This PDF file contains the front matter associated with SPIE Proceedings Volume 10048, including the Title Page, Copyright information, Table of Contents, and Conference Committee listing.

Photobiomodulation (PBM) describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. One of the organ systems of the human body that is most necessary to life, and whose optimum functioning is most worried about by humankind in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: traumatic events (stroke, traumatic brain injury, and global ischemia), degenerative diseases (dementia, Alzheimer’s and Parkinson’s), and psychiatric disorders (depression, anxiety, post traumatic stress disorder). There is some evidence that all these seemingly diverse conditions can be beneficially affected by applying light to the head. There is even the possibility that PBM could be used for cognitive enhancement in normal healthy people. In this transcranial PBM (tPBM) application, near-infrared (NIR) light is often applied to the forehead because of the better penetration (no hair, longer wavelength). Some workers have used lasers, but recently the introduction of inexpensive light emitting diode (LED) arrays has allowed the development of light emitting helmets or “brain caps”. This presentation will cover the mechanisms of action of photobiomodulation to the brain, and summarize some of the key pre-clinical studies and clinical trials that have been undertaken in this area.

Photobiomodulation (PBM) is an effective tool for the management of spinal pain including inflammation of facet joints. Apart from cervical and lumbar joint pain the upper cervical spine facet joint inflammation can result in the CGH (traumatic or atraumatic in origin). This condition affects children, adults and elders and is responsible for 19% of chronic headache and up to 33% of patients in pain clinics. The condition responds well to physiotherapy, facet joint injection, radiofrequency neurotomy and surgery at a rate of 75%. The other 25% being unresponsive to treatment with no identified features of unresponsiveness. In other conditions of chronic unresponsive cervical pain have responded to photobiomodulation at a level of 80% in the short and medium term. A clinical trial was therefore conducted on a cohort of atraumatic patients from the ages of 5-93 (predominantly Neurologist referred / familial sufferers 2/3 generations vertically and laterally) who had responded to a course of PBM and physiotherapy. The CGH sufferers and their non CGH suffering relatives over these generations were then compared for features that distinguish the two groups. Fifty parameters were tested (anthropmetric, movement and neural tension tests included) and there was a noted difference in tandem stance between the groups (.04 significance with repeated measures). As this impairment is common to benign ataxia and migrainous vertigo and in these conditions there is an ion channelopathy (especially potassium channelopathy). A postulated mechanism of action of PBM would involve modulation of ion channels and this is discussed in this presentation.

Evidence from animal and human studies regarding the biological impact of near infrared light stimulation has significantly increased of late noting the disease modifying properties of photobiomodulation for improving physical and cognitive performance in subjects with a variety of neurodegenerative conditions. Concurrently we see a growing body of literature regarding the efficacy of operant conditioning of EEG amplitude and connectivity in remediating both cognitive and behavioral symptoms of both neuropsychiatric and neurodegenerative disorders including traumatic brain injury, ADHD, PTSD, and dementia. This presentation seeks to outline a treatment model combining these two treatment methods to stop the progression of neurodegeneration using pulsed (10hz), brief (5-20minutes) repeated (1-2x/daily) transcranial and intranasal photobiomodulation with 810nm and 1068nm near infrared phototherapy and operant conditioning of EEG amplitude and coherence. Our initial study on treating dementia with EEG biofeedback (N=37) showed neuroplasticity's potential for modifying cognitive and behavioral symptoms using the evidence from decades of neurological research that never felt the warm touch of a translational researcher's hand. The near infrared interventional studies clarified the order of treatment, i.e., tissue health and renewal were achieved, followed by neural connectivity enhancement. Significant improvements in both immediate and delayed recall and praxis memory as well as executive functioning and behavioral regulation were obtained with each intervention. The inferred synergistic impact of properly combining these approaches is what informs our current clinical applications and future research efforts examining the value of combined treatments for all dementias, parkinson’s disease and age-related dry macular degeneration.

