Methods for abdominal tumor ablation through image-guided focused ultrasound

163 Pages·2017·11.99 MB·English

METHODS FOR ABDOMINAL TUMOR ABLATION
THROUGH IMAGE-GUIDED FOCUSED ULTRASOUND
PascalRamaekers
Colophon
Copyright©2017,PascalRamaekers
ISBN:978-90-393-6807-7
Layout: PascalRamaekers
Printing: www.proefschriftmaken.nl
METHODS FOR ABDOMINAL TUMOR ABLATION
THROUGH IMAGE-GUIDED FOCUSED ULTRASOUND
Methodenvoorablatievanabdominaletumoren
doorbeeldgestuurdgefocustultrageluid
(meteensamenvattinginhetNederlands)
PROEFSCHRIFT
terverkrijgingvandegraadvandoctoraandeUniversiteitUtrecht
opgezagvanderectormagnificus,prof. dr. G.J.vanderZwaan,
ingevolgehetbesluitvanhetcollegevoorpromotiesinhetopenbaarteverdedigen
opdonderdag21september2017desmiddagste2:30uur
door
PascalRamaekers
geborenop31oktober1987teRoermond
Promotor: Prof. dr. C.T.W.Moonen
Copromotor: Dr. M.G.Ries
Theworkpresentedinthisdissertationwassupportedbythefollowinggrants:
• TheSeventhFrameworkProgramme(FP7),grantno. 603028(iPaCT)
• TheEuropeanResearchCouncil(ERC),project#ERC-2010-AdG268906-SoundPharma
• TheVOLTAproject,CenterforTranslationalMolecularMedicine(CTMM),project#05T-
201
TABLE OF CONTENTS
1 Introductionandthesisoutline 9
1.1 Prevalenceofhepaticandpancreaticcancer . . . . . . . . . . . . . . . . . . 10
1.2 Invasivetreatmentmodalitiesforpalliationandlifeprolongation . . . . . . . 11
1.2.1 Chemotherapy,radiotherapy,andtransarterialembolization. . . . . . 11
1.2.2 RFA,cryoablation,microwaveablation,andLITT . . . . . . . . . . 12
1.3 Focusedultrasoundtherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.3.1 Thermalablation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
1.3.2 Mechanicaltissuedestruction: cavitation&histotripsy . . . . . . . . 13
1.4 Imageguidanceoffocusedultrasound . . . . . . . . . . . . . . . . . . . . . 15
1.4.1 Ultrasoundimaging. . . . . . . . . . . . . . . . . . . . . . . . . . . 15
1.4.2 Magneticresonanceimaging . . . . . . . . . . . . . . . . . . . . . . 16
1.5 Transducersforfocusedultrasoundtherapy . . . . . . . . . . . . . . . . . . 16
1.5.1 Generationofultrasonicwaves . . . . . . . . . . . . . . . . . . . . . 16
1.5.2 Single-elementtransducers . . . . . . . . . . . . . . . . . . . . . . . 17
1.5.3 Multi-elementphasedarraytransducers . . . . . . . . . . . . . . . . 18
1.6 Challengesforfocusedultrasoundtherapyofhepaticandpancreatictumors . 19
1.6.1 Obstructionbythethoraciccage . . . . . . . . . . . . . . . . . . . . 19
1.6.2 Respiratorymotion . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
1.6.3 Liverperfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
1.6.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
1.7 Thesisoutline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
1.8 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
2 Cavitation-enhancedbackprojectionforacoustic
ribdetectionandattenuationmapping 29
2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
2.1.1 Obstructionoftheultrasonicbeampath . . . . . . . . . . . . . . . . 31
2.1.2 Relatedresearch . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
2.1.3 Proposedmethodforacousticribdetection . . . . . . . . . . . . . . 33
2.2 MaterialsandMethods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.2.1 Hardware . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
5
TABLEOFCONTENTS
2.2.2 Cavitation-enhancedbackprojection. . . . . . . . . . . . . . . . . . 34
2.2.3 Dataacquisitionandprocessing . . . . . . . . . . . . . . . . . . . . 37
2.2.4 Exvivoribdetectionexperiment . . . . . . . . . . . . . . . . . . . . 38
2.2.5 Invivoribdetectionexperiment . . . . . . . . . . . . . . . . . . . . 38
2.2.6 Attenuationmappingexperiment. . . . . . . . . . . . . . . . . . . . 39
2.3 Results. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
2.3.1 Exvivoribdetectionexperiment . . . . . . . . . . . . . . . . . . . . 40
2.3.2 Invivoribdetectionexperiment . . . . . . . . . . . . . . . . . . . . 42
2.3.3 Attenuationmappingexperiment. . . . . . . . . . . . . . . . . . . . 42
2.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
