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Lymphatic and peripheral nervous system imaging is of prime importance for monitoring various important pathologic processes including cancer development and metastasis, and response to therapy.
Aim
Optical coherence tomography (OCT) is a promising approach for this imaging task but is challenged by the near-transparent nature of these structures. Our aim is to detect and differentiate semi-transparent materials using OCT texture analysis, toward label-free neurography and lymphography.
Approach
We have recently demonstrated an innovative OCT texture analysis-based approach that used speckle statistics to image lymphatics and nerves in-vivo that does not rely on negative contrast. However, these two near-transparent structures could not be easily differentiated from each other in the texture analysis parameter space. Here, we perform a rigorous follow-up study to improve upon this differentiation in controlled phantoms mimicking the optical properties of these tissues.
Results
The results of the three-parameter Rayleigh distribution fit to the OCT images of six types of tissue-mimicking materials varying in transparency and biophysical properties demonstrate clear differences between them, suggesting routes for improved lymphatics-nerves differentiation.
Conclusions
We demonstrate a novel OCT texture analysis-based lymphatics-nerves differentiation methodology in tissue-simulating phantoms. Future work will focus on longitudinal in-vivo lymphangiography and neurography in response to cancer therapeutics toward adaptive personalized medicine.
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Spectroscopic and structural imaging of tissue layers is important for investigating tissue health. However, investigating superficial tissue is difficult using optical imaging, due to the convolved absorption and backscatter of light from deeper layers.
Aim
This report investigates the effects of hydration and desiccation of ex vivo porcine skin on the reflectance of polarized light at different wavelengths (light-emitting diodes).
Approach
We developed a spectroscopic polarized imaging system to investigate submicron changes in tissue structures. By separating polarized from depolarized backscattered light, submicron structural changes in subsurface and deeper tissue layers can be separated and monitored.
Results
The results demonstrate that (1) polarized light reflectance is about 2%, consistent with ∼6 scattering events, on average; (2) there was little wavelength dependence to the reflectance of polarized light; (3) increased hydration leads to a modest increase in total reflectance (from 0.8 to 0.9), whereas desiccation had little effect; however, hydration did not affect polarized reflectance, but desiccation slightly lowered polarized reflectance.
Conclusions
Higher scattering from the reticular dermis was likely due to swelling of collagen fiber bundles in the dermal layers, which increased fibril spacing. The epidermal skin surface showed little change due to the stratum corneum resisting desiccation and maintaining hydration.
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The water and lipid content of normal breast tissue showed mammary gland characteristics with less influence from the chest wall using six-wavelength time-domain diffuse optical spectroscopy (TD-DOS) in a reflectance geometry.
Aim
To determine the depth sensitivity of a six-wavelength TD-DOS system and evaluate whether the optical parameters in normal breast tissue can distinguish dense breasts from non-dense breasts.
Approach
Measurements were performed in normal breast tissue of 37 breast cancer patients. We employed a six-wavelength TD-DOS system to measure the water and lipid content in addition to the hemoglobin concentration. The breast density in mammography and optical parameters were then compared.
Results
The depth sensitivity of the system for water and lipid content was estimated to be ∼15 mm. Our findings suggest that the influence of the chest wall on the water content is weaker than that on the total hemoglobin concentration. In data with evaluation conditions, the water content was significantly higher (p < 0.001) and the lipid content was significantly lower (p < 0.001) in dense breast tissue. The water and lipid content exhibited a high sensitivity and specificity to distinguish dense from non-dense breasts in receiver-operating-characteristic curve analysis.
Conclusions
With less influence from the chest wall, the water and lipid content of normal breast tissue measured by a reflectance six-wavelength TD-DOS system, together with ultrasonography, can be applied to distinguish dense from non-dense breasts.
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Deep-imaging of cerebral vessels and accurate organizational characterization are vital to understanding the relationship between tissue structure and function.
Aim
We aim at large-depth imaging of the mouse brain vessels based on aggregation-induced emission luminogens (AIEgens), and we create a new algorithm to characterize the spatial orientation adaptively with superior accuracy.
