Download 2.3. Spatial Selectivity in Optical Stimulation

Transient Optical Nerve Stimulation
(Concepts and Methodology of Pulsed Infrared Laser
Stimulation of Peipheral Nerve In Vivo)
허 정
2011.05.31.
Special thanks to Sang-Kyung Kim & Sung-Jun Kwon
Contents
1. Introduction
1)
Limitation of Standard Electrical Nerve Stimulation
2)
Definition of Optical Stimulation
3)
Previous Work in Optical Stimulation
2. Optical Stimulation
1)
Introduction to the Feasibility, Methodology and Physiological Validity
2)
Generation of an Artifact-Free Nerve Potential Recording
3)
Spatial Selectivity in Optical Stimulation
4)
Threshold for Stimulation Dependence on Wavelength
3. Mechanism
4. Impact : Application & Future Direction
Page  2
1. Introduction
Page  3
1.1. Limitations of Standard Electrical Nerve Stimulation
 Electrical Stimulation
– Standard method for excitation of nerve tissue
– Clinically diagnostics and therapeutics
– Conceptual understanding of action potential propagation/signaling and even
nerve regeneration
 Limitation
– Physical contact with a metal electrode → tissue damage
– Inadequate spatial precision of stimulation due to the size of electrode
– Spread of electrical current → population response → poor spatial specificity
– Stimulation artifact
Page  4
1.2. Definition of Optical Stimulation
 Direct induction of an evoked potential in response to a transient
targeted deposition of optical enery
 Continuous wave(X) → Pulsed source(O)
 Direct incident of light in the neural tissue resulting in an evoked
potential from the neural tissue
 Laser applications(not optical stimulation)
– Using lasers relies on high energy effect (tissue ablation, photoacoustic wave
generation)
– Low power laser application (LLLT : modulate biologycal process such as
inflammation and cell proliferation)
Page  5
1.3. Previous Work in Optical Stimulation
 Optical stimulation(488nm blue laser) was first reported as action
potentials generated in Alpysia neurons through a reversible
mechanism (Fork, 1971)
Page  6
1.3. Previous Work in Optical Stimulation
 A bundle of central nervous
fibers was excited in the rat with
a short pulse (40 ns) of UV light
produced by an excimer laser.
 Evoked responses were
recorded in the thalamic VPN
after stimulation of the medial
lemniscus or the cuneate bundle
in the spinal cord.
recording
Stimulation
Page  7
2. Optical Stimulation
 Contact-free, damage-free, artifact-free stimulation
 The stimulation threshold (0.3 to 0.4 J/cm2) at optimal
wavelengths in the infrared (1.87, 2.1, 4.0μm) is at least two
times less than the threshold at which any histological tissue
damage occurs (0.8 to 1.0 J/cm2)
 Fundamental advantages of Optical Stimulation
– The precision of optically delivered energy
– No stimulation artifact
– Noncontact fashion
Page  8
2.1. Introduction to the Feasibility, Methodology, and
Physiological Validity
Holmium:YAG Laser
Wavelength : 2.12μm
Pulse duration : 350μs
400~600μm diameter
Page  9
2.1. Introduction to the Feasibility, Methodology, and
Physiological Validity
 Consistent evoked potential was recorded
 Light is responsible for CNAP and CMAP
 Both signal were lost when optical energy was blocked with
shutter
 Stimulation was due to only the light
 Application of depolarizing neuromuscular
blocker(succinylcholine) resulted in loss of CMAP
 Normal propagation of impulse from nerve to muscle
CNAP : Compound Nerve Action Potential
CMAP : Compound Muscle Action Potential
Page  10
2.2. Generation of an Artifact-Free Nerve Potential
Recording
Standard peripheral nerve stimulation
– Stimulation & Recording in the same domain, through
electrical means
Artifact
– Inherent to any electrically stimulated nerve
– Much greater than the physiological signal
– Obscure measurement of the physiological signal
Page  11
2.2. Generation of an Artifact-Free Nerve Potential
Recording
0.6ms 1.8ms
 Electrical stimulation
→ artifact
 Optical stimulation
→ no artifact
2.5ms
artifact
 Distance from stimulation to
recording in nerve
– 22 mm
 Two peaks following the laser
stimulus
artifact
– First peak (fast conducting fibers)
 conduction velocity : 36.7 m/s
– Second peak (slower conducting fibers)
 conduction velocity : 8.8 m/s
Page  12
2.3. Spatial Selectivity in Optical Stimulation
Electrical stimulation
– Unconfined spread far from the electrode
– Injected current increase
 Volume of the affected tissue increase
– The greater the energy applied,
 the more fibers recruited
– Limitation : Spatial selectivity
Page  13
2.3. Spatial Selectivity in Optical Stimulation
Optical stimulation (Laser)
– Precise control
– Quantifiable volume of action in biological tissue
Variable Parameter
– Wavelength(penetration depth)
– Spot size
– Laser radiant exposure
Page  14
2.3. Spatial Selectivity in Optical Stimulation
Wavelength
– Penetration depth of photon
– Depth of axons recruited in optical stimulation
Small spot size & Lack of radial diffusion
– Stimulation on extremely small area
 More selective excitation of fascicles
Parameters can be optimized for efficient
stimulation of any tissue geometry
Page  15
2.3. Spatial Selectivity in Optical Stimulation
 Difference in selective activation
for electrical vs. optical stimulation
– CMAP recording electrode
• Gastrocnemius
• Biceps femoris
Lateral gastrocnemius muscle
Page  16
2.3. Spatial Selectivity in Optical Stimulation
 Electrical stimulation
– Simultaneous response within gastrocnemius & Biceps femoris
– Stimulation of neighboring muscle
– Poor selectivity
– Excitation of the entire nerve
– Twitch response from all innervated muscles
Page  17
2.3. Spatial Selectivity in Optical Stimulation
 Optical stimulation at threshold
– No response observed in the biceps femoris
– Extremely precise stimulation of individual fascicles
– Increasing optical energy  linear increase in recruitment of axons
