top of page

3D Imaging of Mice and Zebrafish with High-Resolution Episcopic Microscopy

Imaging of Mice and Zebrafish in 3D at Micron Scale

High-Resolution Episcopic Microscopy (HREM) produces complete, gap-free 3D datasets of mouse and zebrafish samples at histological resolution, from whole embryos to individual organs. Without sample clearing, section distortion, or the tissue loss associated with conventional histology. Image stacks are inherently aligned from acquisition, ready for immediate 3D morphological reconstruction and quantitative analysis.

E9.5 Mouse Embryo Imaged with HREM

Overview of Imaging Mouse and Zebrafish Samples in 3D

High-Resolution Episcopic Microscopy (HREM) is used to capture mouse and zebrafish samples across the full range of developmental stages, from sub-millimetre embryos to adult whole organs. Indigo-Scientific HREM instruments produce large, high-quality image stacks at high throughput, with no requirement for sample clearing and no distortion introduced to the block face during acquisition.

This technique supports both whole 2D section review and complete 3D reconstruction from a single dataset, making it practical for developmental biology, phenotyping screens, and structural research in the same workflow.

Applications in Developmental Biology and Phenotyping

HREM is applied across a wide range of studies in mouse and zebrafish models, including:

Neuroanatomy and brain imaging

Image whole brains for detailed analysis of tissue architecture and structural organisation. Without the distortion introduced by optical clearing. ​

Knockout and phenotyping screens

HREM is routinely used in large-scale phenotyping programmes where embryonic lethal or sub-lethal lines require rapid, standardised 3D characterisation. A single acquisition run can replace weeks of serial histology sectioning, and the resulting datasets are directly comparable across animals within a cohort. Multi-sample scanning stages allow several embryos to be embedded and imaged in a single block, significantly increasing throughput for screen-scale work.

Whole organ morphology

Image individual organs such as kidney, lung, liver, gut for anatomical and developmental analysis. HREM is particularly well suited for knockout models that require complete 3D context to characterise accurately.

Cardiovascular imaging

Visualise whole hearts in both 2D sections and fully reconstructed 3D models. HREM resolves chamber morphology, valve structures, septal anatomy, and outflow tract alignment with the clarity needed to classify congenital defects such as ventricular septal defects (VSD), atrioventricular septal defects (AVSD), and transposition of the great arteries. Ventricular volumes can be quantified directly from the dataset.

Why Use HREM for Mouse and Zebrafish Imaging

<1mm

to 25mm

Broad sample size range

Sample sizes from under 1mm up to 25mm accommodate the full developmental range — from early mouse embryos at E9.5 (approximately 2–3mm crown-rump length) through to postnatal pups and adult zebrafish organs. Larger samples can be accommodated on request.

1-8µm

voxel size

Fine structural detection

Voxel sizes of 1–6 microns enable identification of subtle anatomical changes relevant to phenotyping and disease studies — structures that would be missed at the resolution of micro-CT or MRI.

20+

megapixels

High resolution throughout the volume

Unlike optical methods that degrade with depth, HREM resolution is consistent across the entire z-depth of the sample, because each image is acquired from the freshly cut block face rather than through intervening tissue.

0

gaps

Inherently aligned image stacks

Serial block-face imaging produces datasets that are perfectly registered by acquisition — no computational alignment step is required, and there are no the cumulative registration errors that affect histological section stacks reconstructed post hoc.

No

clearing

No sample clearing required

HREM does not require optical clearing. This is a significant advantage for samples where clearing is impractical — dense tissue, mineralised structures, or specimens where the clearing process itself introduces distortion or shrinkage artefacts.

Full

soft tissue

Excellent soft tissue contrast

Histology-like contrast enables clear visualisation of internal structures such as organs, vasculature, and fine tissue boundaries.

E14.5 Mouse Embryo

3D Mouse Embryo and Mouse Pups in Full

High-Resolution Episcopic Microscopy is widely used to image individual organs dissected from mouse embryos and pups, as well as whole intact specimens. HREM systems are particularly well suited to capturing detailed datasets of the heart, kidney, brain, and gut for structural and developmental analysis, producing data that supports both qualitative assessment and quantitative volumetric measurement from the same acquisition.

Zebrafish Imaging in 3D

Zebrafish is one of the most widely used vertebrate model organisms in developmental biology and genetics, and HREM is well suited to imaging across its full developmental range. Samples including zebrafish larvae, juveniles, and dissected adult organs can all be imaged without clearing, an important advantage for researchers working with denser tissue or mineralised structures where optical clearing methods become unreliable.


Chick embryos, catfish, and other aquatic species at comparable size ranges are also compatible with HREM imaging.

3D Zebrafish with Other Samples
Two diagrams of HREM illustration and Micro-CT illustration

Why Choose HREM Over Other Imaging Techniques

Researchers often evaluate multiple imaging methods when studying morphology or development. High-Resolution Episcopic Microscopy is particularly well suited to applications requiring high-resolution structural detail, consistent contrast, and accurate 3D reconstruction of small biological specimens while remaining economical.

Explore High-Resolution Episcopic Microscopy

Learn more about the technique or explore example datasets to see HREM in practice.

3D HREM plane view cross section
bottom of page