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)
TTRG, Radiation Oncology Department
UCSF Comprehensive Cancer Center
Cellular repair mechanisms lose function or can’t keep
up with accumulating damage.
→ Cell death & necrosis within 3-5 days
Ablation
Chris Diederich
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
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
Interstitial Ultrasound Applicators
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
Cross-section Example
180 deg. Sectoring
RF Feedlines
Active Acoustic Sector
Cylindrical PZTTransducers
1.5 mm OD x 5-10 mm Long
360 degree or Sectored
In
Inactive Sector
Water flow
Polyimide Support Tube
Guidance, Treatment Control, & Assessment
Extrapolate to Other Site Specific Design & Treatment
Active Acoustic Sector
13g Implant Catheter
Out
Ultrasound Applicator
MR Temperature/Ablation Imaging
Inactive Sector
Outer Transducer
Surface
Silicone Sealant
13-g Catheter
4 x 10 mm Applicator
3 x 10 mm
2 x 10 mm
Quick-Connects
RF Power
Hyperthermia
CatheterCatheter-Based Ultrasound For
3D Control of Hyperthermia & Thermal
Ablation with Image Guidance
Water-Flow
Ports
3D Control of Hyperthermia in HDR Implant
Treatment Planning for two prostate target volumes
Technology Implemented for Clinical Hyperthermia
Enhanced spatial control & penetration
Prostate HDR+HT Implant Configuration
60 min HT, 1 Fraction
6-2x10 mm 13- g CC Applicators, ~ 7.3 MHz
Selection of active length, sector, and aiming - a priori
Tailor power control & conformal targeting
360 deg. US
Applicators
2
Peripheral Implant
5
t43>10 min
6
4
Base to Apex Temperature Map
41oC
1
3
50
48
Directional Ultrasound Applicators
Temperature (C)
46
44
42
40
HDR Plan
Probe 1 - Catheter 1
38
Posterior Target
Probe 2 - Catheter 2
C-6
C-1
Probe 3 - Catheter 6
36
Probe 4 - Catheter 3
Probe 5 - Catheter 5
34
Probe 6 - Catheter 4
32
30
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Position (cm)
Applicators
4 x 10 mm Length
180o & 270o Sectors
t43>10 min
USITT - Uterine Sarcoma
HDR+HT Implant Configuration
Local HT + HDR Brachytherapy for Cervical Cancer
Endocavity HDR Ring Applicator
Hyperthermia 4242-45 C for 45 min, 2 Fractions
Sequential HDR Brachytherapy, 4 Fractions
Directional Applicators
- avoid bone & stent
Endocavity Ultrasound Applicator
13-g USITT
Catheters
Bladder
Endocavity US HT + HDR Applicator
2x10 mm ~7MHz
220 and 360 deg. Applicators
Stents
Ultrasound Array
Cooling Balloon
HDR Ring Applicator
Thermocouples
13-g USITT
Catheters
15-g Temp
Catheter
Uterine Cervix
& Target Region
Bowel
Custom Intrauterine Catheter
Rectal Obturator
With Water-Flow Ports
Endocavity Ultrasound Hyperthermia
Dynamic Axial and Directional Control of Ablation
Treatment Simulation of cervix target treatment
