Comparison of three thermotherapy modalities for the ablation of mamma carcinoma in situ using thermal imaging and mapping

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PROCEEDINGS OF SPIE

SPIEDigitalLibrary.org/conference-proceedings-of-spie

Comparison of three thermotherapy

modalities for the ablation of mamma

carcinoma in situ using thermal

imaging and mapping

Klaessens, John, Verdaasdonk, Rudolf, van Esser, Stijn,

Shmatukha, Andriy, de Boorder, Tjeerd, et al.

John H. G. M. Klaessens, Rudolf Verdaasdonk, Stijn van Esser, Andriy

Shmatukha, Tjeerd de Boorder, Richard van Hillegersberg, "Comparison of

three thermotherapy modalities for the ablation of mamma carcinoma in situ

using thermal imaging and mapping," Proc. SPIE 6440, Thermal Treatment of

Tissue: Energy Delivery and Assessment IV, 64400A (9 February 2007); doi:

10.1117/12.701368

Event: SPIE BiOS, 2007, San Jose, California, United States

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Comparison of three thermotherapy modalities for the ablation of

mamma carcinoma in situ using thermal imaging and mapping

John H.G.M. Klaessens

∗1

, Rudolf Verdaasdonk

1

, Stijn van Esser

2

, Andriy Shmatukha

3

,

Tjeerd de Boorder

1

, Richard van Hillegersberg

2

Departments of Clinical Physics

1

, Surgery

2

and Radiotherapy

3

University Medical Center Utrecht, Utrecht, The Netherlands.

ABSTRACT

A larger percentage of small tumors in the breast are being detected due to effective screening programs and improved radiological diagnostic methods. For treatment, less invasive methods are preferred which are still radical but also provide a better aesthetic result. Recently, several ablation techniques have become available to locally ablate tumors in situ. In this study, the effectiveness of three ablation techniques was compared by imaging the thermal distribution and temperature mapping in vitro.

The first system (KLS Martin, Trumpf, Germany) uses Nd:YAG laser light delivered through a single diffusing fiber tip which is positioned direct into the tissue or in a water-cooled needle. The second system (Olympus-Celon, Germany) uses bipolar Radio Frequency currents between electrodes in a water-cooled needle. The RF system has a temperature feedback based on tissue impedance to prevent tissue charring. The third system is a focused ultrasound system developed in the Hospital.

For all three the techniques, the dynamics of temperature gradients around the probe or focus point are visualized using color Schlieren techniques in a transparent tissue model and recorded using thermocouples. The effective lesion size and tissue temperatures were determined in in vitro bovine mamma tissue.

All systems were capable to heat tissue volumes up to 3 cm in diameter. The lesion growth dependent on the power input, temperature gradient around the initial power source and treatment time.

Although the three systems are capable to ablate small mamma carcinoma in situ, they differ in precision, MR compatibility, invasiveness, practical use and treatment time.

The real clinical effectiveness has to be proven in large patient studies with long term follow up.

Keywords: Schlieren imaging, LITT, Laser induced thermal therapy, Radio frequent ablation, RFA, focused ultrasound, mamma carcinoma, thermal treatment.

1. INTRODUCTION

The traditional treatment of breast cancer was total mastectomy 20_{. In the last 50 years breast cancer surgery is}

developing towards less invasive approaches. At this moment sentinel lymph node biopsy and breast conservation therapy represent the standard care for the majority of patients. Breast conservational therapy with ablation techniques could remove the primary tumor without surgery. Radiofrequency ablation (RFA)2,9,11,12,18,20,21_{, Laser Interstitial Thermo}

Therapy (LITT)1,6,14_{, focused ultrasound}3,10,16_{(FUS), cryosurgery}13,17,23_{, and other approaches are being used in clinical}

or in experimental setup. The difficulties in these techniques is the imaging of the precise localization of the tumor, the estimation of the true size and shape and monitoring the treatment in real-time19_.

