Enhancing the Visualization of the Peripheral Retina with Wide Field-of-View Optical Coherence Tomography

The goal of my Ph.D. thesis is to enhance the visualization of the peripheral retina using wide-field optical coherence tomography (OCT) in a clinical setting.

OCT has gain widespread adoption in clinical ophthalmology due to its ability to visualize the diseases of the macula and central retina in three-dimensions, however, clinical OCT has a limited field-of-view of 300. There has been increasing interest to obtain high-resolution images outside of this narrow field-of-view, because three-dimensional imaging of the peripheral retina may prove to be important in the early detection of neurodegenerative diseases, such as Alzheimer's and dementia, and the monitoring of known ocular diseases, such as diabetic retinopathy, retinal vein occlusions, and choroid masses.

Before attempting to build a wide-field OCT system, we need to better understand the peripheral optics of the human eye. Shack-Hartmann wavefront sensors are commonly used tools for measuring the optical imperfections of the eye, but their acquisition speed is limited by their underlying camera hardware. The first aim of my thesis research is to create a fast method of ocular wavefront sensing such that we can measure the wavefront aberrations at numerous points across a wide visual field. In order to address aim one, we will develop a sparse Zernike reconstruction technique (SPARZER) that will enable Shack-Hartmann wavefront sensors to use as little as 1/10th of the data that would normally be required for an accurate wavefront reading. If less data needs to be acquired, then we can increase the speed at which wavefronts can be recorded.

For my second aim, we will create a sophisticated optical model that reproduces the measured aberrations of the human eye. If we know how the average eye's optics distort light, then we can engineer ophthalmic imaging systems that preemptively cancel inherent ocular aberrations. This invention will help the retinal imaging community to design systems that are capable of acquiring high resolution images across a wide visual field. The proposed model eye is also of interest to the field of vision science as it aids in the study of how anatomy affects visual performance in the peripheral retina.

Using the optical model from aim two, we will design and reduce to practice a clinical OCT system that is capable of imaging a large (800) field-of-view with enhanced visualization of the peripheral retina. A key aspect of this third and final aim is to make the imaging system compatible with standard clinical practices. To this end, we will incorporate sensorless adaptive optics in order to correct the inter- and intra- patient variability in ophthalmic aberrations. Sensorless adaptive optics will improve both the brightness (signal) and clarity (resolution) of features in the peripheral retina without affecting the size of the imaging system.

The proposed work should not only be a noteworthy contribution to the ophthalmic and engineering communities, but it should strengthen our existing collaborations with the Duke Eye Center by advancing their capability to diagnose pathologies of the peripheral retinal.

Whole-cell-analysis of live cardiomyocytes using wide-field interferometric phase microscopy.

We apply wide-field interferometric microscopy techniques to acquire quantitative phase profiles of ventricular cardiomyocytes in vitro during their rapid contraction with high temporal and spatial resolution. The whole-cell phase profiles are analyzed to yield valuable quantitative parameters characterizing the cell dynamics, without the need to decouple thickness from refractive index differences. Our experimental results verify that these new parameters can be used with wide field interferometric microscopy to discriminate the modulation of cardiomyocyte contraction dynamics due to temperature variation. To demonstrate the necessity of the proposed numerical analysis for cardiomyocytes, we present confocal dual-fluorescence-channel microscopy results which show that the rapid motion of the cell organelles during contraction preclude assuming a homogenous refractive index over the entire cell contents, or using multiple-exposure or scanning microscopy.

Temporal Coding of Volumetric Imagery

'Image volumes' refer to realizations of images in other dimensions such as time, spectrum, and focus. Recent advances in scientific, medical, and consumer applications demand improvements in image volume capture. Though image volume acquisition continues to advance, it maintains the same sampling mechanisms that have been used for decades; every voxel must be scanned and is presumed independent of its neighbors. Under these conditions, improving performance comes at the cost of increased system complexity, data rates, and power consumption.

This dissertation explores systems and methods capable of efficiently improving sensitivity and performance for image volume cameras, and specifically proposes several sampling strategies that utilize temporal coding to improve imaging system performance and enhance our awareness for a variety of dynamic applications.

Video cameras and camcorders sample the video volume (x,y,t) at fixed intervals to gain understanding of the volume's temporal evolution. Conventionally, one must reduce the spatial resolution to increase the framerate of such cameras. Using temporal coding via physical translation of an optical element known as a coded aperture, the compressive temporal imaging (CACTI) camera emonstrates a method which which to embed the temporal dimension of the video volume into spatial (x,y) measurements, thereby greatly improving temporal resolution with minimal loss of spatial resolution. This technique, which is among a family of compressive sampling strategies developed at Duke University, temporally codes the exposure readout functions at the pixel level.