Photobiomodulation with low-power, high-fluence light in the near-infrared range (600-1100nm), also known as low level laser therapy (LLLT), has been used for promoting healing of wounds, reducing pain, and so on. Understanding its physiological effect is essential for treatment optimization and evaluation. In this study, we used diffuse correlation spectroscopy (DCS) to investigate the changes of regional blood flow in skeletal muscle induced by a single session of LLLT. DCS is an emerging optical modality to probe microvascular blood flow in human tissues in vivo. We have developed a software-based autocorrelator system with the benefits such as flexibility in raw photon count data processing, portability and low cost. LLLT was administered at the human forearm with a 1064-nm, continuous-wave laser. The emitting power was 3.4 W in an area of 13.6 cm², corresponding to 0.25W/cm² irradiance. The emitting duration was 10 minutes. Eight healthy adults of any ethnic background, in an age range of 18-40 years old were included. The results indicate that LLLT causes reliable changes in regional blood flow. However, it remains unclear whether these changes are physiological or attributed to the heating effect of the stimulation laser.

Background: Oral mucositis (OM) is a painful consequence of myeloablative hematopoietic cell transplantation (HCT). Extraorally delivered photobiomodulation therapy (PBMT) is a promising novel intervention for the prevention of OM in children. Objectives: With funding from an NIDCR R34 planning grant, the objectives of this study are 1) to model the dosimetry of external PBMT and the optimal device parameters for the planned clinical trial, and 2) to plan and design a placebo-controlled Phase 2 multicenter clinical trial to determine whether extraorally delivered PBMT can reduce the duration of severe OM in children, with intent for implementation under subsequent U01 funding. Methods: External PBMT dosimetry will be evaluated using pediatric head and neck MRI studies to obtain serial measurements of different tissues that will then be used to develop a sophisticated computational model. We plan to conduct a placebocontrolled Phase 2 multicenter clinical trial in which patients 4 to 21 years of age will be randomized 1:1:1 to receive external PBMT dose 1x, external PBMT dose 2x, or sham PBMT starting from conditioning, daily until day +20 post- HCT. Significance: Extraorally delivered PBMT is a feasible, potentially efficacious intervention that could improve the quality of life for all children undergoing myeloablative HCT. The planned Phase 2 study, based on rigorous dose modeling and with detailed attention to uniform delivery of therapy and OM assessments, will provide critical efficacy data and the potential basis for a subsequent definitive Phase 3 trial. Grant Support: NIDCR R34 DE025908-01

Trigeminal neuralgia (TN) is a disabling syndrome and one of the most painful conditions that are often reported in female patients older than 50 years of age. The treatment generally includes drugs or surgical approaches. Laser Phototherapy -LPT has also been proposed as a safe and effective treatment modality. This work reports a series of patients of the Center of Biophotonics of the Federal University of Bahia (2000-2016) treated with LPT. Following standard anamneses, clinical and imaginologic examination and with the diagnosis of Trigeminal Neuralgia, the patients were set for light treatment. Treatment consisted of three sessions a week during six week. Prior irradiation, the patients were asked to score their pain using a VAS. λ780, λ 790, λ 830nm lasers were used on each session. Most patients were female (74.8%). At the end of the 12 sessions the patients were again examined and score their pain using VAS. No other intervention was carried out during the treatment. The results were statistically analyzed and showed that, the use of lower Energy Density in smaller number of session in younger patients presents higher effectivity on treating the pain on TN patients.

Electromagnetic energy of laser light has some typical properties which are found to be a premise for discussions on laser irradiation abilities to control the severe and chronic disorders in TMJ. In world literature PDT application is recommended when soft tissues in TMJ are damaged, in cases of degenerative diseases of discus articularis, medial and lateral distensions of joint ligaments, chronic inflammatory processes in TMJ, occlusion trauma, etc. The aim of our clinical study was to analyze the theoretical achievements up to now in depth and basing on our clinic al observations suggest new methods guaranteeing high therapeutic efficacy of Photodynamic therapy.

