Analyzing spatial correlations in tissue using angle-resolved low coherence interferometry measurements guided by co-located optical coherence tomography

Kim, Sang-Hoon; Heflin, Stephanie J.; Kresty, Laura A.; Halling, Meredith; Pérez, Laura; Ho, Derek; Crose, Michael; Brown, William J.; Farsiu, Sina; Arshavsky, Vadim Y.; Wax, Adam

doi:10.1364/boe.7.001400

Cited by 18 publications

(12 citation statements)

References 28 publications

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“…Before imaging, each eye was cleared of connective tissue and the superior quadrant was marked. The eye was then positioned with the superior quadrant aligned with the positive vertical scan axis in a custom-designed chamber and stabilized with grease 37 . The chamber design accounted for the eye curvature, which maintained its alignment relative to the custom objective during imaging.…”

Section: Sample Preparationmentioning

confidence: 99%

“…a/ LCI is an optical technique which detects depth-resolved angular scattering distributions from tissue, and has demonstrated high clinical diagnostic accuracy in Barrett's esophagus 35 and cervical dysplasia 36 . Although a/ LCI is not itself an imaging modality, it can be combined with the image guidance of OCT to extract unique light scattering features from distinct layers of the retinal tissue 37 . Co-registration of OCT and a/LCI to an identical imaging volume yields complementary information, specifically by allowing localization of regions of interest in the retina, followed by a/LCI analysis of light scattering parameters.…”

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confidence: 99%

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Multimodal Coherent Imaging of Retinal Biomarkers of Alzheimer’s Disease in a Mouse Model

Song

Steelman

Finkelstein³

et al. 2020

Sci Rep

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We acquired depth-resolved light scattering measurements from the retinas of triple transgenic Alzheimer's Disease (3xTg-AD) mice and wild type (WT) age-matched controls using co-registered angle-resolved low-coherence interferometry (a/LCI) and optical coherence tomography (OCT). Angleresolved light scattering measurements were acquired from the nerve fiber layer, outer plexiform layer, and retinal pigmented epithelium using image guidance and segmented thicknesses provided by coregistered OCT B-scans. Analysis of the OCT images showed a statistically significant thinning of the nerve fiber layer in AD mouse retinas compared to WT controls. The a/LCI scattering measurements provided complementary information that distinguishes AD mice by quantitatively characterizing tissue heterogeneity. The AD mouse retinas demonstrated higher mean and variance in nerve fiber layer light scattering intensity compared to WT controls. Further, the difference in tissue heterogeneity was observed through short-range spatial correlations that show greater slopes at all layers of interest for AD mouse retinas compared to Wt controls. A greater slope indicates a faster loss of spatial correlation, suggesting a loss of tissue self-similarity characteristic of heterogeneity consistent with AD pathology. Use of this combined modality introduces unique tissue texture characterization to complement development of future AD biomarker analysis.

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Section: Sample Preparationmentioning

confidence: 99%

mentioning

confidence: 99%

Multimodal Coherent Imaging of Retinal Biomarkers of Alzheimer’s Disease in a Mouse Model

Song

Steelman

Finkelstein³

et al. 2020

Sci Rep

Self Cite

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“…Angle-resolved OCT is a subset of OCT that provides multiple signals that are sensitive to the angle of light backscattered from the specimen. [36][37][38] A variety of angle-resolved techniques have demonstrated the utility of incorporating angular backscattering information into the OCT signal, including multidirectional OCT for retinal imaging, 39 bright-and dark-field imaging with few-mode fibers for angular multiplexing, 40 and directional OCT for imaging melanin concentration. 41 A specific subtype of angle-resolved OCT, termed scattering-angle-resolved OCT (SAR-OCT), positions an optical element in the pupil of the scanning system that pathlength-encodes angular information of backscattered light from the sample.…”

Section: Introductionmentioning

confidence: 99%

Scattering Angle Resolved Optical Coherence Tomography Detects Early Changes in 3xTg Alzheimer's Disease Mouse Model

Gardner

Baruah

Vargas

et al. 2020

Trans. Vis. Sci. Tech.

