Functional Ultrasound Imaging (fUS) – an emerging technology for functional and vascular neuroimaging of preclinical animal models

Researchers at the newly established Institute for Neuroscience and Cardiovascular Research (INCR) at the University of Edinburgh are investigating how complex biological processes across organ systems influence overall health. A key focus is understanding the interplay between brain and cardiovascular health, particularly how age-related changes in one system may impact the other and shape disease susceptibility throughout the lifespan. Functional ultrasound imaging (fUS) is a highly sensitive imaging technique gaining traction within the international research community for its ability to capture brain blood flow dynamics in preclinical models. Using Ultrafast Ultrasound Imaging1, fUS provides high spatial resolution maps of brain blood volumes with 50-fold greater sensitivity than conventional Doppler imaging. This sensitivity enables detection of small blood volume changes linked to neuronal activity. fUS can be coupled with another emerging technique, Ultrasound Localization Microscopy2 which tracks the path of individual contrast microbubbles enabling spatial resolution of brain vasculature down to microscopic resolutions. Together, these applications enable 3D mapping of task-induced brain activation, resting-state functional connectivity, and brain hemodynamics and vasculature. The Iconeus One fUS system will add transformative mass to the INCR and provide a platform for collaborative projects between INCR researchers. Embedded within our shared preclinical imaging research facilities in the Biological Research Facility at the BioQuarter site, it will complement existing preclinical imaging scanners. The BioQuarter site accommodates over 1200 researchers and the UoE is undertaking large strategic investments on the campus. Our team includes neuroscientists and cardiovascular scientists and research technical professionals working collaboratively to ensure this technology effectively supports transformative and translational research. fUS will facilitate interdisciplinary studies, addressing specific needs, including: Dynamic imaging of blood flow: Crucial for studying conditions like hypertension, heart failure, and vascular diseases, and understanding cerebral blood flow in brain function, development, and neurodegenerative conditions. Repeated measures in the same subjects: Unlike invasive methods, fUS allows non-invasive monitoring over time. Pathophysiological insights: fUS helps understand how cardiovascular diseases affect neurological health, such as the impact of stroke on cognition or blood flow changes during brain development, aiding research on developmental disorders. Therapeutic development: fUS enables the assessment of therapies targeting both cardiovascular and neurological systems, potentially leading to new treatment strategies. While existing methods like high-field MRI, PET, and conventional ultrasound provide valuable anatomical and metabolic data, fUS offers two key advantages. It can capture rapid changes in blood flow during cognitive tasks or experimental interventions in both anaesthetised and awake, behaving animals. Furthermore, fUS enables multi-modal studies by integrating with techniques like EEG, multi-electrode arrays, PET/MRI, optical imaging and optogenetics providing a comprehensive view of brain and cardiovascular interactions. fUS will be a key asset for interdisciplinary research objectives, such as exploring critical biological mechanisms related to development, ageing, and degeneration in the brain and cardiovascular systems. By monitoring real-time functional changes, like cerebral blood flow, it will help investigate ageing and disease progression. Additionally, it will allow researchers to examine how developmental changes influence disease susceptibility later in life. The research will also promote lifelong health by identifying early biomarkers and evaluating therapeutic interventions that aim to improve quality of life. Tanter M, Fink M. (2014) Ultrafast imaging in biomedical ultrasound. IEEE Trans Ultrason Ferroelectr Freq Control. Jan;61(1):102-19. Couture O. et al (2011) Microbubble ultrasound super-localization imaging (MUSLI),2011 IEEE International Ultrasonics Symposium, Orlando, FL, USA, pp.1285-1287.