A smart optical probe that enables in vivo tissue type identification and the measurement of the force applied to the needle during epidural procedures is presented. This probe is meant to reduce the adverse risk associated with needle misplacement. It combines a Bragg sensor with low coherence interferometry (LCI) to measure the force applied by the operator on the standard epidural needle and differentiate tissue type presented at the tip of the epidural needle. The probe enables differentiation between different layers of tissue in the spinal region by making use of a machine-learning algorithm, which was trained on animal spinal cord tissue specimens.
We report a two-photon excitation fluorescence microscopy imager that uses a fiber-delivered fs supercontinuum (SC) generation source to achieve simultaneous dual-wavelength imaging. The SC generation is based on pumping a polarization-maintaining photonic crystal fiber with a fiber laser. The SC is then delivered to the imaging head through a broadband hollow-core fiber. Excitation wavelengths centered at 920 nm and 1180 nm were selected, which enabled simultaneous imaging of neurons transfected with GCaMP6 and administrated with muscimol-conjugated BODIPY. Imaging results of calcium dynamics of in vivo mouse brain and cultured primary neurons were collected to demonstrate the technology feasibility.
KEYWORDS: Optical coherence tomography, Pathology, Cancer, Tumor growth modeling, Tissues, Tissue optics, Position sensors, In vivo imaging, Data processing, Birefringence
Real-time assessment of tissue morphology and function is a pressing clinical need. We present a low cost OCT probe based on combined position sensor feedback, as well as a data processing algorithm that enables real-time display of tissue morphology and birefringence. The preliminary evaluation of this instrument on various biological specimens has demonstrated its capability for real-time diagnosis. Its preclinical assessment in vivo on animal models of cancer was performed at MD Anderson Cancer Center. Reliable assessment of tissue morphology and birefringence has been successfully demonstrated.
In this paper we report the use of a novel multimodal imaging hand-held probe for guiding laser and radiotherapy on nonmelanoma skin cancers (NMSCs) patients. This probe combines the capability of reflectance confocal microscopy (RCM) with that of Optical Coherence Tomography (OCT) to reliably detect cancer markers and measure cancer depth of invasion. These capabilities have shown to be very effective in accurately measuring cancer margins and guiding the therapy.
Sensorineural hearing loss (SNHL) is the most common sensory problem that causes permanent hearing loss due to the damage of cochlear hair cells. Current clinical imaging techniques do not provide sufficient resolution and functional assessment of the intracochlear structures. We developed a dual-mode endoscopic system that combines optical coherence tomography and autofluorescence to visualize the morphology and biochemical changes of the intracochlear structures. The preclinical assessment of the system was performed in a ovine model of SNHL in vivo. The preliminary results suggest that this approach may provide more accurate diagnosis of cochlear pathology and enable targeted SNHL therapies.
A new detection scheme was developed for simultaneous multi-channel imaging that provides isotropic images of retinal structures, free of directionality artifacts. The arrangement consists of light collecting fibers that act as offset apertures. This fiber bundle configuration can be used to retrofit basically any existing AO-SLO platform. The channels can be combined to reveal additional structural and functional details and this kind of retinal imaging with cellular resolution is a valuable new tool for researchers and clinicians.
We developed a novel ophthalmic imaging platform that combines non-invasive measurements of retina/choroid structure and ocular blood flow based on optical coherence tomography (OCT) and wide-field semi-quantitative global flow visualization using line-scanning Doppler flowmetry (LSDF). The combination of these two imaging modalities within the same imaging platform enables comprehensive assessment of blood flow in retina and choroid and provides efficient characterization of blood flow in hemodynamic studies both in human volunteers and in small animals. The platform enables visualization of the entire posterior hemisphere vasculature, including vortex veins, using only light and without additional contrast agent in humans and rats.
We report the development and the pre-clinical testing of a manual scanning OCT-based probe for core needle biopsy guidance. While stereotactic radiography, ultrasound, computed tomography, and magnetic resonance imaging are used to guide needle placement within a tumor, the optical probe provides the radiologist with the capability to examine tissue cellularity at the tip of the biopsy needle. The capability to investigate tissue cellularity prior to taking the biopsy could help reduce the number of non-diagnostic biopsies and increase the amount of viable tumor tissue within the biopsy core. This last aspect is very important in the new era of personalized cancer therapy, because greater tissue quantity is needed for various biomarker assays. This technology has been evaluated by us on a rabbit model of soft tissue cancer. Our results indicate the capability of this OCT-based probe for determining the in situ cellularity of the tissue at the tip of the biopsy needle.