Since video cameras nominally integrate the remaining image volume dimensions (e.g. spectrum and focus) at capture time, spectral (x,y,t,\lambda) and focal (x,y,t,z) image volumes are traditionally captured via sequential changes to the spectral and focal state of the system, respectively. The CACTI camera's ability to embed video volumes into images leads to exploration of other information within that video; namely, focal and spectral information. The next part of the thesis demonstrates derivative works of CACTI: compressive extended depth of field and compressive spectral-temporal imaging. These works successfully show the technique's extension of temporal coding to improve sensing performance in these other dimensions.

Geometrical optics-related tradeoffs, such as the classic challenges of wide-field-of-view and high resolution photography, have motivated the development of mulitscale camera arrays. The advent of such designs less than a decade ago heralds a new era of research- and engineering-related challenges. One significant challenge is that of managing the focal volume (x,y,z) over wide fields of view and resolutions. The fourth chapter shows advances on focus and image quality assessment for a class of multiscale gigapixel cameras developed at Duke.

Along the same line of work, we have explored methods for dynamic and adaptive addressing of focus via point spread function engineering. We demonstrate another form of temporal coding in the form of physical translation of the image plane from its nominal focal position. We demonstrate this technique's capability to generate arbitrary point spread functions.

Beyond the Convent Walls: The Local and Japan-wide Activities of Daihongan’s Nuns in the Early Modern Period (c. 1550–1868)

This dissertation examines the social and financial activities of Buddhist nuns to demonstrate how and why they deployed Buddhist doctrines, rituals, legends, and material culture to interact with society outside the convent. By examining the activities of the nuns of the Daihongan convent (one of the two administrative heads of the popular pilgrimage temple, Zenkōji) in Japan’s early modern period (roughly 1550 to 1868) as documented in the convent’s rich archival sources, I shed further light on the oft-overlooked political and financial activities of nuns, illustrate how Buddhist institutions interacted with the laity, provide further nuance to the discussion of how Buddhist women navigated patriarchal sectarian and secular hierarchies, and, within the field of Japanese history, give voice to women who were active outside of the household unit around which early modern Japanese society was organized.

Zenkōji temple, surrounded by the mountains of Nagano, has been one of Japan’s most popular pilgrimage sites since the medieval period. The abbesses of Daihongan, one Zenkōji’s main sub-temples, traveled widely to maintain connections with elite and common laypeople, participated in frequent country-wide displays of Zenkōji’s icon, and oversaw the creation of branch temples in Edo (now Tokyo), Osaka, Echigo (now Niigata), and Shinano (now Nagano). The abbesses of Daihongan were one of only a few women to hold the imperially sanctioned title of eminent person (shōnin 上人) and to wear purple robes. While this means that this Pure Land convent was in some ways not representative of all convents in early modern Japan, Daihongan’s position is particularly instructive because the existence of nuns and monks in a single temple complex allows us to see in detail how monastics of both genders interacted in close quarters.

This work draws heavily from the convent’s archival materials, which I used as a guide in framing my dissertation chapters. In the Introduction I discuss previous works on women in Buddhism. In Chapter 1, I briefly discuss the convent’s history and its place within the Zenkōji temple complex. In Chapter 2, I examine the convent’s regular economic bases and its expenditures. In Chapter 3, I highlight Daihongan’s branch temples and discuss the ways that they acted as nodes in a network connecting people in various areas to Daihongan and Zenkōji, thus demonstrating how a rural religious center extended its sphere of influence in urban settings. In Chapter 4, I discuss the nuns’ travels throughout the country to generate new and maintain old connections with the imperial court in Kyoto, confraternities in Osaka, influential women in the shogun’s castle, and commoners in Edo. In Chapter 5, I examine the convent’s reliance upon irregular means of income such as patronage, temple lotteries, loans, and displays of treasures, and how these were needed to balance irregular expenditures such as travel and the maintenance or reconstruction of temple buildings. Throughout the dissertation I describe Daihongan’s inner social structure comprised of abbesses, nuns, and administrators, and its local emplacement within Zenkōji and Zenkōji’s temple lands.

Exploring these themes sheds light on the lives of Japanese Buddhist nuns in this period. While the tensions between freedom and agency on the one hand and obligations to patrons, subordination to monks, or gender- and status-based restrictions on the other are important, and I discuss them in my work, my primary focus is on the nuns’ activities and lives. Doing so demonstrates that nuns were central figures in ever-changing economic and social networks as they made and maintained connections with the outside world through Buddhist practices and through precedents set centuries before. This research contributes to our understanding of nuns in Japan’s early modern period and will participate in and shape debates on the roles of women in patriarchal religious hierarchies.