Biomedical optics express最新文献

[This corrects the article on p. 3593 in vol. 13, PMID: 35781949.].

Here, we propose optomechanical devices for steering anesthetized animals during retinal imaging and/or stimulation with stationary ophthalmoscopes. Simple operating procedures ensure that the entrance pupil of the eye remains centered on the exit pupil of the ophthalmoscope during steering, to avoid vignetting. The devices, built with commercially available manual linear stages and motorized rotating devices, can be used to capture image sequences for tiling, as is often done in microscopy. This automated steering system, demonstrated here in mice, is applicable to other animal species and imaging modalities, as well as explanted eyes. The use of these devices can reduce imaging time and retinal light exposure, both of which are important when using ophthalmoscopes with small fields of view, such as adaptive optics ophthalmoscopes, while also improving animal welfare.

Transmission optical coherence tomography (OCT) enables analysis of biological specimens in vitro through the detection of forward-scattered light. Up to now, transmission OCT has been considered a technique that cannot directly retrieve quantitative phase and is thus a qualitative method. In this paper, we present qtOCT, a novel quantitative transmission optical coherence tomography method. Unlike existing approaches, qtOCT allows for a direct, easy, fast, and rigorous retrieval of 2D integrated phase information from transmission full-field swept-source OCT measurements. Our method is based on coherence gating and allows user-defined temporal measurement range selection, making it potentially suitable for analyzing multiple-scattering samples. In the weak-scattering regime, we demonstrate high consistency between qtOCT and digital holographic microscopy phase images, whereas in the multiple-scattering regime, we show the superiority of qtOCT. This approach enhances transmission OCT capabilities, positioning it as a viable alternative to existing quantitative phase imaging techniques.

The guest editors introduce a feature issue on the topic of imaging of tissue and cell dynamics.

Lung cancer is the leading cause of cancer-related mortality worldwide, making early screening crucial for improving patient survival. In recent years, exosomes have garnered significant attention as promising biomarkers for the detection of lung cancer. Their easy isolation from body fluids, such as blood and urine, makes them a perfect sample for liquid biopsy, while liquid biopsy is widely used in clinical research. Droplet coating deposition Raman (DCDR) spectroscopy is well-suited for exosome detection due to its molecular fingerprints, non-invasiveness, low sample volume requirements, and minimal/no sample preparation. In this study, we combined DCDR technology with machine learning algorithms to screen for lung cancer based on plasma-derived exosomes. High-quality exosomes were isolated from clinical blood samples via ultracentrifugation, exhibiting a characteristic cup-shaped morphology with an average diameter of 130 nm and expressing canonical exosome markers (CD63 and CD81). Although subtle differences were observed between the Raman spectra of exosomes from lung cancer patients and from healthy individuals, principal component analysis (PCA) revealed the presence of a batch effect across the samples. To enable diagnosis while minimizing the impact of batch effect, the support vector machine (SVM) model outperformed the linear discriminant analysis (LDA) model, achieving 95.60% accuracy (area under the curve (AUC) = 0.996) at the spectrum level and 100% accuracy at the patient level. These results demonstrate that Raman spectroscopy is an up-and-coming tool for rapid lung cancer screening, offering the advantages of low cost, ease of operation, low sample volume requirements, and high speed.

We utilize periodic structured illumination with pseudo-HiLo (pHiLo) image reconstruction for in vivo voltage imaging. We demonstrate reduced signal from out-of-focus cells, which contaminates voltage activity for in-focus cells of interest, with pHiLo compared to traditional widefield recordings taken with uniform illumination and pseudo-widefield (pWF) reconstructions. We compare spike peak-to-noise ratio (PNR) and cell-background correlation for time courses extracted using pHiLo and soma-targeted widefield illumination (TI). We discuss tradeoffs between out-of-focus light reduction, signal-to-noise ratio, and temporal resolution for pHiLo in the context of high-speed voltage imaging in awake mice.

Laser speckle contrast imaging (LSCI) is an under-utilized retinal imaging modality capable of non-invasively generating contrast-free, widefield maps of retinal blood flow from which multiple metrics of retinal hemodynamic function can be derived using relatively simple flood illumination instrumentation. Technical and computational advancements have improved spatiotemporal resolution and data extraction to the extent that three-peak blood flow waveforms, currently unaccounted for in LSCI nomenclature, are consistently revealed in the murine retina. Herein, we utilize a custom LSCI instrument and newly developed analysis pipeline to demonstrate the prevalence of the triphasic blood flow waveform, map timing of its first and third peaks to systole and diastole, respectively, via corroboration with arterial cannulation, and measure basal hemodynamic values for global, arterial, and venous retinal blood flow.