2.5 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
2.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
3 Increasing the HIFU ablation rate through an MRI-guided sonication strategy
usingshockwaves: feasibilityintheinvivoporcineliver 51
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
3.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
3.2.1 Waveformcharacterization . . . . . . . . . . . . . . . . . . . . . . . 56
3.2.2 Validationofincreasedenergyabsorption . . . . . . . . . . . . . . . 57
3.3 Results. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
3.3.1 Waveformcharacterization . . . . . . . . . . . . . . . . . . . . . . . 60
3.3.2 Increasedabsorption&thermaldose. . . . . . . . . . . . . . . . . . 61
3.3.3 Pre-focaltemperaturechange . . . . . . . . . . . . . . . . . . . . . 64
3.3.4 Ablationrate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
3.3.5 Grossanatomicalinspection . . . . . . . . . . . . . . . . . . . . . . 66
3.3.6 Histopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
3.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
3.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
3.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
4 EvaluationofanoveltherapeuticfocusedultrasoundtransducerbasedonFer-
mat’sspiral 77
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
4.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
4.2.1 Transducerdesigncriteria . . . . . . . . . . . . . . . . . . . . . . . 81
4.2.2 Solutionstrategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
4.2.3 Acousticsimulations . . . . . . . . . . . . . . . . . . . . . . . . . . 86
4.2.4 Hydrophonemeasurements. . . . . . . . . . . . . . . . . . . . . . . 88
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4.3 Results. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
4.3.1 PartI:Evaluationofthedifferentarraydesigns . . . . . . . . . . . . 90
4.3.2 PartII:Experimentalvalidationofthedesign . . . . . . . . . . . . . 97
4.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
4.4.1 PartI:Evaluationofthedifferentarraydesigns . . . . . . . . . . . . 100
4.4.2 PartII:Experimentalvalidationofthedesign . . . . . . . . . . . . . 104
4.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
4.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
5 ImprovedintercostalHIFUablationusingaphasedarraytransducerbasedon
Fermat’sspiralandVoronoitessellation: anumericalevaluation 109
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
5.2 MaterialsandMethods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
5.2.1 FSandVTFSelementgeometry . . . . . . . . . . . . . . . . . . . . 114
5.2.2 Evaluatedtransducerdesigns . . . . . . . . . . . . . . . . . . . . . . 114
5.2.3 Modeledtissuegeometries . . . . . . . . . . . . . . . . . . . . . . . 116
5.2.4 Acousticsimulations . . . . . . . . . . . . . . . . . . . . . . . . . . 116
5.2.5 Thermalsimulations . . . . . . . . . . . . . . . . . . . . . . . . . . 119
5.2.6 Ribexposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
5.2.7 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
5.3 Results. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
5.3.1 Acousticsimulations . . . . . . . . . . . . . . . . . . . . . . . . . . 121
5.3.2 Thermalsimulations . . . . . . . . . . . . . . . . . . . . . . . . . . 126
5.3.3 Overviewofresults . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
5.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
5.4.1 Acousticintensitydistribution . . . . . . . . . . . . . . . . . . . . . 133
5.4.2 Pre-focalenergydensity . . . . . . . . . . . . . . . . . . . . . . . . 133
5.4.3 Energyexposureoftheribs . . . . . . . . . . . . . . . . . . . . . . 134
5.4.4 Limitationsofthemodel . . . . . . . . . . . . . . . . . . . . . . . . 135
5.4.5 Potentialimprovements. . . . . . . . . . . . . . . . . . . . . . . . . 135
5.5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
5.6 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
6 Summaryandgeneraldiscussion 141
6.1 Cavitation-enhancedbackprojection . . . . . . . . . . . . . . . . . . . . . . 142
