This PDF file contains the front matter associated with 11631 Proceedings Volume XXXX including the Title Page, Copyright information, and Table of Contents.

Osteoarthritis (OA) is a painful, debilitating disease characterized by the degeneration of articular cartilage. We have developed a novel multiplexed polarized, hypodermic-needle-compatible Raman arthroscope probe that can achieve intra-articular assessments of the compositional and structural changes to cartilage associated with early-stage OA, including depletion of glycosaminoglycans from the cartilage superficial regions and changes to superficial zone collagen alignment. Through ex vivo models on human and bovine cartilage, we demonstrate that using multivariate linear regression, this platform can accurately measure superficial zone cartilage GAG depletion. This work shows that Raman needle arthroscopy can provide a practical, minimally invasive, point-of-care clinical tool capable of diagnosing OA before irreparable cartilage degeneration is radiographically evident.

Meningiomas are the most common brain neoplasms. They often show a wide distribution of locations and morphological attributes. Therefore, rendering tumor margin status is difficult during surgery. Accurate identification of tumor boundary intraoperatively is essential for total tumor removal and adjacent healthy tissue preservation. Visible resonance Raman (VRR) spectroscopy has been used for detection and diagnosis of human organ lesions since 2011. Here, we report for the first time the preliminary results on the evaluation of a VRR-LRRTM analyzer based on VRR technique to identify human brain meningioma grades and margins.

Here we present a ratiometric intensity analysis of the Raman spectrum in the HWN region of three breast tissue conditions, namely adipose, fibrous and malignant in a broad sampling of lumpectomy specimens. We demonstrate that these intensity ratios can be used as a “molecular barcode” in breast cancer pathology. Our ratiometric-based approach in HWN is simple, interpretable and exhibits distinct barcodes for different tissue types.

Otitis media (OM) is a group of inflammatory diseases of the middle ear and is the most frequent cause of physician visits and antibiotic prescriptions for children. Current diagnostic methods do not differentiate acute otitis media from otitis media with effusion, as both types of OM share many symptomatic features. A cohort of around 50 patients undergoing myringotomy were enrolled in this study, where Raman spectroscopy (RS) allowed non-invasive determination of OM subtype. Here we demonstrate the potential for RS to probe OM infection status in pediatric patients, to guide treatment protocol for ear infections and limit over-prescription of antibiotics.

Radiofrequency ablation is the most common procedure to treat cardiac arrythmias, such as atrial fibrillation. Catheter ablation isolates or eradicates abnormal electrical activity to maintain sinus rhythm. However, inadequate lesion formation permits arrhythmia resurgence. Optical spectroscopic signatures can detect biomolecular and tissue structural changes and can potentially serve as a tool to evaluate lesion quality. In this work, we introduce a near-infrared spectroscopy through fiber-optic integrated catheter to assess contact and predict lesion size using artificial neural network model on both ex-vivo porcine model and non-survival in-vivo pilot experiments in pigs.

Colorectal cancer incidence is increasing globally and represents the fourth leading cause of death due to cancer. In this study, a diffuse reflectance spectroscopic fibre probe is employed for tissue characterization. DRS fibre probes leave no marks on tissue and thus imaging and tracking its tip during tissue scanning would enable the localization of biopsy sites. Two fiducial markers are chosen for the detection and tracking of the probe, providing both spatial and spectral information on the DRS probe. In this way, real-time tissue discrimination and display is enabled.

Oxygen is a vital component in wound healing; however, microvascular dysfunction can impact the wound healing process by restricting the flow of oxygen to the site. Patients afflicted with cardiometabolic diseases, such as diabetes, are predisposed towards microvascular insufficiencies and may experience stagnated healing of injured tissues. In past literature Vascular Occlusion Tests (VOTs), coupled with NIRS-based imaging approaches, have been applies with the goal of assessing oxygenated flow to a site; either as dynamic, point-based, measurements or wide-area measurements at discrete timepoints. Breath-holding (BH), as a stimulus, holds potential to induce oxygenated flow changes without the need for additional equipment and the potential discomfort associated with vascular occlusion. In this study, end-exhalation breath-holding was applied on normal subjects. Each subject was imaged via an in-house build Near InfraRed Optical Scanner (NIROS) to acquire continuous spatio-temporal maps of effective hemoglobinbased parameters. Average trendlines of the effective parameters (via oxy- (ΔHbO), deoxy- (ΔHbR), total hemoglobin (ΔHbT), and oxygen saturation (ΔStO2)) were extracted. In addition, a Pearson’s correlation-based approach was applied to obtain correlation maps in terms of the oxygenated flow. Results indicated that statistically significant changes in the oxygenated flow was observed between the BH phase and post-BH phase, with correlation maps indicating regions of positively correlated flow in control subjects. Breath-holding holds potential as a technique to assess oxygenated flow changes and the extent of change between a given site to its surroundings in disease models, as currently assessed in diabetic foot ulcers and radiation dermatitis applications.

