Improvement of tissue analysis and classification using optical coherence tomography combined with Raman spectroscopy

Optical coherence tomography(OCT)provides significant advantages of high resolution(approaching the histopathology level)realtime imaging of tsess without use of contrast agents.Based on these advantages,the microstructural features of tumors can be visualized and detected intra-operatively.However,it is still not clinically accepted for tumor margin delin-eation due to poor specificity and accuracy.In contrast,Raman spectroscopy(RS)can obtain tissue information at the molecular level,but does not provide real-time inaging capability.Therefore,combining OCT and RS could provide synergy.To this end,we present a tissue analysis and dassification method using both the slope of OCT intensity signal Vs depth and the principle components from the RS spectrum as the indicators for tissuse characterization.The goal of this study was to understand prediction accuracy of OCT and combined OCT/RS method for dassification of optically similar tisues and organs.Our pilot experiments were performed on mouse kidneys,livers,and small intestines(SIs).The prediction accuracy with five-fold cross validation of the method has been evaluated by the support vector machine(SVM)method.The results demonstrate that tissue characterization based on the OCT/RS method was superior compared to using OCT structural information alone.This combined OCT/RS method is potentially useful as a noninvasive optical biopsy technique for rapid and automatic tissue characterization during surgery.

LIVE IMAGING OF EARLY DEVELOPMENTAL PROCESSES IN MAMMALIAN EMBRYOS WITH OPTICAL COHERENCE TOMOGRAPHY

Early embryonic imaging of cardiovascular development in mammalian models requires a methodthat can penetrate through and distinguish the many tissue layers with high spatial and temporalresolution. In this paper we evaluate the capability of Optical Coherence Tomography (OCT)technique for structural 3D embryonic imaging in mouse embryos at different stages of thedevelopmental process ranging from 7.5 dpc up to 10.5 dpc. Obtained results suggest that thecollected data is suitable for quantitative and qualitative measurements to assess cardiovascularfunction in mouse models, which is likely to expand our knowledge of the complexity of theembryonic heart, and its development into an adult heart.

ASSESSMENT OF TISSUE OPTICAL CLEARING AS A FUNCTION OF GLUCOSE CONCENTRATION USING OPTICAL COHERENCE TOMOGRAPHY

One of the major challenges in imaging biological tissues using optical techniques,such as optical coherence tomography(OCT),is the lack of light penetration due to highly turbid structures within the tissue.Optical clearing techniques enable the biological samples to be more optically homogeneous,allowing for deeper penetration of light into the tissue.This study investigates the effect of optical clearing utilizing various concentrations of glucose solution(10%,30%,and 50%)on porcine skin.A gold-plated mirror was imaged beneath the tissue and percentage clearing was determined by monitoring the change in reflected light intensity from the mirror over time.The ratio of percentage clearing per tissue thickness for 10%,30% and 50% glucose was determined to be 4.7±1.6%mm^(−1)(n=6),10.6±2.0%mm^(−1)(n=7)and 21.8±2.2%mm^(−1)(n=5),respectively.It was concluded that while higher glucose concentration has the highest optical clearing effect,a suitable concentration should be chosen for the purpose of clearing,considering the osmotic stress on the tissue sample.

Biomarkers of An Autoimmune Skin Disease——Psoriasis

Psoriasis is one of the most prevalent autoimmune skin diseases. However, its etiology and pathogencsis are still unclear. Over the last decade, omics-based technologies have been exten- sively utilized for biomarker discovery. As a result, some promising markers for psoriasis have been identified at the genome, transcriptome, proteome, and metabolome level. These discoveries have provided new insights into the underlying molecular mechanisms and signaling pathways in psoriasis pathogenesis. More importantly, some of these markers may prove useful in the diagnosis of psoriasis and in the prediction of disease progression once they have been validated. In this review, we summarize the most recent findings in psoriasis biomarker discovery. In addition, we will discuss several emerging technologies and their potential for novel blomarker discovery and diagnostics for psoriasis.

Fully rubbery synaptic transistors made out of all-organic materials for elastic neurological electronic skin

Neurologic function implemented soft organic electronic skin holds promise for wide range of applications,such as skin prosthetics,neurorobot,bioelectronics,human-robotic interaction(HRI),etc.Here,we report the development of a fully rubbery synaptic transistor which consists of all-organic materials,which shows unique synaptic characteristics existing in biological synapses.These synaptic characteristics retained even under mechanical stretch by 30%.We further developed a neurological electronic skin in a fully rubbery format based on two mechanoreceptors(for synaptic potentiation or depression)of pressure-sensitive rubber and an all-organic synaptic transistor.By converting tactile signals into Morse Code,potentiation and depression of excitatory postsynaptic current(EPSC)signals allow the neurological electronic skin on a human forearm to communicate with a robotic hand.The collective studies on the materials,devices,and their characteristics revealed the fundamental aspects and applicability of the all-organic synaptic transistor and the neurological electronic skin.

Constrained regularization for noninvasive glucose sensing using Raman spectroscopy

Multivariate calibration is an important tool for spectroscopic measurermnent of analyte con-centrations.We present a detailed study of a hybrid multivariate calibration technique,con-strained regularization(CR),and demonstrate its utility in noninvasive glucose sensing uasing Raman spectroscopy.Similar to partial least squares(PIS)and principal component regression(PCR),CR builds an implicit model and requires knowledge only of the concentrations of the analyte of interest.Calibration is treated as an inverse problem in which an optimal balance between model complexity and noise rejection is achieved.Prior information is included in the form of a spectroscopic constraint that can be obtained conveniently.When used with an appropriate constraint,CR provides a better calibration model compared to PLS in both numerical and experimental studies.

