Biomedical optics express最新文献

Current subretinal injection systems combine surgical microscopy, optical coherence tomography (OCT), and robotic assistance to enable precise, depth-resolved, and tremor-free drug delivery to targeted retinal sites. Nevertheless, subretinal and intraretinal vascular injections remain constrained by two major challenges: (1) the inherent difficulty in simultaneously achieving wide-field, real-time imaging of fundus lesions at high spatial resolution, and (2) the requirement for precise intraocular localization of the needle tip quickly. Current fundus injection imaging methods provide limited accuracy in needle tip localization and require prolonged procedure time. To address this issue, we present a novel intraoperative OCT (iOCT) imaging system that integrates a single light source and dual-channel OCT detection to simultaneously acquire A-scan and C-scan data without incurring substantial additional cost. Using the A-scan component of the synchronization signal, high-speed and real-time distance detection of the retinal surface is performed in M-scan mode. Meanwhile, the C-scan component of the synchronization signal provides high spatial resolution imaging of retinal depth information. Combined with the ultra-wide field of view afforded by microscopic imaging, this approach facilitates rapid and extensive guidance for lesion localization in the fundus, while also allowing real-time intraoperative assessment of drug injection procedures. This system is integrated into a high-precision robot-assisted platform, enabling subretinal injections and retinal vascular injections within the ocular fundus. To the best of our knowledge, this is the first time that the simultaneous acquisition of A-scan and C-scan data has been proposed for subretinal injection and retinal vascular injection procedures. The A-scan sensitivity roll-off was characterized and exhibited a decrease of approximately 3 dB over a 0.88 mm depth range in water. The B-scan imaging with 1024 × 1024 pixels achieve a 97.7 fps with maximal lateral field of view (FOV) 16 mm. The system achieved an axial measurement accuracy of 15 µm for needle tip localization. The success rate of single attempt subretinal (6 out of 6 attempts) and optic disc vessel injections was 100% in both live (3 out of 3 attempts) and ex vivo pig eyes (100 out of 100 attempts/30 out of 30 attempts), while venous injections in live pig eyes required positional adjustments during injection to achieve a 100% success rate (3 out of 3 attempts). Integrated with a microscope, the A-scan and C-scan OCT system, assisted by a robotic arm, can safely and reliably address the challenges associated with subretinal injection and retinal vascular injection.

We evaluated the effect of intraocular lens (IOL) misalignment on image quality under clinically relevant conditions (0.2, 0.4 mm decentration and 2°, 4° tilt). Two presbyopia-correcting IOLs, an extended depth of focus (EDOF) (Alcon Vivity) and a diffractive multifocal (Alcon PanOptix), were tested. Through-focus modulation transfer function (MTF)-based measures were taken using an on-bench model eye with average corneal spherical aberration and apertures of 3.0 and 4.5 mm. Optical image quality and simulated visual acuity (VA) were assessed for both aligned and misaligned IOLs. The aligned EDOF lens showed superior distance vision quality compared to the multifocal, particularly with the 4.5 mm pupil. The EDOF lens was, however, more sensitive to decentration than the multifocal, which showed very low sensitivity across far, intermediate, and near regions with both apertures. Degradation with IOL tilt occurred at a slower rate than with decentration. Despite the optical degradation produced by mild misalignment (up to 0.4 mm decentration and 4° tilt), the predicted VA demonstrates that these effects should be negligible on postoperative vision with a 3 mm pupil. This holds true not only at a far distance, but also at the relevant intermediate and near foci.

Dynamic optical coherence tomography (dOCT) is a group of techniques primarily applied to visualize intracellular motility within tissue biopsies and cultures as it relates to changes in cell viability, status, and stiffness. Here, we provide an overview of variance-based, autocorrelation-based, and spectral algorithms commonly applied to different types of dOCT signals, how the metrics extracted using these algorithms relate to the underlying intracellular motion, and review how they have been employed in dOCT applications. Detailed guidance is provided for selecting or developing metrics and algorithms to use, depending on the OCT hardware and biological motions of interest.

The shortwave infrared (SWIR) wavelength band (1,000-2,000 nm) has recently garnered increased interest due to its beneficial attributes for tissue imaging and spectroscopy. Lower scattering, increased sensitivity to endogenous water and lipid content, and the reduced influence of melanin offer new measurement opportunities and application areas. SWIR sensor technology is advancing at a rapid pace, fueling growth in academic and commercial instrument development. Here, we review recent progress in SWIR tissue imaging and spectroscopy, provide resources on tissue optical properties at SWIR wavelengths, and offer guidance on the utilization of models, methods, and instruments for SWIR measurements in tissue. One key finding is that while some efforts have exploited the lower scattering in the SWIR to achieve deep tissue imaging, this advantage is highly dependent on the specific choice of wavelength and the measurement geometry. Photon attenuation limits these advantages at wavelengths where water absorption is strong, especially in the context of higher-noise SWIR detectors. However, a growing number of clinical applications are emerging, especially those requiring in vivo water and lipid measurements, such as monitoring of tissue hydration, edema, lipid content, and others. There are further opportunities to expand this work toward more disease states while leveraging the low absorption of melanin in the SWIR. Since the field is currently limited by relatively few sources of tissue optical property data at SWIR wavelengths, we have compiled tabulated extinction values of SWIR chromophores from the literature. There is also a need for continued development of techniques for modeling photon propagation in tissue at SWIR wavelengths due to more moderate levels of tissue scattering compared to absorption, and methods to establish stable tissue-mimicking phantoms. The SWIR wavelength region is coming of age in the biophotonics community, with components and systems creating new opportunities in basic research and clinical applications once current challenges can be overcome.

