A fiber-optic 3D shape, position and temperature sensor is demonstrated with femtosecond laser direct-written optical and Bragg grating waveguides that were distributed axially and radially inside a single coreless optical fiber. Efficient light coupling between the laser-written optical circuit elements and a standard single-mode optical fiber was obtained by 3D laser writing of a 1 × 3 directional coupler and fusion splicing. Coupler optimization by real-time monitoring of Bragg grating strengths is discussed. Simultaneous interrogation of nine Bragg gratings is presented through a single waveguide port to follow the Bragg wavelength shifts and thereby infer shape and temperature profile along the fiber length.
Several therapies make use of a hypo or hyperthermia tissue environment to induce cell death in both benign and
malignant tumors. Current progression in optical technologies, such as optical coherence tomography (OCT) and fiber
Bragg gratings (FBG) sensors, could potentially provide viable information to explore the response of tissue when these
temperature induced treatments are implemented. Studies were conducted with tissue-mimicking phantoms fabricated
with polystyrene microspheres and glycerin to observe any relationship between the pixel intensities of the OCT images
and their concurring envelope statistics. OCT images of the monitored region of interest were taken at 5°C intervals from
25°C to 60°C. Four probability distribution functions (PDF), Rician, Rayleigh, Normal and Generalized Gamma were
used to investigate OCT envelope statistics as the temperature was altered. Using the Kolmogrov-Smirnov goodness of
fit test, it was determined that the Generalized Gamma was the best fit. The scaling and shape parameters associated with
the Generalized Gamma PDF were used to quantify the OCT envelope data to identify temperature changes within the
tissue mimicking media. The Generalized Gamma PDF was verified as the best fit based on the Kolmogorov-Smirnov
(K-S) test correlation factor being less than 0.05 (p = 0.0158). In addition to the PDFs, the OCT speckle decorrelation at
varying temperature were also measured and quantified to detect the microspheres response to temperature changes.
Initial results are very promising with future research focused on extending this methodology to monitor relative
temperature changes in tissue during therapy. Clinical utility can be achieved if these optical techniques are used to
evaluate the temperature-derived biological response of tissue and provide a feedback mechanism to improve procedural
efficiency.
Optical coherence elastography (OCE) provides deformation or material properties, mapping of soft tissue. We aim to develop a robust speckle tracking OCE technique with improved resolution and accuracy. A digital image correlation (DIC)-based OCE technique was developed by combining an advanced DIC algorithm with optical coherence tomography (OCT). System calibration and measurement error evaluation demonstrated that this DIC-based OCE technique had a resolution of ∼0.6 μm displacement and <0.5% strain measurement in the axial scan direction. The measured displacement ranged from 0.6 to 150 μm, obtained via phantom imaging. The capability of the DIC-based OCE technique, for differentiation of stiffness, was evaluated by imaging a candle gel phantom with an irregularly shaped stiff inclusion. OCE imaging of a chicken breast sample differentiated the fat, membrane, and muscle layers. Strain elastograms of an aneurysm sample showed heterogeneity of the tissue and clear contrast between the adventitia and media. These promising results demonstrated the capability of the DIC-based OCE for the characterization of the various components of the tissue sample. Further improvement of the system will be conducted to make this OCE technique a practical tool for measuring and differentiating material properties of soft tissue.
There exist a multitude of therapeutic options for the treatment of both benign and malignant tumors, where several of
these options induce temperature changes in the tissue from several degrees centigrade to temperatures that ablate the
region of interest (ROI). Recent advances in optical imaging technologies, namely optical coherence tomography (OCT)
and Fiber Bragg Gratings (FBG), may provide the necessary hardware/software components to both monitor and
quantify the direct biological response to temperature-mediated cancer therapies. Preliminary research has been
conducted to identify and analyze the trends in temperature measurements from FBG's placed within phantoms that
mimic the optical characteristics of human tissue. Shifts of the Bragg wavelength at selected temperature intervals depict
the temperature of the phantom relative to room temperature. The scattering properties of tissue were achieved in the
phantom by using 0.665 g of titanium dioxide (TiO2 - Titanium (IV) oxide, anatase) nanopowder, with a particle size
smaller than 25 nm, which was mixed into 475 mL of Penecro’s Versagel (hydrocarbon material). This mixture imitates
the tissue’s index of refraction of ~1.4. Shifts in the Bragg wavelength were measured using a spectrum analyzer at
temperature intervals at approximately 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C and 60°C. The results show that the
relative Bragg wavelength is directly proportional to any increase or decrease of temperature in the phantom. In the case
of these experiments, it was observed that the change in the bragg wavelength shift increased the phantom’s temperature
was also increased with respect to the temperature set by the hot plate. The FBG regions that monitored temperature
variations within the tissue-mimicking phantoms were also imaged, via OCT, to investigate temperature induced changes
in the OCT images including investigation of changes in the OCT envelope statistics. This data may provide the base
line to detect changes in the biological response to temperature variations, based solely on OCT images, and ultimately
provide suitable imaging metric(s) to predict therapeutic outcome.
