17.5  Doppler (Blood Flow) Retinal OCT

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Fig. 17.6  PS-OCT images of retina with AMD. (a) Intensity; (b) DOPU (color bar: see fig. 17.1c); (c) intensity overlaid with segmented RPE. Image size: 15° (horizontal) × 1 mm (vertical). (From Götzinger et al. [43] by permission of the Optical Society of America)

boundary between inner and outer photoreceptor segments; ETPR, end tips of photoreceptors; RPE). The retardation image (Fig. 17.5b) shows the different polarizing properties of retinal tissue in this region: most tissues preserve the polarization state, i.e., do not introduce or change retardation (blue colors), only the RPE scrambles the polarization state, generating random retardation values (the mix of all color values appears green in this presentation). Figure 17.5c shows the degree of polarization uniformity (DOPU) [43], a quantity closely related to the degree of polarization known from classical polarization optics. DOPU is high (orange to red colors) in all layers except the RPE, indicating the depolarization caused by the RPE. The DOPU image was used to segment the RPE and to generate an overlay image showing intensity (gray scale) and the segmented RPE in red (Fig. 17.5d).

Similar PS-OCT imaging was performed in numerous patients. Figure 17.6 shows an example of a PS-OCT B-scan obtained in the retina of a patient with AMD.

Summary for the Clinician

■PS-OCT provides, in addition to the usual inten- sity-based images, images of retardation, birefringent axis orientation, and depolarization.

■PS-OCT provides intrinsic, tissue-specific contrast of birefringent (e.g., RNFL) and depolarizing (e.g., RPE) tissue.

■Spectral-domain PS-OCT achieves the same imaging speed, sensitivity, and resolution as commercial intensity-based spectral-domain OCT instruments.

■PS-OCT can possibly be used for glaucoma diagnosis (by RNFL birefringence measurements) and for the diagnosis of RPE disturbances associated with diseases like AMD and others (by measuring depolarization).

■Several hundred patients have been imaged by PS-OCT, with encouraging results. Additional studies are necessary to demonstrate the benefit of the additional technical effort.

17.5  Doppler (Blood Flow) Retinal OCT

Assessment of blood flow and microcirculation is certainly the most direct window to tissue, organ, and general health status. There are different modalities in biomedicine that allow measuring perfusion including ultrasound or CT. In contrast, optical methods such as Laser Doppler flowmetry (LDF) or D-OCT have the advantage of being noncontact, label-free, employing nonhazardous radiation. Like ultrasound flow imaging, they make use of the Doppler effect, named after the

Austrian scientist, Christian Doppler, who described the phenomenon that moving sources appear at higher or lower frequency depending on their relative speed toward or away from the observer. Analogously, light scattered at moving red blood cells experiences a shift in optical frequency that is directly proportional to the flow velocity. LDF analyzes the total spectral content of light scattered from perfused tissue volumes illuminated by a laser. Hence, the extraction of defined absolute flow velocities is not possible due to multiple scattering within the irradiated volume at various angles. Also, depth localization is difficult and mainly determined by the penetration depth of the laser light and its coherence properties [44]. Nevertheless, the easy implementation of the technique allowed a number of clinical studies on retinal blood flow. The results stressed the clinical importance of detecting early changes in retinal perfusion as precursor of important diseases such as glaucoma, diabetic retinopathy, and

age-related macula degeneration [45–47]. Of equal impact were several pharmacological studies that helped in understanding the role of endothelial cells and its release of vasoactive substances such as nitride oxide (NO) for perfusion regulation. The major drawback of LDF is the limited depth discrimination: it would, e.g., be of clinical importance to clearly separate choroidal perfusion from inner retinal blood flow.

Compared with LDF, D-OCT not only allows for micron depth localized flow imaging and efficient separation of different flow beds, but also allows absolute quantification of flow within retinal vessels down to the size of small metarterioles and venules. Early implementations of D-OCT were based on time-domain OCT [48–50], and further improvements enabled initial in vivo results of retinal perfusion [51, 52]. Nowadays, Fourier (also frequency or spectral) domain (FD) OCT is gradually replacing timedomain OCT in ophthalmic imaging, owing to its intrinsic

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sensitivity and speed advantage [53, 54] as well as its ability for in vivo 3D imaging [5, 55–59]. The advantages can be effectively exploited by functional extensions such as Doppler (FD) OCT resulting in higher velocity sensitivity

17  and large bandwidth [60–63]. Today, D-OCT has become an active field of research, and recent developments such as resonant Doppler imaging [64], optical microangiography [65], joint frequency and time-domain D-OCT [66], and other different flow filtering methods [67, 68] provide a wide spectrum of exciting possibilities to characterize and contrast perfusion of full retinal volumes.

