Technology

3Scan is modernizing the field of histopathology by introducing an end-to-end services solution for basic research and drug discovery.

A one-stop shop for digital and computational pathology, 3Scan’s suite of technologies and services allow for higher throughput, greater quantification, and more comprehensive image analysis than is currently possible with traditional histopathology.

3Scan’s data-driven tissue investigation pipeline will expand our current understanding of tissue biology, enabling the next generation of medical and biotech research.

Knife Edge Scanning Microscope

3Scan images entire sample volumes of over 100 cm3 at cellular level resolution, combining elements of non-invasive radiology and light microscopy. Our KESM can process up to 3,600 slices per hour (e.g. a whole mouse brain) of any tissue sample at submicron resolution (a voxel size of 0.6 um x 0.7 um x 1.0 um).

To handle data outputs of up to a terabyte per cm3, 3Scan has built customized processing and analysis software. 3Scan offers data processing software to model 3D tissue reconstructions, provide interactive image views, and apply quantitative analytics

The unprecedented volume of high-resolution 3D data generated by the KESM opens up a new realm of possibilities for meso-and micro-scale insights.

Applications include:

  • Large volume 2D fly-throughs (~200-800 sections per cm3)
  • 3D visualizations and models of various tissues (i.e. tumor morphology)
  • Co-registration of features from non-invasive radiology and light microscopy
  • Automated quantification and analysis of specific tissue structures (e.g. microvasculature)

The KESM is a Knife-Edge Scanning Microscope that produces digital 3D tissue models at micron-scale resolution. Using a diamond bladed knife, nano-positioned motions, and proprietary optics, the KESM deliver trillions of voxels per day at 400 times the throughput of traditional microscopes.

The KESM moves in strips across the surface of a block of tissue, slicing and scanning simultaneously. As the tissue is coming off the knife, it captures one line at a time of image data, ensuring precise spatial alignment. Once the KESM has sliced a layer off the entire surface, it moves down a few microns, slices the next surface, and then repeats this process until it has consumed the entire tissue volume.

Image Processing

Reconstructing trillions of voxels into meaningful, digital histology is a multi-step, multi-disciplinary process. The images below show the key stages and products of KESM image processing.

Step 1: Raw

Every pixel of raw data is saved in long-term storage to guarantee data integrity. Slices are saved with meta-data that contain positional offset coordinates as well as camera-capture data such as gain and pixel sizes.

Step 2: Stitched

Regions of interest are deterministically based on the geometry and selected with a 3D bounding box. Imaging fiducials and areas outside of selected regions are removed before slices are concatenated.

Step 3: Cleaned

The cleaning step removes several classes of image artifacts arising from digital noise and physical factors including uneven illumination, vibration, and variation in tissue material properties.

Step 4: Segmented

The region of interest is subjected to object classification algorithms, segmenting it into sub-regions of interest. The classification employs a combination of morphological, distance, and intensity-based criteria.

Step 5: Vectorized

Raster bitmap images are transformed into a network graph representation. This last step of image processing can be used for creating 3D models or used for analytics and topological statistics.

Step 6: Rendered

Depictions of volumetric datasets are created for presentation. Rendering can take many forms and is dependent on application. Outputs include animated fly-through movies of the image slices as well as the 3D projections pictured here.