BACKGROUND: Photobiomodulation therapy (PBMT) is recommended for the prevention of oral mucositis (OM) in cancer patients. Transcutaneous, extraoral delivery of PBMT with LED arrays, versus intraoral delivery with laser, may be more effective for treatment of at-risk sites and better tolerated by patients. The objective was to develop an evidence-based extraoral PBMT treatment protocol.
METHODS: We previously demonstrated that Monte Carlo modeling accurately simulates in vivo transmittance measurements. Archival MRI studies (n=18) were used to determine anatomical structures along the trajectories of 850 nm light through the cheek, lip, mandible angle and neck. Optical properties of skin, fat, muscle, cartilage, and blood were obtained from literature, and Monte Carlo modeling was performed for skin types I and VI. Simulation results were used to determine the treatment time needed to deliver a median dose between 1 and 6 J/cm2 to the mucosa.
RESULTS: Cheek had greatest variability in thickness (13-29 mm) corresponding to a 25-fold difference in the mucosal fluence rate. Despite tissue differences, fluence attenuation is primarily determined by the overall thickness of all tissue
Background and Objective: Intraoral photobiomodulation therapy (PBMT) is effective at preventing oral mucositis (OM). Extraoral PBMT is a novel approach with distinct advantages over intraoral PBMT, but no evidence-based treatment protocol has been proposed. The goal of this contribution was to develop a practical and effective treatment protocol for extraoral PBMT to prevent OM.
Methods: Extraoral PBMT was modeled using Monte Carlo simulations with parameters established in intraoral PBMT: 50 mW/cm2 (1 minute treatment time), at either 660 nm, used in superficial PBMT, or 850 nm, used in deeper PBMT. The effective therapeutic dose of ~ 2.0 J/cm2 was assumed to be identical for intraoral and extraoral PBMT. The results prompted a review of the literature regarding PBMT parameters for deep tissue treatment, as well as the mechanism of PBMT.
Summary: Per our Monte Carlo simulations, the treatment parameters established for intraoral PBMT are not appropriate for extraoral delivery. Visible light (660 nm) showed poor penetration, producing an insufficient dose at the oral mucosa. The infrared light (850 nm) penetrated deeper. However, at 50 mW/cm2 and 1 minute treatment time, the dose was still less than targeted 2 J/cm2. Therefore, based on the optical properties of tissues, anatomy of the target population, and established protocols for deeper PBMT, we propose a wavelength of 850 nm, at 399 mW/cm2, and exposure time of 1-11 minutes, depending on the treatment site, to achieve the therapeutic dose of ~2 J/cm2 at the depth of the oral mucosa for preventing OM using extraoral PBMT.
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.
Background: Oral mucositis (OM) often occurs after myeloablative hematopoietic cell transplantation. We explore extra-oral photobiomodulation therapy (PBMT) for the prevention of OM in children. Objectives: Our objective was to use modeling of PBMT to determine optimal treatment sites and parameters for a safe and efficacious treatment. Methods: MRI images were analyzed to obtain morphological information on the extent of tissues along the six trajectories passing through the cheek; lips; submandibular and submental regions; neck, transversely and anteroposteriorly. For each treatment site we performed 18 simulations using morphological information from 18 subjects with ages between 5 and 20 years. The simulation technique uses Monte Carlo method to calculate light distribution and finite difference method to solve the heat transfer equation. Our model accounts for the geometry of emitter, optical, thermal, and morphological tissue properties, as well as possible changes of the optical properties during the therapy. We have used a layered tissue model. The optical and thermal properties of tissues were assigned to each pixel individually using published data on the properties of relevant tissues. We evaluated spatially resolved fluence rate, absorbed power, temperature increase and thermal damage. Results and Conclusions: At 850nm and 399mW/cm2, the median dose transmitted ranged from 0.18–2.4J/cm2. As presence of blood hinders light penetration, treatment sites should be chosen to avoid major blood vessels. There was no temperature increase and damage to the tissue. Our results reveal that extra-oral PBMT is safe and shows promise for the prevention of OM in children.
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
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