1. Vital Signs for Vital Organs™ Non-Invasive Blood Flow Measurements Using Ultrasound Modulated Diffused Light N. Racheli a, A. Ron a, Y. Metzger a, I. Breskin a, G. Enden b, M. Balberg a, R. Shechter a a Ornim Medical Ltd, Israel b Biomedical Engineering Department, Ben- Gurion University, Israel

2. Outline Background Phantom Setup Data analysis and Results In vivo evaluation Conclusions Future work

3. Ornim’s Regional Oximeter and Flowmeter Monitor Two Probes (multi-use) Single use adhesive pad Bed Side Monitor Cerebral & Tissue Oximeter – measures brain and muscle underneath the sensor Flow and oxygen saturation monitoring- simultaneously Two probes – independent readings Single use adhesive

4. Background Ornim’s patented technology utilizes principles of the acousto-optic effect The medium is irradiated with NIR coherent light Light is modulated in the tissue by a coded ultrasound series with a narrow autocorrelation: G(t): a series comprising of “1” and ” -1” bits, bit length = 4μ sec. f = 1MHz.

5. Background The detected light I(t) is correlated with the ultrasound series g(t):

6. Background

7. Background The amplitude of the UTL curve is proportional to: Photons’ density Ultrasound field Decorrelation time Movement of scatterers affects the amplitude of the cross correlation 0 1 2 3 4 5 Flow Values [A.U]

8. Experimental setup Phantom Syringe pump Reservoir Tissue mimicking phantom with micro channels simulates small blood vessels Generate flow at the range of 0 to 2.5 mm/sec Deliver coherent light and Ultrasound into the phantom Record and analyze the light signal Fluid: 70% purified H 2 O; 10% Glycerol; 20% Spherotech Inc Polystyrene spheres, 0.4-0.9µm (5% W/V)

9. Data Analysis and Results Extracting the Flow Index ( CFI ) from the UTL curve N K

10. Data Analysis and Results The amplitude of the UTL curve decreases as flow through the channels increases CFI is linear as a function of the flow velocity Sensitivity to flow in deep channels is lower but measurable R 2 =0.97 R 2 =0.99 R 2 =0.90

11. Data Analysis and Results The effect of scatterers concentration was tested Diluted the original liquid from 1% to 0.66% of Polystyrene spheres (W/V) The CFI is linear as a function of the normalized velocity values R 2 =0.87

12. In vivo Evaluation Preclinical model – piglets Comparison to a commercial, invasive, Laser Doppler (LD) Moor Instrument DRT4, with DP3b probe Manipulations Flow increase - Epinephrine Flow decrease -Nitropruside/hyperventilation/occlusion

13. In vivo Evaluation CFI Laser Doppler Epinephrine0.8240.776 Nitropruside0.9140.919 Hyperventilation11 Epinephrine Injection Nitropruside Injection ROC analysis - AUC Hyperventilation

14. Cerox 3210F- Oxygen saturation and blood flow Combined display of saturation and flow per channel Saturation Flow Blood occlusionExercise Saturation

15. Conclusions A novel method for continuously and non invasively measuring flow in deep tissue based on ultrasound modulated diffused light was presented Data demonstrates a linear correlation of CFI to flow in channels deeper than 1cm in a synthetic phantom A very good in vivo correlation to Laser Doppler readings was demonstrated

16. Future Work Clinical studies – cerebral flow monitoring during surgeries Calibrate CFI Numerical model

17. Vital Signs for Vital Organs™ THANK YOU http://www.ornim.com Vital Signs for Vital Organs™