Retinal imaging with polarization-sensitive optical coherence tomography and adaptive optics.
ABSTRACT: Various layers of the retina are well known to alter the polarization state of light. Such changes in polarization may be a sensitive indicator of tissue structure and function, and as such have gained increased clinical attention. Here we demonstrate a polarization-sensitive optical coherence tomography (PS-OCT) system that incorporates adaptive optics (AO) in the sample arm and a single line scan camera in the detection arm. We quantify the benefit of AO for PS-OCT in terms of signal-to-noise, lateral resolution, and speckle size. Double pass phase retardation per unit depth values ranging from 0.25 degrees/microm to 0.65 degrees/microm were found in the birefringent nerve fiber layer at 6 degrees eccentricity, superior to the fovea, with the highest values being noticeably higher than previously reported with PS-OCT around the optic nerve head. Moreover, fast axis orientation and degree of polarization uniformity measurements made with AO-PS-OCT demonstrate polarization scrambling in the retinal pigment epithelium at the highest resolution reported to date.
Project description:Using a generalized design for a polarization-sensitive optical coherence tomography (PS-OCT) system with a single input polarization state (SIPS), we prove the existence of an infinitely large design space over which it is possible to develop simple PS-OCT systems that yield closed form expressions for birefringence. Through simulation and experiment, we validate this analysis by demonstrating new configurations for PS-OCT systems, and present guidelines for the general design of such systems in light of their inherent inaccuracies. After accounting for systemic errors, alternative designs exhibit similar performance on average to the traditional SIPS PS-OCT system. This analysis could be extended to systems with multiple input polarization states and could usher in a new generation of PS-OCT systems optimally designed to probe specific birefringent samples with high accuracy.
Project description:We present a very simple method of constructing a polarization-sensitive optical coherence tomography (PS-OCT) system. An ordinary fiber-based swept-source OCT system was reconfigured for PS-OCT by adding a long section of polarization-maintaining fiber in the sample arm. Two polarization modes of a large group-delay difference formed spatially distinguished polarization channels. The depth-encoded information on the polarization states was retrieved by an amplitude-based analysis. We found that our method provides an economic scheme of PS-OCT. It demonstrates that an ordinary OCT system can be easily reconfigured for PS-OCT imaging if it has sufficient margins in the imaging range.
Project description:We acquired in vivo images of the human optic nerve head (ONH) using an adaptive optics-optical coherence tomography (AO-OCT) system. In order to improve imaging of the lamina cribrosa in the ONH with high lateral resolution and sensitivity, we implemented a complex conjugate artifact-free Fourier domain OCT (Fd-OCT) acquisition scheme with a reference arm-based phase shifting method. This allowed positioning of the lamina cribrosa structures near the zero path length difference where AO-OCT imaging achieves highest sensitivity. Implementation of our complex conjugate artifact removal (CCR) method required constant phase shifts between consecutive axial scans (A-scans), generated by continuous beam path-length changes from offsetting the pivot point of the scanning mirror placed in the reference arm. Fourier transform along the transverse axis and a filtering algorithm allowed reconstruction of CCR AO-OCT images. The suppression ratio of the mirror artifact was approximately 22 dB (at 18,000 A-scans per second acquisition speed) with a paperboard test target and an optimum phase-shift value. Finally, we reconstructed the three-dimensional structure of human ONH with enhanced depth range and sensitivity using CCR AO-OCT.
