Research Papers

Numerical Study of Transport of Anticancer Drugs in Heterogeneous Vasculature of Human Brain Tumors Using Dynamic Contrast Enhanced-Magnetic Resonance Imaging

[+] Author and Article Information
Ajay Bhandari

Department of Mechanical Engineering,
Indian Institute of Technology,
Kanpur 208016, India
e-mail: ajayb@iitk.ac.in

Ankit Bansal

Department of Mechanical and
Industrial Engineering,
Indian Institute of Technology,
Roorkee 247677, India
e-mail: abansfme@iitr.ac.in

Anup Singh

Centre for Biomedical Engineering,
Indian Institute of Technology,
Delhi 110016, India;
Department of Biomedical Engineering,
All India Institute of Medical Sciences,
Delhi 110016, India
e-mail: anupsm@cbme.iitd.ac.in

Niraj Sinha

Department of Mechanical Engineering,
Indian Institute of Technology,
Kanpur 208016, India
e-mail: nsinha@iitk.ac.in

1Corresponding author.

Manuscript received August 15, 2017; final manuscript received November 7, 2017; published online March 16, 2018. Assoc. Editor: Ram Devireddy.

J Biomech Eng 140(5), 051010 (Mar 16, 2018) (10 pages) Paper No: BIO-17-1366; doi: 10.1115/1.4038746 History: Received August 15, 2017; Revised November 07, 2017

Systemic administration of drugs in tumors is a challenging task due to unorganized microvasculature and nonuniform extravasation. There is an imperative need to understand the transport behavior of drugs when administered intravenously. In this study, a transport model is developed to understand the therapeutic efficacy of a free drug and liposome-encapsulated drugs (LED), in heterogeneous vasculature of human brain tumors. Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) data is employed to model the heterogeneity in tumor vasculature that is directly mapped onto the computational fluid dynamics (CFD) model. Results indicate that heterogeneous vasculature leads to preferential accumulation of drugs at the tumor position. Higher drug accumulation was found at location of higher interstitial volume, thereby facilitating more tumor cell killing at those areas. Liposome-released drug (LRD) remains inside the tumor for longer time as compared to free drug, which together with higher concentration enhances therapeutic efficacy. The interstitial as well as intracellular concentration of LRD is found to be 2–20 fold higher as compared to free drug, which are in line with experimental data reported in literature. Close agreement between the predicted and experimental data demonstrates the potential of the developed model in modeling the transport of LED and free drugs in heterogeneous vasculature of human tumors.

Copyright © 2018 by ASME
Topics: Drugs , Tumors
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Grahic Jump Location
Fig. 2

Contour maps of (a) interstitial volume fraction (porosity), (b) plasma volume fraction, and (c) cell density of slice 8 of MR data set

Grahic Jump Location
Fig. 1

(a) Precontrast T1 weighted MR image of one slice of human brain, (b) postcontrast T1 weighted image, (c) zoomed view of tumor portion, and (d) segmented CFD single slice including tumor (dark blue) and remaining normal tissue

Grahic Jump Location
Fig. 7

Line plots showing comparison of cell density by LRD and free drug along horizontal bisector of slice at different times: (a) 1 h, (b) 12 h, (c) 24 h, and (d) 48 h (dashed lines indicate tumor boundary)

Grahic Jump Location
Fig. 3

Contour maps representing distribution of free drug at different times: (a) 1 h, (b) 12 h, (c) 24 h, and (d) 48 h. Scale bar is same as in Fig. 2.

Grahic Jump Location
Fig. 4

Line plots along horizontal bisector through tumor region of slice at different times of free drug (a) interstitial concentration and (b) intracellular concentration (dashed lines indicate tumor boundary)

Grahic Jump Location
Fig. 5

Line plots along horizontal bisector through tumor region of slice at different times of LRD (a) interstitial concentration and (b) intracellular concentration (dashed lines indicate tumor boundary)

Grahic Jump Location
Fig. 6

Line plots showing comparison of interstitial concentration by LRD and free drug along horizontal bisector of slice at different times: (a) 1 h, (b) 12 h, (c) 24 h, and (d) 48 h (dashed lines indicate tumor boundary)



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