CatheterCatheter--Based Ultrasound ForBased Ultrasound For3D Control of Hyperthermia & Thermal 3D Control of Hyperthermia & Thermal

Ablation with Image GuidanceAblation with Image Guidance

Chris Chris DiederichDiederich

TTRG, Radiation Oncology DepartmentTTRG, Radiation Oncology DepartmentUCSF Comprehensive Cancer CenterUCSF Comprehensive Cancer Center

Thermal Therapy Mediated EffectsThermal Therapy Mediated Effects

� Non-Lethal Moderate Temperature Exposure (40-45 °C [104-113 F])

↑ metabolism, inactivation of enzymes, rupture cell membranes, hyperemia, ↑ oxygenation, ↑ blood vessel permeability, heat shock-stress responseGene therapy, drug delivery and activation, adjunct to RT/CT

� Lethal Moderate Temperature Exposure (41-45+ °C , long duration)

Cellular repair mechanisms lose function or can’t keep up with accumulating damage. → Cell death & necrosis within 3-5 days

� Lethal High Temperature (48-50+ °C, short to long duration)Cellular and tissue structural changes Thermal coagulation-irreversible protein denaturationThermal necrosis & immediate cell death

*Pearce and Thomsen 1995

Hyp

erth

erm

iaA

blat

ion

Catheter-Based Ultrasound for Thermal Therapy3D control of Hyperthermia & Ablation

� Interstitial/Percutaneous Ultrasound ApplicatorsArrays of Tubular RadiatorsProstate, Brain, GYN, Liver, Soft Tissue Sites

Hyperthermia and targeted ablation

� Transurethral/Intraluminal Ultrasound ApplicatorsArrays of Tubular, Planar, & Curvilinear Radiators

Prostate Ablation & Intrauterine HyperthermiaGI/Digestive tumors

� MR Temperature/Ablation ImagingGuidance, Treatment Control, & Assessment

� Extrapolate to Other Site Specific Design & Treatment

Interstitial Ultrasound Applicators

4 x 10 mm Applicator

3 x 10 mm2 x 10 mm Quick-Connects

RF Power

Water-FlowPorts

Ultrasound Applicator 13-g Catheter

In

Cylindrical PZT Transducers 1.5 mm OD x 5-10 mm Long

360 degree or Sectored Silicone Sealant

Polyimide Support TubeWater flow

RF Feedlines

13g Implant Catheter

Out

Cross-section Example180 deg. Sectoring

� Arrays of miniature tubular PZT radiators� 6-10 MHz, collimated beam output� 360° or sectored for angle control (e.g., 90°, 180°, 270°) � Catheter-Cooled Configuration

Inactive Sector

Active Acoustic Sector

Outer TransducerSurface

Inactive Sector

Active Acoustic SectorInactive Sector

Active Acoustic Sector

Outer TransducerSurface

Inactive Sector

Active Acoustic Sector

3D Control of Hyperthermia in HDR ImplantTreatment Planning for two prostate target volumes

� Selection of active length, sector, and aiming - a priori� Tailor power control & conformal targeting

t43>10 min

t43>10 min41oC

Applicators4 x 10 mm Length180o & 270o Sectors

Peripheral Implant

Posterior Target

HDR Plan

Technology Implemented for Clinical HyperthermiaEnhanced spatial control & penetration

Prostate HDR+HT Implant Configuration60 min HT, 1 Fraction6-2x10 mm 13- g CC Applicators, ~ 7.3 MHz

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0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

