A Hydrophobic Gel Phantom for Study ofThermochemical Ablation: Initial Results Usinga Weak Acid and Weak BaseAndrew J. Misselt, MD, Theresa L. Edelman, BS, Jeung H. Choi, PhD, John C. Bischof, PhD, and

Erik N.K. Cressman, PhD, MD

PURPOSE: To develop a model for study of exothermic chemical reactions potentially useful for tissue ablation.

MATERIALS AND METHODS: Seven gelatins ranging from 0.5% to 30% wt/vol with and without 15% or 30% capsand several commercial gels were evaluated. Baseline temperature measurements were taken. Acetic acid andammonium hydroxide were sequentially injected over periods of 10–15 seconds in 1-mL aliquots, forming a discreteaqueous reaction chamber. Congo red pH indicator was included to assess the reaction. A thermocouple allowed datacollection at completion of injection and every 15 seconds for 5 minutes. Injections were performed in triplicate, andaverage temperatures for each time point were reported.

RESULTS: Gelatins fractured or refluxed even at the lowest concentrations tested. Most commercial gels proved tooviscous and likewise led to reflux along the needle tract. A mineral oil–based gel was selected because of its abilityto form a chamber without reflux or fracture and its clear colorless character, hydrophobic nature, chemical stability,viscosity, specific gravity, and cost. Temperatures during the first 60 seconds of the neutralization reaction showed animmediate increase that correlated well with concentration.

CONCLUSIONS: The oil gel phantom is a safe, useful, readily available, inexpensive model to study mixingbehaviors and maximum heating potentials for reactions that may prove useful in thermochemical tissue ablation foroncologic interventions. Measurable temperature changes occurred even at the lowest concentrations, and higherconcentrations produced a greater release of heat energy.

J Vasc Interv Radiol 2009; 20:1352–1358

INTERSTITIAL or intraparenchymalinjection of chemotherapy solutions(1,2) or ablative agents (3) have beeninvestigated by researchers in manyspecialties (4,5) over many years, butsuccess has been somewhat elusive.The potential for high local concentra-

From the Departments of Radiology (A.J.M., T.L.E.,E.N.K.C.) and Mechanical Engineering (J.H.C.,J.C.B.), University of Minnesota Medical Center,MMC 292, 420 Delaware Street Southeast, Minneap-olis, MN 55455. Received October 31, 2008; finalrevision received June 16, 2009; accepted June 29,2009. Address correspondence to E.N.K.C.; E-mail:cress013@umn.edu

From the SIR 2007 Annual Meeting.

None of the authors have identified a conflict ofinterest.

© SIR, 2009

DOI: 10.1016/j.jvir.2009.06.027

1352

tion of a given agent with very littlesystemic exposure nevertheless con-tinues to make such methods attrac-tive (6,7). This is particularly true incases in which, despite the systemicnature of most cancers, a localized tu-mor burden is a significant factor in apatient’s symptoms and/or prognosis.Surgical resection is useful, but inmany instances patients are not suit-able operative candidates. In general,there has been more success with non-specific chemical ablation agents suchas acetic acid or ethanol than with spe-cific drugs dissolved in a vehicle orcarrier. This may be a reflection of thedifficulty in obtaining even distribu-tion within tissues and also the thera-peutic index for the drug being con-sidered. Thermal therapies for tissue

destruction have also become popular,

and data are now accruing to showsurvival benefits in some cases (8).Thermal therapies generally have theadvantage that the shape of a coagu-lation zone is larger and more predict-able in the vast majority of cases (con-duction of heat through tissues vsconvection via hydrostatic interstitialpressure), but they are more suscepti-ble to heat-sink effects leading to inad-equate treatment near larger bloodvessels and the equipment is costly.

