Hart Levy

Introduction: Neural activity correlates

VCSELs: What and Why Source characterization Laser Speckle Contrast Imaging Intrinsic Signal Imaging Future Work Recap

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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

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INTRINSIC SIGNAL IMAGING (IOSI):Use absorption spectroscopy to image HbR/HbO2

Oregon Medical Laser Center

LASER SPECKLE CONTRAST IMAGING (LSCI):Use phenomenon of laser speckle to image flow

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Generally quite invasive! Can only diffusely see through skull

Hillman, E. M. (2007) J Biomed Opt 12(5): 051402.

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Goal: live animal continuous monitoring

e.g. Fluorescence sensing in mice: 2 weeks continuous study

Goal: Implement two methods simultaneously!

Problem: Signal for one technique is noise in the other

P.B. Jones, Harvard Medical School

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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

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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”

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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

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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!

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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 11

What happens when there is movement?

Calculate stdev/mean in 5x5 pixel ROIs

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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!

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Model from Parthasarathy, Dunn, University of Texas

VCSELs are well suited to the task: Pulse current to obtain exposures below 50 us.

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Image series from 20 us to 40 ms

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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%

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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

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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

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Solving linear system gives concentration changes HbO

HbR

HbT

HbO + HbR

Time course from upper arteriole

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Can use comparisons between IOS images and flow maps to distinguish arterioles from venules

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Rapidly switching between single mode and sweep mode allows simultaneous oxygenation and flow imaging

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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)

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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

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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

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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

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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).