FOREWORD

Special Issue Optical Technologies in the Study of Tissues and Biological Fluids We are pleased to present this special issue of JIOHS,which focuses on optical technologies in the study of tissues and biological liquids.The selected papers were presented during Saratov Fall Meeting—XII International School for Junior Scientists and Students on Optics,Laser Physics and Biophotonics(September 23–26,2008,Saratov,Russia)in the framework of the following workshops:“Optical Technologies in Biophysics and Medicine,”“Nanostructures and Nanoparticles,”“Microscopic and Low-Coherence Methods in Biomedical Applications,”and“Internet Biophotonics.”All eight papers in this special issue are research papers.

Flexible organic solar cells for biomedical devices

Organic solar cells(OSCs),particularly made based on solution processing methods,have made significant progress over the past decades through the concurrent evolution of organic photovoltaic materials and device engineering.Recently,high power conversion efficiencies around 18%and over 16%have been demonstrated in both rigid and flexible OSCs,respectively.While most of the OSC research has centered on efficiency and cost,their emerging and potential usages in many critical applications,particularly in biomedical fields have been rising.In this mini-review,we will briefly discuss the high-performance organic photovoltaic materials and the representative flexible OSCs to give a scope on the recent rapid development of OSCs.Besides,we will review some progress on the applications of OSCs in biomedical devices and integrated systems.The potential challenges associated with integrating OSCs for biomedical devices will be put forward.

Neural network-based image reconstruction in swept-source optical coherence tomography using undersampled spectral data

Optical coherence tomography(OCT)is a widely used non-invasive biomedical imaging modality that can rapidly provide volumetric images of samples.Here,we present a deep learning-based image reconstruction framework that can generate swept-source OCT(SS-OCT)images using undersampled spectral data,without any spatial aliasing artifacts.This neural network-based image reconstruction does not require any hardware changes to the optical setup and can be easily integrated with existing swept-source or spectral-domain OCT systems to reduce the amount of raw spectral data to be acquired.To show the efficacy of this framework,we trained and blindly tested a deep neural network using mouse embryo samples imaged by an SS-OCT system.Using 2-fold undersampled spectral data(i.e.,640 spectral points per A-line),the trained neural network can blindly reconstruct 512 A-lines in 0.59 ms using multiple graphics-processing units(GPUs),removing spatial aliasing artifacts due to spectral undersampling,also presenting a very good match to the images of the same samples,reconstructed using the full spectral OCT data(i.e.,1280 spectral points per A-line).We also successfully demonstrate that this framework can be further extended to process 3×undersampled spectral data per A-line,with some performance degradation in the reconstructed image quality compared to 2×spectral undersampling.Furthermore,an A-line-optimized undersampling method is presented by jointly optimizing the spectral sampling locations and the corresponding image reconstruction network,which improved the overall imaging performance using less spectral data points per A-line compared to 2×or 3×spectral undersampling results.This deep learning-enabled image reconstruction approach can be broadly used in various forms of spectral-domain OCT systems,helping to increase their imaging speed without sacrificing image resolution and signal-to-noise ratio.

Curvy surface conformal ultra-thin transfer printed Sioptoelectronic penetrating microprobe arrays

Penetrating neural probe arrays are powerful bio-integrated devices for studying basic neuroscience and applied neurophysiology,underlying neurological disorders,and understanding and regulating animal and human behavior.This paper presents a penetrating microprobe array constructed in thin and flexible fashion,which can be seamlessly integrated with the soft curvy substances.The function of the microprobes is enabled by transfer printed ultra-thin Si optoelectronics.As a proof-of-concept device,microprobe array with Si photodetector arrays are demonstrated and their capability of mapping the photo intensity in space are illustrated.The design strategies of utilizing thin polyimide based microprobes and supporting substrate,and employing the heterogeneously integrated thin optoelectronics are keys to accomplish such a device.The experimental and theoretical investigations illustrate the materials,manufacturing,mechanical and optoelectronic aspects of the device.While this paper primarily focuses on the device platform development,the associated materials,manufacturing technologies,and device design strategy are applicable to more complex and multi-functionalities in penetrating probe array-based neural interfaces and can also find potential utilities in a wide range of bio-integrated systems.

Novel Autoantibodies Related to Cell Death and DNA Repair Pathways in Systemic Lupus Erythematosus

Systemic lupus erythematosus(SLE)is a complex autoimmune syndrome characterized by various co-existing autoantibodies(autoAbs)in patients’blood.However,the full spectrum of autoAbs in SLE has not been comprehensively elucidated.In this study,a commercial platform bearing 9400 antigens(ProtoArray)was used to identify autoAbs that were significantly elevated in the sera of SLE patients.By comparing the autoAb profiles of SLE patients with those of healthy controls,we identified 437 IgG and 1213 IgM autoAbs that the expression levels were significantly increased in SLE(P<0.05).Use of the ProtoArray platform uncovered over 300 novel autoAbs targeting a broad range of nuclear,cytoplasmic,and membrane antigens.Molecular interaction network analysis revealed that the antigens targeted by the autoAbs were most significantly enriched in cell death,cell cycle,and DNA repair pathways.A group of autoAbs associated with cell apoptosis and DNA repair function,including those targeting APEX1,AURKA,POLB,AGO1,HMGB1,IFIT5,MAPKAPK3,PADI4,RGS3,SRP19,UBE2S,and VRK1,were further validated by ELISA and Western blot in a larger cohort.In addition,the levels of autoAbs against APEX1,HMGB1,VRK1,AURKA,PADI4,and SRP19 were positively correlated with the level of anti-dsDNA in SLE patients.Comprehensive autoAb screening has identified novel autoAbs,which may shed light on potential pathogenic pathways leading to lupus.