Exothermic chemical reactions mightoffer a new source of heat energy thatcould augment a chemical ablation. Thisconcept was first reported by Cressmanet al (9) and subsequently by others(10,11). The effect of a hostile environ-ment from the dual components of fluidconvection in tissues and conduction of

heat through tissues might provide ad-

etic

22.4

Misselt et al • 1353Volume 20 Number 10

vantages over existing methods. An in-jected solution distributed through thetissues via convection (12) could becombined with the more predictablethermal injury from conduction as heatfrom an exothermic reaction is released.This might offer a new way to destroytissue that is more controlled than injec-tion alone and could be seen as a crossbetween methods such as ethanol injec-tion (13) and boiling saline solution (14),for example. One simple example ofexothermic chemistry is the neutraliza-tion reaction between an acid and abase, in which the products are heat, asalt, and water. It was desirable to beginthe investigations with a familiar mate-rial already in use for tumor ablationsuch as acetic acid and to combine itwith a relatively safe counterpart, am-monium hydroxide (Fig 1).

To study this area in a detailed andsystematic way, there was a need for asuitable phantom for injectable thera-pies undergoing a chemical reaction insitu. Such a phantom would need to bemore than a simple open calorimeter forreasons discussed later. Inspection ofthe literature showed numerous phan-toms optimized for various purposes,including thermosensitive phantoms(15,16), water mimics for dosimetry (17),and some for intraparenchymal injec-tion (18,19) or ablation in renal (20) orhepatic tissues (21). Among intraparen-chymal phantoms, injection rates ordersof magnitude too slow (on the order ofmicroliters per minute) are clearly not ina useful range for clinical practice out-side the calvarium because of the size oftumor to treat, the time frame required,and respiratory and cardiac motion. Inthe end, none of the reported phantomswere suitable for the task at hand. Giventhese issues, an investigation was begunto interrogate a number of materials andidentify those that might be suitable forthe current purpose.

MATERIALS AND METHODS

University policy did not require in-stitutional review board approval forthis in vitro study. Baby oil gel, hairstyling gel, and mineral oil (ie, baby oil)were purchased at a large retail discountstore and used as supplied. Hydroge-nated polyisobutene gels (Versagel ME500, ME 750, and ME 1600; Penreco,Dickinson, Texas) and silicone viscositystandards (Brookfield Engineering Lab-

oratories, Middleboro, Massachusetts)

were donated samples from the variousmanufacturers and used as supplied.Ultrasound transmission gel (Aqua-sonic 100; Parker Laboratories, Fairfield,New Jersey) was used as supplied. Ace-tic acid, NH4OH, and congo red pH in-dicator (Thermo Fisher Scientific; Wal-tham, Massachusetts) were purchasedand used as supplied. A series of sevendifferent gelatins ranging from 0.5% to30% wt/vol with and without 15% or30% gelatin caps were prepared andcast into small test tubes and allowed toset. The caps were intended to functionas thin, superficial, but very cohesiveseals to prevent reflux along the needletract. In the cases in which caps werepoured, the deep layer was refrigeratedbefore the cap was poured. This wasdone to prevent the second layer frommelting the first during the secondpouring, which could create an uneveninterface. The commercially availablegel products were warmed if necessaryto decrease their viscosity and facilitatepouring into small test tubes or T25flasks. After transfer, materials were al-lowed to cool and equilibrate at roomtemperature, after which baseline tem-perature measurements were taken. Athermocouple probe (type T MT-29/1;Physitemp Instruments, Clifton, NewJersey) was positioned within the

CH3CO2H + NH4OH Figure 1. Exothermic neutralization of ac

Figure 2. Baby oil gel is in a T25 flask ansolution and congo red indicator (blue at ato syringe containing NH4OH solution is asystem as indicated by the thermocouple (

phantom at the point of injection to

collect temperature data over timefrom the moment of completion ofthe injection and every 15 secondsfor 5 minutes (Fig 2) with a T-typethermocouple thermometer (Digi-Sense; Cole-Parmer, Vernon Hills, Il-linois). Equimolar amounts of aceticacid and ammonium hydroxide atfour different concentrations (1, 5,10, and 15 M) were sequentiallyhand-injected over a period of 10 –15seconds in 1-mL aliquots to permitformation of a discrete aqueous reac-tion chamber (Fig 3). The pH indica-tor, congo red, was included in theacid solution before use to assess theextent of the neutralization reactionand completeness of mixing (Fig 4).Injections were performed in tripli-cate, and average temperatures foreach time point were reported.