Page  18
2.4. Threshold for Stimulation Dependence on
Wavelength
 Tissue characteristic
– Refractive index
– Wavelength-dependent coefficients of absorption and scattering
 Laser parameter
– Wavelength
– Exposure time
– Laser power
– Applied energy
– Spot size
– Radiant exposure (energy/unit area)
– Irradiance (power/unit area)
Page  19
2.4. Threshold for Stimulation Dependence on
Wavelength
 Light is treated as photons
– biological tissue is an inhomogeneous mix of compounds, many with unknown
properties
– the opportunity to apply probabilistic approaches that lend themselves
particularly well to numerical solutions that are manageable in computer
simulations
 Photons in a turbid medium (such as tissue)
– moves randomly in all directions
– absorbed (described by its absorption coefficient μa[m-1])
•
Converted to heat, trigger a chemical reaction, or cause fluorescence emission
•
Without absorption, there is no energy transfer to the tissue and the tissue is left unaffected by the
light
– scattered (described by its scattering coefficient μs[m-1])
•
Bumps into a particle and changes direction but continues to exist and has the same energy
•
Negligible relative to absorption
Page  20
2.4. Threshold for Stimulation Dependence on
Wavelength
Chromophores
– Molecules that absorb light are called chromophores
– Water is the major chromophore in the peripheral nerve
• In the IR, tissue absorption is dominated by water
absorption
Page  21
2.4. Threshold for Stimulation Dependence on
Wavelength
 E(z), the irradiance through some distance z of the medium
– Irradiance [W/m2]
• how much light made it to a certain point in the tissue
• Does not mean how much of that light is absorbed at that point.
– Light intensity in a material decays exponentially with depth (z)
– E0, the incident irradiance [W/m2]
– μa(λ), the wavelength-dependent absorption coefficient.
Page  22
2.4. Threshold for Stimulation Dependence on
Wavelength
 Power density [W/m3], rate of heat generation (S)
– the number of photons absorbed per unit volume [W/m3], which can be related
to amount of heat generated
– μa, the probability of absorption of the light at the point
Page  23
2.4. Threshold for Stimulation Dependence on
Wavelength
 Once the power density S(z) [W/m3] is known, the energy density Q(z)
[J/m3] is easily calculated by multiplying the power density by the
exposure duration, Δt
 Laser induced temporature rise
– ρ is the density [kg/m3] and c is the specific heat [J/kg•K] of the
irradiated material
Page  24
2.4. Threshold for Stimulation Dependence on
Wavelength
 Appropriate wavelengths for stimulation depend on the tissue geometry of
the target tissue
 For selective stimulation of individual fascicles within the main nerve, the
penetration depth of the laser must be…
– greater than the thickness of the outer protective tissue (200 μm)
– in between the thickness of the underlying fascicle
(penetration depth of 300 to 500 μm)
– the typical fascicle thickness is constant (between 200 and 400 μm)
Page  25
2.4. Threshold for Stimulation Dependence on
Wavelength
 FEL(Free Electron Laser) : continuously tunable pulsed infrared laser
– operates in the 2- to 10-μm IR region
– emits a pulse with a duration of 5 μs
– excellent for…
• gathering experimental data
– provide guidance for the design of an appropriate and optimized optical
nerve stimulation
• exploring the wavelength dependence of the interaction
– not easy to use, not clinically viable
Page  26
2.4. Threshold for Stimulation Dependence on
Wavelength
Page  27
3. Mechanism
 Mechanism is largely unanswered
 Unraveling these mechanisms is still in its infancy
 Three main interaction mechanisms(hypothesis)
1) Photochemical
2) Photothermal
3) Photomechanical
Page  28
3. Mechanism : Photochemical
 Light can induce chemical effects and reactions within
macromolecules or tissue
Photosynthesis
Photodynamic therapy
Caged compound
Biostimulation
 But photochemaical phenomenin is not responsible because infrared
photon energy is too low for a direct photochemical effect of laser-tissue
interactions.
Page  29
3. Mechanism : Photomechanical
 The change in the shape of a material when it is exposed to light
 The most common mechanism of the photomechanical effect is lightinduced heating (Thermoelastic expansion)
 Pressure wave generation from rapid heating leads to optical stimulation?
 Laser-induced pressure waves are not implicated in the optical stimulation
mechanism
Page  30
3. Mechanism : Photothermal
 Through the process of elimination, we have arrived at the
hypothesis that laser stimulation of neural tissue is mediated by
some photothermal process resulting from transient irradiation of
peripheral nerves using infrared light
 Including a large group of interaction types resulting from the
transfomation of absorbed light energy to heat
 Be mediated primarily by absorption of optical energy
 Depending on the duration and peak value of the temperature
achieved, different effects such as coagulation, vaporization, melting,
or carbonization may be distinguished
Page  31
3. Mechanism : Photothermal
Page  32
4. Impact : Application & Future direction
 Peripheral nerve surgery
– confine the stimulation easily to segments of a nerve without requiring
separation between the intended area to be stimulated and other areas
 Surgeries involving cranial nerves
– precise functional testing, such as differentiating nerve tissue from tumor in
small areas
 Auditory nerve stimulation
– significantly enhanced with a larger number of distinct stimulation sites along
the cochlea
 Chronic implantion
– Longer tissue stability, safe interface materials
Page  33
4. Impact : Application & Future direction
large, cumbersome, and expensive laboratory laser sources
Page  34
simple, user-friendly, portable, reliable, and low-cost device
Thanks for listening