Dual Sector Applicator
CTV
4 - 3.5 mm OD x10 mm Transducers
Dual 180o, 7 MHz, 6 mm OD Applicator
>4 cm diameter 41oC lateral penetration
Variable length & sector control
Biothermal Simulations of HighHigh-Intensity Ultrasound Devices
2.4 mm OD Interstitial Ultrasound Applicator, 4-1.5 mm OD x 10 mm, 7.5 MHz
Thermal Penetration and Collimation
41oC
5 min
10 min
15 min
15 min
52 °C
Clinical Target Volume
Equal Power
4 x 10 mm x 360°
ω=.5 kg m -3 s-1
Equal Power
4 x 10 mm x 360°
ω=.5 kg m -3 s-1
Equal Power
4 x 10 mm x 360°
ω=.5 kg m-3 s-1
1 cm
Equal Power
4 x 10 mm x 180°
ω=2 kg m-3 s-1
Length and Directional Control
t43=10 min
52 °C
Dynamic Axial and Directional Control of Heating
Angular Control
Sectored Tubular Radiators
PrePre-Selected Directivity
70
10
coagulation from
3 minute heating
6
60
4
50
2
0
elem ent 1 @ 18 W
element 2
element 3
-2
40
-2 0
-1 5
-10
-5
in vitro
0
in vivo
5
10
15
20
Applicator Surface Temperature (oC)
12
1
3
3
3
3
3
2
14
70
12
10
60
8
6
50
4
2
40
0
element 1 @ 18W
element 2 @ 12W
element 3 @ 6 W
-2
30
-20
-15
-10
-5
0
5
Axial Position (mm)
10
15
20
Applicator Surface Temperatures
(o C)
80
5
4
3
2
1
0
3
2
9
8
2
6
34
2
3
35
33
4
32
5
6
31
7
30
8
29
9
28
1
0
15
12
9
6
3
0
36
1
6
1
Hysteroscopic or Laparoscopic
Similar to RF, Laser, & Cryo
Fast, Large Volume Ablation
Selective Targeting, MRTI possible
90
applicator
5
2
4
2
1
1
1
2
2
1
2
1
1
2
1
0
1
4
5
6
7
8
9
1
35
32
31
30
29
28
15
12
9
6
3
0
36
2
3
24
Radial Depth of
Coagulation (mm)
5
31
8
30
9
10
11
22
21
20
7
Retracted Introducer Sheath
8
9
Bowel
10
18
13
14
15
17
16
21
12
20
29
28
27
15
12
9
6
3
0
35 36
18
14
15
17
Vagina
16
Uterus
Embedded Fibroid
2
3
High-Power US Applicator
Multi-element & Directional
4
25
24
6
8
9
10
11
12
13
14
15
21 20
18 17
16
3 x 10 mm Active
Experiment
7
23
22
Thermal
Lesion
5
360 o
applicator
26
Deployable Multipoint
Temperature Sensing
Bladder
13
19
1
32
7
12
23
22
34
33
6
270 o
applicator
23
in vivo
in vitro
4
26
24
6
o
3
27
25
5
200
applicator
25
3
34
4
11
2
o
2
3
1
26
2
2
27
7
33
16
15
12
9
6
3
0
3
Axialtransducer
Positiontemperature
(mm)
Radial Depth of Lesion (mm)
Radial Depth of Lesion (mm)
80
1 elemen t
14
Cross-Section
4 x 10 mm x 180°
ω=0.5 kg m -3 s-1
8 WA, 10 min
Concept
1
16
1 cm
Shaped Thermal Coagulation – Ex Vivo Specimens
Axial Control
Multiple Transducer Segments
Independent Power Control
in vi tro
in vi vo
transd ucer temp eratu re
Tapered Power
4 x 10 mm x 180°
ω=0.5 kg m -3 s-1
15 min
Thermal Ablation of Uterine Fibroids
Experiment – ex vivo and in vivo
8
Equal Power
4 x 10 mm x 180°
ω=0.5 kg m -3 s-1
8 W A, 15 min
2 x 10 mm x 360°
ω=0.5 kg m -3 s-1
8 W A, 10 min
41oC
Surgical Specimens
8 min Ablations
Ex Vivo Lesions
TTC Stained
~ 4 cm OD x 5 cm long
4 x 10 mm Active
2 x 10 mm x 180 deg.