Effective light delivery with precise control is critical for achieving safe and efficient photodynamic therapy (PDT). Organic light-emitting diodes (OLEDs) represent an attractive novel light source for PDT due to their large-area, uniform irradiation, and conformal adaptability to irregular lesion geometries. However, conventional OLEDs suffer from low power density, which limits their therapeutic efficacy. In this study, we optimized the multilayer structure of an OLED device, achieving a stable light output of up to 60 mW/cm²-a significant advancement expected to facilitate the development of OLED-based PDT (OLED-PDT). In both in vitro and in vivo studies using an oral squamous cell carcinoma (SCC-25) xenografted mouse model, the high-power OLED device demonstrated significant therapeutic efficacy. The treatment effectively suppresses tumor cell proliferation and angiogenesis while inducing apoptosis, thereby inhibiting tumor progression. Moreover, OLED-PDT shows excellent biosafety, with no detectable damage to normal organs. These findings highlight the promising potential of high-power OLEDs as a next-generation light source for precise and safe PDT.

Both freezing-induced loading (FIL) and freeze-casting (FC) are used for nano- and microstructured materials fabrication, including core-shell structures, shells, porous materials, as well as ceramics. The crystallization front velocity is a critical parameter for these techniques because it defines the period of lamellar structure during FC and FIL. Here, we show that the photoacoustic method allows us not only to detect the phase transition but also to measure the instantaneous velocity of the crystallization front and track ice crystal position during the crystallization of the sample. Moreover, we demonstrate the possibility of detecting a first-order phase transition in pure water using photoacoustics. Thus, the obtained results give the opportunity for in situ monitoring of the freezing-induced loading as well as the freeze-casting to optimize the parameters of nano- and microstructured materials.

Diffuse correlation spectroscopy (DCS) is a widely used noninvasive optical technique for measuring tissue blood flow. Accurate blood flow estimation with DCS requires a high signal-to-noise ratio (SNR), but achieving high SNR is often limited by safety constraints on the optical irradiance (maximum permissible exposure) that can be delivered to tissue. To overcome this limitation, we investigated the possibility of replacing the conventional multi-mode fiber (MMF) with a liquid light guide (LLG) for illumination. The LLG provides a more uniform illumination profile and higher photon throughput to the tissue under the same irradiance limit, resulting in a significantly increased detected photon count rate and enhanced SNR. In experiments under identical power-density conditions, the LLG-based system achieved approximately a three-fold increase in SNR compared to the traditional MMF configuration. This improvement arises from the uniform beam profile and efficient light delivery of the LLG, which permits safe use of higher total power. These results indicate that LLG illumination effectively enhances DCS sensitivity without exceeding safety limits, potentially enabling more sensitive and accurate blood flow monitoring in biomedical applications.

Imaging of metabolic and cellular activity in living tissue is of high interest and represents a prerequisite for an understanding of environmentally induced tissue changes. In this work, we present a dual-beam optical coherence tomography (OCT) instrument that is used to investigate dynamic processes of human skin samples with two different transverse resolutions. The amplitude and the phase of the OCT signal in both channels are exploited to assess these processes. The temporal evolution of dynamic processes in living skin tissue is analyzed and used to provide increased image contrast. This allows for a clear separation between the stratum corneum, the living epidermis, and the dermis that is otherwise not visible in standard OCT images of the system. Thereby, better dynamic contrast was observed using the higher resolution images. The reproducibility of the method is tested, and the imaging results are compared with data from fixated skin samples (where no dynamics were found within the living epidermis) and histology.

Spectral photoacoustic imaging (sPAI) has the potential to detect clinically relevant measurements of blood oxygenation, non-invasively in real time. The unique advantage of sPAI is its ability to probe optical chromophores at extended imaging depths compared to purely optical modalities. PA imaging has previously been demonstrated using benchtop nanosecond pulsed solid-state lasers; however, their size and high cost limit the potential for clinical translation. Microfabricated pulsed laser diodes (PLDs) are miniaturized laser sources that can be fabricated and integrated at relatively low cost; however, microfabricated PLDs have been minimally investigated for the generation of photoacoustic signals due to the significantly lower energies they typically provide. In this work, we integrated an array of PLD diodes with optical excitation in the second near-infrared window, demonstrating deep imaging depths that exceed the imaging depths expected based on fluence alone. Using five PLDs integrated in series at a fluence of 61.5 µJ/cm², a maximum imaging depth of 4.26 cm was achieved with a detectable CNR in a porcine tissue phantom. Additionally, spectrally unmixed hemoglobin oxygenation measurements were accurate up to a depth of 3.11 cm with ∼10% accuracy. We validated device performance using an in vivo rat model, demonstrating a detectable SNR up to a depth of 4.13 cm and accurate tissue oxygenation assessment up to 3.85 cm from the kidney under layers of porcine tissue. Our device demonstrates the feasibility of microfabricated PLDs for clinically relevant photoacoustic imaging depths.

Transcranial photobiomodulation (tPBM) shows promise in delivering beneficial effects to the brain. However, accurately estimating the stimulus energy reaching the targeted brain region remains difficult due to individual differences in anatomy and optical properties. We present a noninvasive method that combines diffuse reflectance spectroscopy with deep learning to predict the fluence rate of the stimulus light. Incorporating tissue layer thicknesses into the model significantly enhances prediction accuracy, reducing errors to approximately 13%, compared to 49% when assuming a constant irradiance at the scalp surface. By eliminating the need for expensive magnetic resonance imaging, our approach offers a scalable solution for optimizing irradiation parameters in future tPBM applications.