Approach
Assisted by AIEgens with near-infrared-II excitation, three-photon fluorescence (3PF) images of large-depth cerebral blood vessels are captured. A window optimizing (WO) method is developed for highly accurate, automated 2D/3D orientation determination. The application of this system is demonstrated by establishing the orientational architecture of mouse cerebrovasculature down to the millimeter-level depth.
Results
The WO method is proved to have significantly higher accuracy in both 2D and 3D cases than the method with a fixed window size. Depth- and diameter-dependent orientation information is acquired based on in vivo 3PF imaging and the WO analysis of cerebral vessel images with a penetration depth of 800 μm in mice.
Conclusions
We built an imaging and analysis system for cerebrovasculature that is conducive to applications in neuroscience and clinical fields.
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The increase in root caries is a serious problem as society ages. Root caries is diagnosed by inspection and palpation, which are qualitative. A method to objectively and quantitatively evaluate the progress of root caries in a clinical setting is strongly desired. The root caries could be diagnosed by measuring hardness because dentin becomes softer as the caries progresses. Vickers hardness has been customarily used as an indicator of tooth hardness. However, this method cannot be used to in vivo teeth because the teeth must be dried prior to measurement to make the indentation. A hardness meter using an indenter with light for tooth monitoring (HAMILTOM) is proposed as an optical device. HAMILTOM could measure hardness of teeth in wet condition as a dark area while applying a load to dentins without drying. Therefore, HAMILTOM may realize hardness measurements of in vivo teeth in a clinical setting quantitatively.
Aim
The aim of our study is to demonstrate the optical dentin hardness measuring device HAMILTOM using bovine dentin with different demineralization times and to evaluate the correlation between the dark areas measured by HAMILTOM and the Vickers hardness measured by the Vickers hardness tester.
Approach
The samples were 20 bovine dentins. They were demineralized by a lactic acid solution with different times and divided into groups 1 and 2 of 10 samples each. In both groups, the dark areas and Vickers hardness were measured for each sample. Group 1 was used to obtain a calibration curve to calculate Vickers hardness from the dark area. Group 2 was used to validate the calibration curve obtained from the dentin samples of group 1.
Results
The areas appearing black without a total internal reflection of the indenter measured by HAMILTOM increased as the demineralization time increased. Additionally, the Vickers hardness of group 2 calculated by the dark areas of group 2 and the calibration curve obtained in group 1 and the Vickers hardness of group 2 measured by the Vickers hardness tester were strongly correlated with a determination coefficient of 0.99.
Conclusions
The results demonstrate that HAMILTOM may be a suitable alternative to the conventional method. Unlike the conventional method, which cannot be used for in vivo teeth, HAMILTOM holds potential to quantitatively evaluate the progress of caries in in vivo teeth.
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Water and lipid are key participants of many biological processes, but there are few label-free, non-contact optical methods that can spatially map these components in-vivo. Shortwave infrared meso-patterned imaging (SWIR-MPI) is an emerging technique that successfully addresses this need. However, it requires a dedicated SWIR camera to probe the 900- to 1300-nm wavelength region, which hinders practical translation of the technology.
Aim
Compared with SWIR-MPI, we aim to develop a new technique that can dramatically reduce the cost in detector while maintaining high accuracy for the quantification of tissue water and lipid content.
Approach
By utilizing water and lipid absorption features in the 900- to 1000-nm wavelength region as well as optimal wavelength and spatial frequency combinations, we develop a new imaging technique based on spatial frequency domain imaging to quantitatively map tissue water and lipid content using a regular silicon-based camera.
Results
The proposed method is validated with a phantom study, which shows average error of 0.9 ± 1.2 % for water content estimation, and −0.4 ± 0.7 % for lipid content estimation, respectively. The proposed method is also demonstrated for ex vivo porcine tissue lipid mapping as well as in-vivo longitudinal water content monitoring.
Conclusions
The proposed technique enables spatial mapping of tissue water and lipid content with the cost in detector reduced by two orders of magnitude compared with SWIR-MPI while maintaining high accuracy. The experimental results highlight the potential of this technique for substantial impact in both scientific and industrial applications.