RESULTS

Visual assessments of materials weremade and are reported in Table 1. Vis-cosity and cohesiveness in varioustested materials proved to be a prob-lem. With gelatins, fracturing occurredduring injection of the solutions with-out exception. This led to cleavageplanes and irregular distribution ofthe injected solutions within the phan-

Heat + NH4Cl + H2O acid with NH4OH.

a ring stand holds a syringe of acetic acidic pH). Thermocouple with probe attachedcent. Note the starting temperature of the°C).

dciddja

tom. Without a contained volume, dis-

1354 • Thermochemical Ablation in Hydrophobic Gel Phantom: Initial Results October 2009 JVIR

tribution and rapid and adequate mix-ing within the gelatin in the desiredmanner could not occur. To address

Figure 3. Injection of acetic acid solutiocongo red pH indicator. Note the roundedcontained within the gel model, facilitatingsolution within the hydrophobic gel.

Table 1Results of Initial Injections to Assess M

Material Con

Gelatin 0.5%0.5%0.5%

1%1%1%2%2%2%5%5%5%

10%10%10%15%15%30%

Versagel MEMEME

Mineral oil 100%Silicone viscosity standard 1 As sSilicone viscosity standard 2 As sBaby oil gel As sUltrasound gel As sHair styling gel As s

fracturing, the concentration of the

gelatin was increased, but this did notimprove the results. In addition tofracture, at the higher gelatin concen-

colored blue by theape of the solution

ixing of the aqueous

Figure 4. ContainedNote the clear NH4Owith the previouslyNote the color changneutralization reactio

rials

tration/Product No. Reflux

t/vol Not/vol; 15% cap Not/vol; 30% cap Not/vol Not/vol; 15% cap Not/vol; 30% cap Not/vol Yest/vol; 15% cap Yest/vol; 30% cap Yest/vol Yest/vol; 15% cap Yest/vol; 30% cap Yest/vol Yest/vol; 15% cap Yest/vol; 30% cap Yest/vol Yest/vol; 30% cap Yes

YesNoNo

0 YesNo

plied Noplied Noplied Noplied Noplied No

trations, an additional problem was

identified: the injected reagents re-fluxed along the needle tract and ex-ited at the surface of the gel, making

utralization reaction within the gel model.solution in the syringe, which has reactedpensed (blue-colored) acetic acid solution.the congo red indicator demonstrating the

racture Appearance

Yes Clear/colorlessYes Clear/colorlessYes Clear/colorlessYes Clear/colorlessYes Clear/colorlessYes Clear/colorlessYes Clear/colorlessYes Clear/colorlessYes Clear/colorlessYes Clear/tingedYes Clear/tingedYes Clear/tingedYes Clear/tingedYes Clear/tingedYes Clear/tingedYes Clear/yellowYes Clear/yellowYes Clear/yellowNo Clear/colorlessNo Clear/colorlessYes Clear/colorlessNo Clear/colorlessNo Clear/colorlessNo Clear/colorlessNo ClearYes Clear/blueNo Clear/colorless, became

hazy, hydrolyzed onexposure to acid

n,sh

m

ate

neH

dise ofn.

cen F

wwwwwwwwwwwwwwwww

500750160

upupupupup

accurate measurements from adequate

Misselt et al • 1355Volume 20 Number 10

mixing all but impossible. Making gelsof a lower concentration with a layerof gelatin cast at a much higher con-

Table 2Thermal Profile of Neutralization of 1 MEach) over a Period of 5 Minutes

Time (h:min)

Temperature (

Run 1 Run 2

0:00 23.3 23.20:15 30.2 29.50:30 29.6 29.30:45 29.2 28.91:00 28.9 28.61:15 28.7 28.31:30 28.5 28.01:45 28.3 27.82:00 28.1 27.52:15 27.9 27.32:30 27.7 27.12:45 27.6 27.03:00 27.5 26.83:15 27.3 26.73:30 27.2 26.53:45 27.1 26.44:00 26.9 26.34:15 26.8 26.24:30 26.7 26.14:45 26.6 26.05:00 26.6 25.9

Table 3Thermal Profile of Neutralization of 5 MEach) over a Period of 5 Minutes

Time (h:min)

