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2. High-Intensity Focused Ultrasound 17 2.1 Ultrasound in Medicine

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High-Intensity Focused Ultrasound 17 2.1 Ultrasound in Medicine girein cieoBdaenicouNf nm rapeD tnemt fo csorueN ecnei dna idemoiB ac l reenignE gni - o t l aA DD Advanced Techniques in 45 / 7102 rednal l iT ittaMMagnetic Resonance- Guided High-Intensity Focused Ultrasound Matti Tillander dnuosar t lU desucoF yt i snetnI -hg iH dediuG-ecnanoseR c i ni tengaM seuqinhceT decnavdA NSI NBS 1-2537-06-259-879 ( p r i n t de ) SSENISUB + NSI NBS 4-1537-06-259-879 ( dp f ) E MONOC Y L-NSI NSS - L 9971 - 4394 NSI NSS 9971 - 4394 ( p r i n t de ) TRA + NSI NSS 9971 - 2494 ( dp f ) NGISED + HCRA I T TCE ERU ytisrevinU otlaA ytisrevinU ceic fo oohcS l o f cS i ecne ECNEICS + n engEla dmi n ce sre otetrapeD tnemt fo csorueN ecnei dna idemoiB ac l reenignE gni T E ONHC L GO Y if.otlaa.www . a a l t o . f i R VOSSORC RE COD T RO A L +bcfdha*GMFTSH9 COD T RO A L SNOITATRESSID SNOITATRESSID otlaA ytisrevinU 7102 Aalto University publication series DOCTORAL DISSERTATIONS 54/2017 Advanced Techniques in Magnetic Resonance-Guided High-Intensity Focused Ultrasound Matti Tillander A doctoral dissertation completed for the degree of Doctor of Science (Technology) to be defended, with the permission of the Aalto University School of Science, at a public examination held at the lecture hall F239a of the school on 28 April 2017 at 12 PM. Aalto University School of Science Department of Neuroscience and Biomedical Engineering Supervising professor Professor Risto Ilmoniemi, Aalto University, Finland Thesis advisor Docent Heikki J. Nieminen, University of Helsinki, Finland Preliminary examiners Professor Gail ter Haar, The Institute of Cancer Research, UK Docent Timo Liimatainen, University of Eastern Finland, Finland Opponent Research Director Cyril Lafon, Inserm, France Aalto University publication series DOCTORAL DISSERTATIONS 54/2017 © Matti Tillander ISBN 978-952-60-7352-1 (printed) ISBN 978-952-60-7351-4 (pdf) ISSN-L 1799-4934 ISSN 1799-4934 (printed) ISSN 1799-4942 (pdf) http://urn.fi/URN:ISBN:978-952-60-7351-4 Unigrafia Oy Helsinki 2017 Finland Abstract Aalto University, P.O. Box 11000, FI-00076 Aalto www.aalto.fi Author Matti Tillander Name of the doctoral dissertation Advanced Techniques in Magnetic Resonance-Guided High-Intensity Focused Ultrasound Publisher School of Science Unit Department of Neuroscience and Biomedical Engineering Series Aalto University publication series DOCTORAL DISSERTATIONS 54/2017 Field of research Biomedical engineering Date of the defence 28 April 2017 Permission to publish granted (date) 30 January 2017 Language English Monograph Article dissertation Essay dissertation Abstract High-intensity focused ultrasound (HIFU) is an emerging therapeutic technique that can be used to heat tissue locally and non-invasively through skin. Heating the tissue to a temperature high enough, e.g., to 57°C, induces instantaneous cell death through thermal coagulative necrosis. Alternatively, HIFU can be used for hyperthermia, in which tissue temperature is maintained within a range of 40–45°C for a longer period of time (e.g., 60 min) to enhance the effect of other therapy modalities, such as radiotherapy and chemotherapy. Magnetic resonance imaging (MRI) as guidance of HIFU treatments (MR-HIFU) provides means for spatially targeting the treatment, measuring the temperature evolution in real-time during heating, and evaluating tissue damage after therapy. The primary aim of this Thesis was to develop a hyperthermia solution for an MR-HIFU system to enable safely heat large volumes at clinically relevant depths from the skin with reliable MRI- based temperature mapping. The solution combined mechanical movements of the ultrasound transducer, electronic ultrasound focus steering, and selective use of transducer elements to control the temperature distribution within the entire acoustic beam path. Several MRI temperature mapping slices were used to control and monitor the heating in real-time. Safe hyperthermia heating with good temperature uniformity was achieved in animal experiments in vivo. Furthermore, in vivo animal experiments and patient imaging study showed that the developed hyperthermia solution was feasible for hyperthermia of recurrent rectal cancer. Finally, technical solutions enabled long-duration MRI-based thermometry with accuracy better than 1°C. The Secondary aim of this Thesis was to present new ways to use phased-array transducers in shaping the emitted acoustic field to gain improvement in performance in different MR-HIFU applications. First, multifoci heating was able to reduce the peak pressure experienced by the tissue in hyperthermia heating when compared to single steered-focus heating. Second, the adjustment of transducer-element phases utilizing time-of-flight estimation