Non-invasive Optical Technique Research Articles

In Vivo Optical Imaging of Bladder Cancer Tissues in an MB49 Bladder Cancer Orthotopic Mouse Model Using the Intravesical or Intravenous Administration of Near-Infrared Fluorescence Probe.

Bladder cancer was the twelfth most common cancer worldwide in 2020. Although bladder cancer has been diagnosed using macroscopic techniques, such as white-light cystoscopy and fluorescence blue-light cystoscopy, there is a need to explore more effective noninvasive optical imaging techniques for accurate bladder cancer diagnosis. This study demonstrates the high effectiveness of the near-infrared fluorescence (NIRF) probe ASP5354, which has been developed for ureteral identification during in vivo diagnosis of bladder cancer in an MB49 bladder cancer orthotopic mouse model. After the intravesical injection of 2.4 μM ASP5354 followed by bladder rinsing with saline at 5 min post injection or intravenous administration of ASP5354 at 240 nmol/kg mouse body weight, followed by a waiting period of 5-24 h in mice, ASP5354 was absorbed specifically by cancerous tissue and not by normal tissues in the bladder. NIRF of ASP5354 in cancer tissues was detected using the NIRF imaging camera system. The NIRF clearly showed a boundary between cancerous and normal tissues. Therefore, ASP5354 provides noninvasive and specific optical in vivo imaging of MB49 bladder cancer using intravesical or intravenous injection of ASP5354. ASP5354 may allow for new diagnostic applications for bladder cancer in humans.

Light-sheet laser speckle imaging for cilia motility assessment

Mucociliary clearance is an important innate defense mechanism predominantly mediated by ciliated cells in the upper respiratory tract. Ciliary motility on the respiratory epithelium surface and mucus pathogen trapping assist in maintaining healthy airways. Optical imaging methods have been used to obtain several indicators for assessing ciliary movement. Light-sheet laser speckle imaging (LSH-LSI) is a label-free and non-invasive optical technique for three-dimensional and quantitative mapping of velocities of microscopic scatterers. Here, we propose to use an inverted LSH-LSI platform to study cilia motility. We have experimentally confirmed that LSH-LSI can reliably measure the ciliary beating frequency and has the potential to provide many additional quantitative indicators for characterizing the ciliary beating pattern without labeling. For example, the asymmetry between the power stroke and the recovery stroke is apparent in the local velocity waveform. PIV (particle imaging velocimetry) analysis of laser speckle data could determine the cilia motion directions in different phases.

Numerical approach to quantify depth-dependent blood flow changes in real-time using the diffusion equation with continuous-wave and time-domain diffuse correlation spectroscopy.

Diffuse correlation spectroscopy (DCS) is a non-invasive optical technique that can measure brain perfusion by quantifying temporal intensity fluctuations of multiply scattered light. A primary limitation for accurate quantitation of cerebral blood flow (CBF) is the fact that experimental measurements contain information about both extracerebral scalp blood flow (SBF) as well as CBF. Separating CBF from SBF is typically achieved using multiple source-detector channels when using continuous-wave (CW) light sources, or more recently with use of time-domain (TD) techniques. Analysis methods that account for these partial volume effects are often employed to increase CBF contrast. However, a robust, real-time analysis procedure that can separate and quantify SBF and CBF with both traditional CW and TD-DCS measurements is still needed. Here, we validate a data analysis procedure based on the diffusion equation in layered media capable of quantifying both extra- and cerebral blood flow in the CW and TD. We find that the model can quantify SBF and CBF coefficients with less than 5% error compared to Monte Carlo simulations using a 3-layered brain model in both the CW and TD. The model can accurately fit data at a rate of <10 ms for CW data and <250 ms for TD data when using a least-squares optimizer.