Liver Ablation
MRTI for Device Evaluation & Control
Example of Tailored Lesions Ex Vivo
0.5T GE Interventional MRT, 1.5T and 3.0T GE
Applications for Prostate Ablation
3x360 ° at 13 W , 10 min
4.2 cm wide x 3.5 cm long
3 x 180° at 12 W, 10 min
2.0 cm radial x 3.2 cm long
3-3 x 360° Cluster Array
7.5 cm x 4.2 cm long
Fast, Conformal, & Large Volume Lesions
MR Thermal Imaging (MRTI)
PhasePhase-difference mapping (PRF shift)
SPGR (TE/TR=10(TE/TR=10-25 ms/120ms/120-190 ms,FA=60
ms,FA=60°°)
Endorectal receive coil maximizes SNR
Resolution: 1.6 mm x 1.6 mm, 11-2 °C
3-5 planes simultaneously, ~10 s updates
Integrated cooling on endorectal coil
ACROSS
Ultrasound Strain Imaging
Terason Imaging probe
External Compression
RF data 15fps, <1 min comp time
0.1
31mm
0.05
RealReal-Time Monitoring Software
Current Temperature
Temperature Thresholds (52 °C)
Thermal Dose (t43>120>120-240 min)
0
33.6mm
MRTI Guided USITT - In Vivo Prostate, 0.5 T
Interstitial Ultrasound
Directional And Longitudinal Control of Lesion
Dynamic Rotation of Interstitial Applicator w/MR Control
Temperature Distribution Mid-Gland
Applicator
5 Minutes
Experimental Setup:
Applicator - 10 mm x 180 deg., 7.2 MHz
Canine Prostate – In Vivo
Ventral Placement, Direct Away from Urethra
Chronic Study -> Slow Controlled Heating
10-14 W Modulated for 15 min
Final Temperature
T1-CE Post Heat
10 Minutes
15 Minutes
Prostate
Endorectal
Coil
Red 52 °C, Orange 47 °C
Thermal Dose
T1-CE 30 day
T1 -CE Post
15–20 mm radial penetration in vivo
Manual rotation/sweeping possible
Conformal treatment
1 cm
Prostate 2.9 cm Apex-Base x 3.8 Wide x 2.0 DV
Conforming Therapy to Target Boundary
Multiple Applicator Implant
In Vivo Prostate –”Posterior” 3- 180° Applicators
Maximum Temp
Urethral Cooling
T1 -CE Post
Targeted Prostate Thermal Therapy w/ MRg
Transurethral Catheter-Based Devices –BPH & Cancer
Design Schema and Strategies
Linear Transducer Array
Flexible Delivery Catheter
Urethral Cooling Balloon
Tubular, Planar, Curvilinear
Real-time MRTI monitoring/control
Endorectal Coil
w/cooling
Thermal Dose
Single-Sector
Tubular Array
Power Applied 5-17 W, 20 min
Nau et al., Medical Physics 2005
Multi-Sector
Tubular Array
TTC Section
3.8 cm AB x 4.3 cm RL x 3 cm AP
Target 52 °C
t43>240 min
Bladder
Applicator
MR Temperature
Monitoring Slices
Single-Sector
Rotating Tubular
Prostate
Planar/Curvilinear
Rotating Array
Develop devices and evaluate approaches for delivering conformal
therapy within in vivo canine prostate with MR temperature monitoring.
MultiMulti-Sectored Tubular Transurethral Applicator
TriTri-Sectored Tubular Transurethral Applicator
Dynamic Angular & Length Control Without Movement
In Vivo Canine Prostate Evaluations (n=3) with MRTI
Bladder Balloon
Tubular Array
3.5 mm x 6 mm PZT
3 x 120° sectors/tube
Case 1 – Dual-sector Control
Tmax
Transient 52 °C
1 cm
Inflatable urethral cooling balloon
Rotation & translation
of assembly for
initial position
Case 3 – Tri-sector Control
TTC
Case 2 – Translation w/ Coronal MRTI
Tmax
Transient t43>240
Fast selective treatment with dynamic angular control (10-15 min)
Practical control with MRI feedback
Kinsey et al. 2008
Curvilinear Transurethral Applicator
In Vivo Canine ProstateProstate- Single Shots
Thermal Dose
In Vivo Canine Prostate –Conformal Targeting
MRTI Control (Power, Position)
~52 °C, t43 > 240 min at boundary
6.5 MHz, 10° sequential rotation
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
Curvilinear Transurethral Applicator
Target 52 °C
t43>240 min
Bladder
1
Discrete Shots
2
TMaxProstate
S-1
TMax
TTC Section
S-2
Ross, et al., Medical Physics 2005
Catheter-Based Ultrasound Thermal Therapy
Summary
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
UCSF
Jeff Wootton
Xin Chen
Punit Prakash
Titania Juang
IC Joe Hsu
Jean Pouliot
Adam Cunha
Paul Stauffer
Will Nau
Tony Ross
Adam Kinsey
Stanford
Kim Butts Pauly
Viola Rieke
Graham Sommer
Harchi Gil
Donna Bouley
Acoustic MedSystems
E. Clif Burdette
t43°C
MRTI Guided USITT
In Vivo Canine Brain Tumor
Setup:
Implanted TVT Tumor
Craniotomy/ 5 mm Burr Hole
PRF -Interleaved gradient echo EPI
(TR/TE=1000ms/40 ms,FA=60o)
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
0 min
2.2 min
3.8 min
ICDC Applicator
Stereotactic
Positioning
t43=50 min
10 min
16 min
Cooling
T1-CE
Surface Coil
Tumor: 1.7 cm OD
t43=50 min