Identification of positive margins during breast cancer conserving surgery is crucial for successful tumor resection. To address this clinical need, we developed a microscope that combines fluorescent microscopy, optical coherence tomography (OCT), and reflectance confocal microscopy (RCM) to identify the presence of positive tumor margins in surgical specimens. A cancer-targeting fluorescent agent is used to highlight potentially positive margins and guide combined RCM/OCT imaging. Combined RCM/OCT is used to accurately determine the extent of the positive margins, aided by custom image-processing techniques. This instrument has the potential to provide tumor margin guidance in the surgical suite, reducing reliance on lengthy histopathological inquiry and reducing the need for repeated surgery.
In the current era of personalized cancer therapy, various drugs need to be rapidly tested to determine their efficacy in killing cancer cells. In this way, the most effective drug can be administered to improve therapy effectiveness. However, since the biopsy specimens are heterogeneous, efficient testing requires the use only of the viable tumor part of the specimen. Therefore, rapid and automated evaluation of specimen heterogeneity is needed. In this paper presents an automated algorithm for tissue heterogeneity estimation based on OCT images. This algorithm use image texture features to differentiate between healthy and cancer tissue.
KEYWORDS: Ear, Optical coherence tomography, Endoscopy, Auto-fluorescence imaging, In vivo imaging, Magnetic resonance imaging, Pathology, Visualization, Sensors, Bone
This study presents a novel technology for in vivo cochlear imaging in sensorineural hearing loss (SNHL). SNHL is the most common type of permanent hearing loss and is associated with damaged hair cells of the cochlea. State of the art clinical imaging does not have sufficient resolution to show inner ear microstructure. We are developing and testing a dual-modal endoscopic instrument that combines optical coherence tomography (OCT) and autofluorescence imaging (AFI) for dynamic cochlear imaging. If successful, this approach will improve our understanding of the cellular basis of SNHL and enable the development of targeted therapies for inner ear disorders.
The limited sampling of biopsy and histopathology can lead to incomplete and/or inaccurate assessment of basal cell carcinomas (BCCs), subtypes and depth, which can affect diagnosis and treatment outcome. Reflectance confocal microscopy (RCM) combined with optical coherence tomography (OCT) can help achieve comprehensive 3-dimensional sampling in vivo, which may improve the diagnostic accuracy and margin assessment of BCCs. In a clinical study, we tested a combined RCM-OCT probe on 85 patients, with either clinically-suspicious (n=60, in intact skin) or biopsy-proven BCCs (n=25, in scarred skin). We correlated BCC features in RCM and OCT images with histopathology, calculated diagnostic accuracy and correlated depth predicted by OCT with histopathologically measured depth. The main features were small tumors extending from the basal cell layer at the dermal-epidermal junction; small and large tumor nests; in dermis; dark silhouettes; dilated blood vessels; horn cyst and bright peritumoral stroma. Deeper features such as necrosis and intratumoral mucin pools were correlated on OCT and histology. Higher sensitivity and negative predictive value (100%) and comparable specificity (48% vs 56% on RCM) and positive predictive value (82.19 vs 84.59 % on RCM) were observed for the combined RCM-OCT device for diagnosis of all lesions (n=85). Relatively higher specificity (94.1%) and positive predictive value (75%) were observed in the clinically suspicious lesions (n=60, in intact skin). High correlation was observed (R=0.86) between the OCT predicted depth and histopathologically measured depth. Therefore, RCM-OCT imaging may be prospectively used to comprehensively diagnose suspicious BCC lesions, determine subtype and triage for treatment.
