Objective: To demonstrate optical coherence tomography for high-resolution, noninvasive imaging of the human retina. Optical coherence tomography is a new imaging technique analogous to ultrasound B scan that can provide cross-sectional images of the retina with micrometer-scale resolution. Design: Survey optical coherence tomographic examination of the retina, including the macula and optic nerve head in normal human subjects. Settings Research laboratory. Participants: Convenience sample of normal human subjects. Main Outcome Measures: Correlation of optical coherence retinal tomographs with known normal retinal anatomy. Results: Optical coherence tomographs can discriminate the cross-sectional morphologic features of the fovea and optic disc, the layered structure of the retina, and normal anatomic variations in retinal and retinal nerve fiber layer thicknesses with 10- μm depth resolution. Conclusion: Optical coherence tomography is a potentially useful technique for high depth resolution, cross-sectional examination of the fundus.

Optical Coherence Tomography of the Human Retina

The diffraction tomography theorem is adapted to one-dimensional length measurement. The resulting spectral interferometry technique is described and the first length measurements using this technique on a model eye and on a human eye in vivo are presented.

Measurement of intraocular distances by backscattering spectral interferometry

Since its introduction, optical coherence tomography OCT technology has advanced from the laboratory bench to the clinic and back again. Arising from the fields of low coherence inter- ferometry and optical time- and frequency-domain reflectometry, OCT was initially demonstrated for retinal imaging and followed a unique path to commercialization for clinical use. Concurrently, sig- nificant technological advances were brought about from within the research community, including improved laser sources, beam delivery instruments, and detection schemes. While many of these technolo- gies improved retinal imaging, they also allowed for the application of OCT to many new clinical areas. As a result, OCT has been clinically demonstrated in a diverse set of medical and surgical specialties, in- cluding gastroenterology, dermatology, cardiology, and oncology, among others. The lessons learned in the clinic are currently spurring a new set of advances in the laboratory that will again expand the clinical use of OCT by adding molecular sensitivity, improving image quality, and increasing acquisition speeds. This continuous cycle of laboratory development and clinical application has allowed the OCT technology to grow at a rapid rate and represents a unique model for the translation of biomedical optics to the patient bedside. This work presents a brief history of OCT development, reviews current clinical applications, discusses some clinical translation challenges, and re- views laboratory developments poised for future clinical application.

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Optical coherence tomography: a review of clinical development from bench to bedside

We demonstrate ultrahigh speed swept source/Fourier domain ophthalmic OCT imaging using a short cavity swept laser at 100,000 – 400,000 axial scan rates. Several design configurations illustrate tradeoffs in imaging speed, sensitivity, axial resolution, and imaging depth. Variable rate A/D optical clocking is used to acquire linear-in-k OCT fringe data at 100kHz axial scan rate with 5.3um axial resolution in tissue. Fixed rate sampling at 1 GSPS achieves a 7.5mm imaging range in tissue with 6.0um axial resolution at 100kHz axial scan rate. A 200kHz axial scan rate with 5.3um axial resolution over 4mm imaging range is achieved by buffering the laser sweep. Dual spot OCT using two parallel interferometers achieves 400kHz axial scan rate, almost 2X faster than previous 1050nm ophthalmic results and 20X faster than current commercial instruments. Superior sensitivity roll-off performance is shown. Imaging is demonstrated in the human retina and anterior segment. Wide field 12×12mm data sets include the macula and optic nerve head. Small area, high density imaging shows individual cone photoreceptors. The 7.5mm imaging range configuration can show the cornea, iris, and anterior lens in a single image. These improvements in imaging speed and depth range provide important advantages for ophthalmic imaging. The ability to rapidly acquire 3D-OCT data over a wide field of view promises to simplify examination protocols. The ability to image fine structures can provide detailed information on focal pathologies. The large imaging range and improved image penetration at 1050nm wavelengths promises to improve performance for instrumentation which images both the retina and anterior eye. These advantages suggest that swept source OCT at 1050nm wavelengths will play an important role in future ophthalmic instrumentation.

