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High-Resolution Episcopic Microscopy (HREM) for 3D Cardiovascular Imaging

  • 18 hours ago
  • 3 min read

Imaging the embryonic heart in mice can often be challenging due to its small size and structural complexity. With typical sizes ranging from under 1 mm to just a few millimetres, detecting subtle cardiovascular abnormalities becomes difficult. This is especially true when accurate 3D cardiac imaging is required.


Traditional histology techniques often lose 3D context, while other 3D imaging technologies can introduce their own limitations when imaging mouse, human, and similar soft tissue samples.


High-Resolution Episcopic Microscopy (HREM) offers the clarity of histology combined with true 3D structural context, making it particularly well suited for embryonic heart imaging and cardiovascular phenotyping.


2D and 3D HREM images of a mouse embryo highlighting heart structure

What is HREM?

HREM is a block-face imaging technique that captures images of a sample during physical sectioning. This approach provides several key advantages, including no need for optical clearing, minimal tissue distortion, and strong compatibility with soft tissue samples.

These features make HREM ideal for soft tissue imaging, embryonic development studies, and preclinical cardiovascular research. As a result, it is widely used in mouse embryo cardiac phenotyping.



What HREM Reveals

HREM is a growing technique within preclinical cardiac imaging and has been applied across a wide range of cardiovascular studies.

Common applications include:

  • Septal defects

  • Valve abnormalities

  • Outflow tract defects

  • Congenital heart disease models


With voxel sizes down to 1 micron and excellent soft tissue contrast, subtle structural abnormalities can be visualised with high precision. These are often difficult to detect using alternative methods such as micro-CT or standard 2D histology.


HREM is also commonly used for comparison between wild-type and mutant models, enabling detailed analysis of developmental differences in cardiac structure.

With emerging biological models such as cardioids and organoids, HREM has the posibility to provide a strong balance between resolution and sample size, making it highly suitable for next-generation cardiovascular research.


3D reconstruction of a dissected mouse heart with cross-sectional view using HREM

Expanding HREM Technology at Indigo Scientific

At Indigo Scientific, we have been developing new technologies to enhance HREM capabilities and improve imaging performance.

Recent developments include:

  • Scanning stage integration across all systems

  • Structured illumination for improved image quality

  • Multi-sample imaging workflows


Structured illumination enhances in-focus detail while reducing out-of-focus signal, improving overall image clarity. It also opens up the possibility to perform fluorescence imaging within HREM workflows, enabling higher contrast and additional biological insight with appropriate sample preparation.


Scanning stages expand the field of view without sacrificing magnification, while still allowing standard single-shot imaging when required. They also enable imaging of up to four samples in a single run, significantly increasing throughput.


These advancements position optical HREM systems as a solution for high-resolution, high-throughput 3D imaging, without clearing or alignment issues.

2D HREM image of soft tissue showing high-resolution structural detail
Scanned HREM Image

Cardiovascular Applications for Optical HREM

Optical HREM can be adapted for a wide range of cardiovascular samples and experimental setups.


Typical applications include:

  • Mouse embryo hearts – detailed imaging of early-stage cardiac development

  • Adult mouse hearts – structural and pathological analysis

  • Whole embryo cardiovascular-lung studies – imaging heart and lung development in context

  • Chicken & other species


Summary of HREM in Cardiovascular Imaging

High-Resolution Episcopic Microscopy provides a reliable method for high-resolution 3D imaging of cardiovascular structures, particularly in small and complex samples such as mouse embryos.


By combining histological detail with true 3D context, HREM enables accurate analysis of cardiac development, structural abnormalities, and comparative models.

With continued advances in optical HREM systems, including structured illumination and expanded imaging capabilities, the technique is becoming increasingly valuable for preclinical cardiovascular research.


 
 
 

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