Oncotarget

Research Papers:

Diffusion-weighted MRI-derived ADC values reflect collagen I content in PDX models of uterine cervical cancer

Anette Hauge, Catherine S. Wegner, Jon-Vidar Gaustad, Trude G. Simonsen, Lise Mari K. Andersen and Einar K. Rofstad _

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Oncotarget. 2017; 8:105682-105691. https://doi.org/10.18632/oncotarget.22388

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Abstract

Anette Hauge1, Catherine S. Wegner1, Jon-Vidar Gaustad1, Trude G. Simonsen1, Lise Mari K. Andersen1 and Einar K. Rofstad1

1Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway

Correspondence to:

Einar K. Rofstad, email: einar.k.rofstad@rr-research.no

Keywords: DW-MRI; ADC; collagen; cervix carcinoma; PDX models

Received: September 05, 2017    Accepted: October 27, 2017    Published: November 11, 2017

ABSTRACT

Apparent diffusion coefficient (ADC) values derived from diffusion-weighted magnetic resonance imaging (DW-MRI) are known to reflect the cellular environment of biological tissues. However, emerging evidence accentuates the influence of stromal elements on ADC values. The current study sought to elucidate whether a correlation exists between ADC and the fraction of collagen I-positive tissue across different tumor models of uterine cervical cancer. Early and late generation tumors of four patient-derived xenograft (PDX) models of squamous cell carcinoma (BK-12, ED-15, HL-16, and LA-19) were included. DW-MRI was performed with diffusion encoding constants (b) of 200, 400, 700, and 1000 s/mm2 and diffusion gradient sensitization in three orthogonal directions. The fraction of collagen I-positive connective tissue was determined by immunohistochemistry. Mono-exponential decay curves, from which the ADC value of tumor voxels was calculated, yielded good fits to the diffusion data. A significant inverse correlation was detected between median tumor ADC and collagen I fraction across the four PDX models, indicating that collagen fibers in the extracellular space have the ability to inhibit the movement of water molecules in these xenografts. The results encourage further exploration of DW-MRI as a non-invasive imaging method for characterizing the stromal microenvironment of tumors.


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