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

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

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

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

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): 051402.

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

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

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”

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

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!

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

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

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.

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

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%

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

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

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

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

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

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)

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

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

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).