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3 pags., 2 figs., This work was completed through funding from an MGH Medicine Innovation Program Spark Innovation Award and support from the MGH Healthcare Transformation Laboratory and Harvard Catalyst. Harvard Catalyst is supported by the Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health award UL1TR002541) and Harvard University and its affiliated academic health care centers. Dr Dickey received funding from a NIH NIAMS K23 grant 1K23AR079586-01.

For field research of non-visual effects of light, accurate measurement of personal light exposure is required. A consensus framework for light-dosimetry could improve non-visual field research and ensure comparability between studies. Here, we present a review of methodologies used in non-visual light-dosimetry studies published to date, focussing on considerations regarding the measurement and preparation of personal light exposure data. Overall, a large variability in the studies’ methodologies is observed, highlighting the need for a consensus framework. We propose methodological considerations that should be included in such a framework and that can guide future studies. Furthermore, we highlight important points that should be addressed in future research to ensure compatibility between different dosimetry studies. Taken together, this review effort underlines the importance of a systematic approach to light-dosimetry in order to harness all the power of integrative lighting research in real life.

BACKGROUND AND OBJECTIVES Photodynamic therapy (PDT) has gained widespread popularity in the last decades because of its distinctive advantages over the other commonly used cancer treatments. PDT dosimetry is a crucial factor in achieving a good optimization of PDT treatment planning. PDT dosimetry is a complex task since light dose as well as photosensitizer and oxygen concentrations in tissue need to be measured (ideally continuously) to be able to fully characterize the biological response. Light dose in PDT is routinely measured by the optical fibers that provide dose data at a limited number of discrete points and are not able to capture spatial dose profiles. The objective of this study is to propose and develop a new optical method for online monitoring of the dose profile data for PDT. STUDY DESIGN/MATERIALS AND METHODS Using the digital holography technique, first, the general sketch of an experimental setup for PDT light dosimetry is provided. The theory behind the proposed method for using the experimental setup in PDT light dosimetry is fully described, and its limits of validity are determined. In a proof of principle study, the ability of the method for online monitoring of the absorbed light dose profile in PDT is evaluated by a simple experimental setup. RESULTS The experimental results confirm the usefulness of the proposed method in providing continuous online dose profiles. The absorbed light dose profiles from an infrared light source in a quartz cell containing water are measured and shown. The depth-dose curves are extracted and it is shown that how these dosimetric data can be used for assisting the physicians in determining the appropriate spatiotemporal characteristics for treating the infected tissues and solid tumors with the required light dose amounts. A conversion relation is also derived for transforming the measured light dose with the proposed method to the most frequently used dose values by PDT practitioners, in terms of light power per square area. CONCLUSIONS There is no restriction in using the method with other commonly used light sources in PDT, like light-emitting diodes and filtered lamps, with different wavelengths in visible or infrared regions of the spectrum. More complex experimental setups can be used in future studies to study the role of accumulated photosensitizers in malignant tissues. The proposed method in this study can also be used for light dose monitoring in other biomedical applications, where light is used for treating special diseases, and patients must receive sufficient amounts of light dose. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

The discovery of coherent laser light in 1960 shifted and expanded the biomedical applications of radiation to the non-ionizing part of the electromagnetic spectrum. As in the case of ionizing radiation, but considering the laser specific features, the effective, safe and ethically acceptable use of biomedical laser technology requires interdisciplinary collaboration between physicists, engineers and physicians. This should extend at the research, preclinical and clinical level, inspiring at this time the dynamic discipline of Medical Physics in new areas. With this work we aim to introduce the interested reader in the need of dosimetry in medical applications of laser radiation, as this field is still unexplored. After some necessary definitions, we give a brief review of the basic biophysical mechanisms of coherent light-matter interactions. The manuscript focuses on biomedical laser applications in diagnosis and therapy (i.e. in Theranostics). From the vast field of laser theranostic applications we have chosen some experimental and theoretical results - examples of quantification of the laser effect, particularly relevant to soft and hard tissue laser ablation, laser induced photodiagnosis and photodynamic therapy of cancer. These topics intend to highlight the important role of Medical Physicists in the optimization of well-established laser based clinical procedures and mainly emerge the necessity of the relevant dosimetry for each application. Finally, we hope that this effort is going to give food for thought and highlight the importance of deep knowledge of the physics behind some everyday medical applications.

