Accurate simulation of temperature distribution in tumors induced by gold nanorods during laser photothermal therapy relies on precise measurements of thermal, optical, and physiological properties of the tumor with or without nanorods present. In this study, a computational Monte Carlo simulation algorithm is developed to simulate photon propagation in a spherical tumor to calculate laser energy absorption in the tumor and examine the effects of the absorption (μa) and scattering (μs) coefficients of tumors on the generated heating pattern in the tumor. The laser-generated energy deposition distribution is then incorporated into a 3D finite-element model of prostatic tumors embedded in a mouse body to simulate temperature elevations during laser photothermal therapy using gold nanorods. The simulated temperature elevations are compared with measured temperatures in PC3 prostatic tumors in our previous in vivo experimental studies to extract the optical properties of PC3 tumors containing different concentrations of gold nanorods. It has been shown that the total laser energy deposited in the tumor is dominated by μa, while both μa and μs shift the distribution of the energy deposition in the tumor. Three sets of μa and μs are extracted, representing the corresponding optical properties of PC3 tumors containing different concentrations of nanorods to laser irradiance at 808 nm wavelength. With the injection of 0.1 cc of a 250 optical density (OD) nanorod solution, the total laser energy absorption rate is increased by 30% from the case of injecting 0.1 cc of a 50 OD nanorod solution, and by 125% from the control case without nanorod injection. Based on the simulated temperature elevations in the tumor, it is likely that after heating for 15 min, permanent thermal damage occurs in the tumor injected with the 250 OD nanorod solution, while thermal damage to the control tumor and the one injected with the 50 OD nanorod solution may be incomplete.

References

References
1.
Bernardi
,
R. J.
,
Lowery
,
A. R.
,
Thompson
,
P. A.
,
Blaney
,
S. M.
, and
West
,
J. L.
,
2008
, “
Immunonanoshells for Targeted Photothermal Ablation in Medullo-Blastoma and Glioma: An In Vitro Evaluation Using Human Cell Lines
,”
J. Neuro-Oncol.
,
86
(
2
), pp.
165
172
.10.1007/s11060-007-9467-3
2.
Gobin
,
A. M.
,
Moon
,
J. J.
, and
West
,
J. L.
,
2008
, “
Ephrin Al-Targeted Nano-Shells for Photothermal Ablation of Prostate Cancer Cells
,”
Int. J. Nanomed.
,
3
(
3
), pp.
351
358
.
3.
Melancon
,
M. P.
,
Lu
,
W.
,
Yang
,
Z.
,
Zhang
,
R.
,
Cheng
,
Z.
,
Elliot
,
A. M.
,
Stafford
,
J.
,
Olson
,
T.
,
Zhang
,
J. Z.
, and
Li
,
C.
,
2008
, “
In Vitro and In Vivo Targeting of Hollow Gold Nanoshells Directed at Epidermal Growth Factor Receptor for Photothermal Ablation Therapy
,”
Mol. Cancer Ther.
,
7
(
6
), pp.
1730
1739
.10.1158/1535-7163.MCT-08-0016
4.
Loo
,
C. H.
,
Hirsch
,
L.
,
Lee
,
M. H.
,
Chang
,
E.
,
West
,
J.
,
Halas
,
N.
, and
Drezek
,
R.
,
2005
, “
Gold Nanoshell Bioconjugates for Molecular Imaging in Living Cells
,”
Opt. Lett.
,
30
, pp.
1012
1014
.10.1364/OL.30.001012
5.
Loo
,
C. L.
,
Lowery
,
A.
,
Halas
,
N.
,
West
,
J.
, and
Drezek
,
R.
,
2005
, “
Immunotargeted Nanoshells for Integrated Cancer Imaging and Therapy
,”
Nano Lett.
,
5
, pp.
709
711
.10.1021/nl050127s
6.
Lal
,
S.
,
Clare
,
S. E.
, and
Halas
,
N. J.
,
2008
, “
Nanoshell-Enabled Photothermal Cancer Therapy: Impending Clinical Impact
,”
Acc. Chem. Res.
,
41
(
12
), pp.
1842
1851
.10.1021/ar800150g
7.
Skrabalak
,
S. E.
,
Chen
,
J.
,
Lu
,
X.
,
Li
,
X.
, and
Xia
,
Y.
,
2007
, “
Gold Nanocages for Biomedical Applications
,”
Adv. Mater.
,
19
, pp.
3177
3184
.10.1002/adma.200701972
8.
