Barry Vuong

Review of speckle and phase variance optical coherence tomography to visualize microvascular networks

Abstract. High-resolution mapping of microvasculature has been applied to diverse body systems, including the retinal and choroidal vasculature, cardiac vasculature, the central nervous system, and various tumor models. Many imaging techniques have been developed to address specific research questions, and each has its own merits and drawbacks. Understanding, optimization, and proper implementation of these imaging techniques can significantly improve the data obtained along the spectrum of unique research projects to obtain diagnostic clinical information. We describe the recently developed algorithms and applications of two general classes of microvascular imaging techniques: speckle-variance and phase-variance optical coherence tomography (OCT). We compare and contrast their performance with Doppler OCT and optical microangiography. In addition, we highlight ongoing work in the development of variance-based techniques to further refine the characterization of microvascular networks.

In vivo feasibility of endovascular Doppler optical coherence tomography

Feasibility of detecting intravascular flow using a catheter based endovascular optical coherence tomography (OCT) system is demonstrated in a porcine carotid model in vivo. The effects of A-line density, radial distance, signal-to-noise ratio, non-uniform rotational distortion (NURD), phase stability of the swept wavelength laser and interferometer system on Doppler shift detection limit were investigated in stationary and flow phantoms. Techniques for NURD induced phase shift artifact removal were developed by tracking the catheter sheath. Detection of high flow velocity (~51 cm/s) present in the porcine carotid artery was obtained by phase unwrapping techniques and compared to numerical simulation, taking into consideration flow profile distortion by the eccentrically positioned imaging catheter. Using diluted blood in saline mixture as clearing agent, simultaneous Doppler OCT imaging of intravascular flow and structural OCT imaging of the carotid artery wall was feasible. To our knowledge, this is the first in vivo demonstration of Doppler imaging and absolute measurement of intravascular flow using a rotating fiber catheter in carotid artery.

Digital image correlation-based optical coherence elastography

Abstract. 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.

Endovascular optical coherence tomography intensity kurtosis: visualization of vasa vasorum in porcine carotid artery

Application of speckle variance optical coherence tomography (OCT) to endovascular imaging faces difficulty of extensive motion artifacts inherently associated with arterial pulsations in addition to other physiological movements. In this study, we employed a technique involving a fourth order statistical method, kurtosis, operating on the endovascular OCT intensity images to visualize the vasa vasorum of carotid artery in vivo and identify its flow dynamic in a porcine model. The intensity kurtosis technique can distinguish vasa vasorum from the surrounding tissues in the presence of extensive time varying noises and dynamic motions of the arterial wall. Imaging of vasa vasorum and its proliferation, may compliment the growing knowledge of structural endovascular OCT in assessment and treatment of atherosclerosis in coronary and carotid arteries.

Intraoperative handheld optical coherence tomography forward-viewing probe: physical performance and preliminary animal imaging

A prototype intraoperative hand-held optical coherence tomography (OCT) imaging probe was developed to provide micron resolution cross-sectional images of subsurface tissue during open surgery. This new ergonomic probe was designed based on electrostatically driven optical fibers, and packaged into a catheter probe in the form factor of clinically accepted Bayonet shaped neurosurgical probes. Optical properties of the probe were measured to have a ~20 μm spot size, 5 mm working distance and 4 mm field of view. Feasibility of this probe for structural and Doppler shift imaging was tested on porcine femoral blood vessel imaging.

High speed, wide velocity dynamic range Doppler optical coherence tomography (Part IV): split spectrum processing in rotary catheter probes

We report a technique for blood flow detection using split spectrum Doppler optical coherence tomography (ssDOCT) that shows improved sensitivity over existing Doppler OCT methods. In ssDOCT, the Doppler signal is averaged over multiple sub-bands of the interferogram, increasing the SNR of the Doppler signal. We explore the parameterization of this technique in terms of number of sub-band windows, width and overlap of the windows, and their effect on the Doppler signal to noise in a flow phantom. Compared to conventional DOCT, ssDOCT processing has increased flow sensitivity. We demonstrate the effectiveness of ssDOCT in-vivo for intravascular flow detection within a porcine carotid artery and for microvascular vessel detection in human pulmonary imaging, using rotary catheter probes. To our knowledge, this is the first report of visualizing in-vivo Doppler flow patterns adjacent to stent struts in the carotid artery.

Imaging the electro-kinetic response of biological tissues with optical coherence tomography.

We demonstrate the feasibility of using optical coherence tomography (OCT) to detect and image an electro-kinetic response: electric-field induced optical changes (EIOC) in soft biological tissues. A low-frequency electric field was applied to ex vivo samples of porcine heart tissues, while OCT signals were acquired continuously. Experimental results show that the amplitude of the OCT signal change is proportional to the amplitude and inversely proportional to the frequency of the applied electric field. We show that the nonconductive component of the sample was eliminated in the normalized EIOC image. To the best our knowledge, this is the first time a two-dimensional image related to the electro-kinetic response of soft tissues is obtained with depth resolution. Since electro-kinetic properties can change during cancerogenesis, EIOC imaging can potentially be used for cancer detection.

Measuring the optical characteristics of medulloblastoma with optical coherence tomography

Medulloblastoma is the most common malignant pediatric brain tumor. Standard treatment consists of surgical resection, followed by radiation and high-dose chemotherapy. Despite these efforts, recurrence is common, leading to reduced patient survival. Even with successful treatment, there are often severe long-term neurologic impacts on the developing nervous system. We present two quantitative techniques that use a high-resolution optical imaging modality: optical coherence tomography (OCT) to measure refractive index, and the optical attenuation coefficient. To the best of our knowledge, this study is the first to demonstrate OCT analysis of medulloblastoma. Refractive index and optical attenuation coefficient were able to differentiate between normal brain tissue and medulloblastoma in mouse models. More specifically, optical attenuation coefficient imaging of normal cerebellum displayed layers of grey matter and white matter, which were indistinguishable in the structural OCT image. The morphology of the tumor was distinct in the optical attenuation coefficient imaging. These inherent properties may be useful during neurosurgical intervention to better delineate tumor boundaries and minimize resection of normal tissue.

Histogram flow mapping with optical coherence tomography for in vivo skin angiography of hereditary hemorrhagic telangiectasia

Speckle statistics of flowing scatterers have been well documented in the literature. Speckle variance optical coherence tomography exploits the large variance values of intensity changes in time caused mainly by the random backscattering of light resulting from translational activity of red blood cells to map out the microvascular networks. A method to map out the microvasculature malformation of skin based on the time-domain histograms of individual pixels is presented with results obtained from both normal skin and skin containing vascular malformation. Results demonstrated that this method can potentially map out deeper blood vessels and enhance the visualization of microvasculature in low signal regions, while being resistant against motion (e.g., patient tremor or internal reflex movements). The overall results are manifested as more uniform en face projection maps of microvessels. Potential applications include clinical imaging of skin vascular abnormalities and wide-field skin angiography for the study of complex vascular networks.

Evaluation of flow velocities after carotid artery stenting through split spectrum Doppler optical coherence tomography and computational fluid dynamics modeling

Hemodynamics plays a critical role in the development of atherosclerosis, specifically in regions of curved vasculature such as bifurcations exhibiting irregular blood flow profiles. Carotid atherosclerotic disease can be intervened by stent implantation, but this may result in greater alterations to local blood flow and consequently further complications. This study demonstrates the use of a variant of Doppler optical coherence tomography (DOCT) known as split spectrum DOCT (ssDOCT) to evaluate hemodynamic patterns both before and after stent implantation in the bifurcation junction in the internal carotid artery (ICA). Computational fluid dynamics (CFD) models were constructed to simulate blood velocity profiles and compared to the findings achieved through ssDOCT images. Both methods demonstrated noticeable alterations in hemodynamic patterns following stent implantation, with features such as slow velocity regions at the neck of the bifurcation and recirculation zones at the stent struts. Strong correlation between CFD models and ssDOCT images demonstrate the potential of ssDOCT imaging in the optimization of stent implantation in the clinical setting.