Journal of Biomedical Optics最新文献

Significance: Airway wall elastography (AWE) is promising for evaluating upper airway obstructive disorders and airway injuries. Technologies for AWE based on endoscopic optical coherence tomography (OCT) provide micron-scale resolution to capture airway wall deformations during tidal breathing. Combined with an intraluminal pressure probe, these technologies can provide quantitative AWE as part of a routine bronchoscopy exam. However, scan times must be of short duration to mitigate risk.

Aim: Our objective is to reduce the scan time necessary to perform OCT elastography over a 50 mm length of the airway wall to less than 1 min.

Approach: We introduce an innovative, 4D OCT imaging technique that scans in a sawtooth pattern to revisit each axial position of the airway over a diversity of respiratory phases. An anatomical (long-range) OCT system capable of capturing cross-sections of the upper airway was employed in conjunction with an intraluminal pressure catheter. Scanned data are retrospectively sorted into axial bins with high- and low-pressure thresholds used to compute cross-sectional compliance (CC) within each bin across the length of the upper airway.

Results: 4D OCT was tested in simulation, on rigid and deformable samples, and on in vivo pigs undergoing bronchoscopy. A precise CC measurement with a 0.5 mm sampling resolution over a 50 mm scan length in under 42 s was achieved.

Conclusions: The retrospective, respiratory-gated 4D aOCT scanning method is a minimally invasive technique for measuring airway wall CC. The method exhibited high precision in controlled models, effectively detected elastic heterogeneity, and yielded clinically relevant results in in vivo pigs.

The editorial introduces the special issue honoring Brian C. Wilson as a pioneer of biomedical optics.

Significance: Photodynamic therapy (PDT) for the treatment of oral cancers and oral potentially malignant lesions can be enhanced by the capability of the photosensitizer to serve as a fluorescence contrast agent for treatment guidance. The development of image-based dosimetry reporters can inform treatment progress in real time to avoid under-treatment, leading to incomplete response and recurrence.

Aim: We investigate the hypothesis that imaging of protoporphyrin IX (PpIX) photoproduct (PP) accumulation may be leveraged as an implicit PDT dosimetry reporter for PDT using 5-aminolevulinic acid (ALA)-induced PpIX photosensitization.

Approach: In initial spectroscopy studies, we investigate dose-dependent changes in absorption and fluorescence spectra of PpIX corresponding to PP accumulation during red light (635 nm) delivery. We use spectral analysis to select fluorescence excitation and spectral filtering components for PP imaging during treatment. We evaluate the capability for imaging PP accumulation concomitant with PpIX photobleaching in tissue phantoms, 3D oral squamous cell carcinoma (OSCC) models, and in murine xenografts.

Results: Spectroscopy shows fluence-dependent changes in PpIX optical properties, and that excitation of photobleached PpIX with 450 nm light produces fluorescence emission associated with PpIX PPs. An existing handheld intraoral probe is shown to be capable of imaging dose-dependent PP accumulation with the addition of a spectral filter to isolate fluorescence emission longer than 650 nm. PP signal increases concomitant with PpIX photobleaching in a fluence-dependent manner and correlates with the extent of cytotoxic response in 3D cultures. PP accumulation is also observed to occur concomitantly with photobleaching in OSCC subcutaneous xenografts.

Conclusions: Overall, the results show that imaging of PP accumulation is feasible by adapting traditional photodiagnosis optical components and may serve as a dosimetry reporter for ALA-PDT, which is complementary to the measurement of PpIX photobleaching.

Significance: Linear-array-based photoacoustic imaging (PAI) combines functional imaging with structural imaging from ultrasound. However, it suffers from depth-dependent optical attenuation due to surface illumination, resulting in decreased signal amplitude and image contrast with depth. Existing attenuation compensation methods often amplify noise, creating a trade-off between depth enhancement and image quality.

Aim: We aim to develop a deep learning method that addresses the coupled problem of optical attenuation compensation and denoising for linear-array-based PAI and test the applicability in vivo.

Approach: We propose a vision-transformer-based generative model to address this coupled problem. A diverse dataset was created using simulated data and experimental twin phantoms. Vascular twin phantoms were made by printing digital images onto polyurethane films to test the performance of the model. We trained and compared three deep learning architectures, Pix2Pix, Residual U-Net, and the proposed Transformer U-Net, using various loss functions, including adversarial, MSE, PSNR, SSIM, and a combined PSNR + SSIM. We tested the model on small animal tumor images.

