Chieh-Li Chen

Quantitative 3D-OCT motion correction with tilt and illumination correction, robust similarity measure and regularization

Variability in illumination, signal quality, tilt and the amount of motion pose challenges for post-processing based 3D-OCT motion correction algorithms. We present an advanced 3D-OCT motion correction algorithm using image registration and orthogonal raster scan patterns aimed at addressing these challenges. An intensity similarity measure using the pseudo Huber norm and a regularization scheme based on a pseudo L0.5 norm are introduced. A two-stage registration approach was developed. In the first stage, only axial motion and axial tilt are coarsely corrected. This result is then used as the starting point for a second stage full optimization. In preprocessing, a bias field estimation based approach to correct illumination differences in the input volumes is employed. Quantitative evaluation was performed using a large set of data acquired from 73 healthy and glaucomatous eyes using SD-OCT systems. OCT volumes of both the optic nerve head and the macula region acquired with three independent orthogonal volume pairs for each location were used to assess reproducibility. The advanced motion correction algorithm using the techniques presented in this paper was compared to a basic algorithm corresponding to an earlier version and to performing no motion correction. Errors in segmentation-based measures such as layer positions, retinal and nerve fiber thickness, as well as the blood vessel pattern were evaluated. The quantitative results consistently show that reproducibility is improved considerably by using the advanced algorithm, which also significantly outperforms the basic algorithm. The mean of the mean absolute retinal thickness difference over all data was 9.9 um without motion correction, 7.1 um using the basic algorithm and 5.0 um using the advanced algorithm. Similarly, the blood vessel likelihood map error is reduced to 69% of the uncorrected error for the basic and to 47% of the uncorrected error for the advanced algorithm. These results demonstrate that our advanced motion correction algorithm has the potential to improve the reliability of quantitative measurements derived from 3D-OCT data substantially.

Longitudinal Change of Circumpapillary Retinal Nerve Fiber Layer Thickness in Children With Optic Pathway Gliomas

PURPOSE To evaluate longitudinal changes in circumpapillary retinal nerve fiber layer (RNFL) thickness, as measured by spectral-domain optical coherence tomography (SD OCT), in children with optic pathway gliomas. DESIGN Longitudinal cohort study. METHODS Global and quadrant-specific circumpapillary RNFL thickness measures were acquired using either a hand-held SD OCT during sedation or a table-top SD OCT in children old enough to cooperate. Vision loss was defined as either a 0.2 logMAR decline in visual acuity or progression of visual field. Percent change in circumpapillary RNFL thickness in eyes experiencing vision loss was compared to eyes with stable vision. RESULTS Fifty-five eyes completed 250 study visits. Ten eyes (18%) from 7 patients experienced a new episode of vision loss during the study and 45 eyes (82%) from 39 patients demonstrated stable vision across study visits. Percent decline of RNFL thickness between the baseline visit and first event of vision loss event was greatest in the superior (-14%) and inferior (-10%) quadrants as well as global average (-13%). Using a threshold of ≥10% decline in RNFL, the positive and negative predictive value for vision loss when 2 or more anatomic sectors were affected was 100% and 94%, respectively. CONCLUSIONS Children experiencing vision loss from their optic pathway gliomas frequently demonstrate a ≥10% decline of RNFL thickness in 1 or more anatomic sectors. Global average and the inferior quadrant demonstrated the best positive and negative predictive values. Circumpapillary RNFL is a surrogate marker of vision and could be helpful in making treatment decisions for children with optic pathway gliomas.

Reproducibility of circumpapillary retinal nerve fiber layer measurements using handheld optical coherence tomography in sedated children.

