e duco jansen - optical stimulation of neural tissue: current state
TRANSCRIPT
![Page 1: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/1.jpg)
Optical Stimulation of Neural Tissue:
Current State and Future Challenges
E. Duco JansenE. Duco Jansen
Department of Biomedical Engineering and
Department of Neurological Surgery
Vanderbilt University
Nashville, TN
[email protected] Bionics Conference, Melbourne, November 23, 2011
![Page 2: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/2.jpg)
With thanks to:• Dr. Peter Konrad, Dr. Chris Kao, Dr. Anita Mahadevan-Jansen, Dr. Mykyta Chermov,
Dr. Kurt Schoener, Dr. Mark Mackanos, Jonathan Cayce, Jonathan Malphrus, Austin
Duke, Melanie Gault (Vanderbilt University – BME, Neurosurgery)
• Dr. Jonathon Wells, Dr. Matt Keller, Dr. Mark Bendett (Lockheed-Martin Aculight)
• Dr. Hillel Chiel, Dr. Dustin Tyler, Dr. Andrew Rollins, Dr. Michael Jenkins (Case
Western Reserve Univ)
• Dr. Claus Peter Richter, Dr. Jay Walsh, Dr. Agnella Izzo-Matic (Northwestern Univ)• Dr. Claus Peter Richter, Dr. Jay Walsh, Dr. Agnella Izzo-Matic (Northwestern Univ)
• Dr. Anna Roe, Dr. Robert Friedman (Psychology, Vanderbilt Univ)
• Dr. Maarten Frens, Dr. Stefan Louw (Neuroscience, Erasmus University, Rotterdam)
• Funding:
� VIO exploratory grant
� DOD - MFEL Program (FA9550-04-1-0045)
� NIH (R01 NS052407, R43 NS051926, R44 NS051926)
� Human Frontiers Science Program (HFSP)
� DOD/DARPA CIPhER Program
� Lockheed-Martin
![Page 3: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/3.jpg)
Neural Stimulation
Since it is known that electrical activity can
be measured with optical techniques (DOT,
OCT, fluorescence imaging) ……OCT, fluorescence imaging) ……
Is it possible to induce electrical activity
with light?
…..and why would one want to do this?
![Page 4: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/4.jpg)
The Challenge• Improving human capabilities through the development
of advanced human-machine interfaces
• Electrical stimulation and recording are state-of-the art and work well (and are being used extensively)
�Cochlear implants, bionic eye
�EMG controlled prosthetics, FES, FINE electrodes, etc.
• Can we do better?
![Page 5: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/5.jpg)
Background
• Electrical stimulation has been and still is the gold
standard in neural activation1
� Applied constant current through metal or ionic electrodes
results in AP
� Inherent and fundamental limitations� Inherent and fundamental limitations
o lack of spatial precision in stimulation (size of electrodes,
electric field)
o electrical stimulation artifact preventing recording from
adjacent stimulation
o Need for physical contact between the nerve and
electrodes (storage of charge � inflammation, necrosis)
o MR compatibility?1. Fritsch, G. and E. Hitzig, Archiv Anatomie, Physiologie, und Wissenschaftlische Medicin 37, 300-32 (1870).
![Page 6: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/6.jpg)
Hypothesis
• Pulsed laser light can be used for contact-free,
damage-free, artifact-free stimulation of discrete
populations of neural fibers.
• Objectives of this research:
� To evaluate and assess the safety and efficacy of optical stimulation
in a comparison with electrical stimulation
� Develop a stand-alone, portable, inexpensive, optical stimulator
� Translation to clinical applications
� Push capabilities beyond current state-of-the-art
![Page 7: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/7.jpg)
What is optical stimulation?
• Optical nerve stimulation = induction of an evoked potential (EP/AP) in response to a transient targeted deposition of optical energy.
• What it is NOT:
�LLLT (low light level therapy)
�Genetic engineering of light-activatable ion channels in neural cells (‘optogenetics’)
�Light activation of caged compounds
![Page 8: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/8.jpg)
Spatially selective stimulation in rat sciatic nerve
![Page 9: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/9.jpg)
Spatial selectivity & no stimulation artifact
Quadriceps Fascicle
Foot fascicle
Rat Sciatic
Electrical Stimulator
0
5
10
CM
AP
(V
)
-5
0
5
10
0 2 4 6 8 10 12 14 16
CM
AP
(V
)
a.
