The clinical prospect of treating spinal cord injury by photobiomodulation therapy (PBMT) is unclear as the spinal dosimetry of transcutaneous laser application is unknown, yet essential for clinical recommendations. Light irradiances at 9 sites over an 8cm length along the thoracic to lumbar segment of the spinal canal were measured in 6 cadaver dogs using a flexible intra-spinal probe, under a surface irradiance of 3.14W/cm2. The skin transmits 4-12% of 980nm PBMT light. On-contact technique is ~5 times more efficient than off-contact technique. Transcutaneous transmission of photobiomodulatory irradiance to the spinal canal will benefit from contact-probe technique and skin-clearing approaches.
Transcutaneous photobiomodulation of the spinal cord in rodent models has shown therapeutic effects to spinal cord injury. For translation to human medicine; however, it remains unknown if a therapeutic dose can reach the spinal cord with a non-invasive treatment protocol that does not cause collateral tissue damage. Our previous pilot test on a cadaver dog using a single photo-diode-sensor demonstrated that the transcutaneous transmission of 980nm light to the spinal canal through the shallowest section of the vertebrae was comparable to the transcranial transmission. The use of a single sensor to measure at multiple positions along the spinal canal challenged correlations of the results, due to variations of sensor-tissue geometry after repositioning the sensor within the spinal canal and closing the tissue for light transmission. To identify a potential transmission window for delivering an effective photobiomodulation therapy dose to the spinal cord, and to evaluate inter-subject variations, it is essential to maintain consistency in intra-spinal measurements at multiple positions for any one subject and across multiple subjects. We developed a flexible multi-channel photo-detector-array specifically for measuring the transmission of light to the spinal canal at multiple sites under fixed surface irradiation. The probe, with a 1/4" stem, contains 9 photo-diodes spaced 1cm apart allowing measurement over an 8cm length. Multi-site dosimetry at 980nm was tested in one cadaver dog at a fixed surface (shaved skin) irradiance of 3.18 W/cm2 by deploying the applicator-probe in the spinal canal after hemilaminectomy, and will be repeated in a total of six dogs.
Noninvasive photobiomodulation therapy (PBMT) of spinal cord disease remains speculative due to the lack of evidence for whether photobiomodulatory irradiances can be transcutaneously delivered to the spinal cord under a clinically acceptable PBMT surface irradiation protocol. We developed a flexible nine-channel photodetection probe for deployment within the spinal canal of a cadaver dog after hemilaminectomy to measure transcutaneously transmitted PBMT irradiance at nine sites over an eight-cm spinal canal length. The probe was built upon a 6.325-mm tubular stem, to the surface of which nine photodiodes were epoxied at approximately 1 cm apart. The photodiode has a form factor of 4.80 mm×2.10 mm×1.15 mm (length×width×height). Each photodiode was individually calibrated to deliver 1 V per 7.58 μW/cm2 continuous irradiance at 850 nm. The outputs of eight photodiodes were logged concurrently using a data acquisition module interfacing eight channels of differential analog signals, while the output of the ninth photodiode was measured by a precision multimeter. This flexible probe rendered simultaneous intraspinal (nine-site) measurements of transcutaneous PBMT irradiations at 980 nm in a pilot cadaver dog model. At a surface continuous irradiance of 3.14 W/cm2 applied off-contact between L1 and L2, intraspinal irradiances picked up by nine photodiodes had a maximum of 327.48 μW/cm2 without the skin and 5.68 μW/cm2 with the skin.
In the past four decades numerous studies have reported the efficacy of low level light (laser) therapy (LLLT) as a
treatment for diverse diseases and injuries. Recent studies have shown that LLLT can biomodulate processes in the
central nervous system and has been extensively studied as a stroke treatment. However there is still a lack of
knowledge on the effects of LLLT at the cellular level in neurons. The present study aimed to study the effect of 810
nm laser on several cellular processes in primary cortical neurons cultured from mouse embryonic brains. Neurons
were irradiated with light dose of 0.03, 0.3, 3, 10 and 30 J/cm2 and intracellular levels of reactive oxygen species,
nitric oxide and calcium were measured. The changes in mitochondrial function in response to light were studied in
terms of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP). Light induced a significant
increase in calcium, ATP and MMP at lower fluences and a decrease at higher fluence. ROS was induced
significantly by light at all light doses. Nitric oxide levels also showed an increase on treatment with light. The
results of the present study suggest that LLLT at lower fluences is capable of inducing mediators of cell signaling
process which in turn may be responsible for the biomodulatory effects of the low level laser. At higher fluences
beneficial mediators are reduced but potentially harmful mediators are increased thus offering an explanation for the
biphasic dose response.
Transcranial laser therapy (TLT) using a near-infrared energy laser system was tested in the 2x Tg amyloid precursor
protein (APP) mouse model of Alzheimer's Disease (AD). TLT was administered 3 times/week at escalating doses,
starting at 3 months of age, and was compared to a control group which received no laser treatment. Treatment sessions
were continued for a total of six months. The brains were examined for amyloid plaque burden, Aβ peptides (Aβ1-40 and
Aβ1-42 ), APP cleavage products (sAPPα, CTFβ) and mitochondrial activity. Administration of TLT was associated with
a significant, dose-dependent reduction in amyloid load as indicated by the numbers of Aβ plaques. Levels of Aβ1-40 and
Aβ1-42 levels were likewise reduced in a dose-dependent fashion. All TLT doses produced an increase in brain sAPPα and
a decrease in CTFβ levels consistent with an increase in α-secretase activity and a decrease in β-secretase activity. In
addition, TLT increased ATP levels and oxygen utilization in treated animals suggesting improved mitochondrial
function. These studies suggest that TLT is a potential candidate for treatment of AD.