PURPOSE To determine the intra- and intervisit reproducibility of circumpapillary retinal nerve fiber layer (RNFL) measures using handheld optical coherence tomography (OCT) in sedated children. DESIGN Prospective cross-sectional and longitudinal study. METHODS Children undergoing sedation for a clinically indicated magnetic resonance imaging for an optic pathway glioma and/or neurofibromatosis type 1 (NF1) had multiple 6 × 6 mm volumes (isotropic 300 × 300 or nonisotropic 1000 × 100 samplings) acquired over the optic nerve. Children with 2 handheld OCT sessions within 6 months were included in the intervisit cohort. The intra- and intervisit coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for the average and anatomic quadrant circumpapillary RNFL thickness. RESULTS Fifty-nine subjects (mean age 5.1 years, range 0.8-13.0 years) comprised the intravisit cohort and 29 subjects (mean age 5.7 years, range 1.8-12.7 years) contributed to the intervisit cohort. Forty-nine subjects had an optic pathway glioma and 10 subjects had NF1 without an optic pathway glioma. The CV was comparable regardless of imaging with an isotropic and nonisotropic volume in both the intra- and intervisit cohorts. The average circumpapillary RNFL demonstrated the lowest CV and highest ICC compared to the quadrants. For the intervisit cohort, the average ICC was typically higher while the CV was typically lower, but not statistically different compared to the other quadrants. DISCUSSION Circumpapillary RNFL measures acquired with handheld OCT during sedation demonstrate good intra- and intervisit reproducibility. Handheld OCT has the potential to monitor progressive optic neuropathies in young children who have difficulty cooperating with traditional OCT devices.

Individual A-Scan Signal Normalization Between Two Spectral Domain Optical Coherence Tomography Devices

PURPOSE We developed a method to normalize optical coherence tomography (OCT) signal profiles from two spectral-domain (SD) OCT devices so that the comparability between devices increases. METHODS We scanned 21 eyes from 14 healthy and 7 glaucoma subjects with two SD-OCT devices on the same day, with equivalent cube scan patterns centered on the fovea (Cirrus HD-OCT and RTVue). Foveola positions were selected manually and used as the center for registration of the corresponding images. A-scan signals were sampled 1.8 mm from the foveola in the temporal, superior, nasal, and inferior quadrants. After oversampling and rescaling RTVue data along the Z-axis to match the corresponding Cirrus data format, speckle noise reduction and amplitude normalization were applied. For comparison between normalized A-scan profiles, mean absolute difference in amplitude in percentage was measured at each sampling point. As a reference, the mean absolute difference between two Cirrus scans on the same eye also was measured. RESULTS The mean residual of the A-scan profile amplitude was reduced significantly after signal normalization (12.7% vs. 6.2%, P < 0.0001, paired t-test). All four quadrants also showed statistically significant reduction (all P < 0.0001). Mean absolute difference after normalization was smaller than the one between two Cirrus scans. No performance difference was detected between health and glaucomatous eyes. CONCLUSIONS The reported signal normalization method successfully reduced the A-scan profile differences between two SD-OCT devices. This signal normalization processing may improve the direct comparability of OCT image analysis and measurement on various devices.

Intra- and inter-visit reproducibility of ganglion cell-inner plexiform layer measurements using handheld optical coherence tomography in children with optic pathway gliomas

PURPOSE To determine the intra- and inter-visit reproducibility of ganglion cell-inner plexiform layer thickness measures using handheld optical coherence tomography (OCT) in sedated children with optic pathway gliomas and/or neurofibromatosis type 1 (NF1). DESIGN Prospective longitudinal cohort study. METHODS Children with sporadic optic pathway gliomas and/or NF1 who had ≥2 volumes acquired over the macula using handheld OCT during sedation for clinically indicated magnetic resonance imaging were eligible for the intra-visit cohort. Children with repeat handheld OCT imaging within 6 months were eligible for the inter-visit cohort. Total retinal thickness and ganglion cell-inner plexiform layer thickness were measured using custom-designed automated segmentation software. Reproducibility was compared across average and anatomic quadrant by calculating the coefficient of variation (CV) and intraclass correlation coefficient (ICC). RESULTS Forty-two subjects (median age 5.4 years, range 0.8-12.7 years) contributed 45 eyes to the intra-visit cohort. Thirty-one subject eyes had normal vision and 14 had abnormal vision (decreased visual acuity and/or visual field). Average and quadrant ganglion cell-inner plexiform layer measures demonstrated CVs ≤4.5% with excellent ICCs (>0.935). The superior quadrant CV differed between subjects with (4.4%) and without (2.1%) vision loss (P < .05). Twenty-five subject eyes were eligible for the inter-visit cohort, demonstrating CVs from 1.6% to 5.2%. Inter-visit ICCs were excellent (0.955-0.995). DISCUSSION Handheld OCT imaging in sedated children with optic pathway gliomas produces highly reproducible measures of ganglion cell-inner plexiform layer thickness.