The different D-OCT modalities can roughly be divided into noninvasive contrasting methods for complementing retinal fluorescent angiography and quantitative methods, that yield absolute flow velocities, flow profiles, and in combination with structure information from standard OCT intensity tomograms, total volume flow within individual vessels.

Contrasting method D-OCT has the advantage of being a fully noninvasive and nonhazardous optical angiographic method [69], allowing frequent monitoring of disease and treatment progression. This might help one to reduce the number of performed fluorescent angiographies, increasing the patient’s comfort by avoiding sideeffects of contrast agent administration. It is however clear that D-OCT alone will only visualize moving red blood cells and thus exhibits no contrast, e.g., for the clinically relevant case of retinal hemorrhages. Also, standard retinal OCT systems yield good contrast for inner retinal structures, but choroidal structures suffer from lower signal and scattering losses, limiting the potential for contrasting the choroidal vascular bed based on D-OCT alone. The latter is particularly interesting for studying the pathogenesis of AMD. Recent developments of optical angiography thus combine intensity information together with D-OCT contrast for compensating this original drawback [70]. Another direction is the use of larger wavelength light sources that exhibit better penetration into posterior retinal structures [71, 72].

The actual power of D-OCT is its ability to quantify blood flow within small vessels with high precision down to the order of 100 µm/s. Typical velocity bandwidths are in the range of 10 mm/s, which covers most of the retinal perfusion. It should however be mentioned that only the velocity component parallel to the observation direction can be quantified. For determination of the true flow speed, the angle between flow vector or vessel and the illumination direction needs to be known. Different methods have been explored for absolute retinal blood velocity values, either in postprocessing by extracting the angle from 3D tomograms [73, 74] or by optical means, using two defined illumination directions for angle independent flow

measurement [75]. Another possibility is to acquire data from two concentric circum-papillar scans of different radii, by measuring the local vessel gradient between both the scans [76]. Patient’s movement however limits the reproducibility of the angle reconstruction, and retinal tracking may be highly beneficial. The angular dependence may be avoided by using angle-independent parameters to characterize flow such as resistance index or pulsatility index, known from ultrasound Doppler imaging.

Fast imaging sequences of vessel dynamics together with blood flow quantification offers unique capabilities to study vascular motion, mechanics, and perfusion regulation. The shearing stress can be readily obtained from the local derivative of the velocity profile [77]. Shear stress causes small deformations of the endothelial cells, which triggers a variety of biochemical and vasomotor functional reactions [78] such as the production of NO. Vascular stiffness is another parameter that can be assessed via the pulsatile properties of retinal vessels. Current studies evoking flicker-stimulated vasomotion investigate the relation of retinal vascular stiffness and predisposition to general vascular diseases based on fast fundus imaging technology [79].

In summary, currently, we have a manifold of D-OCT techniques, yielding qualitative as well as quantitative information with high precision. Initial problems of D-OCT such as phase wrapping or bulk motion artifacts have been largely overcome by refined postprocessing techniques. Interestingly, many Doppler OCT concepts might be easily integrated into commercial OCT platforms, as they mainly involve software adaptations, although retinal tracking would be of advantage. However, the clinical importance still needs to be fully exploited and demonstrated, despite initial promising attempts [80]. Being a fast-evolving field in the last years, D-OCT has the potential to not only become a standard ophthalmology research tool, but also an indispensable diagnosis instrument for enhancing current angiographic techniques far beyond today’s capabilities.

Summary for the Clinician

■D-OCT provides, in addition to standard OCT, intensity contrast information about retinal perfusion.

■Quantitative D-OCT uniquely allows extracting true velocity information of retinal blood flow that can be used in combination with the measured vessel geometry from intensity tomograms to determine total volume flow, dynamic pulsatile flow profiles, vessel compliance, or shear stress.