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Probe 1 - Catheter 1

Probe 2 - Catheter 2

Probe 3 - Catheter 6

Probe 4 - Catheter 3

Probe 5 - Catheter 5

Probe 6 - Catheter 4

Directional Ultrasound Applicators

360 deg. USApplicators

1

2

3

54 6

Directional Ultrasound Applicators

360 deg. USApplicators

Directional Ultrasound Applicators

360 deg. USApplicators

1

2

3

54 6

Base to Apex Temperature Map

C-6C-1

USITT - Uterine SarcomaHDR+HT Implant Configuration

Bladder

Stents

Bowel

13-g USITTCatheters

15-g TempCatheter

13-g USITTCatheters

Hyperthermia 42Hyperthermia 42--45 C for 45 min, 2 Fractions45 C for 45 min, 2 FractionsSequential HDR Brachytherapy, 4 FractionsSequential HDR Brachytherapy, 4 Fractions

Directional Applicators - avoid bone & stent

2x10 mm ~7MHz220 and 360 deg. Applicators

Endocavity Ultrasound Applicator Local HT + HDR Brachytherapy for Cervical Cancer

HDR Ring Applicator

Rectal Obturator

Ultrasound Array

Custom Intrauterine CatheterWith Water-Flow Ports

Cooling Balloon

Thermocouples

Uterine Cervix& Target Region

Endocavity HDR Ring Applicator

Endocavity US HT + HDR Applicator

Endocavity Ultrasound HyperthermiaTreatment Simulation of cervix target treatmentDual Sector Applicator

4 - 3.5 mm OD x10 mm TransducersDual 180o, 7 MHz, 6 mm OD Applicator>4 cm diameter 41oC lateral penetrationVariable length & sector control

41oC

41oC

t43=10 min

Clinical Target Volume

CTV

Dynamic Axial and Directional Control of AblationDynamic Axial and Directional Control of AblationBiothermal Simulations of HighBiothermal Simulations of High--Intensity Ultrasound DevicesIntensity Ultrasound Devices

1 cmEqual Power4 x 10 mm x 180°ω=2 kg m-3 s-1

Equal Power4 x 10 mm x 360°ω=.5 kg m-3 s-1

5 min 10 min 15 min 15 min

Equal Power4 x 10 mm x 360°ω=.5 kg m-3 s-1

Equal Power4 x 10 mm x 360°ω=.5 kg m-3 s-1

52 °C

1 cm

2 x 10 mm x 360°ω=0.5 kg m-3 s-1

8 WA, 10 min

Equal Power4 x 10 mm x 180°ω=0.5 kg m-3 s-1

8 WA, 15 min

Tapered Power4 x 10 mm x 180°ω=0.5 kg m-3 s-1

15 min

Cross-Section4 x 10 mm x 180°ω=0.5 kg m-3 s-1

8 WA, 10 min

52 °C

2.4 mm OD Interstitial Ultrasound Applicator, 4-1.5 mm OD x 10 mm, 7.5 MHz

Thermal Penetration and Collimation

Length and Directional Control

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in vitroin vivotransducer temperature

element 1 @ 18W element 2 @ 12W element 3 @ 6 W

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in vi troin vi votransducer temperature

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urf

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atu

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1 element

element 1 @ 18 W element 2 element 3

coagulation from

3 minute heating

Axial Position (mm)

Dynamic Axial and Directional Control of HeatingDynamic Axial and Directional Control of HeatingExperiment Experiment –– ex vivoex vivo and and in vivoin vivo

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in vivoin vitro

Radial Depth of Coagulation (mm)

90o

applicator

200o

applicator

360o

applicator

Axial ControlAxial ControlMultiple Transducer SegmentsMultiple Transducer Segments

Independent Power ControlIndependent Power Control

Angular ControlAngular ControlSectored Tubular RadiatorsSectored Tubular Radiators

PrePre--Selected DirectivitySelected Directivity

Thermal Ablation of Uterine FibroidsShaped Thermal Coagulation – Ex Vivo Specimens

Bladder

Deployable MultipointTemperature Sensing

High-Power US ApplicatorMulti-element & Directional

Uterus

Bowel

Embedded FibroidThermalLesion

Retracted Introducer Sheath

Vagina

Concept�Hysteroscopic or Laparoscopic �Similar to RF, Laser, & Cryo� Fast, Large Volume Ablation� Selective Targeting, MRTI possible