With the continued development of non-toxic photosensitizer drugs, interstitial photodynamic therapy (iPDT) is showing more favorable outcomes in recent clinical trials. IPDT planning is crucial to further increase the treatment efficacy. However, it remains a major challenge to generate a high-quality, patient-specific plan due to uncertainty in tissue optical properties (OPs), µ a and µ s . These parameters govern how light propagates inside tissues, and any deviation from the planning-assumed values during treatment could significantly affect the treatment outcome. In this work, we increase the robustness of iPDT against OP variations by using machine learning models to recover the patient-specific OPs from light dosimetry measurements and then re-optimizing the diffusers’ optical powers to adapt to these OPs in real time. Simulations on virtual brain tumor models show that reoptimizing the power allocation with the recovered OPs significantly reduces uncertainty in the predicted light dosimetry for all tissues involved.

Photodynamic therapy (PDT) is an innovative treatment of malignant or diseased tissues. The effectiveness of PDT depends on light dosimetry, oxygen availability, and properties of the photosensitizer (PS). Depending on the medium, photophysical properties of the PS can change leading to increase or decrease in fluorescence emission and formation of reactive oxygen species (ROS) especially singlet oxygen (1O2). In this study, the influence of solvent polarity, viscosity, concentration, temperature, and pH medium on the photophysical properties of protoporphyrin IX, pyropheophorbide-a, and Photofrin® were investigated by UV-visible absorption, fluorescence emission, singlet oxygen emission, and time-resolved fluorescence spectroscopies.

Background: Photodynamic therapy (PDT) is a promising treatment option for recurrent sinonasal malignancies. However, light administration in this area is challenging given the complex geometry, varying tissue optical properties and difficult accessibility. The goal of this study was to estimate the temporal and spatial variation in fluence and fluence rate during sinonasal mTHPC-mediated PDT. It was investigated whether the predetermined aim to illuminate with a fluence of 20 J⋅cm−2 and fluence rate of 100 mW⋅cm−2 was achieved. Methods: In eleven patients the fluence and fluence rates were measured using in vivo light dosimetry at the target location during real-time sinonasal PDT. There was a variance in sinonasal target location and type of light diffuser used. In four patients two isotropic detectors were used within the same cavity. Results: All measurements showed major fluence rate fluctuations within each single isotropic detector probe over time, as well as between probes within the same cavity. The largest fluence rate range measured was 328 mW⋅cm−2. Only one probe showed a mean fluence rate of ∼100 mW⋅cm−2. Taken all probes together, a fluence rate above 80 mW⋅cm−2 was measured in 31 % of the total light exposure; in 22 % it was less than 20 mW⋅cm−2. Thirty-three percent showed a fluence of at least 20 J⋅cm−2. Conclusions: The current dosimetry approach for sinonasal intra-cavity PDT shows major temporal and spatial variations in fluence rate and a large variance in light exposure time. The results emphasize the need for improvement of in vivo light dosimetry and dosimetry planning.

An in vivo validation study was performed to confirm the accuracy of extraoral photobiomodulation therapy (PBMT) dosimetry determined by modelling. The Monte Carlo technique was utilized to calculate the fluence rate and absorbed power of light delivered through multi-layered tissue. Optical properties used during Monte Carlo simulations were taken from the literature. Morphological data of four study volunteers were acquired using magnetic resonance imaging (MRI) scans. Light emitting diode (LED) coupled to a power meter were utilized to measure transmitted power through each volunteer’s cheek, in vivo. The transmitted power determined by Monte Carlo modelling was compared to the in vivo measurements to determine the accuracy of the simulations. Experimental and simulation results were in good agreement for all four subjects. The difference between the mean values of the measured transmission was within 12% from the respective transmission obtained using Monte Carlo simulations. The results of the study indicate that Monte Carlo modelling is a robust and reliable method for light dosimetry.

