The OSCAR-MP Consensus Criteria for Quality Assessment of Retinal Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVES: Optical coherence tomography angiography (OCTA) is a noninvasive high-resolution imaging technique for assessing the retinal vasculature and is increasingly used in various ophthalmologic, neuro-ophthalmologic, and neurologic diseases. To date, there are no validated consensus criteria for quality control (QC) of OCTA. Our study aimed to develop criteria for OCTA quality assessment. METHODS: To establish criteria through (1) extensive literature review on OCTA artifacts and image quality to generate standardized and easy-to-apply OCTA QC criteria, (2) application of OCTA QC criteria to evaluate interrater agreement, (3) identification of reasons for interrater disagreement, revision of OCTA QC criteria, development of OCTA QC scoring guide and training set, and (4) validation of QC criteria in an international, interdisciplinary multicenter study. RESULTS: We identified 7 major aspects that affect OCTA quality: (O) obvious problems, (S) signal strength, (C) centration, (A) algorithm failure, (R) retinal pathology, (M) motion artifacts, and (P) projection artifacts. Seven independent raters applied the OSCAR-MP criteria to a set of 40 OCTA scans from people with MS, Sjogren syndrome, and uveitis and healthy individuals. The interrater kappa was substantial (κ 0.67). Projection artifacts were the main reason for interrater disagreement. Because artifacts can affect only parts of OCTA images, we agreed that prior definition of a specific region of interest (ROI) is crucial for subsequent OCTA quality assessment. To enhance artifact recognition and interrater agreement on reduced image quality, we designed a scoring guide and OCTA training set. Using these educational tools, 23 raters from 14 different centers reached an almost perfect agreement (κ 0.92) for the rejection of poor-quality OCTA images using the OSCAR-MP criteria. DISCUSSION: We propose a 3-step approach for standardized quality control: (1) To define a specific ROI, (2) to assess the occurrence of OCTA artifacts according to the OSCAR-MP criteria, and (3) to evaluate OCTA quality based on the occurrence of different artifacts within the ROI. OSCAR-MP OCTA QC criteria achieved high interrater agreement in an international multicenter study and is a promising QC protocol for application in the context of future clinical trials and studies.

Cortical lesions, central vein sign, and paramagnetic rim lesions in multiple sclerosis: Emerging machine learning techniques and future avenues.

The current diagnostic criteria for multiple sclerosis (MS) lack specificity, and this may lead to misdiagnosis, which remains an issue in present-day clinical practice. In addition, conventional biomarkers only moderately correlate with MS disease progression. Recently, some MS lesional imaging biomarkers such as cortical lesions (CL), the central vein sign (CVS), and paramagnetic rim lesions (PRL), visible in specialized magnetic resonance imaging (MRI) sequences, have shown higher specificity in differential diagnosis. Moreover, studies have shown that CL and PRL are potential prognostic biomarkers, the former correlating with cognitive impairments and the latter with early disability progression. As machine learning-based methods have achieved extraordinary performance in the assessment of conventional imaging biomarkers, such as white matter lesion segmentation, several automated or semi-automated methods have been proposed as well for CL, PRL, and CVS. In the present review, we first introduce these MS biomarkers and their imaging methods. Subsequently, we describe the corresponding machine learning-based methods that were proposed to tackle these clinical questions, putting them into context with respect to the challenges they are facing, including non-standardized MRI protocols, limited datasets, and moderate inter-rater variability. We conclude by presenting the current limitations that prevent their broader deployment and suggesting future research directions.

From pathology to MRI and back: Clinically relevant biomarkers of multiple sclerosis lesions.

Focal lesions in both white and gray matter are characteristic of multiple sclerosis (MS). Histopathological studies have helped define the main underlying pathological processes involved in lesion formation and evolution, serving as a gold standard for many years. However, histopathology suffers from an intrinsic bias resulting from over-reliance on tissue samples from late stages of the disease or atypical cases and is inadequate for routine patient assessment. Pathological-radiological correlative studies have established advanced MRI's sensitivity to several relevant MS-pathological substrates and its practicality for assessing dynamic changes and following lesions over time. This review focuses on novel imaging techniques that serve as biomarkers of critical pathological substrates of MS lesions: the central vein, chronic inflammation, remyelination and repair, and cortical lesions. For each pathological process, we address the correlative value of MRI to MS pathology, its contribution in elucidating MS pathology in vivo, and the clinical utility of the imaging biomarker.

Lesion size and shape in central vein sign assessment for multiple sclerosis diagnosis: An in vivo and postmortem MRI study.