Temperature (

Run 1 Run 2

0:00 23.2 22.80:15 49.3 48.90:30 48.2 48.50:45 46.5 46.71:00 45.5 45.21:15 44.1 43.91:30 43.2 42.91:45 42.3 41.92:00 41.4 41.12:15 40.6 40.32:30 39.8 39.62:45 39.3 39.03:00 38.6 38.43:15 38.3 37.93:30 37.8 37.43:45 37.4 36.94:00 37.0 36.54:15 36.6 36.04:30 36.1 35.74:45 35.6 35.35:00 35.3 34.9

centration as a cap or skin to prevent

reflux along the needle tract was suc-cessful to a certain extent, but in gen-eral, reflux occurred to the level of

cetic Acid and 1 M NH4OH (1 mL

Average Temperature (°C)Run 3

23.0 23.229.6 29.829.1 29.328.7 28.928.4 28.628.1 28.427.9 28.127.6 27.927.3 27.627.2 27.527.0 27.326.8 27.126.6 27.026.5 26.826.4 26.726.3 26.626.2 26.526.1 26.426.0 26.325.9 26.225.8 26.1

cetic Acid and 5 M NH4OH (1 mL

Average Temperature (°C)Run 3

22.7 22.936.5 44.937.1 44.636.7 43.335.4 42.033.9 40.633.2 39.832.5 38.932.0 38.231.4 37.431.3 36.931.2 36.531.0 36.030.7 35.630.7 35.330.6 35.030.8 34.830.4 34.330.2 34.030.0 33.629.9 33.4

the cap layer and then dissection oc-

curred, separating the layers. As a lasteffort with gelatin, the concentrationof gelatin was decreased to 0.5%, butfracture still resulted instead of disper-sion. Several alternate materials werethen evaluated, including an ultra-sound transmission gel, commercialcolorless viscosity standards, mineraloil, hydrocarbon gels used in pharma-ceutical and personal care product for-mulations (ie, Versagel; Penreco), ahair styling gel, and a baby oil gel.Baby oil gel had a tendency to trap airbubbles, which, in several instances, ob-scured visualization of the reactions.However, of all the materials examined,it proved most satisfactory, and furtherexperimentation was done with thismodel. Other materials that did not re-flux or fracture were deemed unsuitableas they were of inadequate viscosity andwere too prone to settling of the reagentsolutions to the bottom of the contain-ers.

Tables 2–5 show temperature dataover time for each tested concentrationof acid and base. These data are sum-marized and compared in Fig 5, whichsuperimposes the time and temperaturedata for all four concentrations tested.Temperatures during the first 60 secondsof the neutralization reaction showed animmediate increase that correlated wellwith concentration.

DISCUSSION

Gelatin initially seemed the obvi-ous first choice rather than alginate,agar, or acrylamide gels simply basedon cost, safety, and availability. How-ever, there were difficulties with ob-taining satisfactory measurements asnoted earlier. This exercise led to sep-aration of questions involving distri-bution from questions about thermo-dynamics. The decision was thereforemade to focus first solely on the ener-getics of the reactions. It is worth not-ing at this point that it was anticipatedthat the vast majority of the reactionswould be carried out in aqueous solu-tion. Therefore, hydrophobic materialswere interrogated with the reasoningthat, as oil tends to form droplets inwater, a similar effect might result increation of the desired expandable butvisible reaction chamber. What wasneeded, then, was a medium that wasthin enough in viscosity to allow aninjection to create a focal reaction

A

°C)

A

°C)

chamber but not so thin as to allow

1356 • Thermochemical Ablation in Hydrophobic Gel Phantom: Initial Results October 2009 JVIR

any differences in density between thereagent solutions and the phantom tobecome manifest. This is an issue be-

Table 4Thermal Profile of Neutralization of 10Each) over 5 Minutes

Time (h:min)

Temperature (

Run 1 Run 2

0:00 23.3 23.10:15 88.6 79.80:30 84.1 77.70:45 78.7 74.91:00 75.0 72.61:15 71.9 70.11:30 68.5 67.91:45 66.6 65.82:00 64.7 64.02:15 63.0 62.32:30 61.4 60.82:45 60.0 59.53:00 58.6 58.13:15 57.4 56.93:30 56.2 55.83:45 55.3 54.74:00 54.3 53.74:15 53.3 52.84:30 52.4 51.94:45 51.5 51.05:00 50.7 50.2

