Biomedical optics express最新文献

Diffuse correlation spectroscopy (DCS) enables noninvasive measurement of deep tissue blood flow, but high-speed and multi-channel implementations are often constrained by data throughput. We present an FPGA-based compressed DCS architecture for fast, high-throughput real-time measurements of intensity autocorrelation functions that leverages parity-based 1-bit photon counting to exploit sparse photon arrivals. The system is validated by direct comparison with a conventional research-grade DCS instrument with experiments on solid and liquid tissue-simulating phantoms and in vivo forearm measurements during arm-cuff occlusion. Results demonstrate $96.875\%$ data compression with preservation of autocorrelation fidelity and blood flow estimation performance over practical acquisition rates, enabling compact and scalable real-time DCS instrumentation.

Confocal Raman micro-spectroscopy (CRM) has developed into a versatile tool that is frequently used to determine skin penetration of various compounds. Topically applied optical clearing agents decrease skin scattering, improving CRM imaging abilities. The use of magnetic resonance (MR) and X-ray contrast agents to increase transparency of biological objects has attracted more attention recently. By analysing Raman bands at 1003 and 1663 cm^-1 and applying Fick's second law model, we calculated the diffusion coefficients of 3.51 × 10^-8 cm²/s for Gadovist and 3.20 × 10^-7cm²/s for Omnipaque, with a slower diffusion regime for Dotarem. These diffusion kinetics directly governed penetration depth profiles across the investigated 0-240 µm dermal region and dictated optical clearing efficiency. Gadovist yielded the strongest short-term (30 min, up to 52% signal increase), whereas Omnipaque reached the highest and most depth-uniform optical clearing (60 min), consistent with its one-order-of-magnitude higher diffusivity. In contrast, Dotarem exhibited limited penetration and negligible optical clearing. Autofluorescence enhancement scaled with diffusion-driven refractive index matching, confirming that optical clearing is mechanistically coupled to molecular transport; it may also arise from protein structural modifications, oxidative stress, or increased protein density following contrast agent interaction. Together, these findings establish a quantitative link between contrast-agent diffusivity, dermal penetration depth, optical transparency, and tissue autofluorescence, providing a framework for integrating Raman, MR, and X-ray modalities in multimodal depth-resolved skin imaging.

Conventional unidirectional scanning rigidly couples the scan interval (t _inter) to sampling density in ultra-wide field optical coherence tomography angiography (UWF-OCTA), which impedes optimal imaging of different blood flow velocities. In this study, we implement an adaptive bidirectional interleaved scanning pattern for UWF-OCTA that enables the adjustment of t _inter while keeping the scan area, sampling density, and total acquisition time constant or optimally tuned. We implemented this pattern on our high-speed (800 kHz/1 MHz) swept-source UWF-OCTA prototypes and assessed image quality across several use cases, including pediatric patients, non-human primates, and rodents. This protocol successfully captured detailed UWF-OCTA images with well-defined microvascular patterns. We observed that, while keeping sampling density and total scan acquisition time constant, a longer t _inter enhances sensitivity to slower retinal blood flow, whereas a shorter t _inter yields more robust, motion-resistant images with clearer choroidal vasculature, as supported by quantitative contrast-to-noise ratio analysis. These findings illustrate that the optimal t _inter is dependent on the specific application and pathology, and validate the adaptive scanning pattern as a useful approach for tailoring UWF-OCTA to diverse clinical needs.

We report the development of a novel two-photon excitation stimulated emission depletion microscopy system, namely 2PE-scSTED, featuring a custom light source setup that integrates a supercontinuum (SC) laser light source with our proprietary 1064 nm pulsed semiconductor excitation laser. This SC source provides the capability of emitting a broadband spectral range, enabling highly reliable selection of depletion wavelength. Utilizing 2PE-scSTED, we investigated the depletion characteristics of several fluorophores. By employing a tunable filter to precisely select depletion wavelength from 640 to 800 nm, we systematically measured the depletion efficiency and identified the optimal wavelengths that maximize fluorescence depletion efficiency for four distinct fluorescent probes. This approach yielded super-resolution images with a lateral spatial resolution as fine as 45 nm (approximately λ _2PE /24) with a relatively lower depletion power than our previous reports, and can be principally applicable to all fluorescent probes. Our results demonstrate that the integration of a broadband SC source removes the spectral constraint of fluorescence depletion, enabling tailored 2PE-STED microscopy for individual fluorophores. This enhances the versatility and applicability of 2PE-STED microscopy for super-resolution imaging of biological specimens.

[This corrects the article on p. 2512 in vol. 17, PMID: 42145707.].