International audience; Complete and homogeneous illumination of the target is necessary for the success of a photodynamic therapy (PDT) procedure. In most applications, light dosimetry is done using detectors placed at strategic locations of the target. In this study we propose a novel approach based on the combination of light distribution modeling with spatial localization of the light applicator for real time estimation and display of the applied dose on medical images. The feasibility approach is demonstrated for intrapleural PDT of malignant pleural mesothelioma.

Previous dosimetric studies during photodynamic therapy (PDT) of superficial lesions within a cavity such as the nasopharynx, demonstrated significant intra- and interpatient variations in fluence rate build-up as a result of tissue surface re-emitted and reflected photons, which depends on the optical properties. This scattering effect affects the response to PDT. Recently, a meta-tetra(hydroxyphenyl)chlorin-mediated PDT study of malignancies in the paranasal sinuses after salvage surgery was initiated. These geometries are complex in shape, with spatially varying optical properties. Therefore, preplanning and in vivo dosimetry is required to ensure an effective fluence delivered to the tumor. For this purpose, two 3D light distribution models were developed: first, a simple empirical model that directly calculates the fluence rate at the cavity surface using a simple linear function that includes the scatter contribution as function of the light source to surface distance. And second, an analytical model based on Lambert's cosine law assuming a global diffuse reflectance constant. The models were evaluated by means of three 3D printed optical phantoms and one porcine tissue phantom. Predictive fluence rate distributions of both models are within +/- 20% accurate and have the potential to determine the optimal source location and light source output power settings.

Pleural photodynamic therapy (PDT) is performed intraoperatively for the treatment of microscopic disease in patients with malignant pleural mesothelioma. Accurate delivery of light dose is critical to PDT efficiency. As a standard of care, light fluence is delivered to the prescribed fluence using eight isotropic detectors in pre-determined discrete locations inside the pleural cavity that is filled with a dilute Intralipid solution. An optical infrared (IR) navigation system was used to monitor reflective passive markers on a modified and improved treatment delivery wand to track the position of the light source within the treatment cavity during light delivery. This information was used to calculate the light dose, incorporating a constant scattered light dose and using a dual correction method. Calculation methods were extensively compared for eight detector locations and seven patient case studies. The light fluence uniformity was also quantified by representing the unraveled three-dimensional geometry on a two-dimensional plane. Calculated light fluence at the end of treatment delivery was compared to measured values from isotropic detectors. Using a constant scattered dose for all detector locations along with a dual correction method, the difference between calculated and measured values for each detector was within 15%. Primary light dose alone does not fully account for the light delivered inside the cavity. This is useful in determining the light dose delivered to areas of the pleural cavity between detector locations, and can serve to improve treatment delivery with implementation in real-time in the surgical setting. We concluded that the standard deviation of light fluence uniformity for this method of pleural PDT is 10%.

