Combinations of techniques in imaging the retina with high resolution

https://doi.org/10.1016/j.preteyeres.2008.03.002Get rights and content

Abstract

Developments in optical coherence tomography (OCT) have expanded its clinical applications for high-resolution imaging of the retina, as a standalone diagnostic and in combination with other optical imaging modalities. This review presents currently explored combinations of OCT technology with a variety of complementary imaging modalities along with augmentational technologies such as adaptive optics (AO) and tracking. Some emphasis is on the combination of OCT technology with scanning laser ophthalmoscopy (SLO) as well as on using OCT to produce an SLO-like image. Different OCT modalities such as time domain and spectral domain are discussed in terms of their performance and suitability for imaging the retina. Each modality admits several implementations, such as flying spot or using an area or line illumination. Flying spot has taken two principle forms, en-face and longitudinal OCT. The review presents the advantages and disadvantages of different possible combinations of OCT and SLO with AO, evaluating criteria in choosing the best OCT method to fit a specific combination of techniques. Some of these combinations of techniques evolved from bench systems into the clinic, their merit can be judged on images showing different pathologies of the retina. Other potential combinations of techniques are still in their infancy, in which case the discussion will be limited to their technical principles. The potential of any combined implementation to provide clinical relevant data is described by three parameters, which take into account the number of voxels acquired in unit time, the minimum time required to produce or infer an en-face OCT image (or an SLO-like image) and the number of different types of information provided. The current clinically used technologies as well as those under research are comparatively evaluated based on these three parameters. As the technology has matured over the years, their evolution is discussed as well with their potential for further improvements.

Introduction

Today, ocular imaging technology has reached high heights of sophistication, building on the tremendous progress in the last 5 years. However, none of the current imaging methods available fulfill all the ideal requirements of the ophthalmologist faced with the need for rapid and accurate diagnosis. This has led to exploration of combinations of imaging and assistive techniques by groups attempting to solve these deficiencies. The goals driving the combination of different imaging technologies are diverse, including the need for precise targeting and real-time focusing of the en-face optical coherence tomography (OCT) (which lead to the addition of a scanning laser ophthalmoscopy (SLO) channel to the OCT channel), the need for correlation of retinal blood flow with changes in morphology (such as in the combination of OCT with fluorescence imaging) or the need for enhancing the imaging performance (such as the addition of adaptive optics (AO) and tracking to SLO or OCT or combined OCT/SLO).

Expansion of a familiar perspective found in one type of instrument may stimulate interest in combining it with an additional modality, which shares the same viewpoint. For example, en-face imaging (C-scan) has the advantage that ophthalmologists are more familiar with the interpretation of transversal images since they are of similar orientation as those found in ophthalmoscopes, fundus cameras and SLOs. This was an important factor that stimulated research into combining the OCT with SLO technology.

This review will focus primarily on combinations of techniques where the core technology is OCT. Initially, OCT technology advanced towards enhancing the acquisition rate along a line in depth in the image. Nowadays, OCT imaging is found into an ever-growing collection of combinations, which pair OCT with techniques such as SLO, flow imaging, polarization, multifocal electroretinography (mfERG), optophysiology, oximetry, micro-perimetry, etc.

A major goal of current research is scanning a target volume of the retina as fast as possible. Significant progress has been achieved in terms of line-scanning rate, which increased from tens of Hz in the first OCT implementation (Huang et al., 1991) to tens of kHz (Nassif et al., 2004) to using the channelled spectrum or the Fourier domain OCT (FDOCT), and to hundreds of kHz (Huber et al., 2007) using the swept source OCT (SS-OCT) method (see Table 1). However, a fast line-scanning rate may not be sufficient to guarantee superiority in respect of all performances required by an accurate diagnosis.

For instance, imaging methods that are recognized as very fast in the modern OCT imaging today, such as spectral domain OCT (SD-OCT), operate under fixed focus, limiting the accuracy of three-dimensional (3D) acquisition. If the same sensitivity is required within the whole 3D volume, then repetition of acquisitions under several different positions of the focus could lead to longer acquisition times for high-density, high-resolution volumes than the time required by slower line-scanning methods, which allow focus change. Therefore, specific imaging requirements may take precedence over the raw line-scanning rate in order to respond to the need of good sensitivity and sufficient sampling data.

In the discussion, which follows, different imaging modalities and specific implementations are compared in their performance taking into consideration three parameters:

  • 1.

    Mv/s: The number of pixels along three rectangular directions (two lateral and one in depth) acquired in the unit of time. Sometimes, in order to shorten the overall scanning time required to capture a given retina volume, a coarse sampling size is chosen for one of the axes, leading to enlargement of the pixel size along that particular direction, trade-off best described by the parameter Mv/s.

  • 2.

    Ten−face: The time to produce a two-dimensional (2D) OCT image with the SLO orientation.

  • 3.

    Imaging content units (I): The number of different types of information provided in a system by a specific configuration. As combination of techniques compound different types of information (OCT, SLO, fluorescence), the performance Mv/s is multiplied by I to obtain an overall performance of a given combination of techniques, as IMv. For instance for a combined system incorporating OCT, SLO and fluorescence channels which can deliver images simultaneously, I=3.

