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Emily K. Swingle
a
, Andrew Lang
b
, Aaron Carass
b
, Howard S. Ying
c
,
Peter A. Calabresi
d
, and Jerry L. Prince
b
a
Department of Biomedical Engineering, The Ohio State University
b
Department of Electrical and Computer Engineering, The Johns Hopkins University
c
Wilmer Eye Institute, The Johns Hopkins University School of Medicine
d
Department of Neurology, The Johns Hopkins University School of Medicine
ABSTRACT
Optical coherence tomography (OCT) is a powerful imaging tool that is particularly useful for exploring retinal
abnormalities in ophthalmological diseases. Recently, it has been used to track changes in the eye associated with
neurological diseases such as multiple sclerosis (MS) where certain tissue layer thicknesses have been associated
with disease progression. A small percentage of MS patients also exhibit what has been called microcystic macular
edema (MME), where uid collections that are thought to be pseudocysts appear in the inner nuclear layer. Very
little is known about the cause of this condition so it is important to be able to identify precisely where these
pseudocysts occur within the retina. This identication would be an important rst step towards furthering our
understanding. In this work, we present a detection algorithm to nd these pseudocysts and to report on their
spatial distribution. Our approach uses a random forest classier trained on manual segmentation data to classify
each voxel as pseudocyst or not. Despite having a small sample size of ve subjects, the algorithm correctly
identies 84.6% of pseudocysts as compared to manual delineation. Finally, using our method, we show that
the spatial distribution of pseudocysts within the macula are generally contained within an annulus around the
fovea.
Keywords: OCT, pseudocysts, segmentation, classication, microcystic macular edema
1. INTRODUCTION
Optical Coherence Tomography (OCT) is becoming a useful imaging tool for estimating the severity of retinal
pathology in both ophthalmology
1
and neurology.
2
Near-infrared light from the OCT scanner penetrates retinal
layers at the back of the eye, and detects backscattered light to create an image. In addition to displaying
the retinal layers, these images can be used to identify structural abnormalities within each layer. One such
abnormality is the appearance of small uid lled regions, sometimes called microcysts or pseudocysts, found
within the retinal tissue. In multiple sclerosis (MS), these pseudocysts occur in about 5% of subjects;
3, 4
a
condition that has been termed microcystic macular edema (MME). Specically, MME is most commonly found
in the inner nuclear layer (INL), see Fig. 1 for an example. Little is known about the appearance of these
pseudocysts, or their implications for disease prognosis, but they have been found to be correlated with disease
severity, a reduction of visual acuity, and thinning of the retinal nerve ber layer (RNFL).
4
It also seems that
optic neuropathy may be associated with these pseudocystic changes.
5, 6
In addition to simply exploring the appearance of these pseudocysts, tracking the longitudinal changes may
also prove to be useful to enhance our understanding of MME. In recent studies by Saidha et al.
3
and Gelfand et
al.,
4
longitudinally scanned OCT data were obtained from several patients with MME (ten patients in Ref. 3
and six patients in Ref. 4). In total, ve of the aected eyes exhibited improvement of MME, seven experienced
worsening of MME, and six showed either no apparent change or uctuations over time (noting that MME was
bilateral in two of the patients). Although these studies indicate possible dynamic characteristics of MME over
time, the volume and location of MME was not quantitatively evaluated and therefore much more can be learned
about the pseudocyst volume and location over time in relation to MS.
It is clear that studying the appearance of these pseudocysts, both cross-sectionally and longitudinally, is
necessary to better help study this condition. With so much about MME still unknown, methods for detecting
and quantifying the size and distribution of these uid-lled areas are essential. Due to the sheer amount of
Medical Imaging 2014: Biomedical Applications in Molecular, Structural, and Functional Imaging,
edited by Robert C. Molthen, John B. Weaver, Proc. of SPIE Vol. 9038, 90380G
2014 SPIE CCC code: 1605-7422/14/$18 doi: 10.1117/12.2043910
Proc. of SPIE Vol. 9038 90380G-1
Downloaded From: http://spiedigitallibrary.org/ on 06/23/2014 Terms of Use: http://spiedl.org/terms
(a)
(b)
(c) (d)
(a)
(b)
(c) (d)
(a)
(b)
(c) (d)
Figure 1: (a) Fundus image showing the location of acquired B-Scans; the red line represents the location of
the B-scan portrayed in (b). (b) B-scan image containing pseudocysts which are shown with 3 zoom below.
