Project Summary The goal of this research is to enable the integration of advanced polarimetric imaging into existing optical coherence tomography (OCT) hardware and expedite its clinical translation. OCT is essential in contemporary ophthalmology and is routinely used to guide percutaneous coronary interventions. Extending OCT to measure polarization effects arising from tissue anisotropy affords contrast between tissues that are indiscernible in OCT’s conventional scattering signal. Polarization provides insight into the make-up and physical orientation of tissue microstructure beyond the spatial resolution of OCT. Intravascular polarimetry with polarization-sensitive (PS)-OCT offers refined insight into coronary atherosclerosis in patients suffering from myocardial infarction and other coronary syndromes and may improve patient management and guidance of percutaneous interventions. In the eye, PS-OCT has shown promise to detect alterations of the retinal nerve fiber layer (RNFL) that precede the degeneration of its retinal ganglion cell axons encountered in glaucoma, the leading cause of irreversible blindness. However, the dissemination of PS-OCT relies on adoption by a wider community, which has been hindered by the excessive hardware complexity of conventional PS-OCT. This project develops a universal and robust signal processing framework for optical coherence polarimetry (OCP) that accommodates novel simplified hardware implementations. Coherent measurements of the polarization response to propagation through tissue conventionally require polarization-diverse detection and illumination with two input states. To avoid the acute complexity of multiplexing two input states, prototype PS- OCT systems currently employed for imaging the coronary arteries or the lung use sequential input modulation. Still, this remains incompatible with the substantial commercial OCT instrument infrastructure available in the clinic today. OCP capitalizes on an intrinsic symmetry constraint manifesting in round-trip measurements performed with OCT, which enables the recovery of polarization effects from previously ill-conditioned configurations and enables adaptation of existing commercial OCT instruments to perform advanced tissue polarimetry. Aim 1 integrates concepts from magnetic resonance image reconstruction into OCP to compensate for detrimental system effects and suppress speckle-induced polarization noise. Aim 2 adapts OCP to commercial clinical intravascular OCT instruments using a single, spectrally varying input state and polarization diverse detection for investigating plaque rupture and healing in patients. Aim 3 performs OCP with retinal OCT instruments using a single spectrometer, relying on a rotating waveplate module, fitted into the accessible round-trip path and repeated scan patterns established for OCT angiography. RNFL birefringence will be investigated with the adapted clinical instruments in glaucoma patients and healthy controls. Combin...