Transcript Microwave Ablation of Hepatic Tumors: Simultaneous Use of

Developing New Technology for
Local Tumor Control:
A Bioengineering Approach
Andrew Wright MD
Department of Surgery
1/25/02
Background
Greater than one half of patients with
colorectal cancer will develop liver
metastases at some point in their clinical
course
 Surgical resection of an isolated liver tumor
offers a five-year survival between 25 and
38%, compared to a 0% five-year survival
without resection

Background

Only 10–20% of patients with liver tumors
will have disease amenable to surgical
resection due to high surgical risk or
unfavorable anatomy
Radiofrequency Ablation

High-frequency (460 kHz) alternating
current flows from electrical probe through
tissue to ground
Probe
insertion
Extension of
prongs
RF current
application
Radiofrequency Ablation
9-prong “Starburst” probe, 5 cm diameter
(Rita Medical)
12-prong “Leveen” probe, 4 cm
diameter (Radiotherapeutics)
Cool-Tip probe (17-gauge needle)
(Radionics)
Radiofrequency Ablation

Bioheat Equation
 Lesion  (Energy Applied x Local Tissue
Factors) – Energy Lost
Temperature
Change
c
T
   kT  J  E  hbl (T  Tbl )  Qm
t
Thermal Conductivity
and heat constant
Current Density
*
Electric Field Constant
Heat loss through
blood flow
Finite Element Modeling
Determine material and electrical properties
of tissue and ablation system
 Develop geometric model
 Solve Bioheat equation

c
T
   kT  J  E  hbl (T  Tbl )  Qm
t
Finite Element Modeling
Bioengineering Approach
Define Problem
 Determine Possible Solutions
 Model
 Test
 Refine

Define Problem

Local recurrence as high as 30%
 Uneven or irregular heating
 Heat sink vessels
RF
RF
Several mm’s
Define Problem


Local recurrence as high as 30%
 Uneven or irregular heating
 Heat sink vessels
Difficult to treat large or multiple tumors
Define Problem



Local recurrence as high as 30%
 Uneven or irregular heating
 Heat sink vessels
Difficult to treat large or multiple tumors
Poor imaging and localization
Ultrasound B-scan
Before
RF Ablation
Ultrasound B-scan
After
RF Ablation
Possible Approaches

Bioheat Equation
 Lesion  (Energy Applied x Local Tissue
Factors) – Energy Lost
Temperature
Change
c
T
   kT  J  E  hbl (T  Tbl )  Qm
t
Thermal Conductivity
and heat constant
Current Density
*
Electric Field Constant
Heat loss through
blood flow
Potential Solution #1

Bipolar RF Ablation
 Increase current density between
electrodes
 Increase energy deposition
 More uniform tissue heating
Bipolar RF Ablation
Bipolar RF Ablation

FEM predicts nearly double lesion volume
with bipolar electrode
Bipolar RF

In vivo porcine liver
Monopolar
Bipolar
Bipolar RF
Monopolar 3.93  1.8 cm2
 Bipolar 12.2  3.0 cm2

20
18
16
14
12
10
8
6
4
2
0
12.2
3.93
1
Monopolar
Bipolar
Bipolar RF
Bipolar RF
Monopolar, d=2.3 mm
Bipolar asymmetric,
d=1.8 mm
Bipolar symmetric,
d=1.0 mm
Bipolar RF

Problems
 Inability to control two
electrodes
independently
 Difficult technical
placement
 Unable to treat
multiple tumors
Potential Solution #2

Multiple Probe RF Ablation
 Allows overlapping treatment of large
solitary tumors
 Allows simultaneous treatment of
multiple tumors
Multiple Probe RF Ablation
Disadvantage:
Bipolar
Monopolar
electrical shielding
between electrodes
(Faraday cage)
Multiple Probe RF Ablation
Block diagram of system
Multiple Probe RF Ablation
Bipolar
Monopolar
Alternating Monopolar
Multiple Probe RF Ablation

Prototype Multiple Probe Device
 Computer controlled electromechanical switch
Multiple Probe RF Ablation

Ex Vivo Testing
Multiple Probe RF Ablation

In Vivo Testing
Multiple Probe RF Ablation
Single Probe Ablation
Simultaneous Multiple
Probe Ablation
Multiple Probe RF Ablation

In Vivo Testing
 Lesion Volume
 Single 10.7 cm3
 Dual 17.3 cm3 (per lesion)
 Time to Target Temperature
 Single 2.7 minutes
 Dual 3.4 minutes
Multiple Probe RF Ablation
Change to electrical switch
 Increase number of probes
 Increase speed of switching
 Decrease load on generator
 Evaluate synergism of overlapping multiple
probe RF ablations

Potential Solution #3
Bioheat Equation
 Lesion  (Energy Applied x Local Tissue
Factors) – Energy Lost
 Tissue Impedance (resistivity)

Tumor Resistivity

Electrical properties of normal liver and
tumor (K12/TRb) measured in an in vivo rat
liver model
Tumor vs. Normal Liver Tissue
Resistivity (W cm)
1000
800
Tumor loc 1
600
Tumor loc 1, orthog.
Tumor loc 2
400
Tumor rat, norm. tissue
200
Normal rat, 26.10.
0
Normal rat, 4.10.
1
10
100
1000
10000
Frequency (Hz)
100000 1000000
Tumor Resistivity

Finite Element Model
Tumor diameter = 2 cm
Tumor Resistivity

Current Density
500 kHz
100Hz
Tumor Resistivity

Temperature
500 kHz
100Hz
Tumor Resistivity

Lesion Difference
Gray circle represents
tumor boundary
Tumor Resistivity
Human?
 Colorectal metastasis to liver
Tissue Resistivity
2500
Resistance (ohm)