Reidenbach
,
H.-D.
,
2007
, “
Laser Safety
,”
Springer Handbook of Laser and Optics
,
F.
Traeger
, ed.,
Springer
,
New York
.
9.
Mohammed
,
Y.
, and
Verhey
,
J. F.
,
2005
, “
A Finite Element Method Model to Simulate Laser Interstitial Thermo Therapy in Anatomical Inhomogenous Regions
,”
Biomed. Eng. Online
,
4
(
2
), pp.
10
45
.
10.
Welch
,
A. J.
, and
van Gemert
,
M. J. C.
,
1995
, “
Optical-Thermal Response of Laser-Irradiated Tissue
,”
A. J.
Welch
and
M. J. C.
van Gemert
, eds.,
Plenum Press
,
New York
.
11.
Engin
,
K.
,
1994
, “
Biological Rationale for Hyperthermia in Cancer Treatment (II)
,”
Neoplasma
,
41
(
5
), pp.
277
283
.
12.
Dewhirst
,
M. V.
,
Vujaskovic
,
Z.
,
Jones
,
E.
, and
Thrall
,
D.
,
2005
, “
Resetting the Biologic Rationale for Thermal Therapy
,”
Int. J. Hypotherm.
,
21
(
8
), pp.
779
790
.10.1080/02656730500271668
13.
El-Sayed
, I
. H.
,
Huang
,
X.
, and
El-Sayed
,
M. A.
,
2006
, “
Selective Laser Photo Thermal Therapy of Epithelial Carcinoma Using Anti-EGFR Antibody Conjugated Gold Nanoparticles
,”
Cancer Lett.
,
239
, pp.
129
135
.10.1016/j.canlet.2005.07.035
14.
O'Neal
,
D. P.
,
Hirsch
,
L. R.
,
Halas
,
N. J.
,
Payne
,
J. D.
, and
West
,
J. L.
,
2004
, “
Photo Thermal Tumor Ablation in Mice Using Near Infrared-Absorbing Nanoparticles
,”
Cancer Lett.
,
209
, pp.
171
176
.10.1016/j.canlet.2004.02.004
15.
Xie
,
H.
,
Gill-Sharp
,
K. L.
, and
O'Neal
,
D. P.
,
2007
, “
Quantitative Estimation of Gold Nanoshell Concentrations in Whole Blood Using Dynamic Light Scattering
,”
Nanomed Nanotech. Biol. Med.
,
3
, pp.
89
94
.10.1016/j.nano.2007.01.003
16.
Weissleder
,
R.
,
2001
, “
A Clearer Vision for In Vivo Imaging
,”
Nat. Biotechnol.
,
19
(
4
), pp.
316
317
.10.1038/86684
17.
Huang
,
X. W.
,
Jain
,
P. K.
,
El-Sayed
, I
. H.
, and
El-Sayed
,
M. A.
,
2008
, “
Plasmonic Photothermal Therapy (PPTT) Using Gold Nanoparticles
,”
Lasers Med. Sci.
,
23
, pp.
217
228
.10.1007/s10103-007-0470-x
18.
Ballou
,
B. L.
,
Lagerholm
,
C.
,
Ernst
,
L. A.
,
Bruchez
,
M. P.
, and
Waggoner
,
A. S.
,
2004
, “
Non-Invasive Imaging of Quantum Dots in Mice
,”
Bioconjug. Chem.
,
15
, pp.
79
86
.10.1021/bc034153y
19.
Choi
,
M. R.
,
Stanton-Maxey
,
K. J.
,
Stanley
,
J. K.
,
Levin
,
C. S.
,
Bardhan
,
R.
,
Akin
,
D.
,
Badve
,
S.
,
Sturgis
,
J.
,
Robinson
,
J. P.
,
Bashir
,
R.
,
Halas
,
N. J.
, and
Clare
,
S. E.
,
2007
, “
A Cellular Trojan Horse for Delivery of Therapeutic Nanoparticles into Tumors
,”
Nano Lett.
,
7
, pp.
3759
3765
.10.1021/nl072209h
20.
Khlebtsov
,
B. N.
,
Zharov
, V
.
,
Melnikov
,
A.
,
Tuchin
,
V.
, and
Khlebtsov
,
N.
,
2006
, “
Optical Amplification of Photothermal Therapy With Gold Nanoparticles and Nanoclusters
,”
Nanotechnology
,
17
, pp.
5167
5179
.10.1088/0957-4484/17/20/022
21.
