Building the Foundations for Precision Biomarkers of Brain Health: Linking Retinal Microvascular Structure, Blood Flow and Imaging Measurements

Background

Major neurological disorders, including dementia and cerebrovascular disease, create an urgent need for accessible biomarkers that enable earlier diagnosis, improved risk stratification, and more personalised care. This is particularly important given inequalities in access to specialist investigations such as MRI and other advanced neuroimaging techniques.

The retina offers a unique, non-invasive window into the cerebral microvasculature. As an extension of the central nervous system, retinal blood vessels share anatomical and physiological characteristics with the cerebral circulation. Retinal vascular abnormalities have been associated with neurodegeneration, cerebral small vessel disease, stroke, and dementia [1]. Optical coherence tomography (OCT) is already widely deployed in community optometry and ophthalmology clinics, generating millions of retinal scans annually, making it an attractive platform for future population-scale assessment of vascular health.

Although OCT is routinely used to assess retinal structure, much of the information contained within OCT signals relating to vascular geometry, blood flow, and microvascular function remains poorly understood. Recent advances in OCT instrumentation and image analysis create opportunities to derive quantitative measures of vascular health from retinal scans [2]. However, a critical barrier remains: the relationship between OCT-derived measurements and underlying vascular structure and haemodynamics has not been established quantitatively. Consequently, the biological meaning, accuracy, and limitations of many proposed vascular metrics remain uncertain.

Addressing this challenge requires experimentally controlled systems in which vascular properties and flow characteristics are independently known [3]. Establishing quantitative relationships between OCT signals, vascular structure, and haemodynamics is an essential step towards developing robust, interpretable biomarkers of cerebral microvascular health and enabling future translational studies in dementia, stroke, and related neurological disorders [4].

Aims and Objectives

The project will combine physical modelling, biomedical imaging, and quantitative data analysis to improve understanding of how OCT signals relate to vascular structure and haemodynamics. The overarching aim is to develop the basis for novel OCT biomarkers of microvascular health.

Objectives

1. Develop experimentally controlled retinal microvascular phantoms based on glass capillaries and PDMS microfluidic channels with physiologically realistic dimensions and branching patterns. Flow characteristics will be independently measured using techniques such as particle image velocimetry and volumetric flow measurements [3], providing traceable ground-truth datasets.
2. Characterise OCT-derived vascular measurements using simplified phantom systems consisting of emulsion droplets flowing through narrow transparent channels, enabling direct comparison between measured and known parameters.
3. Investigate the effects of increasing biological complexity by introducing blood-mimicking fluids, whole blood, vessel branching, and compliant vessel walls to model more realistic microvascular environments. PDMS-based systems will additionally enable fluorescent labelling and complementary three-dimensional confocal microscopy for independent structural validation.
4. Develop quantitative analytical methods for extracting vessel morphology and flow metrics from OCT data and evaluating measurement accuracy, precision, and reproducibility.
5. Identify OCT-derived measurements with potential relevance to cerebral microvascular health, providing an evidence base for future translational and clinical studies in neurological disease.

Training Opportunities and Outcomes

The student will be embedded within a highly interdisciplinary environment spanning the School of Physics and Astronomy and the Institute for Neuroscience and Cardiovascular Research (INCR). They will receive training in advanced optics, OCT instrumentation, image processing, fluid dynamics, computational analysis, statistics, vascular physiology, and neuroscience.

The project will provide hands-on experience in microfluidic modelling, imaging system development, quantitative image analysis, experimental design, and reproducible research. The student will gain expertise in the acquisition, management, and analysis of imaging data, while working closely with physicists, engineers, and clinical researchers. Opportunities for engagement with imaging technology developers and external partners will further develop communication, collaboration, and leadership skills.

By the end of the PhD, the student will have developed a unique combination of expertise in optical imaging, quantitative methods, vascular biology, and precision medicine, positioning them to contribute to the development of next-generation imaging biomarkers for neurological.

References:

1. London A, Benhar I, Schwartz M. The retina as a window to the brain: from eye research to CNS disorders. Nat Rev Neurol. 2013;9(1):44–53. doi:10.1038/nrneurol.2012.227
2. Spaide RF, Lee K, Kuo J-W, et al (2025) Ocular Blood Velocity Measurement With Optical Coherence Tomography Using Speckle Analysis. Transl Vis Sci Technol 14:13. https://doi.org/10.1167/tvst.14.11.13 
3. Edwards AMJ, Atkinson PS, Cheung CS, Liang H, Fairhurst DJ, Ouali FF, Density-driven flows in evaporating binary liquid droplets, Physical Review Letters 121 (18), 184501, 2018
4. Hendrikse NM, Llinares Garcia J, Vetter T, Humphreys AJ, Ehmann F. Biomarkers in Medicines Development: From Discovery to Regulatory Qualification and Beyond. Front Med. 2022;9:878942. doi:10.3389/fmed.2022.878942