Fiber Coupled Laser
Hamstring Fascicle
Quadriceps Fascicle
Foot fascicle
Rat Sciatic Nerve
Optical Fiber
Hamstring Fascicle
Rat Sciatic Nerve -5
0
0 2 4 6 8 10 12 14 16
CM
AP
(V
)
-0.1
0
0.1
0.2
0 2 4 6 8 10 12 14 16
CM
AP
(V
)
-0.1
0
0.1
0.2
0 2 4 6 8 10 12 14 16
CM
AP
(V
)
b.
Wells JD, Konrad PE, Kao CC, Jansen ED, Mahadevan-Jansen A – J Neurosci Methods 163(2): 326-37 (2007)
![Page 10: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/10.jpg)
Infrared Nerve
Functional Mapping
Auditory Nerve / Cochlea /
Vestibular System
Laser Parameters
PNS
Cardiac Pacing
CIPhER: all optical
neural interface
Infrared Nerve
Stimulation
Device Development
Efficacy & Safety Testing
Mechanisms
PhysiologicalPhysical
CNS
ImplantsMultiplexing/
Miniaturization
![Page 11: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/11.jpg)
A brief primer on
Laser-Tissue Interaction
Optical properties Absorption Thermal properties
light Light
distribution
Rate of
heat generation
Heat
conduction
Photochemical
processes
Fluorescence
Raman
ReflectanceDiagnosis
TherapyThermo-
mechanical
effects/pressures
![Page 12: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/12.jpg)
Laser output characteristics (1)
•
Laser
![Page 13: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/13.jpg)
Laser output characteristics (2)
•
![Page 14: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/14.jpg)
Pulsed lasers
•
![Page 15: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/15.jpg)
CW Lasers
• Can be used in ‘pulsed’ mode (off-on-off-on-off….)
• Ppeak = Pavg if duty cycle (DC) = 100%
• DC = RR * τp (what fraction of the time is laser on?)• DC = RR * τp (what fraction of the time is laser on?)
• If DC < 100%: Pavg = Ppeak * DC
• Example: Power = 5 W; 1 ms pulse, 100 Hz
�DC = 100 (Hz) * 1 10-3 (s) = 0.1 = 10%
�True Pavg = 5 (mJ/p) * 100 (Hz) = 0.5 (W)
![Page 16: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/16.jpg)
‘Intensity’• Pulsed
�Radiant Exposure, H (J/cm2)
�H = Qpulse / Area
• CW
� Irradiance, E (W/cm2)
�E = Power / Area
What is the area, A?What is the area, A?
r
z
Uniform beam
r
Spotsize fundamentally determined by:
1) Diffraction limit: d ≈ λ / 2 NA ≈ λ / 2
2) Fiber size
![Page 17: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/17.jpg)
Light interaction with tissue
reflection
refraction
scatteringabsorption
![Page 18: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/18.jpg)
Tissue Optics
•
z
E(z
)
0
0.2
0.4
0.6
0.8
1
1.2
0 10 20 30 40 50 60
δ
![Page 19: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/19.jpg)
Effect of absorption
Laser light
increasing
![Page 20: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/20.jpg)
Tissue Optics
•
ϴ
![Page 21: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/21.jpg)
Effect of scattering Water with intralipid
Laser light
Increasing µs
![Page 22: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/22.jpg)
How much light gets to some point (r,z) in tissue?
• If µa>> µs’: Beer’s law & beam profile
• If µa ≤ µs’: Modeling
�Monte Carlo
�Kubelka-Munk
r
�Kubelka-Munk
�Diffusion Approximation
�Adding-Doubling
• Optical properties depend on wavelength, λ
�Over ~8 orders of magnitude in effective penetration depth
z
(r,z)
![Page 23: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/23.jpg)
Scattering and Absorption
Chicken breast (left) and liver (right)
illuminated by red (top image) and
green (bottom image) laser light via
a fiber. Note the effect of the color of
the light and the higher blood
content in the liver on the light
distribution.
