The uDISCO Groove

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Okay, so imagine if you can get a 3-dimensional view of the deepest anatomy of a mouse brain without ever having to dissect the animal. Sounds quite sci-fi, right? Well, this is a real technique developed by Prof. Ali Ertürk’s lab at the Institute for Stroke and Dementia Research at the Ludwig Maximilians University of Munich, Germany, whose work was published in Nature methods this week[1]. The technique uses a solvent that shrinks the specimen up to 65% of its original size and making it transparent – even the bones and is touted to provide the best resolution images. Volumetric shrinkage of the specimen helps to view the whole animal under the microscope. And by removing water (dehydration) using alcohol and fat by using a solvent such as diphenyl ether, allows the specimen to lose its opacity and become transparent thereby reducing light scattered from the tissue. In other words, better resolution. Couple it with a fluorescent protein tagged to neurons that could stay alight for more than a week and you’ve got a cutting-edge volumetric imaging technology surpassing all its predecessors.

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A mouse tagged with fluorescent protein that has undergone treatment with uDisco to become transparent. Courtesy Science AAS

It’s like an X-ray vision camera that has the most powerful magnifying ability getting all the intricate details of the most deep-seated cells and blood vessels.

They have named this technique as uDISCO  or ultimate 3D imaging of solvent-cleared organs a variant of the original 3DISCO technique. However, 3DISCO has a few limitations that the fluorescence doesn’t last for long and the procedure is more tedious compared to that of uDISCO.

What are the advantages one can think of with uDISCO? Intact neurons can be inspected very closely for the first time that can never be achieved with conventional imaging techniques. This could help us understand the mechanisms behind various neurodegenerative diseases such as stroke, Alzheimer’s and Parkinson’s disease. And imagine conducting an autopsy without the need to cut up the corpse. The applications are numerous and promising. Check out this New Scientist video that gives you an idea of how uDISCO works.

 

[1]   Pan C, Cai R, Quacquarelli FP, et al. Shrinkage-mediated imaging of entire organs and organisms using uDISCO. Nat Meth 2016;advance online publication.