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

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.

Associations between apparent diffusion coefficient values and histopathological tissue alterations in myopathies

“…In pathologic tissue alterations, for example in tumors, there is higher cellularity caused by proliferating cells, which reduces the extracellular space and consecutively reduces the proton movement overall, resulting in a lower ADC value in tumors. Moreover, it was shown that other tissue features, such as extracellular matrix proteins are also associated with ADC values (Aoyagi et al., 2012; Hauge et al., 2017). Additionally, there is an influence of perfusion to the DWI signal intensity (De Luca, Bertoldo, & Froeling, 2017; Le Bihan et al., 1988).…”

“…DWI reflects random water motion in tissues and is therefore acknowledged to provide deeper insight into tissue microstructure (Surov, Meyer, & Wienke, 2017). It can be quantified by apparent diffusion coefficient (ADC), which correlates inversely with cellularity, amount of extracellular proteins and other tissue factors (Aoyagi et al., 2012; Hauge et al, 2017; Surov et al., 2017).…”

Measurement of Tumor Pressure and Strategies of Imaging Tumor Pressure for Radioimmunotherapy

“…Researchers have demonstrated that ADC values are inversely correlated with IFP, using the PC method [31]. Moreover, Hauge et al demonstrated that the abundance of collagen fiber and ADC have an inverse correlation with IFP [34]. These works strongly suggest that ADC is significant for the understanding of IFP.…”

The Application of Patient-Derived Xenograft Models in Gynecologic Cancers

“…Apparent diffusion coefficient (ADC) values derived from diffusion-weighted magnetic resonance imaging (DW-MRI) could reflect the cellular environment of biological tissues. In four cervical squamous cell carcinoma PDX models, one group observed that median tumor ADC was negatively related to the fraction of collagen I, suggesting that DW-MRI may be a non-invasive imaging approach for characterizing the stromal microenvironment of cervical cancer 29 . Consistently, four cervical cancer PDX models were used to detect the correlation between dynamic contrast-enhanced (DCE) MRI and parameters of the tumor microenvironment, and it was noticed that DCE-MRI provided valuable information on the hypoxic fraction of cervical squamous cell carcinoma 30 .…”