Photodynamic Therapy (PDT) is a technique used in the selective destruction of cancer cells and requires the previous knowledge of light dosimetry and photosensitizer drug (PS) concentration to apply on cells. Therefore, a laboratory platform is required for further evaluation, e.g. to make evaluation and assays on previously collected cells by biopsy to determine the best combination of light dose and PS concentration. In this context, this paper presents a low-cost, low-sized and flexible Wireless Portable Evaluation Platform for PDT assays on cells. The W-PEP was tested and evaluated using assays with Human Gastric Adenocarcinoma (AGS) cells. The AGS cells were exposed to the 5-aminolevulinic acid (ALA), which is a precursor of the photosensitive agent Protoporphyrin IX (PpIX) with absorption at 635nm. The W-PEP is composed by 16 small-sized LEDs matrix with peak transmittance at 634nm mounted in a PCB and controlled by ESP32-DevKitC®, a power bank to supply the lighting and the controlling systems and 3D printed components specially designed to allow portability and PDT assays. A graphical user interface (GUI) application for mobile devices was developed allowing the bi-directional communication between the smartphone and W-PEP via Bluetooth. The measurements with AGS cells proved this W-PEP was effective in its purpose and promoted cell death in samples treated with ALA and a final light dose of 5J/cm2 after 49 minutes of light exposure. This W-PEP has 140mm of both length and width, 75mm of height and costs about $82.10. To finish, this system checks the optimal conditions that will be applied in the treatment after, thereby decreasing the costs and time of the application.

Daylight activation for photodynamic therapy (PDT) of skin lesions is now widely adopted in many countries as a less painful and equally effective treatment mechanism, as compared to red or blue light activation. However, seasonal daylight availability and transient weather conditions complicate light dose estimations. A method is presented for dose planning without placing a large burden on clinical staff, by limiting spectral measurements to a one-time site assessment, and then using automatically acquired weather reports to track transient conditions. The site assessment tools are used to identify appropriate treatment locations for the annual and daily variations in sunlight exposure for clinical center planning. The spectral information collected from the site assessment can then be integrated with real-time daily electronic weather data. It was shown that a directly measured light exposure has strong correlation (R(2): 0.87) with both satellite cloud coverage data and UV index, suggesting that the automated weather indexes can be surrogates for daylight PDT optical dose. These updated inputs can be used in a dose-planning treatment model to estimate photodynamic dose at depth in tissue. A simple standardized method for estimating light dose during daylight-PDT could help improve intersite reproducibility while minimizing treatment times.

Glioblastoma multiforme, the most common and aggressive type of brain cancer, has a dismal prognosis due to inevitable tumor recurrence after maximum treatment with surgery, radiotherapy, and chemotherapy. Recent advances in miniaturized, implantable wireless light delivery devices have demonstrated the potential of chronic treatment of subcutaneous tumors using photodynamic therapy - the selective activation of light-sensitive drugs (photosensitizers) with light to destroy cancer cells. Here we describe the design of a conformal wireless light-emitting mesh (1 cm diameter) to extend this treatment modality to the cortical surface of the brain. The device is wirelessly powered to enable noninvasive activation of intravenously-delivered photosensitizers for chronic treatment, and integrates multiple light-emitting diodes to illuminate large areas. We demonstrate implantation feasibility in rat brain and a light dosimetry control using a harmonic feedback technique. Deploying this device in vivo in combination with selective photosensitizer uptake may enable prolonged suppression of tumor recurrence and increased survival time.