This study uses a wavefront model to evaluate the effects of contact lenses on retinal image quality (RIQ) as a function of target vergence (TV). Three hundred synthetic eyes were generated using an accommodative wavefront model to simulate the changes in RIQ with accommodation. The synthetic eyes wavefronts were computationally combined using direct wavefront summation with two myopia control CLs. One has a +2.00D treatment zone dual-focus (DF) design (MiSight), and the other has an extended depth of focus (EDOF) design (Mylo). Peak image quality was calculated for the naked eye, with CLs in the relaxed state, and for an accommodative demand of -2.5D. Additionally, the predicted accommodative response (change in accommodative response that maximizes RIQ) was calculated. The mean RIQ (normalized between 0 and 1) for the relaxed eye was 0.42 ± 0.10 in the naked eye. It decreased to 0.26 ± 0.05 with the DF and threefold to 0.15 ± 0.04 with the EDOF. For a TV = -2.5D, the RIQ was 0.34 ± 0.09 in the naked eye condition, 0.24 ± 0.07 with the DF, and 0.19 ± 0.03 with the EDOF. For the TV, the CL's effective add power, the accommodative RIQ showed a secondary peak, with RIQs of 0.08 ± 0.03 (DF) and 0.12 ± 0.04 (EDOF). The theoretical accommodative response (AR) of the naked eye was 2.33 ± 0.20 D, while with the DF and EDOF, it was 2.23 ± 0.39 D and 1.75 ± 0.22 D, respectively. Both myopia control CLs reduced RIQ at a TV of 0 D. At a TV = -2.5D; both lenses caused a secondary peak in the RIQ through focus. With EDOF, the secondary peak was less than 0.1 D from the maximum peak, likely due to its EDOF design. The theoretical AR was reduced with both myopia control CLs, 0.27 D for DF CLs and 0.75 D for EDOF CLs. These results indicate that both lenses impose significant limitations on RIQ and theoretical AR, align with findings from previous studies on subjective optical performance, and validate the model as a useful testing tool.

We have developed an AO-OCT-based method to characterize microscopic vasodilatory responses of peripapillary major retinal artery (ppRA) to the focal luminous flicker stimulation of peripheral retinal neurons (>15^° temporal to the fovea) with various mean illuminance levels, frequencies, and spatial patterns in the living human eye. The results have demonstrated that our proposed method can effectively measure transient, microscopic vasodilatory responses of the ppRA to the focal flicker stimulation, which increased monotonically with mean illuminance levels (1, 5 and 11lx), and exhibited frequency band-pass-like behavior (2, 5, 10, 15, 20 and 30 Hz) consistent with expected increases in the activities of retinal ganglion cells (RGCs) and their associated axons. We also found that the proposed method can be used to measure the spatial interdependency of their neurovascular responses: superior arcuate ppRA response to the superior-temporal flicker was 58% greater than that to the inferior-temporal flicker, and the inferior arcuate ppRA response to the inferior-temporal flicker was 86% greater than that to the superior-temporal flicker. Collectively, these results indicate that, using the proposed method, we can now test the hypothesis that major retinal arteries respond in an orchestrated manner to increased firing activities of RGCs and their associated axons, by accounting for the spatial coordinates between the stimulated neurons and the ppRA arcs in the living human eye.

The retinal phenotype of Alzheimer's disease (AD), its connection to spatial memory, and the influence of sex on the phenotype are poorly understood. Here, we investigate the retina and spatial memory of 5xFAD mouse models of AD by measuring retinal and behavioral parameters. A custom-built optical coherence tomography (OCT) system is used to image the retina of 32 transgenic and 32 non-transgenic 5xFAD mice over the course of 6 months (3-9 months of age). The Morris water maze (MWM) test was performed to examine correlations between the retinal and spatial memory phenotype of the mouse model. Total retinal and inner retinal layer thickness increased slightly over the measurement period, while outer retinal layer and retinal nerve fiber layer thickness showed no significant change. The correlation analysis between MWM and layer thickness data revealed a positive correlation between inner nuclear layer thickness and spatial memory capabilities. OCT and MWM data revealed sex-based differences in the retinal phenotype of the 5xFAD mouse model, with changes in retinal thickness in different stages of the study and dissimilar correlations between retinal and spatial memory phenotype.