We demonstrate optical biopsy of vocal folds to assess its surface and subsurface movement during phonation on ex-vivo calf larynx using parallel OCT (POCT). In this technique, we will enable simultaneous interrogation of multiple locations along the vocal fold, there by eliminating motion-blur artifacts exhibited by the sequential sampling provided by conventional flying-spot OCT. Currently, in voice clinics, laryngologists and speech-language pathologists rely heavily on Video Stroboscopy (VS) coupling with, visual judgments of vocal fold morphology and auditory perceptions of voice quality, to make effective diagnostic, surgical and therapeutic decisions. There is a constant need of an endoscopic imaging tool in voice clinics that can directly capture the three-dimensional (3D) surface motion of the vocal folds in real time as patients phonate. To address the need, we will present a POCT/VS imager that will combine parallel swept source OCT technique with VS to provide a real time display of the vocal folds in all three axial dimensions during phonation. The results will yield cross sections (B-Scans) with ~16 co-linear sampling locations spread over ~5mm on a phonating ex-vivo calf larynx showing fluid periodic cyclic motion of the vocal folds (~A-scan rate) in real time enabled by POCT approach. We will also capture VS images in sync with POCT B-scans validating the real time cross sectional probing of POCT/VS imager.
In this paper, we summarize our recent advances in the development and pre-clinical testing of the 2-nd generation OCT-based probe for core needle biopsy guidance. The acquired OCT images are processed in real-time in a GPU unit to provide the interventional radiologist with the capability to examine the tissue cellularity at the tip of the biopsy needle before deciding to take a biopsy core. The extensive testing of this technology on a rabbit model of soft tissue cancer is discussed in detail. The pre-clinical results demonstrate the capability of this OCT-based probe for determining the in situ cellularity of the tissue at the tip of the biopsy needle and thus its potential use for improving the quality of the sampled biopsy cores.
In this paper we summarize our recent advances in the development of a combined optical coherence tomography (OCT)/ reflectance confocal microscopy (RCM) approach for diagnosing non-melanoma skin cancers and guiding laser ablation therapy. After developing and clinically demonstrating a hand-held probe [1], our current focus is in adding the capability for generating rapid mosaic images of large areas of the skin (~15 mm x 15mm), as well as on developing a post-processing software that allows for rapid 3-D rendering of the collected data. We are also developing an automated segmentation algorithm that might be used to more objectively assess the depth of the non-melanoma tumors. With these capabilities, our integrated RCM and OCT imaging approach will provide 3-D microscopic views in orthogonally oriented and enfaceoriented planes with a range of resolutions and fields of view, which should further advance optical imaging to noninvasively guide both diagnosis as well as therapy of non-melanoma skin cancers.
[1]. N. Iftimia et al., Handheld optical coherence tomography–reflectance confocal microscopy probe for detection of basal cell carcinoma and delineation of margins. J. Biomed. Opt. 22(7), 076006
KEYWORDS: Optical coherence tomography, Reflectivity, Confocal microscopy, Skin, Tumors, In vivo imaging, Spectroscopy, 3D image processing, 3D displays
We present a hand-held implementation and preliminary evaluation of a combined optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) probe for detecting and delineating the margins of basal cell carcinomas (BCCs) in human skin in vivo. A standard OCT approach (spectrometer-based) with a central wavelength of 1310 nm and 0.11 numerical aperture (NA) was combined with a standard RCM approach (830-nm wavelength and 0.9 NA) into a common path hand-held probe. Cross-sectional OCT images and enface RCM images are simultaneously displayed, allowing for three-dimensional microscopic assessment of tumor morphology in real time. Depending on the subtype and depth of the BCC tumor and surrounding skin conditions, OCT and RCM imaging are able to complement each other, the strengths of each helping overcome the limitations of the other. Four representative cases are summarized, out of the 15 investigated in a preliminary pilot study, demonstrating how OCT and RCM imaging may be synergistically combined to more accurately detect BCCs and more completely delineate margins. Our preliminary results highlight the potential benefits of combining the two technologies within a single probe to potentially guide diagnosis as well as treatment of BCCs.
A novel multimodal optical imaging approach for real-time assessment of surgical margins on breast cancer lumpectomy specimens is presented. Our approach is to target cancer cells using an optically silent peptide substrate containing two (NIR) fluorochromes, internally quenched, which are cleaved by highly expressed breast cancer enzymes, like urokinase-type plasminogen activator (uPA). Thus this agent becomes highly fluorescent only on the cancer area when the specimen is excited by a NIR laser beam. A fluorescence imager is used to highlight cancer-suspect margins on the surgical specimen, while high-resolution optical coherence tomography (OCT) imaging is used to visualize tissue morphology on the highlighted areas and confirm or rule out cancer presence. This technology will hopefully increase the success rate of cancer surgeries, reduce the risk of cancer recurrence and significantly reduce US healthcare costs.