Background and Objectives: The focus of this study was to demonstrate the application of our finite element method (FEM) to guide light dosimetry for I-PDT of locally advanced VX2 carcinoma. Methods: VX2 carcinoma was surgically implanted in either the sternomastoid muscle of the neck (n = 6) or the biceps femoris of the thigh (n = 8) of New Zealand White rabbits. Periodic computerized tomography scans were used to assess tumor growth. Once the VX2 tumors reached a volume of approximately 3-15 cm^3, our image-based FEM was used to develop individualized treatment plans for I-PDT to deliver our recently suggested threshold intratumoral light irradiance and fluence (1). I-PDT was performed with 630-nm light that was administered 24 hours after injection of 5 mg/kg porfimer sodium. In several of the VX2 tumors, multiple sessions of consecutive light illumination were required to deliver the threshold light irradiance and the FEM was adjusted to simulate these treatments. Light dosimetry measurements were taken during treatment to monitor the intratumoral irradiance and fluence. Results: Six rabbits had no tumor recurrence within 6-12 weeks post I-PDT. Eight rabbits experienced local control, but were euthanized before the end of the study period due to either metastasis or infection. Tumor metastasis was often observed prior to treatment. Normal tissue damage was observed and managed in some rabbits. There were no treatment related deaths. Conclusions: Our results suggest that our FEM-based treatment planning can be applied in the safe and effective delivery of I-PDT to locally advanced cancers. This work is currently being translated into a clinical study. References 1.Shafirstein G, Bellnier DA, Oakley E, Hamilton S, Habitzruther M, Tworek L, Hutson A, Spernyak JA, Sexton S, Curtin L, Turowski SG, Arshad H, Henderson B. Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer. Br J Cancer. 2018;119(10):1191-9. Acknowledgements: Supported in part by NCI/NIH R01 CA193610 to GS. We thank Diane Filippini and Raymond Wasielewski for their assistance in obtaining the CT scans and Dr. Craig Hendler MD for conducting diagnosis of the CT scans. We thank the staff of Laboratory Animal Shared Resource at Roswell Park. We thank Concordia Laboratories Inc. for providing the Photofrin® at no cost.

Pretreatment Planning and Light Dosimetry for Interstitial PDT of Locally Advanced Cancer Gal Shafirstein¹, David Bellnier¹, Emily Oakley¹, Michael Habitzruther¹, Sasheen Hamilton¹, Hannah Cooper¹, Sarah Chamberlain1, Alan Hutson2, Sandra Sexton3, Leslie Curtin3, Joe Spernyak4, Steven Turowski4, Hassan Arshad5, Lawrence Tworek¹, Matthew Mallory¹ and Barbara Henderson1. ¹ Photodynamic Therapy Center at the Department of Cell Stress Biology, and ² Department of Biostatistics and Bioinformatics, 3Laboratory Animals Shared Resources, 4Translational Imaging Shared Resource, 5Department of Head and Neck Surgery. Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA Objective: To highlight the critical need for pretreatment planning and light dosimetry in administering interstitial photodynamic therapy (I-PDT) in the treatment of locally advanced cancer (LAC). Background: There is no effective standard treatment for LAC that failed to respond to surgery and chemo-radiation. The newest immunotherapies are effective in only 5-16% of the cases. I-PDT can be considered if the target tumor does not invade a major blood vessel, and the tumor is accessible to fiber-optic placement. Multiple fibers are required for interstitial illumination of the target tumor and margins. Image-based pretreatment planning is used to determine the number and proposed location of fibers. Light dosimetry is employed to measure intratumoral light fluence and irradiance. To date, it was acceptable that a threshold intratumoral light fluence is required for adequate response. Whereas, we demonstrated that intratumoral light irradiance impacts tumor response [1]. Overview: This talk will present an image-based finite element method (FEM) approach for guiding I-PDT. We will discuss the importance of delivering a threshold intratumoral light irradiance in addition to threshold fluence. We will demonstrate that even if a threshold fluence is delivered, an inadequate intratumoral irradiance will result in poor response. We will reveal that adequate light irradiance and fluence can yield up to 90% cure rate in mice and excellent local control in rabbits with LAC. We will present our image-based FEM and light dosimetry approach to translate the preclinical findings to test I-PDT in the treatment of patients with locally advanced head and neck cancer. References 1.Shafirstein G, Bellnier DA, Oakley E, Hamilton S, Habitzruther M, Tworek L, Hutson A, Spernyak JA, Sexton S, Curtin L, Turowski SG, Arshad H, Henderson B. Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer. Br J Cancer. 2018;119(10):1191-9. Acknowledgements: Supported in part by NCI/NIH R01 CA193610 to GS, P01CA55791 to Sandra Gollnick, and by Roswell Park Comprehensive Cancer Center Support Grant P30CA16056. We thank Diane Filippini and Raymond Wasielewski for their assistance in obtaining the CT scans and Dr. Craig Hendler MD for conducting diagnosis of the CT scans. We thank the staff of Laboratory Animal Shared Resource at Roswell Park. We thank Concordia Laboratories Inc. for providing the Photofrin® at no cost.