Blood flow velocity and volumetric flow measurements are important parameters for assessment of the severity of stenosis and the outcome of interventional therapy. However, feasibility of intravascular flow measurement using a rotational catheter based phase resolved Doppler optical coherence tomography (DOCT) is difficult. Motion artefacts induced by the rotating optical imaging catheter, and the radially dependent noise background of measured Doppler signals are the main challenges encountered. In this study, a custom-made data acquisition system and developed algorithms to remove non-uniform rotational distortion (NURD) induced phase shift artefact by tracking the phase shift observed on catheter sheath. The flow velocity is calculated from Doppler shift obtained by Kasai autocorrelation after motion artefact removal. Blood flow velocity profiles in porcine carotid arteries in vivo were obtained at 100 frames/s with 500 A-lines/frame and DOCT images were taken at 20 frames/s with 2500 A-lines/frame. Time-varying velocity profiles were obtained at an artery branch. Furthermore, the identification of a vein adjacent to the catheterized vessel based on the color Doppler signal was also observed. The absolute measurement of intravascular flow using a rotating fiber catheter can provide insights to different stages of interventional treatment of stenosis in carotid artery.
Precision depth control of bone resection is necessary for safe surgical procedures in the spine. In this paper, we compare the control and quality of cutting bovine tail bone, as an ex vivo model of laminectomy and bony resection simulating spinal surgery, planned with micro-CT data and executed using two approaches: (a) mechanical milling guided by optical topographical imaging (OTI) and (b) optical milling using closed-loop inline coherent imaging (ICI) to monitor and control the incision depth of a high-power 1070 nm fiber laser in situ. OTI provides the in situ topology of the 2-dimensional surface of the bone orientation in the mechanical mill which is registered with the treatment plan derived from the micro-CT data. The coregistration allows the plan to be programmed into the mill which is then used as a benchmark of current surgical techniques. For laser cutting, 3D optical land marking with coaxial camera vision and the ICI system is used to coregister the treatment plan. The unstable, carbonization-mediated ablation behaviour of 1070 nm light and the unknown initial geometry of bone leads to unpredictable ablation which substantially limits the depth accuracy of open-loop cutting. However, even with such a non-ideal cutting laser, we demonstrate that ICI provides in situ high-speed feedback that automatically and accurately limits the laser’s cut depth to effectively create an all-optical analogue to the mechanical mill.
KEYWORDS: Arteries, Optical coherence tomography, Image resolution, 3D image processing, Imaging systems, Data visualization, Visualization, Blood, 3D vision, Medical imaging
Carotid angioplasty and stenting is a minimally invasive endovascular procedure that may benefit from in vivo high resolution imaging for monitoring the physical placement of the stent and potential complications. The purpose of this pilot study was to evaluate the ability of optical coherence tomography to construct high resolution 2D and 3D images of stenting in porcine carotid artery. Four Yorkshire pigs were anaesthetized and catheterized. A state-of-the-art optical coherence tomography (OCT) system and an automated injector were used to obtain both healthy and stented porcine carotid artery images. Data obtained were then processed for visualization. The state-of-the-art OCT system was able to capture high resolution images of both healthy and stented carotid arteries. High quality 3D images of healthy and stented carotid arteries were constructed, clearly depicting vessel wall morphological features, stent apposition and thrombus formation over the inserted stent. The results demonstrate that OCT can be used to generate high quality 3D images of carotid arterial stents for accurate diagnosis of stent apposition and complications under appropriate imaging conditions.
Rupture of intracranial aneurysm is a common cause of subarachnoid hemorrhage. An aneurysm may undergo
microscopic morphological changes or remodeling of the vessel wall prior to rupture, which could potentially be
imaged. In this study we present methods of tissue sample preparation of intracranial aneurysms and correlation
between optical coherence tomography imaging and routine histology. OCT has a potential future in the
assessment of microscopic features of aneurysms, which may correlate to the risk of rupture.
