In Situ Temperature Measurements WithThermocouple Probes During Laser

Interstitial Thermotherapy (LITT):Quantification and Correction of a

Measurement ArtifactFabrice Manns, PhD,1,2* Peter J. Milne, PhD,2,3 Xochitl Gonzalez-Cirre, MS,1,2

David B. Denham, MS,1,2 Jean-Marie Parel, PhD,1,3 andDavid S. Robinson, MD4

1Department of Biomedical Engineering, University of Miami College of Engineering,Coral Gables, Florida 33146

2Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of MiamiSchool of Medicine, Miami, Florida 33146

3Division of Marine and Atmospheric Chemistry, University of Miami Rosenstiel School ofMarine and Atmospheric Sciences, Key Biscayne, Florida 33149

4Sylvester Comprehensive Cancer Center, University of Miami School of Medicine,Miami, Florida 33136

Background and Objective: The purpose of this work was to quan-tify the magnitude of an artifact induced by stainless steel ther-mocouple probes in temperature measurements made in situ dur-ing experimental laser interstitial thermo-therapy (LITT). A pro-cedure for correction of this observational error is outlined.Study Design/Materials and Methods: A CW Nd:YAG laser systememitting 20W for 25–30 s delivered through a fiber-optic probe wasused to create localized heating. The temperature field around thefiber-optic probe during laser irradiation was measured every 0.3s in air, water, 0.4% intralipid solution, and fatty cadaver pig tis-sue, with a field of up to fifteen needle thermocouple probes.Results: Direct absorption of Nd:YAG laser radiation by the ther-mocouple probes induced an overestimation of the temperature,ranging from 1.8°C to 118.6°C in air, 2.2°C to 9.9°C in water, 0.7°C to4.7°C in intralipid and 0.3°C to 17.9°C in porcine tissue after irra-diation at 20W for 30 s and depending on the thermocouple loca-tion. The artifact in porcine tissue was removed by applying ex-ponential and linear fits to the measured temperature curves.Conclusion: Light absorption by thermocouple probes can in-duce a significant artifact in the measurement of laser-inducedtemperature increases. When the time constant of the thermo-couple effect is much smaller than the thermal relaxation timeof the surrounding tissue, the artifact can be accurately quan-tified. During LITT experiments where temperature differ-ences of a few degrees are significant, the thermocouple artifactmust be removed in order to be able accurately to predict thetreatment outcome. Lasers Surg. Med. 23:94–103, 1998.© 1998 Wiley-Liss, Inc.

Key words: breast cancer; hyperthermia; laser-tissue interaction; tissue tempera-ture measurements

Contract grant sponsor: Department of Defense Breast Can-cer Research Program; Contract grant number: DAMD 17-94-J-4246; Contract grant sponsor: Kemper Foundation, KansasCity, MO.

*Correspondence to: Fabrice Manns, University of Miami,1638 NW 10th Avenue, Miami, FL 33136.

Accepted 11 May 1998

Lasers in Surgery and Medicine 23:94–103 (1998)

© 1998 Wiley-Liss, Inc.

INTRODUCTION

Laser interstitial thermotherapy (LITT) is atechnique for the localized treatment of tumorswherein cancer cell necrosis is produced by mod-erate (noncharring) heating of the tumor with alaser source to temperatures above 43°C [1–4].The lasers used for LITT are typically high powercontinuous-wave (CW), near-infrared lasers, suchas the Nd:YAG laser (1064 nm), or different typesof diode lasers (808–980 nm), which also have fa-vorable tissue transmission characteristics [5,6].The laser energy is generally delivered throughoptical fiber probes inserted into the body underX-ray, MRI, or ultrasonic guidance [7–9].

Ideally, the temperature rise producedwithin the treatment site using LITT must be con-trolled to avoid vaporization and carbonization,yet still ensure total tumor cell necrosis withinthe desired volume of treatment. In vital organssuch as the liver, brain, or prostate, minimizingcollateral thermal damage of healthy tissue sur-rounding the tumor is essential. Currently, one ofthe main limitations in the clinical application oflaser hyperthermia is the lack of real-time intra-operative dosimetry of the laser-induced thermaleffect [10].

