Preclinical in-vivo cerebrovascular imaging in rodent models: Methods and applications in Alzheimer’s disease

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Abstract
The cerebral vasculature maintains brain function through precise blood flow regulation and its disruption is increasingly recognised as an early and functionally significant feature of Alzheimer’s disease. Understanding these pathologies requires high-resolution imaging capturing cerebral microvascular flow in vivo, particularly in rodent models enabling longitudinal investigation. However, existing modalities involve inherent trade-offs between spatial and temporal resolution, depth, sensitivity and accessibility, while anaesthetic and methodological variability limit cross-study comparability. High-resolution optical imaging, such as two-photon microscopy, provides capillary-level visualisation but is limited by imaging depth and invasiveness. Non-invasive techniques like multi-exposure speckle imaging and optical coherence tomography assess superficial cerebral blood flow dynamics, while magnetic resonance imaging and positron emission tomography offer whole-brain coverage at lower resolution and accessibility. Contrast enhanced ultrasound presents a promising balance of resolution, sensitivity, non-invasiveness and depth penetration. Recently, ultrafast ultrasound localisation ultrasound microscopy has enabled super-resolution imaging by tracking individual microbubbles to quantitatively map microvascular flow. This review critically evaluates preclinical imaging techniques for assessing cerebral microvascular flow in rodents, highlighting their methodological considerations, strengths and limitations. We provide a framework for modality selection and identify ultrafast ultrasound localisation microscopy as the modality best positioned to deliver the standardised, longitudinal and multiscale imaging approach currently lacking.
Funding Information
  • Australian Government Research Training Program (RTP) Scholarship
  • Western Australian Future Health Research and Innovation Fund (69433_WANMAIdeas2024-25/2)

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