Kyle H. Cheng, Cuiru Sun, Juan Cruz, Thomas Marotta, Julian Spears, Walter Montanera, Peter Herman, Aman Thind, Brian Courtney, Beau Standish, Victor X. Yang
KEYWORDS: Arteries, Optical coherence tomography, Imaging systems, 3D image processing, Visualization, Blood, Image resolution, Medical imaging, 3D vision, In vivo imaging
Carotid Artery Stenting (CAS) is a procedure that treats carotid atherosclerosis which should be monitored by in vivo
high resolution imaging for the quality of the procedure and potential complications. The purpose of this pilot study is to
evaluate the ability of optical coherence tomography to construct high resolution two and three dimensional images of
stenting in porcine carotid artery for high accuracy diagnostic purposes. Four Yorkshire pigs were anaesthetized and
catheterized. A state-of-the-art optical coherence tomography (OCT) system (Lightlab Imaging, St. Jude Medical Inc.)
and an automated injector were used to obtain both healthy and stented porcine carotid artery images. Data obtained
were then processed for visualization. The state-of-the-art OCT system was able to capture high resolution images of
both healthy and stented carotid arteries. High quality three dimensional images of stented carotid arteries were
constructed, clearly depicting stent apposition and thrombus formation over different stents. The results demonstrated
that current state-of-the-art OCT system can be used to generate high quality three dimensional images of carotid arterial
stents for accurate diagnosis of stent apposition and complications under appropriate imaging conditions.
A prototype neurosurgical hand-held optical coherence tomography (OCT) imaging probe has been developed to provide
micron resolution cross-sectional images of subsurface tissue during open surgery. This new ergonomic hand-held probe
has been designed based on our group's previous work on electrostatically driven optical fibers. It has been packaged
into a catheter probe in the familiar form factor of the clinically accepted Bayonet shaped neurosurgical non-imaging
Doppler ultrasound probes. The optical design was optimized using ZEMAX simulation. Optical properties of the probe
were tested to yield an ~20 um spot size, 5 mm working distance and a 3.5 mm field of view. The scan frequency can be
increased or decreased by changing the applied voltage. Typically a scan frequency of less than 60Hz is chosen to keep
the applied voltage to less than 2000V. The axial resolution of the probe was ~15 um (in air) as determined by the OCT
system. A custom-triggering methodology has been developed to provide continuous stable imaging, which is crucial for
clinical utility. Feasibility of this probe, in combination with a 1310 nm swept source OCT system was tested and images
are presented to highlight the usefulness of such a forward viewing handheld OCT imaging probe. Knowledge gained
from this research will lay the foundation for developing new OCT technologies for endovascular management of
cerebral aneurysms and transsphenoidal neuroendoscopic treatment of pituitary tumors.
Optical coherence tomography (OCT) has several advantages over other imaging modalities, such as angiography and ultrasound, due to its inherently high in vivo resolution, which allows for the identification of morphological tissue structures. Optical coherence elastography (OCE) benefits from the superior spatial resolution of OCT and has promising applications, including cancer diagnosis and the detailed characterization of arterial wall biomechanics, both of which are based on the elastic properties of the tissue under investigation. We present OCE principles based on techniques associated with static and dynamic tissue excitation, and their corresponding elastogram image-reconstruction algorithms are reviewed. OCE techniques, including the development of intravascular- or catheter-based OCE, are in their early stages of development but show great promise for surgical oncology or intravascular cardiology applications.
Multichannel optical coherence tomography (MOCT) imaging is demonstrated using a high-power wavelength-swept
laser source. The main benefit of MOCT is faster image acquisition rates without a corresponding increase in the laser
tuning speed. The wavelength-swept laser was constructed using a compact telescope-less polygon-based filter in
Littman arrangement. High output power, necessary for MOCT, was achieved by incorporating two serial
semiconductor optical amplifiers in a ring laser cavity in Fourier domain mode-locked configuration. The laser has a
measured wavelength tuning range of 111 nm centered at 1329 nm, coherence length of 5.5 mm, and total average
output power of 131 mW at 43 kHz sweeping rate. Using this laser, a six-channel imaging system was constructed. The
imaging arm consisted of a multi-fiber push-on connector mounted on a galvanometer-based scanner. All channels,
spaced 250 μm apart, were focused at the same depth. Six-channel OCT imaging to achieve 258 kHz scan rate is
demonstrated. The increase in effective frame rate using multichannel acquisition may be beneficial for 3-dimensional
in-vivo imaging where bulk tissue motion can adversely affect the image quality.
