Optical system for quantitative 3D imaging of whole brain
- Reference number
- ITM17-0152
- Start and end dates
- 190101-221231
- Amount granted
- 7 975 068 SEK
- Administrative organization
- Lund University
- Research area
- Life Science Technology
Summary
Imaging brains is fundamental for the development of new treatments against neurodegenerative and neuropsychiatric diseases. Advances in tissue clearing have enabled rendering brains semi-transparent, allowing the visible light to fully penetrate through them and excite various fluorescent molecular markers. Despite this breakthrough, Light Sheet Fluorescent Microscopy - the state of the art for 3D imaging of cleared brains - suffers from several limitations that impact the outcome negatively: Image blurs, multiple light scattering, illumination inhomogeneity and light attenuation phenomena. As a result, the current imaging approach is intrinsically biased leading to data misinterpretation, poor reproducibility of the results and impossibility for comparative analysis. The aim of this proposal is to develop a specially designed macro- & micro-scope to overcome these limitations. The instrument will be based on the structured illumination technology, capable of: 1) Correcting for all image artifacts 2) Providing 3D quantitative reconstructions of whole brains 3) Providing information on the level of clearing 4) Allowing high-resolution imaging. The work plan will consist of design and construction of the instrument; development of advanced image post-processing algorithms; and testing in real-world situation on cleared brain tissues, including human post-mortem samples. Finally, a fully functional prototype of the instrument is expected by the end of the project.
Popular science description
Neurodegenerative (e.g. Alzheimer’s and Parkinson’s diseases) and neuropsychiatric (e.g. schizophrenia, depression, etc) diseases constitute a major health problem. In addition, traumatic brain injuries caused by traffic or sport accidents reach ~240/100 000 people, with no existing effective treatments to date. The ability to develop new treatments and especially those that have the potential to alter the course of disease and retain the affected persons active and independent in their daily life, is seriously hampered by lack of our understanding on how the brain is wired and how it responds to therapeutic interventions. To understand brain functions and their response to various therapeutic treatments, it is urgently needed to provide 3D images of their complete inner structure with very high level of details. The traditional method to explore a neural structure at a molecular level consists in cutting the brain tissue into thin slices and images those slices under a microscope. To reconstruct the complete structure in 3D one need to add piece by piece each imaged sample. This approach is very time-demanding requiring months of work. In addition, the 3D reconstruction is rarely satisfactory and the process ultimately destroys the original tissue sample. Recently, a technology called “brain clearing” has allowed to render brains of dead animals semi-transparent. Thanks to this technology, light can now penetrate inside the brain making its structure, which was initially invisible, visible. This has opened up the new possibility for 3D imaging by means of visible light. However, the current 3D images are affected by a number of errors and artifacts, such as image blurs and effects due to light attenuation, ultimately resulting to wrong 3D reconstructions. In this project we intend to use a novel optical technique, originally co-invented and developed by the applicant, to correct for all those errors and to provide true 3D images of brain samples. To this end, a novel instrument will be designed, constructed and tested for real world applications; where not only whole mouse and rats brains, but also pieces of human brains, will be analyzed in 3D.