Ruixuan Gao

Thank you, @giudica.bsky.social ! Hope you are doing well!

Thrilled to share our Science cover! VIPS (volumetric imaging via photochemical sectioning) eliminates working-distance limits for whole-mount, nanoscale imaging. LLSM + photodegradable hydrogel + petabyte-scale compute → mapped axons & myelin across two mouse olfactory bulbs (WT vs NPC1).

This three-dimensional rendering of a mouse olfactory bulb exposes axons and myelin sheaths, the neuronal wiring that transmits odor information.

A new method called VIPS enables organ-wide nanoscale reconstruction for quantitative mapping of connectivity and molecular landscape in intact tissue.

Learn more this week in Science: https://scim.ag/4n4GKPm

(15/x) This work was led by Wei Wang @uic-chemistry.bsky.social @gaogroupuic.bsky.social, Xiongtao Ruan, and Gaoxiang Liu @ABC @berkeleymcb.bsky.social @biosci.lbl.gov, and supported by @NIMH @UIC @cziscience.bsky.social @hhmi.org @ThePhilomathia @sloanfoundation.bsky.social @nersc.bsky.social

(14/x) Finally, we extend our sincere gratitude to the editor, reviewers, collaborators, and colleagues for their time and insightful feedback to this manuscript

(13/x) With the potential for large AI models to unlock and make image analysis and data mining more accessible, we anticipate VIPS will uncover biologically meaningful insights from petabyte-scale or even larger nanoscale resolution imaging datasets

(12/x) VIPS is compatible with various tissue types and labeling strategies, including sparse (e.g., immunofluorescence, FPs) and dense labels. Specifically with the latter, VIPS could form the optical foundation for synaptic-level dense connectome of whole brains

(11/x) This proof-of-concept study highlights the potential of VIPS to advance spatial biology research across various biological domains - from studying biological stereotypy to investigating disease perturbations across whole organs or organisms at subcellular resolution

GitHub - abcucberkeley/PetaVIPS Contribute to abcucberkeley/PetaVIPS development by creating an account on GitHub.

(10/x) Petabyte-scale image processing and olfactory-bulb-wide axon/myeline/tractography analysis with PetaKit5D and PetaVIPS (github.com/abcucberkele...) revealed distinct spatial patterns of axon degeneration and de-/dysmyelination in the neurodegenerative mouse

(9/x) Using light-sheet photochemical sectioning and on-block lattice light-sheet microscopy (LLSM), we imaged two complete adult mouse olfactory bulbs at nanoscale resolution, generating more than a petabyte of data

(8/x) Two modes of photochemical sectioning are possible: (a) complete degradation of the target volume (“photodegradation”) or (b) cross-sectional sectioning and lift-off of the overlaying volume (“photoslicing”). Option b preserves the sectioned volume (image: photoslicing)

(7/x) We then validated spatially confined photochemical sectioning of intact biological specimens embedded in this hydrogel using single- or multiphoton illumination

(6/x) To implement VIPS, we designed and synthesized a photodegradable superabsorbent hydrogel with a custom photocleavable cross-linker (“PC”) that undergoes complete photo-decimation under UV illumination

(5/x) However, these techniques often lead to sample distortion, tearing, and loss with hydrogel-embedded specimens, which escalate computational challenges for tera- to petavoxel datasets

(4/x) Previously, physical sectioning techniques, such as mechanical sectioning and surface ablation, have been combined with on-section or block-face imaging to perform volumetric electron and fluorescence microscopy

(3/x) In more detail, conventional volumetric fluorescence imaging is constrained by a resolution/imaging depth/sample size trade-off. VIPS overcomes the microscope’s working distance limitation using iterative photochemical sectioning and on-block optical imaging

(2/x) In essence, VIPS uses a ray or sheet of light to perform spatially precise sectioning of large biological samples, such as a brain. By iteratively repeating this light-based sectioning and imaging, we can achieve volumetric optical imaging of virtually any sample size

Mesoscale volumetric fluorescence imaging at nanoscale resolution by photochemical sectioning Optical nanoscopy of intact biological specimens has been transformed by recent advancements in hydrogel-based tissue clearing and expansion, enabling the imaging of cellular and subcellular structure...

(1/x) Excited to report VIPS (Volumetric imaging of biological specimens via photochemical sectioning) @science.org! VIPS uses light-based sample sectioning to eliminate the inherent imaging depth limit of high-resolution optical microscopes @supgokul.bsky.social: www.science.org/doi/10.1126/...