∗_{J.H.G.M.Klaessens@UMCUtrecht.nl; phone ++ 31 302505044; Fax ++31 302502002}

Thermal Treatment of Tissue: Energy Delivery and Assessment IV, edited by Thomas P. Ryan, Proc. of SPIE Vol. 6440, 64400A, (2007) · 1605-7422/07/$18 · doi: 10.1117/12.701368

Proc. of SPIE Vol. 6440 64400A-1

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light source time delay cw or pulsed bigger box

delivery system (fiber) cw or pulsed laser illumination fiber (ball-shaped)

p

POINT SOURCE irTage processing flashlight CCD camera

p

COLLIMATING LENS

OBJECT IMAGING FILTER IMAGE

PLANE LENS PLANE PLANE

Heating the tissue above 45 degrees Celsius causes dehydration, denaturation of intracellular proteins and destruction of cell membranes.

In this report we discuss the clinical applications and tissue interactions of three techniques; RFA, LITT and FUS. FUS, LITT and RFA are studied in transparent tissue mimicking gel (polyacrylamide) using the Schlieren imaging technique. LITT and RFA is also studied in vitro using bovine breast tissue to investigate the temperature distribution in the tissue during the ablation. Using MRI temperature mapping (proton resonance frequency shift method) the

temperature in bovine meat was calculated during LITT ablation.

2. MATERIALS AND METHODS 2.1. Schlieren imaging

A color Schlieren system maps the refractive index changes in transparent media into colors. The refractive indices can be changed by variations in pressure or temperature. The Schlieren principle and the system setup is published in several articles 15,22,24_.

In short; an overview of all the components of the color Schlieren setup is shown in Fig. 1. A continuous white light source is coupled into a fiber. The light emitted from a ball-shaped tip is focused, providing a point source and divergences subsequently. The focal point of a collimating lens coincides with the focus of the beam. The diameter of the lens is matched with the divergence of the beam collimated. This provides a parallel bundle to the object plane. A rectangular tank filled with a medium (e.g., water or tissue) is positioned between the collimating and imaging lens. The imaging lens will focus the parallel beam in its focal point on the optical axis. However, due to variations in the

refraction index or irregularities in the medium in the object plane induced by, for example, temperature gradients or local stresses, rays will be deflected. These rays will cross the focal plane at a particular distance d from the optical axis (Fig.3). The nondistorted rays will be focused on the optical axis. By inserting a mask or a filter in the focal plane of the imaging lens, it is possible to block out the nondeflected rays, preventing them from reaching the image plane. By blocking the rays crossing the optical axis, only refracted and diffracted rays will pass the filter plane and contribute to an image restoration at the image plane. The result is an enormous contrast enhancement of the image due to the subtraction of the background light. The information on the degree of deflection can be preserved by color coding the rays coming through the filter plane using a color filter (Fig. 2). This filter consists of concentric rings of discrete color bands separated by small black rings. The center of the filter is a black dot blocking the background light. Rays passing

Fig. 1: Schematic of the components of a color Schlieren setup to study laser-tissue interaction.

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-..

r

hi.

[];

I. I I.. I: . I;I

• I

I

df*tan a

color coded I I OBJECT IMAGE LENS

PLANE PLANE PLANE

object distance image distance

the filter plane will be color coded depending on the deflection distance d and will be reconstructed to an image at the image plane. The color image can be interpreted as a thermal image when the relation between refractive index and temperature gradient is known. The black rings in the filter will result in black lines in the image separating the discrete colors giving an impression of “isotherms”. The CCD camera is positioned in the image plane.

2.2. Laser Interstitial Thermal Therapy (LITT)

The LITT was performed with the NdYag laser (TT Yag-80; Trumpf Medizine Systeme, Umkirch, Germany) with a wave length of 1064 nm. The laser light was delivered through a 1 mm fiber with a core diameter of 400 µm and a diffuser length of 25 mm (Micro dome, Trumpf Medizine Systeme, Umkirch, Germany). The fiber is standard positioned in an applicator (Fig. 6). The applicator is cooled with cold (5 degrees Celsius) NaCL. Up to three laser fibers can be connected to the laser using a splitter after the laser.

Fig.4: TT Yag-80 K LS Martin Trumpf Medizine Systeme, Umkirch, Germany, the down part is the laser and above are two roller pumps and on top is a beam splitter.

Fig.3: Scheme of optical processor for spatial filtering using a either a block filter or a color filter.