Interstitial photodynamic therapy (iPDT) is currently being investigated as a light-based treatment option for highly malignant brain tumours (glioblastomas/GBM). To obtain a sufficient irradiation of the tumour, quantitative knowledge about the light propagation in the tissue is required for the light dosimetry calculations underlying the clinical treatment planning. To individualize the light dosimetry calculations, the optical properties of the irradiated tissue need to be determined in-vivo. A novel approach for this purpose is based on the direction-resolved light detection within the tissue, using a rotating optical side-view probe. During measurement, the tissue is irradiated via a separate interstitially placed light applicator, and from the angular dependence of the recorded signal the optical tissue properties are calculated, based on a solution of the radiative transfer equation (RTE). Measurements were performed on liquid tissue phantoms and biological tissue samples. As a result, an over- and underestimation of the calculated optical absorption and scattering coefficients may arise in some situations, but the effective attenuation coefficient remains largely unaffected and corresponds well with literature values.

INTRODUCTION AND OBJECTIVES:To achieve a pre-defined photosensitizer dose and photon irradiance for PDT of NMIBC, independent of a patient’s bladder volume, shape and bladder wall optical propertie...

BACKGROUND: Complete and homogeneous illumination of the pleural cavity is essential to the success of photodynamic therapy (PDT) for mesothelioma, but remains a challenge. Knowing the repartition and propagation of light around the light applicator could be the first step towards optimizing dosimetry. Here we propose a characterization method of the illumination profile of a specific light device. METHODS: The light wand, made of a cylindrical diffuser located inside an endotracheal tube, was fixed in a tank filled with dilute 0.01% intralipid. Light dosimetry was performed around the tip of the wand using two complementary methods: direct measurements of light power with an isotropic probe and measurements of light distribution characterization. RESULTS: Dosimetry with the isotropic probe showed an ellipse-shaped illumination. An optimized effective attenuation coefficient was deduced. Combined with the spatial representation, a theoretical illumination profile was established with iso-surfaces of fluence rate, defining a gradient light dose according to the distance from the diffuser. CONCLUSION: A theoretical illumination profile of a light device was established and could be part of an intra-operative dosimetry system to improve light delivery during intrapleural PDT. Copyright © 2016. Published by Elsevier B.V.

Background and Objective: Extraoral photobiomodulation therapy (PBM Therapy) is a novel treatment for the prevention of oral mucositis, a painful side effect of myeloablative chemotherapy, and there are no standardized dosimetry protocols for this procedure. We used Monte Carlo modeling to determine optimal parameters for a safe and efficacious treatment. The objective of this work was to experimentally validate the results of Monte Carlo dose modeling of extraoral PBM Therapy by conducting a pilot validation study. Methods: Light penetration through the right cheek of four volunteers with skin types I-VI was measured. A 69-LED array with an area of 31.2 cm2 was applied to the external cheek delivering 26 mW/cm2 at 850 nm to the surface. Power density at the intraoral mucosa was recorded under a controlled pressure of 18gm/cm2. To obtain morphological information, we acquired T1 weighted MRI images of the volunteers' heads and measured the thickness of the skin, fat, and muscle layers of the cheek of each volunteer. These anatomical data together with the optical properties from the literature were used to simulate light propagation through the right cheek. Results and Conclusions: Our study revealed that experimental and simulation results were in good agreement for all 4 subjects. The difference between the mean values of the measured fluence rates was within 16% from the respective fluence rates obtained using Monte Carlo simulations. We confirmed that there was no temperature increase due to illumination. Monte Carlo modeling is a robust and reliable method for PBM Therapy light dosimetry.

