Digital Scanning and MultiBrain® Layouts Technology:
An Interview with NSA’s President, Dr. Bob Switzer
Below is an excerpt from “Neurohistology: How whole slide scanning impacts workflow: An interview with Dr. Robert Switzer, President and Chief Scientific Officer of NeuroScience Associates (NSA), conducted by April Cashin-Garbutt, MA (Cantab)”. Read the entire interview here*.
Can you please outline the vision behind NeuroScience Associates (NSA)?
Leveraging the mass production benefit that MultiBrain® technology brings to neurohistology, NSA can accelerate the R&D preclinical and safety assessment processes many fold and perform them less expensively. This results in faster times for a potential drug to move from R&D to clinical trials and sooner for use in people.
Additionally, utilizing some of the same principles, our proprietary Large Format™ technology enables us to embed and section an entire human brain hemisphere intact. This not only speeds up processing, but dramatically improves visualization of the entire hemisphere, vs the standard practice of viewing small 1-2cm slabs.
How is NSA able to perform neurohistology up to 40X faster than traditional methods?
Traditional histologic methods section one brain at a time using paraffin embedded tissue or freeze-sectioning with cryostats. With MultiBrain® technology we embed up to 40 mouse brain hemispheres or 40 spinal cords into one MultiBrain® gelatin block. The block is freeze-sectioned with all of the cut sections collected into an array of containers filled with ‘antigen preserve’ solution.
The resulting ‘sheets’ of sections are stained, usually ‘free floating’ (not mounted on slides yet) which allows all of the sections from different brains contained in the sheets to be exposed to identical staining conditions. This is extremely important in interpreting staining differences across different brains.
How large is the tissue you are processing?
A wide range of sizes of tissue can be accommodated by our technology: mouse spinal cords to human brain hemispheres. Of course, only one human brain hemisphere can be embedded in one block! Most of the large tissues we process are from the brains of non-human primates, dogs, sheep and pigs. The larger brains are important in that they mimic more closely the human brain.
What are the challenges with sectioning such large tissue?
The challenges of sectioning the Large Format™ tissues are not significant compared to a block of mouse or rat brains. Since the tissue is being frozen and then sectioned, it’s important that the tissue is adequately treated with so called ‘cryo protect’ solutions, which retard the size of ice crystals that form when the block of tissue is frozen.
Such crystals, if allowed to grow, would create large tears in the tissue and ruin the anatomy. Traditionally, sucrose (20-30%) has been used to saturate the tissue, but for the last 30 years we have used a 20% glycerol solution that yields superior results.
What does the multiple embedding process involve?
MultiBrain® technology allows for many brains and/or spinal cords to be embedded in a single gelatin matrix block. From that point forward, the tissues remain together for all staining procedures.
What impact has the TissueScope LE120 whole slide scanner from Huron Digital Pathology had on your workflow? Did anything surprise you when you started scanning?
The Tissue Scope LE120 has allowed us to meet a growing demand from scientists for high quality digital images of the stained sections. Up until a few years ago, we only provided stained slides of brain or spinal cord tissues. At the same time that the demand grew for digital images of the brain and cord sections, the demand for providing image analysis skyrocketed. Of course, in order to perform the analyses, digital images are required.
The LE120 allowed us to leverage MultiBrain® processing because Huron’s software engineers designed programs that could capture images of individual brain sections from one MultiBrain® sheet and group them.
The common practice with other image capture systems on the market is to capture the whole slide (holding up to 40 different specimens) and leave it to the user to pluck out the individual sample images. That calls for human involvement which is costly and time consuming. With Huron’s system we continue to accelerate the process of extracting data from our clients’ experimental tissues.
Our biggest surprise when we first began using the LE120 was how easy it was to use, especially with the accommodations that the software engineers provided to meet our rather unique requirements.
Above excerpt from “An interview with Dr. Robert Switzer, President and Chief Scientific Officer of NeuroScience Associates (NSA), conducted by April Cashin-Garbutt, MA (Cantab)”, read the entire interview here*.
* NSA is not responsible for the contents of any external websites.