Journal of Biomedical Optics最新文献

Significance: Addressing the challenges of accurate dosimetry in photodynamic therapy has motivated some of the earliest work in tissue optics, which then enabled the broader development of biomedical optics. Inadequate use of dosimetry-informed treatments may contribute to heterogeneity in tumor response and variable clinical outcomes that need to be addressed.

Aim: This perspective paper seeks to understand the current status of photodynamic therapy (PDT) dosimetry in preclinical and clinical applications and identify opportunities for improvement. We also identify the "elephant in the room" of photodynamic immune stimulation that presents additional dosimetry challenges and opportunities.

Approach: The origins of PDT dosimetry based on biophysical metrics are considered, and major scientific and technological advances that have underpinned biological and clinical studies are highlighted. The question is posed: "Has the inadequacy of dosimetry for PDT been a major factor in this treatment not achieving widespread adoption into clinical practice, particularly in oncology?" It may be the case that, in the clinic and also frequently in preclinical (especially, in vivo) research, PDT dosimetry is often necessary, occasionally used, sometimes effective, and rarely sufficient. The rapid emergence of research on PDT immune stimulation poses existential challenges for PDT dosimetry as practiced to date, which is based on purely biophysical considerations, and possible approaches are suggested that incorporate immunological factors.

Results: Different clinical situations require different PDT dosimetry approaches, depending on medical complexity and technical dosimetry requirements.

Conclusions: This article is not a comprehensive review, but rather intended to recognize past advances and current limitations, and to stimulate discussion of future directions in PDT dosimetry. Inadequate dosimetry may be a potential impediment to PDT adoption and may have contributed to the failure of some previous and ongoing clinical trials.

Significance: Confocal endomicroscopic image stitching can expand the field of view and improve examination efficiency. However, due to interference from the rolling shutter effect, traditional stitching methods may produce misalignments, leading to structural distortion and artifacts. Suppressing the rolling shutter effect in confocal endomicroscopic images can effectively enhance stitching quality.

Aim: We propose a Dual-Path Gaussian U-Net (DGU-Net)-based framework for confocal endomicroscopic image stitching. The parallel dual-encoder paths of DGU-Net extract Gaussian features and conventional features at different resolutions, respectively, achieving more precise gland segmentation masks. Based on these masks, we filter stable frames and optimize feature matching to effectively suppress rolling shutter interference and improve stitching quality.

Approach: We annotated a segmentation dataset comprising 80 rat confocal laser endomicroscopy (CLE) images to train the segmentation network and validated the frame selection method's effectiveness in suppressing the rolling shutter effect on consecutively acquired rat CLE video sequences. The stitching results generated from the filtered stable image sequences were compared with conventional methods.

Results: Experimental results demonstrate that DGU-Net achieves superior performance with a Dice score of 85.17 on CLE datasets, significantly outperforming existing segmentation networks. Compared with Auto-Stitching, our method improves regional consistency across the panoramic image by eliminating artifacts caused by mismatches while delivering enhanced stitching accuracy and image quality.

Conclusions: The proposed method effectively accomplishes confocal image stitching tasks, significantly enhancing endomicroscopic examination efficiency and contributing to improved diagnostic outcomes.

Significance: Current optical health-sensing devices rely on simplified homogeneous tissue models or semi-empirical ratiometric methods, which inadequately address anatomical complexity and inter-individual optical variability. This introduces systematic errors in light propagation modeling, compromising measurement accuracy and clinical robustness, necessitating organ-specific optical models for reliable physiological sensing.

Aim: To develop a standard optical digital wrist (DW) model by integrating magnetic resonance imaging (MRI) and diffuse optical imaging (DOI), enabling anatomically accurate and optically realistic modeling of wrist tissues for improved precision in wearable optical health monitoring applications.

Approach: The multimodal MRI-DOI framework was implemented, comprising three key components: (1) statistical integration of high-resolution MRI datasets generated a population-averaged anatomical DW template; (2) region-based time-domain diffuse optical tomography (TD-DOT) with MRI-derived anatomical priors, extracted depth-resolved optical properties of subsurface tissues; (3) spatial frequency domain imaging (SFDI) supplemented high-resolution optical properties of superficial skin layers.

