Combined high-frequency ultrasound and photoacoustics imaging platform

• Subject Area: Neurosciences
• Term: Funded in 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544802256

High-frequency ultrasound (US) has so far seen only limited use in preclinical neuroscience research but is emerging as a unique tool to study real-time vascular function and haemodynamics in the brain. This is, because high-frequency US imaging provides high temporal resolution (several thousand frames/sec), deep tissue penetration (>1.5 cm), a large field of view (~1 cm2) and a spatial resolution in the µm range, with recent superresolution approaches even allowing visualisation of the whole vascular tree down to the capillary level. Moreover, US systems when combined with photoacoustic (PA) capabilities provide additional advantages, as they enable multispectral imaging with simultaneous visualisation of e.g., tissue oxygen levels (through detecting de/oxyhaemoglobin levels) and molecular alterations through application of PA dyes and contrast agents. PA and US images acquired in parallel can then be integrated, generating multi-modal images of brain vasculature and pathology. Vascular dysfunction is of high clinical relevance in neurovascular disorders and neurodegenerative diseases such as stroke and Alzheimer’s disease, respectively; however, our understanding of their pathogenesis remains incomplete. Therefore, this proposal concerns the acquisition of a combined US/PA system for integration in the existing imaging unit at the Centre for Stroke and Dementia Research (CSD) at the LMU. The new system will support novel experimental approaches of five research groups as well as DFG-funded consortia (incl. a FOR, a current and planned CRC/TRR and an Excellence Cluster), and access will also be provided to the wider research community in Munich. Notably, the US/PA system will extend the current imaging capabilities at the CSD by bridging the technological gap between existing microscopic setups (such as 2-/3-photon and mesoscale microscopes, with high to medium spatial resolution but low tissue penetration depth) and macroscopic imaging modalities (such as magnetic resonance imaging, which allows for whole organ/body imaging with high anatomical contrast but low temporal resolution) as they are currently in use for preclinical in vivo imaging. Scientifically, the combined US/PA platform will enable novel lines of investigation such as monitoring vascular structure, function and haemodynamics throughout the mouse brain (incl. deep, vulnerable regions such as the hippocampus) through simultaneously visualising anatomy with US and pathology with PA imaging. Moreover, a system that provides both handheld and motorised/mounted US/PA probes will enable direct investigations of how peripheral vascular dysfunction affects pathology in the brain. Thus, this modality will expand state-of-the-art in vivo imaging approaches and enable further cutting-edge research into the role of vascular dysfunction as a driver of neurological disorders at the CSD.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Kombinierte Hochfrequenz Ultraschall und Photoakustik Imaging Plattform
• Instrumentation Group: 3900 Ultraschall-Diagnostikgeräte
• Applicant Institution: Ludwig-Maximilians-Universität München
• Leader: Professor Jonas Neher, Ph.D.