A team with world-class expertise in ophthalmic disease, imaging, retinal pathology, and biomedical engineering will utilize hyperspectral imaging to provide, for the first time, in vivo molecular probing, validated with histopathologic correlation, of age-related macular degeneration (AMD). Their system, a specially modified fundus camera harnessed to cutting-edge biomedical image analysis techniques, will revolutionize the field by identifying the distribution and spectral signature of the various chromophores and fluorophores associated with AMD lesions. Drusen, the hallmark lesions of AMD, are biochemically heterogeneous and are key to understanding this disease. However, their composition cannot be determined in vivo with even the current highest resolution techniques. Hyperspectral imaging data, now uniquely clinically attainable with a new snapshot hyperspectral device, offers a vision of spectral biopsy of the retina. This data is encoded in a four-dimensional """"""""hypercube,"""""""" with two spatial (x and y coordinates) and two spectral (amplitude and wavelength) dimensions. This complex data cube can be explored with advanced unsupervised mathematical tools that search out the dominant spectral signatures in the data matrix. By dissecting the spectral reflectance and autofluorescence (AF) signatures from drusen and other AMD lesions, this research will achieve in vivo spectral classifications of these lesions. To accomplish this, the research team plans to acquire hyperspectral, photographic, AF and infrared scanning laser ophthalmoscope (SLO), and spectral domain optical coherence tomography (SD-OCT) images of all phenotypes of AMD, with analysis of the hyperspectral images by an optimized matrix factorization protocol to recover dominant spectra and their spatial distributions. Hyperspectral AF images will also be acquired simultaneously with the same device by adding appropriate excitation and barrier filters. Further, hyperspectral imaging of genotyped donor eyes will provide histopathologic confirmation of the components of drusen and other AMD lesions that correlate with the drusen spectral signatures, as well as robust genotype/phenotype correlations. Long-term goals: We envision an integrated imaging system for AMD and ophthalmologic care that incorporates this paradigm shift in technology. Having such a system of in vivo molecular probes will be instrumental in research. The insights so obtained will be of high value in clinical diagnosis and treatment. In addition, such a system will accelerate translational research with sensitive and early outcome testing of prospective therapeutic agents, saving sight and thereby providing enormous benefit to society.

Public Health Relevance

Hyperspectral imaging with a specially modified retinal camera will provide, for the first time, molecular probing of living eye tissue, validated by examination of donor eye tissue, in the study of age-related macular degeneration (AMD). Identification of the distribution and biochemical nature of AMD lesions will be uniquely instrumental in understanding AMD, the leading cause of blindness in our country. Insights so obtained will be highly valuable in the clinical care of AMD patients and will result in saving sight, with enormous benefit to our society.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
7R01EY021470-02
Application #
8245691
Study Section
Special Emphasis Panel (ZRG1-ETTN-E (92))
Program Officer
Shen, Grace L
Project Start
2011-04-01
Project End
2015-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
2
Fiscal Year
2012
Total Cost
$785,074
Indirect Cost
$180,037
Name
New York University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Tong, Yuehong; Ben Ami, Tal; Hong, Sungmin et al. (2016) HYPERSPECTRAL AUTOFLUORESCENCE IMAGING OF DRUSEN AND RETINAL PIGMENT EPITHELIUM IN DONOR EYES WITH AGE-RELATED MACULAR DEGENERATION. Retina 36 Suppl 1:S127-S136
Li, Hao; Liu, Wenzhong; Dong, Biqin et al. (2016) J Biophotonics :
Tong, Yuehong; Ben Ami, Tal; Hong, Sungmin et al. (2016) HYPERSPECTRAL AUTOFLUORESCENCE IMAGING OF DRUSEN AND RETINAL PIGMENT EPITHELIUM IN DONOR EYES WITH AGE-RELATED MACULAR DEGENERATION. Retina :
Heiferman, Michael J; Fawzi, Amani A (2016) DISCORDANCE BETWEEN BLUE-LIGHT AUTOFLUORESCENCE AND NEAR-INFRARED AUTOFLUORESCENCE IN AGE-RELATED MACULAR DEGENERATION. Retina 36 Suppl 1:S137-S146
Ben Ami, Tal; Tong, Yuehong; Bhuiyan, Alauddin et al. (2016) Spatial and Spectral Characterization of Human Retinal Pigment Epithelium Fluorophore Families by Ex Vivo Hyperspectral Autofluorescence Imaging. Transl Vis Sci Technol 5:5
Heiferman, Michael J; Fawzi, Amani A (2016) DISCORDANCE BETWEEN BLUE-LIGHT AUTOFLUORESCENCE AND NEAR-INFRARED AUTOFLUORESCENCE IN AGE-RELATED MACULAR DEGENERATION. Retina :
Kaluzny, Joel; Li, Hao; Liu, Wenzhong et al. (2016) Bayer Filter Snapshot Hyperspectral Fundus Camera for Human Retinal Imaging. Curr Eye Res :1-7
Simonett, Joseph M; Sohrab, Mahsa A; Pacheco, Jennifer et al. (2015) A Validated Phenotyping Algorithm for Genetic Association Studies in Age-related Macular Degeneration. Sci Rep 5:12875
Heiferman, Michael J; Fernandes, Joshua K; Munk, Marion et al. (2015) RETICULAR PSEUDODRUSEN ON INFRARED IMAGING ARE TOPOGRAPHICALLY DISTINCT FROM SUBRETINAL DRUSENOID DEPOSITS ON EN FACE OPTICAL COHERENCE TOMOGRAPHY. Retina 35:2593-603
Gao, Liang; Smith, R Theodore (2015) Optical hyperspectral imaging in microscopy and spectroscopy - a review of data acquisition. J Biophotonics 8:441-56

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