Chia-Pin Liang

Towards a discretely actuated steerable cannula for diagnostic and therapeutic procedures

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 an 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 microscale imaging.

A forward-imaging needle-type OCT probe for image guided stereotactic procedures

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.

Review of advanced imaging techniques.

Pathology informatics encompasses digital imaging and related applications. Several specialized microscopy techniques have emerged which permit the acquisition of digital images (“optical biopsies”) at high resolution. Coupled with fiber-optic and micro-optic components, some of these imaging techniques (e.g., optical coherence tomography) are now integrated with a wide range of imaging devices such as endoscopes, laparoscopes, catheters, and needles that enable imaging inside the body. These advanced imaging modalities have exciting diagnostic potential and introduce new opportunities in pathology. Therefore, it is important that pathology informaticists understand these advanced imaging techniques and the impact they have on pathology. This paper reviews several recently developed microscopic techniques, including diffraction-limited methods (e.g., confocal microscopy, 2-photon microscopy, 4Pi microscopy, and spatially modulated illumination microscopy) and subdiffraction techniques (e.g., photoactivated localization microscopy, stochastic optical reconstruction microscopy, and stimulated emission depletion microscopy). This article serves as a primer for pathology informaticists, highlighting the fundamentals and applications of advanced optical imaging techniques.

Quantitative single-mode fiber based PS-OCT with single input polarization state using Mueller matrix

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.

In Vivo Voltage-Sensitive Dye Imaging of Subcortical Brain Function

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.

Real-time epidural anesthesia guidance using optical coherence tomography needle probe

Epidural anesthesia is one of the most widely used anesthesia methods. We developed a small hand-held OCT forward-imaging needle device for real-time epidural anesthesia surgery guidance and demonstrated its feasibility through ex vivo experiments.

Imaging Spinal Structures With Polarization-Sensitive Optical Coherence Tomography

We investigate polarization-sensitive optical coherence tomography (PS-OCT) to obtain both intensity and polarization contrast images of in vivo and ex vivo spinal structures like subcutaneous fat, supraspinous ligament, interspinous ligament, ligamentum flavum, dura, and spinal cord in a piglet model. The PS-OCT can provide enhanced contrast characteristic structures compared to the intensity OCT; therefore it has the potential for guidance in spine interventional procedures.

Real-time monitoring of hemodynamic changes in tumor vessels during photoimmunotherapy using optical coherence tomography

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.

Real-time Epidural Anesthesia Guidance Using Optical Coherence Tomography Needle Probe

Epidural anesthesia is one of the most widely used anesthesia methods. We developed a small hand-held OCT forward-imaging needle device for real-time epidural anesthesia surgery guidance and demonstrated its feasibility through ex vivo experiments.

Concurrent multiscale imaging with magnetic resonance imaging and optical coherence tomography.

Abstract. We develop a novel platform based on a tele-operated robot to perform high-resolution optical coherence tomography (OCT) imaging under continuous large field-of-view magnetic resonance imaging (MRI) guidance. Intra-operative MRI (iMRI) is a promising guidance tool for high-precision surgery, but it may not have sufficient resolution or contrast to visualize certain small targets. To address these limitations, we develop an MRI-compatible OCT needle probe, which is capable of providing microscale tissue architecture in conjunction with macroscale MRI tissue morphology in real time. Coregistered MRI/OCT images on ex vivo chicken breast and human brain tissues demonstrate that the complementary imaging scales and contrast mechanisms have great potential to improve the efficiency and the accuracy of iMRI procedure.