Results: Quantitative evaluation shows that PSNR + SSIM loss is robust in preserving structural details and suppressing noise. Under the pre-specified SSIM + PSNR training objective, Trans U-Net achieves the highest SSIM and PSNR across noise levels on both datasets. In vivo validation using murine breast tumor models and in vivo breast imaging confirmed the model's ability to enhance visualization of deep vascular structures without introducing noise amplification.

Conclusions: The proposed Trans U-Net effectively addresses the coupled problem of attenuation correction and denoising in handheld PAI. This method improves depth-resolved vascular imaging and is potentially useful in clinical and preclinical photoacoustic applications.

Significance: Two-photon (2P) holographic optophysiology, which combines optogenetic actuators and genetically encoded ${\mathrm{Ca}}^{2+}$ indicators (GECIs), enables precise in vivo interrogation of neuronal networks. However, this approach is hindered by crosstalk, which is unintentional activation of actuators by imaging light, especially when using blue-light-activated GECIs (e.g., GCaMP) with red-light-activated actuators (e.g., ChRmine).

Aim: To eliminate crosstalk in 2P holographic optophysiology, we employed the inverse combination, namely red GECIs and blue-light-activated actuators and optimized the excitation wavelength, as conventional 2P excitation failed to detect optogenetically induced GECI responses.

Approach: PC12h cells expressing various combinations of GECIs and optogenetic actuators were subjected to simultaneous ${\mathrm{Ca}}^{2+}$ imaging and optogenetic stimulation under both single-photon (1P) and 2P excitation.

Results: Under 1P excitation, crosstalk was evident in the GCaMP6m (blue)/ChRmine (red) pair, but negligible in the R-CaMP1.07 (red)/eTsChR (blue) pair. Under 2P excitation, R-CaMP1.07 showed significantly enhanced sensitivity at a red-shifted wavelength ( $\sim 1200\mathrm{nm}$ ) compared with the expected 2P excitation wavelength (1125 nm).

Conclusion: Red-shifted excitation was essential for detecting the small ${\mathrm{Ca}}^{2+}$ elevation following optogenetic stimulation. This optimized condition improves the sensitivity of red GECIs and enables a more robust 2P optophysiology free from crosstalk.

Significance: Cardiovascular disease remains one of the leading causes of death in the United States. Wearable optical systems are known to have errors and biases for individuals with different skin tones as well as different levels of obesity. By enabling the development and validation of wearable technologies across diverse populations, we advance equitable healthcare solutions and foster the creation of more reliable, personalized health monitoring systems.

Aim: We aim to develop a dynamic wrist phantom replicating the radial artery pulse, addressing physiological variations such as skin tone and obesity that impact wearable health technologies.

Approach: A silicone-based phantom mimics human tissues' mechanical and optical properties. A cam-driven pulsatile flow system simulated physiological blood flow, with key waveform features controlled by mechanical components. Optical properties were adjusted using titanium dioxide and carbon black to match Fitzpatrick skin tones I to VI, whereas radial artery depth variations simulated the effects of obesity. The phantom system incorporated a blood-mimicking fluid to replicate the optical absorption characteristics of whole blood.

Results: The phantom successfully replicated photoplethysmography (PPG) waveforms at heart rates ranging from 59 to 118 beats per minute, demonstrating physiologically representative features such as systolic and diastolic peaks. Signal degradation was observed with increasing vessel depth and darker skin tones, consistent with real-world challenges in wearable device accuracy. The alternating signal/baseline signal ratio of the PPG signal decreased by up to 77.8% for darker skin tones and deeper vessels. The phantom also validated its performance against commercial wearables, supporting its utility in device testing.

Conclusions: This dynamic wrist phantom provides a robust platform for evaluating optical devices under controlled and representative conditions, addressing critical gaps in inclusivity and accuracy.

Significance: Dental caries is a polymicrobial condition derived from microbial biofilm. There is a lack of studies addressing antimicrobial photodynamic therapy (aPDT) activity against a cariogenic multispecies biofilm.

Aim: We aim to evaluate the activity of aPDT against a cariogenic biofilm composed of a microbial consortium.

Approach: Equal parts of Streptococcus mutans, Lactobacillus rhamnosus, and Candida albicans were used to form a microbial inoculum containing $\sim {10}^7$ colony-forming units/mL, which was placed on cellulose acetate membranes to form biofilm. After biofilm formation, the seven groups, each containing four membranes, were treated as follows: laser 1 J (G1); laser 4 J (G2); photosensitizer methylene blue (G3); photosensitizer + laser 1 J (G4); photosensitizer + laser 4 J (G5); chlorhexidine as positive control (G6); and distilled water (G7).