The combination of techniques is evolving in two principal directions: combination of channels providing multiple information and combination of imaging techniques with assisting technologies, such as AO and tracking. Both lines of development will be presented here.

The quest for faster and more complete acquisition of information from the eye demands evaluation of several trade-offs in the performance of the technologies combined. Such different demands and trade-offs will be discussed, presenting the problems raised by the hardware combination as well as the challenges in developing synergistic interpretations of composite images collected from several imaging channels.

Section snippets

Optical coherence tomography

OCT is a non-invasive high-resolution imaging modality, which employs non-ionizing optical radiation. OCT derives from low-coherence interferometry. This is an absolute measurement technique that was developed for high-resolution ranging and characterization of optoelectronic components (Al-Chalabi et al., 1983, Youngquist et al., 1987). The first application of the low-coherence interferometry in the biomedical optics field was for the measurement of the eye length (Fercher et al., 1988).

Different scanning procedures

To obtain 3D information about the retina, any imaging system is equipped with three scanning means, one to scan the object in depth and two others to scan the object transversally. Depending on the order these scanners are operated and on the scanning direction associated with the line displayed in the raster of the final image delivered, different possibilities exist. One-dimensional (1D) and 2D scans are known. 1D scans are labeled as: A- and T-scans, while 2D scans are labeled as B- and

Different OCT imaging methods

There are two main OCT methods, TD-OCT and SD-OCT. SD-OCT can be implemented in two formats, FD-OCT and SS-OCT. Their utility for retinal imaging has been presented in several recent review articles in this journal (Costa et al., 2006; Drexler and Fujimoto, 2008; van Velthoven et al., 2007). We will shortly review them, to compare their performance and discuss how they can be best combined with other retinal imaging modalities. Each method has its own merits and deficits.

Depth of focus range and dynamic focus in OCT

In order to obtain images with high transverse resolution throughout the whole depth of the retina, dynamic focus is essential. Dynamic focus means maintaining the coherence gate and the focus gate in synchrony in OCT. The confocal core of the OCT channel is what determines the depth of focus in the OCT, and this is an important issue in the progress towards high resolution, sometimes ignored. A good S/N ratio requires that the confocal core of the OCT channel focuses at the same depth where

Combining OCT with SLO

OCT has mainly evolved in the direction of producing cross-sectional images, most commonly perpendicular to the plane orientation of images delivered by a microscope or by an SLO. Several groups have shown that the flying spot concept, utilized in the SLO hardware can be combined with the OCT technology to produce en-face OCT images from the anterior and posterior pole. The depth resolution in SLO is 30–100 μm coarser than that in OCT while the transversal resolution in OCT is affected by random

SLO/fluorescence

The SLO is widely used in fluorescein and ICG angiography to examine human retinal diseases. SLOs have been used for ICG or fluorescein imaging separately, or simultaneously (Holz et al., 1997), although more complex systems performing angiography on both fluorescein and ICG, as well as autofluorescence of the fundus (FAF) have also been reported (Jorzik et al, 2005). Separate optical sources were used to excite the fluorescein (488 nm) and the ICG (790 nm). As with any combination of techniques

SLO+AO

Pioneering work on fundus cameras equipped with AO (Liang et al., 1997) and flying spot SLO systems equipped with AO (Dreher et al., 1989; Roorda et al., 2002) have demonstrated the benefits of AO correction for enhancing the transversal resolution in the image as well as the contrast. The fundus cameras studies (Rha et al., 2006) have paved the way towards combining FF-OCT with AO while the studies on the flying spot represented essential steps in extending this imaging technology towards

Combination of high-resolution imaging technologies with tracking

Eye movements wash out the transverse resolution in both SLO and OCT systems and the axial resolution in OCT. Therefore, tracking must address all three dimensions for OCT while lateral tracking is sufficient for SLO and even for SLO+AO systems. Tracking has evolved from simple CCD-based devices stabilizing the eye via pupil alignment to sophisticated systems, which control the angular orientation of the scanning beam.

Combination of high-resolution imaging technologies with other techniques

Other combinations will be reviewed briefly, such as combinations with physiology methods in both variants, electrical physiology and optophysiology, as well as combinations with polarization, flow imaging and spectroscopic analysis.

Future directions

The future of ophthalmic imaging lies in the integration of different forms of information produced by combinations of techniques. A multi-modal functional imaging concept is of high value for an accurate and early diagnosis of retinal pathologies and pathogenesis. Three parameters have been used in this review to assess comparatively different combinations: (i) the number of Mv/s, (ii) the time to produce a C-scan image, Ten−face and (iii) the number of different types of information provided

Acknowledgments

The authors acknowledge all those who kindly accepted to have their published figures included in this review, as indicated in the corresponding figure caption. A. Podoleanu acknowledges support from Engineering and Physical Sciences Research Council of the UK, European Commission, New York Eye and Ear Infirmary, Ophthalmic Technology Inc., Toronto, Canada. R. Rosen acknowledges support from Ophthalmic Technology Inc., Toronto, Canada, the Bendheim-Lowenstein Family Foundation, the Leon Lane

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