Stern
,
J. M.
,
Stanfield
,
J.
,
Kabbani
,
W.
,
Hsieh
,
J. T.
, and
Cadeddu
,
J. A.
,
2008
, “
Selective Prostate Cancer Thermal Ablation With Laser Activated Gold Nano-Shells
,”
J. Urol.
,
179
, pp.
748
753
.10.1016/j.juro.2007.09.018
22.
Krag
,
D. N.
,
Fuller
,
S. P.
,
Oligino
,
L.
,
Pero
,
S. C.
,
Weaver
,
D. L.
,
Soden
,
A. L.
,
Hebert
,
C.
,
Mills
,
S.
,
Liu
,
C.
, and
Peterson
,
D.
,
2002
, “
Phage-Displayed Random Peptide Libraries in Mice: Toxicity After Serial Panning
,”
Cancer Chemother. Pharmacol.
,
50
, pp.
325
332
.10.1007/s00280-002-0489-4
23.
Hirsch
,
L. R.
,
Stafford
,
R. J.
,
Bankson
,
J. A.
,
Sershen
,
S. R.
,
Rivera
,
B.
,
Price
,
R. E.
,
Hazle
,
J. D.
,
Halas
,
N. J.
, and
West
,
J. L.
,
2003
, “
Nanoshell-Mediated Near-Infrared Thermal Therapy of Tumors Under Magnetic Resonance Guidance
,”
Proc. Natl. Acad. Sci. USA
,
100
(
23
), pp.
13549
13554
.10.1073/pnas.2232479100
24.
Qin
,
Z.
, and
Bischof
,
J. C.
,
2010
, “
One-Dimensional Experimental Setup to Study the Heating of Nanoparticle Laden Systems
,”
Proceedings of the ASME Summer Bioengineering Engineering Conference
, Naples, FL, June 16–19, 2010, ASME Paper No. SBC2010-19676.
25.
Elliott
,
A. M.
,
Stafford
,
R. J.
,
Schwartz
,
J.
,
Wang
,
J.
,
Shetty
,
A. M.
,
Bourgoyne
,
C.
,
O'Neal
,
P.
, and
Hazle
,
J. D.
,
2007
, “
Laser-Induced Thermal Response and Characterization of Nanoparticles for Cancer Treatment Using Magnetic Resonance Thermal Imaging
,”
Med. Phys.
,
34
, pp.
3102
3108
.10.1118/1.2733801
26.
Anvari
,
B.
,
Rastegar
,
S.
, and
Motamedi
,
M.
,
1994
, “
Modeling of Intraluminal Heating of Biological Tissue: Implications for Treatment of Benign Prostatic Hyperplasia
,”
IEEE Trans. Biomed. Eng.
,
41
(
9
), pp.
854
864
.10.1109/10.312093
27.
Wang
,
L.
,
Jacques
,
S. L.
, and
Zheng
,
L.
,
1995
, “
MCML—Monte Carlo Modeling of Light Transport in Multi-Layered Tissues
,”
Comput. Meth. Prog. Biomed.
,
47
(
2
), pp.
131
146
.10.1016/0169-2607(95)01640-F
28.
Wilson
,
B. C.
, and
Adam
,
G.
,
1983
, “
A Monte Carlo Model for the Absorption and Flux Distributions of Light in Tissue
,”
Med. Phys.
,
10
(
6
), pp.
824
830
.10.1118/1.595361
29.
Prahl
,
S. A.
,
Keijzer
,
M.
,
Jacques
,
S. L.
, and
Welch
,
A. J.
,
1989
, “
A Monte Carlo Model of Light Propagation in Tissue
,”
SPIE Proc. Dosim. Laser Rad. Med. Biol.
,
5
, pp.
102
111
.
30.
Flock
,
S. W.
,
Wilson
,
B. C.
, and
Patterson
,
M. S.
,
1989
, “
Monte Carlo Modeling of Light Propagation in Highly Scattering Tissues-II: Comparison With Measurements in Phantoms
,”
IEEE Trans. Biomed. Eng.
,
36
(
12
), pp.
1169
1173
.10.1109/10.42107
31.
Keijzer
,
M.
,
Pickering
,
J. W.
, and
van Gemert
,
M. J. C.
,
1991
, “
Laser Beam Diameter for Port Wine Stain Treatment Lasers
,”
Laser. Surg. Med.
,
11
, pp.
601
605
.10.1002/lsm.1900110616
32.
