June 6-10, 2004CRI Workshop, Haifa Treatment Planning for Radiofrequency Ablation of Liver Tumors...

June 6-10, 2004 CRI Workshop, Haifa

Treatment Planning for Radiofrequency Ablation of

Liver Tumors

Ariela Sofer, George Mason UniversityMasami Stahr, George Mason University

Bradford J. Wood, National Institutes of Health


Agenda

• Introduction:Liver Cancer and Radiofrequency Ablation

• The Temperature Distribution

• Challenges in Treatment Planning

• Final Thoughts


Agenda




• Final Thoughts


Primary and Secondary Liver Tumors

• Primary liver cancer is among the most common cancers worldwide:– Over one million new cases annually– Death rate ~ occurrence rate

• Even higher rates for colorectal carcinoma metastases (“secondary tumors”) in the liver

• Surgical resection - the gold standard of therapy

• But most patients are poor candidates for surgery

• Radiofrequency ablation - a promising treatment option for unresectable hepatic tumors.


Radiofrequency Ablation (RFA)

• A noninvasive technique for killing tumors by heat.

• A needle electrode is placed at the tumor site and an electrical current applied. This generates frictional heat. Heat in excess of 50oc will kill the tumor.


Ablation Treatment Planning

Determine the number of needles, their position, size, and power applied, to guarantee that the entire tumor is killed while damage to vital healthy tissue is limited.


• May be safely performed on an outpatient basis with conscious sedation

• Complex cases may require general anesthesia and overnight observation.

• Commonly performed percutaneously

• May also be implemented in open or laparoscopic surgery

• Treatment sessions about 10--30 minutes long.

Features of RFA


• Can treat small and (sometimes) mid-size tumors.

• May convert an inoperable patient into a surgical candidate.

RFA for Liver Tumors


• No long-term, prospective randomized clinical trials yet. However, early results are optimistic and suggest that RFA provides safe and effective local treatment of some cancers, with very small complication rates.

• Failures of RFA often associated with under-ablation and/or failure to create an adequate tumor-free margin

• Higher success rates for HCC tumors than for metastases

RFA for Liver Tumors


The Needle Electrodes

A variety of RF needle electrodes in different sizes and configurations.


The RFA Procedure

A closed-loop circuit is made by placing grounding pads on the thighs and connecting then in series with the generator, and the needle electrode.

Ultrasound and/or CT used for guidance


At 50oc protein is damagedpermanently and cell membranes fuse. Coagulation necrosis.

Alternating current at high frequency (500 KHz) is applied. Tissue ions are agitated as they attempt to follow the changes in direction of AC.

Frictional heat. Heat extends to adjacent tissue by

conductance

RF Heating Mechanism


More on Thermal Damage

45oC: heating for several hours irreversible damage

42oC: tissue susceptible to chemo / radiation

50oC: heating 4-6 minutes irreversible damage

60oC-100oC: near immediate protein coagulation

100oC-110oC: tissue vaporizes and carbonizes


Factors Impeding Ablation

• Temperatures > 100oC: – Charring of tissue close to needle that

prevents transfer of heat to tissue further away.

– Vaporization. Gas acts as insulator.

• Blood vessels near the tissue:– convection of thermal energy away

from the target tissue into the cooler blood.


Increasing the Lesion Size

• Internally cooled electrodes

•Saline solution injection

•Energy pulsing

•Hepatic blood flow reduction


CT: Pre-treatment

RFA Before and After

C:\Documents and Settings\Ariela Sofer\My Documents\talks\Haifa\charbroil.mpg.mpeg


Killed tumor cells are replaced by fibrosis and scar tissue

CT: Pre-treatment CT: 6 months after

RFA Before and After

Consecutive CT images - the input to the 3-D optimization


The Ablation Process

• Nitrogen micro-bubbles gradually create a hyperechogenic area on ultrasound that provides a rough estimation of the treated tissue

• Larger tumors can be treated by multiple needles with overlapping treatment regions. Because of changes in conductivity of ablated tissues, and because microbubbles can obscure visualization, the deepest tumor regions should be treated first.


Other Thermal Ablation Techniques

• Microwave Ablation

• Laser Ablation

• Ultrasound Ablation

• Cryoblation


Agenda




• Final Thoughts


Temperature Distribution: the Bioheat Equation

change in energy stored within

heat conduct

ed in

heat conducted out

heat generated within

= +-

tissuedensity

specific heat

thermal conductivit

y

T=T(x,t) temp.

• = div

=grad

heat loss toblood perfusionRFA heat

source


T=T(x,t) temp.

heat loss toblood

perfusion

The Bioheat Equation: The Heat Source

RFA heat source

V=V(x,t) electricalpotential

electricalconductivit

y


The Bioheat Equation – Boundary Conditions

Electrical Potential

Temperature


Numerical Solution of Bioheat Equation

Via the finite element method. Here: FEMLAB

Electrical Potential Temperature Distribution


Numerical Solution of Bioheat Equation: Slice

Electrical Potential Temperature Distribution


Heat Loss from Blood Vessels

blood density

flow rate

blood temperatur

e

specific heat

• Small vessels:

• Large vessels: Heat transport solved inside vessel. Flow field: incompressible Navier-Stokes eqs.


Effect of Blood Flow (Large Vessel)

needle

blood vessel

convective heat transport by blood


Agenda

• Introduction:Liver Cancer and RadioFrequency Ablation



• Final Thoughts


The Ideal Ablation Treatment Plan

Entire tumor (+ 1cm margin) is

killed

No thermal damage to critical organs

In reasonable time!

Limited damage to healthy tissue


Further Considerations

No. of puncture holes

Is resection part of overall treatment plan?

Convenient access


Treatment Planning Features

• Small number of decision variables:– Number of needles and their

configuration– Placement of needles

• But (potentially) lots of state variables:– Temperature at grid points on volume of

interest

• Temperature requires solution of a set of coupled partial differential equations


Treatment Planning Features (cont’d)

Temperature “dose” is not cumulative

IMRT key factor:

Total dose

RFA key factor:

Maximum dose


Challenge: Constraints Governed by PDE’s

•Each 3-D PDE solution takes many minutes

•The optimization involves repeated PDE’s

•Moreover, as needle position changes, the needle boundary “moves” and entire mesh changes

•But treatment plans must be available within just a few hours


Challenge: Large Tumors - Multiple Needles

Overlapping spheres? Overlapping cylinders?

Images from Dodd. et als, Radiographics 2000

Added combinatorial complexity!


Challenge: What Objective? What Constraints?

Minimize: underheating in tumorWhile prohibiting damage to critical structure limit damage to normal tissue But - may lead to many slightly underheated cells. Or to an awkward lesion shape Minimize: damage to critical structureWhile killing every cell in tumor limiting damage to normal tissue May not be achievable or medically acceptable

Minimize: damage to normal tissueWhile: killing every cell in tumor prohibiting damage to critical structureBut - may not be achievable


Challenge: Those Pesky Coefficients

Factors affecting thermal properties of tissue:

– normal tissue– cirrhotic tissue– HCC– metastases– vascularization– effect of temperature on parameters


Challenge: Complexity of Energy Sources

• Needle Electrodes:– Single, multiple, multi tined

• Energy Deposition– Pulsed, impedance regulated, internally

cooled

• Adjuvant Therapies– Use of saline solution to alter electrical and

thermal conductivity


Agenda




• Final Thoughts


Final Thoughts

• RFA treatment planning poses many complex mathematical and practical challenges

• Much to learn from the radiation therapy community

• Research relevant not only to RFA, but other thermal ablation modalities

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