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Dosimetry for photodynamic therapy is dependent on multiple parameters. Critically, in vivo tissue optical properties and hemodynamics must be determined carefully to calculate the total delivered light dose.
Aim
Spectroscopic analysis of diffuse reflectance measurements of tissues taken during a clinical trial of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a-mediated photodynamic therapy for pleural malignancies.
Approach
Diffuse reflectance measurements were taken immediately before and after photodynamic therapy. Measurements were analyzed with a nonlinearly constrained multiwavelength, multi-distance algorithm to extract tissue optical properties, tissue oxygen saturation, StO2, and total hemoglobin concentration (THC).
Results
A total of 25 patients were measured, 23 of which produced reliable fits for optical property extraction. For all tissue types, StO2 ranged through [24, 100]% and [22, 97]% for pre-photodynamic therapy (PDT) and post-PDT conditions, respectively. Mean THC ranged through [ 69,152 ] μM and [ 48,111 ] μM, for pre-PDT and post-PDT, respectively. Absorption coefficients, μa, ranged through [ 0.024 , 3.5 ] cm − 1 and [ 0.039 , 3 ] cm − 1 for pre-PDT and post-PDT conditions, respectively. Reduced scattering coefficients, μs′, ranged through [ 1.4 , 73.4 ] cm − 1 and [ 1.2 , 64 ] cm − 1 for pre-PDT and post-PDT conditions, respectively.
Conclusions
There were similar pre- and post-PDT tissue optical properties and hemodynamics. The high variability in each parameter for all tissue types emphasizes the importance of these measurements for accurate PDT dosimetry.
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Flexible endoscopes are essential for medical internal examinations. Digital endoscopes are connected to a video processor that can apply various operations to enhance the image. One of those operations is edge enhancement, which has a major impact on the perceived image quality by medical professionals. However, the specific methods and parameters of this operation are undisclosed and the arbitrary units to express the level of edge enhancement differ per video processor.
Aim
Objectively quantify the level of edge enhancement from the recorded images alone, and measure the effect on sharpness and noise.
Approach
Edge enhancement was studied in four types of flexible digital ear nose and throat endoscopes. Measurements were performed using slanted edges and gray patches. The level of edge enhancement was determined by subtracting the step response of an image without edge enhancement from images with selected settings of edge enhancement and measuring the resulting peak-to-peak differences. These values were then normalized by the step size. Sharpness was characterized by observing the normalized modulation transfer function (MTF) and computing the spatial frequency at 50% MTF. The noise was measured on the gray patches and computed as a weighted sum of variances from the luminance and two chrominance channels of the pixel values.
Results
The measured levels were consistent with the level set via the user interface on the video processor and varied typically from 0 to 1.3. Both sharpness and noise increase with larger levels of edge enhancement with factors of 3 and 4 respectively.
Conclusions
The presented method overcomes the issue of vendors expressing the level of edge enhancement each differently in arbitrary units. This allows us to compare the effects, and we can start exploring the relationship with the subjectively perceived image quality by medical professionals to find substantiated optimal settings.
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Biological cell imaging has become one of the most crucial research interests because of its applications in biomedical and microbiology studies. However, three-dimensional (3D) imaging of biological cells is critically challenging and often involves prohibitively expensive and complex equipment. Therefore, a low-cost imaging technique with a simpler optical arrangement is immensely needed.
Aim
The proposed approach will provide an accurate cell image at a low cost without needing any microscope or extensive processing of the collected data, often used in conventional imaging techniques.
Approach
We propose that patterns of surface plasmon coupled emission (SPCE) features from a fluorescently labeled biological cell can be used to image the cell. An imaging methodology has been developed and theoretically demonstrated to create 3D images of cells from the detected SPCE patterns. The 3D images created from the different SPCE properties at the far-field closely match the actual cell structures.
