1. 1 Fibrosis in Spinal Cord Stimulation (SCS): Validation and Improvement of a Computational Model Dongchul Lee PhD, Kerry Bradley MS, Nicholas Kormylo MD, Tobias Moeller-Bertram MD MAS

2. 2 Why do we care about the computer model? Computational model is One of tools used for product development in SCS history Used to understand the mechanism of the SCS More advanced model means –Better understanding about the mechanism –Better potential to predict clinical outcomes –Better product Based on understood mechanism SCS Product development Clinical study Computational model Prediction Modification

3. 3 Computational models in SCS Holsheimer - 1980s Mathematical model of Spinal Cord Stimulation Defined anatomy, fiber diameters Defined conductivity of various components − Dorsal root vs dorsal column fibers − Gray matter vs white matter − CSF, dura, and epidural fat Boston Scientific Model - 2007 Based on Holsheimer model Additional features –Various size of nerve fibers: dorsal column and roots –Fiber distribution: Feirabend et al. 2002 –Spinal cord cross-section: Kameyama et al. 1996 11.5 um (0.25%) Fiber diameters 8.7 um (3%) 5.7 um (25%) 7.5 um (10%) 12.8 um (0.08%) 14.0 um (0.025%) Stimulated fiber distribution

4. 4 Perception threshold Cathode E1 E2 E3 E4 E5 E6 E7 E8 E1 E2 E3 E4 E5 E6 E7 E8 0.5 1 1.5 420 Monopole Clinical data 812162428 mm Bipole distance Relative threshold ratio

5. 5 Perception threshold Cathode Anode E1 E2 E3 E4 E5 E6 E7 E8 0.5 1 1.5 420 Monopole 812162428 mm 28 mm Bipole distance Relative threshold ratio E1 E2 E3 E4 E5 E6 E7 E8 Clinical data

6. 6 Perception threshold Cathode Anode E1 E2 E3 E4 E5 E6 E7 E8 0.5 1 1.5 420 Monopole 812162428 mm 28 mm Bipole distance Relative threshold ratio E1 E2 E3 E4 E5 E6 E7 E8 Clinical data

7. 7 Perception threshold Cathode Anode E1 E2 E3 E4 E5 E6 E7 E8 0.5 1 1.5 420 Monopole 812162428 mm 28 mm Bipole distance Relative threshold ratio E1 E2 E3 E4 E5 E6 E7 E8 Clinical data

8. 8 Perception threshold Cathode Anode E1 E2 E3 E4 E5 E6 E7 E8 0.5 1 1.5 420 Monopole 812162428 mm 28 mm Bipole distance Relative threshold ratio E1 E2 E3 E4 E5 E6 E7 E8 Clinical data

9. 9 Perception threshold Cathode Anode E1 E2 E3 E4 E5 E6 E7 E8 E1 E2 E3 E4 E5 E6 E7 E8 0.5 1 1.5 420 Monopole Model (no encapsulation) 812162428 mm 28 mm Bipole distance Relative threshold ratio Clinical data ? ?

10. 10 Activating function and bipole distance Depolarization Hyperpolarization Cathode Anode Without encapsulation layer

11. 11 Activating function and bipole distance Depolarization Hyperpolarization Cathode Anode 0.5 1 1.5 420 Monopole Model (no encapsulation) 812162428 mm Bipole distance Relative threshold ratio Clinical data Without encapsulation layer

12. 12 Activating function and bipole distance Depolarization Cathode Anode 0.5 1 1.5 420 Monopole Model (no encapsulation) 812162428 mm Bipole distance Relative threshold ratio Clinical data Without encapsulation layer

13. 13 Modification of BSN model Encapsulation layer Fibrosis Fibrous sheath observed in chronic goat model (15wks post-implant) Epidural fibrous

14. 14 SCS model with encapsulation layer Effect of encapsulation layer Spreading the field along the axial direction Minimum threshold was observed at bipole distance of 16 mm. Threshold at tight bipole (4 mm) was matched to clinical data, 60% higher than monopole threshold. 0.5 1 1.5 0102030Monopole Clinical data Model (no encapsulation) Model (encapsulation) Bipole distance Relative threshold ratio

15. 15 Conclusions Due to the encapsulation layer, electric field from one contact reached further than expected from previous mathematical modeling. Prediction of threshold by the BSN computational model has been improved by adding an encapsulation layer to mimic chronic fibrotic growth. Therefore, when using computational modeling to predict technical outcomes in SCS, geometrical and bioelectric factors in the spinal column should be considered as critical components.

16. 16 Perception threshold Cathode Anode E1 E2 E3 E4 E5 E6 E7 E8 E1 E2 E3 E4 E5 E6 E7 E8 0.5 1 1.5 420 Monopole Clinical data Model (no encapsulation) 812162428 mm 28 mm Bipole distance Relative threshold ratio

17. 17 Perception threshold Cathode Anode E1 E2 E3 E4 E5 E6 E7 E8 E1 E2 E3 E4 E5 E6 E7 E8 0.5 1 1.5 420 Monopole Clinical data Model (no encapsulation) 812162428 mm 28 mm Bipole distance Relative threshold ratio

18. 18 Effect of fibrosis on threshold Depolarization Hyperpolarization Cathode Anode 0.5 1 1.5 420 Monopole Model (no encapsulation) 812162428 mm Bipole distance Relative threshold ratio Clinical data