MR Elastography in Cancer
Ralph Sinkus1

1Imaging Sciences & Biomedical Engineering Division, King's College London

Synopsis

Highlights

  • MR-elastography (MRE) is clinically feasible and has been applied to the characterization of breast lesion, liver tumours, brain lesions and various pre-clinical models
  • Pre-clinical models have found correlation between cell density as well as vascular density with visco-elastic parameters
  • Anti-vascular drugs or radiation therapy lead to significant changes in biomechanics
  • Shear wave dispersion allows to reveal microstructural properties of vessel architecture
  • The application of shear waves in the context of mechanotransduction offers new horizons

Target Audience

Oncologists, clinicians, and physicists who are searching for novel concepts to describe tumour development, metastatic spread, and response to therapy

Outcome/Objectives

Upon completion of this course, participants should be able to:

  • understand the concept of MRE;
  • appreciate the hypothesis why shear stiffness could play an important parameter in oncology;
  • understand why IFP, chaotic vasculature, and remodeled tumour habitat should impact stiffness;
  • understand the current pre-clinical and clinical evidence indicating the value of MRE for lesion characterization, staging, and potentially prediction of response to therapy;
  • appreciate the concept of shear wave scattering for vessel organization characterization
  • understand the potential in mechanotransduction

Purpose

The aims of this module on MRE in cancer are to:

  • show the various pre-clinical and clinical approaches to MRE;
  • present the pathologic determinants impacting tissue stiffness in oncology;
  • discuss the impact on tumour stroma and habitat in the context therapy and metastatic process; and
  • raise the attention to the domain of mechanotransduction.

Required Hardware and Software for MR-Elastography

Pre-clinical and clinical MRE requires the emission of low frequency mechanical waves into the target area with simultaneous and synchronized motion-sensitized MRI imaging. Subsequent extraction of viscoelastic parameters requires full 3D acquisition and reconstruction to avoid intrinsic biases in parameter estimation.

Pathologic Determinants

Preclinical tumour models have shown sensitivity of viscoelastic parameters to cellular density and vascular density. Studies investigating response to vascular disrupting agents have seen dramatic changes in biomechanics after application of the drug while ADC did not change compared to control at that time point. The changes seen in MRE due to vascular density might have their origin in multiple scatter of shear waves on the microvascular bed. This opens up an exciting avenue for the characterization of the spatial architecture of microvascular.

Clinical Results

Trials in breast, liver, and brain tumours have shown differences in biomechanics between benign and malignant lesions with stiffness not necessarily the most discriminant parameter. Enhanced viscosity correlated to lesion aggressiveness. Those findings are corroborated by in-vivo work demonstrating that metastatic processes are facilitated in viscous environments. Hence, more work is needed to investigate whether enhance viscous properties of the tumour habitat are potential proxies for metastatic propensity.

Future

The role of cancer cell behavior (proliferation and migration) in the context of active forces is currently subject of exciting results. Shear waves offer here a unique window of opportunities. Initial results obtained in breast cancer spheroids will be discussed.

Acknowledgements

Ralph Sinkus has received funding from the European Union’s Horizon 2020 research and innovation programme und grant agreement N0 668039 (FORCE). He would like to acknowledge the enormous efforts made by all members of the Horizon2020 consortium in developing novel MRE hardware, MRE acquisition sequences and protocols, and MRE postprocessing software for the clinical trials in breast cancer, liver cancer, and brain lesions.

References

[1] Butcher, D. T. A tense situation: forcing tumour progression, Nature reviews. Cancer 9 (2) 2009

[2] Swartz, M. A. Lymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity, Nature reviews. Cancer 12 (3) 2012

[3] Sudhakar K Venkatesh Magnetic Resonance Elastography of Liver Tumors- Preliminary Results, AJR Am J Roentgenol. 190 (6) 2008

[4] Garteiser, P. MR elastography of liver tumours: value of viscoelastic properties for tumour characterization, Eur Radiol 22 (10) 2012

[5] Xu, L. Magnetic resonance elastography of brain tumors: preliminary results, Acta Radiol 48 (3) 2007

[6] Kaspar-Josche Streitberger High-Resolution Mechanical Imaging of Glioblastoma by Multifrequency Magnetic Resonance Elastography, PLoS One 9 (10) 2014

[7] Sinkus, R. MR elastography of breast lesions: understanding the solid/liquid duality can improve the specificity of contrast-enhanced MR mammography, Magn Reson Med 58 (6) 2007

[8] Li, J. Tumour biomechanical response to the vascular disrupting agent ZD6126 in vivo assessed by magnetic resonance elastography, Br J Cancer 110 (7) 2014

[9] Jamin, Y. Exploring the biomechanical properties of brain malignancies and their pathologic determinants in vivo with magnetic resonance elastography, Cancer Res 75 (7) 2015

[10] Juge, L. Microvasculature alters the dispersion properties of shear waves--a multi-frequency MR elastography study, NMR Biomed 28 (12) 2015

[11] Lambert, S. A. Bridging Three Orders of Magnitude: Multiple Scattered Waves Sense Fractal Microscopic Structures via Dispersion, Phys Rev Lett 115 (9) 2015

[12] Motosugi, U. Liver stiffness measured by magnetic resonance elastography as a risk factor for hepatocellular carcinoma: a preliminary case-control study, Eur Radiol 23 (1) 2012

[13] Kraning-Rush, C. M. Cellular traction stresses increase with increasing metastatic potential, PLoS One 7 (2) 2012

Proc. Intl. Soc. Mag. Reson. Med. 25 (2017)