Level set segmentation of retinal structures

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University London.Changes in retinal structure are related to different eye diseases. Various retinal imaging techniques, such as fundus imaging and optical coherence tomography (OCT) imaging modalities, have been developed for non-intrusive ophthalmology diagnoses according to the vasculature changes. However, it is time consuming or even impossible for ophthalmologists to manually label all the retinal structures from fundus images and OCT images. Therefore, computer aided diagnosis system for retinal imaging plays an important role in the assessment of ophthalmologic diseases and cardiovascular disorders. The aim of this PhD thesis is to develop segmentation methods to extract clinically useful information from these retinal images, which are acquired from different imaging modalities. In other words, we built the segmentation methods to extract important structures from both 2D fundus images and 3D OCT images. In the first part of my PhD project, two novel level set based methods were proposed for detecting the blood vessels and optic discs from fundus images. The first one integrates Chan-Vese's energy minimizing active contour method with the edge constraint term and Gaussian Mixture Model based term for blood vessels segmentation, while the second method combines the edge constraint term, the distance regularisation term and the shape-prior term for locating the optic disc. Both methods include the pre-processing stage, used for removing noise and enhancing the contrast between the object and the background. Three automated layer segmentation methods were built for segmenting intra-retinal layers from 3D OCT macular and optic nerve head images in the second part of my PhD project. The first two methods combine different methods according to the data characteristics. First, eight boundaries of the intra-retinal layers were detected from the 3D OCT macular images and the thickness maps of the seven layers were produced. Second, four boundaries of the intra-retinal layers were located from 3D optic nerve head images and the thickness maps of the Retinal Nerve Fiber Layer (RNFL) were plotted. Finally, the choroidal layer segmentation method based on the Level Set framework was designed, which embedded with the distance regularisation term, edge constraint term and Markov Random Field modelled region term. The thickness map of the choroidal layer was calculated and shown.Department of Computer Science, Brunel University London

Normative Data and Minimally Detectable Change for Inner Retinal Layer Thicknesses Using a Semi-automated OCT Image Segmentation Pipeline

Neurodegenerative and neuroinflammatory diseases regularly cause optic nerve and retinal damage. Evaluating retinal changes using optical coherence tomography (OCT) in diseases like multiple sclerosis has thus become increasingly relevant. However, intraretinal segmentation, a necessary step for interpreting retinal changes in the context of these diseases, is not standardized and often requires manual correction. Here we present a semi-automatic intraretinal layer segmentation pipeline and establish normative values for retinal layer thicknesses at the macula, including dependencies on age, sex, and refractive error. Spectral domain OCT macular 3D volume scans were obtained from healthy participants using a Heidelberg Engineering Spectralis OCT. A semi-automated segmentation tool (SAMIRIX) based on an interchangeable third-party segmentation algorithm was developed and employed for segmentation, correction, and thickness computation of intraretinal layers. Normative data is reported froma 6mmEarly Treatment Diabetic Retinopathy Study (ETDRS) circle around the fovea. An interactive toolbox for the normative database allows surveying for additional normative data. We cross-sectionally evaluated data from218 healthy volunteers (144 females/74males, age 36.5 ± 12.3 years, range 18–69 years). Average macular thickness (MT) was 313.70 ± 12.02 μm, macular retinal nerve fiber layer thickness (mRNFL) 39.53 ± 3.57 μm, ganglion cell and inner plexiform layer thickness (GCIPL) 70.81 ± 4.87 μm, and inner nuclear layer thickness (INL) 35.93 ± 2.34 μm. All retinal layer thicknesses decreased with age. MT and GCIPL were associated with sex, with males showing higher thicknesses. Layer thicknesses were also positively associated with each other. Repeated-measurement reliability for the manual correction of automatic intraretinal segmentation results was excellent, with an intra-class correlation coefficient >0.99 for all layers. The SAMIRIX toolbox can simplify intraretinal segmentation in research applications, and the normative data application may serve as an expandable reference for studies, in which normative data cannot be otherwise obtained

A Deep Learning Approach to Denoise Optical Coherence Tomography Images of the Optic Nerve Head

