Abstract
Macular diseases, including neovascular age-related macular degeneration (nvAMD), are leading causes of irreversible blindness and visual impairment. One prominent feature of nvAMD is the detachment of the retinal pigment epithelium. The aim of this study is to implement an automated method for the segmentation of the pigment epithelial detachment (PED) using optical coherence tomography (OCT). OCT datasets from 8 patients with nvAMD were acquired during multiple sessions. At each session, 17 images with a resolution of 1020
Keywords
Introduction
The neovascular age-related macular degeneration (nvAMD) is a progressive disorder leading to severe visual impairment or even vision loss. Loss of vision in patients diagnosed with age-related macular degeneration (AMD) occurs due to the development of geographic atrophy (GA) and choroidal neovascularization (CNV) [1, 2, 3]. In those cases, it has been proven that the admission of anti-vascular endothelial growth factor (anti-VEGF) agents has dramatically improved the clinical condition of nvAMD patients [4]. As a result, those anti-VEGF therapeutic schemes have become the standard treatment for nvAMD. Despite this fact, there are limitations associated with anti-VEGF based treatments. The primary reason for this is that anti-VEGF therapeutic schemes require frequent clinical assessment in order to monitor the response of the patient to treatment. Moreover, in some cases, monthly intravitreal injections are required for amending the selected treatment plan [5, 6].
In general, nvAMD can be diagnosed using spectral domain optical coherence tomography (SD-OCT). OCT is a powerful imaging modality used to image various aspects of biological tissues, such as structural information, blood flow, elastic parameters, change of polarization state, and molecular content. SD-OCT provides the same high-resolution images as spectral-domain-based devices, which measure the intensity of the backscattered light. In order to provide additional information, polarization-sensitive OCT is often employed for identifying the polarization state of the examined retina. Studies have shown that most cellular parts of the retina preserve the polarization state of the incoming and reflected light, with the exception of melanin [7]. Melanin is found mostly in retinal pigment epithelium (RPE) cell organelles, but was also observed in other structures, including cells affected by pathologic conditions such as pigmentary changes, as well as inside pigment epithelium detachments (PED) [8].
Usually, the definition of the required regions of interest (ROI) is performed manually, through visual inspection by medical experts. However, this is a cumbersome and highly subjective process, which may lead to inconsistencies and reduced accuracy, especially in cases where poor quality OCT images are involved. Alternatively, diagnosis or treatment evaluation may be greatly improved through the application of semi- or fully automatic computer algorithms for detecting the required ROI. In digital imaging, this process is often referred to as image segmentation [8]. Numerous image segmentation algorithms have been proposed over the years, some of which are specially tailored for particular medical imaging data, such as CT, MRI, fundus or dental radiographs [9].
In general, segmentation techniques can be grouped in three wide categories: (a) intensity-based, (b) region-based and (c) model-based. Intensity-based techniques range from conceptually simple algorithms, such as Watershed and various thresholding approaches, to more complex classification schemes, such as Bayesian or k-Means classifiers [10, 11, 12]. In any case, those techniques examine the intensity level of individual image pixels, in order to classify them in two or more groups (background/foreground or several independent ROIs). On the other hand, region-based methods, detect and isolate regions as groups of pixels with common properties, based on specific correlations (such as intensity differences) between neighbouring pixels. This category includes more complex techniques, such as Fuzzy Connectedness, Region Growing or filters based on Markov Random Fields [13, 14, 15]. Model-based segmentation methods rely on predefined geometrical models for detecting depicted objects. Those techniques usually employ a repetitive process where the selected model is constantly updated (morphed), until it successfully detects the shape of the desired ROI. Deformable models, such as Active Contours (snakes) or Level-set based algorithms fall into this category of techniques, which can achieve accurate ROI detection, given an appropriate initial model estimate, but due to their iterative nature, they usually come with an increased computational cost [16, 17].
The isolation of anatomical regions of interest can also be achieved through the definition of the region’s boundaries, through the employment of intensity, region or model-based segmentation algorithms. The identification of anatomical structures (such as the PED) in OCT images is a common application for such techniques. To that end, several studies have presented numerous approaches for detecting or segmenting retinal layer boundaries with varying levels of success. Garvin et al. developed a specific automated approach for three-dimensional (3D) macular segmentation on OCT scans for the division of the retina into five layers [18]. This method was applied to 24 images acquired from 12 patients. The particular technique was assessed by comparing the detected ROIs to the ones defined by experts (golden standard), in terms of the perceived border distance between the two cases, which was found to be 6.1
In this context, the present study proposes a novel image processing technique for detecting PED regions and estimating their volume in SD-OCT images. The proposed technique is defined as a three-step procedure for (a) detecting the upper PED border, (b) detecting the lower PED border and (c) estimate the volume of the area included within the detected PED borders. The detection of the borders, which is the core of the proposed methodology, is based on multiscale Gaussian filtering. The proposed technique was applied to a total of 19 SD-OCT datasets from eight patients and achieved high levels of agreement with the manual segmentation from an expert.
Proposed framework
Data acquisition
The case samples consist of 2 women and 6 men,
High level diagram of the segmentation system for OCT image.
The retinal pigment epithelium forms the upper border of PED.
The proposed methodology consists of three steps, as shown in Fig. 1:
Detection of the upper border of the PED. Detection of the lower border of the PED. Estimation of the volume of the segmented PED.
