Optimising MRI Susceptibility Mapping Methods to Investigate the Effects of Sickle Cell Anaemia on Iron Levels in the Brains of Young Patients
Project Allocated in 2016-2017
Sickle cell anaemia (SCA) is a single-gene disorder that affects haemoglobin, causing red blood cells (RBCs) to become abnormal, fragile and ‘sickle’-shaped. SCA affects 1 in 2000 UK births and as many as 1 in 53 births in sub-Saharan Africa. SCA patients have increased risk of stroke and often have regular blood transfusions to decrease this. Transfused patients are known to have iron overload, particularly in the liver, and may receive iron chelation therapy. However, most young SCA patients in the UK are not regularly transfused, have a lower haematocrit (RBC level) than healthy controls and are not orally supplemented with iron. In Africa, iron deficiency and low haematocrit are prevalent in the general paediatric population as well as those with SCA. The key question is what effect iron deficiency, SCA and transfusion have on iron levels in the brain as this could be related to cognitive effects. It is unknown whether iron levels change in the brains of SCA patients compared with iron-deficient or iron-replete age-matched controls. This is clinically important as it could inform their treatment in future.
Tissue magnetic susceptibility derived by MRI susceptibility mapping (SM) has been shown to correlate strongly with tissue iron content. This makes SM an ideal candidate to investigate brain tissue iron content in young SCA patients. This project will involve optimisation of image acquisition and processing techniques to calculate brain tissue magnetic susceptibility maps in SCA patients and controls.
In addition to expertise in MRI SM, we have access to unique patient cohorts in the UK and sub-Saharan Africa. It may also be possible to use SM techniques to investigate further hypotheses focusing on Auto-adjusting Positive Airway Pressure therapy in SCA as part of ongoing clinical research studies including randomised controlled trials in collaboration with UCL CCTU.
This project will focus on acquiring images in paediatric patients of at least 8 years of age up to young adults in their early thirties. The median age of the cohort is around 13 years of age placing it firmly into the paediatric imaging theme. It is important to understand the effect of SCA on the brains of young patients to inform their future treatment. This project also fits into the neuroimaging theme as we aim to investigate the effect of SCA on regional brain iron content giving us unique insights into pathogenic mechanisms in the brain in SCA and potentially revealing imaging biomarkers which could be used as outcome measures in future clinical studies.
Sickle cell anaemia patients have regular MRI scans of their brains and we aim to develop artefact-free susceptibility mapping MRI pulse sequences that are short enough for patient comfort while also providing accurate measures of brain tissue iron content. As well as these image acquisition challenges, we will optimise the image processing methods required for image reconstruction: calculation of accurate tissue susceptibility maps from MRI phase images using and developing the wide variety of exciting new susceptibility mapping techniques to solve this inverse problem.