Multiple wavefronts originating from axially and/or transversely displaced light sources are known to introduce artifactual aberrations in Shack-Hartmann wavefront sensors (SHWSs). These aberrations are primarily dominated by defocus, followed by spherical aberration and coma, depending on whether an on-axis or off-axis binary transmission pupil mask is used in the illumination path. In an earlier study, such artifactual aberrations-caused by multiple reflections from displaced sources-were predicted using rigorous diffraction-theory-based integral calculations. However, such calculations are computationally intensive, and were therefore limited to modeling only two reflecting layers. Moreover, the low Fresnel number associated with SHWS lenslets introduces a focal shift, complicating the application of the discrete Fourier transform (DFT). Here, we showed that, with an appropriate coordinate transformation, the diffraction integrals that account for focal shift can be expressed as Fourier transform integrals. Using this approach to model human retinal reflectivity from 75 axially separated layers, we demonstrate a computational speed-up of over three orders of magnitude. Our results reveal that wavefront error in multilayered structures is fundamentally sensitive to both retinal architecture and centroiding strategy. While dynamic beacon positioning remains a primary mitigation strategy, small on-axis illumination paired with polarizers offers a robust alternative for substantially minimizing these artifactual aberrations. These findings have broad implications for optical systems requiring precise wavefront sensing in volumetric samples, including microscopy, retinal imaging, and astronomy.

We present the development of a corneal phantom designed to enable resolution assessment for non-contact corneal microscopy. The phantom was fabricated by casting a UV-curable epoxy mixed with 400-nm-diameter gold nanoparticles into a polydimethylsiloxane (PDMS) mold with a curved surface to achieve a cornea-like geometry. The radius of curvature of the final manufactured phantom was 8.14-8.17 mm with a refractive index of 1.39, similar to the adult human cornea. The optical phantom was used to evaluate the resolution of a prototype non-contact confocal microscope, the portable in vivo confocal ophthalmoscope (PICO). PICO images of the optical phantom allowed for evaluation of the resolution change as a function of depth.

This joint feature issue of Optics Express, Applied Optics, and Biomedical Optics Express showcases recent work from the Computational Optical Sensing and Imaging community. The issue reflects the continuing expansion of computational optical sensing and imaging, where optical design, detection, calibration, physical optical system modeling, signal processing, and machine learning to acquire task-relevant information. The selected papers span computational microscopy and biomedical imaging, adaptive optics, wavefront sensing, holography, phase retrieval, single-pixel and ghost imaging, hyperspectral and polarization imaging, non-line-of-sight imaging, LiDAR, photon-efficient sensing, optical-system co-design, and emerging applications in medicine, remote sensing, manufacturing, and environmental metrology. Together, these contributions illustrate how computationally co-designed optical systems are moving from algorithmic demonstrations toward robust, application-specific imaging and sensing platforms.

Polarization-sensitive optical coherence tomography (PS-OCT) systems employing a single polarized input state are widely used due to their simple system architecture and commercial availability. However, such configurations are inherently susceptible to polarization ambiguities that can lead to inaccurate polarimetric reconstruction, particularly when estimating depth-resolved birefringence. Our previous work demonstrated that these artifacts can be mitigated by illumination exhibiting spectral polarization spread (SPS), arising from polarization mode dispersion present in some imaging systems. SPS effectively provides additional polarization diversity across the source spectrum, reducing ambiguity in the measured retardance signals. In this work, we introduce a compact waveplate stack module that introduces controlled, intentional SPS in arbitrary single-input PS-OCT systems. We demonstrate the approach by integrating the module into the round-trip portion of the sample arm of a commercially available PS-OCT platform, enabling robust and unambiguous depth-resolved polarimetric reconstruction. The minimal hardware modification and simple calibration procedure allow straightforward retrofitting of existing single-input PS-OCT systems, facilitating broader adoption of reliable, depth-resolved birefringence imaging.

Deep ultraviolet has emerged as a robust imaging method for label-free histopathology and cytology. This study quantitatively evaluates various mounting media to optimize transmissive DUV imaging. We identified glycerol as the optimal candidate, achieving an internal transmittance of 99.15% at 265 nm and providing a refractive index (n ≈ 1.53) that matches biological specimens and fused silica substrates. While alcohol offers high transparency, its volatility prevents extended imaging; conversely, traditional xylene-based media exhibit near total DUV extinction. Quantitative validation using local entropy, Tenengrad sharpness, and speckle contrast confirms that glycerol suppresses interfacial scattering and improves nuclear visualization across cervical cells and various murine and human tissues. These results establish glycerol as a robust, high-performance medium for enhancing diagnostic fidelity in label-free deep ultraviolet microscopy.