What is 3D Optical High-Resolution Episcopic Microscopy (HREM)?

3D Optical HREM is a block-face imaging technique that captures high-resolution images of a sample as it is sectioned. Each slice is imaged at the block surface and stacked into a 3D reconstruction with minimal distortion.

How does HREM differ from confocal and light-sheet microscopy?

HREM physically sections the sample and images the freshly cut surface, producing aligned, high-contrast slices. Confocal and light-sheet rely on optical sectioning and perform best on fluorescent or transparent samples, while HREM is suited to dense or opaque tissue.

What sample types are suitable for HREM imaging?

HREM works well with embryos, small organs, tissue blocks, plant material and other dense or opaque specimens. It is especially useful for samples that confocal or light-sheet microscopes struggle to image.

What resolution can HREM imaging achieve?

HREM typically achieves 1–8 µm voxel size. X–Y resolution is often higher than Z resolution.

What are the advantages of HREM over traditional sectioning methods?

HREM avoids distortion by imaging the block face directly, producing aligned, high-contrast slices. This enables cleaner 3D reconstructions, less manual handling and faster workflow compared to manual sectioning.

How long does a typical HREM imaging session take?

Imaging usually runs at 6–7 seconds per section. Total time depends on section thickness and sample depth; for example, 1 µm sections take around 2 hours per mm of tissue. Larger embryos can take several hours. Multiple blocks can be imaged in one run to improve efficiency.

What sample preparation is required for HREM?

Samples must be fixed, dehydrated and resin-embedded to allow clean sectioning. The polymerised block provides stability for consistent slicing and high-contrast block-face images.

What software is used for 3D reconstruction and analysis?

HREM datasets can be processed in ImageJ/Fiji, Imaris, Amira and other volume-rendering tools for 3D reconstruction, segmentation and measurement.

Do you supply HREM systems worldwide?

Yes. We supply HREM systems worldwide and offer remote support, installation guidance, servicing and customised configurations with international shipping.

What support or training is provided after installation?

We provide ongoing support, remote assistance, software help, troubleshooting and training on system operation, sample preparation and data handling.

How do I request a quotation or discuss a custom HREM setup?

Contact us via form, phone or email with your application, sample type and imaging requirements, and we will prepare a suitable configuration and quotation.

What are the limitations of HREM imaging?

HREM requires resin embedding and physical sectioning, so it is destructive and not suitable for live samples. Fluorescence cannot be captured directly, datasets can be large and calcified or very large samples may need extra preparation.

Products / High-Resolution Episcopic Microscopy (HREM)

High-Resolution Episcopic Microscopy (HREM)

High-Resolution 3D Imaging for Biological Structure

High-Resolution Episcopic Microscopy (HREM) volumetric imaging systems for structural analysis of samples in 2D and 3D

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High-Resolution Episcopic Microscopy (HREM) Micro 3D Imaging System Showing a Mouse Embryo Being Imaged on Monitor.

1-8 µm

Voxel resolution achievable

<1-25 mm

Sample size achievable

2

Dedicated systems for HREM

50+

Existing publications

HREM image of a mouse embryo sample alongside its corresponding 2D block-face section.

3D reconstruction of a mouse heart imaged using High-Resolution Episcopic Microscopy (HREM), showing detailed internal anatomy as the structure rotates.

What is High-Resolution Episcopic Microscopy (HREM)?

High-Resolution Episcopic Microscopy (HREM) is a 3D imaging technique for visualising samples ranging from 1-25mm. Resin mounted samples are stained, then sectioned repeatedly with the remaining block face imaged, creating high-resolution 3D stacks at 1–8-micron voxel resolution.

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High-Resolution Episcopic Microscopy (HREM) Workflow

Sample preparation for High-Resolution Episcopic Microscopy showing a stained specimen embedded in resin prior to serial sectioning

1. Sample Preparation

Fix, dehydrate, and embed in resin. Multiple samples can be embedded in a single block for batch runs.

Serial sectioning in High-Resolution Episcopic Microscopy illustrating thin section removal from a resin block

2. Sectioning

Blocks sectioned at consistent 1–8µm intervals. Each face imaged immediately with no section loss and no mounting.

Block-face imaging step in HREM capturing the exposed resin surface during serial sectioning

3. Imaging

Block surface captured at each step. Scanning stages and structured illumination can be integrated to extend resolution and field of view.

3D reconstruction from sequential HREM block-face images forming a volumetric dataset

4. Reconstruction

Image stacks (e.g TIF) export inherently aligned images for immediate 3D reconstruction, no registration step needed.