Stroke is the one of the leading causes of mortality in the United States, claiming 600,000 lives each year. Evidence
suggests that near infrared (NIR) illumination has a beneficial effect on a variety of cells when these cells are exposed to
adverse conditions. Among these conditions is the hypoxic state produced by acute ischemic stroke (AIS). To
demonstrate the impact NIR Transcranial Laser Therapy (TLT) has on AIS in humans, a series of double blind, placebo
controlled clinical trials were designed using the NeuroThera(R) System (NTS). The NTS was designed and developed
to treat subjects non-invasively using 808 nm NIR illumination. TLT, as it applies to stroke therapy, and the NTS will
be described. The results of the two clinical trials: NeuroThera(R) Safety and Efficacy Trial 1 (NEST-1) and
NeuroThera(R) Safety and Efficacy Trial 2 (NEST-2) will be reviewed and discussed.
Studies using the rabbit small clot or rabbit large clot embolic stroke models (RSCEM and RLCEM respectively)
allowed us to alter a single NILT variable while keeping all other variables constant to investigate the variable's effect
on the rabbit's behavioral performance following embolization. In this paper we review results from multiple studies.
Using the RSCEM, we found that Continuous Wave (CW) NILT significantly improves behavioral function when NILT
is administered up to 6 hour post-embolization at 808nm; a durable effect that can last up to 21 days following a single
treatment. Using the RLCEM we found that NILT did not significantly alter intracerebral hemorrhage (ICH) incidence
following embolization, and since intravenous (IV) tissue plasminogen activator (tPA) is currently the primary treatment
of acute ischemic stroke (AIS), we used the RLCEM to determine the safety profile of NILT in combination with tPA.
IV tPA increased ICH incidence by 160%. NILT did not affect the tPA-induced increase in ICH. Lastly, since the
cellular mechanism(s) involved in NILT-mediated neuroprotection have not been elucidated, we measured the effect of
CW and Pulse Wave (PW) NILT on cortical adenosine triphosphate (ATP) content as an indicator of improved cellular
energetics using the RSCEM. Embolization decreased cortical ATP content by 45% compared to naive rabbits, a
decrease that was attenuated by CW NILT (p>0.05). Following PW NILT, delivering 5-35 times higher peak cortical
irradiances than CW NILT, we measured larger increases in cortical ATP content. This is the first demonstration that
NILT significantly increased cortical ATP content in embolized animals.
Large core multimode fibers (MMF) in the range of 100-1000 μm core diameter are commonly used
with infrared lasers in medical, bio-photonics and other fiber optics applications. Angular misalignment of the laser
source to the multimode fiber can lead to unusual angular patterns at the exit of the fiber. The angular content of the
launch beam can result in under-filling, non-uniform angular filling, or over-filling of the MMF modes. Typically,
the beam condition optics at the distal end of the device has a limited impact on these angular modes. The result is
often loss of output power at the distal end or an uncontrolled angular and/or spatial distribution of light. We have
investigated angular misalignment perturbations of various fiber and coupling optics combinations in a medical laser
therapy device. We have quantified the resulting far field perturbations, as well as the resulting broadening of the
fiber output numerical aperture (NA). Angular misalignment may cause the development of so called "donut modes"
with highly inhomogeneous far field mode distribution, as well as a substantial NA broadening effect which may
impact therapy. We have shown that in order to avoid these perturbations, tight tolerancing of fiber coupling opto-mechanics
as well as a thorough alignment procedure is required.
The results of measurements of transmittance of high power laser irradiation through skull bones and scalp are presented. Dependences of transmittance on sample thickness were received. Character of transmittance was investigated and characteristics of heterogeneity of the scattering structure of the skull bones are proposed. Besides that, variation of temperature of skull and scalp surfaces under exposure of high power laser irradiation during experiments was controlled. Experimental results were verified by Monte-Carlo simulations.
Laser devices in clinical applications must eventually be tested via clinical trials. An essential component in clinical
trials is the double-blind study whereby the patient and the treating physician have no knowledge as to whether a given
treatment is active or placebo. In pharmaceuticals, the problem is easily addressed. With laser therapy this can be very
challenging. For some optical therapies, laser heating of tissue, by even as little as a few degrees can indicate to the
patient and/or the physician that the device is active, un-blinding the study. This problem has been analyzed for a
specific laser therapy using a combination of clinical data, analytical methods, finite element modeling, and laboratory
testing. The methods used arrived at a solution, but not necessarily one that could have been predicted easily. This
paper will present a model of tissue heating and the methods used to mask the effects from the laser in an effort to make
active treatment and placebo indistinguishable.
The results of measurements of transmittance of high power laser irradiation through skull bones and scalp are presented. Dependences of transmittance on sample thickness were received. Character of transmittance was investigated and characteristics of heterogeneity of the scattering structure of the skull bones are proposed. Besides that, variation of temperature of skull and scalp surfaces under exposure of high power laser irradiation during experiments was controlled. Experimental results were verified by Monte-Carlo simulations.
The main idea of our work is studying of human brain activity for intense NIR-radiation, cold stress or visual stimulation. For the first part of solution we need to find the power density, which needed for brain response observation. For this, we created Monte-Carlo simulation software and make a comparing with out experimental data.
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