based on MRI images improved the focus sharpness in heterogeneous phantom simulating conditions of breast tissue. Third, simulated acoustic intensity predicted heating of bones, which enables fast quantitative reduction of bone heating through deactivation of transducer elements in the context of intercostal sonications. The technological solutions presented in this Thesis advance the field of MR-HIFU towards translation into clinical practice. Keywords high-intensity, focused, ultrasound, hyperthermia, thermal ablation, magnetic resonance, imaging, MR-HIFU ISBN (printed) 978-952-60-7352-1 ISBN (pdf) 978-952-60-7351-4 ISSN-L 1799-4934 ISSN (printed) 1799-4934 ISSN (pdf) 1799-4942 Location of publisher Helsinki Location of printing Helsinki Year 2017 Pages 156 urn http://urn.fi/URN:ISBN:978-952-60-7351-4 Tiivistelmä Aalto-yliopisto, PL 11000, 00076 Aalto www.aalto.fi Tekijä Matti Tillander Väitöskirjan nimi Edistyneet tekniikat magneettiresonanssikuvausohjatussa korkeaintensiteettisessä fokusoidussa ultraääniterapiassa Julkaisija Perustieteiden korkeakoulu Yksikkö Lääketieteellinen tekniikka Sarja Aalto University publication series DOCTORAL DISSERTATIONS 54/2017 Tutkimusala Lääketieteellinen tekniikka Väitöspäivä 28.04.2017 Julkaisuluvan myöntämispäivä 30.01.2017 Kieli Englanti Monografia Artikkeliväitöskirja Esseeväitöskirja Tiivistelmä Korkeaintensiteettinen fokusoitu ultraääni (engl. high-intensity focused ultrasound, ts. HIFU) on yleistyvä terapeuttinen tekniikka, jolla voidaan lämmittää kudosta paikallisesti ja ei-invasiivisesti ihon läpi. Kudoksen lämmittäminen esimerkiksi 57 °C:seen aiheuttaa nopean koagulatiivisen nekroosin. HIFU-lämmitystä voidaan käyttää myös hypertermiaan, jossa kudoksia ylläpidetään (60 min) kohotetussa lämpötilassa (40 – 45 °C). Hypertermia tehostaa muiden terapiamuotojen, kuten sädehoidon ja kemoterapian tehoa. Magneettiresonanssikuvauksen (engl. magnetic resonance imaging, ts. MRI) käyttäminen HIFU-terapian ohjaukseen (engl. MRI-guided HIFU, ts. MR-HIFU) mahdollistaa hoidon kohdennuksen, reaaliaikaisen lämpötilan seurannan hoidon aikana sekä hoidon tehon arvioinnin hoidon jälkeen. Tämän väistökirjan ensisijainen tavoite oli kehittää MR-HIFU-hypertermiamenetelmä, joka pystyy lämmittämään suuren kudostilavuuden kliinisesti relevantilla syvyydellä ihon pintaan nähden. Lisäksi tarkoitus oli kehittää luotettava MRI-pohjainen lämpötilamittausmenetelmä hypertermialämmityksen ohjaamiseen. Kehitetty lämmitysmenetelmä pyrki kontrolloimaan lämpenemistä akustisen kentän sisällä liikuttaen ultraäänilähetintä mekaanisesti, ohjaamalla fokuspistettä elektronisesti sekä kontrolloimalla aktiivisten ultraäänielementtien jakaumaa. Reaaliaikainen, MRI-lämpötilamittaus ohjasi lämmitystä hyödyntäen useita kuvausviipaleita. Kehitetyllä lämmitysmenetelmällä saavutettiin in vivo-eläinkokeissa turvallinen sekä tasainen hyperterminen lämmitys. Menelmän soveltuvuus uusiutuneen peräsuolensyövän hoitoon osoitettiin eläinkokeilla sekä potilailla tehdyllä kuvantamistutkimuksella. Lämmityksen ohjaamiseen kehitetyn MRI-lämpötilamittauksen tarkkuus oli parempi kuin 1 °C. Väitöskirjan toinen tavoite oli hyödyntää vaiheistettua ultraäänilähetintä uusilla tavoilla akustisen kentän muokkaamisessa parantamaan hoitolaitteen suoristuskykyä eri MR-HIFU- sovelluksissa. Ensinnäkin, hyperterminen lämmitysmenetelmä, joka käytti ultraäänielementtien vaiheistuksella tuotettua montaa yhtäaikaista fokuspistettä yhden siirrettävän sijaan, laski merkittävästi kodoksiin kohdistuvaa maksimipainetta. Toiseksi, elementtien vaiheistus käyttäen MRI-kuvista laskettuja, kudosten heterogeenisyydestä aiheutuvia ultraäänen kulkuaikaeroja paransi akustisen fokuksen terävyyttä selvästi. Kolmanneksi, akustisen kentän intensiteettilaskenta ennusti tarkasti ultraäänen aiheuttaman luun lämpenemisen, jota voidaan käyttää perusteena ultraäänielementtien sulkemiseen ja näin ollen vähentää kvantitatiivisesti luun lämpenemistä esimerkiksi maksaan kohdistuvassa MR-HIFU-hoidossa. Tässä väitöskirjassa esityt tekniset ratkaisut auttavat osaltaan MR-HIFU-tekniikan jalkauttamista kliiniseen käyttöön. Avainsanat korkeaintensiteettinen, fokusoitu, ultraääni, hypertermia, lämpöablaatio, magneettiresonanssikuvaus, magneettikuvausohjaus ISBN (painettu) 978-952-60-7352-1 ISBN (pdf) 978-952-60-7351-4 ISSN-L 1799-4934 ISSN (painettu) 1799-4934 ISSN (pdf) 1799-4942 Julkaisupaikka Helsinki Painopaikka Helsinki Vuosi 2017 Sivumäärä 156 urn http://urn.fi/URN:ISBN:978-952-60-7351-4 Preface The work presented herein has been performed at Philips MR-Therapy during the years 2012–2016 in collaboration with University of Bordeaux 2, France; National Institutes of Health, Bethesda, MD, USA; Aarhus University Hospital, Aarhus, Denmark; Sunnybrook Health Sciences Cen- tre, Toronto, Canada; and University of Texas Southwestern Medical Cen- ter, Dallas, TX, USA. First and
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