Compatible Analysis Software

Fiji/ImageJ

Dragonfly

Imalytics Preclinical

Imaris

3D Slicer

Output Formats

TIF/TIFF

JPG

PNG

BMP

Output Formats

Want to visualise HREM data?

Try our 3D viewer with a dedicated embryonic mouse sample crop, explore, and export.

3D Viewer

Advantages of High-Resolution Episcopic Microscopy (HREM)

High-Resolution Episcopic Microscopy (HREM) as a serial block-face 3D imaging technique offers several practical advantages to other volumetric imaging methods. Because imaging occurs prior to section removal, geometric fidelity is preserved without the requirement for tissue clearing, manual slide alignment or complex post-acquisition registration.

Intrinsic Alignment

HREM produces inherently registered stacks by imaging the block surface, reducing registration complexity and preserving spatial accuracy.

Quantitative Stability

HREM is suitable for volumetric measurement, surface area quantification, branching analysis and phenotypic screening due to the repeatability, resolution and scale.

High Contrast in Dense Samples

Surface-based imaging enables consistent capture of bone, pigmented tissue, opaque tissue and dense organs which may be limited by optical penetration limits on other volumetric techniques.

Large Volume with Micro Detail

Samples up to ~25mm can be imaged while maintaining micron-scale resolution, with scanning extending field of view possibilities.

True Volumetric Resolution

Consistent section 1-5 micron section thickness allows for accurate 3D measurements, suitable for morphometric analysis.

No Tissue Clearing Required

As imaging is performed directly on the block surface, optical clearing is not necessary, which reduces preparation complexity and other complications.

Applications of High-Resolution Episcopic Microscopy (HREM)

HREM has been widely used in multiple disciplines and can be applied to a wide range of morphological studies. Imaging denser samples up to 25mm down to below 1mm with voxel sizes down to 1 micron. Most commonly, samples in the range of 1-12 mm are imaged for detailed structural analysis.

Early stage and late stage 3D mouse embryo

Mouse Embryos

HREM has been widely used to image full mouse embryos across all stages of development

Full 3D reconstruction of whole mouse embryos in high detail
Track developmental abnormalities across gestational stages
Quantify organ formation and spatial relationships

Mouse Hearts

HREM has been used extensively for mouse heart imaging at stages E9.5+

Visualise intricate 3D cardiac structures and vasculature
Study congenital heart defects (CHD) and structural remodelling
Ideal for phenotyping mutant mouse lines

Plant Samples/Seeds

3D imaging of seed structures and root development
Image vascular bundles, meristems and embryogenesis
Ideal for agricultural trait research and seed phenotyping

Small Animal Organs

Capture kidney, liver, placenta and lung in full 3D under 1 mm up to 20mm
Measure volume, surface area and branching networks

Chick Embryos

Large scale imaging of early vertebrate development
Assess segmentation, heart looping and organogenesis
Bridge developmental biology with anatomical analysis

More

Zebrafish
Drosophila (fruit flies)
Human biopsy samples
Nervous system/Brain imaging
Much more

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Publications

Flexibility for a Range of Samples

High Resolution Episcopic Microscopy is less impacted by optical penetration depth than other volumetric techniques, as imaging is performed directly on the resin block surface. This produces reliable three-dimensional imaging of structures including bone, calcified structures and pigmented tissue with complex samples with mixed density producing high contrast.

HREM supports imaging across a wide range of biological samples, including mixed density tissues within a sample.

Drosophila imaged with high-resolution episcopic microscopy

Bone & calcified structures

Dense tissue imaged with consistent contrast, no clearing related artefacts or penetration limits.

Mixed density samples

Soft and hard tissue in the same block with no trade-off in contrast quality across the sample.

Pigmented tissue

No optical interference contrast is consistent regardless of pigmentation.

Intact whole samples

Up to 25mm in a single acquisition. Larger samples accommodated with scanning configurations.

HREM 3D embryonic mouse cross section captured with HREM morphology imaging system

High-resolution stitched Optical HREM Ultra image of a mouse section, revealing fine structural detail across the tissue.

High Resolution for Various Tissue and Sample Types

HREM typically operates within the voxel size range between 1-8 microns, with section thickness defining the Z resolution, enabling accurate 3D measurements and reliable structural reconstruction.

At these resolutions, fine structures can be visualised and quantified/segmented such as small vessels, branching networks, nerve structures and tissue boundaries. Unlike conventional imaging approaches where resolution can decrease with sample size, HREM maintains resolution with scanning configurations.

1-8 Micron voxel resolution for detailed volumetric imaging
Defined axial resolution via physical section thickness
Scanning configurations for extended field of view at maintained resolution

Configurable to your requirements

XY

SCANNING

Scanning stages

Extend field of view across larger samples. Resolution no longer limited by sample size.