Table 5Thermal Profile of Neutralization of 15Each) over a Period of 5 Minutes

Time (h:min)

Temperature (

Run 1 Run 2

0:00 23.8 23.00:15 101.3 80.60:30 91.2 78.70:45 85.6 77.31:00 81.1 76.81:15 75.3 73.71:30 70.7 71.41:45 68.6 69.32:00 66.5 67.32:15 63.2 65.52:30 61.1 63.72:45 60.0 62.03:00 58.2 60.63:15 56.6 59.23:30 55.0 57.83:45 53.7 56.64:00 52.7 55.54:15 51.5 54.64:30 50.4 53.34:45 49.4 52.35:00 48.5 51.4

cause hydrocarbons, which typically

have a density lower than water,would not support an aqueous solu-tion. Rather, the aqueous injections

Acetic Acid and 10 M NH4OH (1 mL

Average Temperature (°C)Run 3

22.8 23.184.6 84.379.5 80.474.2 75.970.7 72.868.0 70.065.4 67.363.3 65.262.0 63.660.4 61.959.0 60.457.8 59.156.6 57.855.7 56.754.6 55.554.3 54.853.6 53.952.8 53.052.0 52.151.3 51.350.6 50.5

Acetic Acid and 15 M NH4OH (1 mL

Average Temperature (°C)Run 1

23.0 23.3105.9 95.9

95.0 88.386.1 83.079.8 79.275.8 74.972.7 71.669.9 69.366.8 66.963.9 64.263.0 62.661.4 61.160.4 59.759.4 58.458.2 57.057.2 55.855.6 54.653.8 53.352.9 52.252.0 51.251.2 50.4

would simply flow to the bottom of a

container and away from a thermo-couple. This problem would be exag-gerated when higher concentrations ofreactants were studied because thesalts formed would significantly in-crease solution density while, at thesame time, the warmer environmentwould inherently decrease viscosity ofthe phantom medium. At the oppositeextreme, a very dense hydrocarbonmedium would likely cause a reactionmixture to rise to the top of the cham-ber, resulting in an uncontrolled re-lease of reactants and loss of data. Anideal setup, when identified, couldthen be used to gather temperaturedata from exothermic reactions, essen-tially as a hybrid between an open and“bomb-type” calorimeter.

A summary of the development ofa new phantom and the requirementsand reasoning are listed in Table 6. Anideal tissue phantom for better distri-bution studies would embody manyof these characteristics with some ex-ceptions. For instance, the hydropho-bic nature of the current gel phantomand the viscosity would be actually beantagonistic. An ideal tissue phantommight have a hydraulic conductivityor intrinsic permeability and elasticitycloser to the target tissue, such as cir-rhotic liver and/or tumor.

When a suitable phantom was iden-tified, the data shown were obtained.Measurable temperature changes oc-curred even at the lowest concentra-tions, and higher concentrations pro-duced a greater release of heat energy.Indeed, the reaction of 1-mL aliquotsof 15 M acetic acid and NH4OH withinthe gel model proved quite vigorous,demonstrating potential for creating azone of tissue coagulation based ontemperature alone. The peak tempera-ture in two of three trials was morethan 100°C and the average was 95°C.After only a 15-second input of chem-ical energy, a temperature still in ex-cess of 50°C was observed at the endof the 5-minute data collection period.

Incomplete mixing would be ex-pected to cause inaccurate data, hencethe need for a means of visualizationwith a pH indicator. Congo red wasspecifically chosen because of its rangeof transition (pH 3–5) and its distinctcolor change, although other indica-tors such as litmus could also be used.The congo red pH indicator is blue insolutions with a pH lower than 3 and

M

°C)

M

°C)

red in solutions with a pH greater than

an

Misselt et al • 1357Volume 20 Number 10

5, making it straightforward to deter-mine when all the acid had reacted inthe solution. In general, with aceticacid and NH4OH, mixing occurredreadily and the indicator was easilyseen. The only issue identified was atthe higher temperatures, at which vig-orous reaction may have had an ad-verse effect as a result of disruption of

Time 0

0:15

0:30

0:45

1:00

1:15

1:30

1:45

2:00

2:15

2:30

2:45

10

20

30

40

50

60

70

80

90

100

Tem

pera

ture

(Þ

C)

Time

AcO

Figure 5. Graphical summation of the thfour tested concentrations of the reaction btemperatures are reached at 10-M (88.6°C)

Table 6Desired Properties and Rationale for Inj

Characteristic Selection

Clarity TransparentColor ClearViscosity Medium

Density Matched or lowerthan reactionsolutions

Toxicity None

Cost LowMiscibility Hydrophobic

Chemical stability Nonreactive

Volatility Very low volatility/high flashpoint

the in situ reaction chamber.

