Biology subjects

Valdez, T. A.

Publications and source records attributed to Valdez, T. A..

4 recordsLinked to original sources

bioRxiv2024

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↗

bioRxiv2023

Development of Oxadiazolone Activity-Based Probes Targeting FphE for Specific Detection of S. aureus Infections

Staphylococcus aureus is a major human pathogen responsible for a wide range of systemic infections. Since its propensity to form biofilms in vivo poses formidable challenges for both detection and treatment, tools that can be used to specifically image S. aureus biofilms are highly valuable for clinical management. Here we describe the development of oxadiazolone-based activity-based probes to target the S. aureus-specific serine hydrolase FphE. Because this enzyme lacks homologs in other bacteria, it is an ideal target for selective imaging of S. aureus infections. Using X-ray crystallography, direct cell labeling and mouse models of infection we demonstrate that oxadiazolone-based probes enable specific labeling of S. aureus bacteria through the direct covalent modification of the FphE active site serine. These results demonstrate the utility of the oxadizolone electrophile for activity-based probes (ABPs) and validate FphE as a target for development of imaging contrast agents for the rapid detection of S. aureus infections.

microbiology↗

bioRxiv2023

Novel Imaging Guidance for Cholesteatoma Surgery usingTissue Autofluorescence

SignificanceCholesteatoma is an expansile destructive lesion of the middle ear and mastoid, which can result in significant complications by eroding adjacent bony structures. Currently, there is an inability to accurately distinguish cholesteatoma tissue margins from middle ear mucosa tissue, causing a high recidivism rate. Accurately differentiating cholesteatoma and mucosa will enable a more complete removal of the tissue. AimDevelop an imaging system to enhance the visibility of cholesteatoma tissue and margins during surgery. ApproachCholesteatoma and mucosa tissue samples were excised from the inner ear of patients and illuminated with 405, 450, and 520 nm narrowband lights. Measurements were made with a spectroradiometer equipped with a series of different longpass filters. Images were obtained using a red-green-blue (RGB) digital camera equipped with a long pass filter to block reflected light. ResultsCholesteatoma tissue fluoresced under 405 and 450 nm illumination. Middle ear mucosa tissue did not fluoresce under the same illumination and measurement conditions. All measurements were negligible under 520 nm illumination conditions. All spectroradiometric measurements of cholesteatoma tissue fluorescence can be predicted by a linear combination of emissions from keratin and flavin adenine dinucleotide (FAD). We built a prototype of a fluorescence imaging system using a 495 nm longpass filter in combination with an RGB camera. The system was used to capture calibrated digital camera images of cholesteatoma and mucosa tissue samples. The results confirm that cholesteatoma emits light when it is illuminated with 405 and 450 nm, whereas mucosa tissue does not. ConclusionsWe prototyped an imaging system that is capable of measuring cholesteatoma tissue autofluorescence.

bioengineering↗

bioRxiv2022

Development of a shortwave infrared (SWIR) sinuscope for the detection of cerebrospinal fluid (CSF) leaks

SignificanceCSF rhinorrhea (leakage of brain fluid from the nose) can be difficult to identify and currently requires invasive procedures such as intrathecal fluorescein which requires a lumbar drain placement. Fluorescein is also known to have rare but significant side effects including seizures and death. As the number of endonasal skull base cases increase, the number of CSF leaks have also increased for which an alternative diagnostic method would be highly advantageous to patients. AimTo develop an instrument to identify CSF leaks based on water absorption in the SWIR without the need of intrathecal contrast agents. This device needed to be adapted to the anatomy of the human nasal cavity while maintaining low weight and ergonomic characteristics of current surgical instruments. ApproachAbsorption spectra of CSF and artificial CSF were obtained to characterize the absorption peaks that could be targeted with SWIR light. Different illumination systems were tested and refined prior to adapting them into a portable endoscope for testing in 3D printed models and cadavers for feasibility. ResultsWe identified CSF to have an identical absorption profile as water. In our testing, a narrow band laser source at 1480nm proved superior to using a broad 1450 nm LED. Using a SWIR enabling endoscope set up, we tested the ability to detect artificial CSF in a cadaver model. ConclusionsAn endoscopic system based on SWIR narrow band imaging can provide an alternative in the future to invasive methods of CSF leak detection.

bioengineering↗