Fig. 6: Laser applicator

Fig. 5: Laser fiber with diffuser tip at the end Fig. 2: An example of a

'Rainbow' color filter

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2.3. Radio Frequent Ablation (RFA)

The principle of radiofrequency ablation is frictional heating that is caused when ions in the tissue attempt to follow the changing directions of a high-frequency alternating current.

2.3.1. RFA systems

On the market are many RFA systems, some of them are: RITA® Model 1500X RF generator, Cool-tip RF and the Olympus Celon . We used the Olympus Celon system for our experiments.

2.3.1.1. CelonLab Power

This Radio Frequency Ablation system (Fig.8) is manufactured by Celon in Germany (CelonLab Power; Celon Medical Instruments, Teltow, Germany) can be used as a bi or multipolar RF ablation system7,8_{. The system operates at}

ac-currents with a frequency of 470 kHz, the tissue dissipates powers up to 250 Watts. During treatment the system measures the resistance between the electrodes on the probe(s). The power output is automatically feedback controlled by measuring the tissue resistance. The tissue resistance can change due to heating and coagulation. Around boiling temperature, vapor might create electrical isolation; this prevents the system temporary from energy dissipation. The coagulation probes are cooled with saline solution at room temperature (Fig. 7), this to prevent that the temperature of the tissue adjacent to the applicator becomes too high. The system can simultaneously operate 3 bipolar probes (Fig.10), this is needed for large tumors. The active tip lengths are available at 20, 30 or 40 mm, the diameter of the probe is 1.8 mm and the shaft length is 10-25 cm.

Fig. 7: Schematic internal cooling (with saline solution at room temperature) of the tip of the coagulation probe.

Fig.8: The CelonPOWER System, on top the power control unit, CelonLab POWER, down the triple peristaltic pump, CelonAquaflow III. On top of the system the three CelonProSurge applicator needles that can be used multipolar

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I

II

Ii,

For small tumors only one applicator is needed. The applicator is positioned in the middle of the tumor using ultrasound echo guidance. An oval area around the two electrodes is heated (Fig.9) and the tissue will dehydrate and coagulate (Fig.9).

2.4. Focus Ultrasound

We used a single element high power Imasonic (Besancon, France) ultrasound transducer (Fig.12). The transducer is acoustically matched for a water environment. The active diameter is 120 mm with a spherical focusing of 80 mm ± 1mm, the focal beam length and width were 19 mm and 3 mm. The maximum efficiency frequency is 1.5 MHz and the required acoustical power is 150 Watt.

In the waist of the ultrasound beam the energy density is the highest (Fig. 11), here we expect the start of the heating and ablation process.

2.5. Magnetic Resonance Temperature Imaging

During hyperthermic procedures it would be helpful to have continuous thermometry to correct for local difference in temperature. Tissues in and around a tumor have different composition with different energy absorption properties which will result in different temperatures. Heat conduction through diffusion and perfusion may be different because of tissue structures. Also the energy deposition can vary during the ablation process caused by changes in energy

absorption. With magnetic resonance (MR) it is feasible to measure a three-dimensional mapping of temperature changes. This can be based on the relaxation time T1, the diffusion coefficient, or on the proton resonance frequency (PRF) of the water in the tissue. Using temperature-sensitive contrast agents and proton spectroscopic imaging can give

Fig.9: Bi-polar applicator positioned in the tumor. With this technique no ground plate is needed.

Fig.10: Simultaneous operation of up to three bipolar electrodes within or around a tumor. The electrical current runs between the applicators (15 possible electrode combinations).

Fig.12: Imasonic ultrasound transducer Fig. 11: Typical ultrasound beam profile.

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absolute temperature measurements. We used the PRF method because of temperature linearity, the good temperature sensitivity and is relatively independent for tissue type4,5,16_{. The PRF method can achieve a}_{resolution of}_{1 degree}

Celsius, within 1 s in a tissue area of 2 mm.

3. Measurements and Results

The measurements and the results are discussed for each method of ablation. First we will present experiments the heating tissue mimicking gel with the Schlieren imaging technique, followed by in vitro tissue experiments. With the Schlieren experiments we can study were en how deep tissue will be heated.