Keijzer
,
M.
,
Jacques
,
S. L.
,
Prahl
,
S. A.
, and
Welch
,
A. J.
,
1989
, “
Light Distributions in Artery Tissue: Monte Carlo Simulations for Finite-Diameter Laser Beams
,”
Laser. Surg. Med.
,
9
, pp.
148
154
.10.1002/lsm.1900090210
33.
Jacques
,
S.
,
1989
, “
Time-Resolved Propagation of Ultra-Short Laser Pulses Within Turbid Tissues
,”
Appl. Opt.
,
28
, pp.
2223
2229
.10.1364/AO.28.002223
34.
Jacques
,
S.
,
1989
, “
Time-Resolved Reflectance Spectroscopy in Turbid Tissues
,”
IEEE Trans. Biomed. Eng.
,
36
, pp.
1155
1161
.10.1109/10.42109
35.
Wang
,
L.
, and
Jacques
,
S. L.
,
1993
, “
Hybrid Model of Monte Carlo Simulation and Diffusion Theory for Light Reflectance by Turbid Media
,”
J. Opt. Soc.
,
10
, pp.
1746
1752
.10.1364/JOSAA.10.001746
36.
Wang
,
L.
, and
Jacques
,
S. L.
,
1994
, “
Optimized Radial and Angular Positions in Monte Carlo Modeling
,”
Med. Phys.
,
21
, pp.
1081
1083
.10.1118/1.597351
37.
Wang
,
L.
,
Jacques
,
S. L.
, and
Zheng
,
L. Q.
,
1997
, “
CONV—Convolution for Responses to a Finite Diameter Photon Beam Incident on Multi-Layered Tissues
,”
Comput. Meth. Prog. Biomed.
,
54
, pp.
141
150
.10.1016/S0169-2607(97)00021-7
38.
Gardner
,
C. W.
, and
Welch
,
A. J.
,
1994
, “
Monte Carlo Simulation of Light Transport in Tissue: Unscattered Absorption Events
,”
Appl. Opt.
,
33
(
13
), pp.
2743
2745
.10.1364/AO.33.002743
39.
Feng
,
Y. F.
,
Fuentes
,
D.
,
Hawkins
,
A.
,
Bass
,
J.
,
Rylander
,
M. N.
,
Elliott
,
A.
,
Shetty
,
A.
,
Stafford
,
R. J.
, and
Oden
,
J. T.
,
2010
, “
Nanoshell-Mediated Laser Surgery Simulation for Prostate Cancer Treatment
,”
Eng. Comp.
,
25
(
1
), pp.
3
13
.10.1007/s00366-008-0109-y
40.
Gardner
,
C. M.
,
Jacques
,
S. L.
, and
Welch
A. J.
,
1996
, “
Light Transport in Tissue: Accurate Expressions for One-Dimensional Fluence Rate and Escape Function Based Upon Monte Carlo Simulation
,”
Laser. Surg. Med.
,
18
(
2
), pp.
129
138
.10.1002/(SICI)1096-9101(1996)18:2<129::AID-LSM2>3.0.CO;2-U
41.
Chen
,
Y.
,
2012
, “
Monte Carlo Simulation of Enhanced Laser Absorption in Tumors With Gold Nano-rod Inclusions: A Study of Laser Thermal Therapy Applied in Tumor Ablation
,” M.S. thesis, University of Maryland Baltimore County, Baltimore, MD.
42.
Mourant
,
J. R.
,
Fuselier
,
T.
,
Boyer
,
J.
,
Johnson
,
T. M.
, and
Bigio
,
I. J.
,
1997
, “
Predictions and Measurements of Scattering and Absorption Over Broad Wavelength Ranges in Tissue Phantoms
,”
Appl. Opt.
,
36
(
4
), pp.
949
957
.10.1364/AO.36.000949
43.
Piao
,
D. B.
,
Bartels
,
K. E.
,
Jiang
,
Z.
,
Holyoak
,
G. R.
,
Ritchey
,
J. W.
,
Xu
,
G.
,
Bunting
,
C. F.
, and
Slobodov
,
G.
,
2010
, “
Alternative Transrectal Prostate Imaging: A Diffuse Optical Tomography Method
,”
IEEE J. Sel. Topics Quant. Electron.
,
16
(
4
), pp.
715
729
.10.1109/JSTQE.2009.2034026
44.
Piao
,
D. B.
,
Jiang
,
Z.
