Developing New Technology for Local Tumor Control:

1. Developing New Technology for Local Tumor Control: A Bioengineering Approach Andrew Wright MD Department of Surgery 1/25/02

2. Background • Greater than one half of patients with colorectal cancer will develop liver metastases at some point in their clinical course • Surgical resection of an isolated liver tumor offers a five-year survival between 25 and 38%, compared to a 0% five-year survival without resection

3. Only 10–20% of patients with liver tumors will have disease amenable to surgical resection due to high surgical risk or unfavorable anatomy Background

4. Radiofrequency Ablation • High-frequency (460 kHz) alternating current flows from electrical probe through tissue to ground Probe insertion Extension of prongs RF current application

5. Cool-Tip probe (17-gauge needle) (Radionics) Radiofrequency Ablation 12-prong “Leveen” probe, 4 cm diameter (Radiotherapeutics) 9-prong “Starburst” probe, 5 cm diameter (Rita Medical)

6. TemperatureChange Heat loss through blood flow Thermal Conductivityand heat constant Current Density * Electric Field Constant Radiofrequency Ablation • Bioheat Equation • Lesion  (Energy Applied x Local Tissue Factors) – Energy Lost

7. Finite Element Modeling • Determine material and electrical properties of tissue and ablation system • Develop geometric model • Solve Bioheat equation

8. Finite Element Modeling

9. Bioengineering Approach • Define Problem • Determine Possible Solutions • Model • Test • Refine

10. RF RF Define Problem • Local recurrence as high as 30% • Uneven or irregular heating • Heat sink vessels Several mm’s

11. Define Problem • Local recurrence as high as 30% • Uneven or irregular heating • Heat sink vessels • Difficult to treat large or multiple tumors

12. Define Problem • Local recurrence as high as 30% • Uneven or irregular heating • Heat sink vessels • Difficult to treat large or multiple tumors • Poor imaging and localization Ultrasound B-scan After RF Ablation Ultrasound B-scan Before RF Ablation

13. TemperatureChange Heat loss through blood flow Thermal Conductivityand heat constant Current Density * Electric Field Constant Possible Approaches • Bioheat Equation • Lesion  (Energy Applied x Local Tissue Factors) – Energy Lost

14. Potential Solution #1 • Bipolar RF Ablation • Increase current density between electrodes • Increase energy deposition • More uniform tissue heating

15. Bipolar RF Ablation

16. Bipolar RF Ablation • FEM predicts nearly double lesion volume with bipolar electrode

17. Bipolar RF • In vivo porcine liver Monopolar Bipolar

18. Bipolar RF • Monopolar 3.93  1.8 cm2 • Bipolar 12.2  3.0 cm2

19. Bipolar RF

20. Bipolar RF Monopolar, d=2.3 mm Bipolar asymmetric, d=1.8 mm Bipolar symmetric, d=1.0 mm

21. Bipolar RF • Problems • Inability to control two electrodes independently • Difficult technical placement • Unable to treat multiple tumors

22. Potential Solution #2 • Multiple Probe RF Ablation • Allows overlapping treatment of large solitary tumors • Allows simultaneous treatment of multiple tumors

23. Bipolar Monopolar Multiple Probe RF Ablation • Disadvantage: electrical shielding between electrodes (Faraday cage)

24. Block diagram of system Multiple Probe RF Ablation

25. Bipolar Monopolar Alternating Monopolar Multiple Probe RF Ablation

26. Multiple Probe RF Ablation • Prototype Multiple Probe Device • Computer controlled electromechanical switch

27. Multiple Probe RF Ablation • Ex Vivo Testing

28. Multiple Probe RF Ablation • In Vivo Testing

29. Multiple Probe RF Ablation Single Probe Ablation Simultaneous Multiple Probe Ablation

30. Multiple Probe RF Ablation • In Vivo Testing • Lesion Volume • Single 10.7 cm3 • Dual 17.3 cm3 (per lesion) • Time to Target Temperature • Single 2.7 minutes • Dual 3.4 minutes

31. Multiple Probe RF Ablation • Change to electrical switch • Increase number of probes • Increase speed of switching • Decrease load on generator • Evaluate synergism of overlapping multiple probe RF ablations

32. Potential Solution #3 • Bioheat Equation • Lesion  (Energy Applied x Local Tissue Factors) – Energy Lost • Tissue Impedance (resistivity)

33. Tumor Resistivity • Electrical properties of normal liver and tumor (K12/TRb) measured in an in vivo rat liver model

34. Tumor Resistivity • Finite Element Model Tumor diameter = 2 cm

35. Tumor Resistivity • Current Density 500 kHz 100Hz

36. Tumor Resistivity • Temperature 500 kHz 100Hz

37. Gray circle represents tumor boundary Tumor Resistivity • Lesion Difference

38. Tumor Resistivity • Human? • Colorectal metastasis to liver

39. Alternative Solution • Microwave Ablation • Theoretical advantages over radiofrequency ablation • No ground pad • Not limited by tissue charring and impedance changes • Use of Multiple Probes

40. Microwave Ablation • Larger zone of active heating 1-2 mm MW 1-2 cm MW

41. Microwave Ablation RF MW

42. Multiple Probe Ablation • Null Hypothesis • Because microwave and radiofrequency ablation are both heat based, there will be no difference in ablation size or lesion pathology between the two technologies

43. Methods • Microwave Ablation • Vivant Medical prototype system • 10 minute ablation, 40 Watts • Radiofrequency Ablation • RITA Medical Systems Starburst • 10 minute ablation, 3cm deployment 100oC target temperature

44. Microwave Ablation System • Vivant Medical • 13g, 15cm dipole antenna • 915MHz generator • Fiberoptic temperature monitor

45. Radiofrequency Ablation System • RITA Medical • 14g, 15cm expandable array • 460 kHz generator • Integrated thermocouple

46. Lesion Volume * * * p=.02

47. Lesion Length * ▪ ▪ ◦ * ◦ * p<.001 ▪ p=.02 ◦ p<.001

48. Lesion Diameter

49. 48o Pathology RFA MW Immediate 4 weeks

50. Laboratory Data • No significant difference in AST, ALT, LDH, Alkaline Phosphatase, WBC, or HCT * * p<0.001