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Clinical intensity-based optical coherence tomographic retinal imaging is unable to resolve some of the earliest changes to Alzheimer's disease (AD) neurons. The aim of this pilot study was to demonstrate that scattering-angle-resolved optical coherence tomography (SAR-OCT), which is sensitive to changes in light scattering angle, is a candidate retinal imaging modality for early AD detection. SAR-OCT signal data may be sensitive to changes in intracellular constituent morphology that are not detectable with conventional OCT. Methods: In this cross-sectional study, retinas of a triple transgenic mouse model of AD (3xTg-AD) were imaged alongside age-matched control mice (C57BL/6J) using SAR-OCT. A total of 32 mice (12 control, 20 3xTg-Ad) at four ages (10, 20, 30, and 45 weeks) were included in this cross-sectional study, and three retinal feature sets (scattering, thickness, and angiography) were examined between the disease and control groups. Results: AD mice had significantly increased scattering diversity (lower SAR-OCT C parameter) at the earliest imaging time (10 weeks). Differences in the C parameter between AD and control mice were diminished at later times when both groups showed increased scattering diversity. AD mice have reduced retinal thickness compared to controls, particularly in central regions and superficial layers. No differences in vascular density or fractional blood volume between groups were detected. Conclusions: SAR-OCT is sensitive to scattering angle changes in a 3xTg-AD mouse model and could provide early-stage biomarkers for neurodegenerative diseases such as AD. Translational Relevance: Clinical OCT systems may be modified to record SAR-OCT images for non-invasive retinal diagnostic imaging of patients with neurodegenerative diseases such as AD. Recent guidelines and criteria for diagnosing AD include a category for a symptomatic, pre-dementia phase termed "mild cognitive impairment due to AD" 4,5 ; however, even in this early disease state, significant pathophysiological changes are observed. 6 In fact, changes in the brain can begin more than 20 years prior to the onset of AD symptoms. 7-9 Early detection of AD is believed to represent the best path forward for

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“…Previously, angle-resolved interferometric imaging approaches have been used to detect sub-wavelength cellular properties such as the size distribution of nuclei and more recently to characterize nuclear morphology, in situ, of both a rodent model for esophageal carcinogenesis and murine retinas [8,9]. Thus, while several cell culture and ex-vivo tissue studies have been reported involving angle-resolved imaging, similar optical imaging techniques have not been extensively explored for retinal imaging.…”

Section: Introductionmentioning

confidence: 99%

Design Considerations for Murine Retinal Imaging Using Scattering Angle Resolved Optical Coherence Tomography

et al. 2018

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Optical coherence tomography (OCT), an optical imaging approach enabling cross-sectional analysis of turbid samples, is routinely used for retinal imaging in human and animal models of diseases affecting the retina. Scattering angle resolved (SAR-)OCT has previously been demonstrated as offering additional contrast in human studies, but no SAR-OCT system has been reported in detail for imaging the retinas of mice. An optical model of a mouse eye was designed and extended for validity at wavelengths of light around 1310 nm; this model was then utilized to develop a SAR-OCT design for murine retinal imaging. A Monte Carlo technique simulates light scattering from the retina, and the simulation results are confirmed with SAR-OCT images. Various images from the SAR-OCT system are presented and utility of the system is described. SAR-OCT is demonstrated as a viable and robust imaging platform to extend utility of retinal OCT imaging by incorporating scattering data into investigative ophthalmologic analysis.

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Analyzing spatial correlations in tissue using angle-resolved low coherence interferometry measurements guided by co-located optical coherence tomography

Cited by 18 publications

References 28 publications

Multimodal Coherent Imaging of Retinal Biomarkers of Alzheimer’s Disease in a Mouse Model

Multimodal Coherent Imaging of Retinal Biomarkers of Alzheimer’s Disease in a Mouse Model

Scattering Angle Resolved Optical Coherence Tomography Detects Early Changes in 3xTg Alzheimer's Disease Mouse Model

Design Considerations for Murine Retinal Imaging Using Scattering Angle Resolved Optical Coherence Tomography

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