Inadvertent nerve injury is a common complication during many surgical procedures. Intraoperative localization of nerves could reduce the risk of nerve injury and improve patients’ quality of life post-operation. To address this need, we combine diffuse reflectance and polarization imaging techniques into a single imaging system for in vivo nerve mapping. Both modalities successfully localize nerves within the field of view in an in vivo rat model and together provide enhanced contrast in relation to the surrounding tissues. The results of this study provide valuable insight into the future development of a real-time imaging system for clinical translation.

We are developing a new IR imaging technique, enhanced thermal imaging, that can delineate blood vessels embedded in water-rich tissue in real time. The technique is a combination of thermal IR imaging (8-10 μm) and selective heating of blood (∼0.5°C) relative to surrounding water-rich tissue using LED sources (530 nm) at low powers (irradiance <500 mW/cm² ). Blood absorbs light strongly at these wavelengths, while absorption by soft tissues is lower. Illumination of tissue containing vessels with the LED heats the blood compared to surrounding tissue so that the vessels look brighter in the thermal image. In previous work, we successfully highlighted vessels embedded in porcine heart tissue and the blood-rich vascular region that is routinely targeted for surgical excision around mammary tumor masses in a murine model. However, in this earlier work the IR images were recorded, and post-acquisition processing was necessary to highlight the presence of the vascular structures. In this work, we describe recent progress in making enhanced thermal imaging a real-time technique. A porcine tissue model with simulated blood vessels and the wrist/forearms of two human subjects were imaged with a FLIR thermal camera. The frame-to-frame temporal and spatial derivatives were calculated in real-time and then used to identify regions exhibiting rapid changes in temperature, thus highlighting the structure of blood-rich regions.

We report the design, development, and characterization of the first multispectral fluorescence lifetime imaging platform designed for clinical application based on avalanche photodiodes (APD). Consistent and accurate measurement of fluorescence lifetimes is achieved. Fast dynamic gain adjustment via APD bias modulation is implemented independently for each spectral channel, maximizing photon economy and greatly improving signal quality. Compared to conventional MCP-PMT based systems, the new platform presents 5-fold reduction of lifetime measurement variability under identical experiment conditions. This improved photon economy leads to 35 times faster coverage of imaging field in clinical practice with identical tissue exposure, making the new platform better suited for clinical application.

Inadequacy of tumor tissue in transthoracic core needle biopsy (CNB) and transbronchial biopsy specimens, often due to contamination by fibrosis and normal lung elements, precludes accurate diagnosis, tumor subtyping and molecular testing, and impedes biobanking for research. Frozen section and touch prep methods are not utilized for adequacy assessment because they are destructive and consume tissue. We investigate polarization sensitive optical coherence tomography (PS-OCT), including birefringence and degree of depolarization uniformity metrics, for non-destructive, volumetric quantification of tumor yield in lung CNB specimens. PS-OCT distinguishes tumor, fibrosis and lung parenchyma with high accuracy, demonstrating potential for rapid CNB adequacy assessment.

Percutaneous renal access remains the cornerstone initial step in varied clinical settings. For obtaining the best surgical outcome and minimizing patient morbidity, an appropriate access to the target calyx is needed. In our study, we built a forward-view endoscopic OCT system for PCN guidance. Pig kidneys were imaged to demonstrate the feasibility of the imaging system. Different parts of pig kidneys (cortex, medulla and renal pelvis) can be clearly differentiated. Furthermore, machine learning based computer aided diagnosis platform was developed to distinguish different tissue types automatically and the accuracy of recognition was as high as 90%.

