Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) of the normal bone marrow in children and effects of local and systemic cancer therapies

Abstract

Bone marrow, one of the largest organs in the body, is a highly proliferative tissue because of its dynamic function in providing the cellular elements of blood. In a paediatric population, the proportion of red marrow (cellular compartment) and yellow marrow (fatty stroma) vary with age and with location within the skeleton. The cellular component may be imaged with diffusion-weighted imaging: the sensitivity of the technique to tissue cellularity and its integral fat suppression mean the hametopoietic cellular marrow is differentiated from yellow marrow with high contrast. As prospective studies in children to investigate normal bone marrow are ethically difficult, the work in this thesis is largely retrospective. In the first instance, I undertook to establish the variation of the apparent diffusion coefficient (ADC) quantified from diffusion-weighted MRI of the skull with child's age and gender. The work in chapter 2 shows a significant reduction in ADC at puberty, likely due to a replacement of red with yellow marrow, without gender related differences. Chapter 3 examines the effects of local cancer treatments (radiation therapy and proton therapy to brain tumours) on normal marrow in the clivus and interprets these changes in the context of the reproducibility of the measurement. An early (within 3 months of treatment) increase in ADC with both techniques (reflecting oedema) was followed by a decrease between 3 and 6 months. With systemic treatment, (described in chapter 4), there was a reduction in lumbar vertebral ADC at 3 months, which stabilised or continued to fall by 6 months. The oedematous response seen with local treatment was absent, but replacement of haematopoietic tissue with fat still resulted. Finally, I designed a protocol investigating the effects of bone marrow transplantation on the ADC during engraftment. This prospective study currently open to recruitment will accrue patients over the next 12 months.