Catheter Catheter-Based Ultrasound For Based Ultrasound For 3D Control of Hyperthermia & Thermal 3D Control of Hyperthermia & Thermal Ablation with Image Guidance Ablation with Image Guidance Chris Chris Diederich Diederich TTRG, Radiation Oncology Department TTRG, Radiation Oncology Department UCSF Comprehensive Cancer Center UCSF Comprehensive Cancer Center Thermal Therapy Mediated Effects Thermal 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 response Gene 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 denaturation Thermal necrosis & immediate cell death *Pearce and Thomsen 1995 Hyperthermia Ablation Catheter-Based Ultrasound for Thermal Therapy 3D control of Hyperthermia & Ablation Interstitial/Percutaneous Ultrasound Applicators Arrays of Tubular Radiators Prostate, Brain, GYN, Liver, Soft Tissue Sites Hyperthermia and targeted ablation Transurethral/Intraluminal Ultrasound Applicators Arrays of Tubular, Planar, & Curvilinear Radiators Prostate Ablation & Intrauterine Hyperthermia GI/Digestive tumors MR Temperature/Ablation Imaging Guidance, Treatment Control, & Assessment Extrapolate to Other Site Specific Design & Treatment Interstitial Ultrasound Applicators 4 x 10 mm Applicator 3 x 10 mm 2 x 10 mm Quick-Connects RF Power Water-Flow Ports Ultrasound Applicator 13-g Catheter In Cylindrical PZTTransducers 1.5 mm OD x 5-10 mm Lon g 3 60 degree or Sec to red S ilicone Sealant Polyimide Support Tube Water flow RFFeedlines 13g Imp lant Catheter Out Cross-section Example 180 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 Transducer Surface Inactive Sector Active Acoustic Sector Inactive Sector Active Acoustic Sector Outer Transducer Surface Inactive Sector Active Acoustic Sector
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Thermal Therapy Mediated Effects · Endocavity Ultrasound Hyperthermia Treatment Simulation of cervix target treatment Dual Sector Applicator 4 -3.5 mm OD x10 mm Transducers Dual
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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
� 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
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
-2
0
2
4
6
8
10
12
14
16
-20 -15 -10 -5 0 5 10 15 20
Axial Position (mm)
Rad
ial D
epth
of
Les
ion
(mm
)
30
40
50
60
70
80
in vitroin vivotransducer temperature
element 1 @ 18W element 2 @ 12W element 3 @ 6 W
App
licat
or S
urfa
ce T
empe
ratu
res
(o C)
-2
0
2
4
6
8
10
12
14
16
-20 -15 -10 -5 0 5 10 15 20
40
50
60
70
80
in vi troin vi votransducer temperature
Rad
ial
Dep
th o
f L
esio
n (
mm
)
Ap
pli
cato
r S
urf
ace
Tem
per
atu
re (
o C)
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
�� 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
� 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