6.1.1 Passivecavitationdetection . . . . . . . . . . . . . . . . . . . . . . 142
6.1.2 Cavitationandmetastasis. . . . . . . . . . . . . . . . . . . . . . . . 143
6.2 Shockwaveenhancedheating . . . . . . . . . . . . . . . . . . . . . . . . . 143
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6.2.1 RealtimeMRguidanceofcavitation-basedmethods . . . . . . . . . 143
6.3 Systemdesignforfocusedultrasoundablationtherapy . . . . . . . . . . . . 144
6.3.1 Additionalphasedarrayimprovements . . . . . . . . . . . . . . . . 144
6.4 Futureperspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
6.4.1 Hybridsystems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
6.4.2 Phasedarrayswithλ/2inter-elementspacing . . . . . . . . . . . . . 148
6.4.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
6.5 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
Nederlandsesamenvatting 153
Acknowledgments 157
Publications 159
Authorbiography 163
8
1
INTRODUCTION AND THESIS OUTLINE
9
1.1.Prevalenceofhepaticandpancreaticcancer
1.1 Prevalenceofhepaticandpancreaticcancer
Cancer is considered to be a major global public health problem. According to the latest
reportoncancerstatisticsintheUnitedStatesintheyear2016,canceristhesecondleading
cause of death following heart disease, with 1.685.210 new cancer diagnoses and 595.690
cancerdeathsprojectedtooccur1,accountingfor24%ofthetotalamountofdeaths. While
cancermortalityrateintheUnitedStateshasseenadropof23%withrespectto1991,mor-
talityrateshavebeenincreasingforcancersintheabdominalorganssuchastheliverandthe
pancreassince2003. Formales,cancersoftheliver&intrahepaticbileduct(18.280deaths)
and pancreas (21.450 deaths) are estimated to be the 5th and 4th ranking causes of cancer
deathintheUnitedStatesrespectively. Forfemales,cancersoftheliver&intrahepaticbile
duct(8.890deaths)andpancreas(20.330deaths)areranked8thand4threspectively.InAsia,
liver cancer incidence rates rank the highest in the world. A 2012 summary on global can-
cerstatisticsreportedmalelivercancerincidenceratesof31,9per100.000inEasternAsia
and22,2per100.000inSouth-EasternAsia2. Forfemales,theincidencerateswere10,2per
100.000inEasternAsiaand7,2per100.000inSouth-EasternAsia.Chinaalonewasreported
toaccountformorethan50%ofalllivercancercasesanddeathsworldwide. A2004study
reportedhighincidenceratesforlivercancerincountriessuchasKorea(48,77per100.000)
and Mongolia (98,93 per 100.000), but also in African countries such as Congo (32,33 per
100.000), and Gambia (39,67 per 100.000)3. Other regions such as Europe, Australia, and
NewZealandgenerallyshowincidenceratesbelow10per100.000. Contrarytolivercancer,
theincidenceofpancreaticcancerisingenerallowerinAsiathaninmostWesterncountries,
but nevertheless pancreatic cancer still ranked as the 4th cause of cancer-induced death in
China in 2005, due to its low 5-year survival rate of less than 1%4. In Europe, pancreatic
canceraccountedfor5,4%ofmalecancerdeathsand6,7%offemalecancerdeathsin20125.
Forlivercancers,hepatocellularcarcinoma(HCC)accountsfor70-85%ofallcases,mak-
ingitthemostprevalentsubtypeworldwide6. Animportantriskfactorconcerningtheinci-
dence of HCC is infection by the Helicobacter pylori bacterium and the hepatitis B and C
viruses7,whicharemostcommoninpartsofAsiaandsub-SaharanAfrica8. Incontrast,the
mostprevalentlivertumorsintheWesternworldaremetastatictumors,whichpredominantly
originateinthecolorectalregion8.Riskfactorsfortheoccurenceofsuchtumorsincludeobe-
sity,excessivealcoholconsumption,smoking,andredandprocessedmeatconsumption8.
The most common type of pancreatic cancer is pancreatic adenocarcinoma, which ac-
countsforapproximately95%ofallcases9. ItismostprevalentinWesterncountries,andas-
sociatedwithenvironmentalandlifestylefactorssuchassmoking10,alcoholconsumption11,
anda high-fatdiet12. Inaddition, itisestimatedthat 10%ofpancreatic cancershasa large
geneticcomponent13. Despitethefactthatpancreaticcancerisarelativelyraredisease,ithas
ahighmortalityrateduetothefactthatthediseaseistypicallydiagnosedinalatestageof
10