Busto Arsizio November 10th, 2010 MASTER CLASS ON MICROWAVE THERMOABLATION Coordinator: Dr Luigi Solbiati Principles of

1. Busto Arsizio November 10th, 2010 MASTER CLASS ON MICROWAVE THERMOABLATION Coordinator: Dr Luigi Solbiati Principles of MW thermoablation and presentation of HS AMICA Nevio Tosoratti, PhD R&D Unit Director HS Hospital Service S.p.A.

2. Outline: • Thermal Ablation • Electromagnetic field • Microwave Vs Radiofrequency Ablation • HS AMICA

3. Outline: • Thermal Ablation • Electromagnetic field • Microwave Vs Radiofrequency Ablation • HS AMICA

4. Tumour ablation Destruction of pathologic tissues through local delivery of energy through a minimally invasive approach Energy source Necrotic effect

5. Choice of most appropriate ablative tool Radiofrequency currents (RFs) Microwave radiations (MWs) EM action Laser Electroporation High Intensity Focused Ultrasound (HIFU) Mechanical action Thermal action Cryoablation Percutaneous ethanol injection (PEI) Chemical action Transarterial Chemoembolization(TACE)

6. Thermal Ablation: basics • Cellular heat damage starts at 45°C: • at 46°C: irreversible damage in 60 min • at 50°C: irreversible damage in 4-6 min • at 60°C: instanteneous irreversible damage • at 100°C: vaporization and carbonization • TARGET: TO REACH 60 °C Rhim H, Goldberg SN, Dodd GD, et al. Essential techniques for successful radio-frequency thermal ablation of malignant hepatic tumors. Radiographics 21: S17-35; 2001.

7. Heat sources Heat diffusion (indirect) Blood perfusion Metabolic heat Direct heating The bioheat equation Heating of living tissues is regulated by the “bioheat equation” H. H. Pennes, “Analysis of tissue and arterial blood temperatures in resting forearm,” J. Appl. Physiol., vol. 1, pp. 93–122, 1948

8. Direct Vs Indirect heating zones Direct heating zone: Energy deposition zone.“Fast” heating, Heat sinking effects easily overcome. Max temperatures achieved. Mixed heating zone: Hybrid direct and indirect heating zone. Intermediate behaviour. Indirect heating zone: Passive heating due to thermal conduction: “slow” heat propagation. Heat sinking effects become more relevant with increasing distance from the applicator. • The relative dimensions of the zones depend on the specific thermal ablation technique • The absolute dimensions of the zones depend on the amount of power delivered and on the effectiveness of energy transfer to tissues.

9. Direct (active) heating • the direct heating is the heat directly provided by the heat source employed by the physician (radiofrequencies, microwaves, cryogenic fluids, ultrasounds…) • it is the only phyisical feature of a specific thermoablation technique which actually makes the difference • it is the fast engine of the thermal ablation • it is characterized by two quantities: the energy absorption rate (SAR) and the penetration depth (Dp) • SAR measures the actual amount and distribution of energy provided to tissues and turned into heat • Dpis the radius of the active heating volume

10. Heat diffusion (indirect heating) • Heat diffuses from hot to cold zones like a colouring droplet in water. • Heat diffusion is a slow heating mechanism. • The rate of heat diffusion is proportional to the difference of temperature between the hot and cold zone. • For a given temperature gradient, heat diffusion is the same for all thermal ablation techniques. These techiques differ in their capability of generating adequate temperature gradients.

11. Metabolic heat and blood perfusion • Tissues react to heating, trying to survive. • There are two kind of reactions: • increased local metabolism (negligible) • increased blood perfusion, proportional to the temperature reached Both stop when T>60°C, due to cell death.

