Automated Whole-Brain Scanning System to Accelerate Research

Automated Whole-Brain Scanning System to Accelerate Research

CSHL team introduces automated imaging to greatly speed whole-brain mapping efforts

PostDateIconThursday, 12 January 2012 17:06 | Print

Cold Spring Harbor, N.Y. – A new technology developed by neuroscientists at Cold Spring Harbor Laboratory (CSHL) transforms the way highly detailed anatomical images can be made of whole brains. Until now, means of obtaining such images – used in cutting-edge projects to map the mammalian brain — have been painstakingly slow and available only to a handful of highly specialized research teams.

By automating and standardizing the process in which brain samples are divided into sections and then imaged sequentially at precise spatial orientations in two-photon microscopes, the team, led by Assoc. Prof. Pavel Osten and consisting of scientists from his CSHL lab and the Massachusetts Institute of Technology, has opened the door to making whole-brain mapping routine.

Specifically, says Osten, “the new technology should greatly facilitate the systematic study of neuroanatomy in mouse models of human brain disorders such as schizophrenia and autism.”pavel_brain3-D rendering of coronal section of a mouse brain imaged with STP tomography at 20x at a resolution of half a micron. GFP-expressing pyramidal neurons in hippocampus and cortex are targeted.

The new technology, developed in concert with TissueVision of Cambridge, Mass. and reported on in a paper appearing online Jan. 15 in Nature Methods, is called Serial Two-Photon Tomography, or STP tomography. Tomography refers to any process (including the familiar CAT and PET scans used in medical diagnostics) that images an object section by section, by shooting penetrating waves through it. Computers powered by mathematical formulae reassemble the results to produce a three-dimensional rendering. Two-photon imaging is a type used in biology laboratories, particularly in conjunction with fluorescent biomarkers, which can be mobilized to illuminate specific cell types or other anatomical features. The two-photon method allows deeper optical penetration into the tissue being sampled than conventional confocal microscopy.

As Osten explains, STP tomography achieves high-throughput fluorescence imaging of whole mouse brains via robotic integration of the two fundamental steps — tissue sectioning and fluorescence imaging. In their paper, his team reports on the results of several mouse-brain imaging experiments, which indicate the uses and sensitivity of the new tool. They conclude that it is sufficiently mature to be used in whole-brain mapping efforts such as the ongoing Allen Mouse Brain Atlas project.

One set of experiments tested the technology at different levels of resolution. At 10x magnification of brain tissue samples, they performed fast imaging “at a resolution sufficient to visualize the distribution and morphology of green-fluorescent protein-labeled neurons, including their dendrites and axons,” Osten reports.

A full set of data, including final images, could be obtained by the team in 6.5 to 8.5 hours per brain, depending on the resolution. These sets each were comprised of 260 top-to-bottom, or coronal, slices of mouse brain tissue, which were assembled by computer into three-dimensional renderings themselves capable of a wide range of “warping,” i.e., artificial manipulation, to reveal hidden structures and features.

“The technology is a practical one that can be used for scanning at various levels of resolution, ranging from 1 to 2 microns to less than a micron,” Osten says. Scans at the highest resolution level take about 24 hours to collect. This makes possible an impressive saving of time, Osten says, compared to methods that are now in use. Using these, it would take an experienced technician about a week to collect a set of whole-brain images at high resolution, he noted.

“What is most exciting about this tool is its application in the study of mouse models of human illness, which we are already doing in my lab,” Osten says. “We are focusing on making comparisons between different mouse models of schizophrenia and autism. Many susceptibility genes have been identified in both disorders – one recent estimate by Dr. Mike Wigler’s team here at CSHL put the figure at over 250 for autism spectrum disorders, for instance. Dr. Alea Mills at CSHL has published a mouse model of one genetic aberration in autism – a region on chromosome 16 – and soon we will have tens of models, each showing a different aberration.

“We will want to compare these mice, and that is essentially why we designed STP tomography – to automate and standardize the process of collecting whole-brain images in which different cell-types or circuit tracings have been performed. This makes possible comparisons across different mouse models in an unbiased fashion.”