Can ‘light’ be a Drug? To satisfy this definition as a pharmaceutical agent, light must be absorbed and change bodily function. Much evidence from our understanding of our visual cycle and Vitamin D metabolism have all noted this phenomenon. Advances in optophotonic technologies along with a better understanding of light-tissue interactions, especially in in vivo optical imaging and optogenetics, are spearheading the popularity of biophotonics in biology and medicine. The use of lasers and light devices at high doses in dermatology, ophthalmology, oncology and dentistry are now considered mainstream for certain clinical applications such as surgery, skin rejuvenation, ocular and soft tissue recontouring, anti-tumor and anti-microbial photodynamic therapy. In contrast, therapeutic use of low dose biophotonics devices is called Low Level Light / Laser Therapy (LLLT), now termed Photobiomodulation (PBM) Therapy. This therapy is defined as a non-thermal use of non-ionizing forms of electromagnetic radiation to alleviate pain, inflammation, modulating the immune responses and promoting wound healing and tissue regeneration. Surprisingly, despite vast volumes of scientific literature from both clinical and laboratory studies noting the phenomenological evidences for this innovative therapy, limited mechanistic insights have prevented the development of rigorous, reproducible clinical protocols. This presentation will outline our current efforts at ongoing efforts in our group to assess molecular pathways and precisely define clinical treatment variables to enable clinical translation with PBM therapies.

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP.

Photobiomodulation stands as a recommended therapy for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. We assessed cancer cell metabolism and proliferation in vitro and in vivo after exposure to different laser protocols. We exploited both ectopic melanoma and a more physiological oral carcinogenesis mouse model, followed by molecular, histological and immunohistochemical characterization. Laser irradiation resulted in a slightly increase in cell metabolism and proliferation in vitro, albeit each protocol exerted a difference response. Of notice, in vivo laser light reduced tumour growth and invasiveness, indicating e beneficial effect on tumor microenvironment. Laser-treated tumors were surrounded and infiltrated by immune cells, mainly lymphocytes and dendritic cells, paralleled by an enhanced secretion of type I interferons. In contrast, the number of pro-angiogenic macrophages was reduced in response to laser irradiation, with consequent normalization of the tumor vasculature. Based on these finding we have also started exploring the effect of photobiomodulation on lymphocyte response in an experimental model of vaccination. Preliminary data indicate that laser light induced antigen-specific CD8+ and CD4+ T cell responses. In conclusion, our data point toward photobiomodulation as an effective strategy to boost the immune response in vivo, with relevant, therapeutic activities in both cancer and vaccination experimental models. These results support the safe use of laser light on cancer patients and open the way to innovative therapeutic opportunities.

Laser acupuncture is an effective photochemical and nonthermal stimulation of traditional acupuncture points with lowintensity laser irradiation, which is advantageous in painless, sterile, and safe compared to traditional acupuncture. Laser diode (LD) provides single wavelength and relatively-higher power light for phototherapy. The quantitative effect of illumination parameters of LD in use of laser acupuncture is crucial for practical operation of laser acupuncture. However, this issue is not fully demonstrated, especially since experimental methodologies with animals or human are pretty hard to address to this issue. For example, in order to protect viability of cells and tissue, and get better therapeutic effect, it’s necessary to control the output power varied at 5mW~10mW range, while the optimized power is still not clear. This study aimed to quantitatively optimize the laser output power, wavelength, and irradiation direction with highly realistic modeling of light transport in acupunctured tissue. A Monte Carlo Simulation software for 3D vowelized media and the highest-precision human anatomical model Visible Chinese Human (VCH) were employed. Our 3D simulation results showed that longer wavelength/higher illumination power, larger absorption in laser acupuncture; the vertical direction emission of the acupuncture laser results in higher amount of light absorption in both the acupunctured voxel of tissue and muscle layer. Our 3D light distribution of laser acupuncture within VCH tissue model is potential to be used in optimization and real time guidance in clinical manipulation of laser acupuncture.

The effect of LED phototherapy on blood lactate level in the muscle was studied. A 450cm² large red and near infrared LED pad with its irradiance of 10mW/cm² was applied for 10 minutes to brachial muscle and quadriceps muscle of thigh to the participants before and after the Taekwondo contest. Blood samples from the participants were taken at 5 minutes after the competition and 10 minutes after the recovery. The test results showed that the LED therapy (LEDT) before and after the competition had a significant effect on the decrease of blood lactate level of the participants.