The purpose of this study was to develop a generalizable convolutional neural network (CNN) classification technique of optical coherence tomography (OCT) images of breast tissue acquired from multiple OCT systems. We imaged lumpectomy and mastectomy specimens (acquired through the Columbia University Tissue Bank) from 31 patients. In our early results, we classified the images into healthy tissue (adipose and stroma) and diseased, which included ductal carcinoma in situ (DCIS), mucinous carcinoma, and invasive ductal carcinoma (IDC). Our goal is to expand our classification to differentiate the diseased tissue into subclasses of DCIS, IDC, mucinous carcinoma, and benign tissue.

Fluorescence-based slide-free digital pathology techniques, including 3D microscopy, are gaining interest as alternatives to traditional slide-based histology. Since pathologists are accustomed to the appearance of standard histology stains, the ability to render grayscale fluorescent images with color palettes that mimic traditional histology is valuable. We present FalseColor-Python, an open-source rapid digital-staining package that renders two-channel fluorescence images to mimic standard histology. Our package offers consistent color-space representations that are robust to both intra-specimen and inter-specimen variations in staining and imaging conditions, along with GPU-accelerated methods to process large datasets efficiently.

In digital pathology, the practice of scanning slides at a single resolution results in more data than is clinically useful. In contrast, using a light microscope, the pathologist adapts magnification according to specimen content. We developed a method of digitizing the analog microscope workflows of pathologists using a microscope camera and video mosaicking with the Scale Invariant Feature Transform (SIFT). Matching this digital record to the whole slide image generates a slide interaction map over time and magnification tiers. The results of the pilot studies suggest data size can be significantly reduced without diminishing the information content required for diagnosis.

Glandular architecture is currently the basis for the Gleason grading of prostate biopsies. To visualize and computationally analyze glandular features in large 3D pathology datasets, we developed an annotation-free segmentation method for 3D prostate glands that relies upon synthetic 3D immunofluorescence (IF) enabled by generative adversarial networks. By using a fluorescent analog of H and E (cheap and fast stain) as an input, our strategy allows for accurate glandular segmentation that does not rely upon subjective and tedious human annotations or slow and expensive 3D immunolabeling. We aim to demonstrate that this 3D segmentation will enable improved prostate cancer prognostication.

Accurate cancer margin assessment prior to surgical resection is a key factor influencing the long-term survival of oral and oropharyngeal cancer patients. This leads to the need for additional guidance tools for real-time delineation of cancer margins. In this work, fiber-based fluorescence lifetime Imaging (FLIm) was combined with machine learning to perform intraoperative tumor identification. The developed classifier achieved a measurement-level ROC-AUC of 0.89±0.03 on an N=62 patient dataset. A transparent overlay of classifier output was augmented onto the surgical field and updated through tissue motion correction, ensuring co-registration between tissue and spectroscopic data/classifier output was maintained during imaging..

A key step for mitigating tumor recurrence for patients with head and neck cancer is adequate surgical margin delineation. Presently available techniques however limit accurate tumor margin detection during surgery. Herein, we report on tumor visualization using deep learning by combining autofluorescence images acquired by a fiber-based fluorescence lifetime imaging (FLIm) system and white light images (WLI) obtained by surgical cameras. To accomplish accurate registration between FLIm and WLI, a tissue motion correction algorithm was employed as a pre-processing step. The trained model was applied to differentiation of healthy and cancerous tissues in a 50 head and neck cancer patients dataset (ROC-AUC : 0.87).

Choroidal neovascularization (CNV) is a hallmark of advanced age-related macular degeneration and is a leading cause of irreversible vision loss and blindness in the world. There is a lack of imaging modalities that can detect CNV early. Photoacoustic microscopy (PAM) combines acoustic and optical imaging to create high-resolution images that can delineate microvasculature non-invasively and permit for visualization of CNV. However, to distinguish CNV from native microvasculature, molecular contrast agents can be applied to increase the sensitivity of PAM imaging. In this study, functionalized indocyanine green (ICG) with RGD ligands (ICG-RGD) was synthesized and applied to in vivo imaging of CNV in the rabbit retina using a custom-built high-resolution PAM imaging system. RGD ligands selective binds to integrins present in neovascularization. The CNV model was created in three New Zealand White rabbits via subretinal injection of human vascular endothelial grow factor (VEGF-165). Three-dimensional in vivo PAM images of CNV were acquired before and after intravenous injection of 400 µL ICG-RGD at a concentration of 2.5 mg/mL over a period of 14 days. In addition, color fundus photography and fluorescence imaging were also acquired. This enables visualization of the newly developed CNV as well as monitoring the changes in CNV over time. With the administration of ICG-RGD, PAM signal amplitudes enhanced up to 15.7-fold at day 1 post-injection and persisted up to 5 days. The PAM results were also confirmed by fluorescence imaging. Biosafety studies show no systemic toxicity of the ICG-RGD. These studies demonstrate the potential of molecular PAM imaging for the characterization of microvasculature pathologies.

Patient simulations can be a powerful tool to plan placement of photoacoustic imaging components for surgical guidance. We previously used compressional-wave-only simulations to identify optimal acoustic windows for transcranial photoacoustic imaging. Elastic simulations, which include both compressional and shear waves, are expected to more accurately represent the physical transcranial acoustic process. However, elastic simulations are timing-consuming and memory intensive. This paper contains a comparison of compressional and elastic wave simulations to determine which option is more suitable for preoperative surgical planning. Compressional and elastic photoacoustic k-Wave simulations were performed based on a CT volume of a human cadaver head. Photoacoustic sources were placed in the locations of the internal carotid arteries and likely positions of neurosurgical instrument tips. Transducers received signals from three acoustic windows (i.e., the ocular, nasal, and temporal regions). Target visibility, image-based target size estimates, and target-to-instrument distances were measured using the generalized contrast-to-noise ratio, resolution, and relative source distances, respectively, for each simulation method. The generalized contrast-to-noise ratio and resolution measurements were equivalent between compressional and elastic simulations. Relative source distance measurements were within 0.1 mm of the true distances. These results indicate that it is sufficient to utilize the less time-consuming, less memory-intensive compressional wave simulations for presurgical planning.

In plastic surgery, free tissue graft procedures are an essential part of fixing tissue-lack injuries or diseases. However, tissue necrosis caused by vascular occlusions or poor vascular anastomosis is a severe problem for prognosis. Follow-up surgery in the early-stage of necrosis caused by congestion or ischemia is essential to salvage the tissue, but making a diagnosis is difficult because of the slight features of these states. Therefore, a diagnosis support system that can capture the features of blood circulation of the skin flap is required to improve prognosis. We focused on system design and analysis by using spectral characteristics of blood circulation of a skin flap for this purpose. The system to be constructed is composed of a two-channel narrow-band illuminant and a color camera and can capture six-channel spectral signals. The narrow-band illuminant is designed by combining 13 kinds of light-emitting diode (LED) spectra. In this study, we first measured reflectance spectra of the early-stage skin flap necrosis of the rat model to design the narrow-band illuminant spectra. We blocked the flow of the target vessel and observed necrosis progression. A prototyped skin flap chamber was used for stable observation of spectral reflectance measurements. An evaluation experiment was conducted using a color camera and the spectrally tunable light source. Skin flap images were captured under the designedilluminants and a conventional illuminant reproduced by the spectrally tunable light source. We confirmed the effectiveness of the designed system by improvements in necrosis region detection.

Microcirculation plays an important role by supplying oxygen and nutrients to maintain our lives. It is known that, as pathogenesis of sepsis, the microcirculation is impaired at the early stage of sepsis. In this case, it is expected that thrombomodulin alfa (TM alfa) works for the recovery of microcirculation. Direct observation of the impairment and recovery of microcirculation related to sepsis may give us clear understanding of those phenomena. In this study, we conducted experiments to observe microcirculation of septic model rats with an optical system. In these experiments, by attaching a chamber to the back of each rat, the same region of the microcirculation was consecutively monitored. Then, these rats were divided into three groups: control model rats (sham group), septic model rats (diseased group), and septic model rats to which TM alfa was administered (treated group). Each group includes five rats. In the diseased group smaller vessels disappeared and larger vessels became thinner. On the other hand, the treated group showed at first the degradation of microcirculation then the recovery. This may indicate effectiveness of TM alfa. We also estimated the blood velocity and blood vessel diameter from the acquired motion pictures to evaluate condition of the microcirculation. As a result, we quantitatively confirmed while blood velocity and blood vessel diameter of the diseased group decreased, that of the treated group decreased and then recovered. It should be noted that the set of motion pictures obtained in these experiments has potentially useful information for further analysis and is to be open to relevant researchers.

The status of lymph node is considered a critical prognostic factor for staging and guiding the future adjuvant treatment in many cancer types. The estimation of undetected micrometastases (0.2-2mm diameter) by conventional pathology was around 30-60% cases which has created a demand for the development of more fast and accurate approaches. In response, a paired-agent imaging approach is presented by employing a control imaging agent to allow rapid, quantitative mapping of microscopic cancer cells in lymph nodes to guide pathology sectioning. To identify the most feasible and effective protocol using this approach to detect micrometastases intraoperatively, swine cervical lymph nodes were used to evaluate the potential of different protocols for the agents to diffuse into and out of intact nodes. Aby-029, an anti-EGFR affibody molecule labeled with IRDye-800CW was used as targeted imaging agent, and the IRDye-700DX carboxylate was used as control agent. The time-course paired-agent fluorescence of whole lymph node were recorded to monitor the uptake and washout kinetics. Subsequently, lymph nodes were frozen-sectioned and imaged under an 85-um resolution fluorescence imaging system (Pearl, LICOR) to confirm equivalence of spatial distribution of both agents in the entire node. After much trial-and error, the intranodal infusion staining and rinsing protocol demonstrated promising results that both imaging agents shown strong correlation with each other in the absence of cancer cells (r=0.99, p<0.001). This methodology indicated the potential of using paired-agent imaging approach to allow rapid and sufficient detection of micrometastases in excised lymph nodes intraoperatively.

Identifying parathyroid glands can be challenging for surgeons during head and neck operations. For the surgeon, it becomes essential to preserve healthy parathyroid glands, while successfully removing diseased parathyroid glands. This study presents PTeye – a commercial fiber probe-based device that was designed for intraoperative parathyroid identification by detecting near infrared autofluorescence. The results of this study demonstrate that PTeye had 95% accuracy in identifying parathyroid glands in 78 patients. The device had an overall detection rate of 97% for healthy and diseased parathyroid glands. PTeye could also quantify parathyroid vascularity in real-time by using indocyanine green during neck surgeries.

Oral cavity and oropharyngeal cancers are leading pathologies, representing 3% of all new cancer cases in the United States. Adequate intraoperative marginal clearance of these malignancies is essential for long-term survival; however, presently available techniques limit precise instantaneous tumor margin characterization. Herein, we report the clinical validation of a fiber-based fluorescence lifetime imaging device for real-time intraoperative tumor delineation. Results from 72 human patients are reported (autofluorescence trends, ROC-AUC), including diverse cancer histologies, anatomic sites (e.g. tongue, tonsil, etc.), and patient medical histories. Emphasis is placed on results governing the detection of unknown primary tumors from 4 patients, as well as data from 5 patients presenting with residual carcinoma.

Hypoparathyroidism is a major complication after thyroid surgery, due to damage to healthy parathyroid glands. Near infrared autofluorescence imaging and laser speckle contrast imaging have been shown to address the two causes of parathyroid function loss – accidental removal, and damage to the parathyroid blood supply respectively. Here, we present an instrument that combines both techniques to enable intraoperative parathyroid identification and viability assessment in real-time and without the need for contrast agents. The performance of the device was evaluated intraoperatively in patients undergoing thyroidectomy and parathyroidectomy.

Robotic and endoscopic surgery is increasingly used in clinical practice and typically relies on stereoscopic vision to enable 3D visualization of the surgical field. We combined this capability with a FLIm acquisition system suitable for the identification of tumor tissue to generate a 3D map of the surgical field that comprises both FLIm and white light image information. This result is achieved using semi-global matching and deep stereo matching neural network. In addition to the generation of a 3D model of the surgical cavity, this approach leads to a more realistic rendering of FLIm maps by including tissue shading.

Spatial Frequency Domain Imaging (SFDI) is a powerful technique for non-contact tissue optical property and chromophore mapping over a large field of view. However, a major challenge that limits the clinical adoption of SFDI is that it requires carefully-controlled imaging geometry and the projection of known spatial frequencies. We present speckle-illumination SFDI (si-SFDI), a projector-free technique that measures tissue optical properties from structured illumination formed by randomized speckle patterns. We compute the local power spectral density of images under speckle illumination, from which a high-frequency and a low-frequency tissueresponse parameter can be characterized for each pixel. A lookup table generated by Monte-Carlo simulations is subsequently used to accurately determine optical absorption and reduced scattering coefficients. Compared to conventional SFDI, si-SFDI may be particularly useful for endoscopic applications due to its utilization of simple coherent illumination, which makes it more easily incorporated into existing endoscopic systems. Moreover, speckle illumination offers a large depth of focus compared to projector-based illumination. In this study, we explore wide-field optical property mapping with an endoscope camera and fiber-coupled laser speckle illumination. We apply this technique to tissue-mimicking silicone phantoms and biological tissues. The accuracy of si-SFDI is evaluated by comparing to optical properties measured by conventional SFDI. Future work could accelerate si-SFDI reconstruction by using parallel computing or machine learning algorithms.