(c) and (d) shows areas with small and large pseudocysts, respectively.
data output from OCT, this analysis is only feasible with an automatic detection method. To the best of our
knowledge, there has been no previous research to automatically detect and analyze the spatial conguration of
these pseudocysts within the retina for MME patients. Although a method for identifying closed-contour features
in the retina has been investigated,
7
and a 3D process has been analyzed to locate retinal abnormalities,
8
this
research was not done to identify and analyze the types of cystic areas found in MME, specically.
In this work, we created an algorithm to automatically identify pseudocysts in the retina. The algorithm
uses a simple classication approach where each voxel is classied as pseudocyst or not based on the output
of a trained classier. This detection allows us to both quantify the number of pseudocysts, and display their
spatial distribution across the retina. Overall, our method could be used to give more insight on the cause and
progression of these pseudocysts.
2. METHODS
In our analysis, we used OCT images of the retina acquired over the macular cube. A fundus image, illustrated
in Fig. 1(a), displays the anterior portion of the retina where these images were obtained. The overall volume
comprises 49 OCT images, called B-scans (Fig. 1(b)). Each column of a B-scan is called an A-scan. These B-scans
are acquired over the macula as shown in Fig. 1(a), with the horizontal blue lines representing the location of
each B-scan. Each 2D image portrays details of the retinal layers, as well as abnormalities that may be located
within these layers. Examples of small and large pseudocysts in the INL are shown in Figs. 1(c) and (d).
Our pseudocyst detection algorithm uses a pixel classication approach. Before the classication stage, we
use two preprocessing steps, which are summarized here and described in detail in Lang et al.
9
In the rst step,
we normalize the intensities of the images; the intensity range of each B-scan is clamped and rescaled based on
a robust estimate of the maximum intensity. The purpose of this step is to obtain a more consistent intensity
distribution to improve the performance of the classier. Second, we estimate the location of the inner and outer
retina boundaries, the inner limiting membrane (ILM) and Bruchs membrane (BM), respectively. Knowledge of
these boundaries allows us to restrict the search area for the pseudocysts and also to incorporate the relative
distance of pseudocysts from the retina boundaries as a feature, as we only expect to see them in or near the INL.
Briey, these boundaries are found by looking for large vertical gradients in each image. The inner and outer
boundaries are roughly estimated from the largest positive and negative gradients along each A-scan, respectively.
Final boundary positions were constrained by an estimated position of the photoreceptor junction (a large positive
gradient near the bottom of the retina), median ltered to remove outliers, and nally smoothed using a Gaussian
kernel.
Proc. of SPIE Vol. 9038 90380G-2
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With knowledge of where the retinal boundaries are, our pseudocyst detection algorithm uses a random
forest (RF) classier.
10
We use the RF classier since it has a small number of parameters, is ecient, can extract
highly nonlinear correlations, and its performance is as good or better than other state-of-the-art methods. A RF
works by constructing a forest of multiple decision trees. Each tree is independently trained using a random
sample of the training data and, given an input feature vector, provides a decision about what class the input
belongs to. By aggregating the classication result of each tree and using a majority vote rule, a nal classication
estimate is obtained.
To use RF for our problem, we look at each pixel independently, using a set of 14 features to classify whether
or not each pixel is pseudocyst or non-pseudocyst. As the pseudocysts appear darker than the surrounding retinal
tissue, we primarily use intensity-based features. For the rst two features, we use the voxel intensity and voxel
intensity after a gray-scale morphological closing operation (using a disk structuring element with a radius of
5 pixels). Closing acts to remove the pseudocysts providing a contrast to the original intensity. The next nine
features are the voxel intensity after Gaussian ltering at various scales. The next two features are the Laplacian
and Laplacian of Gaussian of the image as ways to enhance the smaller, narrow pseudocysts. Finally, we use the
relative distance to the retina boundaries as a spatial feature to localize the position of the pseudocysts within
the retina. Specically, we look at the proportional distance of a pixel along each A-scan; for instance, looking at
Fig. 1(b), we might generally expect to nd the pseudocysts at around 30% of the distance from the ILM to the
BM.
To compute a nal pseudocyst segmentation, we simply compute these features at each pixel and evaluate
them using the trained RF classier. Since classication in this manner will produce several spurious pixels
classied as pseudocyst, we simply remove all connected components below a specied threshold. The best value
of this threshold is explored in the next section.
3. EXPERIMENTS AND RESULTS
We used available data with pseudocysts from ve MS subjects having MME. Additionally, we used two
pseudocyst-free healthy controls to aid in training. The OCT scans (20
20