Photoplethysmograph based arrhythmia detection using morphological features

Photoplethysmography (PPG) is a non-invasive optical technique that is used for the detection of cardiovascular diseases. The paroxysmal nature of arrhythmic events and the lack of timely recorded data emphasize the need to develop an automated method for the identification of arrhythmias. The literature shows the detection of a single type of arrhythmia using PPG. However, limited research has been carried out for the detection of multiple types of arrhythmia. In this research work, a new set of morphological features have been proposed for the automated detection of multiple arrhythmias using rule-based and statistical learning-based approaches. The proposed work has been implemented on the retrospective dataset and validated on the prospective dataset. The results show that the rule-based arrhythmia detection method is equipollent to the statistical learning approach with an accuracy of 98.43%/94.16% on the retrospective dataset and 94.16%/93% on the prospective dataset.

Near-infrared spectroscopy in child and adolescent neurodevelopmental disorders.

Near-infrared spectroscopy (NIRS) is a noninvasive optical technique that uses the near-infrared spectrum for functional neuroimaging by measuring oxygenation and hemodynamic changes in the cerebral cortex. The advantages of NIRS include its portability and ease of application, which allows for testing with the subject in natural positions, such as sitting or standing. Since 1994, NIRS has been increasingly used to conduct functional activation studies on different psychiatric disorders, most prominently schizophrenia, depression, bipolar disorder, and neurodevelopmental disorders. However, limited information on its use among child and adolescent patients is available. We herein review recent findings obtained using NIRS measurements of the brain during cognitive tasks in neurodevelopmental disorders, such as autism spectrum disorder, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and Tourette's disorder. This will facilitate evaluations of the causation and treatment of prefrontal cortex dysfunctions.

Modeling optical second harmonic generation for oxide/semiconductor interface characterization

In this work, we present physics-based numerical modeling of experimental time-dependent optical second harmonic generation data from an oxide/semiconductor (SiO2/Si) interface. A comprehensive numerical solution to the Poisson–Boltzmann equation has been developed here, using the Newton–Raphson method at different time instances. It incorporates the trapping behavior of photo-excited charge carriers at the silicon dioxide/silicon (SiO2/Si) interface, within the silicon dioxide (SiO2) and at the SiO2 surface, in order to model the second harmonic photon count data obtained from our in-house experimental setup. This yields a quantitative analysis of the SiO2/Si interface, oxide, and surface charge densities, and provides a contact-less and non-invasive optical technique for oxide/semiconductor interface characterization.

ABPO-TVSCAD: alternating Bregman proximity operators approach based on TVSCAD regularization for bioluminescence tomography

Objective. Bioluminescence tomography (BLT) is a promising non-invasive optical medical imaging technique, which can visualize and quantitatively analyze the distribution of tumor cells in living tissues. However, due to the influence of photon scattering effect and ill-conditioned inverse problem, the reconstruction result is unsatisfactory. The purpose of this study is to improve the reconstruction performance of BLT. Approach. An alternating Bregman proximity operators (ABPO) method based on TVSCAD regularization is proposed for BLT reconstruction. TVSCAD combines the anisotropic total variation (TV) regularization constraints and the non-convex smoothly clipped absolute deviation (SCAD) penalty constraints, to make a trade-off between the sparsity and edge preservation of the source. ABPO approach is used to solve the TVSCAD model (ABPO-TVSCAD for short). In addition, to accelerate the convergence speed of the ABPO, we adapt the strategy of shrinking the permission source region, which further improves the performance of ABPO-TVSCAD. Main results. The results of numerical simulations and in vivo xenograft mouse experiment show that our proposed method achieved superior accuracy in spatial localization and morphological reconstruction of bioluminescent source. Significance. ABPO-TVSCAD is an effective and robust reconstruction method for BLT, and we hope that this method can promote the development of optical molecular tomography.

Diffuse Reflectance Spectroscopy of Changes in Tumor Microenvironment in Response to Different Doses of Radiation.

