Title: Advancing MRI Biomarkers of the Tumour Microenvironment for Patient Benefit
Funder: Cancer Research UK

Abstract: BACKGROUND There is a continuing need to develop and exploit imaging technology to enable personalised adaptation of treatment for improved patient outcomes. Multiparametric magnetic resonance imaging (MRI) affords quantitative biomarkers to non-invasively visualise spatial variations and temporal evolution of tissue structure-function in vivo, which can enable accurate tumour detection, an understanding of the microenvironment, and inform on drug delivery and treatment response. New MRI biomarker development demands close imaging-pathology correlation, to understand the biology underpinning the imaging measurement, which can be meaningfully studied using animal models AIMS Tumour hypoxia and aberrant tensional homeostasis are two key features of cancer that adversely affect patient prognosis, and for which reliable clinical imaging methods are lacking. This programme of work will focus on the evaluation of two innovative MRI methodologies, oxygen-enhanced (OE)-MRI and magnetic resonance elastography (MRE), for mapping tumour hypoxia and viscoelasticity respectively, to predict, assess and improve treatment response in clinically relevant models of cancer in vivo. Computational pathology will be used to address whether spatial heterogeneity seen in MRI data in vivo is directly linked to regional variations in cellular and microenvironmental properties observed within and between tumours. METHODS The utility of OE-MRI to i) identify, quantify and map hypoxia, ii) predict radiation response and iii) identify hypoxic subvolumes for targeted radiotherapy, in hypoxic HNSCC and rhabdomyosarcoma xenografts will be assessed. MRE will be exploited for quantitatively mapping tumour viscosity and elasticity in stromal dense orthotopic breast and pancreatic cancer xenografts. The ability of MRE to inform on metastatic propensity of breast cancer xenografts, and for monitoring the effects of stromal modulating therapies for enhancing treatment response in breast and pancreatic tumours, will also be investigated. Advanced image analysis of digitised pathology from aligned tissue sections and computational pathology will be used to validate and define OE-MRI and MRE-derived biomarkers, and imaging-defined sub-regions of hypoxia and viscoelasticity. HOW THE RESULTS OF THIS RESEARCH WILL BE USED Both OE-MRI and MRE can be implemented on conventional clinical MRI scanners. Our strategy will promote the adoption of imaging biomarkers of hypoxia and viscoelasticity provided by OE-MRI and MRE to i) guide their deployment into aligned clinical imaging-embedded investigations/trials and ii) improve diagnosis and patient stratification.

Lay abstract: BACKGROUND There is a continuing need to develop and exploit imaging technology to enable personalised adaptation of treatment for improved patient outcomes. Multiparametric magnetic resonance imaging (MRI) affords quantitative biomarkers to non-invasively visualise spatial variations and temporal evolution of tissue structure-function in vivo, which can enable accurate tumour detection, an understanding of the microenvironment, and inform on drug delivery and treatment response. New MRI biomarker development demands close imaging-pathology correlation, to understand the biology underpinning the imaging measurement, which can be meaningfully studied using animal models AIMS Tumour hypoxia and aberrant tensional homeostasis are two key features of cancer that adversely affect patient prognosis, and for which reliable clinical imaging methods are lacking. This programme of work will focus on the evaluation of two innovative MRI methodologies, oxygen-enhanced (OE)-MRI and magnetic resonance elastography (MRE), for mapping tumour hypoxia and viscoelasticity respectively, to predict, assess and improve treatment response in clinically relevant models of cancer in vivo. Computational pathology will be used to address whether spatial heterogeneity seen in MRI data in vivo is directly linked to regional variations in cellular and microenvironmental properties observed within and between tumours. METHODS The utility of OE-MRI to i) identify, quantify and map hypoxia, ii) predict radiation response and iii) identify hypoxic subvolumes for targeted radiotherapy, in hypoxic HNSCC and rhabdomyosarcoma xenografts will be assessed. MRE will be exploited for quantitatively mapping tumour viscosity and elasticity in stromal dense orthotopic breast and pancreatic cancer xenografts. The ability of MRE to inform on metastatic propensity of breast cancer xenografts, and for monitoring the effects of stromal modulating therapies for enhancing treatment response in breast and pancreatic tumours, will also be investigated. Advanced image analysis of digitised pathology from aligned tissue sections and computational pathology will be used to validate and define OE-MRI and MRE-derived biomarkers, and imaging-defined sub-regions of hypoxia and viscoelasticity. HOW THE RESULTS OF THIS RESEARCH WILL BE USED Both OE-MRI and MRE can be implemented on conventional clinical MRI scanners. Our strategy will promote the adoption of imaging biomarkers of hypoxia and viscoelasticity provided by OE-MRI and MRE to i) guide their deployment into aligned clinical imaging-embedded investigations/trials and ii) improve diagnosis and patient stratification.

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