Optical Coherence Tomography Structural Images Research Articles

Evaluating the effects of three anesthetic regimens on retinal structure and function in the living mouse eye using a customized bimodal OCT/ORG system

Abstract Optical coherence tomography (OCT) is a non-invasive imaging technique that generates cross-sectional images of biological tissues at millimeter-level penetration depth with micron-level resolution. In this study, we developed a custom spectral-domain OCT system equipped with a flash stimulus module for dual-modality imaging of mouse retinal structure and function. The axial resolution of the system reached ∼2.7/2 μm in air/tissue following optimization and calibration. We deployed this system to conduct in vivo OCT structural imaging and optoretinography (ORG) functional assessment of mouse retina to investigate the effects of three anesthesia regimens. Statistical analysis of the results indicates that anesthesia results in a smaller relative intensity of inner/outer segment junction and external limiting membrane and a thickening of the outer segment compared to an awake state. Meanwhile, significant differences were observed in the effects on retinal structure and function between isoflurane and tribromoethanol anesthesia, while differences between isoflurane and esketamine+xylazine groups were small. These findings suggest that the type of anesthetic should be taken into account when comparing imaging results across studies reported in the literature.

IStent insertion orientation and impact on trabecular meshwork motion resolved by optical coherence tomography imaging.

The iStent is a popular device designed for glaucoma treatment, functioning by creating an artificial fluid pathway in the trabecular meshwork (TM) to drain aqueous humor. The assessment of iStent implantation surgery is clinically important. However, current tools offer limited information. We aim to develop innovative assessment strategies for iStent implantation using optical coherence tomography (OCT) to evaluate the position and orientation of the iStent and its biomechanical impact on outflow system dynamics. We examined four iStents in the two eyes of a glaucoma patient. Three-dimensional (3D) OCT structural imaging was conducted for each iStent, and a semi-automated algorithm was developed for iStent segmentation and visualization, allowing precise measurement of position and orientation. In addition, phase-sensitive OCT (PhS-OCT) imaging was introduced to measure the biomechanical impact of the iStent on the outflow system quantified by cumulative displacement (CDisp) of pulse-dependent trabecular TM motion. The 3D structural image processed by our algorithm definitively resolved the position and orientation of the iStent in the anterior segment, revealing substantial variations in relevant parameters. PhS-OCT imaging demonstrated significantly higher CDisp in the regions between two iStents compared to locations distant from the iStents in both OD ( ) and OS ( ). Our proposed structural imaging technique improved the characterization of the iStent's placement. The imaging results revealed inherent challenges in achieving precise control of iStent insertion. Furthermore, PhS-OCT imaging unveiled potential biomechanical alterations induced by the iStent. This unique methodology shows potential as a valuable clinical tool for evaluating iStent implantation.

Artificial neural network for enhancing signal-to-noise ratio and contrast in photothermal optical coherence tomography

Optical coherence tomography (OCT) is a medical imaging method that generates micron-resolution 3D volumetric images of tissues in-vivo. Photothermal (PT)-OCT is a functional extension of OCT with the potential to provide depth-resolved molecular information complementary to the OCT structural images. PT-OCT typically requires long acquisition times to measure small fluctuations in the OCT phase signal. Here, we use machine learning with a neural network to infer the amplitude of the photothermal phase modulation from a short signal trace, trained in a supervised fashion with the ground truth signal obtained by conventional reconstruction of the PT-OCT signal from a longer acquisition trace. Results from phantom and tissue studies show that the developed network improves signal to noise ratio (SNR) and contrast, enabling PT-OCT imaging with short acquisition times and without any hardware modification to the PT-OCT system. The developed network removes one of the key barriers in translation of PT-OCT (i.e., long acquisition time) to the clinic.

High-speed k-linear swept laser using acousto-optic deflectors with Doppler shift compensation for optical coherence tomography.

