published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy

By integrating three complementary imaging techniques - ultrasound, elasticity and photoacoustic imaging, a hybrid imaging system utilizing an array transducer is proposed for various biomedical imaging applications including cancer detection, diagnosis and therapy monitoring. Simultaneous imaging of the anatomy (ultrasound imaging), changes in biomechanical properties (elasticity imaging) and cancer-induced angiogenesis (photoacoustic imaging) of tissue is based on many synergistic features of these modalities and may result in a unique and important imaging tool. In this study, numerical analysis and experimental studies are presented to demonstrate the feasibility, to evaluate the performance, and also to improve the quality of the combined array-based ultrasound, elasticity and photoacoustic imaging system. To estimate spatial resolution, a point source was imaged using ultrasound and photoacoustic imaging modes. Then, several tissue mimicking phantoms were examined using ultrasound, photoacoustic and elasticity imaging. In elasticity imaging, ultrasound frames were acquired during deformation of the tissue. To reduce the data acquisition time of the system, high frame rate imaging was used. High frame rate imaging is possible by transmitting a broader and less focused ultrasound beam but the image quality is sacrificed. Thus, we compared the quality of the high frame rate and conventional ultrasound images. In photoacoustic imaging, acoustic transients are generated simultaneously in the entire volume of the laser irradiated tissue. Hence, image formation (beamforming) algorithms were developed based on the characteristics of the photoacoustic signals. Then, adaptive beamforming method is suggested to improve the image quality of the photoacoustic imaging. The results of the numerical analyses and experimental studies clearly indicate that ultrasound, elasticity and photoacoustic imaging techniques complement each other and together provide critical information needed for the reliable detection and diagnosis of diseases. / text

Over the past 25 years of development and innovation, optical coherence tomography (OCT) has successfully fills the gap between the ex vivo high-resolution optical microscopy technologies and in vivo low-resolution medical imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US). Ultrahigh resolution (UHR) OCT categorizes OCT systems with an axial resolution below 3 µm in tissue. With the improved resolution, UHR OCT may impart the knowledge of detailed structures of the tissues that are almost close to what histology may provide. This is how UHR OCT can act as a bridge between radiology and histology. This thesis will present an ultrahigh-resolution (UHR) spectral domain (SD) OCT system that features both high axial resolution and long imaging range, and will demonstrate its applications in human myocardium and breast tissue imaging. The UHR OCT system accommodates a supercontinuum light source, and a home-built spectrometer designed to achieve optimized imaging performance. Specifically, the spectrometer features a customized focusing lenses that are comprised of off-the-shelf optics and a 2k-pixel camera to minimize the cost of the instrument. The system manifests an axial resolution of 2.72 µm and a lateral resolution of 5.52 µm, with a large imaging range of 1.78 mm. The sensitivity of the system is 93 dB with a 6-dB sensitivity fall-off range of 0.89 mm. For human myocardium, currently there is no high-resolution non-destructive real-time imaging modality available for biopsy guidance. As a real-time and non-destructive imaging tool, UHR OCT offers additional benefits compared with standard OCT, which are illustrated by successful delineation of micro-structures such as thin elastic fibers and Purkinje fibers in the endomyocardial side. These structures are otherwise not visible within standard-resolution OCT images. Moreover, by adding the cross-polarization (CP) functionality to the UHR SD system, different types of myocardial tissue can be better delineated through the CP contrast. The functional information provided by CP-OCT may also facilitate automatic tissue classification by using A-line signals. For breast tissue imaging, we show qualitatively and quantitatively that UHR OCT images may enable better visualization of detailed features in different types of breast tissue, including healthy and cancerous ones. UHR OCT images of new breast cancer types such as phyllodes tumor, necrotic tumor and fibrotic focus carcinoma are provided for future references. Features developed from UHR OCT images enable a better yield from relevance vector machine (RVM) based stochastic classification model, compared with that from standard resolution OCT images. UHR OCT shows a great promise for automated classification of different tissue types in human breast tissue based off on UHR OCT images. Lastly, we present our endeavor to miniaturize the UHR OCT system on chip. We explore a chip-based optical frequency comb source that may enable UHR OCT at longer wavelengths to achieve better signal penetration in the future. We characterize the performance of the novel source, including the axial resolution and noise, and show that it holds the promise to be adopted in UHR OCT imaging. In addition, we also demonstrate an on-chip tunable reference arm that allows high-topology high-resolution OCT imaging. The compactness of the devices pave the way to the ultimate miniaturization of OCT system.

