1. Part 01 - fNIRS: a cost-effective and robust technique for measuring neuroactivation 1

2. 2 NIRx Offices (Year Established) New York, USA (1999) Berlin, Germany (2006) Los Angeles, USA (2013) São Paulo, Brazil (2014) Istanbul, Turkey (Pending, October 2014)

3. What is NIRS? NIRS = Near- InfraRed Spectroscopy A form of Optical Imaging. 3

4. … can be used to identify molecular structures. The interaction of EM radiation with matter… A bit about Spectroscopy 4

5. The oxygen transporter in the blood of vertebrate animals. The molecule of interest: Hemoglobin (Hb) 5

6. 6 Neural activation ↓ Metabolic demand ↓ Increased blood flow ↓ Increase in oxy-hemoglobin & Wash-out of deoxy-hemoglobin The Hemodynamic Response

7. To discriminate between HbO and HbR, NIRS systems use multiple wavelengths in measurements. (example: 760nm & 850nm) EM absorption of oxy-Hb and deoxy-Hb 7

8. Best frequencies for physiologic chromophores are partially within the red & NIR spectrum Lower absorption of light = Better transmission through tissue and bone Well suited for modern LED's or lasers (650…900nm) Optimal Light Frequencies of NIRS 8

9. Skin and bone are mostly transparent to near-infrared light and do not significantly impede the signal. 9 Practical Example

10. Relies on properties of absorption and scattering of photons. 10 Principles of Optical Imaging

11. The sensitivity profile light conforms to an elliptical “banana” shape as it travels from source to detector. This is known as a photon banana. 11 Principles of Optical Imaging

12. A single light source sends light out indiscriminately, with signal detected at potentially infinite positions. 12 Principles of Optical Imaging Hemoglobin Detector Light Source Ambient Light

13. Source Detector Collects functional information from top 1cm of cortex, using “nearest neighbor” source-detector measurements. One data channel is produced per wavelength used per source/detector pairing. 13 NIRS Topography The source-to-detector pairing distance effects the depth of the photon banana penetration.

14. 14 S D S D S D S D S 2 – 3 cm ‘Nearest-neighbor’ measurements are done with spacing of 2-3cm between sources and detectors. S D = light source = light detector = data channel NIRS Topography

15. Source Detector 1 Detector 2 Eliminates systemic interference of superficial origin (closest channel => mostly non-cortical signal) 15 NIRS Tomography Like Topography, collects functional information from top 1cm of cortex, but uses multi-distance measurements with a single source sending light to multiple detectors in 1-dimention. Multi-distance measurements allow for depth discrimination of signal

16. 16 Kohl M,.., Dirnagl U. Phys. Med. Bio. 2000 oxy-Hb (HbO) deoxy-Hb (Hb) x10 -3 time in [s] 0246810121416 0 1 2  concentration [mM] Stimulation period The NIRS Hemodynamic Response

17. Spatial resolution of neuro-activation within the mm-to-cm range (depending on probe density) Excellent sensitivity to Hb and HbO Excellent sampling rate (several Hz to 60Hz+) Measures top 1cm of cortex Greatest light transmission is on forehead (prefrontal) due to lack of hair, supporting vascular structure, and sinuses 17 Physical and Biological Principles

18. How does NIRS compare to more well-known functional brain-imaging modalities? 18

19. BOLD fMRI Identifies deoxyhemoglobin as well as detailed tissue structure from entire brain Hundreds of thousands of peer- reviewed publications Large form-factor, noisy operation, very expensive systems and operation Confined environment 19 Functional Hemodynamic Modalities

20. fNIRS Identifies deoxyhemoglobin as well as oxyhemoglobin (total hemoglobin derived) from top 1cm of cortex (deeper at forehead) Thousands of peer-reviewed publications, but rapidly increasing in number Relatively small form-factor (portable options available) Silent system operation (ideal for sensitive subjects) System cost is a fraction of the cost of fMRI, operational cost is very low 20 Functional Hemodynamic Modalities

21. Comparison - fMRI vs. fNIRS Spatial mapping of activation area in response to right-hand activity NIRS,  HbR fMRI BOLD Jan Mehnert, OHBM Annual Meeting, 2010 L L 21

22. fNIRS fMRI seconds Jan Mehnert, OHBM Annual Meeting, 2010 22 Most Significant Activation Response

23. 23 EEG Measures cortical electrophysiology from scalp Tens of thousands of peer-reviewed publications Excellent temporal resolution (sampling rates 2kHz+) – Measures very quick paradigms related to action potentials (P300, N200, etc.) as well as frequency bands (alpha, beta, etc.) Relatively poor spatial resolution (several cm) Portable/wearable systems available, but highly sensitive to motion artifacts Small Form-Factor Neuro-Modalities

24. 24 Small Form-Factor Neuro-Modalities fNIRS Measures hemodynamic cortical activity - Similar headgear and form-factor to EEG Lower temporal resolution than EEG (fNIRS typically ~5-10Hz) – Though lower, the sampling rate for fNIRS is more than sufficient for measuring hemodynamic responses of interest (.01 -.2Hz) Greater spatial resolution than EEG (fNIRS is ~6mm) Better noise performance than EEG with even very extreme movements and muscle usage

25. NIRS technology offers: Compact, low cost sensing hardware Noninvasive, continuous measures Highly configurable and scalable platforms Information-rich sensing data –BOLD-like response without the magnet –Source localization >> EEG –Minimal sensitivity to movement artifacts 25 Summary of NIRS

26. Thanks!... Questions? 26