Faculty Bibliography

Despite the prevalence of optical imaging techniques to measure hemodynamics in large retinal vessels, quantitative measurements of retinal capillary and choroidal hemodynamics have traditionally been challenging. Here, a new imaging technique called dynamic contrast optical coherence tomography (DyC-OCT) is applied in the rat eye to study microvascular blood flow in individual retinal and choroidal layers in vivo. DyC-OCT is based on imaging the transit of an intravascular tracer dynamically as it passes through the field-of-view. Hemodynamic parameters can be determined through quantitative analysis of tracer kinetics. In addition to enabling depth-resolved transit time, volume, and flow measurements, the injected tracer also enhances OCT angiograms and enables clear visualization of the choriocapillaris, particularly when combined with a post-processing method for vessel enhancement. DyC-OCT complements conventional OCT angiography through quantification of tracer dynamics, similar to fluorescence angiography, but with the important added benefit of laminar resolution.

PURPOSE:To evaluate the diagnostic performance of a 3-dimensional (3D) neuroretinal rim parameter, the minimum distance band (MDB), using optical coherence tomography (OCT) high-density volume scans for open-angle glaucoma. DESIGN:Reliability analysis. METHODS:setting: Institutional. STUDY POPULATION:Total of 163 patients (105 glaucoma and 58 healthy subjects). OBSERVATION PROCEDURES:One eye of each patient was included. MDB and retinal nerve fiber layer (RNFL) thickness values were determined for 4 quadrants and 4 sectors using a spectral-domain OCT device. MAIN OUTCOME MEASURES:Area under the receiver operating characteristic curve (AUROC) values, sensitivities, specificities, and positive and negative predictive values. RESULTS:The best AUROC values of 3D MDB thickness for glaucoma and early glaucoma were for the overall globe (0.969, 0.952), followed by the inferior quadrant (0.966, 0.949) and inferior-temporal sector (0.966, 0.944), and then followed by the superior-temporal sector (0.964, 0.932) and superior quadrant (0.962, 0.924). All 3D MDB thickness AUROC values were higher than those of 2D RNFL thickness. Pairwise comparisons showed that the diagnostic performance of the 3D MDB parameter was significantly better than 2D RNFL thickness only for the nasal quadrant and inferior-nasal and superior-nasal sectors (P = .023-.049). Combining 3D MDB with 2D RNFL parameters provided significantly better diagnostic performance (AUROC 0.984) than most single MDB parameters and all single RNFL parameters. CONCLUSIONS:Compared with the 2D RNFL thickness parameter, the 3D MDB neuroretinal rim thickness parameter had uniformly equal or better diagnostic performance for glaucoma in all regions and was significantly better in the nasal region.

Myocardial infarction leads to complex changes in the fiber architecture of the heart. Here, we present a novel optical approach to characterize these changes in intact hearts in three dimensions. Optical coherence tomography (OCT) was used to derive a depth-resolved field of orientation on which tractography was performed. Tractography of healthy myocardium revealed a smooth linear transition in fiber inclination or helix angle from the epicardium to endocardium. Conversely, in infarcted hearts, no coherent microstructure could be identified in the infarct with OCT Additional characterization of the infarct was performed by the measurement of light attenuation and with two-photon microscopy. Myofibers were imaged using autofluorescence and collagen fibers using second harmonic generation. This revealed the presence of two distinct microstructural patterns in areas of the infarct with high light attenuation. In the presence of residual myofibers, the surrounding collagen fibers were aligned in a coherent manner parallel to the myofibers. In the absence of residual myofibers, the collagen fibers were randomly oriented and lacked any microstructural coherence. The presence of residual myofibers thus exerts a profound effect on the microstructural properties of the infarct scar and consequently the risk of aneurysm formation and arrhythmias. Catheter-based approaches to segment and image myocardial microstructure in humans are feasible and could play a valuable role in guiding the development of strategies to improve infarct healing.

