Red and NIR light dosimetry in the human deep brain (original) (raw)
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BMC Neurology, 2021
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Scientific Reports, 2017
Optogenetics is widely used in fundamental neuroscience. Its potential clinical translation for brain neuromodulation requires a careful assessment of the safety and efficacy of repeated, sustained optical stimulation of large volumes of brain tissues. This study was performed in rats and not in non-human primates for ethical reasons. We studied the spatial distribution of light, potential damage, and non-physiological effects in vivo, in anesthetized rat brains, on large brain volumes, following repeated high irradiance photo-stimulation. We generated 2D irradiance and temperature increase surface maps based on recordings taken during optical stimulation using irradiance and temporal parameters representative of common optogenetics experiments. Irradiances of 100 to 600 mW/mm2 with 5 ms pulses at 20, 40, and 60 Hz were applied during 90 s. In vivo electrophysiological recordings and post-mortem histological analyses showed that high power light stimulation had no obvious phototoxic...
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Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is an innovative treatment for a wide range of neurological and psychological conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover, light absorption by ion channels results in release of Ca 2+ and leads to activation of transcription factors and gene expression. Brain PBM therapy enhances the metabolic capacity of neurons and stimulates anti-inflammatory, anti-apoptotic, and antioxidant responses, as well as neurogenesis and synaptogenesis. Its therapeutic role in disorders such as dementia and Parkinson's disease, as well as to treat stroke, brain trauma, and depression has gained increasing interest. In the transcranial PBM approach, delivering a sufficient dose to achieve optimal stimulation is challenging due to exponential attenuation of light penetration in tissue. Alternative approaches such as intracranial and intranasal light delivery methods have been suggested to overcome this limitation. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of brain PBM therapy.
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Photochemistry and Photobiology, 1996
Normal brain tissue response to photodynamic therapy (PDT) must be quantified in order to implement PDT as a treatment of brain neoplasm. We therefore calculated the threshold for PDT-induced tissue necrosis in normal brain using Photofrin (porflmer sodium, Quadralogic Technologies Inc., Vancouver, BC) as the photosensitizer. The absolute light fluence-rate distribution for superficial irradiation and effective attenuation depth were measured in vivo using an invasive optical probe. Photosensitizer uptake in cerebral cortex was measured with chemical extraction and fluorometric analysis. Photodynamic therapy-induced lesion depths at various drug dose levels were measured as a biological end point. The PDT threshold for normal brain necrosis was calculated as in the magnitude of 1OI6 photons/cm3. Thus normal rat brain is extremely vulnerable to PDT damage. This suggests that extra precautions must be exercised when PDT is used in brain.
Near-infrared light penetration profile in the rodent brain
Journal of Biomedical Optics, 2013
Near-infrared (NIR) lasers find applications in neuro-medicine both for diagnostic and treatment purposes. Penetration depth and profile into neural tissue are critical parameters to be considered in these applications. Published data on the optical properties of rodent neural tissue are rare, despite the frequent use of rats as an animal model. The aim of this study was to measure the light intensity profile inside the rat brain using a direct method, while the medium is being illuminated by an NIR laser beam, and compare the results with in vitro measurements of transmittance in the rat brain slices. The intensity profile along the vertical axis had an exponential decline with multiple regions that could be approximated with different coefficients. The Monte Carlo method that was used to simulate light-tissue interactions and predict the scattering coefficient of brain tissue from the measurements suggested that more scattering occurred in deeper layers of the cortex. A single scattering coefficient of 125 cm −1 was estimated for cortical layers from 300 to 1500 μm and a gradually increasing value from 125 to 370 cm −1 for depths of 1500 to 3000 μm. The deviations of in vivo results from the in vitro transmittance measurements, as well as the postmortem in vivo results from the alive measurements were significant.
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The recent development of optogenetic tools, to manipulate neuronal activity using light, provides opportunities for novel brain-machine interface (BMI) control systems for treating neurological conditions. An issue of critical importance, therefore, is how well light penetrates through brain tissue. We took two different approaches to estimate light penetration through rodent brain tissue. The first employed so-called “nucleated patches” from cells expressing the light-activated membrane channel, channelrhodopsin (ChR2). By recording light-activated currents, we used these nucleated patches as extremely sensitive, microscopic, biological light-meters, to measure light penetration through 300-700µm thick slices of rodent neocortical tissue. The nucleated patch method indicates that the effective illumination drops off with increasing tissue thickness, corresponding to a space constant of 317µm (95% confidence interval between 248-441µm). We compared this with measurements taken from...
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SPIE Proceedings, 2013
Over the last few years, low-level light therapy (LLLT) has shown an incredible suitability for a wide range of applications for central nervous system (CNS) related diseases. In this therapeutic modality light dosimetry is extremely critical so the study of light propagation through the CNS organs is of great importance. To better understand how light intensity is delivered to the most relevant neural sites we evaluated optical transmission through slices of rat brain point by point. We experimented red (λ = 660 nm) and near infrared (λ = 808 nm) diode laser light analyzing the light penetration and distribution in the whole brain. A fresh Wistar rat (Rattus novergicus) brain was cut in sagittal slices and illuminated with a broad light beam. A high-resolution digital camera was employed to acquire data of transmitted light. Spatial profiles of the light transmitted through the sample were obtained from the images. Peaks and valleys in the profiles show sites where light was less or more attenuated. The peak intensities provide information about total attenuation and the peak widths are correlated to the scattering coefficient at that individual portion of the sample. The outcomes of this study provide remarkable information for LLLT dose-dependent studies involving CNS and highlight the importance of LLLT dosimetry in CNS organs for large range of applications in animal and human diseases.
Modulation of light delivery in photodynamic therapy of brain tumours
Journal of Clinical Neuroscience, 1999
This study was performed to determine whether modulation of light delivery could improve tumour kill in photodynamic therapy (PDT) of brain tumours, as optimal dosimetry has not been fully established. One hundred and sixty-five adult Wistar rats were treated, of which 70 had an implanted C6 ce-rebral glioma. Haematoporphyrin derivative (HpD) was injected at doses between 0 and 20 mg/kg, 24 h prior to irradiation with 630 nm laser light. The total energy dose was varied from 0 to 1200 J/cm 2, with fluence rates of 625, 3125 or 9375 mW/cmL In some studies, the light delivered at 3125 mW/cm 2 was divided into 10 fractions of approximately 13 s, with refractory intervals of 60 s. The most striking finding was that HpD was much more potent than previously reported. All doses greater than 1.0 mg/kg resulted in normal brain damage with light doses above 50 J/cmL However, at 1.0 mg/kg, significant normal injury was not apparent until 1200J/cmL Failure of drug-light dose reciprocity indicated that photobleaching occurred, protecting normal tissue. Selective tumour kill was observed to 2.2 mm depth (SE _+ 0.44 mm). Using lower power or fractionated light did not improve tumour kill and normal tissue injury occured with fluence rates of 9375 mW/cmL In conclusion, the doses of HpD currently used in clinical brain tumour trials may be too high to achieve selective tumour kill. Higher light fluence rates allowed shorter intraoperative irradiation times with no loss of efficacy. Photodynamic therapy continues to demonstrate potential as an effective treatment for local control of cerebral lesions.