![Page 24: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/24.jpg)
Heat Source and Temperature Rise
•
![Page 25: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/25.jpg)
Peripheral Nerve Geometry & desired
penetration depth
Nerve diameter 1-2 mm
Outer sheath ~ 150 um
Fascicles 50-400 um
Need penetration depth of 250-500 um (for peripheral nerves)
Wells, et al, Optics Letters, 30(5): 504-507 (2005)Wells, et al, J. Biomed Optics, 10(6):064003 (2005)
δ = 1/µa
![Page 26: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/26.jpg)
We need penetration depth of 250-500 um
(for peripheral nerves)
10000
100000
ab
so
rptio
n c
oe
ffic
ien
t (1
/cm
)
Ho
:YA
G
1.8
75
dio
de
1.4
5 d
iod
e
Fiber optic transmissionwindow
0.0001
0.001
0.01
0.1
1
10
100
1000
10000
0 1 2 3 4
ab
so
rptio
n c
oe
ffic
ien
t (1
/cm
)
wavelength (um)
Ho
:YA
G
1.8
75
dio
de
1.4
5 d
iod
e
![Page 27: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/27.jpg)
Translational Research
Free Electron LaserFree Electron Laser
IRCM laser development /
Dual use
![Page 28: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/28.jpg)
Parameter Value
Mode of operation Pulsed
Polarization Non-Polarized
Emission wavelength 1.85- 1.88 µm
Bandwidth (FWHM) <20 nm
Fiber Diameter 100-600 µm core
Fiber Coupling SMA
LMA Capella R-1850
Infrared Neuro-Stimulator
Fiber Coupling SMA
Pulse duration (FWHM) 10 µs to 100ms
Rep rate 0.4 – 1000 Hz
Pulse energy < 5 mJ (@ 1ms)
Power requirements 115 or 220 V AC
Dimensions (Power Sup.) 12.5” x 13.25” x 4.75”
Weight 11.5 lbs
Cooling Air Cooled
![Page 29: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/29.jpg)
80%
100%
Damage versus Stimulation Thresholds
0%
20%
40%
60%
80%
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
Radiant Exposure (J/cm2)
P(d
am
ag
e)
ST: low-->high
survival (14 day)
ST: high-->low
survival(3-5day)
n-=34
n-=16
n=32
n=32
Wells JD et al. – Lasers in Surgery and Medicine (39(6): 513-26 (2007))
![Page 30: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/30.jpg)
Near-term light-based implant development
• Battery � Photons demonstrated
• Next steps� Single channel light-based stimulator
o Miniaturize
o Implant delivered for chronic safety studies
10 channels6 x 50 x 84 mm47 grams
� Three channel light-based stimulator (cochlear implant)o Multiple channels
o Wireless controls
o Light delivery development
o Long-term primate safety and efficacy studies with optimized parameters
� VCSEL array development in parallelo Wavelength: 1850nm ± 10nm
o Peak power of 10mW
o Array size: 10 x 10
o Array spacing: Approximately 100µm
o Drive electronics on chip1 mm x 1 mm
4 x 12 x 12 mm
![Page 31: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/31.jpg)
Towards an optical neural interface:
• Develop multichannel INS probe
– Co-aligned configuration with nerve
– Multiplexed (4�8� ….channels)
– Parameter optimization
– In vitro / in vivo testing:
– Feasibility / efficacy
– Tissue damage assessment
• Integrate in nerve cuff & fully optical neural interface
31
![Page 32: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/32.jpg)
Stimulation with a cuff
32
![Page 33: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/33.jpg)
Can we hear light???
![Page 34: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/34.jpg)
Optical Stimulation of the auditory nerve
![Page 35: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/35.jpg)
High Repetition Rate – single nerve recording
![Page 36: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/36.jpg)
Extended Optical Stimulation
400Hz, 15 mJ/cm2
![Page 37: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/37.jpg)
Courtesy of Dr. Claus-Peter Richter
![Page 38: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/38.jpg)
Conclusions – Cochlear stimulation
• Cochlear stimulation is feasible
�Threshold much lower than motor nerve stim
�High rep rate stimulation is feasible without damaging
tissuetissue
�Spatial precision comparable with acoustic stimulation
• Challenges
�Wavelength optimization
�Miniaturization
�Multiplexing
�Delivery interface
![Page 39: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/39.jpg)
Combined electrical and optical
stimulation
![Page 40: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/40.jpg)
80%
100%
Damage versus Stimulation Thresholds
0%
20%
40%
60%
80%
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
Radiant Exposure (J/cm2)
P(d
am
ag
e)
ST: low-->high
survival (14 day)
ST: high-->low
survival(3-5day)
n-=34
n-=16
n=32
n=32
Wells JD et al. – Lasers in Surgery and Medicine (39(6): 513-26 (2007))
![Page 41: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/41.jpg)
Can the optical stimulation threshold
be lowered?