Signal Normalization Reduces Systematic Measurement Differences Between Spectral-Domain Optical Coherence Tomography Devices

PURPOSE To test the effect of a novel signal normalization method for reducing systematic optical coherence tomography (OCT) measurement differences among multiple spectral-domain (SD) OCT devices. METHODS A total of 109 eyes from 59 subjects were scanned with two SD-OCT devices (Cirrus and RTVue) at the same visit. Optical coherence tomography image data were normalized to match their signal characteristics between the devices. To compensate signal strength differences, custom high dynamic range (HDR) processing was also applied only to images with substantially lower signal strength. Global mean peripapillary retinal nerve fiber layer (RNFL) thicknesses were then measured automatically from all images using custom segmentation software and were compared to the original device outputs. Structural equation models were used to analyze the absolute RNFL thickness difference between original device outputs and our software outputs after signal normalization. RESULTS The device-measured RNFL thickness showed a statistically significant difference between the two devices (mean absolute difference 10.58 μm, P < 0.05), while there was no significant difference after normalization on eyes with 62.4-μm or thicker RNFL (mean absolute difference 2.95 μm, P < 0.05). CONCLUSIONS The signal normalization method successfully reduces the systematic difference in RNFL thickness measurements between two SD-OCT devices. Enabling direct comparison of RNFL thickness obtained from multiple devices would broaden the use of OCT technology in both clinical and research applications.

Histogram Matching Extends Acceptable Signal Strength Range on Optical Coherence Tomography Images

PURPOSE We minimized the influence of image quality variability, as measured by signal strength (SS), on optical coherence tomography (OCT) thickness measurements using the histogram matching (HM) method. METHODS We scanned 12 eyes from 12 healthy subjects with the Cirrus HD-OCT device to obtain a series of OCT images with a wide range of SS (maximal range, 1-10) at the same visit. For each eye, the histogram of an image with the highest SS (best image quality) was set as the reference. We applied HM to the images with lower SS by shaping the input histogram into the reference histogram. Retinal nerve fiber layer (RNFL) thickness was automatically measured before and after HM processing (defined as original and HM measurements), and compared to the device output (device measurements). Nonlinear mixed effects models were used to analyze the relationship between RNFL thickness and SS. In addition, the lowest tolerable SSs, which gave the RNFL thickness within the variability margin of manufacturer recommended SS range (6-10), were determined for device, original, and HM measurements. RESULTS The HM measurements showed less variability across a wide range of image quality than the original and device measurements (slope = 1.17 vs. 4.89 and 1.72 μm/SS, respectively). The lowest tolerable SS was successfully reduced to 4.5 after HM processing. CONCLUSIONS The HM method successfully extended the acceptable SS range on OCT images. This would qualify more OCT images with low SS for clinical assessment, broadening the OCT application to a wider range of subjects.

High Dynamic Range Imaging Concept-Based Signal Enhancement Method Reduced the Optical Coherence Tomography Measurement Variability

PURPOSE To develop and test a novel signal enhancement method for optical coherence tomography (OCT) images based on the high dynamic range (HDR) imaging concept. METHODS Three virtual channels, which represent low, medium, and high signal components, were produced for each OCT signal dataset. The dynamic range of each signal component was normalized to the full gray scale range. Finally, the three components were recombined into one image using various weights. Fourteen eyes of 14 healthy volunteers were scanned multiple times using time-domain (TD)-OCT before and while preventing blinking in order to produce a wide variety of signal strength (SS) images on the same eye scanned on the same day. For each eye, a pair of scans with the highest and lowest SS with successful retinal nerve fiber layer (RNFL) segmentation was selected to test the signal enhancement effect. In addition, spectral-domain (SD)-OCT images with poor signal qualities were also processed. RESULTS Mean SS of good and poor quality scans were 9.0 ± 1.1 and 4.4 ± 0.9, respectively. TD-OCT RNFL thickness showed significant differences between good and poor quality scans on the same eye (mean difference 11.9 ± 6.0 μm, P < 0.0001, paired t-test), while there was no significant difference after signal enhancement (1.7 ± 6.2 μm, P = 0.33). However, HDR had weaker RNFL compensation effect on images with SS less than or equal to 4, while it maintained good compensation effect on images with SS greater than 4. Successful signal enhancement was also confirmed subjectively on SD-OCT images. CONCLUSION The HDR imaging successfully restored OCT signal and image quality and reduced RNFL thickness differences due to variable signal level to the level within the expected measurement variability. This technique can be applied to both TD- and SD-OCT images.

