Developing New Technology for Local Tumor Control:

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Developing New Technology for Local Tumor Control

• A Bioengineering Approach

Andrew Wright MD Department of Surgery 1/25/02
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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

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Background

• Only 1020 of patients with liver tumors will
  have disease amenable to surgical resection due
  to high surgical risk or unfavorable anatomy

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Radiofrequency Ablation

• High-frequency (460 kHz) alternating current
  flows from electrical probe through tissue to
  ground

Probe insertion
Extension of prongs
RF current application
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Radiofrequency Ablation
12-prong Leveen probe, 4 cm diameter
(Radiotherapeutics)
9-prong Starburst probe, 5 cm diameter (Rita
Medical)
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Radiofrequency Ablation

• Bioheat Equation
• Lesion ? (Energy Applied x Local Tissue Factors)
  Energy Lost

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Finite Element Modeling

• Determine material and electrical properties of
  tissue and ablation system
• Develop geometric model
• Solve Bioheat equation

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Finite Element Modeling
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Bioengineering Approach

• Define Problem
• Determine Possible Solutions
• Model
• Test
• Refine

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Define Problem

• Local recurrence as high as 30
• Uneven or irregular heating
• Heat sink vessels

Several mms
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Define Problem

• Local recurrence as high as 30
• Uneven or irregular heating
• Heat sink vessels
• Difficult to treat large or multiple tumors

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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 After RF Ablation
Ultrasound B-scan Before RF Ablation
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Possible Approaches

• Bioheat Equation
• Lesion ? (Energy Applied x Local Tissue Factors)
  Energy Lost

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Potential Solution 1

• Bipolar RF Ablation
• Increase current density between electrodes
• Increase energy deposition
• More uniform tissue heating

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Bipolar RF Ablation
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Bipolar RF Ablation

• FEM predicts nearly double lesion volume with
  bipolar electrode

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Bipolar RF

• In vivo porcine liver

Monopolar Bipolar
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Bipolar RF

• Monopolar 3.93 ? 1.8 cm2
• Bipolar 12.2 ? 3.0 cm2

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Bipolar RF
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Bipolar RF
Monopolar, d2.3 mm
Bipolar asymmetric, d1.8 mm
Bipolar symmetric, d1.0 mm
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Bipolar RF

• Problems
• Inability to control two electrodes independently
• Difficult technical placement
• Unable to treat multiple tumors

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Potential Solution 2

• Multiple Probe RF Ablation
• Allows overlapping treatment of large solitary
  tumors
• Allows simultaneous treatment of multiple tumors

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Multiple Probe RF Ablation

• Disadvantage electrical shielding between
  electrodes (Faraday cage)

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Multiple Probe RF Ablation
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Multiple Probe RF Ablation
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Multiple Probe RF Ablation

• Prototype Multiple Probe Device
• Computer controlled electromechanical switch

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Multiple Probe RF Ablation

• Ex Vivo Testing

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Multiple Probe RF Ablation

• In Vivo Testing

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Multiple Probe RF Ablation
Single Probe Ablation
Simultaneous Multiple Probe Ablation
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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

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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

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Potential Solution 3

• Bioheat Equation
• Lesion ? (Energy Applied x Local Tissue Factors)
  Energy Lost
• Tissue Impedance (resistivity)

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Tumor Resistivity

• Electrical properties of normal liver and tumor
  (K12/TRb) measured in an in vivo rat liver model

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Tumor Resistivity

• Finite Element Model

Tumor diameter 2 cm
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Tumor Resistivity

• Current Density

500 kHz
100Hz
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Tumor Resistivity

• Temperature

500 kHz
100Hz
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Tumor Resistivity

• Lesion Difference

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Tumor Resistivity

• Human?
• Colorectal metastasis to liver

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Alternative Solution

• Microwave Ablation
• Theoretical advantages over radiofrequency
  ablation
• No ground pad
• Not limited by tissue charring and impedance
  changes
• Use of Multiple Probes

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Microwave Ablation

• Larger zone of active heating

1-2 mm
MW
1-2 cm
MW
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Microwave Ablation
RF
MW
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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

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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

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Microwave Ablation System
Vivant Medical 13g, 15cm dipole antenna
915MHz generator Fiberoptic temperature monitor
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Radiofrequency Ablation System
RITA Medical 14g, 15cm expandable array 460
kHz generator Integrated thermocouple
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Lesion Volume


p.02
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Lesion Length

?
?
?

?
plt.001 ? p.02 ? plt.001
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Lesion Diameter
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Pathology
RFA
MW
Immediate
4 weeks
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Laboratory Data

• No significant difference in AST, ALT, LDH,
  Alkaline Phosphatase, WBC, or HCT

plt0.001
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CT Imaging
48 Hours
4 Weeks
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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

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Multiple Probe Microwave Ablation

• Hypothesis
• Multiple probe hepatic ablation will result in
  synergistically larger lesion sizes by shielding
  lesion center from blood-flow mediated cooling

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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

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Methods

• Microwave Protocol

Single Probe
Multiple Probe
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Assessment

• Lesion dimensions calculated
• Multiple Probe lesions scored for shape

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Results
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Results
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Results
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Results

• Size by Separation

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Results

• Lesion Shape

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Results

• Lesion Shape

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Results
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Results

• 5 Probes

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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

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Microwave Ablation

• Phase I Clinical Study

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Improved imaging

• Physical characteristics of tissue change with
  ablation

Initial Speed of Sound
Tissue Dependent Parameter
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Improved Imaging
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Improved Imaging
Ultrasound B-scan Before RF Ablation
Ultrasound B-scan After RF Ablation
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Future Directions

• Further development and clinical testing
• Multiple Probe RF
• Variable-frequency RF
• Microwave Ablation
• Elastography and Thermal Monitoring

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Future Directions

• Modify local tissue factors
• Tumor-specific ablation sensitizers
• Adjuvant or neo-adjuvant chemotherapy
• Alternative Technologies
• Biomolecular Engineering
• Confocal Microwave
• ?

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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