In the past decades, the performance of swept source optical coherence tomography (SS-OCT) has experienced an unprecedented improvement which is mainly driven by the rapidly evolving laser technologies: the state-of-art SS-OCT is now tens of dB more sensitive, six orders of magnitude faster, and seeing ten times deeper than the original version of time domain OCT. Regardless of the abovementioned progress, the phase instability is always considered the biggest weakness of SS-OCT and the mainstream belief often states that the mechanical tuning mechanism of the swept source is to blame. In my study, I first developed a high-speed phase-stable SS-OCT based on a new-generation akinetic laser source, which is electrically tuned in wavelength, in the hope of reducing the phase noise to a shot-noise limited level. The experimental results turned out to be contradicted to the conventional phase noise theory, which inspires my discovery of a completely new interpretation for the phase noise in SS-OCT: I proposed that the timing jitter and scanning variability has to be taken into the consideration in the noise model as multiplicative noises. The theory was later validated by another SS-OCT using a different light source. This study for the first time articulated the phase noise’s origin and composition in the SS-OCT. Although the SS-OCT performs relatively worse in phase stability compared with its spectral-domain counterpart (SD-OCT), it is still valuable since it images at a much faster rate than SD-OCT. Therefore, a better temporal resolution could be achieved, which is particularly attractive in areas such as time lapse imaging. I therefore utilize the system along with other two systems to conduct ex vivo imaging on human tracheobronchial epithelium. It is shown that the SS-OCT system could achieve equally good performance in this task. Moreover, thanks to the higher temporal and temporal frequency resolution, finer structure within the frequency response of the ciliary motion is picked up by our system. During the study of ex vivo ciliary imaging, one of the challenges I was confronted with was the enormous amount of data generated by the SS-OCT, especially when high temporal frequency resolution is required. We thus came up with an idea of applying the compressive sensing (CS) to reduce the data size. Currently, we have demonstrated some preliminary results with using CS on reference k-clock channel compression. In the future, we will apply the same theory to compress the sample channel data, especially or time lapse OCT imaging.

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.

