Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Real X-ray vision: See-through brains ready for study

15.09.2015

Researchers at the RIKEN Brain Science Institute in Japan have developed a new technique for creating transparent tissue that can be used to illuminate 3D brain anatomy at very high resolutions. Published in Nature Neuroscience, the work showcases the new technology and its practical importance in clinical science by showing how it has given new insights into Alzheimer's disease plaques.

"The usefulness of optical clearing techniques can be measured by their ability to gather accurate 3D structural information that cannot be readily achieved through traditional 2D methods," explains lead scientist Atsushi Miyawaki. "Here, we achieved this goal using a new procedure, and collected data that may resolve several current issues regarding the pathology of Alzheimer's disease. While Superman's x-ray vision is only the stuff of comics, our method, called ScaleS, is a real and practical way to see through brain and body tissue."


This is a 3-D visualization of Aβ plaques (green) and blood vessels (red) in a region of cerebral cortex from a 20-month-old AD model mouse.

Credit: RIKEN

In recent years, generating see-through tissue--a process called optical clearing--has become a goal for many researchers in life sciences because of its potential to reveal complex structural details of our bodies, organs, and cells--both healthy and diseased--when combined with advanced microscopy imaging techniques. Previous methods were limited because the transparency process itself can damage the structures under study.

The original recipe reported by the Miyawaki team in 2011--termed Scale--was an aqueous solution based on urea that suffered from this same problem. The research team spent 5 years improving the effectiveness of the original recipe to overcome this critical challenge, and the result is ScaleS, a new technique with many practical applications.

"The key ingredient of our new formula is sorbitol, a common sugar alcohol," reveals Miyawaki. "By combining sorbitol in the right proportion with urea, we could create transparent brains with minimal tissue damage, that can handle both florescent and immunohistochemical labeling techniques, and is even effective in older animals."

The new technique creates transparent brain samples that can be stored in ScaleS solution for more than a year without damage. Internal structures maintain their original shape and brains are firm enough to permit the micron-thick slicing necessary for more detailed analyses.

"The real challenge with optical clearing is at the microscopic level," said Miyawaki, "In addition to allowing tissue to be viewable by light microscopy, a practical solution must also ensure accurate tissue preservation for effective electron microscopy."

On these tests, ScaleS passed with flying colors providing an optimal combination of cleared tissue and fluorescent signals, and Miyawaki believes that the quality and preservation of cellular structures viewed by electron microscopy is unparalleled.

The team has devised several variations of the Scale technique that can be used together. By combining ScaleS with AbScale--a variation for immunolabeling--and ChemScale--a variation for fluorescent chemical compounds--they generated multi-color high-resolution 3D images of amyloid beta plaques in older mice from a genetic mouse model of Alzheimer's disease developed at the RIKEN BSI by Takaomi Saido team.

After showing how ScaleS treatment can preserve tissue, the researchers put the technique to practical use by visualizing in 3D the mysterious "diffuse" plaques seen in the postmortem brains of Alzheimer's disease patients that are typically undetectable using 2D imaging. Contrary to current assumptions, the diffuse plaques proved not to be isolated, but showed extensive association with microglia --mobile cells that surround and protect neurons.

Another example of ScaleS's practical application came from examining the 3D positions of active microglial cells and amyloid beta plaques. While some scientists suggest that active microglial cells are located near plaques, a detailed 3D reconstruction and analysis using ScaleS clearing showed that association with active microglial cells occurs early in plaque development, but not in later stages of the disease after the plaques have accumulated.

"Clearing tissue with ScaleS followed by 3D microscopy has clear advantages over 2D stereology or immunohistochemistry," states Miyawaki. "Our technique will be useful not only for visualizing plaques in Alzheimer's disease, but also for examining normal neural circuits and pinpointing structural changes that characterize other brain diseases."

###

Reference:

Hama H et al. (2015) ScaleS: An Optical Clearing Palette for Biological Imaging. Nature Neuroscience, doi: 10.1038/nn.4107.

Adam Phillips | EurekAlert!

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A cavity leads to a strong interaction between light and matter

Researchers have succeeded in creating an efficient quantum-mechanical light-matter interface using a microscopic cavity. Within this cavity, a single photon is emitted and absorbed up to 10 times by an artificial atom. This opens up new prospects for quantum technology, report physicists at the University of Basel and Ruhr-University Bochum in the journal Nature.

Quantum physics describes photons as light particles. Achieving an interaction between a single photon and a single atom is a huge challenge due to the tiny...

Im Focus: Solving the mystery of quantum light in thin layers

A very special kind of light is emitted by tungsten diselenide layers. The reason for this has been unclear. Now an explanation has been found at TU Wien (Vienna)

It is an exotic phenomenon that nobody was able to explain for years: when energy is supplied to a thin layer of the material tungsten diselenide, it begins to...

Im Focus: An ultrafast glimpse of the photochemistry of the atmosphere

Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.

The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...

Im Focus: Shaping nanoparticles for improved quantum information technology

Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.

Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...

Im Focus: Novel Material for Shipbuilding

A new research project at the TH Mittelhessen focusses on the development of a novel light weight design concept for leisure boats and yachts. Professor Stephan Marzi from the THM Institute of Mechanics and Materials collaborates with Krake Catamarane, which is a shipyard located in Apolda, Thuringia.

The project is set up in an international cooperation with Professor Anders Biel from Karlstad University in Sweden and the Swedish company Lamera from...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Symposium on Functional Materials for Electrolysis, Fuel Cells and Metal-Air Batteries

02.10.2019 | Event News

NEXUS 2020: Relationships Between Architecture and Mathematics

02.10.2019 | Event News

Optical Technologies: International Symposium „Future Optics“ in Hannover

19.09.2019 | Event News

 
Latest News

Kirigami inspires new method for wearable sensors

22.10.2019 | Materials Sciences

3D printing, bioinks create implantable blood vessels

22.10.2019 | Medical Engineering

Ionic channels in carbon electrodes for efficient electrochemical energy storage

22.10.2019 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>