Sensorineural hearing loss (SNHL), which typically originates in the cochlea, is the most common otologic problem caused by aging and noise trauma. The cochlea, a delicate and complex biological mechanosensory transducer in the inner ear, has been extensively studied with the goal of improving diagnosis of SNHL. However, the difficulty associated with accessing the cochlea and resolving the microstructures that facilitate hearing within it in a minimally-invasive way has prevented us from being able to assess the pathology underlying SNHL in humans. To address this problem we investigated the ability of a multimodal optical system that combines optical coherence tomography (OCT) and single photon autofluorescence imaging (AFI) to enable visualization and evaluation of microstructures in the cochlea. A laboratory OCT/AFI imager was built to acquire high resolution OCT and single photon fluorescence images of the cochlea. The imager’s ability to resolve diagnostically-relevant details was evaluated in ears extracted from normal and noise-exposed mice. A prototype endoscopic OCT/AFI imager was developed based on a double-clad fiber approach. Our measurements show that the multimodal OCT/AFI imager can be used to evaluate structural integrity in the mouse cochlea. Therefore, we believe that this technology is promising as a potential clinical evaluation tool, and as a technique for guiding otologic surgeries such as cochlear implant surgery.
We present a novel method, based on encoder mapping OCT imaging, for real-time guidance of core biopsy procedures. This method provides real-time feedback to the interventional radiologist, such that he/she can reorient the needle during the biopsy and sample the most representative area of the suspicious mass that is being investigated. This aspect is very important for tailoring therapy to the specific cancer based on biomarker analysis, which will become one of the next big advances in our search for the optimal cancer therapy. To enable individualized treatment, the genetic constitution and the DNA repair status in the affected areas is needed for each patient. Thus, representative sampling of the tumor is needed for analyzing various biomarkers, which are used as a tool to personalize cancer therapy. The encoder-based OCT enables samping of large size masses and provides full control on the imaging probe, which is passed through the bore of the biopsy guidance needle. The OCT image is built gradually, based on the feedback of an optical encoder which senses the incremental movement of the needle with a few microns resolution. Tissue mapping is independent of the needle speed, while it is advanced through the tissue. The OCT frame is analyzed in real-time and tissue cellularity is reported in a very simple manner (pie chart). Our preliminary study on a rabbit model of cancer has demonstrated the capability of this technology for accurately differentiating between viable cancer and heterogeneous or necrotic tissue.
The use of a Prosthetic Replacement of the Ocular Surface Environment (PROSE) device is a revolutionary treatment for military patients that have lost their eyelids due to 3rd degree facial burns and for civilians who suffer from a host of corneal diseases. However, custom manual fitting is often a protracted painful, inexact process that requires multiple fitting sessions. Training for new practitioners is a long process. Automated methods to measure the complete corneal and scleral topology would provide a valuable tool for both clinicians and PROSE device manufacturers and would help streamline the fitting process.
PSI has developed an ocular anterior-segment profiler based on Optical Coherence Tomography (OCT), which provides a 3D measure of the surface of the sclera and cornea. This device will provide topography data that will be used to expedite and improve the fabrication process for PROSE devices. OCT has been used to image portions of the cornea and sclera and to measure surface topology for smaller contact lenses [1-3]. However, current state-of-the-art anterior eye OCT systems can only scan about 16 mm of the eye’s anterior surface, which is not sufficient for covering the sclera around the cornea. In addition, there is no systematic method for scanning and aligning/stitching the full scleral/corneal surface and commercial segmentation software is not optimized for the PROSE application.
Although preliminary, our results demonstrate the capability of PSI’s approach to generate accurate surface plots over relatively large areas of the eye, which is not currently possible with any other existing platform. Testing the technology on human volunteers is currently underway at Boston Foundation for Sight.
We present a combined reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) approach, integrated within a single optical layout, for diagnosis of basal cell carcinomas (BCCs) and delineation of margins. While RCM imaging detects BCC presence (diagnoses) and its lateral spreading (margins) with measured resolution of ∼1 μm, OCT imaging delineates BCC depth spreading (margins) with resolution of ∼7 μm. When delineating margins in 20 specimens of superficial and nodular BCCs, depth could be reliably determined down to ∼600 μm, and agreement with histology was within about ±50 μm.
