1. Multimodal Neural Optical Imaging with Current Swept VCSELs
Hart Levy
Multimodal Neural Optical Imaging with Current Swept VCSELs

2. Overview Introduction: Neural activity correlates VCSELs: What and Why
Source characterization
Laser Speckle Contrast Imaging
Intrinsic Signal Imaging
Future Work
Recap

3. Introduction: Neural Activity Correlates
Common clinical technique: fMRI
Principle: blood oxygenation (Hbr/HbO2) is correlated with neural activity
Disadvantage: Expensive, low temporal and spatial resolution
FMRIB center, University of Oxford
Scripps Research Institute

4. Optical Techniques for Neural Imaging
INTRINSIC SIGNAL IMAGING (IOSI): Use absorption spectroscopy to image HbR/HbO2
LASER SPECKLE CONTRAST IMAGING (LSCI): Use phenomenon of laser speckle to image flow
Oregon Medical Laser Center

5. Portable In-vivo Imaging
Generally quite invasive! Can only diffusely see through skull
Goal: live animal continuous monitoring
e.g. Fluorescence sensing in mice: 2 weeks continuous study
Hillman, E. M. (2007) J Biomed Opt 12(5):

6. Portable In-vivo Imaging
Goal: Implement two methods simultaneously!
Problem: Signal for one technique is noise in the other
P.B. Jones, Harvard Medical School

7. Solution: VCSELs Vertical Cavity Surface Emitting Lasers
Very small (~50 um), low operating current, GaAs substrate
Currently using CCD detectors for imaging. In future, on-chip photodiode arrays

8. Solution: VCSELs Interesting optical property: Somewhat tunable
Single mode near threshold, multi mode as current increases
Sweeping current
“broadband laser”
Only works if we do this fast enough, camera sees all “modes”

9. Coherence Length and Speckle
Q: Why does this matter?
A: Speckle contrast ~ coherence length, coherence length is related to spectrum (Fourier pair)
Contrast reduction:
Surface variation, in our case penetration depth in tissue

10. VCSEL characterization
We use 3 wavelengths for oxygenation imaging: 670 nm, 795 nm, 850 nm
Can obtain similar coherence profiles for all 3, lc ~0.2 mm
For tissue penetration of 5 mm, expect ~5x reduction in speckle!

11. More on LSCI Speckle is an interference phenomenon
Constructive/destructive interference of diffusely reflected light at detector
Static speckle spot size based on imaging system
f/1.4
f/5.6

12. More on LSCI What happens when there is movement?
Calculate stdev/mean in 5x5 pixel ROIs

13. Making LSCI quantitative: MESI
We can relate contrast values to flow rates!
Relation is not trivial: Multiexposure speckle imaging
In order to fit, we need images at exposure times covering 3 orders of magnitude!
Model from Parthasarathy, Dunn, University of Texas
VCSELs are well suited to the task: Pulse current to obtain exposures below 50 us.

14. Making LSCI quantitative: MESI
Image series from 20 us to 40 ms

15. Making LSCI quantitative: MESI
Concern: enough signal/noise?
After contrast calculation, noise becomes additive constant, known based on camera characteristics!
Proof of concept: Maps produced at f numbers 1.4, 2.0, 2.8, 4.0 (factor of 8 change in intensity).
Results are identical within 20%

16. IOSI with current swept VCSELs
Recall we use 3 wavelengths: 670, 795, 850 nm
795 is near ISOBESTIC POINT: blood volume changes
670 dominated by HbR, 850 dominated by HbO2
Apply Beer-Lambert system to extract concentration changes

17. IOSI application: Ischemia model
IOSI can only quantify concentration changes
To induce changes, we use an ischemic stroke model
Circle of Willis maintains flow to all parts of brain we don’t expect drastic variations, can get reperfusion

18. IOSI application: Ischemia model
Solving linear system gives concentration changes
HbO
HbT
Time course from upper arteriole
HbR
HbO + HbR

19. IOSI application: Vessel identification
Can use comparisons between IOS images and flow maps to distinguish arterioles from venules

20. Dual Mode Simultaneous Imaging
Rapidly switching between single mode and sweep mode allows simultaneous oxygenation and flow imaging

21. Future Work Sensory stimulation model
Physiological study with neuroscientists (epilepsy model, EEG, neurovascular coupling)
Rapid real time image processing (EMCCD camera)
Miniaturization for continuous monitoring (CMOS detector arrays)

22. Recap
Monitor oxygenation and blood flow as correlates of neural activity
Utilize VCSELs to simultaneously use two techniques
Noise correction algorithms allow robust flow monitoring
Future goals: apply to neuro studies, miniaturize for continuous imaging

23. References
A. B. Parthasarathy, et. Al., “Robust flow measurement with multiexposure speckle imaging,” Optics Express 16(3), 2008.
Z. Luo, et. al,. “Simultaneous imaging of cortical hemodynamics and blood oxygenation change during cerebral ischemia using dual-wavelength laser speckle contrast imaging,” Optics Letters 34(9), 2009.
S. Sakadzic, et. al., “Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression,” Applied Optics, 48(10), 2009.
B.W. Zeff, et. al.,“Retinotopic mapping of adult human visual cortex with high-density diffuse optical tomography,” PNAS 24(109), 2007.
Acknowledgements: Prof. Ofer Levi, Dene Ringuette, Elizabeth Munro, Xiaofan Jin, Thomas O’Sullivan

24. Backup: Why these methods?
Epilepsy localization:
Stroke: After ischemia, we know blood flow can return, but cerebral circulation response to neural activity is alterted
Alzheimers: Neurovascular degeneration precedes cognitive impairment. Mechanisms need further investigation
T. H. Schwartz, Cornell
H. Girouard and C. Iadecola, “Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease,” J. Appl. Physiol. 100, 328–335 (2006).