Measurement of cerebral microvascular compliance in a model of atherosclerosis with optical coherence tomography.

Optical coherence tomography (OCT) has recently been used to produce 3D angiography of microvasculature and blood flow maps of large vessels in the rodent brain in-vivo. However, use of this optical method for the study of cerebrovascular disease has not been fully explored. Recent developments in neurodegenerative diseases has linked common cardiovascular risk factors to neurodegenerative risk factors hinting at a vascular hypothesis for the development of the latter. Tools for studying cerebral blood flow and the myogenic tone of cerebral vasculature have thus far been either highly invasive or required ex-vivo preparations therefore not preserving the delicate in-vivo conditions. We propose a novel technique for reconstructing the flow profile over a single cardiac cycle in order to evaluate flow pulsatility and vessel compliance. A vascular model is used to simulate changes in vascular compliance and interpret OCT results. Comparison between atherosclerotic and wild type mice show a trend towards increased compliance in the smaller arterioles of the brain (diameter < 80µm) in the disease model. These results are consistent with previously published ex-vivo work confirming the ability of OCT to investigate vascular dysfunction.

In vivo functional imaging of intrinsic scattering changes in the human retina with high-speed ultrahigh resolution OCT.

Non-invasive methods of probing retinal function are of interest for the early detection of retinal disease. While retinal function is traditionally directly measured with the electroretinogram (ERG), recently functional optical imaging of the retina has been demonstrated. In this manuscript, stimulus-induced, intrinsic optical scattering changes in the human retina are measured in vivo with high-speed, ultrahigh resolution optical coherence tomography (OCT) operating at 50,000 axial scans per second and ~3.3 micron axial resolution. A stimulus and measurement protocol that enables measurement of functional OCT retinal signals is described. OCT signal changes in the photoreceptors are demonstrated. Two distinct responses having different temporal and spatial properties are reported. These results are discussed in the context of optical intrinsic signals measured previously in the retina by fundus imaging and scanning laser ophthalmoscopy. Finally, challenges associated with in vivo functional retinal imaging in human subjects are discussed.

Projection OCT fundus imaging for visualising outer retinal pathology in non-exudative age-related macular degeneration.

AIMS: To demonstrate ultrahigh-resolution, three-dimensional optical coherence tomography (3D-OCT) and projection OCT fundus imaging for enhanced visualisation of outer retinal pathology in non-exudative age-related macular degeneration (AMD). METHODS: A high-speed, 3.5 mum resolution OCT prototype instrument was developed for the ophthalmic clinic. Eighty-three patients with non-exudative AMD were imaged. Projection OCT fundus images were generated from 3D-OCT data by selectively summing different retinal depth levels. Results were compared with standard ophthalmic examination, including fundus photography and fluorescein angiography, when indicated. RESULTS: Projection OCT fundus imaging enhanced the visualisation of outer retinal pathology in non-exudative AMD. Different types of drusen exhibited distinct features in projection OCT images. Photoreceptor disruption was indicated by loss of the photoreceptor inner/outer segment (IS/OS) boundary and external limiting membrane (ELM). RPE atrophy can be assessed using choroid-level projection OCT images. CONCLUSIONS: Projection OCT fundus imaging facilities rapid interpretation of large 3D-OCT data sets. Projection OCT enhances contrast and visualises outer retinal pathology not visible with standard fundus imaging or OCT fundus imaging. Projection OCT fundus images enable registration with standard ophthalmic diagnostics and cross-sectional OCT images. Outer retinal alterations can be assessed and drusen morphology, photoreceptor impairment and pigmentary abnormalities identified.

Fourier domain mode locking at 1050 nm for ultra-high-speed optical coherence tomography of the human retina at 236,000 axial scans per second.

A Fourier domain mode-locked (FDML) laser at 1050 nm for ultra-high-speed optical coherence tomography (OCT) imaging of the human retina is demonstrated. Achievable performance, physical limitations, design rules, and scaling principles for FDML operation and component choice in this wavelength range are discussed. The fiber-based FDML laser operates at a sweep rate of 236 kHz over a 63 nm tuning range, with 7 mW average output power. Ultra-high-speed retinal imaging is demonstrated at 236,000 axial scans per second. This represents a speed improvement of approximately10x over typical high-speed OCT systems, paving the way for densely sampled volumetric data sets and new imaging protocols.

High-speed, high-resolution optical coherence tomography retinal imaging with a frequency-swept laser at 850 nm.

High-speed, high-resolution optical coherence tomography (OCT) imaging of the human retina is demonstrated using a frequency-swept laser at 850 nm. A compact external cavity semiconductor laser design, optimized for swept-source ophthalmic OCT, is described. The laser enables an effective 16 kHz sweep rate with >10 mm coherence length and a tuning range of approximately 35 nm full width at half-maximum, yielding an axial resolution of <7 micro m in tissue.

In vivo measurement of retinal physiology with high-speed ultrahigh-resolution optical coherence tomography.

Noninvasive in vivo functional optical imaging of the intact retina is demonstrated by using high-speed, ultrahigh-resolution optical coherence tomography (OCT). Imaging was performed with 2.8 microm resolution at a rate of 24,000 axial scans per second. A white-light stimulus was applied to the dark-adapted rat retina, and the average reflectivities from different intraretinal layers were monitored as a function of time. A 10%-15% increase in the average amplitude reflectance of the photoreceptor outer segments was observed in response to the stimulus. The spatial distribution of the change in the OCT signal is consistent with an increase in backscatter from the photoreceptor outer segments. To our knowledge, this is the first in vivo demonstration of OCT functional imaging in the intact retina.