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Infrared Laser Stimulation of Cerebral Cortex Cells - Aspects of Heating and Cellular Responses
KTH, School of Technology and Health (STH), Medical Engineering, Neuronic Engineering. (Implantat)
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The research of functional stimulation of neural tissue is of great interest within the field of clinical neuroscience to further develop new neural prosthetics. A technique which has gained increased interest during the last couple of years is the stimulation of nervous tissue using infrared laser light. Successful results have been reported, such as stimulation of cells in both the central nervous system, and in the peripheral nervous system, and even cardiomyocytes. So far, the details about the stimulation mechanism have been a question of debate as the mechanism is somewhat hard to explain. The mechanism is believed to have a photo-thermal origin, where the light from the laser is absorbed by water, thus increasing the temperature inside and around the target cell. Despite the mechanism questions, the technique holds several promising features compared to traditional electrical stimulation. Examples of advantages are that it is contact free, no penetration is needed, it has high spatial resolution and no toxic electrochemical byproducts are produced during stimulation. However, since the laser pulses locally increase the temperature of the tissue, there is a risk of heat induced damage. Therefore, the effect of increased temperatures must be investigated thoroughly. One method of examining the changes in temperature during stimulation is to model the heating.

This thesis is based on the work from four papers with the main aim to investigate and describe the response of heating, caused by laser pulses, on central nervous system cells. In paper one, a model of the heating during pulsed laser stimulation is established and used to describe the dynamic temperature changes occurring during functional stimulation of cerebral cortex cells. The model was used in all four papers. Furthermore, single cell responses, as action potentials, as well as network responses, as activity inhibition, were observed. In paper two, the response of rat astrocytes exposed to laser induced hyperthermia was investigated. Cellular migration was observed and the migration limit was used to calculate the kinetic parameters for the cells, i.e., the reaction activation energy, Ea (321.4 kJmol-1), and the frequency factor, Ac (9.47 x 1048 s-1). Furthermore, a damage signal ratio (DSR) for calculating a threshold for cellular damage was defined, and calculated to six percent. In paper three, the response of hyperthermia to cerebral cortex cells was investigated, in the same way as in the second paper. Fluorescence staining of the metabolic activity was used to reveal the heat response, and by using the limit of the observed increased fluorescence the kinetic parameters, Ea (333.6 kJmol-1), and Ac (9.76 x 1050 s-1), were calculated. The DSR for the cells was calculated to five percent. In paper four, the behavior of action potentials triggered by laser stimulation was investigated. More specifically, the time delay from the start of a laser pulse to the detection of an action potential, delta-t, were investigated. Two different behaviors for the initial action potentials were observed: fast decreasing delta-t and slow decreasing delta-t. The results show the dynamic behavior of action potential responses to infrared light.

The work of this thesis show the dynamic changes of the temperature during optical stimulation, using an infrared laser working at 1,550 nanometers. It also shows how the changes cause astrocytes to migrate for pulses several seconds long, and neurons to fire action potentials for pulses in the millisecond range. Furthermore, a damage signal ratio was defined and calculated for the cell systems.

Place, publisher, year, edition, pages
Huddinge: KTH Royal Institute of Technology, 2013. , x, 54 p.
Trita-STH, 2013:10
Keyword [en]
laser, modeling, heating, infrared neural stimulation, astrocytes, neurons, damage
National Category
Cell Biology Other Mathematics
URN: urn:nbn:se:kth:diva-138511ISBN: 978-91-7501-979-6OAI: diva2:681219
Public defence
2014-01-29, 3-221, Alfred Nobels Allé 10, Huddinge, 10:00
Available from: 2014-01-07 Created: 2013-12-19 Last updated: 2014-01-07Bibliographically approved
List of papers
1. Heating during infrared neural stimulation
Open this publication in new window or tab >>Heating during infrared neural stimulation
2013 (English)In: Lasers in Surgery and Medicine, ISSN 0196-8092, E-ISSN 1096-9101, Vol. 45, no 7, 469-481 p.Article in journal (Refereed) Published
Abstract [en]

Background and Objective Infrared neural stimulation (INS) has recently evoked interest as an alternative to electrical stimulation. The mechanism of activation is the heating of water, which induces changes in cell membrane potential but may also trigger heat sensitive receptors. To further elucidate the mechanism, which may be dependent on cell type, a detailed description of the temperature distribution is necessary. A good control of the resulting temperature during INS is also necessary to avoid excessive heating that may damage the cells. Here we present a detailed model for the heating during INS and apply it for INS of in vitro neural networks of rat cerebral cortex neurons. Study Design/Materials and Methods A model of the heating during INS of a cell culture in a non-turbid media was prepared using multiphysics software. Experimental parameters such as initial temperature, beam distribution, pulse length, pulse duration, frequency and laser-cell distance were used. To verify the model, local temperature measurements using open pipette resistance were conducted. Furthermore, cortical neurons in culture were stimulated by a 500 mW pulsed diode laser (wavelength 1,550 nm) launched into a 200 μm multimodal optical fiber positioned 300 μm from the glass surface. The radiant exposure was 5.2 J/cm2. Results The model gave detailed information about the spatial and temporal temperature distribution in the heated volume during INS. Temperature measurements using open pipette resistance verified the model. The peak temperature experienced by the cells was 48°C. Cortical neurons were successfully stimulated using the 1,550 nm laser and single cell activation as well as neural network inhibition were observed. Conclusion The model shows the spatial and temporal temperature distribution in the heated volume and could serve as a useful tool for future studies of the heating during INS.

cortical neurons, heat transfer, INS, laser, modeling, optical stimulation, simulation
National Category
Medical Engineering
urn:nbn:se:kth:diva-134091 (URN)10.1002/lsm.22158 (DOI)000329282100008 ()23832680 (PubMedID)2-s2.0-84882642675 (ScopusID)

QC 20131204

Available from: 2013-11-15 Created: 2013-11-15 Last updated: 2014-01-23Bibliographically approved
2. Quantification of a Thermal Damage Threshold for Astrocytes Using Infrared Laser Generated Heat Gradients
Open this publication in new window or tab >>Quantification of a Thermal Damage Threshold for Astrocytes Using Infrared Laser Generated Heat Gradients
2014 (English)In: Annals of Biomedical Engineering, ISSN 0090-6964, E-ISSN 1521-6047, Vol. 42, no 4, 822-832 p.Article in journal (Refereed) Published
Abstract [en]

The response of cells and tissues to elevated temperatures is highly important in several research areas, especially in the area of infrared neural stimulation. So far, only the heat response of neurons has been considered. In this study, primary rat astrocytes were exposed to infrared laser pulses of various pulse lengths and the resulting cell morphology changes and cell migration was studied using light microscopy. By using a finite element model of the experimental setup the temperature distribution was simulated and the temperatures and times to induce morphological changes and migration were extracted. These threshold temperatures were used in the commonly used first-order reaction model according to Arrhenius to extract the kinetic parameters, i.e., the activation energy, E (a), and the frequency factor, A (c), for the system. A damage signal ratio threshold was defined and calculated to be 6% for the astrocytes to change morphology and start migrating.

Arrhenius, Heating, Cell Damage, Modeling, Astrocytes
National Category
Other Mathematics Biophysics Cell Biology
urn:nbn:se:kth:diva-138509 (URN)10.1007/s10439-013-0940-1 (DOI)000333010900012 ()2-s2.0-84898601975 (ScopusID)

QC 20140318

Available from: 2013-12-19 Created: 2013-12-19 Last updated: 2014-12-10Bibliographically approved

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