Photobiomodulation therapy (PBMt) has been used to increase muscle performance and improve recovery when applied before exercise. We aimed to evaluate the effects of PBMt using LASER on muscle oxygenation and performance. The study was a randomized, participant and assessor-blinded, within-subject crossover trial with placebo control to test the viability of the methods. Five physically active young women were randomly assigned to either placebo, or active PBMt (12 diode cluster probe; 904 nm; 60 mW; 250 Hz; 43.2 J per site, 129.6 J total) in contact over rectus femoris (RF) muscle of the dominant limb immediately before an isokinetic fatigue protocol. A one-week wash-out period preceded cross-over. Electromyography and isokinetic performance measures were evaluated. Absolute concentrations of deoxygenated haemoglobin and myoglobin (deoxy[Hb + Mb]) of the RF, an index of local microvascular fractional O2 extraction, was monitored continuously by near-infrared spectroscopy (NIRS). Total haemoglobin concentration as an indicator of microvascular haematocrit was calculated as the sum of the deoxy[Hb + Mb] and oxy[Hb + Mb] signals. PBMt pre-conditioning reduced time to peak torque when compared to placebo (P<0.05). PBMt resulted in a noticeably reduced trend in deoxy[Hb + Mb] during exercise compared to placebo (P>0.05). PBMt before exercise improves indicators of muscle performance, potentially by increasing local matching of bulk and microvascular O2 delivery relative to skeletal muscle O₂ utilisation. Further work is required to understand the effect of PBMt on haemodynamic and metabolic characteristics of muscle.

A novel treatment modality for photobiomodulation (PBM) is introduced called High Intensity Physio Light (HIPL) Therapy with a light source at 640 nm wavelength, 20 nm bandwidth, and up to 20 W in large 10 cm flat beam. This report exemplifies the efficacy performance of this method with three pre-clinical cases: (i) ankle: sport injury, (ii) foot: bone fractures, and (iii) shoulder: musculoskeletal disorder (MSD). In all cases, the patients systematically experienced a significant pain reduction (by 2 / 10 - 4 / 10) on a visual pain scale. In case (ii) and (iii), a steady improvement and complete recovery of the patient was respectfully obtained. This report describes the experimental treatment condition for each case, and introduces an intensity-dependant propagation model to explain our observation.

Photobiomodulation (PBM) has been used successfully for the treatment of nervous system and has been demonstrated in the rodent model. In contrast, the percutaneous use of PBM to treat spinal cord of companion animals is expected to be challenging due to the significant attenuation of light energy as it travels through the thick and heterogeneous layers of tissue and bone to reach the level of the spinal cord. This pilot study was performed on a cadaverous dog to determine if the recommended bio-stimulatory treatment dose can be delivered to the spinal canal via percutaneous application of a clinically acceptable surface dose. The dose reaching the spinal canal after percutaneous application was measured at 980nm by using a miniature photo-diode sensor with a dose-response sensitivity of 1V per 1mW/cm2 dose and a 2mm spherical isotropic fiber-optical diffusor probe. The two sensors were embedded in different longitudinal positions along the dorsal portion of the spinal canal just below the soft tissues and vertebral processes in a 40lbs cadaverous dog. The spinal cord was then accessed via a hemilaminectomy. Once embedded in the target tissue, 1W-10 W surface irradiation was applied. At the T12/13 and T13/L1 intervertebral disc positions, photo-diode sensors detected the intra-spinal dose above the noise floor at the 10W surface dose. A narrow treatment window for percutaneous PBM in large dog may exist only for the shallowest segment of the spinal cord, which may be important to avoid potential collateral photothermal effects. Works for simultaneous multi-site intra-spinal measurements are on-going.