Hypothesis:
Combining subthreshold electrical stimulation with
optical stimulation lowers the optical stimulation
threshold while maintaining the benefits of high
spatial selectivity of optical stimulation
![Page 42: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/42.jpg)
If possible, such an approach….
• Would increase safety margin
• Allow higher repetition rate stimulation
• Facilitate multiplexing (arrays)• Facilitate multiplexing (arrays)
• Reduce power requirements on laser end
�Facilitate implantable devices
• May facilitate acceptance in electrical stimulation
community
![Page 43: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/43.jpg)
Controlling Hybrid StimulationComparative Physiology Approach
Duke et al., J Neural Eng, In Review
![Page 44: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/44.jpg)
Optical threshold as function of Electrical Stimulation
60
80
100
Energ
yof th
reshold
)
0
20
40
60
0 20 40 60 80 100
Optical E
nerg
y(%
of th
reshold
Electrical Stimulation (% of threshold)
Duke et al., J Biomed Optics 14, 060501 (2009)
![Page 45: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/45.jpg)
Characterization of hybrid stimulation in Aplysia
Role of:
- Spatial overlap
- Temporal overlap
Duke et al., J Neural Eng, in review (2011)
- Temporal overlap
- Drift in threshold
Optimize n-dimensional
parameter space
![Page 46: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/46.jpg)
Optical Inhibition
Duke et al., J Neural Eng, in review (2011)
• A novel enabling tool in neuroscience
• Clinical utility to ‘silence’ (over)active neurons?
� Parkinson’s, Epilepsy, ET, etc.
![Page 47: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/47.jpg)
Conclusion
• Electrical ‘priming’ of system lowers optical
stimulation threshold
� But modalities do not appear to follow simple linear � But modalities do not appear to follow simple linear
superposition
� Why? Should they?
� What does this tell us about mechanism?
• Spatial precision is maintained
• Development of integrated probe under way
� Optimize spatial and temporal superposition
![Page 48: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/48.jpg)
Translation to Human: Dorsal Rhizotomy
• Perfect procedure for clinical trial
� Safety Study
� Efficacy Study
• Employ Ho:YAG
� 2.12 µm, 2 Hz, 0.2 - 1.5 J/cm2, 20 pulses, 600 micron fiber probe
� 7 cases to date
![Page 49: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/49.jpg)
Results:Electrical Stimulation:
Activation of all left side muscles
and contralateral crosstalk
Optical Stimulation: 0.2 J/cm2, λ =2.12 µm,
600 µm fiber, 2 Hz, 20 pulses
Left side Stim- Right Hamstring activation
![Page 50: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/50.jpg)
Conclusions:
• Optical stimulation presents a simple yet novel
approach to contact-free, damage-free, artifact-
free, spatially specific in vivo neural activation
• Pulsed infrared light is used to evoke physiologically • Pulsed infrared light is used to evoke physiologically
valid action potentials in neural tissues (PNS and
CNS, motor and sensory)
• Optimal stimulation wavelengths must be matched to
tissue morphology
![Page 51: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/51.jpg)
Opportunities and challenges• Towards human applications (FDA/IDE)
• An optical pacemaker
• Moving to spinal cord, cortex, cerebellum
•• Neurobiological mechanism
• Better recording methods
• Devices: miniaturization, multiplexing, interfaces
• Chronic studies
• Training people in neurophotonics
• ……
![Page 52: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/52.jpg)
Acknowledgments• Dr. Peter Konrad, Dr. Chris Kao, Dr. Anita Mahadevan-Jansen, Jonathan Cayce,
Jonathan Malphrus, Austin Duke (Vanderbilt University - BME)
• Dr. Sharon L. Thomsen
• Dr. Tom Milner, Dr. Bo Chen, Dr. Jihoon Kim (UT Austin)
• Dr. Claus Peter Richter, Dr. Jay Walsh, Dr. Agnella Izzo-Matic (Northwestern
University)
•• Jim Webb, Dr. Jonathon Wells, Dr. Mark Bendett (Lockheed-Martin Aculight)
• Dr. Anna Roe, Dr. Robert Friedman (VU Psychology)
• Dr. Hillel Chiel, Dr. Andrew Rollins, Dr. Michael Jenkins (Case Western Reserve Univ)
• W.M. Keck Foundation Free Electron Laser Center staff
• Funding:
� DOD - MFEL Program (FA9550-04-1-0045)
� NIH (R01 NS052407, R43 NS051926, R44 NS051926)
� Human Frontiers Science Program (HFSP)
� DOD/DARPA CIPhER Program
![Page 53: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/53.jpg)
![Page 54: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/54.jpg)
Translation to Human: Dorsal Rhizotomy
![Page 55: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/55.jpg)
Mechanisms
By now you’re probably wondering…..
how does INS work?how does INS work?