2000
Normal Surface
1500
Tumor Center
1000
Tumor Surface
500
0
10
100
1000
10000 100000 1E+06
Frequency (Hz)
Alternative Solution

Microwave Ablation
 Theoretical advantages over
radiofrequency ablation
 No ground pad
 Not limited by tissue charring and
impedance changes
 Use of Multiple Probes
Microwave Ablation

Larger zone of active heating
MW
1-2 mm
MW
1-2 cm
Microwave Ablation
RF
MW
Multiple Probe Ablation

Null Hypothesis
 Because microwave and radiofrequency
ablation are both heat based, there will be
no difference in ablation size or lesion
pathology between the two technologies
Methods
Microwave Ablation
 Vivant Medical prototype system
 10 minute ablation, 40 Watts
 Radiofrequency Ablation
 RITA Medical Systems Starburst
 10 minute ablation, 3cm deployment
100oC target temperature

Microwave Ablation System
• Vivant Medical
• 13g, 15cm dipole antenna
• 915MHz generator
• Fiberoptic temperature monitor
Radiofrequency Ablation System
• RITA Medical
• 14g, 15cm expandable array
• 460 kHz generator
• Integrated thermocouple
Lesion Volume
Lesion Volume
Volume (cm 3)
25
20
15
*
MW
RF
10
*
5
0
0
2
Day
28
* p=.02
Lesion Length
Lesion Length
Length (cm)
10
8
▪
*
6
▪
*
4
MW
◦
2
◦
RF
0
0
2
Day
28
* p<.001
▪ p=.02
◦ p<.001
Lesion Diameter
Lesion Diameter
Height (cm)
5
4
3
MW
2
RF
1
0
0
2
Days
28
Pathology
RFA
MW
Immediate
48o
4 weeks
Laboratory Data
No significant difference in AST, ALT,
LDH, Alkaline Phosphatase, WBC, or HCT
Platelet Count
Platelet Count (K/uL)

700
600
500
400
MW
300
RF
*
200
100
0
0
5
10
15
Days
20
25
30
* p<0.001
CT Imaging
48 Hours
4 Weeks
Microwave Ablation
Pathological and radiologic characteristics
similar between RF and MW ablation
 MW lesions larger than RF
 MW ablation technically easier than
multiple-prong RF ablation

Multiple Probe Microwave Ablation

Hypothesis
 Multiple probe hepatic ablation will
result in synergistically larger lesion sizes
by shielding lesion center from bloodflow mediated cooling
Methods
Microwave Protocol
 Domestic Swine
 10 minute ablation, 40 Watts
 Single Probe Ablation
 Multiple Probe Ablation
 3 parallel probes in triangular array
 Separation between probes varied
from 0.5 to 3.5cm

Methods

Microwave Protocol
Single Probe
Multiple Probe
Assessment
Lesion dimensions calculated
 Multiple Probe lesions scored for shape

Score
1
2
3
4
5
Criteria
Discontinuous
>25% Deflection
10-25% Deflection
<10% Deflection
Round
Results
Results
Lesion Diam eter
6
Diam eter (cm )
5
4
3
2
1
0
Single Probe
Multiple Probe
p<0.001
Results
Lesion
eter
LesionDiam
Volum
e
6.0
70
3
Volum
))
e (cm
Dim
ension
(cm
60
5.0
50
4.0
40
3.0
30
2.0
20
1.0
10
0.0
0
SingleProbe
Probe
Single
Multiple Probe
p<0.001
p<0.001
Results
Volum e (cm 3)

Lesion Volume by Measured Probe Separation
Size by Separation
80
70
60
50
40
30
20
10
0
0.0
0.5
1.0
1.5
2.0
2.5
Average Probe Spacing (cm )
r=0.24, p=0.43
3.0
3.5
Results

Shape by Measured Probe Separation
LesionLesion
Shape
6
Shape
5
4
3
2
1
0
0.0
0.5
1.0
1.5
2.0
Probe Separation (cm )
r=-0.75, p=0.003
2.5
3.0
3.5
Results

Lesion Shape
Results
Results

5 Probes
Microwave Ablation
Microwave ablation has several theoretical
advantages over RF ablation
 Multiple probe microwave ablation may
allow for treatment of larger, more complex
tumors as well as simultaneous treatment of
multiple tumors
 Multiple probe ablation may improve
treatment of tumors near blood vessels

Microwave Ablation

Phase I Clinical Study
Improved imaging

Physical characteristics of tissue change
with ablation
Base Line RF echo-signal
z
1
 2 ........ n
RF echo-signal after a 10C Temperature Increase
ΔT z  c γ τ z  c γ τ τ
2 z
2 z






0






0
2

1
c Initial Speed of Sound
0
 Tissue Dependent
Parameter
Improved Imaging
Ultrasound B-scan
Before
RF Ablation
Thermal Image
After
10 seconds
Thermal Image
After
2 Minutes
Improved Imaging
Ultrasound B-scan
Before
RF Ablation
Elastogram
Showing The
Thermal Lesion
Ultrasound B-scan
After
RF Ablation
Softer Region
(Normal Tissue)
Stiffer Region
(Thermal Lesion)
Future Directions

Further development and clinical testing
 Multiple Probe RF
 Variable-frequency RF
 Microwave Ablation
 Elastography and Thermal Monitoring
Future Directions
Modify local tissue factors
 Tumor-specific ablation sensitizers
 Adjuvant or neo-adjuvant chemotherapy
 Alternative Technologies
 Biomolecular Engineering
 Confocal Microwave
?

Acknowledgments



David Mahvi MD
Fred Lee MD
John Webster PhD





Dieter Haemmerich
PhD
Tomy Varghese PhD
Tyler Staelin MD
Chris Johnson
Vivant Medical
http//rf-ablation.engr.wisc.edu