Purpose: To develop a deep learning approach to de-noise optical coherence tomography (OCT) B-scans of the optic nerve head (ONH). Methods: Volume scans consisting of 97 horizontal B-scans were acquired through the center of the ONH using a commercial OCT device (Spectralis) for both eyes of 20 subjects. For each eye, single-frame (without signal averaging), and multi-frame (75x signal averaging) volume scans were obtained. A custom deep learning network was then designed and trained with 2,328 "clean B-scans" (multi-frame B-scans), and their corresponding "noisy B-scans" (clean B-scans + gaussian noise) to de-noise the single-frame B-scans. The performance of the de-noising algorithm was assessed qualitatively, and quantitatively on 1,552 B-scans using the signal to noise ratio (SNR), contrast to noise ratio (CNR), and mean structural similarity index metrics (MSSIM). Results: The proposed algorithm successfully denoised unseen single-frame OCT B-scans. The denoised B-scans were qualitatively similar to their corresponding multi-frame B-scans, with enhanced visibility of the ONH tissues. The mean SNR increased from $4.02 \pm 0.68$ dB (single-frame) to $8.14 \pm 1.03$ dB (denoised). For all the ONH tissues, the mean CNR increased from $3.50 \pm 0.56$ (single-frame) to $7.63 \pm 1.81$ (denoised). The MSSIM increased from $0.13 \pm 0.02$ (single frame) to $0.65 \pm 0.03$ (denoised) when compared with the corresponding multi-frame B-scans. Conclusions: Our deep learning algorithm can denoise a single-frame OCT B-scan of the ONH in under 20 ms, thus offering a framework to obtain superior quality OCT B-scans with reduced scanning times and minimal patient discomfort

FloatingCanvas: quantification of 3D retinal structures from spectral-domain optical coherence tomography

Spectral-domain optical coherence tomography (SD-OCT) provides volumetric images of retinal structures with unprecedented detail. Accurate segmentation algorithms and feature quantification in these images, however, are needed to realize the full potential of SD-OCT. The fully automated segmentation algorithm, FloatingCanvas, serves this purpose and performs a volumetric segmentation of retinal tissue layers in three-dimensional image volume acquired around the optic nerve head without requiring any pre-processing. The reconstructed layers are analysed to extract features such as blood vessels and retinal nerve fibre layer thickness. Findings from images obtained with the RTVue-100 SD-OCT (Optovue, Fremont, CA, USA) indicate that FloatingCanvas is computationally efficient and is robust to the noise and low contrast in the images. The FloatingCanvas segmentation demonstrated good agreement with the human manual grading. The retinal nerve fibre layer thickness maps obtained with this method are clinically realistic and highly reproducible compared with time-domain StratusOCT™

Optic Nerve Head Quantification in Idiopathic Intracranial Hypertension by Spectral Domain OCT

Objective: To evaluate 3D spectral domain optical coherence tomography (SDOCT) volume scans as a tool for quantification of optic nerve head (ONH) volume as a potential marker for treatment effectiveness and disease progression in idiopathic intracranial hypertension (IIH). Design and Patients: Cross-sectional pilot trial comparing 19 IIH patients and controls matched for gender, age and body mass index. Each participant underwent SDOCT. A custom segmentation algorithm was developed to quantify ONH volume (ONHV) and height (ONHH) in 3D volume scans. Results:Whereas peripapillary retinal nerve fiber layer thickness did not show differences between controls and IIH patients, the newly developed 3D parameters ONHV and ONHH were able to discriminate between controls, treated and untreated patients. Both ONHV and ONHH measures were related to levels of intracranial pressure (ICP). Conclusion: Our findings suggest 3D ONH measures as assessed by SDOCT as potential diagnostic and progression markers in IIH and other disorders with increased ICP. SDOCT may promise a fast and easy diagnostic alternative to repeated lumba

Testing a phantom eye under various signal-to-noise ratio conditions using eleven different OCT devices

We compared eleven OCT devices in their ability to quantify retinal layer thicknesses under different signal-strength conditions, using a commercially available phantom eye. We analyzed a medium-intensity 50 µm layer in an identical manner for all devices, using the provided log-scale images and a reconstructed linear-scale tissue reflectivity metric. Thickness measurements were highly comparable when the data were analyzed in an identical manner. With optimal signal strength, the thickness of the 50 µm layer was overestimated by a mean of 4.3 µm in the log-scale images and of 2.7 µm in the linear-scale images