Results: Simulation experiments demonstrated the high accuracy of region-based TD-DOT reconstruction, with mean errors below 8.57% ( ${\mu }_a$ ) and 9.63% ( ${\mu }_s^{\text{'}}$ ), quantitatively supporting the precision of the proposed approach. Phantom experiments with wrist-mimicking phantoms yielded mean reconstruction errors of 10.52% ( ${\mu }_a$ ) and 13.23% ( ${\mu }_s^{\text{'}}$ ) for TD-DOT, and the SFDI top-layer quantification yielded lower errors of 4.48% ( ${\mu }_a$ ) and 8.69% ( ${\mu }_s^{\text{'}}$ ), validating the performance of the TD-DOT system and the SFDI system. Furthermore, in vivo optical property measurements showed strong agreement with literature values, further validating the reliability and practicality of the methodology.

Conclusions: We establish a standard DW template and develop an in vivo optical structure acquisition methodology, transitioning biosensing models from homogeneous approximations to anatomically layered models. The approach can enhance the customization, dynamic adaptability, and clinical validity of biosensing technologies.

Significance: Estimating biomechanical properties of the in vivo crystalline lens remains a challenge and is a barrier to evaluating novel lens softening therapies. There is a need to estimate quantitative biomechanical properties of the human anterior and mid segments of the eye in vivo for conditions such as presbyopia.

Aim: We aim to develop a multimodal elastography device that enables high-performance sequential 3D imaging with both Brillouin microscopy and optical coherence elastography (OCE).

Approach: We combined Brillouin spectroscopy and OCE on a modified slit lamp platform for human measurements. The multimodal system was first characterized and then tested on both a porcine eye and a human subject.

Results: Both OCE and Brillouin microscopy were characterized at peak operating performance for clinical imaging. Successful measurements of an in situ porcine lens and a human in vivo lens are reported.

Conclusion: We demonstrated the first successful multimodal OCE and Brillouin microscopy measurement in a human subject. This instrument offers the potential to characterize the biomechanical status of presbyopia with age.

Significance: The relationship between spatial offset and tissue sensing depth is not well understood in spatial offset Raman spectroscopy (SORS). Detection of the subsurface biochemical composition could improve clinical translation of SORS-based methods, including for lumpectomy margin characterization in breast cancer surgery.

Aim: We aimed at developing an experimental method to establish a relationship between spatial offset in SORS and sampling depth. The technique was developed using a custom hyperspectral line-scanning imaging system optimized for Raman spectroscopy detection.

Approach: Bilayer phantoms were produced with top and bottom layers made of material with different Raman spectroscopy signatures, i.e., poly(dimethylsiloxane) polymer (PDMS) and Nylon. The top layer of PDMS had different values of absorption and reduced elastic scattering coefficients, as well as a thickness up to $\sim 3\mathrm{mm}$ . A metric was used, called spectral angle mapper, that allowed for comparing SORS measurements with reference spectra of pure PDMS and Nylon. That metric was used to develop a technique predicting sensing depth for different values of spatial offset. A proof-of-concept study was performed to assess the performance of the method in biological tissue, demonstrating detectability of protein-rich tissue across layers of Intralipid and porcine fat to simulate the optical properties of human adipose tissue.

Results: A total of 60 optical phantoms with varying optical properties and top layer thicknesses were imaged and processed to estimate sampling depth as a function of spatial offset. The study demonstrated the detectability of the underlying Nylon layer across a PDMS layer up to 3 mm in thickness. Similarly, the detectability of protein-rich tissue was demonstrated across layers of Intralipid up to 3 mm thick and $<2\mathrm{mm}$ for porcine fat.

Conclusions: We showed the feasibility of using bilayer solid optical phantoms to create correlation curves between the optimal spatial offset for a desired probed depth given the optical properties of the top layer. The technique could facilitate the clinical translation of SORS measurements for tumor detection and margins assessment.

Significance: Accurate estimation of hydrogel phantom elasticity in 3D cell culture systems provides valuable insights into cellular responses to various mechanical stimuli. Although reverberant wave elastography has been applied to measure hydrogel elasticity in 3D cell cultures using multi-point loading, achieving a high-quality reverberant displacement field remains critical for accurate reverberant wave elastography.

Aim: We develop an innovative approach using 3D-printed randomly distributed scatterers to improve displacement field quality in reverberant wave elastography, inspired by scattering-coded architectured boundaries in object localization.

