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Yiu, J.

Publications and source records attributed to Yiu, J..

3 recordsLinked to original sources

Macroscopic label-free biomedical imaging withshortwave infrared Raman scattering

Shortwave infrared (SWIR) imaging provides enhanced tissue penetration and reduced autofluorescence in clinical and pre-clinical applications. However, existing applications often lack the ability to probe chemical composition and molecular specificity without the need for contrast agents. Here, we present a SWIR imaging approach that visualizes spontaneous Raman scattering with remarkable chemical contrast deep within tissue across large fields of view. Our results demonstrate that Raman scattering overcomes autofluorescence as the predominant source of endogenous tissue background at illumination wavelengths as short as 892 nm. We highlight the versatility of SWIR Raman imaging through in vivo monitoring of whole-body tissue composition dynamics and non-invasive detection of fatty liver disease in mice, and identification of calcification and lipids in unfixed human atherosclerotic plaques. Moreover, our approach facilitates the visualization of nerves embedded in fatty tissue, a major advancement for surgical applications. With a simple wide-field setup orthogonal to fluorescence, SWIR Raman imaging holds promise for rapid adoption by clinicians and biologists. This technique opens new possibilities for contrast agent-free visualization of pathophysiology in whole animals and intraoperative imaging in humans. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/597863v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@394289org.highwire.dtl.DTLVardef@13f3289org.highwire.dtl.DTLVardef@ee6f7org.highwire.dtl.DTLVardef@5d7399_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Shortwave infrared (SWIR) fluorescence imaging of peripheral organs in awake and freely moving mice

Extracting biological information from awake and unrestrained mice is imperative to in vivo basic and pre-clinical research. Accordingly, imaging methods which preclude invasiveness, anesthesia, and/or physical restraint enable more physiologically relevant biological data extraction by eliminating these extrinsic confounders. In this article we discuss the recent development of shortwave infrared (SWIR) fluorescent imaging to visualize peripheral organs in freely-behaving mice, as well as propose potential applications of this imaging modality in the neurosciences.

bioengineering↗

Acoustically Targeted Noninvasive Gene Therapy in Large Brain Regions

Focused Ultrasound Blood-Brain Barrier Opening (FUS-BBBO) can deliver adeno-associated viral vectors (AAVs) to treat genetic disorders of the brain. However, such disorders often affect large brain regions. Moreover, the applicability of FUS-BBBO in the treatment of brain-wide genetic disorders has not yet been evaluated. Herein, we evaluated the transduction efficiency and safety of opening up to 105 sites simultaneously. Increasing the number of targeted sites increased gene delivery efficiency at each site. We achieved transduction of up to 60% of brain cells with comparable efficiency in the majority of the brain regions. Furthermore, gene delivery with FUS-BBBO was safe even when all 105 sites were targeted simultaneously without negative effects on animal weight, neuronal loss, or astrocyte activation. To evaluate the application of multi-site FUS-BBBO for gene therapy, we used it for gene editing using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system, and found effective gene editing, but also a loss of neurons at the targeted sites. Overall, this study provides a brain-wide map of transduction efficiency and the first example of gene editing after site-specific noninvasive gene delivery to a large brain region.

bioengineering↗