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. 2022 Feb 16;14(4):999.
doi: 10.3390/cancers14040999.

Non-Invasive Monitoring of Increased Fibrotic Tissue and Hyaluronan Deposition in the Tumor Microenvironment in the Advanced Stages of Pancreatic Ductal Adenocarcinoma

Ravneet Vohra  1 , Yak-Nam Wang  2 , Helena Son  3 , Stephanie Totten  3 , Akshit Arora  4 , Adam Maxwell  5 , Donghoon Lee  1
Affiliations

Non-Invasive Monitoring of Increased Fibrotic Tissue and Hyaluronan Deposition in the Tumor Microenvironment in the Advanced Stages of Pancreatic Ductal Adenocarcinoma

Ravneet Vohra et al. Cancers (Basel). .

Abstract

Pancreatic ductal adenocarcinomas are characterized by a complex and robust tumor microenvironment (TME) consisting of fibrotic tissue, excessive levels of hyaluronan (HA), and immune cells. We utilized quantitative multi-parametric magnetic resonance imaging (mp-MRI) methods at 14 Tesla in a genetically engineered KPC (KrasLSL-G12D/+, Trp53LSL-R172H/+, Cre) mouse model to assess the complex TME in advanced stages of tumor development. The whole tumor, excluding cystic areas, was selected as the region of interest for data analysis and subsequent statistical analysis. Pearson correlation was used for statistical inference. There was a significant correlation between tumor volume and T2 (r = -0.66), magnetization transfer ratio (MTR) (r = 0.60), apparent diffusion coefficient (ADC) (r = 0.48), and Glycosaminoglycan-chemical exchange saturation transfer (GagCEST) (r = 0.51). A subset of mice was randomly selected for histological analysis. There were positive correlations between tumor volume and fibrosis (0.92), and HA (r = 0.76); GagCEST and HA (r = 0.81); and MTR and CD31 (r = 0.48). We found a negative correlation between ADC low-b (perfusion) and Ki67 (r = -0.82). Strong correlations between mp-MRI and histology results suggest that mp-MRI can be used as a non-invasive tool to monitor the tumor microenvironment.

Keywords: amide proton transfer (APT); apparent diffusion coefficient (ADC); chemical exchange saturation transfer (CEST); glycosaminoglycan (Gag); multi-parametric magnetic resonance imaging (mp-MRI); pancreatic ductal adenocarcinoma (PDAC).

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Relationship between Tumor volume and MR parameters in advanced stages of PDAC. (A) showing relationship between Tumor volume and T1 (ms); (B) showing relationship between Tumor Volume and T2 (ms); (C) showing relationship between Tumor volume and MTR (%).
Figure 2
Figure 2
Relationship between Tumor volume and ADC in advanced stages of PDAC. (A) showing relationship between Tumor volume and ADC (mm2/s); (B) showing relationship between Tumor Volume and ADC low b values (pseudo-diffusion); (C) showing relationship between Tumor volume and ADC (high b values).
Figure 3
Figure 3
Relationship between Tumor volume and CEST parameters in the advanced stages of PDAC. (A) showing relationship between Tumor volume and Amide proton transfer (APT%); (B) showing relationship between Tumor Volume and Glycosaminoglycans (GagCEST).
Figure 4
Figure 4
Relationship between MR and histological parameters in the advanced stages of PDAC. (A) showing relationship between Tumor volume (mm3) and Fibrosis (%); (B) showing relationship between T2 (ms) and Fibrosis (%); (C) relationship between MTR (%) and Fibrosis (%); (D) ADC low b (×10−3 mm2/s) and Fibrosis (%); (E,F) Representative images of Masson’s Trichrome and H&E stained tumor.
Figure 5
Figure 5
Relationship between MR and histological parameters in the advanced stages of PDAC. (A) showing relationship between Tumor volume and Hyaluronan (HA%); (B) showing relationship between GagCEST and HA (%); (C) relationship between MTR (%) and CD31; (D) ADC low b and Ki67. (E–G) Representative images of HA, CD31 and Ki67 stained slides.
See this image and copyright information in PMC

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