12. Thermal necrosis formation MW thermolesion expansion diagram in muscle-equivalent phantom 35 W / 2450 MHz. The thermal necrosis forms very rapidly at the beginning, eventually slowing down as time passes by. Picture courtesy of prof. M. Cavagnaro, University of Rome “La Sapienza”, Dept. Electronic Engineering

13. Outline: • Thermal Ablation • Electromagnetic field • Microwave Vs Radiofrequency Ablation • HS AMICA

14. EM Thermoablation At present, electromagnetic heating still seems to offer the best trade off among very different requirements: • control over the geometry of the induced necrosis • safety and ease of use • cost effectiveness

15. The electromagnetic field The electromagnetic (EM) field is a force field. There are two sources: ”positive” and “negative” electric charges.

16. EM waves The EM field propagates in the form of a wave. A wave is described by it’s wavelength , frequency  velocity v and amplitude A. v =  The power density (P) of a wave is proportional to the square of its amplitude (A) and is inversely proportional to the square of the distance from the emitting point (r): P ≈ A2 / r2

17. The EM spectrum The properties of EM waves mainly depend on their frequency. This dependence is so strong that we ususally assign different names to different portions of the EM spectrum: radiowaves, microwaves, infrared, light, x-rays and -rays.

18. Resonances • The response of a system to an alternate force is highly dependent on the frequency of the force. • big response if the frequency is close to the “proper frequency(s)” • nearly no response if the frequency is far from the proper frequency(s).

19. Response to RF currents: ionic drift ~ 500 kHz Radiofrequency excites movement of ions between the electrodes. Direct heating is proportional to the density of the current.

20. water dipole oxygen hydrogen Response to MWs: electric dipoles rotation ~ 1 GHz MWs excite dipole rotations. Direct heating is proportional to the density of the electric field.

21. Response to infrared laser: intra-molecular vibrations ~ 100 THz Infrared laser excites intramolecular vibrations. Direct heating is proportional to the density of the photons.

22. 10 4 10 13 10 16 10 22 Freq. (Hz)‏ 10 6 10 4 Microwave Energy absorption rate 10 2 RF X rays 1 Laser 10 -2 10 -4 Visible Light Energy absorption rate of water For frequencies below visible light (RF, MW, IR) the energy absorption rate increases with frequency

23. Penetration depth • The distance reached by the EM field is called penetration depth. • The penetration depth determines the volume of active heating. • The penetration depth is roughly inversely proportional to the frequency • The higher the energy absorption rate the smaller the penetration depth.

24. EM ablation: options • The penetration depth is: • few mm for laser, • few cm for MWs • many cm for RFs. • The energy absorption rate is: • excellent for laser, • very good for MWs • relatively poor for RFs. • Conclusion: • laser provide exceptional short range heating performance, but are inadequate for the treatment of medium/large tumors, • the real technical and clinical challenge is MWs vs RFs.

25. Outline: • Thermal Ablation • Electromagnetic field • Microwave Vs Radiofrequency Ablation • HS AMICA

26. RFs vs MWs: Basic differences Heating velocity Due to a much higher efficient mechanism of heat transfer, MWs heat tissues faster than radiofrequency AMICA vs COOLTIP_liver.avi

27. RFs vs MWs: Basic differences Reduced sensitivity to tissue properties MWs can penetrate and heat any kind of tissue whereas RFs circulation is hindered by high impedance issues AMICA vs COOLTIP_soap.avi

28. RFs vs MWs: Basic differences Energy confinement Radiofrequency set-up Microwave set-up RF electrode Ellipsoidal radiation pattern MW probe Current Grounding pads MWs are confined close (<2cm) to the antenna, whereas RFs flow through the body to reach the grounding pads.

29. MWs vs RFs: Performance differences Larger Coagulation volumes The higher heating efficency and the possibility to operate at temperatures >>100 °C allow MWs to produce significantly larger necrosis than RFs

30. MWs vs RFs: Performance differences Reduced heat sink effect • The heating efficency makes microwave less sensitive to • heat sinks • blood perfusion • blood vessels AMICA vs COOLTIP_vessel.avi

31. MWs vs RFs: Performance differences No interference with implanted metallic devices Ellipsoidal radiation pattern MW probe • MWs are confined around the antenna • No interactions with • pace-makers • metallic clips • introducing needles

32. MWs vs RFs: Performance differences Homogeneous heating RFs MWs Ablated volume Ablated volume Irregular contour ‘Skipped’ areas Regular contour ‘Skipping’ No ‘skipping’ MWs propagate into fat and calcifications, directly heating such tissues. The higher operating temperatures with respect to RFs ensures more heat diffusion.

