MRI methods for quantifying tumour microstructure

Imaging tissue microstructure in vivo may provide a clinical tool for detecting tumour cell proliferation, death and infiltration of healthy tissues. Tissue microstructure can be assessed using diffusion magnetic resonance imaging (dMRI), which is sensitive to the diffusion of tissue water over distances of a few microns. However, dMRI’s use in a clinical setting has two significant limitations: Firstly, it is impossible to unambiguously relate changes in the apparent diffusion coefficient (ADC) of water to changes in cell size, packing density or membrane permeability, which are possible indicators of cancer cell infiltration, proliferation and therapy response. Secondly, current strategies for alleviating the effects of motion on dMRI are unsatisfactory and can blur tumour features or substantially extend scan durations.

Advanced tissue-mimetic phantom materials for
imaging enable improved validation and calibration
of quantitative microstructure imaging methods.

We and others have demonstrated that tissue microstructure quantification using dMRI is possible in brain and other neural tissues. We have shown that it is possible to measure axon diameter in the whole brain and are involved in creating the first neuroanatomical atlas of tissue microstructure. This will help when assessing changes in cellularity and infiltration associated with brain tumours. However, validation of these measurements is limited and they are challenging to implement on many clinical scanners. They have also, to date, not been employed successfully in a clinical setting to measure tumour cellular architecture, although early work from our group and others suggests that such measurements are possible.

We are developing optimised data acquisitions that provide information on cell packing, density and cell membrane permeability. These are being validated using a number of strategies including novel tissue mimetic phantoms. For clinical translation, we will derive optimised acquisition protocols by employing the latest strategies for accessing short diffusion times and scanning acceleration methods. We will reduce motion in abdominal and thoracic dMRI by implementing novel registration methods. We will compare dMRI measurements with other advanced imaging techniques to assess the relative merits of each approach for quantifying aspects of tumour microstructure. We will apply these optimised methods in studies of a range of tumour studies in order to provide method validation and to demonstrate clinical utility.

Professor Geoff Parker

Chair in Biomedical Imaging at The University of Manchester.

Dr Sarah Bohndiek

Leader of the Imaging Oxygen and Oxidative Stress group at the University of Cambridge.

Professor Kevin Brindle

Chair in Biomedical Magnetic Resonance at the University of Cambridge.

Dr Ferdia Gallagher

Cancer Research UK Clinician Scientist Fellow at the Cancer Research UK Cambridge Institute and Honorary Consultant Radiologist at Cambridge University Hospitals NHS Foundation Trust.

Professor Alan Jackson

Chair in Radiology at The University of Manchester.

Professor Kaye Williams

Head of the Hypoxia and Therapeutics group in the Manchester Pharmacy School at The University of Manchester.