Antonio Rampoldi Struttura Complessa di Radiologia Interventistica Azienda Ospedale Niguarda Ca Granda, Milano. Terminology

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1 Biophysical principles and clinical applications of MRgFUS Alberto Torresin Struttura Complessa di Fisica Sanitaria Azienda, Milano Università degli Studi di Milano Dip. di Fisica Antonio Rampoldi Struttura Complessa di Radiologia Interventistica Azienda, Milano Terminology HIFU (High Intensity Focus Ultrasound) HAIFU MRgFUS Magnetic Resonance guided Focus Ultrasound Surgery Torresin A, Fisica Sanitaria - Milano- 1

2 Main questions Why focussed ultrasound? Why Magnetic Resonance Imaging (MRI)? US UltraSound (for Therapy) Torresin A, Fisica Sanitaria - Milano- 2

3 FUNDAMENTAL PHYSICS US Ultrasound Ultrasound waves are high frequency sound waves that are generated with a transducer, or device that converts electrical energy to mechanical (sound) energy. The Curie brothers noted that when pressure was applied to quartz crystals (A), an electrical current resulted. Conversely, if the current was an alternating voltage (B), the crystal oscillated with a frequency that correlated with that of the drive current. This piezoelectric phenomenon was the foundation for studies on ultrasonic energy. Jagannathan, et al, Neurosurgery, 2009 Subsonic < 20 Hz US spectrum Sonic or audible from the man (20 Hz-20 khz) Ultrasound > 20 khz Torresin A, Fisica Sanitaria - Milano- 3

4 How Diagnostic Ultrasound Works Transducer Intensity The intensity of an ultrasound beam represents the quantity of energy that traverses a unitary surface perpendicular to the direction of propagation per unit of time Unit for the measurement of ultrasonic intensity is the W/cm 2 Diagnostic US: ~ 100 mw/cm 2 Therapeutic US: ~ 1500 W/cm 2 Torresin A, Fisica Sanitaria - Milano- 4

5 Acoustic Impedance The acoustic impedance represents a measurement of the resistance offered by the medium to the propagation of the wave. Novario et al, 2003 INTERACTIONS OF ULTRASONIC WAVES WITH BIOLOGICAL TISSUES direct effects Thermal effect Cavitational effects formation of vapour bubbles of a flowing liquid Torresin A, Fisica Sanitaria - Milano- 5

6 US in diagnostic procedure The US intensity is low (~ 100 mw/cm 2 ) No biological effects US in therapeutic procedure: thermal effect The heat produced when ultrasound is absorbed may lead to an increase in temperature to a level at which irreversible tissue damage occurs. Many human tissues are irreversibly damaged by heating to temperatures in excess of about 50 o C. This is the principle of HIFU; pathogenic tissue is heated and destroyed by high energy focused ultrasound. Torresin A, Fisica Sanitaria - Milano- 6

7 Thermal Therapy When tissue is heated and exceeds a thermal dose threshold, tissue ablation occurs Thermal dose of 100% tissue ablation*: At 43 o C 240 minutes Or at 54 o C 3 second Or at 57 o C 1 second T ref : reference temperature Δt: time interval t final = t heating + t cooling R= 0.5 (>43 C); 0.25 (<43 C) (*) Sapareto, S.A. et al (1984). Int J Radiat Oncol Biol Phys. Chung, et al, Med Phys, 1999 Thermal Therapy Total ablation Torresin A, Fisica Sanitaria - Milano- 7

8 MRI Magnetic Resonance Imaging Imaging Why MRI? MRI offers precise targeting, visualization, and quantification of temperature changes and the ability to immediately evaluate the treatment. Personal planning of the treatment. We are able to avoid critical structures and define the US trajectory Torresin A, Fisica Sanitaria - Milano- 8

9 Thermal imaging MR imaging is used to measure the temperature changes in tissue while FUS is being applied. The thermal imaging method relies on small changes of the proton resonant frequency (PRF) in water that occur as a function of temperature. The temperature is primarily due to temperatureinduced distortion Measuring absolute temperature of tissue using PRF imaging is not possible MRgFUS Magnetic Resonance guided Focus Ultrasound Surgery Torresin A, Fisica Sanitaria - Milano- 9

10 MRgFUS at Niguarda Technical data Phased array transducer with 208 transmitting elements + 3 receiving elements for cavitation detection US: range of 0.9 to 1.3 MHz with controlled power Focal depth : ranges from 1 to 14 cm in tissue Focal spot size: varies from 8x2x2mm 3 to 10x10x45mm 3 Torresin A, Fisica Sanitaria - Milano- 10

11 How does ExAblate work? MR guided focused ultrasound combines: High intensity focused ultrasound that heats and destroys targeted tissue, non-invasively. Magnetic Resonance Imaging system (MRI) which allows the physician to identify and target tumors, and provides temperature monitoring of the treated tissue in real time. Focused Ultrasound generates heat by focusing ultrasound waves, ablating tissue only at the focal point an effect similar to a magnifying glass used to focus the sun s energy on a single point. How Diagnostic Ultrasound Works Transducer Torresin A, Fisica Sanitaria - Milano- 11

12 How Focused Ultrasound Works Similar to how a magnifying glass focuses light energy, ultrasound (high frequency sound waves) can be focused on a specific point Treated spot Tumor Transducer Energy pass zone By Insightec Focused Ultrasound Transducer Torresin A, Fisica Sanitaria - Milano- 12

13 High-Focus Ultrasound As a Heat Source Ultrasound Effect on Tissue Thermal simulations show the shape of the focus Parallel to beam path Perpendicular to beam path Torresin A, Fisica Sanitaria - Milano- 13

14 Thermal Development of a 10 Seconds Sonication 1.1 seconds 4.5 seconds 7.9 seconds 11.3 seconds Magnetic Resonance The patient - Uterine Fibroid Imaging Torresin A, Fisica Sanitaria - Milano- 14

15 What does MR guidance provide? 3D anatomic information for exact tumor targeting Beam path visualization for safe treatment Real time temperature feedback to control treatment Immediate treatment outcome assessment Real time controlled therapy vs guided therapy By Gedroyc, London Coagulative necrosis FUS treated turkey breast Individual sonications induced in turkey breast tissue. Torresin A, Fisica Sanitaria - Milano- 15

16 Daily acceptance test at Niguarda Ca Granda Treatment at Niguarda Ca Granda Torresin A, Fisica Sanitaria - Milano- 16

17 ExAblate current research Ongoing research in: selected oncology indications in (properly designed) phase II trials(s) Uterine fibroids - fertility Breast Brain Liver Uterine Prostate Fibroids Bone Exploring additional research applications. Possible treatment applications (Niguarda Ca Granda) Thermal ablation fibroids Breast Bone Torresin A, Fisica Sanitaria - Milano- 17

18 MRgFUS for Palliation of Bone Metastasis Treatment principles Bone heating is used to ablate the adjacent periosteum Palliation achieved by the ablation of the bone periosteum Ablated Tissue Bone Soft tissue Acoustic Beam Transducer Transducer Acknowledgments Paola Colombo Alessio Moscato Stefano Pasetto Paola Quellari Alfeo Montesi Paul Wragg Torresin A, Fisica Sanitaria - Milano- 18

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