Project description:PURPOSE:With recent advancements in personalized medicine, biopsies must contain sufficient tumor for histologic diagnosis and molecular testing. However, inadvertent biopsy of tumor-associated fibrosis compromises tumor yield, resulting in delayed diagnoses and/or repeat procedures when additional tumor is needed. The ability to differentiate tumor from fibrosis intraprocedurally during biopsy could significantly increase tumor yield. Polarization-sensitive optical coherence tomography (PS-OCT) is an imaging modality that is endoscope- and/or needle-compatible, and provides large volumetric views of tissue microstructure with high resolution (?10 ?m) while simultaneously measuring birefringence of organized tissues such as collagen. We aim to determine whether PS-OCT can accurately detect and distinguish tumor-associated fibrosis from tumor. EXPERIMENTAL DESIGN:PS-OCT was obtained ex vivo in 64 lung nodule samples. PS-OCT birefringence was measured and correlated to collagen content in precisely matched histology, quantified on picrosirius red (PSR) staining. RESULTS:There was a strong positive correlation between PS-OCT measurement of birefringent fibrosis and total collagen content by PSR (r = 0.793; P < 0.001). In addition, PS-OCT was able to accurately classify tumor regions with >20% fibrosis from those with low fibrosis (?20%) that would likely yield higher tumor content (P < 0.0001). CONCLUSIONS:PS-OCT enables accurate fibrosis detection and can distinguish tumor regions with low fibrosis. PS-OCT has significant potential for clinical impact, as the ability to differentiate tumor from fibrosis could be used to guide intraprocedural tissue sampling in vivo, or for rapid biopsy adequacy assessment ex vivo, to increase diagnostic tumor yield essential for patient care and research.
Project description:Purpose:Subretinal fibrosis (SRFib) is an important cause of permanent loss-of-vision diseases with submacular neovascularization, but a reliable diagnostic method is currently missing. This study uses polarization-sensitive optical coherence tomography (PS-OCT) to detect SRFib within retinal lesions by measurement of its birefringent collagen fibers. Methods:Twenty-five patients were enrolled with retinal pathology in one or both eyes containing (1) suspected SRFib, (2) lesions suspected not to be fibrotic, or (3) lesions with doubtful presence of SRFib. All eyes were evaluated for SRFIb using conventional diagnostics by three retinal specialists. PS-OCT images were visually evaluated for SRFib based on cumulative phase retardation, local birefringence, and optic axis uniformity. Results:Twenty-nine eyes from 22 patients were scanned successfully. In 13 eyes, SRFib was diagnosed by all retinal specialists; of these, 12 were confirmed by PS-OCT and one was inconclusive. In nine eyes, the retinal specialists expected no SRFib, which was confirmed by PS-OCT in all cases. In seven eyes, the retinal specialists' evaluations were inconsistent with regard to the presence of SRFib. PS-OCT confirmed the presence of SRFib in four of these eyes and the absence of SRFib in two eyes and was inconclusive in one eye. Conclusions:In 21 out of 22 eyes, PS-OCT confirmed the evaluation of retinal specialists regarding the presence of SRFib. PS-OCT provided additional information to distinguish SRFib from other tissues within subretinal neovascular lesions in 6 out of 7 eyes. Translational Relevance:PS-OCT can identify and quantify SRFib in doubtful cases for which a reliable diagnosis is currently lacking.
Project description:To image the retinal pigment epithelium (RPE) after macular laser and to monitor healing responses over time in vivo in patients with diabetic maculopathy using polarization-sensitive optical coherence tomography (OCT).Prospective, nonrandomized clinical trial.In this single-center trial (Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria), 13 patients (13 eyes) underwent grid photocoagulation for diabetic maculopathy. Retinal healing processes were continuously followed over the course of 3 months. A polarization-sensitive OCT prototype was used, allowing detection and measurement of the RPE changes based on their specific polarization-scrambling qualities.After 1 day, the intraretinal photocoagulation lesions were sharply demarcated, whereas RPE changes were rather subtle. At 1 week, all lesions exhibited traction of the inner retinal layers toward the RPE and loss of photoreceptor cells. In tissue-sensitive polarization-sensitive OCT imaging, polarization-scrambling columns were found at the level of the RPE. During follow-up, different healing responses were seen in the polarization-scrambling RPE layer, ranging from hyperproliferation to focal atrophy.Because of the properties of the polarization state of backscattered light, polarization-sensitive OCT revealed specific morphologic changes in the RPE and outer retinal layers secondary to retinal laser treatment undetectable with intensity-based spectral-domain OCT. The increase in polarization-scrambling tissue over the course of 3 months indicates a more intense healing reaction and proliferation of RPE cells than previously characterized in rodent studies.
