Interferometric optical fiber sensor for optoacoustic endomicroscopy

Optical fiber sensors can offer robust and miniaturized detection of wideband ultrasound, yielding high sensitivity and immunity to electromagnetic interference. However, the lack of cost-effective manufacturing methods prevents the disseminated use of these sensors in biomedical applications. In this study, we developed and optimized a simple method to create optical cavities with high-quality mirrors for acoustic sensing based on micro-manipulation of UV-curable optical adhesives and electroless chemical silver deposition. This approach enables the manufacturing of ultrasound sensors based on Fabry-Pérot interferometers on optical fiber tips with minimal production costs. Characterization and high-resolution optoacoustic imaging experiments show that the manufacturing process yielded a fiber sensor with a small NEP () over a broad detection bandwidth (25 MHz), generally outperforming conventional piezoelectric based transducers. We discuss how the new manufacturing process leads to a high-performance acoustic detector that, due to low cost, can be used as a disposable sensor.     

LV-GAN: A deep learning approach for limited-view optoacoustic imaging based on hybrid datasets

The optoacoustic imaging (OAI) methods are rapidly evolving for resolving optical contrast in medical imaging applications. In practice, measurement strategies are commonly implemented under limited-view conditions due to oversized image objectives or system design limitations. Data acquired by limited-view detection may impart artifacts and distortions in reconstructed optoacoustic (OA) images. We propose a hybrid data-driven deep learning approach based on generative adversarial network (GAN), termed as LV-GAN, to efficiently recover high quality images from limited-view OA images. Trained on both simulation and experiment data, LV-GAN is found capable of achieving high recovery accuracy even under limited detection angles less than 60^°. The feasibility of LV-GAN for artifact removal in biological applications was validated by ex vivo experiments based on two different OAI systems, suggesting high potential of a ubiquitous use of LV-GAN to optimize image quality or system design for different scanners and application scenarios.     

光声成像及其在生物医学中的应用

光声成像是一种新近迅速发展起来、基于生物组织内部光学吸收差异、以超声作媒介的无损生物光子成像方法,它结合了纯光学成像的高对比度特性和纯超声成像的高穿透深度特性的优点,以超声探测器探测光声波代替光学成像中的光子检测,从原理上避开了光学散射的影响,可以提供高对比度和高分辨率的组织影像,为研究生物组织的结构形态、生理特征、代谢功能、病理特征等提供了重要手段,在生物医学临床诊断以及在体组织结构和功能成像领域具有广泛的应用前景.对光声成像技术的机理、光声成像技术和方法、光声图像重建算法以及光声成像在生物医学上的应用情况作一个简单介绍,希望有助于推动我国在该领域的科研和开发应用工作的迅速发展.     

Label‐free multi‐parametric imaging of single cells: dual picosecond optoacoustic microscopy

Advances in microscopy with new visualization possibilities often bring dramatic progress to our understanding of the intriguing cellular machinery. Picosecond optoacoustic micro‐spectroscopy is an optical technique based on ultrafast pump‐probe generation and detection of hypersound on time durations of picoseconds and length scales of nanometers. It is experiencing a renaissance as a versatile imaging tool for cell biology research after a plethora of applications in solid‐state physics. In this emerging context, this work reports on a dual‐probe architecture to carry out real‐time parallel detection of the hypersound propagation inside a cell that is cultured on a metallic substrate, and of the hypersound reflection at the metal/cell adhesion interface. Using this optoacoustic modality, several biophysical properties of the cell can be measured in a noncontact and label‐free manner. Its abilities are demonstrated with the multiple imaging of a mitotic macrophage‐like cell in a single run experiment.      

Biophotonics methods for functional monitoring of complications of diabetes mellitus

The prevalence of diabetes complications is a significant public health problem with a considerable economic cost. Thus, the timely diagnosis of complications and prevention of their development will contribute to increasing the length and quality of patient life, and reducing the economic costs of their treatment. This article aims to review the current state‐of‐the‐art biophotonics technologies used to identify the complications of diabetes mellitus and assess the quality of their treatment. Additionally, these technologies assess the structural and functional properties of biological tissues, and they include capillaroscopy, laser Doppler flowmetry and hyperspectral imaging, laser speckle contrast imaging, diffuse reflectance spectroscopy and imaging, fluorescence spectroscopy and imaging, optical coherence tomography, optoacoustic imaging and confocal microscopy. Recent advances in the field of optical noninvasive diagnosis suggest a wider introduction of biophotonics technologies into clinical practice and, in particular, in diabetes care units.     

Imaging atoms in medicine

The innovations in science and technology have allowed researchers to look inside the human body. In some cases, like MRI, the protons present in the body generate enough signal for an image. However, the employ of certain atoms, metallic or non-metallic, enable detection through different imaging techniques (computed tomography, nuclear imaging, ultrasound or optical imaging), and improve the quality of the images. Here we discuss the different imaging atoms used depending on the imaging technique and the new possible imaging atoms for medical applications.     

Nonlinear optoacoustic readings from diffusive media at near‐infrared wavelengths

Optoacoustic (photoacoustic) imaging assumes that the detected signal varies linearly with laser energy. However, nonlinear intensity responses as a function of light fluence have been suggested in optoacoustic microscopy, that is, within the first millimeter of tissue. In this study, we explore the presence of nonlinearity deeper in tissue (~4 mm), as it relates to optoacoustic mesoscopy, and investigate the fluence required to delineate a switch from linear to nonlinear behavior. Optoacoustic signal nonlinearity is studied for different materials, different wavelengths and as a function of changes in the scattering and absorption coefficient of the medium imaged. We observe fluence thresholds in the mJ/cm² range and preliminary find that different materials may exhibit different nonlinearity patterns. We discuss the implications of nonlinearity in relation to image accuracy and quantification in optoacoustic tomography.      

Surface plasmon resonance based biosensor technique: A review

Optical Surface plasmon resonance (SPR) biosensors represent the most advanced and developed optical label‐free biosensor technology. Optical SPR biosensors are a powerful detection and analysis tool that has vast applications in environmental protection, biotechnology, medical diagnostics, drug screening, food safety and security. This article reviews the recent development of SPR biosensor techniques, including bulk SPR and localized SPR (LSPR) biosensors, for detecting interactions between an analyte of interest in solution and a biomolecular recognition. The concepts of bulk and localized SPs and the working principles of both sensing techniques are introduced. Major sensing advances on biorecognition elements, measurement formats, and sensing platforms are presented. Finally, the discussions on both biosensor techniques as well as comparison of both SPR sensing techniques are made. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Imaging of fatty tumors: appearance of subcutaneous lipomas in optoacoustic images

A wide variety of subcutaneous soft‐tissue masses may be seen in clinical practice. Clinical examination based on palpation alone is often insufficient to identify the nature and exact origin of the mass, in which case imaging is necessary. We used handheld multispectral optoacoustic imaging technology (MSOT) in a proof‐of‐principle study to image superficial fatty tumors and compare the images with diagnostic ultrasound. Fatty tumors were clearly visualized by MSOT and exhibited a spectral signature which differed from normal fatty tissue or muscle tissue. Our findings further indicated that MSOT offers highly complementary contrast to sonography. Based on the performance achieved, we foresee a promising role for MSOT in the diagnosis and evaluation of subcutaneous soft‐tissue masses. Picture : Pseudo‐color representation of a cross‐sectional multi‐spectral optoacoustic slice through a subcutaneous lipoma. Multi‐spectral information is encoded in color. The lipoma can clearly be distinguished from the surrounding tissue based on its color. Scalebar 1 cm.     

Optical fiber-based sensors: application to chemical biology

Optical fibers have been used to develop sensors based on nucleic acids and cells. Sensors employing DNA probes have been developed for various genomics applications and microbial pathogen detection. Live cell-based sensors have enabled the monitoring of environmental toxins, and have been used for fundamental studies on populations of individual cells. Both single-core optical fiber sensors and optical fiber sensor arrays have been used for sensing based on nucleic acids and live cells.     

Uniform light delivery in volumetric optoacoustic tomography

Accurate image reconstruction in volumetric optoacoustic tomography implies the efficient generation and collection of ultrasound signals around the imaged object. Non‐uniform delivery of the excitation light is a common problem in optoacoustic imaging often leading to a diminished field of view, limited dynamic range and penetration, as well as impaired quantification abilities. Presented here is an optimized illumination concept for volumetric tomography that utilizes additive manufacturing via 3D printing in combination with custom‐made optical fiber illumination. The custom‐designed sample chamber ensures convenient access to the imaged object along with accurate positioning of the sample and a matrix array ultrasound transducer used for collection of the volumetric image data. Ray tracing is employed to optimize the positioning of the individual fibers in the chamber. Homogeneity of the generated light excitation field was confirmed in tissue‐mimicking agar spheres. Applicability of the system to image entire mouse organs ex vivo has been showcased. The new approach showed a clear advantage over conventional, single‐sided illumination strategies by eliminating the need to correct for illumination variances and resulting in enhancement of the effective field of view, greater penetration depth and significant improvements in the overall image quality.      

Effects of multispectral excitation on the sensitivity of molecular optoacoustic imaging

Molecular optoacoustic (photoacoustic) imaging typically relies on the spectral identification of absorption signatures from molecules of interest. To achieve this, two or more excitation wavelengths are employed to sequentially illuminate tissue. Due to depth‐related spectral dependencies and detection related effects, the multispectral optoacoustic tomography (MSOT) spectral unmixing problem presents a complex non‐linear inversion operation. So far, different studies have showcased the spectral capacity of optoacoustic imaging, without however relating the performance achieved to the number of wavelengths employed. Overall, the dependence of the sensitivity and accuracy of optoacoustic imaging as a function of the number of illumination wavelengths has not been so far comprehensively studied. In this paper we study the impact of the number of excitation wavelengths employed on the sensitivity and accuracy achieved by molecular optoacoustic tomography. We present a quantitative analysis, based on synthetic MSOT datasets and observe a trend of sensitivity increase for up to 20 wavelengths. Importantly we quantify this relation and demonstrate an up to an order of magnitude sensitivity increase of multi‐wavelength illumination vs. single or dual wavelength optoacoustic imaging. Examples from experimental animal studies are finally utilized to support the findings.

In vivo MSOT imaging of a mouse brain bearing a tumor that is expressing a near‐infrared fluorescent protein. ( a ) Monochromatic optoacoustic imaging at the peak excitation wavelength of the fluorescent protein. ( b ) Overlay of the detected bio‐distribution of the protein (red pseudocolor) on the monochromatic optoacoustic image. ( c ) Ex vivo validation by means of cryoslicing fluorescence imaging.     

Smart and intelligent optical materials for sensing applications

This special issue (SI) entitled ‘Smart and intelligent optical materials for sensing applications’, published by Luminescence, Wiley focuses on the recent advancement of smart and intelligent optical materials for the fabrication of sensor technology for use in numerous fields such as pharmaceutical, biomedical, and environmental. Also, detailed highlights of their prospects in the fields, for example, of personalized health care, wearable devices, and plant stress monitoring are given. This SI includes 46 peer-reviewed articles, of which 15 are reviews written by well established researchers with expertise in the field, and the remaining 31 are research articles from world-leading scientists.     

Intravascular molecular-structural imaging with a miniaturized integrated near-infrared fluorescence and ultrasound catheter

Coronary artery disease (CAD) remains a leading cause of mortality and warrants new imaging approaches to better guide clinical care. We report on a miniaturized, hybrid intravascular catheter and imaging system for comprehensive coronary artery imaging in vivo. Our catheter exhibits a total diameter of 1.0 mm (3.0 French), equivalent to standalone clinical intravascular ultrasound (IVUS) catheters but enables simultaneous near-infrared fluorescence (NIRF) and IVUS molecular-structural imaging. We demonstrate NIRF-IVUS imaging in vitro in coronary stents using NIR fluorophores, and compare NIRF signal strengths for prism and ball lens sensor designs in both low and high scattering media. Next, in vivo intravascular imaging in pig coronary arteries demonstrates simultaneous, co-registered molecular-structural imaging of experimental CAD inflammation on IVUS and distance-corrected NIRF images. The obtained results suggest substantial potential for the NIRF-IVUS catheter to advance standalone IVUS, and enable comprehensive phenotyping of vascular disease to better assess and treat patients with CAD.     

A simple,real-time assay of horseradish peroxidase using biolayer interferometry

ABSTRACT

Horseradish peroxidase (HRP) isoenzyme C1a is one of the most widely used enzymes for various analytical methods in bioscience research and medical fields. In these fields, real-time monitoring of HRP activity is highly desirable because the utility of HRP as a reporter enzyme would be expanded. In this study, we developed a simple assay system enabling real-time monitoring of HRP activity by using biolayer interferometry (BLI). The HRP activity was quantitatively detected on a BLI sensor chip by tracing a binding response of tyramide, a substrate of HRP, onto an immobilized protein. This system could be applied to analyses related to oxidase activity, as well as to the functional analysis of recombinant HRP.     

Influence of Design Parameters on the Performance of a Surface Plasmon Sensor Based Fiber Optic Sensor

In the present work, the influence of two key design parameters, namely, fiber core diameter and sensing region length on the performance of a fiber optic surface plasmon resonance sensor, was experimentally observed. The sensor was designed with a multimode optical fiber of numerical aperture 0.40 and a thin silver layer of 50 nm thickness. The performance evaluation was carried out in terms of three performance parameters: sensitivity, signal-to-noise ratio and resolution. It was found that performance of the sensor tends to improve if fiber of large core diameter is used. Further, sensing region length should be taken as small as possible to attain highly sensitive and accurate sensing procedure. The experimental results are explained in terms of related physical background and mathematical expressions.     

Contact‐free endoscopic photoacoustic sensing using speckle analysis

Photoacoustic endoscopy (PAE) is an emerging imaging modality, which offers a high imaging penetration and a high optical contrast in soft tissue. Most of the developed endoscopic photoacoustic sensing systems use miniaturized contact ultrasound transducers or complex optical approaches. In this work, a new fiber‐based detection technique using speckle analysis for contact‐free signal detection is presented. Phantom and ex vivo experiments are performed in transmission and reflection mode for proof of concept. In summary, the potential of the technique for endoscopic photoacoustic signal detection is demonstrated. The new technique might help in future to broaden the applications of PAE in imaging or guiding minimally invasive laser procedures.      

活体动物体内光学成像技术的研究进展

生物发光和荧光成像作为近年来新兴的活体动物体内光学成像技术,以其操作简便及直观性成为研究小动物活体成像的一种理想方法,在生命科学研究中得以不断发展。利用这种成像技术,可以直接实时观察标记的基因及细胞在活体动物体内的活动及反应。利用光学标记的转基因动物模型可以研究疾病的发生发展过程,进行药物研究及筛选等。本文综述了现有活体动物体内光学成像技术的原理、应用领域及发展前景,比较了生物发光与几种荧光技术的不同特点和应用。     

Tapered plastic optical fiber-based biosensor--tests and application

Cells detection is crucial in microbiological analysis of clinical, food, water or environmental samples. However, currently employed methods are time consuming. Plastic optical fiber (POF) biosensors consist in a viable alternative for rapid and inexpensive scheme for detection. In order to study the sensitivity of tapers for microbiological detection, geometric parameters are studied, such as the taper waist diameter since the formation of taper regions are the key sensing element in this particular type of sensors. In this study, a series of POF taper sensors were prepared using a specially developed tapering machine, and the dispersion of geometric dimensions is evaluated, aiming to achieve the best tapering characteristics which will provide a better sensitivity on the sensor response. The fiber tapers that presented the finest results were those constructed in U-shaped (bended) configurations, with taper waist diameters ranging from 0.40 mm up to 0.50 mm. These fiber tapers were used as the main section of the monitoring device, and when chemically treated as immunosensors for the detection of bacteria, yeast and erythrocytes.     

A dissolved oxygen sensor based on composite fluorinated xerogel doped with platinum porphyrin dye

A new functional fluorinated material taking n‐propyltrimethoxysilicane (n‐propyl‐TriMOS) and 3,3,3‐trifluoropropyltrimethoxysilicane (TFP‐TriMOS) as precursors was applied to construct a novel dissolved oxygen sensing film. The sensing film was fabricated by dip‐coating the functional fluorinated material‐doped [meso‐tetrakis(pentafluorophenyl) porphyinato] platinum(II) (PtF₂₀TPP) onto a glass slide. The oxygen sensing film exhibited a good linear relationship, fast response time, long stability and high sensitivity to dissolved oxygen. In the developed optical oxygen sensor, an LED and a photodiode were composed to construct a back‐detection optical system not needing an optical fiber based on fluorescence intensity detection. The smart optical oxygen sensor based on the PtF₂₀TPP fluorescence quenching possesses the advantages of portability and low cost and can be applied to the dissolved oxygen in situ monitoring in seawater. Copyright © 2009 John Wiley & Sons, Ltd.