Swept laser based on the acousto-optic deflector (AOD) is a promising swept source in optical coherence tomography (OCT) applications for its high wavenumber linear sweep without mechanical motion. However, the poor coherence length and the elongated cavity of the laser imposed limitations on the acquisition of high-quality images with adequate imaging depth and high imaging speed. In this Letter, we demonstrate a compact high-speed wavenumber linear swept laser based on AOD using Doppler shift compensation, achieving a high linearity of Pearson's R of 0.999991, a duty cycle of ∼100%, an extended coherence length of 5.7 mm, an output power of 18 mW, and excellent phase stability at a sweep speed of 500 kHz. OCT structural images with a system sensitivity of 103.2 dB and OCT angiography (OCTA) of human palm in vivo have been successfully performed, serving as a compelling demonstration of the excellent performance of this swept laser. We believe that the proposed laser will be of high potential in various clinical and industrial applications in the future.

Non-Destructive Evaluation of Regional Cell Density Within Tumor Aggregates Following Drug Treatment.

Multicellular tumor spheroid (MCTSs) models have demonstrated increasing utility for in vitro study of cancer progression and drug discovery. These relatively simple avascular constructs mimic key aspects of in vivo tumors, such as 3D structure and pathophysiological gradients. MCTSs models can provide insights into cancer cell behavior during spheroid development and in response to drugs; however, their requisite size drastically limits the tools used for non-destructive assessment. Optical Coherence Tomography structural imaging and Imaris 3D analysis software are explored for rapid, non-destructive, and label-free measurement of regional cell density within MCTSs. This approach is utilized to assess MCTSs over a 4-day maturation period and throughout an extended 5-day treatment with Trastuzumab, a clinically relevant anti-HER2 drug. Briefly, AU565 HER2+ breast cancer MCTSs were created via liquid overlay with or without the addition of Matrigel (a basement membrane matrix) to explore aggregates of different morphologies (thicker, disk-like 2.5D aggregates or flat 2D aggregates, respectively). Cell density within the outer region, transitional region, and inner core was characterized in matured MCTSs, revealing a cell-density gradient with higher cell densities in core regions compared to outer layers. The matrix addition redistributed cell density and enhanced this gradient, decreasing outer zone density and increasing cell compaction in the cores. Cell density was quantified following drug treatment (0 h, 24 h, 5 days) within progressively deeper 100 µm zones to assess potential regional differences in drug response. By the final timepoint, nearly all cell death appeared to be constrained to the outer 200 µm of each aggregate, while cells deeper in the aggregate appeared largely unaffected, illustrating regional differences in the drug response, possibly due to limitations in drug penetration. The current protocol provides a unique technique to non-destructively quantify regional cell density within dense cellular tissues and measure it longitudinally.

Robust three-dimensional registration on optical coherence tomography angiography for speckle reduction and visualization.

In the clinical applications of optical coherence tomography angiography (OCTA), the repeated scanning and averaging method can provide better contrast with reduced speckle noises in the final results, which are useful for visualizing and quantifying vascular components with high accuracy, reproducibility, and reliability. However, the inevitable patient motion presents a challenge to this method. The objective of this study is to meet this challenge by introducing a 3D registration method to register optical coherence tomography (OCT)/OCTA scans for precise volume averaging of multiple scans to improve the signal-to-noise ratio (SNR) and increase quantification accuracy. The proposed method utilized both rigid affine transformation and non-rigid B-spline transformation in which their parameters were optimized and calculated by the average stochastic gradient descent on OCT structural images. In addition, we also introduced a multi-level resolution approach to further improve the robustness and computational speed of our proposed method. The imaging performance was tested on in vivo imaging of human skin and eye and assessed by SNR, peak signal-to-noise ratio (PSNR) and normalized correlation coefficient (NCC). Five subjects were enrolled in this study for obtaining in vivo images of skin and retina. The proposed registration and averaging method provided substantial improvements of the imaging performance in terms of vessel connectivity and signal to noise ratio. The increase of repeated volume numbers in the averaging improves all the metrics assessed, i.e., SNR, PSNR and NCC. An improvement of the SNR from 10 to 40 dB after 10 repeated volumetric averaging was achieved. The proposed 3D registration and averaging method is effective in reducing speckle noises and suppressing motion artifacts, thereby improving SNR, PSNR and NCC metrics for final averaged images. It is expected that the proposed algorithm would be practically useful in better visualization and more reliable quantification of in vivo OCT and OCTA data, which would be beneficial to OCT clinical applications.

