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.”
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.”
The Latest on: Optical clearing techniques
via Google News
The Latest on: Optical clearing techniques
- Photochromic Lenses Market: Increase in Online Sales to Drive Global Marketon February 23, 2021 at 12:04 am
Transparency Market Research (TMR) has published a new report titled, “Photochromic Lenses Market - Global Industry Analysis, Size, Share, Growth, Trends, ...
- Global Silicon Photonics-based Optical I/O Modules Market 2020 Potential Growth, Competitive Landscape and Development of Industry by 2025on February 22, 2021 at 7:37 pm
Global Silicon Photonics-based Optical I/O Modules Market 2020 by Manufacturers, Type and Application, Forecast ...
- Global Optical Interconnect Cable Assemblies Market 2020 Technological Strategies, Business Advancements and Top-Vendor Landscape by 2025on February 22, 2021 at 9:43 am
The report analyzes possible constraints of the market along with significant factors that are likely to promote the growth of the global Optical Interconnect Cable Assemblies market. The research ...
- Standard CMOS Yields Integrated Photonic 100-Gb/s Optical Modulatoron February 15, 2021 at 2:25 pm
Researchers devised an electro-optical modulator that can be fabricated using standard CMOS processes and achieve over 100-Gb/s performance, with power requirements of 2 pJ/bit.
- The Nail Trends That Are Poised to Take Over in 2021on February 15, 2021 at 5:12 am
From sculptural 3D press-ons to metallic French tips and an explosion of animal print, nail artists weigh in on the trends they predict will be everywhere in 2021.
- The assessment of the usability of selected instrumental techniques for the elemental analysis of biomedical sampleson February 12, 2021 at 3:00 am
Instrumental techniques are a group of research tools applied for investigation of analytes in various types of matter. These include i.a. spectroscopic techniques and mass spectrometry. Spectroscopic ...
- Feasibility and safety study of a high resolution wide field-of-view scanning endoscope for circumferential intraluminal intestinal imagingon February 11, 2021 at 2:48 am
High resolution anoscopy (HRA) currently screens for anal cancer, although the definitive test remains unknown. To improve on intraluminal imaging of the anal canal, we conducted a first-in-human ...
- These unexpected nail trends will be absolutely huge in 2021on February 9, 2021 at 12:23 am
From sculptural 3D press-ons to metallic French tips and an explosion of animal print—you have to try these epic nail trends ...
- 3D imaging of optically cleared tissue using a simplified CLARITY method and on-chip microscopyon February 2, 2021 at 4:00 pm
1 Electrical Engineering Department, University of California, Los Angeles, Los Angeles, CA 90095, USA. 2 Bioengineering Department, University of California, Los Angeles, Los Angeles, CA 90095, USA.
- WAYKEN Rapid's Automotive Lighting Prototypes Display the Best Optical Detailson January 30, 2021 at 5:20 pm
WayKen provides auto lighting assembly, ranging from proof-of-concept design reviews and optical system development ... As such, it is easy to machine clear plastic parts without blemishes.
via Bing News