33. Why RF ablation is leading? RF technology is easier to design and realize. When percutaneous thermoablation started, about 20 years ago, MW technology was still “immature”, lacking adequate solutions for MW generation and irradiation. Conventional interstitial MW antennas exhibit a tear-drop shaped heating pattern Picture courtesy of prof. M. Cavagnaro, University of Rome “La Sapienza”, Dept. Electronic Engineering

34. Outline: • Thermal Ablation • Electromagnetic field • Microwave Vs Radiofrequency Ablation • HS AMICA

35. HS AMICA: minichoke - 1 Conventional choked antenna MINI-CHOKED applicator • worldwide patent (CNR)‏ • spherical radiation pattern • no increase of the gauge • mimimum insertion depth required Introducing needle /4Choke

36. HS AMICA: minichoke - 2 distribution of the microwave field of conventional MW probes distribution of the microwave field of HS AMICA Probe Pictures courtesy of prof. M. Cavagnaro, University of Rome “La Sapienza”, Dept. Electronic Engineering

37. HS AMICA: minichoke - 3 without choke with choke I. Longo, G. Biffi Gentili, M. Cerretelli, N. Tosoratti, “A coaxial Antenna with Miniaturized Choke for Minimally Invasive Interstitial Heating”. IEEE Trans. on Biomed. Eng. Vol 50 N. 1; 2003.

38. Metal ring Dielectric feed Metallic point Choke section Cooling chamber 20 mm 5 mm AMICA PROBE: appearance Picture courtesy of Dr T. De Baere, IGR, Villejuif, France

39. AMICA PROBE: performance • Ex vivo bovine liver at 25 °C • dimensions are controlled with time and power • necrosis between 2 cm and 4 cm in diameter • - length grows first => sphericity increases with time

40. Electric field (a.u.) SAR (a.u.) Distance from applicator (m) Distance from applicator (m) 915 MHz vs 2450 MHz Calculation of the electric field intensity (on the right) and of the specific absorption rate (on the left) in a muscle-equivalent phantom as functions of the distance from elementary dipoles, respectively operated at 915MHz (red curves) and at 2450 MHz (blue curves). The 2450 MHz field turns out to be definitely higher than the 915 MHz field up to 4cm away from the antenna. (Courtesy of the Electronic Engineering Department of the University of Rome “La Sapienza”, Prof. Marta Cavagnaro)

41. Metal ring Dielectric feed Metallic point Choke section Cooling chamber 20 mm 5 mm “False friends” for RF users turning into MW users • only one “active length” instead of many exposed tip lengths • lesion dimensions are controlled through time and power • the hyper-echogenic spot appears much earlier • probe tip not cooled (“hot tip”), T >> 100 °C • MW probes require a non metallic “window” (ceramic or plastic) on their distal active tip to allow for energy drop out => intrinsic mechanical fragility

42. Multiple probes 3 probes at 20 mm 60 Watt / 10 minutes 6cm

43. AMICA GEN MW enable Power ON LCD Touchscreen Probe Link Remote port Knob MW out Foot switch • solid state generator • 2.45 GHz, up to 140 Watt CW output • user friendly interface • open digital architecture • connectivity with external devices

44. Remote connectivity AMICA GEN can be connected to a PC to download data or control ablation

45. HS AMICA: hybrid RF&MW system Dual generator, 2450 MHz / 450 kHz AMICA-PROBE: MW interstitial antenna, mini-choked, internally cooled RF AMICA-PROBE: RF interstitial electrode, monopolar, internally cooled

