit Skull NILT Transmission.

<p>(A) NILT Treatment at Bregma showing the laser spotting light, (B) NILT Penetration and Scatter- Ventral surface of the rabbit skull showing the NILT penetration profile (A) and extensive diffusion pattern observed (B).</p

CT Scan Analysis of Calvaria #12–325.

<p>(A) Radio-opaque skull- Human Calvaria Measurement Point coordinates; (B) Skull Thickness Profiles and (C) Skull Density Profiles. Parametric maps of overall skull thickness and density. Vector positions for measurements are shown in A, Thickness (B) and density (C). Left panels dehydrated calvaria measurement in air; Right panels hydrated degassed measured in air.</p

NILT Penetration Physical Set-up.

<p>Penetration Assembly and NILT Treatment at Bregma for example human calvaria #12–325.</p

Correlation analysis: Human Calvaria- Thickness & Density.

<p>Plots of NILT penetration (mW/cm²) vs. thickness (mm) or density (HU). For each of the panels A-D, Pearson correlations are provided. Significant correlation between NILT penetration and thickness (p<0.05), but not density (p>0.05).</p

Animal Skull Transmission: Comparison of Dehydrated- Hydrated State (Surface power density: 700 mW/cm²).

<p>Hydrated state measured in air after degassing. Dehydrated state measured in air. Thickness & Mean Power Applied are provided as Mean ± SEM.</p><p>*Significantly different p<0.05. Mouse dia 2.5mm, Rat/Rabbit dia 11.7mm.</p><p>Animal Skull Transmission: Comparison of Dehydrated- Hydrated State (Surface power density: 700 mW/cm²).</p

Human Calvaria NILT Profiles (Dry State- Air Scan): Surface power density 700 mW/cm².

<p>Measures are provided as Mean ± SEM</p><p>Human Calvaria NILT Profiles (Dry State- Air Scan): Surface power density 700 mW/cm².</p