Results: The number of viable microbial cells per biofilm varied between $1.40\times {10}^8$ (G5) and $7.28\times {10}^8$ (G1), whereas the negative control group (G7) reached $1.38\times {10}^9$ . Compared with G7, all groups presented a reduction, with the percentage varying from 47.05% (G1) to 89.85% (G5). However, G5 (photosensitizer + laser 4 J) was the only group to present a statistical reduction ( $p<0.05$ ).

Conclusion: aPDT represents an important antibiofilm adjunct therapy, resulting in a significant reduction in microbial cells within a cariogenic biofilm model.

Significance: In vivo optical coherence tomography (OCT) of the mouse vitreoretinal vasculature in full depth is technically challenging. Conventional OCT techniques employ axial confocal gating, which induces signal drop-off and limits spatial resolution outside the Rayleigh range.

Aim: Our aim is to develop a multifocal OCT imaging approach using a tunable lens and a registration method that allows the generation of a composite image of the vitreoretinal vasculature while preserving high and uniform lateral spatial resolution, signal intensity, and image contrast in full depth.

Approach: A calibration target was developed to characterize the multifocal optical system and quantify the signal intensity, contrast, and resolution. These optical specifications were used to image mice at postnatal day 14. Intra- and inter-volume registration methods were necessary to correct for motion and generate a composite image from single-focus images using weighted averaging.

Results: In the calibration target, signal intensity and contrast were 20 dB higher in the composite compared with single-focus images. Lateral resolution remained uniform (4 to $6\mu m$ ). In animals, signal intensity and contrast were 10 to 15 dB higher in the composite compared with single-focus images and highest in the hyaloid vasculature.

Conclusions: This technique is promising in studying the mouse vitreoretinal vasculature during eye development and disease.

Significance: Accurate and efficient photon modeling plays an essential role in the rapidly developing field of diffuse optical imaging, whereby the use of model-based analysis and image reconstruction can provide both educational and research benefits.

Aim: NIRFASTerFF is a cross-platform (Linux, macOS, and Windows) Python package for finite element method (FEM)-based light propagation modeling, supporting continuous-wave, frequency-domain, and time-resolved data for both exogenous and endogenous optical imaging applications. It also enables modeling of the autocorrelation function ( $G_1$ ) for diffuse correlation spectroscopy. Validation is performed through comparison with the original NIRFAST and gold-standard Monte Carlo simulations.

Approach: NIRFASTerFF incorporates highly parallelized FEM solvers for efficient computation on both CPU and GPU, leveraging OpenMP and CUDA acceleration. To support image reconstruction tasks, voxel-based interpolation of the optical fluence is implemented, providing a flexible and accurate representation of the forward solution suitable for inverse problem formulations.

Results: Compared with its predecessor, NIRFASTer, the optimized algorithms provide a performance boost of 25% to 45% on GPU and up to 20% on CPU, and the results show good agreement with both Monte Carlo and analytical solutions.

Conclusion: The NIRFASTerFF package provides a fast and license-free tool for photon modeling and can further streamline Python-based data processing in diffuse optical imaging, benefiting the biophotonics community.

Significance: Dental implants (DI) are among the most effective solutions for restoring masticatory function in patients with tooth loss. The success of these implants often depends on selecting appropriate design parameters, such as length and diameter, to ensure optimal outcomes. Understanding how these variables influence load transfer to the surrounding bone is essential for improving DI performance.

Aim: We aimed to evaluate the effects of implant diameter and length on static load distribution to surrounding bone-mimicking material (BMM) under identical optical and mechanical conditions, using an original and more accurate photoelastic testing method.

Approach: Epoxy resin was used to replicate the mechanical behavior of the bone under static load conditions. A total of 12 DI designs with varying lengths and diameters were tested, with three replicas each ( $n=36$ ). Polarized light was applied to the apex of each implant to detect optical intensity changes ( $\Delta I$ ) in the BMM under a 150-N static load and at rest.

Results: A significant correlation was found between implant diameter and load distribution ( $p<0.05$ ). Wider implants showed more uniform load transfer, with 4.5-mm versus 5.5-mm-diameter implants showing 2.47 times less polarized light change, and 4.5-mm versus 6.9-mm implants showing 18.38 times less. By contrast, implant length had no statistically significant impact on load distribution ( $p>0.05$ ). The 6.9-mm diameter and longest implants transmitted the highest load to the BMM, whereas 11.5-mm length implants showed the lowest optical intensity changes ( $\Delta I$ ) under static load.

Conclusions: Implant diameter has a greater impact than length on stress distribution to surrounding structures. Emphasizing diameter selection may enhance implant longevity and clinical success.