Project description:Remodeling of tissue, such as airway smooth muscle (ASM) and extracellular matrix, is considered a key feature of airways disease. No clinically accepted diagnostic method is currently available to assess airway remodeling or the effect of treatment modalities such as bronchial thermoplasty in asthma, other than invasive airway biopsies. Optical coherence tomography (OCT) generates cross-sectional, near-histological images of airway segments and enables identification and quantification of airway wall layers based on light scattering properties only. In this study, we used a custom motorized OCT probe that combines standard and polarization sensitive OCT (PS-OCT) to visualize birefringent tissue in vivo in the airway wall of a patient with severe asthma in a minimally invasive manner. We used optic axis uniformity (OAxU) to highlight the presence of uniformly arranged fiber-like tissue, helping visualizing the abundance of ASM and connective tissue structures. Attenuation coefficient images of the airways are presented for the first time, showing superior architectural contrast compared to standard OCT images. A novel segmentation algorithm was developed to detect the surface of the endoscope sheath and the surface of the tissue. PS-OCT is an innovative imaging technique that holds promise to assess airway remodeling including ASM and connective tissue in a minimally invasive, real-time manner.
Project description:One major hallmark of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) is the deposition of extracellular senile plaques and vessel wall deposits composed of amyloid-beta (A?). In AD, degeneration of neurons is preceded by the formation of A? plaques, which show different morphological forms. Most of them are birefringent owing to the parallel arrangement of amyloid fibrils. Here, we present polarization sensitive optical coherence microscopy (PS-OCM) for imaging mature neuritic A? plaques based on their birefringent properties. Formalin-fixed, post-mortem brain samples of advanced stage AD patients were investigated. In several cortical brain regions, neuritic A? plaques were successfully visualized in tomographic and three-dimensional (3D) images. Cortical grey matter appeared polarization preserving, whereas neuritic plaques caused increased phase retardation. Consistent with the results from PS-OCM imaging, the 3D structure of senile A? plaques was computationally modelled for different illumination settings and plaque sizes. Furthermore, the birefringent properties of cortical and meningeal vessel walls in CAA were investigated in selected samples. Significantly increased birefringence was found in smaller vessels. Overall, these results provide evidence that PS-OCM is able to assess amyloidosis based on intrinsic birefringent properties.
Project description:Purpose:The purpose of this paper was to determine the architecture of the collagen fibers of the peripapillary sclera, the retinal nerve fiber layer (RNFL), and Henle's fiber layer in vivo in 3D using polarization-sensitive optical coherence tomography (PS-OCT). Methods:Seven healthy volunteers were imaged with our in-house built PS-OCT system. PS-OCT imaging included intensity, local phase retardation, relative optic axis, and optic axis uniformity (OAxU). Differential Mueller matrix calculus was used for the first time in ocular tissues to visualize local orientations that varied with depth, incorporating a correction method for the fiber orientation in preceding layers. Results:Scleral collagen fiber orientation images clearly showed an inner layer with an orientation parallel to the RNFL orientation, and a deeper layer where the collagen was circularly oriented. RNFL orientation images visualized the nerve fibers leaving the optic nerve head (ONH) in a radial pattern. The phase retardation and orientation of Henle's fiber layer were visualized locally for the first time. Conclusions:PS-OCT successfully showed the orientation of the retinal nerve fibers, sclera, and Henle's fiber layer, and is to the extent of our knowledge the only technique able to do so in 3D in vivo. Translational Relevance:In vivo 3D imaging of scleral collagen architecture and the retinal neural fibrous structures can improve our understanding of retinal biomechanics and structural alterations in different disease stages of myopia and glaucoma.
Project description:Using a fiber-based swept-source (SS) polarization-sensitive optical coherence tomography (PS-OCT) system, we investigate the degree of polarization (DOP) of light backscattered from the retinal nerve fiber layer (RNFL) in normal human subjects. Algorithms for processing data were developed to analyze the deviation in phase retardation and intensity of backscattered light in directions parallel and perpendicular to the nerve fiber axis (fast and slow axes of RNFL). Considering superior, inferior, and nasal quadrants, we observe the strongest degradation in the DOP with increasing RNFL depth in the temporal quadrant. Retinal ganglion cell axons in normal human subjects are known to have the smallest diameter in the temporal quadrant, and the greater degradation observed in the DOP suggests that higher polarimetric noise may be associated with neural structure in the temporal RNFL. The association between depth degradation in the DOP and RNFL structural properties may broaden the utility of PS-OCT as a functional imaging technique.