Children with sickle cell disease (SCD) accumulate numerous tiny strokes during childhood – affecting cognition and motor skills – but difficult to detect on standard MRI scans. Their cause is not well understood but likely involves damage/occlusion of the brain’s tiny end arteries by sickle-shaped red blood cells.
Treatment is based on detecting stenosis (narrowing) in large arteries on transcranial doppler ultrasound (TCD) and magnetic resonance angiography (MRA). However, these significantly underestimates vascular disease burden. Crucially, these do not assess small blood vessels (lenticulostriate arteries), nor provide assessments of brain function (oxygenation or perfusion).
7 Tesla (7T) MRI – twice the strength of standard scanners – allows the high resolution necessary to directly see and measure flow in these tiny perforating brain arteries affected in SCD. However there has been minimal work assessing the vasculature using 7T in children.
This PhD builds on recent funding to scan children with SCD using our latest 7T Terra.X scanner (only system in U.K.) at St. Thomas’ Hospital (https://www.kcl.ac.uk/news/mri-research-funded-to-detect-sickle-cell-injuries-in-children).
SCD affects >15,000 in the UK but receives significantly less funding than other genetic conditions – this project aims to address an important health inequality.
Skills Development:
• Interdisciplinary: close working with clinicians, physicists, AI scientists, physiologists
• 7T MRI physics, operating 7T scanner, image analysis, transcranial doppler
• Paediatric, vasculopathy/stroke imaging.
• Conducting a clinical research project
Aims:
Use 7T MRI to:
-Characterise small vessel vasculature (anatomy and flow) in healthy children
-Identify new and more sensitive biomarkers of vascular injury and stroke risk in children with SCD
By learning and using 7T techniques including:
-High-resolution brain vessel MRI (MRA and susceptibility imaging)
-Small artery phase-contrast flow, venous oxygenation (susceptibility mapping), cerebral perfusion (arterial spin labelling)
Objectives:
Year 1
• Literature review of 7T MRI vascular methods and cerebrovascular disease applications
• Training in operating 7T MRI scanner and image optimisation
• Acquisition of data in volunteer healthy children; begin data collection in SCD children
• Observe clinical TCD scanning of children.
Year 2
• Complete healthy and SCD cohort imaging
• Creation of novel 7T atlas of small vessel anatomy in healthy children
• Characterise normal small vessel flow in healthy children
• Exploration of analysis techniques – such as AI-based analysis of the vascular tree, advanced quantitative flow and perfusion methods
Year 3
• Data Analysis – compare small vessel anatomy and flow between SCD and controls; comparing SCD 7T findings to standard MRIs, TCD, blood tests and cognitive scores
Year 4
• Develop a preliminary predictive model of clinical risk above TCD based on 7T imaging, test this model using 1 year follow up of the imaging cohort.
• Thesis writing and preparation of journal papers for publication
