PUFFINS Brain Health Study

Cerebral small vessel disease (SVD) is a major underlying contributor to ischaemic and haemorrhagic stroke, cognitive decline, and dementia. Neuroimaging features of SVD have been shown to be associated with increased risk of stroke occurrence, reoccurrence, and cognitive decline post-stroke. New approaches are needed that target SVD diagnosis, monitoring, and treatment, to improve outcomes across the stroke and cognitive decline care pathways. However, providing equitable access to advanced medical technologies across the Scottish population is becoming a significant burden on the NHS and wider clinical community. Low-field MRI, which is both more cost-effective and less complex to operate, has the potential to address this growing societal burden at a whole-population level. Whilst on-going research efforts remain focussed on developing new interventions to slow progression of SVD and improve treatment outcomes, work is also needed to improve approaches to assess SVD pathophysiology, severity, progression, and treatment outcome. Repeated assessment with magnetic resonance imaging (MRI), is recognised as the best solution to detect the multiple features that combine to produce SVD. This has the potential to identify markers of stroke risk and cognitive decline and, in future, guide tailored treatments to better manage stroke risk and improve post-stroke long-term outcomes. No other imaging technique, blood test or other assessment can provide the necessary information. However, the high cost and infrastructure demands of conventional MRI means that while it is feasible for clinical trials and research, it cannot realistically be used for widespread repeated brain imaging assessment, or screening, for SVD. For this reason, robust and reliable imaging methods that can be easily implemented across the whole Scottish population, rural/urban, wealthy/deprived must be developed. Operating at magnetic field strengths up to 10,000 times lower than conventional MRI, low-field MRI technologies provide a unique opportunity to make repeated brain imaging cost-effective and accessible in community and outpatient settings. The utility of commercially available portable low-field MRI technology, operating at a fixed field of 64 mT (milliTesla), has already been proven for imaging acute stroke at the bedside of patients and recent preliminary findings have indicated its feasibility to detect moderate and severe SVD. However, the novelty of portable low-field MRI means that its full potential has yet to be realised, and work is now required to develop low-field quantitative imaging approaches to enhance the capabilities of low-field MRI to extract underlying features related to brain health and SVD severity. We aim to provide a stepping-stone to optimised fixed low-field MRI technology by leveraging the unique capabilities of field-cycling imaging (FCI), a unique whole-body MRI technology developed at the University of Aberdeen. IRAS Form Reference: 25/PR/0216 IRAS Version 6.4.1 Date: 13/02/2025 350553/1711955/37/104 7Investigations using field-cycling technologies, which vary the strength of the magnetic field during acquisition, have shown unique sensitivity to tissue features and contrast mechanisms that are invisible at higher, fixed, magnetic fields such as 1.5 and 3T. Furthermore, using FCI, differences between healthy tissue and stroke pathology have been observed. Our own preliminary results, using the mark 2 FCI scanner to image patients with SVD at field strengths between 0.2 and 200 mT have shown a significant positive linear correlation between the volume of SVD extracted from FCI images and from 3T MRI images. However, these preliminary results, limited to a single slice acquisition at 3.1 x 3.1 x 10 mm resolution, do not provide the full evidence needed to design new, cost-effective and accessible, lowfield MRI scanners that would enable widespread, repeated brain imaging assessment for SVD. The objective of this proposal is therefore to address this evidence gap and to inform the design of new low-field MRI technologies tailored to extracting key markers of SVD. First, by utilising the unique capabilities of the new mark 3 FCI scanner, now onsite at Aberdeen Royal Infirmary, imaging data will be acquired at multiple different field strengths, and a higher pixel resolution. This data will be used to determine the most effective low-field approach to identify markers of SVD (e.g., white matter changes, reduced perfusion, microbleeds, recent lacunar infarcts) and SVD progression. Second, by acquiring imaging data from both field-cycling imaging (FCI) and a separate fixed low-field MRI scanner, the extent of agreement between assessments of SVD will be examined.

• Small vessel disease volume agreement between enrolment Field-Cycling Imaging and enrolment Ultra-low Field MRI. [Time frame: At enrolment]
• Small vessel disease volume agreement between follow up Field-Cycling Imaging and follow up Ultra-low Field MRI. [Time frame: At 18 month follow up]
• Strength of association between small vessel disease volume obtained from Field-Cycling Imaging, with small vessel disease severity (Fazekas score), age, mood, and cognition. [Time frame: At enrolment]
• Strength of association between small vessel disease volume obtained from Ultra-low Field MRI, with small vessel disease severity (Fazekas score), age, mood, and cognition. [Time frame: At 18 month follow up]