Title: Development of non-ionising and non-invasive, personalised colorectal cancer staging using novel multimodal contrast agents and magnetomotive ultrasound imaging
Funder: Cancer Research UK

Abstract: Colorectal cancer (CRC) is the fourth most common cancer in UK. Treatment is dominated by major surgery because current imaging modalities cannot accurately determine lymph node involvement or vascular invasion. Although potentially curative, surgery carries high risk of short- and long-term morbidity including stoma formation. Optimized pre-treatment imaging would decrease the number of patients requiring major surgery. It would also be equally applicable to other cancers where local resection could significantly improve patient quality of life, without compromising long-term outcomes (e.g. melanoma, head and neck cancers, gastro-oesophageal, bladder). Magnetomotive ultrasound (MMUS) is an emerging technique which combines the advantages of ultrasound, which is non-invasive, non-ionising, low cost and portable, with the advantages of nanoparticles for molecular imaging. Super-paramagnetic iron-oxide nanoparticles (SPIONs), used routinely in MRI, injected close to the tumour, accumulate in the lymph. When exposed to a low frequency magnetic field (5-15 Hz) this tissue is displaced axially and the movement detected with ultrasound. Phase and frequency filtering is used to generate micron-scale images of displacement and fine delineation of structures. Displacement is influenced by tissue elasticity and SPION density. Since pathology indicative of cancer progression is known to alter tissue elasticity and SPION uptake, the approach holds significant potential to non-invasively image tumour development. Sensitivity of the technique could be significantly improved through monitoring of the shear waves which result from axial displacements to estimate shear modulus, a far more sensitive descriptor of soft tissue properties. Our multidisciplinary team, comprising engineers with expertise in ultrasound contrast imaging, microbubble fabrication and MMUS development, a CRC geneticist who has recently developed a novel mouse model of anorectal adenocarcinoma, and a colorectal surgeon committed to improving patient outcomes and translating our research to clinical practice, will develop MMUS shear wave estimation (SWE) and MMUS transient elastography (TE). Beginning in tissue phantom models, approaches for estimating tissue viscoelasticity will be developed through shear wave estimation and impulse response before the technique is demonstrated in our unique animal model. Multimodal contrast agents will be developed to deliver this. Validation will be performed against post-excision tissue mechanical properties and pathology. The approach will demonstrate delineation of sentinel draining lymph nodes (SLN) and tumour extent and provide biomechanical information indicative of cancer pathology. Multimodal MMUS will deliver functional advances in CRC treatment and provide significant opportunity to extend the technique towards other


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS