Superficial photothermal laser ablation of ex vivo sheep esophagus using a cone‐shaped optical fiber tip

Superficial photothermal laser ablation (SPLA) may be useful as a therapeutic approach producing a depth of injury that is sufficient to eliminate mucosal lesion but not deep enough to induce thermal effects in deeper tissue layers. The purpose of this preliminary study is twofold: (a) to describe design steps of a fiber probe capable of delivering a tightly focused laser beam, including Monte‐Carlo‐based simulations, and (b) to complete the initial testing of the probe in a sheep esophagus model, ex vivo. The cone‐shaped (tapered) fiber tip was obtained by chemical etching of the optical fiber. A 1505 nm diode laser providing power up to 500 mW was operated in continuous wave. The successful SPLA of the sheep mucosa layer was demonstrated for various speed‐power combinations, including 300 mW laser power at a surface scanning rate of 0.5 mm/s and 450 mW laser power at a surface scanning rate of 2.0 mm/s. Upon further development, this probe may be useful for endoscopic photothermal laser ablation of the mucosa layer using relatively low laser power.     

Dual‐ and single‐shot susceptibility ratio measurements with circular polarizations in second‐harmonic generation microscopy

Polarization‐resolved second‐harmonic generation (P‐SHG) microscopy is a technique capable of characterizing nonlinear optical properties of noncentrosymmetric biomaterials by extracting the nonlinear susceptibility tensor components ratio , with z‐axis parallel and x‐axis perpendicular to the C₆ symmetry axis of molecular fiber, such as a myofibril or a collagen fiber. In this paper, we present two P‐SHG techniques based on incoming and outgoing circular polarization states for a fast extraction of : A dual‐shot configuration where the SHG circular anisotropy generated using incident right‐ and left‐handed circularly‐polarized light is measured; and a single‐shot configuration for which the SHG circular anisotropy is measured using only one incident circular polarization state. These techniques are used to extract the of myosin fibrils in the body wall muscles of Drosophila melanogaster larva. The results are in good agreement with values obtained from the double Stokes‐Mueller polarimetry. The dual‐ and single‐shot circular anisotropy measurements can be used for fast imaging that is independent of the in‐plane orientation of the sample. They can be used for imaging of contracting muscles, or for high throughput imaging of large sample areas.     

Optical fan for single‐cell screening

The single‐cell screening has attracted great attentions in advanced biomedicine and tissue biology, especially for the early disease diagnosis and treatment monitoring. In this work, by using a specific‐designed fiber probe with a flat facet, we propose an “optical fan” strategy to screen K562 cells at the single‐cell level from a populations of RBCs. After the 980‐nm laser beam injected into the fiber probe, the RBCs were blown away but holding target K562 cells in place. Further, multiple leukemic cells can be screened from hundreds of red blood cells, providing an efficient approach for the cell screening. The experimental results were interpreted by the numerical simulation, and the stiffness of optical fan was also discussed.     

Front Cover: Implantable self‐aligning fiber‐optic optomechanical devices for in vivo intraocular pressure‐sensing in artificial cornea

This work addresses an unmet clinical need, that of glaucoma monitoring through intraocular pressure (IOP) interrogation in patients with artificial corneas (keratoprost hesis). We demonstrate direct integration of a low‐drift, fiber‐optic Fabry‐Perot pressure sensor embedded in the keratoprosthesis via rapid, non‐contact micromagnetic fiber alignment. IOP interrogation is achieved by using white‐light interferometry, which provides sub‐mmHg IOP sensitivity. Further details can be found in the article by Pui‐Chuen Hui, Katia Shtyrkova, Chengxin Zhou, et al. ( e202000031 ).

     

Miniaturized all fiber probe for optical coherence tomography and pH detection of biological tissue

We present a novel all-fiber probe with 710-μm outside diameter for combined optical coherence tomography and pH detection. In cancer surgery, a significant challenge is how to completely remove the malignant tumor without cutting too much normal tissue. The difference between cancer tissue and normal tissue not only lies in morphology and structure but also in tissue pH, where malignant tissue has a lower pH. This dual-modality probe combined optical coherence tomography and pH detection of biological tissue, is expected to determine whether the tissue is cancerous quickly and accurately. The probe utilizes a typical three-segment structure (double-clad fiber - no-core fiber - graded-index fiber). We obtained a lateral resolution of ~10.6 μm, a working distance of ~506 μm and a pH measurement accuracy of 0.01 pH unit for the probe. The performance of the all-fiber probe was verified through an ex vivo experiment using the porcine brain specimen.     

Full‐field swept‐source optical coherence tomography and neural tissue classification for deep brain imaging

Optical coherence tomography can differentiate brain regions with intrinsic contrast and at a micron scale resolution. Such a device can be particularly useful as a real‐time neurosurgical guidance tool. We present, to our knowledge, the first full‐field swept‐source optical coherence tomography system operating near a wavelength of 1310 nm. The proof‐of‐concept system was integrated with an endoscopic probe tip, which is compatible with deep brain stimulation keyhole neurosurgery. Neuroimaging experiments were performed on ex vivo brain tissues and in vivo in rat brains. Using classification algorithms involving texture features and optical attenuation, images were successfully classified into three brain tissue types.     

Microfocusing sapphire capillary needle for laser surgery and therapy: Fabrication and characterization

A sapphire shaped capillary needle designed for collimating and focusing of laser radiation was proposed and fabricated by the edge‐defined film‐fed growth technique. It features an as‐grown surface quality, high transparency for visible and near‐infrared radiation, high thermal and chemical resistance and the complex shape of the tip, which protects silica fibers. The needle's geometrical parameters can be adjusted for use in various situations, such as type of tissue, modality of therapy and treatment protocol. The focusing effect was demonstrated numerically and observed experimentally during coagulation of the ex vivo porcine liver samples. This needle in combination with 0.22NA optical fiber allows intensive and uniform coagulation of 150 mm³ volume interstitially and 30 mm³ superficially by laser exposure with 280 J without tissue carbonization and fiber damaging along with delicate treatment of small areas. The demonstrated results reveal the perspectives of the proposed sapphire microfocusing needle for laser surgery and therapy.     

Fan‐shaped scanning approach for miniaturized photoacoustic tomography

We describe a novel scanning approach for miniaturized photoacoustic tomography (PAT), based on fan‐shaped scanning of a single transducer at one or two discrete positions. This approach is tested and evaluated using several phantom and animal experiments. The results obtained show that this new scanning approach provides high image quality in the configuration of miniaturized handheld or endoscopic PAT with improved effective field of view and penetration depth.     

Preclinical mouse model of optical coherence tomography for subcortical brain imaging without dissection

The purpose of this study was to investigate the feasibility of using optical coherence tomography (OCT) to identify internal brain lesions, specifically intracerebral hemorrhage, without dissection. Mice with artificially injected brain hematomas were used to test the OCT system, and the recorded images were compared with microscopic images of the same mouse brains after hematoxylin and eosin staining. The intracranial structures surrounding the hematomas were clearly visualized by the OCT system without dissection. These images reflect the ability of OCT to determine the extent of a lesion in several planes. OCT is a useful technology, and these findings could be used as a starting point for future research in intraoperative imaging.     

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.     

Comparison of the Iowa Reference Algorithm to the Heidelberg Spectralis optical coherence tomography segmentation algorithm

For spectral‐domain optical coherence tomography (SD‐OCT) studies of neurodegeneration, it is important to understand how segmentation algorithms differ in retinal layer thickness measurements, segmentation error locations and the impact of manual correction. Using macular SD‐OCT images of frontotemporal degeneration patients and controls, we compare the individual and aggregate retinal layer thickness measurements provided by two commonly used algorithms, the Iowa Reference Algorithm and Heidelberg Spectralis, with manual correction of significant segmentation errors. We demonstrate small differences of most retinal layer thickness measurements between these algorithms. Outer sectors of the Early Treatment Diabetic Retinopathy Study grid require a greater percent of eyes to be corrected than inner sectors of the retinal nerve fiber layer (RNFL). Manual corrections affect thickness measurements mildly, resulting in at most a 5% change in RNFL thickness. Our findings can inform researchers how to best use different segmentation algorithms when comparing retinal layer thicknesses.     

Characterizing thrombus with multiple red blood cell compositions by optical coherence tomography attenuation coefficient

Embolectomy is one of the emergency procedures performed to remove emboli. Assessing the composition of human blood clots is an important diagnostic factor and could provide guidance for an appropriate treatment strategy for interventional physicians. Immunostaining has been used to identity compositions of clots as a gold-standard procedure, but it is time-consuming and cannot be performed in situ. Here, we proposed that the optical attenuation coefficient of optical coherence tomography (OCT) can be a reliable indicator as a new imaging modality to differentiate clot compositions. Fifteen human blood clots with multiple red blood cell (RBC) compositions from 21% to 95% were prepared using healthy human whole blood. A homogeneous gelatin phantom experiment and numerical simulation based on the Lambert–Beer's law were examined to verify the validity of the attenuation coefficient estimation. The results displayed that optical attenuation coefficients were strongly correlated with RBC compositions. We reported that attenuation coefficients could be a promising biomarker to guide the choice of an appropriate interventional device in a clinical setting and assist in characterizing blood clots.     

Development of highly reliable SERS‐active photonic crystal fiber probe and its application in the detection of ovarian cancer biomarker in cyst fluid

Conventionally Surface‐enhanced Raman spectroscopy (SERS) is realized by adsorbing analytes onto nano‐roughened planar substrate coated with noble metals (silver or gold) or their colloidal nanoparticles (NPs). Nanoscale irregularities in such substrates/NPs could lead to SERS sensors with poor reproducibility and repeatability. Herein, we demonstrate a suspended core photonic crystal fiber (PCF) based SERS sensor with extremely high reproducibility and repeatability in measurement with a relative SD of only 1.5% and 4.6%, respectively, which makes it more reliable than any existing SERS sensor platforms. In addition, our platform could improve the detection sensitivity owing to the increased interaction area between the guided light and the analyte, which is incorporated into the holes that runs along the length of the PCF. Numerical calculation established the significance of the interplay between light coupling efficiency and evanescent field distribution, which could eventually determine the sensitivity and reliability of the developed SERS active‐PCF sensor. As a proof of concept, using this sensor, we demonstrated the detection of haptoglobin, a biomarker for ovarian cancer, contained within the ovarian cyst fluid, which facilitated in differentiating the stages of cancer. We envision that with necessary refinements, this platform could potentially be translated as a next‐generation highly sensitive SERS‐active opto‐fluidic biopsy needle for the detection of biomarkers in body fluids.     

Inside Front Cover: Neurosurgical brain tumor detection based on intraoperative optical intrinsic signal imaging technique: A case report of glioblastoma (J. Biophotonics 1/2020)

Intraoperative neurosurgical diagnosis of brain tumor determines the success rate of patients' prognoses. We firstly proposed a novel approach based on an optical method to distinguish the site of the tumor functionally. The promoted technique is non‐invasive, non‐radioactive, dye‐free, and potential of real‐time monitoring, which is still not available nowadays by using other techniques. The method could be applied to neuroimage guiding system for precision surgery of brain. Further details can be found in the article by Xin‐Rui Liu, Tien‐Yu Hsiao, Yun‐Qian, et al. ( e201900200 ).

     

Novel optical fiber Vernier immunosensor based on cascading Sagnac loops embedded with excessively tilted fiber grating for specific detection of canine distemper virus

A novel optical fiber Vernier effect (VE) biosensor based on cascading Sagnac loops embedded with excessively tilted fiber grating (ExTFG) is proposed for the label free and specific detection of canine distemper virus (CDV). The VE was realized by cascading two different Sagnac loops with similar free spectrum range (FSR), one of which was integrated with panda-type polarization maintaining fiber (PMF) as the reference loop, and the other was embedded with ExTFG as the sensing loop. Owning to the amplified function of the VE, the refractive index (RI) sensitivity of the proposed sensing structure reached −1914.89 nm/RIU, which is approximately 12 times higher than that of the single ExTFG based RI sensor. Furthermore, the ExTFG in sensing loop was modified by graphene oxide (GO) and bio-functionalized by the CDV monoclonal antibodies (anti-CDV MAbs) for the specific detection of the CDV. Experimental results show that the proposed optical fiber Vernier sensor could detect the CDV in buffer solution with concentration as low as 1 pg/mL, and the sensitivity was about −1.18 nm/[log(mg/ml)] in the concentration range of 1 pg/mL ~ 50 ng/mL. The excellent specific and clinical properties of the biosensor were verified by immunoassays for fetal bovine serum, Toxoplasma gondii, rabies virus and CDV serum in sequence. Due to the sensitivity amplification function of VE, dense comb spectrum of the Sagnac loop and the stable interference spectra maintained by the polarized light, the proposed biosensor possesses the combined advantages of high sensitivity, high Q-factor and high stability, which may have potential applications in biosensing fields.     

Single probe diffuse reflectance spectroscopy to assess the effect of sarcopoterium spinosum treatment on the cerebral tissue properties of ApoE knockout mouse

In this work, diffuse near-infrared light reflectance spectroscopy based on a single optical probe, contains central single collection fiber surrounded by a circular array of illumination fibers, was used to quantify cerebral tissue properties in ApoE knockout mice following Sarcopoterium spinosum treatment. Sarcopoterium spinosum, also known as Thorny burnet, is a Mediterranean plant widely used as a traditional therapy for the treatment of a variety of pathologies, primarily type 2 diabetes mellitus (T2D). While it's efficacy in the treatment of T2D, and of other components of metabolic syndrome, have already been validated by us, the aim of this study was to investigate the effects of Sarcopoterium spinosum extract (SSE) on dyslipidemia and vascular functions. We utilized ApoE deficient mice (ApoE^−/−, Atherosclerosis-prone apolipoprotein E-deficient), who have a severe impairment in plasma lipoprotein clearance and thus develop alterations in blood lipid profile and are highly susceptible to atherogenic plaque formation. A total of 34 male mice were divided into five groups representing various genetic, dietary, and treatment configurations. Optical measurements were used to assess changes in diffused reflectance spectra, optical properties (absorption and scattering), and cerebral tissue chromophore contents. Specifically, significant improvement in cerebral hemoglobin level was observed in ApoE KO mice, fed an artherogenic diet (ATD), upon SSE treatment. Biochemical and histological analyses of ApoE^−/−ATD mice showed elevated body weight and a high level of blood triglycerides, free fatty acids and cholesterol. In contrast, in SSE treated mice improvement was observed, suggesting beneficial effects of SSE. In ApoE^−/−ATD mice group a higher levels of deoxyhemoglobin was monitored indicating that the rate of oxygen release to the tissue is low. This was supported by decrease in oxygen saturation. It was also shown a reduction in water content in the brain of ApoE KO. Mice fed with the atherogenic diet demonstrated increased water content as compared to STD-fed ApoE KO mice, while SSE administration reversed the effect of the diet. To our knowledge, no such study has been reported before.     

A review of specialty fiber biosensors based on interferometer configuration

Optical fiber biosensors have attracted extensive research attention in fields such as public health research, environmental science, bioengineering, disease diagnosis and drug research. Accurate detection of biomolecules is essential to limit the extent of disease outbreaks and provide valuable guidance for regulatory agencies to take timely measures. Among many optical fiber sensors, optical fiber biosensors based on specialty fibers have the advantages of biocompatibility, small size, high measurement resolution, high stability and immunity to electromagnetic interference. In this paper, four types interferometer biosensors based on specialty fiber, namely Mach-Zehnder interferometer, Michelson interferometer, Fabry - Perot interferometer and Sagnac interferometer, are reviewed in terms of operating principles, sensing structure and application fields. The fiber types are further divided into micro-nano optical fiber, thin core fiber, polarization maintaining fiber, polymer fiber, microstructure optical fiber. Furthermore, this paper evaluates the advantages and disadvantages of these interferometer biosensors. Finally, main challenging problems and expectational development direction of specialty fiber interferometer biosensors are summarized. This text clearly shows the huge development potential of optical fiber biosensors in biomedical.     

Wave optical simulation of retinal images in laser safety evaluations

Lasers with wavelengths in the visible and near infrared region, pose a potential hazard to vision as the radiation can be focused on the retina. The laser safety standard IEC 60825–1:2014 provides limits and evaluation methods to perform a classification for such systems. An important parameter is the retinal spot size which is described by the angular subtense of the apparent source. In laser safety evaluations, the radiation is often described as a Gaussian beam and the image on the retina is calculated using the wave optical propagation through a thin lens. For coherent radiation, this method can be insufficient as the diffraction effects of the pupil aperture influence the retinal image. In this publication, we analyze these effects and propose a general analytical calculation method for the angular subtense. The proposed formula is validated for collimated and divergent Gaussian beams.     

Detecting metabolic differences in fetal and adult sheep adipose and skeletal muscle tissues

The primary metabolic pathway required to produce ATP differs as a result of tissue type, developmental stage and substrate availability. We utilized molecular and histological techniques to define the metabolic status in foetal and adult, adipose and skeletal muscle tissues. Redox ratios of these tissues were also determined optically by two‐photon microscopy. Adult perirenal adipose tissue had a higher optical redox ratio than fetal perirenal adipose tissue, which aligned with glycolysis being used for ATP production; whereas adult skeletal muscle had a lower optical redox ratio than fetal skeletal muscle, which aligned with oxygen demanding oxidative phosphorylation activity being utilized for ATP production. We have compared traditional molecular and microscopy techniques of metabolic tissue characterization with optical redox ratios to provide a more comprehensive report on the dynamics of tissue metabolism.     

Snapshot polarized light scattering spectroscopy using spectrally-modulated polarimetry for early gastric cancer detection

Polarized light scattering spectroscopy (PLSS) is a promising optical technique developed for the detection of cancer, which extracts the single scattering light to infer morphological information of epithelial cells. However, traditional PLSS uses either a rotatable polarizer or two orthogonal polarizers to purify the single scattering light, which makes it complicated and challenged to build a PLSS endoscope. Herein, we propose a snapshot PLSS with a single optical path to directly get the single scattering light for the first time. The single scattering light is encoded using the spectrally - modulated polarimetry and decoded using the continuous slide iterative method. Both the polystyrene microsphere solutions and the ex vivo gastric cancer samples are used to verify the method. The experimental results of the snapshot PLSS are consistent well with that of the traditional PLSS. The proposed method has a potential for the building of snapshot PLSS endoscope systems in future.