“Serial two-photon tomography: an automated method for mouse brain imaging” appears online in Nature Methods on January 15, 2012. The authors are: Timothy Ragan, Lolahon R Kadiri, Kannan Umadevi Venkataraju, Karsten Bahlmann, Jason Sutin, Julian Taranda, Ignacio Arganda-Carreras, Yongsoo Kim, H Sebastian Seung and Pavel Osten. the paper can be obtained online at http://www.nature.com/nmeth/index.html

This research was supported by grants from: The Simons Foundation, The McKnight Foundation, the Howard Hughes Medical Institute, and the National Institutes of Health.

About Cold Spring Harbor Laboratory

Founded in 1890, Cold Spring Harbor Laboratory (CSHL) has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. CSHL is ranked number one in the world by Thomson Reuters for impact of its research in molecular biology and genetics. The Laboratory has been home to eight Nobel Prize winners. Today, CSHL’s multidisciplinary scientific community is more than 360 scientists strong and its Meetings & Courses program hosts more than 12,500 scientists from around the world each year to its Long Island campus and its China center. Tens of thousands more benefit from the research, reviews, and ideas published in journals and books distributed internationally by CSHL Press. The Laboratory’s education arm also includes a graduate school and programs for undergraduates as well as middle and high school students and teachers. CSHL is a private, not-for-profit institution on the north shore of Long Island. For more information, visit www.cshl.edu.

We recently reported on a probe developed by IBM that will allow pathologists to take smaller biopsies. Now there may be a way to perform such histology faster, at least for brain studies. The conventional technique is to freeze a fluorescence-tagged whole brain or fix it in paraffin wax and then proceed to meticulously slice it into hundreds or thousands of micron-wide sections that are then mounted on slides and imaged. This takes huge investments of time and effort, so scientists usually focus on mapping specific regions of interest (e.g. cortex or amygdala). At least one project, the Allen Brain Atlas, emerged in response with the goal to map the entire mouse brain so that all researchers may rely upon it for their work.

Similar atlases may now be created even faster thanks to researchers at Cold Spring Harbor Laboratory, who announced in Nature Methods the development of a novel technique that automates and accelerates histological sectioning for 3D brain-mapping. Known as serial two-photon (STP) tomography, the technique

… achieves high-throughput fluorescence imaging of whole mouse brains via robotic integration of the two fundamental steps — tissue sectioning and fluorescence imaging…

A full set of data, including final images, could be obtained by the team in 6.5 to 8.5 hours per brain, depending on the resolution. These sets each were comprised of 260 top-to-bottom, or coronal, slices of mouse brain tissue, which were assembled by computer into three-dimensional renderings themselves capable of a wide range of “warping,” i.e., artificial manipulation, to reveal hidden structures and features.

“The technology is a practical one that can be used for scanning at various levels of resolution, ranging from 1 to 2 microns to less than a micron,” [Professor Pavel] Osten says. Scans at the highest resolution level take about 24 hours to collect. This makes possible an impressive saving of time, Osten says, compared to methods that are now in use. Using these, it would take an experienced technician about a week to collect a set of whole-brain images at high resolution, he noted.

euf1hhdh Automated Whole Brain Scanning System to Accelerate Research

In terms of applications and future work, according to the Nature Methods paper:

STP tomography is particularly well-suited for systematic studies of brain anatomy in genetic mouse models of cognitive disorders, such as autism and schizophrenia. To provide quantitative measurements for such studies, we are now focusing on anatomical registration and the development of computational methods for detection of fluorescence signals in whole-brain datasets generated by STP tomography.

This system, along with other emerging automated brain-scanning techniques, may have the same effect on neuroscience as next generation sequencing technologies had on genetics. It used to be prohibitively expensive to sequence an entire genome (which is why the NIH had to step in for the Human Genome Project), but automated and high-throughput technologies have reduced the time and cost required so researchers can simply sequence an entire sample rather than just a specific region. We hope to see more cool 3D brain maps, and the discoveries and innovations they inspire, in the near future.

Source : http://www.cshl.edu/Article-Osten/cshl-team-introduces-automated-imaging-to-greatly-speed-whole-brain-mapping-efforts

Related Posts Plugin for WordPress, Blogger...
Be Sociable, Share!

About the Author

has written 1822 posts on this blog.

Copyright © 2017 Medical Technology & Gadgets Blog MedicalBuy.net. All rights reserved.
Proudly powered by WordPress. Developed by Deluxe Themes