Radiation therapy plays an important role in cancer treatment, as it is an established method used as part of the treatment plan for the majority of cancer patients. Real-time monitoring of the effects of radiation on the tumor microenvironment can contribute to the development of better treatment plans. In this study, we use diffuse reflectance spectroscopy, a non-invasive optical fiber-based technique, to determine the effects of different doses of radiation on the tumor microenvironment, as well as to determine the sensitivity of diffuse reflectance spectroscopy to low doses of radiation that are used in the treatment of certain cancers. We injected 4T1 cells into 50 Balb/c mice to generate tumor xenografts. When the tumors grew to 200 mm3, we distributed the mice into a control group or one of three radiation groups: 1, 2, or 4 Gy/fraction, and they underwent treatment for five consecutive days. We measured the tumor volume and collected diffuse reflectance spectra every day, with optical measurements being acquired both before and one h postirradiation on the five days of treatment. Based on the diffusely reflected light, we quantified vascular oxygenation, total hemoglobin content, and tissue scattering within these tumors. There was a significant increase in tumor vascular oxygenation, which was primarily due to an increase in oxygenated hemoglobin, in response to a 1 Gy/fraction of radiation, while there was a decrease in tissue scattering in response to all doses of radiation. Immunohistochemical analysis revealed that tumor cell proliferation and apoptosis were higher in irradiated groups compared to the control group. Our findings show that diffuse reflectance spectroscopy is sensitive to microenvironmental changes in tumors treated with doses of radiation as low as 1 Gy/fraction.

Combining robust level extraction and unsupervised adaptive classification for high-accuracy fNIRS-BCI: An evidence on single-trial differentiation between mentally arithmetic- and singing-tasks.

Functional near-infrared spectroscopy (fNIRS) is a safe and non-invasive optical imaging technique that is being increasingly used in brain-computer interfaces (BCIs) to recognize mental tasks. Unlike electroencephalography (EEG) which directly measures neural activation, fNIRS signals reflect neurovascular-coupling inducing hemodynamic response that can be slow in time and varying in the pattern. The established classifiers extend the EEG-ones by mostly employing the feature based supervised models such as the support vector machine (SVM) and linear discriminant analysis (LDA), and fail to timely characterize the level-sensitive hemodynamic pattern. A dedicated classifier is desired for intentional activity recognition of fNIRS-BCI, including the adaptive acquisition of response relevant features and accurate discrimination of implied ideas. To this end, we herein propose a specifically-designed joint adaptive classification method that combines a Kalman filtering (KF) for robust level extraction and an adaptive Gaussian mixture model (a-GMM) for enhanced pattern recognition. The simulative investigations and paradigm experiments have shown that the proposed KF/a-GMM classification method can effectively track the random variations of task-evoked brain activation patterns, and improve the accuracy of single-trial classification task of mental arithmetic vs. mental singing, as compared to the conventional methods, e.g., those that employ combinations of the band-pass filtering (BPF) based feature extractors (mean, slope, and variance, etc.) and the classical recognizers (GMM, SVM, and LDA). The proposed approach paves a promising way for developing the real-time fNIRS-BCI technique.

Skin autofluorescence as tool for cardiovascular and diabetes risk prediction.

Advanced glycation endproducts (AGE) have an important role in the development of chronic complications in diabetes mellitus and in renal failure. Skin autofluorescence (SAF) is a simple noninvasive optical technique to estimate AGE levels in the dermis. SAF increases with age, but rises more rapidly in diabetes and renal failure, and is also associated with, and a predictor of their complications. In recent large population studies, SAF is a strong predictor of development of type 2 diabetes (T2D), and in persons with known diabetes of its complications. SAF also predicts new cardiovascular disease (CVD) and mortality not only in individuals with known type 2 diabetes but also in the general population. SAF is a simple, powerful and independent predictor for development of type 2 diabetes (T2D), and also for cardiovascular disease and mortality in both persons with diabetes, and in the general population.

NIRS: Past, Present, and Future in Functional Urology.