Approach: Numerical simulations were performed to analyze the reverberant displacement fields under various loading conditions. The results were compared to determine the optimal loading configuration to enhance the reverberation level of the displacement field. Subsequently, both numerical and experimental reverberant wave elastography were carried out to validate the elasticity measurement with 3D-printed randomly distributed scatterers.

Results: The comparison of reverberant displacement patterns under various loading conditions revealed that the displacement pattern under circular loading with 64 scatterers most closely approximated a diffuse wave field, exhibiting both spatial uniformity and directional isotropy. Numerical reverberant wave elastography was subsequently performed, successfully demonstrating its capability for elasticity measurements. Furthermore, the shear wave speeds obtained through optical coherence elastography showed good agreement with shear rheometry measurements.

Conclusions: The developed 3D-printed randomly distributed scatterers successfully enhanced the quality of the reverberant displacement field for reverberant wave elastography. Our approach presents a novel and promising tool for quantifying tissue elasticity in reverberant wave elastography applications.

The editorial introduces the JBO Special Section "Advances in Optical Elastography" for Volume 30 Issue 12.

Significance: Topical photodynamic therapy (PDT) with protoporphyrin IX (PpIX) converted from 5-aminolevulinic acid (ALA) is a well-established noninvasive method of treating skin conditions and lesions. During PDT, there can be response dynamics within the tissue that are affected by the light delivery, seen with fractionated delivery and in subcurative priming delivery. Fractionated light doses can considerably increase efficacy of 5-ALA PDT response.

Aim: We aim to examine the changes in physiological blood flow, tissue oxygenation, and PpIX concentration during and after light delivery in topical ALA-PDT in nude mouse skin.

Approach: We compared three schemes of light delivery for topical ALA-PDT in nude mice, including (1) full light delivery without fractionation, (2) two equal fractions (50% and 50%) of light separated by 2 h, and (3) a 5% light dose fractionation by 2 h prior to the main 95% light dose. Tissue oxygen imaging was assessed with the hypoxia signal from delayed fluorescence of PpIX itself within the tissue, as well as by confirmation with Oxyphor phosphorescence lifetime quenching imaging.

Results: The results of blood flow imaging and hypoxia imaging from PpIX and oxygen imaging with Oxyphor each showed evidence of increased capillary flow and tissue oxygenation after the initial 5% light dose, increased at the side of irradiation. This increased capillary flow and tissue oxygenation are presumably from vasodilation and local capillary flow increase. PpIX replenishment occurs during the intervening dark period after the initial light delivery.

Conclusion: These observations suggest that increasing oxygen and capillary flow combined with increased PpIX production together yield increased PDT efficiency, amplified by this initial light dose from a photodynamic optical priming event occurring 2 h prior to full PDT light delivery.

Significance: Current methods of measuring dosimetry for photodynamic therapy (PDT) have proven to be inadequate in their inability to provide accurate, real-time, and spatially resolved monitoring without interrupting the PDT treatment.

Aim: Our goal was to develop and validate a combined treatment and dosimetry system capable of monitoring implicit and explicit dosimetry in real time during non-contact PDT.

Approach: By employing both fluorescence imaging and spatial frequency domain imaging (SFDI), designed with low-cost, off-the-shelf components, the combined imaging system would be able to provide information on the spatial distributions of photosensitizer concentrations, tissue oxygenation, and delivered light dose, all while monitoring the photobleaching dynamics of the photosensitizer. Although the concept behind the combined system is not specific to any one photosensitizer, we focused on designing the system for the endogenous PDT of Gram-positive bacteria which utilizes coproporphyrin III as the photosensitizer.

Results: The overall performance of the system was assessed, with the accuracy, precision, and resolution of the SFDI-derived optical property maps being determined to fall within comparable ranges to other systems, despite the $1.0{\mathrm{mm}}^{-1}$ spatial frequency utilized for the shorter wavelengths. After validating the ability of the system to correct for tissue-like optical properties, and thus produce accurate quantitative fluorescence images, a preliminary assessment of antimicrobial PDT photobleaching dosimetry was performed, and high correlations were found between the fluorescence and PDT outcomes.

Conclusions: Overall, the developed imaging system showcases the potential to enable a more thorough analysis of PDT dosimetry and the impact of different variables on treatment outcomes.