In endoscopy, the position and orientation of the endoscope’s distal tip are important for locating lesions. Currently, position is estimated using scale lines on the endoscope’s surface and orientation is estimated based on the position of the proximal handle. Both these estimates are inaccurate and cannot be continuously recorded. Real-time endoscope motion tracking should improve tumor localization during colonoscopy. We developed an endoscope tracker that uses a pair of trackballs and two video cameras. It can track real-time changes in insertion length and rotation during an endoscopic procedure. A prototype device has been built and its performance has been evaluated.

Distinguishing the diseased breast tissue from the healthy tissue is a sorely challenging task for the surgeons during breast conserving surgery (BCS) as both tissues own relatively similar visual and haptic characteristics. It has been shown that diffused reflectance spectroscopy (DRS) has the potential to be used as a real-time tumor margin detection technique during BCS. In this research, an electrosurgical knife is equipped with fiber-based DRS sensing to provide the surgeon with real-time oncological guidance during BCS. To prevent overheating of the fibers, they were placed inside quartz tubes which were mounted on the electrosurgical knife. The effect of using quartz tubes and debris formation during electrosurgery on the DRS measurements on porcine tissue was investigated. Furthermore to investigate the performance of the new device, a heterogeneous breast phantom representing optical properties and anatomical shape of the real breast was developed. The new device was then used to cut through the phantom’s layers to assess the performance of the new knife while cutting. Finally, a BCS was performed on the phantom using the new knife without receiving visual and haptic feedback from the tissue. The results show that both using the quartz tubes and the formed debris do not have a significant effect on the DRS output. Moreover, the DRS outputs obtained during cutting the layered phantom showed the transition between the layers clearly, demonstrating that the cutting effect on the phantom tissue does not significantly affect the measurements . The X-ray images from the phantom before and after BCS using the new device confirmed the complete resection of the tumors from the breast phantom. The results indicate that the electrosurgical knife equipped with DRS is a promising technique for simultaneously distinguishing and cutting the tissue, and assessing real-time tumor margins during BCS.

Tissue sampling is required for disease diagnostics and research. Traditional tissue sampling tools often remove more tissue than required, causing unnecessary pain and morbidity. We report a minimally invasive laser microbiopsy system to sample sub-microliter (<1mm³ ) tissue sections. A focused annular beam cuts conical-shaped tissue sections. Compatible diagnostic methods may include standard histopathology, rapid point-of-care microscopy, and genetic testing. An objective of the approach is to harvest a minimal volume while limiting damage to retain tissue integrity for diagnosis. The laser microbiopsy system consists of a Ho:YAG laser (Lumenis P120), a ZnSe aspheric collimator (ISP optics, f = 50.8 mm), two fused silica axicons (Thorlabs, α = 20°), and an aspheric focusing lens (ISP optics, f = 25.4 mm). The system is characterized to evaluate the required laser dosimetry, range of harvested tissue volumes, and residual thermal damage. We first characterized the system in silico using raytracing (Zemax) and a heat transfer modeling. We then characterized the system experimentally performing micro-biopsies in ex vivo porcine skin. Raytracing and experimental measurements show agreement in annular beam shape with an inner and outer radius of 300 μm and 400 μm near the beam focus. Experimental results show ability to harvest tissue sections ranging from 0.009 to 0.10 mm3 using pulse energies from 1 - 2 J.