2 x 10 mm x 180 deg.3 x 10 mm Active

4 x 10 mm Active

Experiment�Surgical Specimens� 8 min Ablations� Ex Vivo Lesions� TTC Stained� ~ 4 cm OD x 5 cm long

Liver AblationExample of Tailored Lesions Ex Vivo

0

0.05

0.1

31mm

33.6mm

ACROSS

Ultrasound Strain ImagingTerason Imaging probeExternal CompressionRF data 15fps, <1 min comp time

3x360 ° at 13 W , 10 min4.2 cm wide x 3.5 cm long

3 x 180° at 12 W, 10 min2.0 cm radial x 3.2 cm long

3-3 x 360° Cluster Array7.5 cm x 4.2 cm long

Fast, Conformal, & Large Volume Lesions

MRTI for Device Evaluation & Control0.5T GE Interventional MRT, 1.5T and 3.0T GEApplications for Prostate Ablation

MR Thermal Imaging (MRTI)MR Thermal Imaging (MRTI)

�� PhasePhase--difference mapping (PRF shift)difference mapping (PRF shift)�� SPGR (TE/TR=10SPGR (TE/TR=10--25 ms/12025 ms/120--190 190 ms,FAms,FA=60=60°°))�� EndorectalEndorectal receive coil maximizes SNRreceive coil maximizes SNR�� Resolution: 1.6 mm x 1.6 mm, 1Resolution: 1.6 mm x 1.6 mm, 1--2 2 °°CC�� 33--5 planes simultaneously, ~10 s updates5 planes simultaneously, ~10 s updates�� Integrated cooling on Integrated cooling on endorectalendorectal coilcoil

RealReal--Time Monitoring SoftwareTime Monitoring Software

�� Current TemperatureCurrent Temperature�� Temperature Thresholds (52 Temperature Thresholds (52 °°C)C)�� Thermal Dose (tThermal Dose (t4343>120>120--240 min)240 min)

Final Temperature

Interstitial Ultrasound Directional And Longitudinal Control of Lesion

T1-CE Post Heat T1-CE 30 day

Experimental Setup:Applicator - 10 mm x 180 deg., 7.2 MHzCanine Prostate – In VivoVentral Placement, Direct Away from UrethraChronic Study -> Slow Controlled Heating10-14 W Modulated for 15 min

1 cm

Prostate 2.9 cm Apex-Base x 3.8 Wide x 2.0 DV

Prostate

Applicator

EndorectalCoil

MRTI Guided USITT MRTI Guided USITT -- In Vivo In Vivo Prostate, 0.5 TProstate, 0.5 TDynamic Rotation of Interstitial Applicator w/MR ControlDynamic Rotation of Interstitial Applicator w/MR Control

5 Minutes5 Minutes 10 Minutes10 Minutes 15 Minutes15 Minutes

Temperature Distribution Mid-Gland

� 15–20 mm radial penetration in vivo� Manual rotation/sweeping possible

� Conformal treatment

T1 -CE PostThermal Dose

Red 52 °C, Orange 47 °C

�� Conforming Therapy to Target BoundaryConforming Therapy to Target Boundary

Multiple Applicator Implant In Vivo Prostate –”Posterior” 3- 180° Applicators

3.8 cm AB x 4.3 cm RL x 3 cm AP

T1 -CE Post

TTC Section

Maximum Temp

Thermal Dose

Endorectal Coil w/cooling

Urethral Cooling

Nau et al., Medical Physics 2005

Power Applied 5-17 W, 20 min

Targeted Prostate Thermal Therapy w/ MRgTransurethral Catheter-Based Devices –BPH & Cancer

� Develop devices and evaluate approaches for delivering conformal therapy within in vivo canine prostate with MR temperature monitoring.