EF

FOCUS

Electronic focus module

Adjust focus across the full block face with ease from the dedicated software application, for multiple samples or simply ease of use.

SI

ILLUMINATION

Structured illumination

Improves fluorescence contrast and rejects out-of-focus background for targeted channel imaging.

Det.

SESNORS

Detector options

Choice of detectors from low-noise sensors to high-resolution single-shot sensors, matched to your resolution and sensitivity needs.

4×

BLOCKS/RUN

Multiple samples

Image up to 4 blocks per session. Increases throughput for cohort phenotyping and knockout screening.

↗

CUSTOM

Custom configurations

Specific requirement? We work with you on optics, blade types, illumination, and software to meet your exact imaging needs.

Every HREM system can be upgraded or configured to match your application across resolution, throughput, illumination, and sample handling. Options shown with system compatibility.

Stitched Optical HREM 3x2

Optical HREM Systems

We offer two main Optical HREM system solutions, available worldwide, offering flexibility in budget and in capture. Each system can achieve highly detailed 3D image stacks, while allowing the systems to be accessible to more.

Optical HREM Micro 3D block face imaging sstem, imaging mose embryo with 3D running

OHREM Micro

Micro OHREM Systems offer simple imaging of samples up to 25mm in FOV, featuring single shot optics.

Highlights

25 × 20 × 20mm field of view
Single-shot optics
Compact form factor
Optional scanning and focus module

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Optical HREM Ultra block face 3D imaging system imaging a mouse embryo with a 3D

OHREM Ultra

Ultra OHREM systems offer flexible imaging with XY scanning stages with various illumination and optical setups.

Highlights

Larger field of view with scanning
Structured illumination option
Multi-sample up to 4 blocks/run
Electronic focus module

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Not sure which fits your work?

CHOOSE MICRO IF...

Samples are consistently under 20mm
Single-sample runs suit your workflow
Lab space or budget is a consideration

CHOOSE ULTRA IF...

Scanning or larger field of view needed
3+ Fluorescence channels are required
High throughput or multi-sample runs

HREM Products

Dr Duncan Sparrow

DPAG, University of Oxford

'We are extremely happy with the high quality 3D imaging of our samples. The OHREM system is very flexible, and fully upgradable. We initially only had funds for the single-channel model. However, when we got another grant 12 months later, able to upgrade our system to a 2-channel model with less than 24 hours downtime. The system is very reliable, with virtually no maintenance required. For example, we have used our machine 24/7 for months on end, without any repairs required. In the 2 years we have had the OHREM, we have achieved completely consistent data quality. Aftersales service is friendly, prompt and informative. '

Frequently asked questions

HREM samples can be imaged at 6–7 seconds per section, though this varies with section thickness and sample size. Approximate imaging speed per millimetre • 1 µm → 1000 sections → ~1 hr 57 mins • 2 µm → 500 sections → ~58 mins • 3 µm → 333 sections → ~39 mins • 4 µm → 250 sections → ~29 mins • 5 µm → 200 sections → ~23 mins • Real-world example timings • Embryonic mouse heart (E14–E16, ~1.5–2.0 mm deep) • 1 µm: 2.5–3.3 hrs • 2 µm: 1.3–1.9 hrs • 3 µm: 1.0–1.3 hrs • E10–E11 mouse embryo (small, ~4–6 mm deep) • 1 µm: 6.7–11.7 hrs • 2 µm: 3.3–7.0 hrs • 3 µm: 2.2–3.9 hrs • E14–E15 mouse embryo (larger, ~8–10 mm deep) • 1 µm: 13–19 hrs • 2 µm: 6.7–9.7 hrs • 3 µm: 4.4–6.5 hrs Time efficiencies can be achieved by combining samples into one block or by imaging multiple blocks in a single run using the Ultra system, which reduces sectioning overheads and allows the instrument to run unattended.

HREM is a block-face imaging technique, while confocal and light-sheet systems capture images through intact tissue. HREM physically sections the sample and images the freshly cut surface, producing perfectly aligned slices with high structural contrast. Confocal and light-sheet are excellent for fluorescent, transparent or cleared samples, but HREM is ideal for dense or opaque tissues and for capturing fine anatomical detail across larger volumes.

Contact our High-Resolution Episcopic Microscopy (HREM) Experts

Want to know more about HREM, ask for a quote or get questions answered. Contact us and we can help answer all your questions.

Phone:
+44(0) 1462633500

Email:
hello@indigo-scientific.co.uk