![Page 56: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/56.jpg)
Mechanisms: Summary• Physical basis of optical stimulation
� electric field effect – highly unlikely
�photochemical effect – would expect a wavelength dependence (other than water absorption)
�photomechanical effect – no pressure waves, unlikely role for thermal expansionrole for thermal expansion
�photothermal effect – appears to be the driving mechanism (dT/dz or dT/dt)
• Biological mechanism: undetermined at this point
�dT/dz dependence of state of Na+ channels
�T-dependent ion channels (TRPV-1)
�Thermally induced change in membrane capacitanceWells JD, et al. – Biophysical J, 93:2567-80 (2007).
![Page 57: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/57.jpg)
Spatial selectivity is maintained
CMAP from gastrocnemius (target)
Combined optical and electrical stimulation in nerve
CMAP from biceps femoris
![Page 58: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/58.jpg)
Thermal response
40
50
60
Te
mp
era
ture
(C
)
max temp
max temp increase
Mitochondrial Damage
Protein Denaturation
y = 27.151x + 23.54
R2 = 0.8982
y = 27.117x - 3.2732
R2 = 0.90150
10
20
30
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9Radiant Exposure (J/cm2)
Te
mp
era
ture
(C
)
Stimulation Threshold Damage threshold
Wells et al. - Biophysical Journal 93(7) 2567–2580 (2007)
![Page 59: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/59.jpg)
Optical Stimulation:
Strength-response curveRange of Laser Energy
resulting in normal
physiologic responseDamaged physiologic
response
0.3
0.35
Range of Laser Energy
resulting in normal
physiologic responseDamaged physiologic
response
0.3
0.35
Threshold response to
Electrical Stimulation
Threshold response to
Optical Stimulation
y = 0.1809x + 0.008
R2 = 0.992
0
0.05
0.1
0.15
0.2
0.25
0.3
0 1 2 3Laser Radiant Exposure (J/cm2)
Pe
ak
EN
G (
V)
Threshold response to
Electrical Stimulation
Threshold response to
Optical Stimulation
y = 0.1809x + 0.008
R2 = 0.992
0
0.05
0.1
0.15
0.2
0.25
0.3
0 1 2 3Laser Radiant Exposure (J/cm2)
Pe
ak
EN
G (
V)
![Page 60: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/60.jpg)
Electrical Stimulation
Spiral ganglion cells
Apex
Electrode
contacts
Spiral ganglion cells
Base
![Page 61: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/61.jpg)
Optical Stimulation
Spiral ganglion cells
Apex
Spiral ganglion cells
Optical
Sources
Base
![Page 62: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/62.jpg)
Optical Pacing of the Embryonic Heart
New Scientist.Home
A heart beats to a different drummer
16.08.2010
Researchers pace embryonic heart with laser
New Scientist.Home
|Tech |Health | News
Laser sets quail embryos' hearts racing 18:00 15 August 2010 by Jeff Hecht
Laser mends broken heart
Jenkins MW, Duke AR, Gu S, Chiel HJ, Watanabe M, Jansen ED, Rollins AM – Optical pacing of the embryonic heart –
Nature Photonics, Aug 15, doi:10.1038/nphoton.2010.166 (2010).
![Page 63: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/63.jpg)
Pacing Movie
63
![Page 64: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/64.jpg)
Laser-tissue Interactions
1.E+09
1.E+12
1.E+15Ir
rad
ian
ce
[W
/cm
2] Plasma-
induced
ablation
Photodisruption
1,000 J/cm 2
1.E-03
1.E+00
1.E+03
1.E+06
1.E-15 1.E-12 1.E-09 1.E-06 1.E-03 1.E+00 1.E+03
Exposure time [s]
Irra
dia
nce
[W
/cm
2]
Photochemical interaction
Thermal interaction
Photoablation1 J/cm 2
EDJLasers in Medicine
![Page 65: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/65.jpg)
Mechanisms: Hypotheses
• Electric field effect?
• Photochemical
� Alteration in the state of the ion channels?
� Targeting specific neuro-transmitters?� Targeting specific neuro-transmitters?
