Dosage – Irradiance

Lasers Med Sci. 2007 Oct 31; [Epub ahead of print]

Relevance of laser irradiance threshold in the induction of alkaline phosphatase in human osteoblast cultures.

Haxsen V, Schikora D, Sommer U, Remppis A, Greten J, Kasperk C.

Faculty of Science, Biophotonics Group, University of Paderborn, Paderborn, Germany,

Induction of matrix synthesis by low-level laser has been demonstrated extensively. However, the question of dose- or power intensity-dependency is under-investigated. To address this issue we chose human osteoblast cell cultures and measured their alkaline phosphatase (ALP) activity after laser irradiation. The cell cultures were irradiated periodically by 690 nm radiation via optical transmission fiber-based laser needles, reaching into the culture dishes. The osteoblasts showed no induction of ALP activity when we used a single laser needle stimulation with a laser irradiance of 51 mW/cm(2), an increase of approximately 43% at 102 mW/cm(2) irradiance (two needles per well) and a ninefold increase at 204 mW/cm(2) irradiance (four needles per well), leaving the temperature of the culture medium unaffected. We concluded that the osteoblastic response in ALP activity to a laser stimulus shows a logarithmic relationship, with a distinct threshold, rather than a linear dose-dependency. Secondly, the laser irradiance, rather than the dose, is relevant for the impact of the laser.

Photomed Laser Surg. 2006 Dec;24(6):705-14

Effect of multiple exposures of low-level laser therapy on the cellular responses of wounded human skin fibroblasts.

  • Hawkins D,
  • Abrahamse H.

Laser Research Unit, Group of Health Sciences, University of Johannesburg, Doornfontein, Johannesburg, South Africa.

Objective: This study aimed to establish the behavior of wounded human skin fibroblasts (HSF) after heliumneon (HeNe) (632.8 nm) laser irradiation using one, two, or three exposures of different doses, namely, 2.5, 5.0, or 16.0 J/cm(2) on each day for 2 consecutive days. Background Data: Low-level laser therapy (LLLT) is a form of phototherapy used to promote wound healing in different clinical conditions. LLLT at than adequate wavelength, intensity, and dose can accelerate tissue repair. However, there is still conflicting information about the effect of multiple irradiations on the cellular responses of wounded cells. Methods: Cellular responses to HeNe laser irradiation were evaluated by measuring changes in cell morphology, cell viability, cell proliferation, and damage caused by multiple irradiations. Results: A single dose of 5.0 J/cm(2), and two or three doses of 2.5 J/cm(2) had a stimulatory or positive effect on wounded fibroblasts with an increase in cell migration and cell proliferation while maintaining cell viability, but without causing additional stress or damage to the cells. Multiple exposures at higher doses (16 J/cm(2)) caused additional stress, which reduces cell migration, cell viability, and ATP activity, and inhibits cell proliferation. Conclusion: The results show that the correct energy density or fluence (J/cm(2)) and number of exposures can stimulate cellular responses of wounded fibroblasts and promote cell migration and cell proliferation by stimulating mitochondrial activity and maintaining viability without causing additional stress or damage to the wounded cells. Results indicate that the cumulative effect of lower doses (2.5 or 5 J/cm(2)) determines the stimulatory effect, while multiple exposures at higher doses (16 J/cm(2)) result in an inhibitory effect with more damage.

Photomed Laser Surg. 2006 Aug;24(4):458-66.

Effects of power densities, continuous and pulse frequencies, and number of sessions of low-level laser therapy on intact rat brain.

Ilic S, Leichliter S, Streeter J, Oron A, DeTaboada L, Oron U.

Photothera Inc., Carlsbad, California, USA.

OBJECTIVE: The aim of the present study was to investigate the possible short- and long-term adverse neurological effects of low-level laser therapy (LLLT) given at different power densities, frequencies, and modalities on the intact rat brain. BACKGROUND DATA: LLLT has been shown to modulate biological processes depending on power density, wavelength, and frequency. To date, few well-controlled safety studies on LLLT are available. METHODS: One hundred and eighteen rats were used in the study. Diode laser (808 nm, wavelength) was used to deliver power densities of 7.5, 75, and 750 mW/cm2 transcranially to the brain cortex of mature rats, in either continuous wave (CW) or pulse (Pu) modes. Multiple doses of 7.5 mW/cm2 were also applied. Standard neurological examination of the rats was performed during the follow-up periods after laser irradiation. Histology was performed at light and electron microscopy levels. RESULTS: Both the scores from standard neurological tests and the histopathological examination indicated that there was no long-term difference between laser-treated and control groups up to 70 days post-treatment. The only rats showing an adverse neurological effect were those in the 750 mW/cm2 (about 100-fold optimal dose), CW mode group. In Pu mode, there was much less heating, and no tissue damage was noted. CONCLUSION: Long-term safety tests lasting 30 and 70 days at optimal 10x and 100x doses, as well as at multiple doses at the same power densities, indicate that the tested laser energy doses are safe under this treatment regime. Neurological deficits and histopathological damage to 750 mW/cm2 CW laser irradiation are attributed to thermal damage and not due to tissue-photon interactions.

J Clin Laser Med Surg. 2001 Feb;19(1):29-33.

Biostimulatory windows in low-intensity laser activation: lasers, scanners, and NASA’s light-emitting diode array system.

Sommer AP, Pinheiro AL, Mester AR, Franke RP, Whelan HT.

Central Institute of Biomedical Engineering, Department of Biomaterials, University of Ulm, Germany.

OBJECTIVE: The purpose of this study was to assess and to formulate physically an irreducible set of irradiation parameters that could be relevant in the achieving reproducible light-induced effects in biological systems, both in vitro and in vivo. BACKGROUND DATA: Light-tissue interaction studies focusing on the evaluation of irradiation thresholds are basic for the extensively growing applications for medical lasers and related light-emitting systems. These thresholds are of central interest in the rejuvenation of collagens, photorefractive keratectomy, and wound healing. METHODS: There is ample evidence that the action of light in biological systems depends at least on two threshold parameters: the energy density and the intensity. Depending on the particular light delivery system coupled to an irradiation source, the mean energy density and the local intensity have to be determined separately using adequate experimental methods. RESULTS: From the observations of different research groups and our own observations, we conclude that the threshold parameters energy density and intensity are biologically independent from each other. CONCLUSIONS: This independence is of practical importance, at least for the medical application of photobiological effects achieved at low-energy density levels, accounting for the success and the failure in most of the cold laser uses since Mester’s pioneering work.