Results
The developed technique has been applied to different regular and irregular cell shapes. In each case, the calculated root-mean-square error (RMSE) of the created images from the cell structures remains within a few percentages. Our work recreates the base of a circular-shaped cell with an RMSE of ≲1.4 % . In addition, the images of irregular-shaped cell bases have an RMSE of ≲2.8 % . Finally, we obtained a 3D image with an RMSE of ≲6.5 % for a random cellular structure.
Conclusions
Despite being in its initial stage of development, the proposed technique shows promising results considering its simplicity and the nominal cost it would require.
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Hyperspectral reflectance imaging can be used in medicine to identify tissue types, such as tumor tissue. Tissue classification algorithms are developed based on, e.g., machine learning or principle component analysis. For the development of these algorithms, data are generally preprocessed to remove variability in data not related to the tissue itself since this will improve the performance of the classification algorithm. In hyperspectral imaging, the measured spectra are also influenced by reflections from the surface (glare) and height variations within and between tissue samples.
Aim
To compare the ability of different preprocessing algorithms to decrease variations in spectra induced by glare and height differences while maintaining contrast based on differences in optical properties between tissue types.
Approach
We compare eight preprocessing algorithms commonly used in medical hyperspectral imaging: standard normal variate, multiplicative scatter correction, min–max normalization, mean centering, area under the curve normalization, single wavelength normalization, first derivative, and second derivative. We investigate conservation of contrast stemming from differences in: blood volume fraction, presence of different absorbers, scatter amplitude, and scatter slope—while correcting for glare and height variations. We use a similarity metric, the overlap coefficient, to quantify contrast between spectra. We also investigate the algorithms for clinical datasets from the colon and breast.
Conclusions
Preprocessing reduces the overlap due to glare and distance variations. In general, the algorithms standard normal variate, min–max, area under the curve, and single wavelength normalization are the most suitable to preprocess data used to develop a classification algorithm for tissue classification. The type of contrast between tissue types determines which of these four algorithms is most suitable.
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TOPICS: 3D modeling, Data modeling, Tissue optics, Absorption, Signal to noise ratio, Inverse optics, Image quality, Gallium nitride, Breast, Acoustics
Significance: Quantitative optoacoustic imaging (QOAI) continues to be a challenge due to the influence of nonlinear optical fluence distribution, which distorts the optoacoustic image representation. Nonlinear optical fluence correction in OA imaging is highly ill-posed, leading to the inaccurate recovery of optical absorption maps. This work aims to recover the optical absorption maps using deep learning (DL) approach by correcting for the fluence effect.
Aim: Different DL models were compared and investigated to enable optical absorption coefficient recovery at a particular wavelength in a nonhomogeneous foreground and background medium.
Approach: Data-driven models were trained with two-dimensional (2D) Blood vessel and three-dimensional (3D) numerical breast phantom with highly heterogeneous/realistic structures to correct for the nonlinear optical fluence distribution. The trained DL models such as U-Net, Fully Dense (FD) U-Net, Y-Net, FD Y-Net, Deep residual U-Net (Deep ResU-Net), and generative adversarial network (GAN) were tested to evaluate the performance of optical absorption coefficient recovery (or fluence compensation) with in-silico and in-vivo datasets.
Results: The results indicated that FD U-Net-based deconvolution improves by about 10% over reconstructed optoacoustic images in terms of peak-signal-to-noise ratio. Further, it was observed that DL models can indeed highlight deep-seated structures with higher contrast due to fluence compensation. Importantly, the DL models were found to be about 17 times faster than solving diffusion equation for fluence correction.
Conclusions: The DL methods were able to compensate for nonlinear optical fluence distribution more effectively and improve the optoacoustic image quality.
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Hypoxia imaging for surgical guidance has never been possible, yet it is well known that most tumors have microregional chronic and/or cycling hypoxia present as well as chaotic blood flow. The ability to image oxygen partial pressure (pO2) is therefore a unique control of tissue metabolism and can be used in a range of disease applications to understand the complex biochemistry of oxygen supply and consumption.
