Faculty Bibliography

Recent hardware advances in optical coherence tomography (OCT) have led to ever higher A-scan rates. However, the estimation of blood flow axial velocities is limited by the presence and type of noise. Higher acquisition rates alone do not necessarily enable precise quantification of Doppler velocities, particularly if the estimator is suboptimal. In previous work, we have shown that the Kasai autocorrelation estimator is statistically suboptimal under conditions of additive white Gaussian noise. In addition, for practical OCT measurements of flow, decorrelation noise affects Doppler frequency estimation by broadening the signal spectrum. Here, we derive a general maximum likelihood estimator (MLE) for Doppler frequency estimation that takes into account additive white noise as well as signal decorrelation. We compare the decorrelation MLE with existing techniques using simulated and flow phantom data and find that it has better performance, achieving the Cramer-Rao lower bound. By making an approximation, we also provide an interpretation of this method in the Fourier domain. We anticipate that this estimator will be particularly suited for estimating blood flow in in vivo scenarios.

The hemodynamic response to neuronal activation is a well-studied phenomenon in the brain, due to the prevalence of functional magnetic resonance imaging. The retina represents an optically accessible platform for studying lamina-specific neurovascular coupling in the central nervous system; however, due to methodological limitations, this has been challenging to date. We demonstrate techniques for the imaging of visual stimulus-evoked hyperemia in the rat inner retina using Doppler optical coherence tomography (OCT) and OCT angiography. Volumetric imaging with three-dimensional motion correction, en face flow calculation, and normalization of dynamic signal to static signal are techniques that reduce spurious changes caused by motion. We anticipate that OCT imaging of retinal functional hyperemia may yield viable biomarkers in diseases, such as diabetic retinopathy, where the neurovascular unit may be impaired.

High-resolution angiography and total average blood flow measurements in the rat retina using optical coherence tomography (OCT) are presented. Recently, an en face integration method, which does not require explicit calculation of vessel angles, was introduced to calculate blood flow using Doppler OCT. Using this method, rapid two-dimensional scanning has been shown to quantify pulsatile flow. However, high scanning speeds sacrifice transverse sampling density and may lead to biased velocity estimates. Alternatively, we show here that by using a volumetric scanning protocol that asynchronously samples a single vessel with respect to the heartbeat, it is possible to obtain accurate time-averaged flow measurements, even without explicit information about the pulsatile waveform. Total average retinal blood flows calculated using either arteries or veins are comparable, supporting the accuracy of this method.

In optical coherence tomography (OCT) and ultrasound, unbiased Doppler frequency estimators with low variance are desirable for blood velocity estimation. Hardware improvements in OCT mean that ever higher acquisition rates are possible, which should also, in principle, improve estimation performance. Paradoxically, however, the widely used Kasai autocorrelation estimator's performance worsens with increasing acquisition rate. We propose that parametric estimators based on accurate models of noise statistics can offer better performance. We derive a maximum likelihood estimator (MLE) based on a simple additive white Gaussian noise model, and show that it can outperform the Kasai autocorrelation estimator. In addition, we also derive the Cramer Rao lower bound (CRLB), and show that the variance of the MLE approaches the CRLB for moderate data lengths and noise levels. We note that the MLE performance improves with longer acquisition time, and remains constant or improves with higher acquisition rates. These qualities may make it a preferred technique as OCT imaging speed continues to improve. Finally, our work motivates the development of more general parametric estimators based on statistical models of decorrelation noise.

Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties.

Optical Coherence Tomography (OCT) angiography was applied to image functional hyperemia in different vascular compartments in the rat somatosensory cortex. Dynamic backscattering changes, indicative of changes in dynamic red blood cell (dRBC) content, were used to monitor the hemodynamic response. Three-dimensional movies depicting the microvascular response to neuronal activation were created for the first time. An increase in the attenuation coefficient during activation was identified, and a simple normalization procedure was proposed to correct for it. This procedure was applied to determine compartment-resolved backscattering changes caused by dRBC content changes during functional activation. Increases in dRBC content were observed in all vascular compartments (arterial, arteriolar, capillary, and venular), with the largest responses found in the arterial and arteriolar compartments. dRBC content increased with dilation in arteries but with barely detectable dilation in veins. dRBC content increased in capillaries without significant "all or none" capillary recruitment.