Purpose of ReviewNear infrared spectroscopy (NIRS) is a non-invasive optical technique that uses near infrared light to detect the oxygenation status and hemodynamics of various organs. This article reviews the use of NIRS for the non-invasive assessment of lower urinary tract dysfunction (LUTD). Applications include assessment of bladder outlet obstruction, overactive and underactive bladder, neurogenic LUTD, pediatric LUTD, interstitial cystitis/bladder pain syndrome, and pelvic floor dysfunction. In addition, the article describes how NIRS is elucidating more about the brain-bladder connection. Technological advancements enabling these applications are also discussed.Recent FindingsWhile evidence exists for the application of NIRS throughout a wide range of LUTD, most of these studies are limited by small sample sizes without matched controls. Investigators have experienced problems with reproducibility and motion artifacts contaminating the data. The literature is also becoming dated with use of older technology.SummaryNIRS holds potential for the non-invasive acquisition of urodynamic information over time scales and activities not previously accessible, but it is not yet ready for use in routine clinical practice. Advances in wearable technology will address some of the current limitations of NIRS, but to realize its full potential, larger scale validation studies will be required. Moreover, multidisciplinary collaboration between clinicians, scientists, engineers, and patient advocates will be critical to further optimize these systems.

Analysis of Stability, Rheological and Structural Properties of Oleogels Obtained from Peanut Oil Structured with Yellow Beeswax.

The aim of this study was to evaluate the macro- and microscopic properties of oleogels with yellow beeswax using different methods, especially modern optical techniques. Microrheological properties, physical stability and morphology of oleogel crystals obtained by structuring of peanut oil with yellow beeswax was analyzed. It was observed that oleogels, even with the smallest concentration of beeswax (2%), were resistant to centrifugal force. Increase in yellow beeswax concentration (from 2, 4, 6 to 8 %) resulted in significant differences in the characteristics of oleogels: increased elasticity (EI), macroscopic viscosity (MVI) and the firmness values of oleogels. It was concluded that non-invasive optical techniques (multi-speckle diffusing wave spectroscopy—Rheolaser Master) are useful in obtaining a quick evaluation of physical properties of oleogels at the microstructural level, and the received information allows for quality assessment.

Clenching-Related Motion Artifacts in Functional Near-Infrared Spectroscopy in the Auditory Cortex.

Functional near-infrared spectroscopy (fNIRS), a non-invasive optical neuroimaging technique, has demonstrated its great potential in monitoring cerebral activity as an alternative to functional magnetic resonance imaging (fMRI) in research and clinical usage. fNIRS has seen increasing applications in studying the auditory cortex in healthy subjects and cochlear implant users. However, fNIRS is susceptible to motion artifacts, especially those related to jaw movement, which can affect fNIRS signals in speech and auditory tasks. This study aimed to investigate the motion artifacts related to jaw movements including clenching, speaking, swallowing, and sniffing in a group of human subjects, and test whether our previously established denoising algorithm namely PCA-GLM can reduce the motion artifacts. Our results have shown that the jaw movements introduced artifacts that resemble task-evoked activations and that the PCA-GLM method effectively reduced the motion artifacts due to the clenching movements. The preliminary results of the present study underline the importance of the removal of the jaw-movement-related artifacts in fNIRS signals and suggest the efficacy of our PCA-GLM method in reducing the motion artifacts. Clinical Relevance- This work studies the motion artifacts due to jaw movements that frequently occur in speech perception and production tasks and validates the efficacy of an established denoising algorithm which benefits fNIRS studies on auditory and language functions.

The Role of Neuroglobin in Retinal Hemodynamics and Metabolism: A Real-Time Study.

PurposeIn this study, we used broadband near-infrared spectroscopy, a non-invasive optical technique, to investigate in real time the possible role of neuroglobin in retinal hemodynamics and metabolism.MethodsRetinae of 12 C57 mice (seven young and five old) and seven young neuroglobin knockouts (Ngb-KOs) were exposed to light from a low-power halogen source, and the back-reflected light was used to calculate changes in the concentration of oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HHb), and oxidized cytochrome c oxidase (oxCCO).ResultsThe degree of change in the near-infrared spectroscopy signals associated with HHb, HbO2, and oxCCO was significantly greater in young C57 mice compared to the old C57 mice (P < 0.05) and the Ngb-KO model (P < 0.005).ConclusionsOur results reveal a possible role of Ngb in regulating retinal function, as its absence in the retinae of a knockout mouse model led to suppressed signals that are associated with hemodynamics and oxidative metabolism.Translational RelevanceNear-infrared spectroscopy enabled the non-invasive detection of characteristic signals that differentiate between the retina of a neuroglobin knockout mouse model and that of a wild-type model. Further work is needed to evaluate the source of the signal differences and how these differences relate to the presence or absence of neuroglobin in the ganglion, bipolar, or amacrine cells of the retina.

