Noninvasive characterization of pancreatic tumor mouse models using magnetic resonance imaging

Abstract

The preclinical models of pancreatic adenocarcinoma provide an alternative means for determining the mechanisms of malignancy and possibilities for treatments, thus representing a resource of immense potential for cancer treatment in medicine. To evaluate different tumor models, quantifiable magnetic resonance imaging (MRI) techniques can play a significant role in identifying valuable in vivo biomarkers of tumor characteristics. We characterized three models of pancreatic cancer with multiparametric MRI techniques. Tumor stromal density of each tumor was measured using diffusion‐weighted imaging and magnetization transfer (MT‐MRI). Histologic measurement showed a similar trend with tumor fibrosis levels. Results indicated that MRI measurements can serve as a valuable tool in identifying and evaluating tumor characteristics.

Evaluation of pancreatic tumor development in KPC mice using multi-parametric MRI

“…However, T 1 and T 2 measures alone may not be sensitive enough to investigate the entire spectrum of tumor properties. Recently, diffusion weighted imaging (DWI) [ 14 , 15 ] and magnetization transfer imaging (MTI) [ 16 – 18 ] have been used as complementary imaging techniques to conventional MR measures to characterize adenocarcinoma. Finally, amide proton transfer (APT) imaging based on the chemical exchange saturation transfer (CEST) approach, which provides valuable information regarding the tumor microenvironment, has drawn considerable attention as a novel MRI contrast agent in the field of molecular imaging [ 19 , 20 ].…”

Non-invasive tracking of disease progression in young dystrophic muscles using multi-parametric MRI at 14T

“…MT could still prove to be useful in measurements of mdx mice because fatty tissue does not show MT due to the lack of water molecules [ 44 ]. Additionally, MT has been shown to be sensitive to fibrosis formation in other diseases such as Crohn’s disease [ 47 ] and pancreatic tumors [ 48 , 49 ]. Thus, measurements of MT in mdx 4cv mice at a young age could be further refined to capture early fibrotic tissue formation in young muscle as well as fibrosis seen in older mdx 4cv mice for useful translation to human studies of DMD where fatty infiltration and higher levels of fibrosis also occur in skeletal muscle.…”

Non-invasive dynamic monitoring initiation and growth of pancreatic tumor in the LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC) transgenic mouse model

“…Tumor desmoplasia is one of the common pathological features of human PDAC, characterized by dense fibrotic connective tissue that penetrates and envelopes the tumor (Li et al, 2012). These extracellular matrix is related with tumor progression, metastasis, and drug resistance (Farr et al, 2017). Hence, it is significantly important to characterize the tumor fibrosis to predict tumor grade and response to treatments.…”

“…The results demonstrated a significant difference between the ADC values of the tumor and pancreatic tissue. This can be explained by the accumulation of fibrotic tissue, which may be associated with restricted motion of the water protons (Farr et al, 2017).…”

“…and therapeutic strategies (Torres et al, 2013). Several GEM models that accurately mimic the pathophysiological characteristics of human PDAC have been described (de Latouliere et al, 2016;Farr et al, 2017;Ijichi, 2011). In particular, the LSL-Kras G12D/+ ;LSL-Trp53 R172H/+ ;Pdx-1-Cre, termed KPC mouse has attracted increasing attention, because it recapitulates the pathophysiological aspects and the biology features of human PDAC (Bai et al, 2017;Courtin et al, 2013;Hingorani et al, 2005).…”