Single-SectorTubular Array

Design Schema and Strategies� Linear Transducer Array� Flexible Delivery Catheter� Urethral Cooling Balloon� Tubular, Planar, Curvilinear � Real-time MRTI monitoring/control

Multi-SectorTubular Array

Single-SectorRotating Tubular

Planar/CurvilinearRotating Array

Bladder

Prostate

Target 52 °Ct43>240 min

MR Temperature Monitoring Slices

Applicator

Bladder

Prostate

Target 52 °Ct43>240 min

MR Temperature Monitoring Slices

Applicator

MultiMulti--Sectored Tubular Transurethral ApplicatorSectored Tubular Transurethral ApplicatorDynamic Angular & Length Control Without MovementDynamic Angular & Length Control Without Movement

Tubular Array3.5 mm x 6 mm PZT3 x 120° sectors/tube

Bladder Balloon

Inflatable urethral cooling balloon

Rotation & translationof assembly for initial position

TriTri--Sectored Tubular Transurethral ApplicatorSectored Tubular Transurethral ApplicatorIn Vivo Canine Prostate Evaluations (n=3) with MRTIIn Vivo Canine Prostate Evaluations (n=3) with MRTI

Tmax

Tmax

� Fast selective treatment with dynamic angular control (10-15 min)� Practical control with MRI feedback

Case 2 – Translation w/ Coronal MRTI

Case 1 – Dual-sector Control Case 3 – Tri-sector Control

1 cm

TTCTransient 52 °C

Transient t43>240

Kinsey et al. 2008

Curvilinear Transurethral ApplicatorCurvilinear Transurethral ApplicatorIn Vivo Canine ProstateIn Vivo Canine Prostate-- Single ShotsSingle Shots

� Lightly Focused Transducers, 6.5 MHz� Multiple transducers (2-10mm x 3.5mm)�15-20 mm penetration, 1-2 minute shots� Narrow lesions (~10-20°, 5 mm wide)� Rotational sweeping w/ MRI compatible motor

Maximum Temp Thermal Dose

TTC Section

Ross, et al., Medical Physics 2005

Discrete Shots

Curvilinear Transurethral ApplicatorCurvilinear Transurethral ApplicatorIn Vivo Canine Prostate In Vivo Canine Prostate ––Conformal TargetingConformal Targeting

� MRTI Control (Power, Position)� ~52 °C, t43 > 240 min at boundary� 6.5 MHz, 10° sequential rotation

TMax t43°C

S-1

S-2

TMax

Bladder

Prostate

Target 52 °Ct43>240 min

1 2

Catheter-Based Ultrasound Thermal TherapySummary

� Produce 3D conformable and effective heating patterns – penetration, dynamic axial and variable angular control

� Tailor heating for sequential hyperthermia within an HDR Implant

� Transurethral and interstitial provide conformal & selective ablation

� Coupling MRTI with dynamic power control has potential for “precise”therapy targeting to prescribed boundary

� Dual mode devices – potential for delivery and guidance

� More complex but precise therapy possible

� Configurations adaptable for site and disease specific therapy

Acknowledgments

UCSFJeff WoottonXin ChenPunit PrakashTitania JuangIC Joe HsuJean PouliotAdam CunhaPaul Stauffer Will NauTony RossAdam Kinsey

StanfordKim Butts PaulyViola RiekeGraham SommerHarchi GilDonna Bouley

Acoustic MedSystemsE. Clif Burdette

MRTI Guided USITT MRTI Guided USITT In Vivo Canine Brain Tumor In Vivo Canine Brain Tumor

ICDC Applicator:2.2 mm OD x 10 mm, ~7.1 MHz, 360o

~4-12 W for 10 min, 20 ml/min at 22 oC

Tumor: 1.7 cm OD

Setup:Implanted TVT Tumor Craniotomy/ 5 mm Burr HolePRF -Interleaved gradient echo EPI(TR/TE=1000ms/40 ms,FA=60o)

Surface Coil

StereotacticPositioning

ICDC Applicator

0 min 2.2 min 3.8 min

10 min 16 minCooling

T1-CE

t43=50 min

t43=50 min