High-Resolution Episcopic Microscopy Benefits & Applications
- ashley7671
- Jul 25
- 4 min read
High-Resolution Episcopic Microscopy (HREM) technique offers a unique visualisation of fixed tissue samples at micrometre resolution. It bridges the gap between traditional histology and more advanced volumetric imaging making it ideal for the study of mice embryos, mice organs, plant samples and more.
Introduction to High-Resolution Episcopic Microscopy
High-Resolution Episcopic Microscopy (HREM) is a serial block-face imaging technique that combines a modified microtome with an optical imaging system. A resin block contains the fixed sample. As the block is sectioned, each newly exposed surface is imaged directly. This process captures high-resolution 2D data without the optical distortion common in other volumetric techniques. Because the imaging is done at the block face, alignment is inherently precise, and resolution in the Z-axis is consistent, typically ranging from 1 to 8 microns, with even finer resolution in the X and Y axes.
Applications of HREM in Research and Industry
HREM is used in a variety of applications currently, due to its high resolution over denser volumes it is often used in Heart imaging in mice for dine morphological studies.
Benefits
High-Resolution Episcopic Microscopy (HREM) bridges a critical gap between high resolution and sample size, making it ideal for detailed morphological analysis. It offers strong contrast without the need for complex sample clearing, interpolation, or post-processing that can introduce distortion.
High Z-Axis Resolution
Achieve consistent resolution between 1–8 microns in the Z-axis, enabling precise 3D visualization of fine structures like blood vessels and tissue layers.
Sub-Micron XY Resolution
By scanning the block face, sub-micron resolution can be achieved in the X and Y axes even across large sample areas of up to 60 mm, depending on configuration.
No Sample Clearing Required
Unlike many 3D imaging methods, HREM does not require optical clearing, making sample preparation simpler and preserving natural contrast.
Low Distortion and Inherent Alignment
Because each slice is imaged directly from the block face, there's no need for realignment or interpolation resulting in accurately aligned, high-fidelity volumes.
Cost-Effective
Compared to other high-resolution 3D imaging techniques, HREM remains relatively affordable), especially for labs focused on fixed-sample analysis with high precision needs.
Challenges and Limitations
While HREM provides high resolution and structural detail, there are a few practical considerations to keep in mind. Most notably, HREM is a destructive technique, meaning it can only be used on fixed samples. This makes it ideal for endpoint imaging rather than live or dynamic studies.
Sample size is another factor. Though HREM can section and image a maximum of 60mm x 30mm x 60mm, most imaged samples fall within the 1–15 mm range. The limitations are largely due to the physical properties of the embedding resin and the staining. That said, larger samples can still be imaged with some experimentation.
Traditional HREM relies on inverted fluorescence, where the block itself fluoresces. This method produces strong morphological contrast but can limit flexibility in using multiple stains or dyes. However, ongoing research is expanding HREM’s capabilities, recent work has shown success in combining this approach with targeted fluorescence staining, allowing for richer biological insights beyond morphology alone.
As HREM continues to grow in users and develop limitations are being addressed and solved from application to application.
Why Choose Indigo for HREM?
Indigo offers a range of dedicated and cost-effective solutions for High-Resolution Episcopic Microscopy (HREM). Our fully integrated systems are purpose-built for block-face imaging, combining precision engineering with robust software and support.
Dedicated Software
We provide a purpose-built HREM imaging suite that integrates microtome control, image acquisition, and management. The software balances simplicity and power, offering a streamlined interface alongside advanced features developed in collaboration with our users.
Seamless Hardware Integration
Our systems include custom-designed microtomes, XY stages, focus control, and optical platforms, all engineered to work together for reliable, high-resolution block-face imaging.
High Throughput & Resolution Enhancements
Indigo systems are built for efficiency. We've enhanced traditional HREM workflows with faster, more robust sectioning platforms and high-precision XY stages, enabling imaging of multiple blocks or larger samples in a single experiment. We also support wide field-of-view imaging through scanning.
Custom Add-Ons & Configurations
From fluorescence compatibility to extended field imaging, we offer a wide range of add-ons and hardware customizations to meet diverse research needs.
Expert Support & Training
With years of experience in serial sectioning and imaging systems, our team offers worldwide support and specialized training tailored to your application and workflow.
Our HREM Platforms
Micro - A compact, cost-effective platform designed for traditional HREM imaging. Ideal for smaller labs or single-sample workflows.
Ultra - A high-throughput system with enhanced capabilities for imaging larger samples, performing multi-fluorescence studies, or scanning multiple specimens in one session.
Conclusion
HREM is a powerful tool for high-resolution 3D analysis, especially in samples that are challenging to visualize using conventional techniques. With inherently aligned volumes and Z-axis resolutions as fine as 1–8 microns, it is ideal for detailed morphological studies — and increasingly applicable in broader biological imaging.
For more information or to request a quote for one of our HREM systems, please get in touch.
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