,
Bartels
,
K. E.
,
Holyoak
,
G. R.
,
Ritchey
,
J. W.
,
Xu
,
G.
,
Bunting
,
C. F.
, and
Slobodov
,
G.
,
2009
, “
In Vivo Trans-Rectal Ultrasound-Coupled Near-Infrared Optical Tomography of Intact Normal Canine Prostate
,”
J. Innovat. Opt. Health Sci.
,
2
(
3
), pp.
215
225
.10.1142/S1793545809000620
45.
Manuchehrabadi
,
N. A.
,
Attaluri
,
A.
,
Cai
,
H.
,
Edziah
,
R.
,
Lalanne
,
E.
,
Bieberich
,
C.
,
Ma
,
R.
,
Johnson
,
A. M.
, and
Zhu
,
L.
,
2012
, “
MicroCT Imaging and In Vivo Temperature Elevations in Implanted Prostatic Tumors in Laser Photothermal Therapy Using Gold Nanorods
,”
ASME J. Nanotech. Eng. Med.
,
3
(
2
), p.
021003
.10.1115/1.4007161
46.
Pennes
,
H. H.
,
1948
, “
Analysis of Tissue and Arterial Blood Temperature in the Resting Human Forearm
,”
J. Appl. Physiol.
,
1
, pp.
93
122
.
47.
Fujita
,
S. T.
,
Tamazawa
,
M.
, and
Kuroda
,
K.
,
1998
, “
Effects of Blood Perfusion Rate on the Optimization of RF-Capacitive Hyperthermia
,”
IEEE Trans. Biomed. Eng.
,
45
(
9
), pp.
1182
1186
.10.1109/10.709562
48.
Gore
,
J. P.
, and
Xu
,
L. X.
,
2003
, “
Thermal Imaging for Biological and Medical Diagnostics
,”
Biomedical Photonics Handbook
,
T.
Vo-Dinh
, ed.,
CRC Press
, Boca Raton, FL.
49.
von Maltzahn
,
G.
,
Park
,
J. H.
,
Agrawal
,
A.
, and
Bandaru
,
N. K.
,
2009
, “
Computationally Guided Photothermal Tumor Therapy Using Long-Circulating Gold Nanorod Antennas
,”
Cancer Res. Suppl. Data
,
69
(
9
), pp.
3892
3900
.10.1158/0008-5472.CAN-08-4242
50.
Manuchehrabadi
,
N.
,
Attaluri
,
A.
,
Cai
,
H.
,
Edziah
,
R.
,
Lalanne
,
E.
,
Bieberich
,
C.
,
Ma
,
R.
,
Johnson
,
A. M.
, and
Zhu
,
L.
,
2013
, “
Tumor Shrinkage Studies and Histological Analyses after Laser Photothermal Therapy Using Gold Nanorods
,”
International Journal of Biomedical Engineering and Technology
,
12
(
2
), pp.
157
174
.
51.
Jain
,
P. K.
,
Lee
,
K. S.
,
El-Sayed
,
I. H.
, and
El-Sayed
M. A.
,
2006
, “
Calculated Absorption and Scattering Properties of Gold Nanoparticles of Different Size, Shape, and Composition: Applications in Biological Imaging and Biomedicine
,”
J. Phys. Chem.
,
110
, pp.
7238
7248
.
52.
Arnifield
,
M. R.
,
Mathew
,
R. P.
,
Tulip
,
J.
, and
Mcphee
,
M. S.
,
1992
, “
Analysis of Tissue Optical Coefficients Using an Approximate Equation Valid for Comparable Absorption and Scattering
,”
Phys. Med. Biol.
,
37
, pp.
1219
1230
.10.1088/0031-9155/37/6/002
53.
Song
,
C. W.
,
1984
, “
Effect of Local Hyperthermia on Blood Flow and Microenvironment: A Review
,”
Cancer Res.
,
44
, pp.
4721s
4730s
.
54.
Zhu
,
L.
,
2009
, “
Heat Transfer Applications in Biological Systems
.,”
Biomedical Engineering & Design Handbook
, Volume 1: Bioengineering Fundamentals,
M.
Kutz
, editor-in-chief,
McGraw-Hill
, New York, pp.
2.33
2.67
.
55.
Moritz
,
A. R.
, and
Henriques
,
F. C.
1947
, “
The Relative Importance of Time and Surface Temperature in the Causation of Cutaneous Burns
,”
Am. J. Pathol.
,
23
, pp.
695
720
.
You do not currently have access to this content.