Optical coherence tomography (OCT) has been emerging as a promising imaging technique, with a strong capability of non-invasive, in vivo, high resolution, depth-resolved imaging. There is a great potential to use OCT to guide the treatment of arrhythmias, to prevent preterm birth, and to detect breast cancer. To facilitate the clinical applications, this thesis presents three image analytic tools to characterize biological tissue: 1) automated fiber direction analysis; 2) automated volumetric stitching; 3) automated tissue classification. The fiber direction analysis consists of a particle-filter-based 3D tractography scheme and a pixel-wise fiber analysis scheme. The stitching algorithm enlarges the field of view of current OCT system from millimeter to centimeter level by volumetric stitching using scale-invariant feature transform. Based on relevance vector machine, a region-based classification scheme and a grid-based classification scheme are developed to automatically identify tissue composition in human cardiac tissue and human breast tissue. These tools are collaboratively used to study OCT images from cardiac, cervical, and breast tissue. In cardiac tissue, we apply the fiber orientation analysis to reconstruct 3D cardiac myofibers tractography and perform pixel-wise fiber analysis on the collagen region within human heart. In addition, we apply the region-based algorithm to segment and classify tissue compositions, such as collagen, adipose tissue, fibrotic myocardium, and normal myocardium, over a single or a stitched OCT volume. Using our algorithm, we observe fiber directionality change over depths and find that the fiber orientation changes more dramatically in atria than in ventricle. We also observe different dispersion patterns within collagen layer. In cervical tissue, our stitching algorithm enables a paramount 3D view of entire axial slices. Together with pixel-wise fiber orientation scheme, we analyze the difference of dispersion property within inner/outer regions of four quadrants. We observe two dispersion patterns in pregnant and non-pregnant cervical tissue at the location close to upper cervix. In addition, we discover that an increasing trend of dispersion and an increasing trend of penetration depth from internal orifice (os) to external os. In breast tissue, we visualize various features in both benign and malignant tissues such as invasive ductal carcinoma (IDC), ductal carcinoma in situ, cyst, and terminal duct lobule unit in stitched OCT images. Focusing on the automated detection of IDC, we propose a hierarchy framework of classification model and apply our classifier in two OCT systems and achieve both reasonable sensitivity and specificity in identifying cancerous region.

This thesis is concerned with exploiting the native optical coherence tomography (OCT) contrast mechanism in new ways and with a new contrast mechanism, in both cases to enhance the information content of the tomographic image. Through experiments in microsphere solutions, we show that static speckle contains information about local particle density when the effective number of scatterers in the OCT resolution volume is less than about five. This potentially provides contrast enhancement in OCT images based on local scatterer density, and we discuss the experimental conditions suited to utilising this in biological tissue. We also describe the corrupting effects of multiple scattering, a ubiquitous phenomenon in OCT, on the information content of the static speckle. Consequently, we detail the development of polarisation-based metrics for characterising multiple scattering in OCT images of solid biological tissues. We exploit a detection scheme used for polarisation-sensitive contrast for a new purpose. We present experiments demonstrating the behaviour of these metrics in liquid phantoms, and in biological tissues, ranging from homogeneous non-birefringent to highly heterogeneous and birefringent samples. We discuss the conditions under which these metrics could be used to characterise the relative contribution of single and multiple scattering and, thus, aid in the study of penetration depth limits in OCT. We present a study of a new contrast mechanism - dynamic elastography which seeks to determine the dynamic mechanical properties of tissues. We present a framework for describing the OCT signal in samples undergoing vibrations, and perform experiments at vibration frequencies in the order of tens to hundreds of Hertz, to confirm the theory, and demonstrate the modes of measurement possible with this technique. These modes of measurement, including acoustic amplitude-sweep and frequency-sweep, could provide new information about the local mechanical properties of a sample. We describe a technological advancement enabling, in principle, measurements of local tissue refractive index contrast much deeper within a sample, than is possible with conventional OCT imaging. The design is based on measurement of the optical path length through tissue filling a fixed-width channel situated at the tip of a needle. The needle design and calibration is presented, as well as measurements of scattering phantoms and various biological tissues. This design potentially enables the use of refractive index-based contrast enhancement in the guidance of breast biopsy procedures.