Cardiovascular diseases are major causes of morbidity and mortality in Western-style populations. Atherosclerosis and Abdominal Aortic Aneurysms (AAAs) are two prevalent vascular diseases that may progress without symptoms and contribute to acute cardiovascular events such as stroke and AAA rupture, which are consistently among the leading causes of death worldwide. The imaging methods used in the diagnosis of these diseases, have been reported to present several limitations. Given that both are associated with mechanical changes in the arterial wall, imaging of the arterial mechanical properties may improve early disease detection and patient care. Pulse wave velocity (PWV) refers to the velocity at which arterial waves generated by ventricular ejection travel along the arterial tree. PWV is a surrogate marker of arterial stiffness linked to cardiovascular mortality. The foot-to-foot method that is typically used to calculate PWV suffers from errors of distance measurements and time-delay measurements. Additionally, a single PWV estimate is provided over a relatively long distance, thus inherently lacking the capability to provide regional arterial stiffness measurements. Pulse Wave Imaging (PWI) is a noninvasive, ultrasound-based technique for imaging the propagation of pulse waves along the wall of major arteries and providing a regional PWV value for the imaged artery. The aim of this work was to enable PWI to provide more localized PWV and stiffness measurements within the imaged arterial segment and to further extend it into a 2-D and 3-D technique for the detection and monitoring of focal vascular disease at high temporal and spatial resolution. The improved modality was integrated with blood flow imaging modalities aiming to render PWI a comprehensive methodology for the study of arterial biomechanics in vivo. Spatial information was increased with the introduction of piecewise PWI. This novel technique was used to measure PWV within small sub-regions of the imaged vessel in murine aneurysmal (n = 8) and atherosclerotic aortas (n = 11) in vivo. It provided PWV and stiffness maps while capturing the progressive arterial stiffening caused by atherosclerosis. PWI was further augmented with a sophisticated adaptive algorithm, enabling it to optimally partition the imaged artery into relatively homogeneous segments, automatically isolating arterial stiffness inhomogeneities. Adaptive PWI was validated in silicone phantoms consisting of segments of varying stiffness and then tested in murine aortas in vivo. Subsequently, the conventional tradeoff between spatial and temporal resolution was addressed with a plane wave compounding implementation of PWI, allowing the acquisition of full field of view frames at over 2000 Hz. A GPU-accelerated PWI post-processing framework was developed for the processing of the big bulk of generated data. The parameters of coherent compounding were optimized in vivo. The optimized sequences were then used in the clinic to assess the mechanical properties of atherosclerotic carotids (n=10) and carotids of patients after endarterectomy (n=7), a procedure to remove the plaque and restore blood flow to the brain. In the case of atherosclerotic patients undergoing carotid endarterectomy, the results were compared against the histology of the excised plaques. Investigation of the mechanical properties of plaques was also conducted for the first time with a high-frequency transducer (18.5 MHz). Additionally, 4-D PWI was introduced, utilizing high frame rate 3-D plane wave acquisitions with a 2-D matrix array transducer (16x16 elements, 2.5 MHz). A novel methodology for PWV estimation along the direction of pulse wave propagation was implemented and validated in silicone phantoms. 4-D PWI provided comprehensive views of the pulse wave propagation in a plaque phantom and the results were compared against conventional PWI. Finally, its feasibility was tested in the carotid arteries of healthy human subjects (n=6). PWVs derived in 3-D were within the physiological range and showed good agreement with the results of conventional PWI. Finally, PWI was integrated with flow imaging modalities (Color and Vector Doppler). Thus, full field-of-view, high frame-rate, simultaneous and co-localized imaging of the arterial wall dynamics and color flow as well as 2-D vector flow was implemented. The feasibility of both techniques was tested in healthy subjects (n=6) in vivo. The relationship between the timings of the flow and wall velocities was investigated at multiple locations of the imaged artery. Vector flow velocities were found to be aligned with the vessel’s centerline during peak systole in the common carotid artery and interesting flow patterns were revealed in the case of the carotid bifurcation Consequently, with the aforementioned improvements and the inclusion of 3-D imaging, PWI is expected to provide comprehensive information on the mechanical properties of pathological arteries, providing clinicians with a powerful tool for the early detection of vascular abnormalities undetectable on the B-mode, while also enabling the monitoring of fully developed vascular pathology and of the recovery of post-operated vessels.

The phosphatidylinositol-3-kinase/AKT (Protein Kinase B)/mammalian target of rapamycin (PI3K/AKT/mTOR) signalling pathway, downstream of tyrosine kinase receptors, is upregulated in human cancers including breast and colon cancers. Glycogen synthase kinase 3 (GSK 3) is a serine/threonine protein kinase plays important role in various cellular processes including glycogen synthesis mediated by insulin signalling pathway. Moreover, 5' adenosine monophosphate activated protein kinase (AMPK), a crucial cellular energy sensor, has regulatory role in cell growth and proliferation through mTOR pathway. Phosphatidylcholine (PtdCho) is the major phospholipid in the mammalian cell membranes and is mainly synthesized by the CDP-choline pathway. Malignant transformation has been reported to be associated with altered choline metabolism. Hyperactivation of the PI3K/AKT signalling pathway upregulates the key enzymes of phospholipid metabolism. The first line antidiabetic drug, metformin, modulates glucose and concomitant lipid metabolism through AMPK activation. Studies suggest phosphatidylcholine biosynthesis and breakdown through CDP-choline pathway are modulated by glucose metabolism and de novo fatty acid synthesis. Cancer cell growth inhibitory effect of PI3K/AKT/mTOR/GSK3 pathway inhibitors and metformin were investigated by cytotoxic assay, western blot and cell cycle analysis in breast and colon cancer cells. IC50 values of anticancer drugs and combination indices between drug combinations were determined. 31P-NMR was carried out on cell extracts after drug treatments. [14C (U)] glucose and [3H] choline incorporation into lipids were also determined. All inhibitors targeting PI3K/AKT/mTOR signaling pathway, GSK3 and metformin have cancer cell growth inhibition. By 31P-NMR, PI3K/AKT/mTOR pathway inhibition induced agent-specific changes in PCho intensity. Increased UDP-sugars observed in breast and colon cancer cell extracts treated with LY294002 and AZD8055, an effect abrogated by inclusion of a GSK3 inhibitor. A link between glycolytic intermediates and phosphatidylcholine biosynthesis was investigated by metformin and GSK3 inhibitor in breast and colon cancer cells.

