A forward-imaging needle-type optical coherence tomography (OCT) probe with Doppler OCT (DOCT) capability has the potential to solve critical challenges in interventional procedures. A case in point is stereotactic neurosurgery where probes are advanced into the brain based on predetermined coordinates. Laceration of blood vessels in front of the advancing probe is an unavoidable complication with current methods. Moreover, cerebrospinal fluid (CSF) leakage during surgery can shift the brain rendering the predetermined coordinates unreliable. In order to address these challenges, we developed a forward-imaging OCT probe (740 μm O.D.) using a gradient-index (GRIN) rod lens that can provide real-time imaging feedback for avoiding at-risk vessels (8 frames/s with 1024 A-scans per frame for OCT/DOCT dual imaging) and guiding the instrument to specific targets with 12 μm axial resolution (100 frames/s with 160 A-scans per frame for OCT imaging only). The high signal-to-background characteristic of DOCT provides exceptional sensitivity in detecting and quantifying the blood flow within the sheep brain parenchyma in real time. The OCT/DOCT dual imaging also demonstrated its capability to differentiate the vessel type (artery/vein) on rat's femoral vessels. We also demonstrated in ex vivo human brain that the location of the tip of the OCT probe can be inferred from micro-anatomical landmarks in OCT images. These findings demonstrate the suitability of OCT guidance during stereotactic procedures in the brain and its potential for reducing the risk of cerebral hemorrhage.

We have designed, developed, and evaluated the performance of a multi-degree-of-freedom discretely actuated steerable cannula with shape memory alloy (SMA)actuators. This will enable us to deliver diagnostic as well as therapeutic devices to the target location through the hollow inner core of the cannula. We propose to use SMAs to generate bending forces due to its small size and high power density. We annealed the SMA wires through a customized training process in arc shape and mounted them at discrete locations on the outer surface of the cannula to enable joint motion. A pulse width modulation(PWM)-based control scheme was implemented to control all SMA actuators simultaneously to enable multiple joint motion using a single power supply. The proposed controller was validated through an experiment inside gelatin to mimic the motion of the cannula inside a medium which requires a significant amount of force to move the joints of the cannula. Trajectory planning using a suitable metric and trajectory execution were successfully implemented. To demonstrate the delivery of a diagnostic tool through our cannula, we demonstrate that we can pass an optical coherence tomography probe through the cannula and perform in situ micro-scale imaging.

Optical coherence tomography (OCT) is an attractive medical modality due to its ability to acquire high-resolution, cross-sectional images inside the body using flexible, small-diameter, scanning fiber optic probes. Conventional, cross-sectional OCT imaging technologies have approximately 10-μm axial resolution and 30-μm lateral resolution, specifications that enable the visualization of microscopic architectural morphology. While this resolution is useful for many clinical applications, it is insufficient for resolving individual cells that characterize many diseases. To address this gap, a supercontinuum-laser-based, μm-resolution OCT (μOCT) system and a 500 μm-diameter, extended depth of focus single fiber optic probe for endoscopic and intravascular imaging were designed and fabricated. At the distal tip of the fiber optic probe, a cylindrical waveguide was used to divide the wavefront to provide multiple circular propagation modes. Once transmitted through a relatively high NA lens (NA >0.1), these modes were projected as multiple coaxial foci (~3 μm full width at half maximum (FWHM)) over a greatly extended focal depth range. The distal tip of the probe also contained a common-path reference reflectance to minimize polarization and dispersion imbalances between sample and reference arm light. Measurements showed that the probe provides a 20-fold depth of focus extension, maintaining a 3-5 µm lateral resolution (FWHM of PSF) and a 2 μm axial resolution over a depth range of approximately 1 mm. These results suggest that this new optical configuration will be useful for achieving high-resolution, cross-sectional OCT imaging in catheter/endoscope-based medical imaging devices.

We present a simple but effective method to quantitatively measure the birefringence of tissue by an all single-mode fiber (SMF) based polarization-sensitive optical coherence tomography (PS-OCT) with single input polarization state. We theoretically verify that our SMF based PS-OCT system can quantify the phase retardance and optic axis orientation after a simple calibration process using a quarter wave plate (QWP). Based on the proposed method, the quantification of the phase retardance and optic axis orientation of a Berek polarization compensator and biological tissues were demonstrated.

Abstract. Photoimmunotherapy (PIT) is a cell-specific cancer therapy based on an armed antibody conjugate that induces rapid and highly selective cancer cell necrosis after exposure to near-infrared (NIR) light. The PIT treatment also induces the superenhanced permeability and retention effect, which allows high concentrations of nanoparticles to accumulate in the tumor bed. In our pilot studies, optical coherence tomography (OCT) reveals dramatic hemodynamic changes during PIT. We developed and applied speckle variance analysis, Doppler flow measurement, bulk motion removal, and automatic region of interest selection to quantify vessel diameter and blood velocity within tumors in vivo. OCT imaging reveals that blood velocity in peripheral tumor vessels quickly drops below the detection limit while the vessel lumen remains open (4 vessels from 3 animals). On the other hand, control tumor vessels (receive NIR illumination but no PIT drug) do not show the sustained blood velocity drop (5 vessels from 3 animals). Ultraslow blood velocity could result in a long drug circulation time in tumor. Increase of the blood pool volume within the central tumor (shown in histology) may be the leading cause of the periphery blood velocity drop and could also increase the drug pool volume in tumor vessels. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

The whisker system of rodents is an excellent model to study peripherally evoked neural activity in the brain. Discrete neural modules represent each whisker in the somatosensory cortex (“barrels”), thalamus (“barreloids”), and brain stem (“barrelettes”). Stimulation of a single whisker evokes neural activity sequentially in its corresponding barrelette, barreloid, and barrel. Conventional optical imaging of functional activation in the brain is limited to surface structures such as the cerebral cortex. To access subcortical structures and image sensory-evoked neural activity, we designed a needle-based optical system using gradient-index (GRIN) rod lens. We performed voltage-sensitive dye imaging (VSDi) with GRIN rod lens to visualize neural activity evoked in the thalamic barreloids by deflection of whiskers in vivo. We stimulated several whiskers together to determine the sensitivity of our approach in differentiating between different barreloid responses. We also carried out stimulation of different whiskers at different times. Finally, we used muscimol in the barrel cortex to silence the corticothalamic inputs while imaging in the thalamus. Our results show that it is possible to obtain functional maps of the sensory periphery in deep brain structures such as the thalamic barreloids. Our approach can be broadly applicable to functional imaging of other core brain structures.

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Epidural anesthesia is one of the most widely used anesthesia methods. Due to lack of visual feedback to guide needle navigation, failure rate of epidural anesthesia is up to 20%, and the complication rate of peripheral nerve block approaches 10%, with the potential of permanent nerve damage. To address these difficulties, needle insertion under ultrasound guidance and fluoroscopy has been introduced. However, they do not provide adequate resolution and contrast to distinguish the tissue layers that the needle travels through or to specifically identify the epidural space. To improve the accuracy of epidural space identification, we developed a small hand-held optical coherence tomography (OCT) forward-imaging needle device for real-time epidural anesthesia surgery guidance and demonstrated its feasibility through ex vivo and in vivo animal experiments. With tissue structures visualized and differentiated at the needle tip, OCT needle imaging device will enhance clinical outcomes with regards to complication rates, induced pain, and procedure failure when compared to standard practice. Furthermore, this technology could be used in combination with ultrasound/fluoroscopy to enhance outcomes.