Laser treatment parameters (such as power,duration, wavelength) and the resultant radiantfield of the fiber for a given treatment procedureare initially selected by predicting the laser-induced temperature rise with tissue thermo-optical models of varying complexity [11–14].However, because of tissue inhomogeneity, an-isotropy, and variations of the optical and thermalproperties of the tissues with temperature,thermo-optical models are not always sufficientlywell parametrized to predict the temperature risewithin the tissue with the desired accuracy or re-liability. The suitability of the selected treatmentparameters must, therefore, be demonstrated ex-perimentally in tissue phantoms or in animalmodels. In situ interstitial temperatures gener-ated during clinical or experimental laser irradia-tion are generally measured with thermocoupleprobes [15,16], infrared optical fibers [17,18], op-tical temperature sensors such as temperature-sensitive fluorescent probes [19,20], and MRImonitoring [21].

Thermocouple probes are more accurate andless expensive than fiber-optic or fluorescent tem-perature probes. However, they usually consist ofthermocouple wires embedded in a thin needlemade of stainless steel, which itself strongly ab-sorbs near-IR radiation ∼1,000 nm. Because this

absorption induces a direct temperature increaseof the needle, temperatures measured with ther-mocouple probes during laser irradiation of tissuemay be significantly larger than the actual sur-rounding tissue temperature [22,23]. The ampli-tude of this artifact is usually assumed to be equalto the temperature jump recorded when the laseris switched on or off [22–24]. However, this cor-rection technique does not provide an accuratequantification of the artifact because the end-points of the jump usually cannot be identifiedaccurately. In a variation of this technique [24],the laser was turned off for a short duration (1 s)at regular intervals during the treatment, and theartifact was assumed to be equal to the resultingtemperature jumps. With this technique, the ar-tifact is accurately quantified only if the laser isswitched off longer than the time it takes for thethermocouples to reach thermal equilibrium withthe surrounding tissue. If the laser is switched offfor a shorter time, then the amplitude of the arti-fact is underestimated.

As part of the optimization of a procedure forstereotactic X-ray-guided LITT of small breastcancers [25,26], we have designed a system for insitu real-time temperature measurements duringexperimental LITT, using several needle thermo-couple probes placed within the tissue around theLITT fiber probe [26–28]. The purpose of the pres-ent study was to quantify and subsequently cor-rect for the artifact induced in temperature mea-surements made with thermocouples duringLITT. This further enables us accurately to modelthe actual temperature increase in the treated tis-sue volume associated with a given set of lasertreatment parameters.

MATERIALS AND METHODS

Laser and Fiber-Optic Probes

In all experiments, a CW Nd:YAG laser sys-tem (FiberTome™, Dornier Medical Systems,Germany) was set to a constant power output of20W for 25–30 s. The laser energy was deliveredthrough a silica fiber-optic probe, which consistedof a 600-mm core optical fiber terminated with a200-mm-long quartz tip having an outer diameterof 1.9 mm (H-6190-1, Dornier Deutsche Aero-space, Germany). In the Dornier system, the axisof the LITT fiber is tilted by a small angle withrespect to the optical axis of the laser beam andlaser-to fiber coupling lens. With this design, theemission pattern at the fiber output is a divergingring (Fig. 1). A quartz cap protects the fiber end

Thermocouple Probes During LITT 95

face to ensure consistent light emission of theprobe. The quartz cap increases the irradiatedarea at the output of the probe and thus helpsreduce the temperature increase close to the tip toavoid charring. The power emitted by the LITTfiber probes was measured before and after eachexperiment by placing the output end of the fiberin an integrating sphere (UDT 2525, United De-tector Technologies, Santa Monica, CA) throughthe input port and connecting a photodiode to theoutput port. The integrating sphere was initiallycalibrated at 1064 nm against a calibrated powermeter (210, Coherent, Auburn, CA).

Temperature Measurements

Temperatures around the LITT probe weremeasured during laser irradiation in ambient air,water, 0.4% intralipid solution, and fatty cadaverporcine tissue with up to 15 separate 23-gauge(635 mm diameter), 5-cm-long, stainless-steelneedle thermocouple probes with a time constantof 0.15s (MT-23/5, Physitemp Instruments,Clifton, NJ) held in position with a Plexiglas grid.The holes in the Plexiglas grid and weights addedto the thermocouple probe helped avoid lateraland vertical movements of the probes during ex-periments. The thermocouples were connected toa 16 channel data acquisition system (DAS-TC,Omega Engineering, Stamford, CT), which al-lowed temperatures to be recorded every 0.3 s anddisplayed in real-time with a personal computer.One of the 16 channels of the data acquisitionsystem was connected to an internal laser powersignal to monitor and record the laser outputpower during the treatment cycle. After their in-dividual calibration, temperatures recorded byeach thermocouple were within 0.1°C of the tem-

peratures measured against a calibrated preci-sion thermometer in a water bath. The thermo-couple needle probes had a manufacturer speci-fied time constant of 0.15s and an operating rangeof −273–200°C.

