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Research Papers

Evaluation of the Laser-Induced Thermotherapy Treatment Effect of Breast Cancer Based on Tissue Viscoelastic Properties

[+] Author and Article Information
Jiayao Chen, Bin Zhou, Dan Li, Hong Shan

Guangdong Provincial Engineering Research
Center of Molecular Imaging,
The Fifth Affiliated Hospital,
Sun Yat-sen University,
Zhuhai 519000, Guangdong, China

Suhao Qiu

Institute for Medical Imaging Technology,
School of Biomedical Engineering,
Shanghai Jiao Tong University,
Shanghai 200000, China;
Center for Molecular Imaging and
Nuclear Medicine,
School of Radiological and Interdisciplinary
Sciences (RAD-X),
Soochow University,
Collaborative Innovation Center of Radiation
Medicine of Jiangsu Higher Education
Institutions,
Suzhou 215123, Jiangsu, China

Shengyuan Ma

Institute for Medical Imaging Technology,
School of Biomedical Engineering,
Shanghai Jiao Tong University,
Shanghai 200000, China;
Center for Molecular Imaging
and Nuclear Medicine,
School of Radiological and Interdisciplinary
Sciences (RAD-X),
Soochow University,
Collaborative Innovation Center of Radiation
Medicine of Jiangsu Higher Education
Institutions,
Suzhou 215123, Jiangsu, China

Chung-Hao Lee

School of Aerospace and Mechanical
Engineering,
Institute for Biomedical Engineering,
Science, and Technology,
University of Oklahoma,
Norman, OK 73019

Ankush Aggarwal

Zienkiewicz Centre for Computational
Engineering,
College of Engineering,
Swansea University,
Swansea SA1 8EN, UK

Jianfeng Zeng, Mingyuan Gao

Center for Molecular Imaging and Nuclear
Medicine,
School of Radiological and Interdisciplinary
Sciences (RAD-X),
Soochow University,
Collaborative Innovation Center of Radiation
Medicine of Jiangsu Higher Education
Institutions,
Suzhou 215123, Jiangsu, China

Yuan Feng

Institute for Medical Imaging Technology,
School of Biomedical Engineering,
Shanghai Jiao Tong University,
Shanghai 200000, China;
Center for Molecular Imaging and Nuclear
Medicine,
School of Radiological and Interdisciplinary
Sciences (RAD-X),
Soochow University,
Collaborative Innovation Center of Radiation
Medicine of Jiangsu Higher Education
Institutions,
Suzhou 215123, Jiangsu, China

1Corresponding authors.

2The authors contributed equally to the paper.

Manuscript received June 19, 2018; final manuscript received September 10, 2018; published online October 5, 2018. Assoc. Editor: Mostafa Fatemi.

ASME J of Medical Diagnostics 1(4), 041009 (Oct 05, 2018) (9 pages) Paper No: JESMDT-18-1030; doi: 10.1115/1.4041502 History: Received June 19, 2018; Revised September 10, 2018

Photothermal therapy (PTT) has been emerging as an effective, minimally invasive approach to treat cancers. However, a method to quantitatively evaluate the treatment effect after laser-induced thermotherapy (LITT) is needed. In this study, we used 808 nm laser radiation with three different power densities to treat the breast cancer tissue from 4T1 cell lines in a mouse model. The viscoelastic properties of the treated cancer tissues were characterized by a two-term Prony series using a ramp-hold indentation method. We observed that instantaneous shear modulus G0 was significantly higher for the treated cancer tissues than that of the untreated tissue when treated with a power density of 1.5 W/cm2, but significantly lower with a power density of 2.5 W/cm2. The long-term shear modulus G was also significantly higher for the cancer tissue at 1.5 W/cm2, compared to the untreated tissue. The treatment effects were verified by estimating the cell apoptosis rate using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Our results indicate that the viscoelastic properties of the tissue could potentially be used as biomarkers for evaluating the LITT treatment effect. In addition, we also observed a strain-independent behavior of the treated cancer tissue, which provided useful information for applying in vivo imaging method such as magnetic resonance elastography (MRE) for treatment evaluation based on biomechanical properties.

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Figures

Grahic Jump Location
Fig. 1

(a) Two solid tumors (arrows) implanted on both sides of the rear leg of a mouse after injection of 4T1 cancer cells subcutaneously, (b) irradiation of the implanted tumor with an 808 nm laser, (c) a tissue sample of solid tumor dissected for measurements, and (d) indentation of a tissue sample with a cylindrically shaped indenter

Grahic Jump Location
Fig. 2

(a) Distributions of the mouse body temperature during photothermal imaging. The highest temperature was observed at the tumor site after 10 min of LITT with a power density of 2.5 W/cm2. (b) The temperature of the treated tumor over time under power densities of 1.5 W/cm2, 2.0 W/cm2, and 2.5 W/cm2.

Grahic Jump Location
Fig. 3

(a) Typical experimental and fitted force–displacement curves for indentation strain levels of 2%, 4%, 6%, 8%, and 10%. The R2 values of the fittings were 0.99 for all cases. (b) A typical average force relaxation curve of 6 tumor samples with an indentation strain level of 6% (1.5 W/cm2). The shaded area indicates the standard deviation of the measured relaxation curves.

Grahic Jump Location
Fig. 4

Comparisons of the treated and untreated cancer tissues in terms of ((a), (c), and (e)) instantaneous shear modulus G0, and ((b), (d), and (f)) long-term shear modulus G (mean±95% confidence interval). The power density applied were ((a) and (b)) 1.5 W/cm2, ((c) and (d)) 2.0 W/cm2, and ((e) and (f)) 2.5 W/cm2.

Grahic Jump Location
Fig. 5

Ratios of (a) G0 and (b) G values at each indentation strain level for the three irradiation power densities (mean±95% confidence interval). The ratio was defined by dividing the modulus of the treated tissue with that of the untreated tissue.

Grahic Jump Location
Fig. 6

Relaxation time of the treated and untreated tumor tissues for the power density groups of (a) 1.5 W/cm2, (b) 2.0 W/cm2, and (c) 2.5 W/cm2. The relaxation time was estimated based on the 60% relaxation of the average indentation force.

Grahic Jump Location
Fig. 7

Transferase dUTP nick end labeling stain using 400× microscopy for (a, c, e) the treated tumor tissues and (b, d, f) the corresponding labeled live and apoptosis cells. The normal tumor cells were labeled with green color and the apoptosis cells were labeled with red color. Power densities of (a, b) 1.5 W/cm2, (c, d) 2.0 W/cm2, and (e, f) 2.5 W/cm2 are illustrated.

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