Several other observations can bemade. Hyperthermia and cryoablationcould be viewed for the purpose ofthis discussion as therapies with fa-vorable therapeutic indices based onhigh local toxicity and low systemictoxicity. This is a result of the con-tained distribution of the input vari-able or treatment. Survival of the

3:15

3:30

3:45

4:00

4:15

4:30

4:45

5:00

1

5

10

15

Molarity

nd NH4OH

al neutralization profiles (averages) of alleen acetic acid and NH4OH. Tumoricidal

d 15-M (101.3°C) concentrations.

ion Phantom

Rationale

Visibility in containerAllows use of pH indicatorsLow- or high-viscosity fluids would

not form a satisfactory reactionchamber

Ensures that reaction solutions remainin phantom

Exposure to personnel, disposal issuesafter assays

High throughput likelyReaction solutions aqueous and could

mix with hydrophilic mediaMany materials hydrolyze or become

opaque; potential for reprocessingand reuse

Anticipated temperatures couldpotentially cause evaporation oreven ignition of volatile materials

whole organism is indeed in jeopardy

if, in the case of hyperthermia, the sys-temic thermal dose is sufficient to in-crease the body temperature greaterthan a relatively low threshold. Fortu-nately, this does not occur in clinicalapplications. Temperatures for 10 Mand 15 M concentrations were greaterthan the tumoricidal range, even ifonly hyperthermic effects are invoked.

With chemical ablation, the natureof the injected material and the poten-tial for systemic exposure from intra-vascular access is inherently greaterand therefore must be taken into ac-count. The salt product in the presentcase is NH4Cl, which is a relativelybenign product if this type of reactionwere to see eventual use in mammalsand some portion were to result insystemic exposure. In fact, NH4Cl isused clinically as an acidifying agentin some conditions and is metabolizedto urea for eventual excretion by thekidneys. In addition, the byproductsof many reactions would ensure thatthe local environment would be ordersof magnitude greater in osmolaritythan the physiologic range of 270–300mOsm for an indeterminate length oftime. The local hyperosmolarity makesthis strategy even more appealing froma local cytotoxicity standpoint. This re-sidual toxicity might be of benefit indecreasing local recurrence from dor-mant or “hibernating” tumor cells.

These initial experiments were per-formed with use of a weak acid and aweak base. It is known that, for anygiven concentration of acid and base,the actual amount of energy releasedduring neutralization depends on thestrength of each of the reactants. In thecase of a weak acid and weak basepairing, the expected amount of en-ergy is approximately 30 kJ/mol. Moreheat should be released with the use of astrong acid and base (approximately 55kJ/mol) as such reagents are alreadyfully ionized and therefore no energy islost for ionization before reaction.

Further investigation with the gelmodel will involve reactions with strongacids, strong bases, various combina-tions, and other exothermic reactionsbeyond neutralization. Other avenues ofinvestigation might involve variationsin the injection technique such as con-comitant rather than sequential injec-tions or the use of alternating fraction-ated boluses of each reagent. Suchtechniques may offer better reaction

3:00

H a

ermetw

ect

control with an even greater exotherm

1358 • Thermochemical Ablation in Hydrophobic Gel Phantom: Initial Results October 2009 JVIR

and potential for tissue ablation. In sum-mary, the oil gel phantom is a useful,readily available, inexpensive model tostudy mixing behaviors and calorimetry(ie, maximum heating potentials) forexothermic reactions. Further studywith the gel model and the exothermicpotential of neutralization reactions willbe reported in due course.

References1. Emerich DF, Snodgrass P, Lafreniere

D, et al. Sustained release chemother-apeutic microspheres provide superiorefficacy over systemic therapy and lo-cal bolus infusions. Pharm Res 2002;19:1052–1060.