46. HS AMICA, Dual ablation system • The only ablation apparatus comprising in the same hardware both a MW and a RF energy generation, delivery and monitoring system • Capability of driving either RF monopolar electrodes or MW antennas • Automatic identification of probe type (RF or MW) and selection of corresponding output energy type • Embedded peristaltic pump serving for internal cooling of either type of applicator

47. HS AMICA: MWA TECHNOLOGY • Interstitial probes 11G, 14G and 16G x 150mm, 200mm and 270mm • Flexible probes 2.5mm x 1800mm • Internal water cooling combined with a special miniaturized trap for reflected waves (mini-choke*) yields quasi-spherical and perfectly controllable ablation volumes • Large and fast ablations: more than 5cm in diameter in 10 minutes, with a single probe, in a single insertion • No grounding pads • Microwave output: up to 140W CW at 2450 MHz • Continuous monitoring of delivered MW power, reflected power, temperature • Possibility of simultaneous multi-probe operation * Worldwide patent by CNR –Italian National Council for Research-, exclusively licensed to HS.

48. HS AMICA: RFA TECHNOLOGY • 17G interstitial electrodes • Exposed tip lengths: 1cm, 2cm, 3cm • Shaft lengths: 150mm, 200mm, 250mm • Internally cooled • Straight, pyramidal penetration point • Embedded thermocouple for probe temperature monitoring • Manual and automatic (impedance-driven) energy delivery modes supported • RF output: up to 200W at 450 kHz on a 50 Ohm load • Continuous monitoring of delivered power and current, tissue impedance, temperature • Grounding pads and complete tubing set for water cooling included in the disposable kit

49. RFs vs MWs • RF probes are monolithic metallic electrodes and thus are intrinsically more robust than MW antennas, which instead need a non metallic window at their distal end for irradiating tissues. • The RF technology is less complex and slightly less expensive than the MW technology • It is quite difficult to obtain with MW probes lesion sizes along the probe insertion track less than 2cm: this may sometimes be an issue (very superficial lesions, osteoma osteoids, etc.) • MWs provide a heating speed largely superior than RFs and thus are much less affected by heat sinking effects due to blood perfusion • The coagulative performance of MWs is remarkably less affected than that of RFs by variations in tissues physical properties (e.g. electrical conductivity): MWA provides a definitely wider scope of applications than RFA, with quite repeatable performance in different organs for a given set of working parameters (ablation time and power) • Unlike RFA, MWA is not hindered by tissue charring and therefore much higher intra-tumoral temperatures may be achieved, which in turn leads to a sensibly larger final lesion size • Unlike RF electrodes, multiple MW applicators simultaneously active are not at risk of mutual interference: simultaneous (and not only switched mode) multi-probe operation is therefore practicable for MWs • MWA doesn’t require current circulation through the patients: no grounding pads and less restraints on patients bearing pacemakers or metallic prosthesis

50. When to use RFs, when MWs? • RFs have proven to be very effective in the treatment of HCC nodules less than 3cm. • Percutaneous targeting of a lesion with MW probes generally requires more attention than with standard RF electrodes, due to tip fragility issues: this should be taken into proper account when puncturing very hard cyrrhotic tissue or when reaching the lesion through an intercostal access • The use of MWs may prove very beneficial in the treatment of large nodules (up to 5cm in a single probe/single insertion procedure), of metastases (which usually require larger safety margins) and of tumours located nearby major vessels or other heat sinks • The use of a single MW probe may often replace RF clusters or multiple RF electrodes used in switched mode. • For most applications, it is correct to state that anything achievable with RFs is also achievable with MWs, though not viceversa. Cost issues should also be taken into account. • Since MWs provide a more powerful heating tool than RFs, users must be more cautious in their use, spend more time on treatment planning and go through an intensive training programme. • Even if most procedural aspects of RFA and MWA look quite the same, there are many “false friends” to be avoided: MWA requires a learning curve even in advanced RF users