• Photothermal
�Transient membrane permeability?
�Alteration of transmembrane proteins?
�T or ∆T (dT/dx or dT/dt)??
• Photomechanical
� Light induced stress waves (TE or recoil?)
![Page 66: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/66.jpg)
Electric field effect• Theoretical calculations do not predict voltage increase
sufficient to produce current needed to drive action potential
� Sthreshold = ½ cεoEmax2
� Emax = 0.155 V/mm2 � 0.05 mA/mm2 (surface)
� Field oscillations at ~1014 Hz
• Excite with Alexandrite laser (λ = 760 nm, 350 µs)
� Fiber delivered (600 µm spotsize)
• Observations:
� No stimulation for Ep < 200 mJ (70.7 J/cm2)
• Conclusion: electric field effect is not the mechanism for
optical stimulation
![Page 67: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/67.jpg)
Do axons have unique optical properties?
1
1.2
Rel
ati
ve
ma
gn
itu
de
1
1.2
Rel
ati
ve
ma
gn
itu
de
Axon
Pellet
Sucrose
Water
Axon
Pellet
Sucrose
Water
Axon
Pellet
Sucrose
Water
FTIR
2 3 4 5 6 7 8 9 100
0.2
0.4
0.6
0.8
Wavelength (µµµµm)
Rel
ati
ve
ma
gn
itu
de
2 3 4 5 6 7 8 9 100
0.2
0.4
0.6
0.8
Wavelength (µµµµm)
Rel
ati
ve
ma
gn
itu
de
WaterWaterWater
![Page 68: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/68.jpg)
Photochemical effect• Photon energy in IR too low for direct photochemistry
(< 0.1 eV), intensity insufficient for multiphoton
effects
• Would expect wavelength dependence other than • Would expect wavelength dependence other than
simply following the water absorption curve – not
observed
• Conclusion: photochemical effect is not the
mechanism for optical stimulation
![Page 69: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/69.jpg)
Thermal responsey p
ositio
n (
mm
)
-2 -1 0 1 2
-0.5
0
0.5
Ho:YAG
600 µm fiber
0.4 J/cm2
Tmax = 35.9 oC
∆Tmax = 8.9 oC
∆Taverage = 3.6 oC
x position (mm)-2 -1 0 1 2
26 27 28 29 30 31 32 33 34 35
-1 -0.5 0 0.5 10
2
4
6
8
position (mm)
Te
mp
era
ture
Ch
an
ge
(C
)
-1 -0.5 0 0.5 10
2
4
6
8
10
position (mm)
Te
mp
era
ture
Ch
an
ge
(C
)
Temperature (C)
![Page 70: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/70.jpg)
100
101
[m
m]
stress confinement thermal confinement
Ho:YAGQ-sw
Nd:YAGNd:YAG
Q-sw
Confinement Zones
5 µs
250 µs
10-3
10-2
10-1
100
101
10-3
10-2
10-1
10
102
103
104
105
106
Pulse duration [ s]µ
Pen
etra
tio
n d
epth
[
no confinement
Q-sw Er:YAG
Ho:YAGQ-sw
XeCl
ArF
τδ
=
τδ
κ=
4
2
vs
250 µs
1 ms
5 ms
![Page 71: E Duco Jansen - Optical Stimulation of Neural Tissue: Current State](https://reader031.vdocument.in/reader031/viewer/2022021421/5868d8ca1a28ab12578bdb69/html5/thumbnails/71.jpg)
Current Nerve Stimulator Areas of ActivityVestibular infrared nerve stimulation Univ of Washington (Harris)
CNS stimulation MIT (Boyden)
Eye pain sensor Univ of Maryland (Kao)
Cochlear scanner Baylor (Saggau)
Vestibular nerve stimulation Harvard (Merfeld/Lee)Vestibular nerve stimulation Harvard (Merfeld/Lee)
Sweat gland neuropathy study Mayo
Central and renal nerve Johns Hopkins
Cavernous nerve NC State (Fried)
Whisker nerves Washington State University (Rector)
CNS and PNS Vanderbilt (Jansen)
Cochlear INS Northwestern University (Richter/Walsh/Izzo-Matic)
Facial nerve monitor Northwestern University (Richter)
Facial nerve UC Irvine (Wong)
Cardiac stimulation CWRU (Rollins/Chiel)
Aplysia studies CWRU/Vanderbilt (Chiel/Jansen)