This work presents a method of needle shape reconstruction, which can serve as potential guidance technology for minimally invasive surgeries, such as epidural anesthesia. The suggested technology applies four optical fibers, which are glued along the Tuohy needle at an angle of 90 degrees from each other thus creating two pairs of opposite fibers. Optical fibers are used to achieve high resolution distributed strain sensing along the needle, which working principle is based on the Optical Backscattering Reflectometry (OBR). Since OBR is limited to a single-fiber measurement and the setup requires four sensing fibers, the multiplexing method has been suggested. The multiplexing approach is based on the spatial separation of four high-scattering nanoparticles doped fibers (used as sensing fibers) by the single-mode regions with a lower scattering level. As a result of such configuration, the strain sensed by each sensing point along the pairs of opposite fibers is used to reconstruct the inclination of the needle in two perpendicular directions. The approach has been tested in the needle calibration experiment when it has been manually bent to different directions and the setup allowed to accurately reconstruct the direction of the needle‘s inclination. The potential application of the setup for the minimally invasive therapies has been tested on the example of epidural anesthesia. The needle has been inserted into a medical phantom, which models human spinal anatomy, and the shape of the needle at each moment of insertion has been reconstructed.

In cardiac surgery, a method avoids cutting the sternum and ribs using an endoscope is known as Minimally Invasive Cardiac Surgery (MICS). MICS can be used for mitral valve prolapse. In this surgery, an annuloplasty ring is inserted to form the valve and since each person has a different valve size, an appropriate size must be selected by applying a sizer. We propose a system that supports surgery by superimposing a virtual image of the valve ring on the endoscopic image using Augmented reality (AR) technology. Marker detection needs to be performed for AR display. However, since organ surfaces are similar in color, we use the spectral reflectance of the material to obtain more information than RGB image. To avoid the use of special optics to measure the spectral reflectance, we estimate spectral reflectance from RGB images using principal component analysis. The areas containing the marker are obtained by similarity index and the 3D positions of the markers are determined from center of gravity measurements. Then, we superimpose the AR image onto the endoscope image by perspective transformation to the image plane and masking using estimated 3D position of markers. To evaluate our method, we validated the spectral reflectance estimation and AR display using pig hearts marked with crystal violet. We found that the accuracy of spectral reflectance estimation is sufficient for AR display and the AR image was almost the same as the actual ring size. Therefore, our proposed method is expected to increase the efficiency of the operation.

We conduct a pilot study using photoacoustic imaging (PAI) technique as a new catheter guiding method. The ex vivo experiment was implemented with three different states of balloon catheter consist of no injection, air injection, and pure water injection. A simple surface removing method was applied to catheter signal extraction. The high-resolution maximum amplitude projection (MAP) images were achieved as results of the experiment.

As the body's largest solid organ, the liver plays a very important role in the body's metabolism. More and more studies have shown that the liver may be an immune organ. A large amount of blood containing nutrients and pathogenic bacteria enters the liver. The liver is extremely rich in blood vessels, including the hepatic artery and portal vein. In the liver circulation, hepatic sinusoids have a unique structure and maintain normal immune homeostasis. More importantly, many liver diseases will directly affect liver sinusoids, such as hepatitis and liver fibrosis. Therefore, the ability to obtain high-resolution images of liver sinusoids of living livers is of great significance for the study of liver diseases. Photoacoustic imaging is becoming a very promising tool for the research of living organisms. It combines the high contrast of optical imaging and the high resolution of acoustic imaging to realize the imaging of absorption clusters in biological tissues. Since the scattering of ultrasound signals in biological tissues is 2-3 orders of magnitude weaker than the scattering of light in biological tissues, the endogenous absorption difference of tissues is directly used in the imaging process, so photoacoustic imaging has the advantages of deep imaging depth and non-destructive. As an important branch of photoacoustic imaging, photoacoustic microscopy can provide micron-level or even sub-micron-level imaging resolution, which is of great significance for biological research such as liver blood vessel detection. Since the lateral resolution of the photoacoustic microscopy imaging system depends on the focus of the laser, a higher resolution can be obtained by increasing the numerical aperture of the condenser objective. However, a large numerical aperture usually means a shorter working distance and makes the entire imaging system very sensitive to small optical defects. Therefore, the improvement of resolution through this method will be limited in practical applications. This paper implements a method of using iterative deconvolution to obtain a high-resolution photoacoustic image of the liver blood vessel. The focal spot of the photoacoustic microscopy is measured to obtain the lateral PSF (point spread function) of the system. Making the measured PSF as the initial system PSF to perform Lucy- Richardson (LR) deconvolution. The image resolution of liver lobules obtained by this method is higher. The full width at half maximum (FWHM) of the same liver sinusoid width before and after deconvolution are 9.52 μm and 6.65 μm, respectively, and the image definition is increased by about 1.4 times. Experiments show that this method can further improve the clarity of photoacoustic images of liver blood vessels, which lays the foundation for further research on liver diseases.