KEYWORDS: Birefringence, Control systems, Skin, In vivo imaging, Injuries, Optical coherence tomography, Tissues, 3D image processing, Video, Polarization
The accurate determination of burn depth is critical in the clinical management of burn wounds. Polarization-sensitive optical coherence tomography (PS-OCT) has been proposed as a potentially non-invasive method for determining burn depth by measuring thermally induced changes in the structure and birefringence of skin, and has been investigated in pre-clinical burn studies with animal models and ex vivo human skin. In this study, we applied PS-OCT to the in-vivo imaging of two pediatric burn patients. Deep and superficial burned skins along with contralateral controls were imaged in 3D. The imaging size was 8 mm × 6 mm × 2 mm in width, length, and depth in the air respectively, and the imaging time was approximately 6 s per volume. Superficially burned skins exhibited the same layered structure as the contralateral controls, but more visible vasculature and reduced birefringence compared to the contralateral controls. In contrast, a deeply burned skin showed loss of the layered structure, almost absent vasculature, and smaller birefringence compared to superficial burns. This study suggested the vasculature and birefringence as parameters for characterizing burn wounds.
Micromirrors used to steer optical beams at the tip of an endoscope are an active area of research. MEMS mirrors with
various actuation mechanisms have been reported including rotating micromotors, parallel plate electrostatic drive,
electrothermal and electrostatic comb drive. This paper presents a two-axis magnetically actuated micromirror designed
for an OCT (Optical Coherence Tomography) endoscope. Magnetic actuation allows large angular deflections at low
voltage (1-3 V), a significant advantage for patient safety relative to the high voltages used for electrostatic mirrors.
Actuation is accomplished with small coils in proximity to the moving mirror, which contains a small permanent
magnet. The endoscope scan engine is contained in a 2.8 mm ID plastic tube. The MEMS scan mirror was fabricated by
a simple process using an SOI wafer and only 2 photo-steps. The mirror is supported by silicon springs on both axes,
and can scan to +/- 20 degrees mechanical on both axes. Both time domain and spectral domain OCT have been used to
take cross-sectional tissue images. By operating the 2-axis mirror in a raster scan, a sequence of cross-sections is taken
to form a 3-D image. Details of the endoscope design, MEMS fabrication, and sample OCT images are presented.
Optoacoustic systems making use of optical detection probes are potentially advantageous over contact transducers for noncontact, noninvasive high-resolution near surface imaging applications. In this work, an interferometer is used for high-frequency optoacoustic microscopy. The limitations of this system in terms of both sensitivity and resolution are discussed. A theoretical model has been developed for two-dimensional excitation source geometries, which can be used to predict the optoacoustic signal from a target material with an arbitrary through-thickness optical absorption distribution. The model incorporates the temporal and spatial profile of the excitation laser pulse, and is used to predict the actual out-of-plane displacement at the target surface. An adaptive, photorefractive crystal-based interferometry system has been used to measure the optically induced displacement on the surface of target materials, and the results show reasonable quantitative agreement with theory. The detection system has a 200 MHz bandwidth allowing for high-resolution imaging, and the use of optical probes for both generation and detection allows for the probes to be easily co-aligned on the sample surface. Preliminary experimental results are presented demonstrating the feasibility of using all-optical optoacoustic microscopy for near surface imaging of small-scale spatial variations in optical absorption.
Acousto-photonic imaging (API) is a dual-wave sensing technique in which a diffusive photon wave in a turbid medium interacts with an imposed acoustic field that drives scatterers to coherent periodic motion. A phase-modulated photon field emanates from the interaction region and carries with it information about the local opto-mechanical properties of the insonated media. A technological barrier to API has been sensitivity - the flux of phase-modulated photons is very small and the incoherence of the resulting speckle pattern reduces the modulation of the scattered light leading to low sensitivity. We report preliminary results from a new detection scheme in which a photorefractive crystal is used to mix the diffusively scattered laser light with a reference beam. The crystal serves as a dynamic holographic medium where the signal beam interferes with the reference beam, creating a photorefractive grating from which beams diffract. In addition, the phase modulation is converted to an amplitude modulation so that the API signal can be detected. Measurements of the API signal are presented for gel phantoms with polystyrene beads used as scatterers, showing a qualitative agreement with a simple theoretical model developed.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.