Assessing the viscoelastic properties of abdominal tumour models in vivo using MRE
Jin Li1, Lisa Asher1, Filipa Lopes2, Craig Cummings1, Alexander Koers2,3, Laura S. Danielson2,3, Louis Chesler2,3, Caroline J. Springer2, Jeffrey C. Bamber1, Ralph Sinkus4, Yann Jamin1, and Simon P. Robinson1

1Division of Radiotherapy & Imaging, The Institute of Cancer Research, London, United Kingdom, 2Division of Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom, 3Division of Clinical Studies, The Institute of Cancer Research, London, United Kingdom, 4Division of Imaging Sciences and Biomedical Engineering, King’s College London, King’s Health Partners, St. Thomas’ Hospital, London, United Kingdom


MRE was applied to assess the viscoelastic properties of orthotopic pancreatic ductal adenocarcinoma (PDAC) xenografts, and tumours arising in a transgenic mouse model of MYCN-amplified neuroblastoma, within the mouse abdomen. The stromal-rich PDAC tumours were quantified with markedly elevated elasticity (Gd) and viscosity (Gl), whilst the pathologically diverse neuroblastomas exhibit more heterogeneity in their biomechanical properties and were relatively soft. MRE can non-invasively assess the viscoelastic properties of deep-seated tumours arising within the abdomen of mice in vivo.

Introduction / Purpose

In cancer, there is a strong body of evidence that increased tissue stiffness contributes to tumour progression1. The mechano-sensing mechanisms by which tumour cells adapt to microenvironmental changes leading to tumour growth are being actively pursued2. These differences are also being exploited in the development of drugs targeting the mechanical properties of the matrix, as therapeutic prevention of tissue stiffening is predicted to impede cancer progression and metastasis1. Methods to accurately quantify tissue matrix stiffening in vivo may thus provide prognostic biomarkers of tumour progression, and prove useful for monitoring treatment response.

Magnetic resonance elastography (MRE) is being increasingly exploited to directly visualise and quantify tumour mechanical properties in vivo. Our initial pre-clinical MRE investigations have demonstrated that MRE can provide acute imaging biomarkers of treatment-induced tumour necrosis3, and that intracranially-implanted tumours are significantly softer and less viscous than surrounding brain parenchyma4. Orthotopic and transgenic mouse models of cancer, which more faithfully emulate human tumour growth patterns and tumour-host stromal interactions, are being increasingly exploited for pre-clinical cancer research. Their effective use must be underpinned by case-specific evidence, establishing that tumour development, progression, radiology and chemoresponsiveness recapitulates the human disease.

In this study, the feasibility of using MRE to assess the viscoelastic properties of orthotopic pancreatic ductal adenocarcinoma (PDAC) xenografts, and tumours arising in a transgenic mouse model of MYCN-amplified neuroblastoma, within the mouse abdomen, was assessed.


All experiments were performed in accordance with the UK Animals (Scientific Procedures) Act 1986. Anaesthetised CD1 nu/nu mice bearing orthotopic PDAC tumours derived from PANC-1 cells (n=2), and Th-MYCN transgenic mice bearing spontaneous neuroblastomas (n=5)5, were imaged using a 3cm birdcage coil on a 7T Bruker MicroImaging horizontal MRI system (Bruker Instruments, Ettlingen, Germany). MRE data was acquired in the axial plane using a purpose built platform as previously described3. Maps of the total amplitude of the mechanical wave (Atot, µm), and absolute value of elasticity Gd and viscosity Gl (both kPa), were reconstructed with an isotropic pixel size of 300 µm, and Gd and Gl determined from a region of interest covering the whole tumour (mean ± 1 s.e.m.).


Atot was larger than 0.3 µm through both tumour types, with wave attenuation along the propagation depth (Figure 1). Homogeneously appearing PDAC xenografts in T2-weighted images were associated with elevated and discretely distributed regions of elasticity and viscosity, and which enabled clear tumour delineation from surrounding (normal) tissue (Figure 1A). Neuroblastomas appeared more heterogeneous in both T2-weighted images and maps of Gd and Gl (Figure 1B). Interestingly, the displaced aorta commonly associated with abdominal neuroblastoma, and evident with marked hypointensity in T2-weighted images (arrowed), was associated with relatively lower Gd and higher Gl (Figure 1B). Comparison of the quantitative viscoelastic properties between the two tumour types revealed the PDAC tumours to be markedly stiffer (Gd: PDAC 5.9 ± 1.0, neuroblastoma 4.1 ± 0.5 kPa) and viscous (Gl: PDAC 4.5 ± 1.1, neuroblastoma 2.3 ± 0.3 kPa).


The feasibility of applying MRE to abdominal tumours using our preclinical platform was clearly demonstrated using orthotopic PDAC xenografts, and neuroblastomas arising in a transgenic mouse model. The markedly elevated viscosity and elasticity quantified in the PDAC tumours is wholly in agreement with the well-described stromal-rich environment associated with solid pancreatic tumours6. Neuroblastoma is a pathologically diverse disease, with extensive vascularisation. Mechanical cues from the extracellular matrix have been shown to modulate the proliferation, differentiation and expression of MYCN in neuroblastoma in vitro7, providing a strong motivation to exploit MRE-derived measurements of viscoelasticity in vivo in the Th-MYCN model shown here. Such measurements may provide additional, complementary imaging biomarkers of neuroblastoma progression and treatment response to those we have already evaluated8.


MRE can be used as a non-invasive pre-clinical imaging tool to assess the viscoelastic properties of deep-seated tumours arising within the abdomen of mice in vivo. Pancreatic tumours are markedly stiff, whilst neuroblastomas exhibit more heterogeneity in their biomechanical properties and are relatively soft.


We acknowledge the CRUK and EPSRC support to the Cancer Imaging Centre at ICR in association with MRC and Department of Health C1060/A16464 and NHS funding to the NIHR Biomedicine Research Centre, an EPSRC summer vacation studentship and a Paul O’Gorman Postdoctoral Fellowship funded by Children with Cancer UK.


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Figure 1. T2-weighted images and associated parametric maps of total amplitude Atot, elasticity Gd and viscosity Gl obtained from (A) an orthotopic PDAC xenograft and (B) a neuroblastoma arising in a Th-MYCN transgenic mouse respectively. The arrows indicate a small hypo-intense region in the T2-weighted image associated with the typically displaced aorta, and is associated with reduced Gd and elevated Gl.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)