To our knowledge, we report the first Fourier domain modelocked laser (FDML) constructed using optical parameter
amplifier (OPA) in conjunction with an erbium-doped fiber amplifier (EDFA), centered at ~1556nm. We utilized a onepump
OPA and a C-band EDFA in a series configuration with a polygon-grating wavelength filter to generate a hybrid
FDML spectrum. Results demonstrate a substantially higher output power, better spectral shape and significantly more
stable bandwidth than individual configurations. We believe this technique has the potential to enable several amplifiers
to complement individual deficiencies resulting in improved spectral shapes and power generation for imaging
applications such as optical coherence tomography (OCT).
In this study, a cascaded Raman fiber laser in Fourier domain mode lock operation (FDML) is presented. This
laser utilizes a Ytterbium doped twin core pump laser source at 1109 nm. The pump light is directed to a
cascaded Raman cavity, which consists of multiple cascaded fiber Bragg grating pairs and 3.86 km of dispersion
compensation fiber, which provides Raman gain. The output wavelength of a cascaded Raman laser is determined
by the Stoke's shift (≈ 60 to 70 nm in optical fiber) and the pump laser wavelength. The power build up in the
cascaded Raman cavity and shift to higher Stoke's orders produce multiple spectral peaks. At higher Stoke's
orders, the overlapping Raman peaks create broad bandwidth gain with relatively large gain ripples. FDML
operation using a polygon-based tunable filter helps to suppress the ripples. The overall laser in linear operation
has a bandwidth of 316 nm with a center wavelength of 1445 nm. An output optical power was measured to be
(> 10 mW). On the other hand, the sweeping bandwidth was 35 nm with an output power in the micro-watt
range. The utilization of broadband tunable lasers are important in applications such as swept-source optical
coherence tomography for use in biomedical imaging.
We demonstrate high efficiency and wide bandwidth gain in a Ytterbium doped fiber amplifier. The highpowered
amplifier has potential applications for use with a swept-source fiber ring laser in multi-channel optical
coherence tomography (OCT) system. The ring cavity design includes a 976nm pumped dual core Yb doped fiber as the
gain medium, where a rotating polygon mirror is used as a wavelength-sweeping filter for this source. The amplified
spontaneous emission (ASE) had a spectral bandwidth of 1037-1145nm at -60dBm, where a tunable lasing bandwidth of
the ring cavity ranged from 1057-1115nm. The highest output power, for both the ASE and lasing spectrum, with this
configuration was ~200mW, however it is possible to have a larger bandwidth and a larger output power. Higher power,
in the wattage range is achievable if free space components are employed. Pumped with 976nm light at 1.27W, the use
of this novel dual core Yb doped fiber as an amplifier has been successfully demonstrated, as it provided a small signal
gain of 29.6 dB at 1085nm, where the gain medium was successfully saturated during operation. This is important for the
spectral shaping requirements of OCT to improve image quality. The gain was demonstrated for several different
wavelengths and for several pumping powers at a 1085nm wavelength. Fourier domain mode locked operation (FDML)
was achieved with a bandwidth of 15nm and a sweep rate of 51.4kHz. This laser source offers a low-cost, high power
alternative for biomedical imaging with multi-channel optical coherence tomography.
We demonstrate the potential of a forward-looking Doppler optical coherence tomography (OCT) probe for color flow imaging in several commonly seen narrowed artery morphologies. As a proof of concept, we present imaging results of a surgically exposed thrombotic occlusion model that was imaged superficially to demonstrate that Doppler OCT can identify flow within the recanalization channels of a blocked artery. We present Doppler OCT images in which the flow is nearly antiparallel to the imaging direction. These images are acquired using a flexible 2.2-mm-diam catheter that used electrostatic actuation to scan up to 30 deg ahead of the distal end. Doppler OCT images of physiologically relevant flow phantoms consisting of small channels and tapered entrance geometries are demonstrated.
We measure the tumor vascular response to varying irradiance rates during photodynamic therapy (PDT) in a Dunning rat prostate model with interstitial Doppler optical coherence tomography (IS-DOCT). Rats are given a photosensitizer drug, Photofrin, and the tumors are exposed to light (635 nm) with irradiance rates ranging from 8 to 133 mW/cm2 for 25 min, corresponding to total irradiance of 12 to 200 J/cm2 (measured at surface). The vascular index computed from IS-DOCT results shows the irradiance rate and total irradiance dependent microvascular shutdown in the tumor tissue during PDT. While faster rates of vascular shutdown were associated with increasing PDT irradiance rate and total irradiance, a threshold effect was observed as irradiance rates above 66 mW/cm2 (surface), where no further increase in vascular shutdown rate was detected. The maximum post-treatment vascular shutdown (81%) without immediate microcirculatory recovery was reached with the PDT condition of 33 mW/cm2 and 50 J/cm2. Control groups without Photofrin show no significant microvascular changes. Microvascular shutdown occurs at different rates and shows correlation with PDT total irradiance and irradiance rates. These dependencies may play an important role in PDT treatment planning, feedback control for treatment optimization, and post-treatment assessment.