The upper border of the PED is the retinal pigment epithelium (RPE) and can be detected by taking into account that RPE is a bright structure surrounded by darker pixels, as shown in Fig. 2.
(a) Zoomed version of Fig. 2. (b) Pixel values along the black line (perpendicular to RPE).
The eigenvectors (white lines) corresponding to the most negative eigenvalue are perpendicular to a bright structure (RPE in our case).
Specifically, the pixels lying at the centerline of the RPE can be detected as the local maxima of the image in the direction that is perpendicular to the RPE’s local orientation (Fig. 3). As is known, a function of one variable will present local maximum at a point, if the first derivative vanishes at that point and the second derivative is negative. For a function of two variables, such as an image, the corresponding conditions in order to identify whether a pixel belongs to the centerline of the RPE are: the Hessian matrix should possess a negative eigenvalue and the first derivative of image along the corresponding eigenvector should be zero [24].
The detection of the centerline pixels of the RPE is performed using differential geometry as follows [24]. Let
where
The partial derivatives are estimated by convolving the image
Since the Hessian matrix is symmetric, it possesses real eigenvalues. The pixel at
Having identified the pixels
where
Centrelines detection after Gaussian filtering for various values of the standard deviation (
As mentioned above, the parameter
For each pixel
Using the values of
Image with the maximal eigenvalues.
Binary image after thresholding.
Example of labelling the binary image.
Figure 6 shows the image with the maximal eigenvalues for the aforementioned example.
The next step is to create a binary image,
The next step is to isolate the RPE from the other structures: each column of the image
Then the connected components of the image
Examples of RPE border detection.
(a) Image without RPE border. (b) Corresponding binary image.
In this stage, the upper border of the PED is available for every OCT image. Since the lower border cannot be easily isolated, due to the inherent noise of the OCT images, a semi-automated approach is applied, based on the observation that usually the first images of an OCT scan do not contain RPE. Thus, one such image is selected by the user, serving as a reference image (Fig. 10).
The two characteristic points on the RPE border, where a change of the sign of the orientation takes place.
Purple line is from upper border and green line is from reference image. (a) After vertical displacement of the green line. (b) After rotation of the green line with respect to P1.
(a) Superposition of the detected on the original image. (b) Segmented image.
For each subsequent image, the RPE is scanned from left to right and the first pixel
Using the points P1 and P2, the border of the reference image is displaced and rotated: initially the border is displaced vertically by
Figure 13 displays an example of superimposing the detected PED on the original image, as well as the corresponding segmented image.
Example of images without a PED.
The proposed method was applied on the datasets described in the previous Section. A total number of 323 images were available. Since 141 images did not include a PED (see Fig. 14), the method was applied on the remaining 182 images.
The performance of the method was initially evaluated by means of visual inspection. Figure 15 presents several examples of successful detection of PED.
Furthermore, the performance of the method was evaluated quantitatively using the manual segmentation of the PED from an expert (A. Charonis) as ground truth. Specifically, let
DICE coefficient: True positive rate: Positive Predictive Value: False positive rate:
Examples of successful segmentation using the proposed method.
Comparison of results from the proposed method and other methods from the literature
(a) Regression analysis. (b) Bland Altman plot. The dashed lines denote the limits of agreements (LoA) and the vertical bars the 95% confidence intervals for the LoA.
Different images with low value of 
Examples of binary images with different hysteresis thresholds with 
Images with unclear borders and PED.
In the above formulae,
The proposed method was compared with the methods by [28, 29, 30, 31] with respect to the aforementioned metrics. Table 1 lists the average value and the standard deviation of the metrics for all methods.
The relationship and the agreement of the measurements between the proposed method and the manual ground truth were quantified by means of regression analysis and the Bland-Altman analysis, respectively. Figure 16a presents the regression analysis of the segmentation volume (mm
Since the upper order of the PED is a curvilinear structure, like the ones met in retinal or satellite images, MGF seems like a good candidate for its detection. MGF relies on the definition of the values of the standard deviation (
Furthermore, it was also studied the effect of the thresholding process on the results. Figure 18, shows the binary images that were obtained for the following combinations of the threshold pairs
Figure 19 provides cases where the method did not detect the PED successfully.
In this paper, we proposed a segmentation method for detecting the PED from OCT images. The method comprises two stages: detection of the upper border of the PED based on multiscale Gaussian filtering (MGF) and detection of the lower border by comparing the current image with a properly selected reference one. MGF is a well-known technique that has been widely used for detection of edges, vessel segmentation in colour retinal images [32], extraction of streets from satellites images [24].
Regarding the detection of the lower border of the PED, a registration process was applied. The registration process aligns the border of the reference image with the corresponding parts of the lower border of the current image, using translational and rotational transformations. The proposed approach is quite simple and fast and provides satisfactory results. More sophisticated methods could also be used involving the use of an optimization technique to find the optimum of an evaluation function (for example some kind of distance function) with respect to the parameters of the transform.
The proposed method has similar or better performance with other state of the art methods. According to Table 1, the proposed method ranks second with respect to TPR and Dice coefficient, first with respect to PPV and second with respect to FPR. However, the proposed method will fail to detect the PED, if the dataset does not contain an image that can be used as a reference one or the PED has too unclear borders.
Finally, the average running time is 17 s, using a desktop PC with i7 at 3.6 GHz CPU 16 GB DDR3 RAM under the Matlab programming environment.
Footnotes
Conflict of interest
None to report.