Virtual Averaging Making Nonframe-Averaged Optical Coherence Tomography Images Comparable to Frame-Averaged Images

Purpose Developing a novel image enhancement method so that nonframe-averaged optical coherence tomography (OCT) images become comparable to active eye-tracking frame-averaged OCT images. Methods Twenty-one eyes of 21 healthy volunteers were scanned with noneye-tracking nonframe-averaged OCT device and active eye-tracking frame-averaged OCT device. Virtual averaging was applied to nonframe-averaged images with voxel resampling and adding amplitude deviation with 15-time repetitions. Signal-to-noise (SNR), contrast-to-noise ratios (CNR), and the distance between the end of visible nasal retinal nerve fiber layer (RNFL) and the foveola were assessed to evaluate the image enhancement effect and retinal layer visibility. Retinal thicknesses before and after processing were also measured. Results All virtual-averaged nonframe-averaged images showed notable improvement and clear resemblance to active eye-tracking frame-averaged images. Signal-to-noise and CNR were significantly improved (SNR: 30.5 vs. 47.6 dB, CNR: 4.4 vs. 6.4 dB, original versus processed, P < 0.0001, paired t-test). The distance between the end of visible nasal RNFL and the foveola was significantly different before (681.4 vs. 446.5 μm, Cirrus versus Spectralis, P < 0.0001) but not after processing (442.9 vs. 446.5 μm, P = 0.76). Sectoral macular total retinal and circumpapillary RNFL thicknesses showed systematic differences between Cirrus and Spectralis that became not significant after processing. Conclusion The virtual averaging method successfully improved nontracking nonframe-averaged OCT image quality and made the images comparable to active eye-tracking frame-averaged OCT images. Translational Relevance Virtual averaging may enable detailed retinal structure studies on images acquired using a mixture of nonframe-averaged and frame-averaged OCT devices without concerning about systematic differences in both qualitative and quantitative aspects.

Signal Normalization Reduces Image Appearance Disparity Among Multiple Optical Coherence Tomography Devices

Purpose To assess the effect of the previously reported optical coherence tomography (OCT) signal normalization method on reducing the discrepancies in image appearance among spectral-domain OCT (SD-OCT) devices. Methods Healthy eyes and eyes with various retinal pathologies were scanned at the macular region using similar volumetric scan patterns with at least two out of three SD-OCT devices at the same visit (Cirrus HD-OCT, Zeiss, Dublin, CA; RTVue, Optovue, Fremont, CA; and Spectralis, Heidelberg Engineering, Heidelberg, Germany). All the images were processed with the signal normalization. A set of images formed a questionnaire with 24 pairs of cross-sectional images from each eye with any combination of the three SD-OCT devices either both pre- or postsignal normalization. Observers were asked to evaluate the similarity of the two displayed images based on the image appearance. The effects on reducing the differences in image appearance before and after processing were analyzed. Results Twenty-nine researchers familiar with OCT images participated in the survey. Image similarity was significantly improved after signal normalization for all three combinations (P ≤ 0.009) as Cirrus and RTVue combination became the most similar pair, followed by Cirrus and Spectralis, and RTVue and Spectralis. Conclusions The signal normalization successfully minimized the disparities in the image appearance among multiple SD-OCT devices, allowing clinical interpretation and comparison of OCT images regardless of the device differences. Translational Relevance The signal normalization would enable direct OCT images comparisons without concerning about device differences and broaden OCT usage by enabling long-term follow-ups and data sharing.