Microcirculatory changes, such as vascular shutdown, may be a predictor to the therapeutic efficacy of
photodynamic therapy (PDT). The aim of this study was to measure the tumour vascular response to varying irradiance
rates during PDT deep within prostate tumour xenograft, via interstitial Doppler optical coherence tomography
(DOCT).
DOCT provides micron-scale spatial resolution allowing visualization of structures at near histological levels,
and yields flow velocity resolution of ~20 μm/s. Current in vivo DOCT imaging probes are limited to intraluminal and
near-surface sites. To improve the accessibility of DOCT to anatomically relevant sites deep within the body (e.g.,
prostate), an interstitial (IS) needle (~700μm diameter) probe was developed for minimally invasive monitoring of the
microvascular response to PDT (irradiance administered superficially) within tumour tissue. Rats were given a
photosensitizer drug, Photofrin, and 20-24 h later the tumours were exposed to light (635nm) with an irradiance rate of
8-133 mW/cm2 for 25 minutes to a total irradiance of 12-200 J/cm2. Results illustrated different rates of vascular
shutdown within the tumour as imaged by IS-DOCT, related to the administered PDT irradiance rate and total
irradiance. Controls (probe only, probe + light) showed no significant microvascular changes.
IS-DOCT was able to detect and monitor microvascular changes during PDT. Microvascular shutdown
occurred at different rates and showed correlation with PDT light dose and irradiance rate. These dependencies may
play an important role in PDT treatment planning, feedback control for treatment optimization, and post treatment
assessment.
Time domain Doppler optical coherence tomography (DOCT) is a promising non-invasive imaging system with high spatial (~20μm) and velocity resolution (~20μm/s) that can image microvascular blood flow. It is important to understand and account for the complicated 3D nature of small blood vessels. To address this problem, two realistic flow phantoms were designed with known geometries -- an occluded flow path to model vessel narrowing, and a Y-bifurcation to simulate vessel branching. The current DOCT system produces 2D images, which when stacked sequentially can yield 3D images of microstructure and perfusion-level blood flow. 3D reconstructions allow the investigation of internal flow profiles, including an abrupt stenosis in the occluded phantom. This research will help guide our image interpretation of in-vivo DOCT studies, including treatment response monitoring in animal tumours and endoscopic assessment of the human GI tract.
Chronic total occlusions (CTOs) are defined as complete occlusions of an artery older than one month. Minimally invasive catheter-based interventions commonly employed for partial occlusions (e.g., balloon angioplasty followed by stenting) are problematic in CTOs because of the phycisian's inability to pass the device through the occlusion without a significant risk of arterial wall perforations. Furthermore, successfully treated CTOs exhibit a high re-occlusion rate. As a result, these cases are mostly sent to bypass surgery. With the advent of drug-eluting stents that reduce the incidence of re-occlusion, and thus, eliminating the second problem, new devices have begun to emerge that aim to recanalize CTOs without the cost and trauma of bypass surgery. These devices, however, need effective image guidance methods to ensure successful crossing of the CTOs.
Optical coherence tomography (OCT) is being evaluated as an intravascular imaging modality for guiding catheter-based interventions of CTOs. Occluded ex vivo human arterial samples were used to produce longitudinal cross-sections using an OCT system. These OCT images were compared with histology to assess OCT's ability to identify different components of the occluded artery, evaluate the imaging depth, and determine the ability to detect the underlying vessel wall.
Given the inherent difficulties of creating a mechanically scanning OCT probe in the distal tip of a catheter for use in a stenotic artery, we directed our initial efforts towards developing a "motionless" fiber based OCT system using a single mode fiber array. We discuss design considerations for implementing a forward viewing intravascular OCT probe.
Doppler optical coherence tomography (OCT) can image tissue structure and blood flow at micrometer-scale resolution, with limited imaging penetration depth. We report a novel linear-scanning needle-based Doppler OCT system using angle-polished gradient-index or ball-lensed fibers. A prototype system using a 19-guage (diameter ~0.9 mm) echo-genic needle is constructed and demonstrates in vivo imaging of bidirectional blood flow in rat leg and abdominal cavity. To our knowledge this is the first demonstration of Doppler OCT through a needle probe in interstitial applications to visualize deeply situated microcirculation.
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