Multimodal Neural Optical Imaging with Current Swept VCSELs

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

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

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

5. Portable In-vivo Imaging • 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. Generally quite invasive! Can only diffusely see through skull

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

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

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

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

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

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

13. Making LSCI quantitative: MESI Model from Parthasarathy, Dunn, University of Texas VCSELs are well suited to the task: Pulse current to obtain exposures below 50 us. 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!

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

15. Making LSCI quantitative: MESI 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% Concern: enough signal/noise? After contrast calculation, noise becomes additive constant, known based on camera characteristics!

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 HbO HbT Time course from upper arteriole HbR Solving linear system gives concentration changes 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? 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). 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