Ultrahigh speed 1050nm swept source/Fourier domain OCT retinal and anterior segment imaging at 100,000 to 400,000 axial scans per second.

We demonstrate ultrahigh speed spectral / Fourier domain optical coherence tomography (OCT) using an ultrahigh speed CMOS line scan camera at rates of 70,000 - 312,500 axial scans per second. Several design configurations are characterized to illustrate trade-offs between acquisition speed, resolution, imaging range, sensitivity and sensitivity roll-off performance. Ultrahigh resolution OCT with 2.5 - 3.0 micron axial image resolution is demonstrated at approximately 100,000 axial scans per second. A high resolution spectrometer design improves sensitivity roll-off and imaging range performance, trading off imaging speed to 70,000 axial scans per second. Ultrahigh speed imaging at >300,000 axial scans per second with standard image resolution is also demonstrated. Ophthalmic OCT imaging of the normal human retina is investigated. The high acquisition speeds enable dense raster scanning to acquire densely sampled volumetric three dimensional OCT (3D-OCT) data sets of the macula and optic disc with minimal motion artifacts. Imaging with approximately 8 - 9 micron axial resolution at 250,000 axial scans per second, a 512 x 512 x 400 voxel volumetric 3D-OCT data set can be acquired in only approximately 1.3 seconds. Orthogonal registration scans are used to register OCT raster scans and remove residual axial eye motion, resulting in 3D-OCT data sets which preserve retinal topography. Rapid repetitive imaging over small volumes can visualize small retinal features without motion induced distortions and enables volume registration to remove eye motion. Cone photoreceptors in some regions of the retina can be visualized without adaptive optics or active eye tracking. Rapid repetitive imaging of 3D volumes also provides dynamic volumetric information (4D-OCT) which is shown to enhance visualization of retinal capillaries and should enable functional imaging. Improvements in the speed and performance of 3D-OCT volumetric imaging promise to enable earlier diagnosis and improved monitoring of disease progression and response to therapy in ophthalmology, as well as have a wide range of research and clinical applications in other areas.

Ultrahigh speed spectral / Fourier domain OCT ophthalmic imaging at 70,000 to 312,500 axial scans per second

Optical frequency domain imaging (OFDI) in the 800-nm biological imaging window is demonstrated by using a novel wavelength-swept laser source. The laser output is tuned continuously from 815 to 870 nm at a 43.2-kHz repetition rate with 7-mW average power. Axial resolution of 10-µm in biological tissue and peak sensitivity of 96 dB are achieved. In vivo imaging of Xenopus laevis is demonstrated with an acquisition speed of 84 frames per second (512 axial lines per frame). This new imaging technique may prove useful in comprehensive retinal screening for medical diagnosis and contrast-agent-based imaging for biological investigations.

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Optical frequency domain imaging with a rapidly swept laser in the 815-870 nm range

Three dimensional rapid large depth range imaging of the anterior segments of the human eye by an optical frequency domain imaging system is presented. The tunable source spans from 1217 to 1356 nm with an average output power of 60 mW providing a measured axial resolution of 10 mum in air based on the coherence envelope. The effective depth range is 4 mm, defined as the distance over which the sensitivity drops by 6 dB, achieved by frequency shifting the optical signal using acousto-optic modulators. The measured maximum sensitivity is 109 dB at a sample arm power of 14.7mW and A-lines rate of 43,900 per second. Images consisting of 512 depth profiles are acquired at an acquisition rate of 85 frames per second. We demonstrate an optical frequency domain imaging system capable of mapping in vivo the entire area of the human anterior segment (13.4 x 12 x 4.2 mm) in 1.4 seconds.

/pdf/large-depth-high-resolution-full-3d-imaging-of-the-anterior-4uaofdmzla.pdf

de J.F. Boer

Papers

Optical frequency domain imaging with a rapidly swept laser in the 815-870 nm range

Large depth-high resolution full 3D imaging of the anterior segments of the eye using high speed Optical Frequency Domain Imaging