Theranostics 2019; 9(22):6369-6379. doi:10.7150/thno.34066

Research Paper

Experimental pancreatic cancer develops in soft pancreas: novel leads for an individualized diagnosis by ultrafast elasticity imaging

Nicole Therville1,2, Silvia Arcucci1,2, Aurélie Vertut1,2, Fernanda Ramos-Delgado1,2, Dina Ferreira Da Mota3, Marlène Dufresne1, Céline Basset1,2,3,4, Julie Guillermet-Guibert1,2✉

1. INSERM U1037, CRCT, Université Paul Sabatier, Toulouse
2. Laboratoire d'Excellence TouCAN
3. Laboratoire d'Histologie et d'Embryologie, Faculté de médecine de Rangueil, Toulouse
4. Service d'Anatomo-Pathologie, IUCT-O, Toulouse

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Citation:
Therville N, Arcucci S, Vertut A, Ramos-Delgado F, Da Mota DF, Dufresne M, Basset C, Guillermet-Guibert J. Experimental pancreatic cancer develops in soft pancreas: novel leads for an individualized diagnosis by ultrafast elasticity imaging. Theranostics 2019; 9(22):6369-6379. doi:10.7150/thno.34066. Available from http://www.thno.org/v09p6369.htm

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Abstract

Rapid, easy and early pancreatic cancer diagnosis and therapeutic follow up continue to necessitate an increasing attention towards the development of effective treatment strategies for this lethal disease. The non invasive quantitative assessment of pancreatic heterogeneity is limited. Here, we report the development of a preclinical imaging protocol using ultrasonography and shear wave technology in an experimental in situ pancreatic cancer model to measure the evolution of pancreatic rigidity.

Methods: Intrapancreatic tumors were genetically induced by mutated Kras and p53 in KPC mice. We evaluated the feasiblity of a live imaging protocol by assessing pancreas evolution with Aixplorer technology accross 36 weeks. Lethality induced by in situ pancreatic cancer was heterogeneous in time.

Results: The developed method successfully detected tumor mass from 26 weeks onwards at minimal 0.029 cm3 size. Elastography measurements using shear wave methodology had a wide detection range from 4.7kPa to 166.1kPa. Protumorigenic mutations induced a significant decrease of the rigidity of pancreatic tissue before tumors developed in correlation with the detection of senescent marker p16-positive cells. An intratumoral increased rigidity was quantified and found surprisingly heterogeneous. Tumors also presented a huge inter-individual heterogeneity in their rigidity parameters; tumors with low and high rigidity at detection evolve very heterogeneously in their rigidity parameters, as well as in their volume. Increase in rigidity in tumors detected by ultrafast elasticity imaging coincided with detection of tumors by echography and with the detection of the inflammatory protumoral systemic condition by non invasive follow-up and of collagen fibers by post-processing tumoral IHC analysis.

Conclusion: Our promising results indicate the potential of the shear wave elastography to support individualization of diagnosis in this most aggressive disease.

Keywords: pancreatic cancer, tumor rigidity, quantitative live imaging, tumor heterogeneity, personalized medecine