Tissue Preparation

Fatty cadaver porcine tissue was obtainedfrom the Division of Veterinary Resources, Uni-versity of Miami. The skin, subcutaneous fat, andunderlying muscle were obtained as a unit. Uponreceipt, the tissues were sealed in plastic bags,and stored at 3°C for 2–6 weeks. Prior to testing,the tissue samples in sealed plastic bags wereplaced under flowing warm water until the coretemperature was 35–37°C. The samples werethen slightly compressed to prevent motion dur-ing fiber and thermocouple insertion and placedin the container of a temperature-controlled wa-ter bath that brought the initial tissue tempera-ture to between 33–36°C.

Placement of Fiber and Thermocouple Probes

The LITT fiber was inserted laterally in thetissue through a port in the side of the water bath.To allow accurate positioning deep within the tis-sue while avoiding bending of the fiber, a guid-ance channel was first opened in the tissue with a13-gauge stainless steel trocar-cannula assemblyprior to fiber insertion. The trocar was then re-moved and the fiber was inserted in its placethrough the cannula. The cannula was then re-tracted so as to expose the quartz tip of the fiber.

The thermocouple probes were held in posi-tion above the water bath by a Plexiglass lid ar-rayed with holes spaced at 5 mm intervals forinsertion of the thermocouples (Fig. 2). The verti-

Fig. 1. Emission pattern at the output of the Dornier LITT probe in air.

96 Manns et al.

cal position of each of the thermocouples was ad-justed with depth stops so that all tips werebrought to the same plane orthogonally to the lidand at the depth of the LITT fiber axis. To facili-tate insertion of the thermocouple probes into thetissue, each insertion site was punctured before-hand with a 20-gauge hypodermic needle. Thesame technique for fiber and thermocouple place-ment was used in the experiments in the othermedia, except that the container was either leftempty for the experiments in air, or filled withwater or 0.4% intralipid solution.

RESULTS

Temperature Recordings

The observed temperature increase recordedfor one of the thermocouples (TC5) in each of air,water, 0.4% intralipid solution, and porcine tissueis shown in Figure 3. The temperature of each ofthe 15 thermocouples in air varied exponentiallywith time. The temperature curves in air were fitwith a function of the form:

DT(t) = AS1 − e−ttD (Eq. 1)

where DT (in units of °C) is the temperature in-crease, A (in units of °C) is the asymptotic tem-perature, and t (in units of s) is the time constantdefined as the time to reach 63% of the asymptoticvalue. For irradiation in air, the asymptotic tem-perature reached up to 118.6°C for the thermo-couple (TC15) subject to the most direct irradia-tion (Table 1, Fig. 3). The observed time constantsfor irradiation in air varied from 4.6–48 s (Table1). Because air does not appreciably absorb near-infrared radiation, these temperature increaseswere the result of direct light absorption by thethermocouple probes themselves. Since the emis-sion pattern of the LITT probe in air was a for-wardly diverging annulus, only the thermocoupleprobes placed directly in the light cone underwenta significant temperature increase. As shown inTable 1, the thermocouple placed immediately infront of the probe (TC15) was located in a region ofhigher radiance in this medium than the otherthermocouples, whose observed temperature riseswere all <5% that of TC15. These thermocoupleswere located outside the main emission field ofthe LITT probe. The higher temperature increaseof TC15 also indicates that a significant amount T

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of light is emitted in the forward direction outsidethe main emission ring.

To analyze the temperatures recorded in wa-ter, intralipid, and porcine tissue, we assumedthat the recorded temperature increase was thesum of two terms: the temperature increase dueto light absorption in the medium and the tem-perature increase due to direct absorption of lightby the thermocouple (Eq. 1). Because the esti-mated thermal relaxation times of water, 0.4%intralipid solution and porcine fatty tissue at1,064 nm (e.g. >1,800s for water, calculated at1,064 nm) are so much longer than the irradiationtime (30 s) of these experiments, the resultingtemperature increase in the tissue, DT(r,t), wasexpected to vary linearly with time under con-stant power input [29]:

DT(r,t) =ma

r cF(r) t

(Eq. 2)

where ma (in units of cm−1) is the absorption coef-ficient at 1,064 nm, r (in units of g.cm−3 is the

density, c (in units of J.g−1.°C−1) is the heat ca-pacity, and F(r) (in units of W/cm2) is the fluencerate. Accordingly, the temperature curves mea-sured in water, intralipid solution and porcine tis-sue were fit with functions of the form:

DT(t) = A(1 − e−tt) + Bt (Eq. 3)

where the exponential term represents the tem-perature increase due to direct absorption of lightby the thermocouple, and B (°C.s−1) is the slope ofthe linear temperature increase due to absorptionof light by the medium. The fitted values of A, tand B for all thermocouples in water, intralipidand porcine tissue experiments are shown inTable 1.

In water as in air, only those thermocoupleslocated in regions of direct laser radiance under-went significant temperature increase. Otherthermocouples, not shown in Table 1, experiencedtemperature increases of <3°C, with variable de-lays of 6–12 s after the laser irradiation was com-menced. These thermocouples were heated by ad-vection. In intralipid solution, the thermocoupleslocated farthest from the probe (TC 1, 2, 3, 4, 7, 8)recorded temperature increases of <2°C, againwith initial delays of up to 5 s. The fluence rate atthese locations was probably not sufficient to in-duce a measurable temperature increase due tolight absorption either by the thermocoupleneedles or by the immediately surrounding in-tralipid itself. These thermocouples were alsoprobably heated by advective process.

Removal of Thermocouple Artifact in Pig Tissue

The artifact due to light absorption by thethermocouples was simply removed from the mea-surements in porcine tissue by subtracting the ex-ponential term in Eq. (3) from the measured tem-perature increases (Fig. 4). This correction wasmade for each thermocouple by using the corre-sponding values of A and t listed in Table 1. Fortimes greater than 4.6 (2 × e) times the time con-stant t, the value of the exponential term iswithin 1% of the asymptotic value, so that theartifact for these times was effectively equal tothe asymptotic value, A, of the exponential term.In porcine tissue, the magnitude of the direct ab-sorption artifact varied from 0.3–17.9°C depend-ing upon the placement of the thermocouple in thetissue light field.

Fig. 2. Position of the 15 thermocouples around the LITTfiber. The tip of each thermocouple was located in the planeperpendicular to the thermocouples and containing the axis ofthe fiber probe.

98 Manns et al.

DISCUSSION

Effect of Thermocouple

The experiments in air demonstrated thatthe temperature increase due to direct absorptionof light by the thermocouple probes varied expo-nentially with time. These variations can be ex-plained by using a heat conduction model whereinthe thermocouple probe is considered to be a thinsolid cylinder of thermal conductivity muchhigher than air heated by a constant heat sourceand immersed in a medium maintained at uni-form temperature. Such a system can be analyzedby using a ‘‘lumped system formulation’’ wherethe variation of temperature within the thermo-couple probe is neglected due to its higher ther-mal conductivity [30]. One can show that the so-lution of such a transient heat conduction prob-lem with heat generation yields an exponentialfunction of the form of Eq. (1), wherein the asymp-

totic value, A, represents the temperature at ther-mal equilibrium, and the time constant, t, is rep-resentative of the time needed to reach thermalequilibrium.

In porcine tissue, a highly scattering me-dium, the time constant of the exponential func-tion representing the temperature increase due tolight absorption by the thermocouple probes var-ied between 1.2–3.0 s depending on the exact spa-tial location of the thermocouple in the measure-ment grid pattern. The temperature change dueto light absorption by the tissue during the timetaken for the thermocouple probes to reach ther-mal equilibrium (defined as 2.3 times the timeconstant t of the exponential temperature in-crease, which is the time to reach 90% of the as-ymptotic value of the exponential term), was cal-culated for each thermocouple by using the corre-sponding values of B (Table 1). This temperaturechange varied between 0.2–3.6°C. Thus the tem-

Fig. 3. Temperature increase recorded by the thermocouple at grid position 5 (TC5) in air, water, 0.4% intralipid solution, andporcine fat during Nd:YAG laser irradiation at 20W. Insert shows the temperature increase of thermocouple 15 (TC15) in air.Plotted symbols represent the measured temperature points. Solid lines are calculated curve fits.

Thermocouple Probes During LITT 99

Fig. 4. Temperature increase of four thermocouples in porcine fat during Nd:YAG laser irradiation at 20W before and afterremoval of the thermocouple artifact. Plotted symbols represent the measured temperatures. Solid lines are the calculatedcurve fits.