Artificial intelligence and hyperspectral imaging for image-guided assistance in minimally invasive surgery

Intraoperative imaging assists surgeons during minimally invasive procedures. Hyperspectral imaging (HSI) is anoninvasive and noncontact optical technique with great diagnostic potential in medicine. The combination with artificial intelligence (AI) approaches to analyze HSI data is called intelligent HSI in this article. What are the medical applications and advantages of intelligent HSI for minimally invasive visceral surgery? Within various clinical studies HSI data from multiple in vivo tissue types and oncological resections were acquired using an HSI camera system. Different AI algorithms were evaluated for detection and discrimination of organs, risk structures and tumors. In an experimental animal study 20different organs could be differentiated with high precision (> 95%) using AI. In vivo, the parathyroid glands could be discriminated from surrounding tissue with an F1 score of 47% and sensitivity of 75%, and the bile duct with an F1 score of 79% and sensitivity of 90%. Furthermore, ex vivo tumor tissue could be successfully detected with an area under the receiver operating characteristic (ROC) curve (AUC) larger than 0.91. This study demonstrates that intelligent HSI can automatically and accurately detect different tissue types. Despite great progress in the last decade intelligent HSI still has limitations. Thus, accurate AI algorithms that are easier to understand for the user and an extensive standardized and continuously growing database are needed. Further clinical studies should support the various medical applications and lead to the adoption of intelligent HSI in the clinical routine practice.

NIRS Hemodynamic Response to Methylphenidate in Children with Attention Aeficit Hyperactivity Disorder: First Administration, Titration Phase and Associations with Clinical Severity

IntroductionAttention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by lack of self-regulation and deficits in organizing behaviors in response to emotional stimuli. Methylphenidate (MPH) is one of the most effective psychostimulant drugs for ADHD, however, a possible predictive utility of brain hemodynamic data related to MPH administration and its relation to clinical symptomatology is still not clear. To address these questions, we used Near Infrared Spectroscopy (NIRS) technology, a non-invasive optical technique that allows to investigate the effect of psychopharmacological treatment on cortical hemodynamics.MethodsTwenty children with ADHD underwent a three-waves study and 25 healthy controls were recruited at W1. At W2 children with ADHD received first MPH administration and at W3 they reached the titration phase. At each phase children performed - during NIRS recording - an emotional continuous performance task with visual stimuli of different emotional content. Clinical data were also collected at W1 and W3. We investigated the relationship among the difference between NIRS activation at W2 and W1 (Delta1) and W3 and W2 (Delta2), for each subject, task condition and brain region. Lastly, we investigated correlations between the Delta1 and clinical symptomatology indexes at W1 and between Delta2 and clinical data at W3.ConclusionsOur study results suggest that hemodynamic changes in right prefrontal region probably induced by first MPH administration could predict hemodynamic changes related to MPH titration phase. These biological indexes could be associated to clinical evidences related not only to core ADHD symptoms but also to affective correlates.DisclosureNo significant relationships.

Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury.

Mild traumatic brain injuries (mTBIs) are a significant public health problem. Repeated exposure to mTBI can lead to cumulative, long-lasting functional deficits. Numerous studies by our group and others have shown that mTBI stimulates cytokine expression and activates microglia, decreases cerebral blood flow and metabolism, and impairs cerebrovascular reactivity. Moreover, several works have reported an association between derangements in these neuroinflammatory and hemodynamic markers and cognitive impairments. Herein we detail methods to characterize the neuroinflammatory and hemodynamic tissue response to mTBI in mice. Specifically, we describe how to perform a weight-drop model of mTBI, how to longitudinally measure cerebral blood flow using a non-invasive optical technique called diffuse correlation spectroscopy, and how to perform a Luminex multiplexed immunoassay on brain tissue samples to quantify cytokines and immunomodulatory phospho-proteins (e.g., within the MAPK and NFκB pathways) that respond to and regulate activity of microglia and other neural immune cells. Finally, we detail how to integrate these data using a multivariate systems analysis approach to understand the relationships between all of these variables. Understanding the relationships between these physiologic and molecular variables will ultimately enable us to identify mechanisms responsible for mTBI.