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.

It is a major challenge to understand functional neuronal circuits across the whole brain. Existing methods for observing neuronal activity represent a major bottleneck in addressing biological problems. In our lab, we developed Swept Confocally Aligned Planar Excitation (SCAPE) microscopy, which offers the ability to image a large 3D volume (e.g. 1000x800x250um) at speeds exceeding 10 volumes per second. Used with different genetically encoded fluorescent indicators, SCAPE enables us to observe neuronal activity across the whole brain of different small animal models, or a much larger volume of intact cortex/tissue compared to traditional approaches. The unique single objective design and flexible system layout of SCAPE makes it simple to image different samples without complex sample preparation and restraint. During this thesis work, I collaborated with biology and neuroscience labs to develop and optimize a range of novel in-vivo/in-vitro neuroimaging applications using SCAPE microscopy. In particular, my research has focused on using SCAPE to image freely crawling Drosophila Melanogaster larvae, intact mouse olfactory epithelium, head fixed behaving adult Drosophila, larval zebrafish brain and beating heart, and the neuronal system of behaving C. elegans, all in collaboration with experts in these models from Columbia University and other research institutions. I also developed and optimized different sample preparations and experimental procedures to take full advantage of the high-speed 3D imaging capabilities and flexibility of SCAPE microscopy. Finally, I optimized computational and image analysis techniques for large scale 5D SCAPE imaging datasets, including 3D cell tracking, large scale 3D data motion correction/registration, and cellular level neuronal activity extraction with different dimensionality reduction methods. The experiments I have performed in different animal models have enriched the long-term development of SCAPE by providing valuable feedback for system improvement and dissemination, and pushing the SCAPE design towards a more interchangeable platform with diverse capabilities suitable for routine uses by our collaborators and the wider neuroscience community.

Abstract not available

"In this thesis, the two problems of image formation for a Multichannel Synthetic Aperture Radar (MSAR) and suppressing interferences while forming a good quality image have been addressed. For the first problem, three wavefront reconstruction algorithms were presneted based on the multichannel Matched Filter (MF) imagining equation which demonstrated differing levels of performance and accuracy. A fourth algorithm known as multichannel backprojection was also presented to provide comparative quality with a reduced computational load. To address the second problem, a detailed jammer model was described and tested with a multichannel imaging algorithm to demonstrate the effect of hot-clutter on a SAR image. Multi-channel imaging and optimal slow-time Space Time Adaptive Processing (STAP) were shown to only partially suppress the hot-clutter interference, while optimal fast-time STAP demonstrated a much greater performance." --p. 185 of source document. / Thesis (Ph.D.)--School of Electrical and Electronic Engineering, 2007.

MRI as a non-invasive method for studying the internal structure and function of the human body was developed over the past three decades. In MRI, radiofrequency (RF) field inhomogeneity is an unavoidable problem in practice and becomes severe at high magnetic fields due to the dependence of B1 on the sample. It leads to nonuniformities in image intensity and contrast, causing difficulties in quantitative interpretation and image segmentation. In this thesis, we report an interesting observation that the fast low-angle shot (FLASH) sequence, which is often used for anatomic imaging and morphometric studies, can be insensitive to RF inhomogeneity when the same coil is used for both transmission and reception and a proper nominal flip angle is employed. Recommendations also are given for optimum processing procedures for FLASH imaging. This observation can be useful in understanding the signal behavior of FLASH in the presence of RF inhomogeneity and provides a guide for selecting parameters in FLASH imaging.

No description available.