100 Manns et al.

perature of the medium surrounding the thermo-couple probe can be assumed to be constant dur-ing the time taken for the thermocouple to reachthermal equilibrium. The lumped system analy-sis, therefore, can also be applied for porcine fattytissue and any other biological tissue exhibitingcomparable absorption and scattering character-istics towards near-IR radiation.

Removal of Thermocouple Artifact

In order to be able accurately to predict thedosimetry of an applied laser fluence rate in agiven tissue, it is first necessary to remove anythermocouple artifact from the recorded tempera-ture field. The thermocouple artifact was simplyremoved from the porcine tissue data by subtract-ing the exponential term of the fitted curve fromthe measured data. This correction is possibleonly if the time constant of the exponential termis much smaller than the thermal relaxation timeof the tissue. Additionally, the temperature in-crease due to light absorption by the thermo-couple probes can be fit accurately only if the tem-perature is measured at a rate sufficiently high toprovide enough data points to characterize the ex-ponential rise. In porcine tissue, having time con-stants ranging from 1.2–3.0 s, the temperaturemust be measured at least every 0.5 s. However,even with slower data acquisition rates, the re-corded data still can be corrected for times largerthan 4.6 times the time constant (time to reach99% of the asymptotic value of the exponentialfunction), by taking the intercept on the ordinateaxis of the linear part of the temperature curve.The temperature at the ordinate intercept corre-sponds to the asymptotic value of the exponentialfunction, A, which is the thermocouple artifact.

An alternate analysis of the observed tem-perature decrease immediately after the laser isturned off should also provide a means of account-ing for the thermocouple artifact discussed here.Further analysis of the laser-induced tempera-ture rise in our tissue model will be the subject ofadditional publications.

Other Possible Artifacts Due to Presence ofThermocouple Probes

Typically, thermocouple probes are only par-tially immersed in the test medium for tempera-ture measurements, leaving the proximal end andthe shaft of the stainless steel probes exposed toair at room temperature. Because of their highthermal conductivity, the thermocouple probesact as heat sinks, and a temperature gradient is

thus formed along the probes and in the sur-rounding tissue when thermal equilibrium isreached in the absence of laser radiation. Heatingof the thermocouple probes by direct light absorp-tion induces an additional temperature gradientin the medium nearby the thermocouple probe.For these reasons, the temperatures obtained af-ter removal of the artifact due to direct light ab-sorption by the thermocouples may still not be thetrue tissue temperatures. Ideally, the tissue tem-perature can be measured without artifact only ifthe thermocouple probes have the same thermaland optical properties as the surrounding me-dium [31].

The temperature gradients induced by thepresence of the thermocouples may be a signifi-cant source of measurement error in the absoluterecorded temperature, T(r,t), but most likely notin the relative temperature increase, DT(r,t). Ac-cording to the simple model of Eq. (2), when theirradiation time is much shorter than the thermalrelaxation time of the tissue, the temperature in-crease due to light absorption in the tissue is in-dependent of the initial temperature distribution.In other words, the temperature gradient causedby each thermocouple probe after it reaches ther-mal equilibrium does not substantially affect thesubsequent change in tissue temperature due tolight absorption in the tissue. It is only when heatdiffusion becomes significant, i.e., when the irra-diation time is on the order of the thermal relax-ation time, that the temperature gradients due tothe thermocouples also may induce a significanterror in the calculated temperature increases. Fi-nally, it may be noted that the absorption proper-ties of the thermocouples may themselves be afunction of the laser irradiation wavelength, sothat the magnitude of any thermocouple errormay change with the use of different laser radia-tion sources.

CONCLUSIONS

Our experiments demonstrate that absorp-tion of laser radiation by stainless steel thermo-couple probes may induce a significant overesti-mation of the temperature measured during laserirradiation of tissue. When the time constant ofthe thermocouple effect is much smaller than thethermal relaxation time of the surrounding tis-sue, the artifact can be clearly and accuratelyquantified and if need be, corrected for. In LITT,where differences of a few degrees in temperatureare significant to the desired therapeutic out-

Thermocouple Probes During LITT 101

come, correction of experimentally recorded ther-mocouple measurements is necessary in order tobe able to predict the treatment effect and accu-rately to model experimentally recorded tempera-ture fields.

ACKNOWLEDGMENTS

We thank Dornier USA for the loan of theNd:YAG laser.

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