Temporomandibular disorders - TMDs are common painful multifactorial conditions affecting the temporomandibular joint whose treatment depends on the type and symptoms. Initially it requires pain control and for this, drugs, biting plates, occlusal adjustment, physiotherapy or their association are used. Laser-phototherapy (LPT) has been used on the treatment of pain of several origins including TMDs. It is known that wavelength, energy density, frequency of application influences the outcome of many clinical protocols. This work reports a series of patients of the Center of Biophotonics of the Federal University of Bahia over 15 years. Following standard anamneses, clinical and imaginologic examination and with the diagnosis of any type of TMD, the patients were set for light treatment. Treatment consisted of three sessions a week during six week. Prior irradiation, the patients were asked to score their pain using a VAS. IR and/or Red diode lasers were used on each session. The medical records of 432 patients (73 male and 359 female) suffering from TMJ disorders were revised. Most patients were female (~47.9 years old). At the end of the 12 sessions the patients were again examined and score their pain using VAS. No other intervention was carried out during the treatment. The results were statistically analyzed and showed that 51.16 % of the patients were asymptomatic or improved after treatment. It is concluded that LPT was effective on pain reduction on TMJ disorders of several origins.

The aim of this study is to evaluate the Antimicrobial Photodynamic Therapy (AmPDT) of microorganisms mediated by red LED (λ640 ± 5 ηm, 120 mW, spot of 0.785 cm²) associated with Photogem. Microorganisms of the posterior dorsal region of the tongue and oral mucosa were collected and inoculated in 8 mL of TSB medium overnight followed by inverse homogenization. Culture plates with 24 wells were used for the irradiated and non-irradiated species. Each well received 400 μL of the suspension containing the microorganisms. In eight wells no Photogem was used and they were the irradiated and non-irradiated controls. The remain of the wells had Photogem applied with a pre-irradiation time of 5 min in concentrations of 40, 20, 10, 5 e 2.5 μg/mL. LED was applied for 5 min and 45 sec (50 J/cm²). After agitation, 200 μL were withdrawn from each well and colorimetric measurements were immediately taken. Other 200 μL were withdrawn from the wells after 1 hour in bacteriological incubator for a second measurement. The best results found were for 40 μg/mL of Photogem associated with LED irradiation and immediate (36.7%) and for 5 μg/mL with LED irradiation with measurements one hour after incubation (42.8%). This study suggests that antimicrobial photodynamic therapy with Photogem associated to red LED can be a potential mechanism of control of oral microorganisms.

Introduction Laser light Electromagnetic energy has some typical properties for discussions on laser irradiation abilities to control the acute and chronic disorders in TMJ. Material and Methods During the last six years we have been completed well controlled clinical trials based on the criteria of the American Academy of orofacial pain. The study over the 600 patients (300 women and 300 men), mean age of 47 years have been developed. Patients have been selected on the main clinical sign of TMJ pain and have been divided into four main groups according to the type of PDT method. Based on the action spectra, various wavelengths have been used for TMJ Photodynamic Therapy. Constant dose and time of exposition, as well as various range of frequencies have been applied. In this way the Laser biostimulation response has been directly proportional to the total energy dose, depending of light intensity. Physiological and clinical effects of the followed “active regions”– 660 – 680, 760 – 780, 810 – 830 and 904 – 987 nm have been valued by method of comparative analysis. Methods applied: LLLT - TENS - red surface laser acupuncture (LA), PIPBM – LA, Laser bioenergetics approach, Complex therapeutic program (CTP). Results evaluation will be demonstrated by comparative digital ortopantomograph analysis, EEG brain maps, VAS, a metric analysis of the level of the maximum active Mandible opening and EPST through electrophysiological signal evaluation of the patient’s body.

Overexpression of the Epidermal Growth Factor Receptor (EGFR) by cancer cells is associated with a poor prognosis for the patient. For several decades, therapies targeting EGFR have been designed, including the use of monoclonal antibodies and small molecule tyrosine kinase inhibitors. The use of these molecules had good clinical results, although its efficiency (and specificity) is still far from being optimal. In this paper, we present a new approach for a possible new cancer therapy targeting EGFR and using low intensity 280nm light. The influence of 280nm UVB illumination on cancer cells stimulated with 2nM of EGF was followed by time-lapse confocal microscopy. The 280nm illumination of the cancer cells blocks EGFR activation, inhibiting EGFR internalization and cell migration thus inhibiting the transition to the metastatic phenotype. Exposure time is a very important factor. The higher the illumination time the more significant differences were observed: 280nm light delayed or completely halted EGFR activation in the cell membrane, mainly at the cell junction level, and delayed or halted EGFR endocytic internalization, filopodia formation and cell migration.