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

(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

(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