2. Caton T, Thibeault SL, Klemuk S, et al.Viscoelasticity of hyaluronan and non-hyaluronan based vocal fold injectables:implications for mucosal versus muscleuse. Laryngoscope 2007; 117:516–521.

3. Clark TWI. Chemical ablation of livercancer. Tech Vasc Interv Radiol 2007; 10:58–63.

4. Vogl TJ, Engelmann K, Mack MG, et al.CT-guided intratumoural administrationof cisplatin/epinephrine gel for treatmentof malignant liver tumours. Br J Cancer2002; 86:524–529.

5. Celikoglu F, Celikoglu SI, Goldberg EP.Bronchoscopic intratumoral chemother-apy of lung cancer. Lung Cancer 2008;61:1–12.

6. Plante MK, Gross AL, Kliment J, Kida M,

Zvara P. Intraprostatic ethanol chemoa-

blation via transurethral and transperinealinjection. BJU Int 2003; 91:94–98.

7. Chowning SL, Susil RC, Krieger A, Fich-tinger G, Whitcomb LL, Atalar E. Apreliminary analysis and model of pros-tate injection distributions. Prostate 2006;66:344–357.

8. Lencioni R, Crocetti L. Image-guidedthermal ablation of hepatocellular carci-noma. Crit Rev Oncol Hematol 2008; 66:200–207.

9. Cressman ENK, Misselt AJ, Brix TL,Choi JH, Bischof JC. A new hydropho-bic gel phantom for study of thermo-chemical ablation: initial results using aweak acid and weak base (abstr.). J VascInterv Radiol 2007; 18(suppl 1):S154.

10. Deng Z, Liu J. Minimally invasive ther-motherapy method for tumor treatmentbased on an exothermic chemical reac-tion. Minim Invas Ther Allied Technol2007; 16:341–346.

11. Rao W, Liu J. Tumor thermal ablationtherapy using alkali metals as powerfulself-heating seeds. Minim Invas Ther2008; 17:43–49.

12. Zhang XY, Luck J, Dewhirst MW, YuanF. Interstitial hydraulic conductivity ina fibrosarcoma. Am J Physiol Heart CircPhysiol 2000; 279:H2726–H2734.

13. Huang GT, Lee PH, Tsang YM, et al.Percutaneous ethanol injection versussurgical resection for the treatment ofsmall hepatocellular carcinoma a pro-spective study. Ann Surg 2005; 242:36 – 42.

14. Honda N, Guo Q, Uchida H, Ohishi H,

Hiasa Y. Percutaneous hot saline injec-

tion therapy for hepatic tumors: analternative to percutaneous ethanolinjection therapy. Radiology 1994;190:53–57.

15. Kuroda M, Kato H, Hanamoto K, et al.Development of a new hybrid gel phan-tom using carrageenan and Gellan gumfor visualizing three-dimensional tem-perature distribution during hyperther-mia and radiofrequency ablation. Int JOncol 2005; 27:175–184.

16. Lafon C, Zderic V, Noble M, et al. Gelphantom for use in high-intensity fo-cused ultrasound dosimetry. UltrasoundMed Biol 2005; 31:1383–1389.

17. Homolka P, Gahleitner A, Nowotny R.Temperature dependence of HU valuesfor various water equivalent phantommaterials. Phys Med Biol 2002; 47:2917–2923.

18. Chen Z, Gillies G, Broaddus W, et al. Arealistic brain tissue phantom for intra-parenchymal infusion studies. J Neuro-surg 2004; 101:314–322.

19. Wientjes MG, Zheng JH, Hu L, Gan Y,Au JL. Intraprostatic chemotherapy:distribution and transport mechanisms.Clin Cancer Res 2005; 11:4204–4211.

20. Taylor GD, Johnson DB, Hogg DC, Cad-eddu JA. Development of a renal tu-mor mimic model for learning mini-mally invasive nephron sparing surgicaltechniques. J Urol 2004; 172:382–385.

21. Scott DJ, Young WN, Watumull LM, et al.Development of an in vivo tumor-mimicmodel for learning radiofrequency abla-

tion. J Gastrointest Surg 2000; 4:620–625.