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Veeraraghavan, A.

Publications and source records attributed to Veeraraghavan, A..

5 recordsLinked to original sources

Interpretable computational SHG microscopy enables quantitative tissue phenotyping of cardiac remodeling in nonischemic heart failure

Heart failure is characterized by extracellular matrix remodeling and collagen deposition that impair myocardial function. Second harmonic generation (SHG) microscopy provides label-free visualization of fibrillar collagen and myosin but lacks standardized, interpretable, and quantitative frameworks with clinical-level performance. We present a feature extraction pipeline integrating 87 biologically interpretable SHG-derived metrics for automated classification of nonischemic heart failure in murine specimen. The framework distinguished normal, heart failure, and natural recovery states with area-under-the-curve values of 0.84-0.99, outperforming established open-source SHG feature extraction tools. These findings support interpretable, SHG-based quantification of cardiac remodeling and establish a methodology for future multimodal biophotonics applications.

bioengineering↗

Dual-modality, deep-learning-enabled endomicroscope with large field-of-view and depth-of-field for real-time in vivo imaging of epithelial hallmarks of cancer

In vivo microscopy (IVM) has shown great promise to improve early detection of epithelial precancer, but it suffers from fundamental trade-offs that limit the resolution, field-of-view (FOV) and depth-of-field (DOF). Here, we present PrecisionView, a compact, deep-learning-enabled endomicroscope that breaks these constrains and achieves 20 mm2 FOV and 500 {micro}m DOF with 4 {micro}m resolution, representing approximately 5x increase in FOV and 8x larger DOF compared to conventional IVM with similar resolution. PrecisionView integrates a deep-learning optimized phase mask and real-time reconstruction, enabling rapid in vivo assessment of two key hallmarks of cancer: epithelial cell nuclear morphology and subsurface microvasculature through fluorescence and reflectance imaging. By imaging oral cavity of healthy volunteers and cervical specimens with precancerous lesions, PrecisionView generates large-scale (1-3 cm2) co-registered maps of cellular and vascular structures, revealing distinct microscopic patterns associated with anatomic structures and precancerous lesions. Our results suggest the potential of this computational endomicroscope to address the unmet need for early cancer detection at the point-of-care.

bioengineering↗

Subdural CMOS optical probe (SCOPe) for bidirectional neural interfacing

Optical neurotechnologies use light to interface with neurons and can monitor and manipulate neural activity with high spatial-temporal precision over large cortical extents. While there has been significant progress in miniaturizing microscope for head-mounted configurations, these existing devices are still very bulky and could never be fully implanted. Any viable translation of these technologies to human use will require a much more noninvasive, fully implantable form factor. Here, we leverage advances in microelectronics and heterogeneous optoelectronic packaging to develop a transformative, ultrathin, miniaturized device for bidirectional optical stimulation and recording: the subdural CMOS Optical Probe (SCOPe). By being thin enough to lie entirely within the subdural space of the primate brain, SCOPe defines a path for the eventual human translation of a new generation of brain-machine interfaces based on light.

neuroscience↗

In vivo fluorescence imaging with a flat, lensless microscope

Fluorescence imaging over large areas of the brain in freely behaving animals would allow researchers to better understand the relationship between brain activity and behavior; however, traditional microscopes capable of high spatial resolution and large fields of view (FOVs) require large and heavy lenses that restrict animal movement. While lensless imaging has the potential to achieve both high spatial resolution and large FOV with a thin lightweight device, lensless imaging has yet to be achieved in vivo due to two principal challenges: (a) biological tissue typically has lower contrast than resolution targets, and (b) illumination and filtering must be integrated into this non-traditional device architecture. Here, we show that in vivo fluorescence imaging is possible with a thin lensless microscope by optimizing the phase mask and computational reconstruction algorithms, and integrating fiber optic illumination and thin-film color filters. The result is a flat, lensless imager that achieves better than 10 m spatial resolution and a FOV that is 30x larger than other cellular resolution miniature microscopes.

neuroscience↗

Determining the Depth Limit of Bioluminescent Sources in Scattering Media

Bioluminescence has several potential advantages compared to fluorescence microscopy for in vivo biological imaging. Because bioluminescence does not require excitation light, imaging can be performed for extended periods of time without phototoxicity or photobleaching, and optical systems can be smaller, simpler, and lighter. Eliminating the need for excitation light may also affect how deeply one can image in scattering biological tissue, but the imaging depth limits for bioluminescence have yet to be reported. Here, we perform a theoretical study of the depth limits of bioluminescence microscopy and find that cellular resolution imaging should be possible at a depth of 5-10 mean free paths (MFPs). This limit is deeper than the depth limit for confocal microscopy and slightly lower than the imaging limit expected for two-photon microscopy under similar conditions. We also validate our predictions experimentally using tissue phantoms. Overall we show that with advancements in the brightness of bioluminescent indicators, it should be possible to achieve deep, long-term imaging in biological tissue with cellular resolution.

bioengineering↗