Optical coherence tomography microangiography for monitoring the response of vascular perfusion to external pressure on human skin tissue.

Characterization of the relationship between external pressure and blood flow is important in the examination of pressure-induced disturbance in tissue microcirculation. Optical coherence tomography (OCT)-based microangiography is a promising imaging technique, capable of providing the noninvasive extraction of functional vessels within the skin tissue with capillary-scale resolution. Here, we present a feasibility study of OCT microangiography (OMAG) to evaluate changes in blood perfusion in response to externally applied pressure on human skin tissue in vivo. External force is loaded normal to the tissue surface at the nailfold region of a healthy human volunteer. An incremental force is applied step by step and then followed by an immediate release. Skin perfusion events including baseline are continuously imaged by OMAG, allowing for visualization and quantification of the capillary perfusion in the nailfold tissue. The tissue strain maps are simultaneously evaluated through the available OCT structural images to assess the relationship of the microcirculation response to the applied pressure. The results indicate that the perfusion progressively decreases with the constant increase of pressure. Reactive hyperemia occurs right after the removal of the pressure. The perfusion returns to the baseline level after a few minutes. These findings suggest that OMAG may have great potential for quantitatively assessing tissue microcirculation in the locally pressed tissue in vivo.

Correlating optical coherence tomography images with dose distribution in late oral radiation toxicity patients

AbstractBackground and objective:Late oral radiation toxicity occurs in about half of the patients who undergo head-and-neck radiotherapy, reducing the quality of life drastically. The total delivered radiation dose has been shown to be one of the predictors of these late complications. To demonstrate this, the studies carried out so far have used either visual observation together with symptom-based scoring systems or histology to evaluate the tissue response. However, the former lacks imaging information on tissue subsurface and the latter is invasive and exposes the patients to additional risks. Therefore, there is a need for a non-hazardous, non-invasive subsurface monitoring tool that can provide more objective information on dose-dependent response of normal oral tissue to radiation.Materials and methods:To address this unmet clinical need, optical coherence tomography (OCT) was used. A clinical study was conducted on 14 late oral radiation toxicity patients and 5 age-matched healthy volunteers. OCT structural images were acquired from different oral regions in both cohorts and were then de-speckled in order to provide a better visualization of the subsurface layers and features. The alterations in patients’ de-speckled OCT images compared to the healthy cohort are reviewed, and potential correlations between the total dose to specific regions and the abnormal features observed in the OCT images of the same sites are discussed.Results:OCT images were acquired from 32 sites in 14 patients, 15 of these sites belonged to the regions which received >50 Gy radiation dose and the rest to the region which was irradiated to <50 Gy. The de-speckled OCT images from the former group showed major differences, such as total layer disruption, compared to the images of healthy oral tissue. The de-speckled OCT images from all but one of the regions which received <50 Gy showed normal features and layer definition compared to healthy oral OCT images. Same results were observed in an intra-patient comparison of the ipsilateral (dose >70 Gy) and contralateral (dose <25 Gy) soft palate of one of the patients, suggesting the results are independent of anatomical differences between individuals.Conclusion:This preliminary clinical study showed the ability of OCT to differentiate subsurface features in the oral regions that received high radiation dose (>50 Gy) compared to healthy oral tissue. These results can be used to design a prospective study to monitor oral subsurface changes periodically (e.g., every 6 months) following radiotherapy, to further understand the mechanism of late radiation toxicity and its relation to dose.

Automated segmentation of intramacular layers in Fourier domain optical coherence tomography structural images from normal subjects

Segmentation of optical coherence tomography (OCT) cross-sectional structural images is important for assisting ophthalmologists in clinical decision making in terms of both diagnosis and treatment. We present an automatic approach for segmenting intramacular layers in Fourier domain optical coherence tomography (FD-OCT) images using a searching strategy based on locally weighted gradient extrema, coupled with an error-removing technique based on statistical error estimation. A two-step denoising preprocess in different directions is also employed to suppress random speckle noise while preserving the layer boundary as intact as possible. The algorithms are tested on the FD-OCT volume images obtained from four normal subjects, which successfully identify the boundaries of seven physiological layers, consistent with the results based on manual determination of macular OCT images.