3.1. Schlieren temperature imaging of RFA and LITT in Gel

For Schlieren imaging of the temperature gradients we used polyacrylamide gel to mimic the tissue. For the NdYag laser and RFA heating we had to modify the standard gel. For absorption of the NdYag light we added 5% copper sulfate (CuSO45H2O) to mimic the blood absorption in tissue. For the RFA measurement we need electric conductivity,

we replaced the water in the gel with NaCl. In Fig. 14 and Fig. 15 we positioned the RFA applicator and the LITT fiber in the gel. Starting the ablation will heat the gel. We see the temperature gradients in the figures. On the left of them the absolute temperature curves are given corresponding with the thermocouples.

NdYag in Gel 20Watt

15 20 25 30 35 0.00 1.00 2.00 3.00 4.00 5.00 6.00 Time [min] T e mp er at u re d e g rees C e lsi u s T1 T2 T3 T4

Fig. 16: Heating polyacrylamide gel with a NdYag laser.

Fig. 15: Schlieren image of temperature changes during LITT in poly acryl amide gel.

RFA in Gel 20 Watt

20 30 40 50 60 70 0 1 2 3 4 5 6 7 8 Time [min] Te mpe ratur e de gr ee s C e lsi u s T1 T2 T3 T4

Figure 13: Heating polyacrylamide gel with RFA.

Fig. 14: Schlieren temperature image using RFA in gel.

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-f-I

lcm 1cm 1cm 1cm Fiber or RFA probe

Ti

T2 T3 Tissue T4

3.2. Experimental setup of RFA and LITT in bovine breast tissue

In vitro experiments were setup to study the temperature distribution and the ablation area in bovine breast tissue. The tissue is warmed till 37 degrees Celsius in a water bath. The tissue is cut open to place the RFA probe or the laser fiber in a homogeneous breast tissue area. The temperature is measured with thermo couples positioned at the end of twisted wires. The positioning scheme is shown in Figure 17.

3.3. Results of RFA and LITT in bovine breast tissue

A study on the heat distribution in tissue during ablation is going on. Some preliminary results are given in Fig 14 and 15. The temperature distributions around the applicator during bovine breast tissue ablation are different using RFA and LITT. The temperature at 1cm (T1), 2 cm (T2) and 3cm (T3) from the applicator have for LITT and RFA nearly the same shape. The end temperatures are comparable if we take the difference in starting temperature into account. The temperature in the prolongation of the applicator differs. The LITT fiber transmits light to the front of the fiber while RFA only heats tissue side ways. This results for the RFA in a round ablation area with a diameter of 2 cm, the shape of the LITT ablation area is more ellipsoid; length 3 cm and width 2 cm.

Figure 17: Scheme of the fiber or RFA applicator and the four thermocouples positioning in the bovine breast tissue.

RFA 5 Watt 30 40 50 60 70 80 90 100 0 5 10 15 20 25 time [min] Tempe rature degr ees Cel si u s T1 T2 T3 T4

Fig.18: Temperature distribution during RFA ablation of bovine breast tissue. The total energy 5.1 kJoule.

LITT 5 Watt 20 minutes

30 40 50 60 70 80 90 100 0 5 10 15 20 25 Time [min] Temper ature degre es C el sius T1 T2 T3 T4

Fig.19: Temperature distribution during LITT ablation of bovine breast tissue

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80 70 0 so

4o

30

Time series image number

3.4. Magnetic Resonance Temperature mapping during LITT

The experiments were done on bovine muscle meat, the MR imaging was performed on 1.5 T MR scanner (Philips Medical Systems, Best, Netherlands) using a 14 cm diameter circular flexible surface coil. The temperatures were calculated using the proton resonance frequency shift method16_.

The bovine meat was positioned in the MRI with the diffuser of the LITT fiber positioned in the center of a 15 cm thick meat slice. The NdYag laser was set at 7 Watt CW. The light was transmitted through a fiber 400µm core diameter and a diffuser tip (25mm).

In Fig.20 the temperature time evolution in the ROI of 3x3 pixels marked in Fig.21 is shown.

The temperature map slices are 47x47 mm and the time between two successive measurements was 15 seconds. Examples of the axial and sagittal slices are shown in Fig.23 and Fig.22.

