Bray, Timothy JP; (2018) Magnetic resonance imaging of skeletal inflammation: a quantitative approach. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

‘Spondyloarthritis’ is an umbrella term referring to a group of inflammatory diseases characterized by spinal inflammation and new bone formation, which cause pain, disability and reduced quality of life. Magnetic resonance imaging (MRI) is commonly used to identify, quantify and monitor inflammation in patients with spondyloarthritis, and can therefore help to guide treatment aimed at reducing inflammation. However, conventional methods for interpretation of MRI scans are qualitative, lack reproducibility and provide only indirect information about tissue pathology. Therefore, there is a need for a more objective method for identifying and quantifying inflammation using MRI. Quantitative MRI (qMRI) enables objective physical measurements of tissue characteristics to be made directly from the image, and is a candidate tool. In this thesis, two main qMRI techniques - diffusion- weighted imaging and chemical shift-encoded MRI, which derive apparent diffusion coefficient (ADC) and proton density fat fraction (PDFF) measurements respectively - have been considered as potential methods for quantifying inflammation. ADC measurements are known to increase in areas of bone marrow oedema; here, it was shown that ADC measures reflect response to treatment in patients undergoing tumour necrosis factor inhibitor (TNFi) therapy. CSE-MRI was optimized as a new method for imaging inflammation, and new fat-water-bone phantoms were designed enabling technical validation of PDFF measurements. PDFF was compared in areas ofbone marrow oedema, fat metaplasia and normal marrow, and was shown to decrease in oedematous sites and increase in areas of fat metaplasia. A new partially- automated tool for measuring ADC and PDFF measurements in the subchondral bone using histographic analysis was developed, and histographic parameters were compared in a prospective study of 53 patients. Histographic analysis was shown to improve the performance of both ADC and PDFF measurements for identifying inflammation and fat metaplasia. Additionally, potential methods for quantifying bone mineral density (BMD) – and thus quantifying bone formation and bone loss – were evaluated. R2* and quantitative susceptibility measurements were shown to reflect bone mineral density (BMD) in fat-water-bone phantoms, and also showed differences in areas offat metaplasia compared to normal bone marrow. The results confirm the feasibility of using qMRI to quantify inflammation in spondyloarthritis. The fat-water-bone phantom and quantification tools described here could be used in future studies aiming to quantify and characterize bone inflammation.

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