Although the versatility of photodynamic therapy (PDT) is well established, the technical aspects of light delivery systems vary significantly depending on the targeted organ. This article describes the optical properties of a light and drug delivery system (catheter and light diffuser) suitable for intra-arterial PDT by using a planar imaging goniometer to measure the full radiance longitudinal and angular profiles at the surface of the diffuser at 652 nm. The results show that the system emits almost Lambertian and &ldquo, top hat&rdquo, profiles, an interesting feature to determine the light dosimetry in the many vascular applications of PDT.

Significance: Photodynamic therapy (PDT) could become a treatment option for nonmuscle invasive bladder cancer when the current high morbidity rate associated with red light PDT and variable PDT dose can be overcome through a combination of intravesical instillation of the photosensitizer and the use of green light creating a steep PDT dose gradient. Aim: To determine how a high PDT selectivity can be maintained throughout the bladder wall considering other efficacy determining parameters, in particular, the average optical properties of the mucosal layer governing the fluence rate multiplication factor, as well as the bladder shape and the position of the emitter in relationship to the bladder wall. Approach: We present three irradiance monitoring systems and evaluate their ability to enable selective bladder PDT considering previously determined photodynamic threshold values for the bladder cancer, mucosa and urothelium in a preclinical model, and the photosensitizer’s specific uptake ratio. Monte Carlo-based light propagation simulations performed for six human bladders at the time of therapy for a range of tissue optical properties. The performance of one irradiance sensing device in a clinical phase 1B trial is presented to underline the impact of irradiance monitoring, and it is compared to the Monte Carlo-derived dose surface histogram. Results: Monte Carlo simulations showed that irradiance monitoring systems need to comprise at least three sensors. Light scattering inside the bladder void needs to be minimized to prevent increased heterogeneity of the irradiance. The dose surface histograms vary significantly depending on the bladder shape and bladder volume but are less dependent on tissue optical properties. Conclusions: We demonstrate the need for adequate irradiance monitoring independent of a photosensitizer’s specific uptake ratio.

Photobiomodulation therapy (PBMT) has been widely used for the promotion of tissue repair. Despite these therapeutic benefits, in some cases, PBMT appears to be unsuccessful, and the strongest hypothesis is that this failure is due to inadequate light dosimetry and wavelengths. The objective of the present critical review was to evaluate the effects of PBMT on cultured keratinocytes using blue, red, or near-infrared light categorized into arbitrary ranges of energy density (0.1–5.0, 5.1–10.0, 10.1–15.0, and over 15.0 J/cm2). The electronic searches were conducted in PubMed, Web of Science, Scopus and LILACS databases, and included LASER or LED devices. A total of 55 articles evaluating the effects of PBMT on cell viability, proliferation, migration, and cytokine and growth factor production were included. Overall, the studies failed to provide detailed information about light dosimetry or detailed experimental conditions. The vast majority of the energy densities tested produced unmodified results regardless of the wavelength applied. However, it was possible to observe that red and near-infrared light had more stimulatory effects than blue light. In addition, for all parameters analyzed, favorable outcomes were mostly obtained in the range of 0.1–5.0 J/cm2. The less explored energy densities were within the 10.1–15.0 J/cm2 range. Energy densities above 15.0 J/cm2 were ineffective or tended to cause cell death. The heterogeneity of the data does not allow us to define a PBMT range setting protocol that would have beneficial effects on keratinocytes.

The optical penetration depth is one of the important parameters needed for the calculations of light dosimetry in various medical applications like photodynamic therapy. In this study, the optical penetration depths in chicken breast and liver tissues have been measured by using the LED light sources with the wavelengths of 635 and 660 nm. Experimental results of this study have been compared with the ones from the Monte Carlo simulations in order to test the simulation toolkit. Based on the agreement between the experimental and simulated data, it is concluded that tissue optics plug-in interfacing with GAMOS architecture is a reasonable software for investigating the light distribution in biological tissues.