The tissue damage area is defined as: 45 degrees Celsius for more then 5 minutes. From the temperature maps of our experiments we measured an ellipsoid ablated area with diameters: 30 mm by 35 mm.

Fig.21: The Region of Interest (ROI) were the temperature evolution was calculated, the fiber was positioned in the centre of the hotspot.

Fig.20: The MRI temperature averaged over an area (ROI) of 3x3 pixels.

Fig.22: Axial projection, temperature map at time serie 90. The colors represent temperature in degrees Celsius. Fig.23: Sagittal projection, temperature map at time

series 90.

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3.5. Schlieren imaging of FUS ablation.

The FUS transducer is connected to the bottom of a transparent container. The container is filled with water to make a good acoustic coupling. In the focus point of the transducer a tissue mimicking gel (poly acryl amide) is placed. The gel is positioned on top of a thin plastic film. This whole setup is placed in the object plane of a Schlieren imaging system.

The gel block is placed in the focusing point of the ultrasound transducer (Fig.24).

3.6. Schlieren imaging of FUS ablation in gel.

To study the ablation using FUS we used tissue mimicking gel as tissue model. The ablation process was visualized in

the Schlieren setup. In Fig.26 the beam profile of the ultrasound transducer is visible, in the beam waist the ablation is starting. The ablation area spreads out within the beam in the direction of the transducer. The ablation zone has a triangle shape with an average width of 3 mm and a height of 5 mm (Fig.27).

Fig.24: FUS transducer in a water container. The tissue mimicking gel is positioned above the transducer. The whole is placed in a Schlieren imaging system.

Fig.26: A Schlieren image of the start of FUS ablation in Gel. The US transducer is placed down of the image. In this image you can also see the shape of the ultrasound beam profile.

Fig.25: Schlieren image of the ablation area after 15 seconds FUS in gel. The ablation zone is half the waist of the US bundle.

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4. DISCUSSION

The first results from LITT and RFA in tissue mimicking gel showed temperature profiles and shapes of heating volumes. The absolute temperatures were not according to the in vitro bovine breast temperature measurements. The cause of this can be the difference in absorption of NdYag light in Copper sulfate compared to real tissue or the difference in electrical conductivity in saline polyaclylamide compared to the electrical conductivity of tissue. We are working to improve the tissue phantoms for these ablation techniques. From the gel en bovine breast tissue experiments we would conclude that the shape of the ablation area for LITT is more ellipsoidal and for RFA more spherical. The diameter of the ablated area with RFA and LITT was about 3 cm.

From the MR temperature mapping of LITT heating of bovine tissue we see first symmetrical heating around the diffusing fiber tip. But after 10-15 minutes we see an asymmetrical temperature profile. This can be caused by in-homogeneities in the tissue. Also heating and air bubbles can cause artifacts in the MR temperature mapping. Further study needs to be done.

MRI temperature mapping gives 3D information. For treatment of a tumor all the tumor cells in that area need to be heated to make them a-vital. Local tissue temperature information would be desirable for clinical ablation treatments. The FUS starts the ablation in the waist of the ultrasound bundle. In the gel experiments we had to move the gel a few mm to position an in-homogeneity in the waist of the bundle. At this point the ablation started. In real tissue this will not be necessary because there are always in-homogeneities in the tissue. On the other hand the tissue will scatter the bundle more then the gel which will reduce the US intensity in the waist. More experiments have to be done to study the FUS ablation in tissue.

With all the information gathered in the in vitro experiments a clinical trial will be started which will include patients with T1 breast tumors smaller then 2 cm diameter for LITT treatment.

5. CONCLUSION

The FUS ablation technique is promising for the future. Development of array transducers which can position the focusing point over a lager area could make this technique useful for tumor treatment.

The LITT and RFA techniques give both good and comparable results and can create ablation area’s that are large enough to treat mamma carcinoma smaller then 2-3 cm diameter.

All the ablation techniques give in tissue ablation shapes depending on local cooling and tissue composition. To be curtain that all the tumor tissue is avital after the treatment 3D temperature mapping would be very useful.

Fig.27: Picture of a series of ablation areas created with FUS in the Gel. The size of the ablation zone is width: 3 mm end height: 5 mm. The transducer was placed below this block gel with the focus in the top of the tiangle.

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