Neurovascular imaging · Preclinical models

What tools are available to study the brain and blood vessels in preclinical models?

Researchers studying the brain and its blood supply in mouse, rat, zebrafish, and non-human primate models have many imaging options — but most require removing the brain from the skull and preparing separate specimens for each modality. That extraction disrupts meningeal vessels and skull–brain vascular connections that are now understood to be biologically important, and it can change tissue morphology in ways that affect interpretation.

What researchers typically do

Typical neurovascular and cranial vascular workflows combine hematoxylin and eosin (H&E) histology, immunohistochemistry (IHC) for vascular endothelial markers or markers of brain cell types, whole-slide imaging (WSI) of serial sections, cleared-tissue light-sheet fluorescence microscopy, and confocal microscopy for fine vessel detail. Each modality is usually analyzed with its own commercial or open-source tool — ImageJ/Fiji, QuPath, Imaris, Aivia, HALO, or custom Python pipelines — with manual or semi-automated segmentation, atlas alignment, and limited cross-modal registration. That approach works for many questions but cannot preserve skull–brain–meningeal interfaces in one intact specimen.

In situ micro-computed tomography for cranial neurovascular and neuroimmune interfaces

The iterative in situ micro-CT workflow published in Cell Reports Methods (Rosenblum et al., 2021) and STAR Protocols (Dang et al., 2023) is the only published method to study skull, brain, and meningeal vasculature together in the same head — without dissection that disrupts cranial interfaces. The NeuroSimplicity Anatomic Imaging Module works seamlessly with this workflow — and is the only analysis tool available that does — providing automatic segmentation, atlas registration to the sample, and quantitative metrics across staged scans of the same specimen. When labs license the full Imaging Suite (Anatomic Imaging, Molecular Imaging, Digital Pathology, and Spatial Omics Modules together), they can register light-sheet, histology, confocal, and other modalities from the same cohort into one native sample-space framework — enabling prospective study design that reduces cost, time, labor, and specimen use.

What the platform enables

  • In situ micro-computed tomography (micro-CT) — skull, brain, and meningeal vasculature in one specimen
  • Iterative scan registration (bone/vasculature → contrast cast → soft tissue) via the Anatomic Imaging Module
  • Cross-modal registration across the full Imaging Suite — light-sheet, histology, confocal, and MRI from the same cohort
  • Atlas registration to the sample (e.g., Allen Atlas CCFv3, NeuroSimplicity Cranial and Vessel Atlases)
  • Automated feature extraction, labeling, and quantitative metrics in native sample space

More detail

In situ micro-computed tomography of murine cranial vasculature from Cell Reports Methods (2021)
In situ micro-computed tomography of murine cranial vasculature from Cell Reports Methods (2021)

NIH NINDS collaborators applied this pipeline in Nature (2024, 2026) to map dural sinuses, venolymphatic hubs, dural-associated lymphoid tissues (DALT), and skull–brain–meningeal interfaces.

For bench adoption, you can explore interactive step-by-step protocol guides on this site — linked in Next steps below — derived from the Cell Reports Methods and STAR Protocols papers.

Peer-reviewed research

This workflow is documented in Cell Reports Methods and STAR Protocols, and applied in Nature discovery studies by NIH NINDS collaborators. Full citations, figures, and paper links are on our publications page.

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Next steps

Neurovascular Imaging Tools for Preclinical Brain & Blood Vessel Studies | NeuroSimplicity