Comprehensive imaging of microcirculatory changes in the foot during endovascular intervention - A technical feasibility study.

Chronic limb-threatening ischemia (CLTI) has a major impact on patients' lives and is associated with a heavy health care burden with high morbidity and mortality. Treatment by endovascular intervention is mostly based on macrocirculatory information from angiography and does not consider the microcirculation. Despite successful endovascular intervention according to angiographic criteria, a proportion of patients fail to heal ischemic lesions. This might be due to impaired microvascular perfusion and variations in the supply to different angiosomes. Non-invasive optical techniques for microcirculatory perfusion and oxygen saturation imaging have the potential to provide the interventionist with additional information in real-time, supporting clinical decisions during the intervention. This study presents a novel multimodal imaging system, based on multi-exposure laser speckle contrast imaging and multi-spectral imaging, for continuous use during endovascular intervention. The results during intervention display spatiotemporal changes in the microcirculation compatible with expected physiological reactions during balloon dilation, with initially induced ischemia followed by a restored perfusion, and local administration of a vasodilator inducing hyperemia. We also present perioperative and postoperative follow-up measurements with a pulsatile microcirculation perfusion. Finally, cases of spatial heterogeneity in the oxygen saturation and perfusion are discussed. In conclusion, this technical feasibility study shows the potential of the methodology to characterize changes in microcirculation before, during, and after endovascular intervention.

Benchmarking Spectroscopic Techniques Combined with Machine Learning to Study Oak Barrels for Wine Ageing.

Due to its physical, chemical, and structural properties, oakwood is widely used in the production of barrels for wine ageing. When in contact with the wine, oak continuously releases aromatic compounds such as lignin, tannin, and cellulose to the liquid. Due to the release process, oak loses its characteristic aromatic compounds in time; hence, the flavour that it gives to the enclosed wine decreases for repeated wine refills and a barrel replacement is required. Currently, the estimation of the maximum number of refills is empirical and its underestimation or overestimation can impose unnecessary costs and impair the quality of the wine. Therefore, there is a clear need to quantify the presence of the aforementioned aromatic compounds in an oak barrel prior to a refill. This work constitutes a study to examine noninvasive optical biosensing techniques for the characterization of an oak barrel used in wine ageing, towards the development of a model to unveil its lifespan without inducing structural damage. Spectroscopic diagnostic techniques, such as reflectance, fluorescence, and Raman scattering measurements are employed to assess the change in the chemical composition of the oakwood barrel (tannin and lignin presence) and its dependence on repeated refills. To our knowledge, this is the first time that we present a benchmarking study of oak barrel ageing characteristics through spectroscopic methods for the wine industry. The spectroscopic data are processed using standard chemometric techniques, such as Linear Discriminant Analysis and Partial Least Squares Discriminant Analysis. Results of a study of fresh, one-time-used, and two-times-used oak barrel samples demonstrate that reflectance spectroscopy can be a valuable tool for the characterization of oak barrels. Moreover, reflectance spectroscopy has demonstrated the most accurate classification performance. The highest accuracy has been obtained by a Partial Least Squares Discriminant Analysis model that has been able to classify all the oakwood samples from the barrels with >99% accuracy. These preliminary results pave a way for the application of cost-effective and non-invasive biosensing techniques based on reflectance spectroscopy for oak barrels assessment.

Use of near infrared spectroscopy for hemodynamic monitoring in pediatrics.

Near infrared spectroscopy (NIRS) is a non-invasive optical technique for the evaluation of regional tissue oxygenation using transcutaneous detectors. In recent years, publications about this topic have increased exponentially; this reflects the growing interest among investigators and clinicians about this new technology and its potential benefits for pediatric patients. The objective of this review is to know the functioning and potential uses of regional saturation measured by NIRS and establish future challenges.