Recently, optical coherence tomography (OCT) angiography has enabled label-free imaging of vasculature based on dynamic scattering in vessels. However, quantitative volumetric analysis of the vascular networks depicted in OCT angiography data has remained challenging. Multiple-scattering tails (artifacts specific to the imaging geometry) make automated assessment of vascular morphology problematic. We demonstrate that dynamically focused optical coherence microscopy (OCM) angiography with a high numerical aperture, chosen so the scattering length greatly exceeds the depth-of-field, significantly reduces the deleterious effect of multiple-scattering tails in synthesized angiograms. Capitalizing on the improved vascular image quality, we devised and tailored a self-correcting automated graphing approach that achieves a reconstruction of cortical microvasculature from OCM angiography data sets with accuracy approaching that attained by trained operators. The automated techniques described here will facilitate more widespread study of vascular network topology in health and disease.

The transit time distribution of blood through the cerebral microvasculature both constrains oxygen delivery and governs the kinetics of neuroimaging signals such as blood-oxygen-level-dependent functional Magnetic Resonance Imaging (BOLD fMRI). However, in spite of its importance, capillary transit time distribution has been challenging to quantify comprehensively and efficiently at the microscopic level. Here, we introduce a method, called Dynamic Contrast Optical Coherence Tomography (DyC-OCT), based on dynamic cross-sectional OCT imaging of an intravascular tracer as it passes through the field-of-view. Quantitative transit time metrics are derived from temporal analysis of the dynamic scattering signal, closely related to tracer concentration. Since DyC-OCT does not require calibration of the optical focus, quantitative accuracy is achieved even deep in highly scattering brain tissue where the focal spot degrades. After direct validation of DyC-OCT against dilution curves measured using a fluorescent plasma label in surface pial vessels, we used DyC-OCT to investigate the transit time distribution in microvasculature across the entire depth of the mouse somatosensory cortex. Laminar trends were identified, with earlier transit times and less heterogeneity in the middle cortical layers. The early transit times in the middle cortical layers may explain, at least in part, the early BOLD fMRI onset times observed in these layers. The layer-dependencies in heterogeneity may help explain how a single vascular supply manages to deliver oxygen to individual cortical layers with diverse metabolic needs.

We introduce and implement interferometric near-infrared spectroscopy (iNIRS), which simultaneously extracts optical and dynamical properties of turbid media through analysis of a spectral interference fringe pattern. The spectral interference fringe pattern is measured using a Mach-Zehnder interferometer with a frequency-swept narrow linewidth laser. Fourier analysis of the detected signal is used to determine time-of-flight (TOF)-resolved intensity, which is then analyzed over time to yield TOF-resolved intensity autocorrelations. This approach enables quantification of optical properties, which is not possible in conventional, continuous-wave near-infrared spectroscopy (NIRS). Furthermore, iNIRS quantifies scatterer motion based on TOF-resolved autocorrelations, which is a feature inaccessible by well-established diffuse correlation spectroscopy (DCS) techniques. We prove this by determining TOF-resolved intensity and temporal autocorrelations for light transmitted through diffusive fluid phantoms with optical thicknesses of up to 55 reduced mean free paths (approximately 120 scattering events). The TOF-resolved intensity is used to determine optical properties with time-resolved diffusion theory, while the TOF-resolved intensity autocorrelations are used to determine dynamics with diffusing wave spectroscopy. iNIRS advances the capabilities of diffuse optical methods and is suitable for in vivo tissue characterization. Moreover, iNIRS combines NIRS and DCS capabilities into a single modality.

White Matter Disease is increasingly being recognized as an important cause of cognitive decline and dementia. Various investigations have linked chronic diet-related conditions to the development of white matter lesions, which appear as white matter hyperintensities on T2-weighted magnetic resonance imaging (MRI) scans of the brain. Thus, it can be postulated that the metabolic, inflammatory, and microvascular changes accompanying a western diet, hyperlipidemia, hypertension, and diabetes mellitus type II (DMII) are potential mediators in the development and progression of white matter disease, which in turn contributes to the development and progression of cognitive decline. This review will examine evidence for potential metabolic, inflammatory, and microvascular determinants of white matter disease and cognitive decline. Specifically, we will focus on the effects of altered insulin signaling in diabetes, obesity-induced oxidative stress, neuroinflammation, arterial stiffness due to hypertension, ischemia secondary to cerebral small vessel disease, and blood brain barrier disturbances.