Aim
Delayed fluorescence (DF) from the endogenous molecule protoporphyrin IX (PpIX) has been shown to be a truly unique reporter of the local oxygen partial pressure in tissue. PpIX is endogenously synthesized by mitochondria in most tissues, and the particular property of DF emission is directly related to low microenvironmental oxygen concentration. Here, it is shown that PpIX has a unique emission in hypoxic tumor tissue regions, which is measured as a DF signal in the red to near-infrared spectrum.
Approach
A time-gated imaging system was used for PpIX DF for wide field direct mapping of pO2 changes. Acquiring both prompt and DF in a rapid sequential cycle allowed for imaging oxygenation in a way that was insensitive to the PpIX concentration. By choosing adequate parameters, the video rate acquisition of pO2 images could be achieved, providing real-time tissue metabolic information.
Results
In this report, we show the first demonstration of imaging hypoxia signals from PpIX in a pancreatic cancer model, exhibiting >5X contrast relative to surrounding normal oxygenated tissues. Additionally, tissue palpation amplifies the signal and provides intuitive temporal contrast based upon neoangiogenic blood flow differences.
Conclusions
PpIX DF provides a mechanism for tumor contrast that could easily be translated to human use as an intrinsic contrast mechanism for oncologic surgical guidance.
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Coronary heart disease has the highest rate of death and morbidity in the Western world. Atherosclerosis is an asymptomatic condition that is considered the primary cause of cardiovascular diseases. The accumulation of low-density lipoprotein triggers an inflammatory process in focal areas of arteries, which leads to the formation of plaques. Lipid-laden plaques containing a necrotic core may eventually rupture, causing heart attack and stroke. Lately, intravascular optical coherence tomography (IV-OCT) imaging has been used for plaque assessment. The interpretation of the IV-OCT images is performed visually, which is burdensome and requires highly trained physicians for accurate plaque identification.
Aim
Our study aims to provide high throughput lipid-laden plaque identification that can assist in vivo imaging by offering faster screening and guided decision making during percutaneous coronary interventions.
Approach
An A-line-wise classification methodology based on time-series deep learning is presented to fulfill this aim. The classifier was trained and validated with a database consisting of IV-OCT images of 98 artery sections. A trained physician with expertise in the analysis of IV-OCT imaging provided the visual evaluation of the database that was used as ground truth for training and validation.
Results
This method showed an accuracy, sensitivity, and specificity of 89.6%, 83.6%, and 91.1%, respectively. This deep learning methodology has the potential to increase the speed of lipid-laden plaques identification to provide a high throughput of more than 100 B-scans/s.
Conclusions
These encouraging results suggest that this method will allow for high throughput video-rate atherosclerotic plaque assessment through automated tissue characterization for in vivo imaging by providing faster screening to assist in guided decision making during percutaneous coronary interventions.
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Malignant skin tumors, which include melanoma and nonmelanoma skin cancers, are the most prevalent type of malignant tumor. Gross pathology of pigmented skin lesions (PSL) remains manual, time-consuming, and heavily dependent on the expertise of the medical personnel. Hyperspectral imaging (HSI) can assist in the detection of tumors and evaluate the status of tumor margins by their spectral signatures.
Aim
Tumor segmentation of medical HSI data is a research field. The goal of this study is to propose a framework for HSI-based tumor segmentation of PSL.
Approach
An HSI dataset of 28 PSL was prepared. Two frameworks for data preprocessing and tumor segmentation were proposed. Models based on machine learning and deep learning were used at the core of each framework.
Results
Cross-validation performance showed that pixel-wise processing achieves higher segmentation performance, in terms of the Jaccard coefficient. Simultaneous use of spatio-spectral features produced more comprehensive tumor masks. A three-dimensional Xception-based network achieved performance similar to state-of-the-art networks while allowing for more detailed detection of the tumor border.
Conclusions
Good performance was achieved for melanocytic lesions, but margins were difficult to detect in some cases of basal cell carcinoma. The frameworks proposed in this study could be further improved for robustness against different pathologies and detailed delineation of tissue margins to facilitate computer-assisted diagnosis during gross pathology.
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