BACKGROUND: The "central vein sign" (CVS), a linear hypointensity on T2*-weighted imaging corresponding to a central vein/venule, is associated with multiple sclerosis (MS) lesions. The effect of lesion-size exclusion criteria on MS diagnostic accuracy has not been extensively studied. OBJECTIVE: Investigate the optimal lesion-size exclusion criteria for CVS use in MS diagnosis. METHODS: Cross-sectional study of 163 MS and 51 non-MS, and radiological/histopathological correlation of 5 MS and 1 control autopsy cases. The effects of lesion-size exclusion on MS diagnosis using the CVS, and intralesional vein detection on histopathology were evaluated. RESULTS: CVS+ lesions were larger compared to CVS- lesions, with effect modification by MS diagnosis (mean difference +7.7 mm3, p = 0.004). CVS percentage-based criteria with no lesion-size exclusion showed the highest diagnostic accuracy in differentiating MS cases. However, a simple count of three or more CVS+ lesions greater than 3.5 mm is highly accurate and can be rapidly implemented (sensitivity 93%; specificity 88%). On magnetic resonance imaging (MRI)-histopathological correlation, the CVS had high specificity for identifying intralesional veins (0/7 false positives). CONCLUSION: Lesion-size measures add important information when using CVS+ lesion counts for MS diagnosis. The CVS is a specific biomarker corresponding to intralesional veins on histopathology.

Central Vein Sign Profile of Newly Developing Lesions in Multiple Sclerosis: A 3-Year Longitudinal Study.

BACKGROUND AND OBJECTIVES: The central vein sign (CVS), a central linear hypointensity within lesions on T2*-weighted imaging, has been established as a sensitive and specific biomarker for the diagnosis of multiple sclerosis (MS). However, the CVS has not yet been comprehensively studied in newly developing MS lesions. We aimed to identify the CVS profiles of new white matter lesions in patients with MS followed over time and investigate demographic and clinical risk factors associated with new CVS+ or CVS- lesion development. METHODS: In this retrospective longitudinal cohort study, adults from the NIH MS Natural History Study were considered for inclusion. Participants with new T2 or enhancing lesions were identified through review of the radiology report and/or longitudinal subtraction imaging. Each new lesion was evaluated for the CVS. Clinical characteristics were identified through chart review. RESULTS: A total of 153 adults (95 relapsing-remitting MS, 27 secondary progressive MS, 16 primary progressive MS, 5 clinically isolated syndrome, and 10 healthy; 67% female) were included. Of this cohort, 96 had at least 1 new T2 or contrast-enhancing lesion during median 3.1 years (Q1-Q3: 0.7-6.3) of follow-up; lesions eligible for CVS evaluation were found in 62 (65%). Of 233 new CVS-eligible lesions, 159 (68%) were CVS+, with 30 (48%) individuals having only CVS+, 12 (19%) only CVS-, and 20 (32%) both CVS+ and CVS- lesions. In gadolinium-enhancing (Gd+) lesions, the CVS+ percentage increased from 102/152 (67%) at the first time point where the lesion was observed, to 92/114 (82%) after a median follow-up of 2.8 years. Younger age (OR = 0.5 per 10-year increase, 95% CI = 0.3-0.8) and higher CVS+ percentage at baseline (OR = 1.4 per 10% increase, 95% CI = 1.1-1.9) were associated with increased likelihood of new CVS+ lesion development. DISCUSSION: In a cohort of adults with MS followed over a median duration of 3 years, most newly developing T2 or enhancing lesions were CVS+ (68%), and nearly half (48%) developed new CVS+ lesions only. Importantly, the effects of edema and T2 signal changes can obscure small veins in Gd+ lesions; therefore, caution and follow-up is necessary when determining their CVS status. TRIAL REGISTRATION INFORMATION: Clinical trial registration number NCT00001248. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that younger age and higher CVS+ percentage at baseline are associated with new CVS+ lesion development.

BK virus-specific T cells for immunotherapy of progressive multifocal leukoencephalopathy: an open-label, single-cohort pilot study.

BACKGROUND: Progressive multifocal leukoencephalopathy, a rare disease of the CNS caused by JC virus and occurring in immunosuppressed people, is typically fatal unless adaptive immunity is restored. JC virus is a member of the human polyomavirus family and is closely related to the BK virus. We hypothesised that use of partly HLA-matched donor-derived BK virus-specific T cells for immunotherapy in progressive multifocal leukoencephalopathy would be feasible and safe. METHODS: We did an open-label, single-cohort pilot study in patients (aged 18 years or older) with clinically definite progressive multifocal leukoencephalopathy and disease progression in the previous month at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Overlapping peptide libraries derived from large T antigen and major capsid protein VP1 of BK virus with high sequence homology to JC virus counterparts were used to generate polyomavirus-specific T cells cross-recognising JC virus antigens. Polyomavirus-specific T cells were manufactured from peripheral blood mononuclear cells of first-degree relative donors aged 18 years or older. These cells were administered to patients by intravenous infusion at 1 × 106 polyomavirus-specific T cells per kg, followed by up to two additional infusions at 2 × 106 polyomavirus-specific T cells per kg. The primary endpoints were feasibility (no manufacturing failure based on meeting release criteria, achieving adequate numbers of cell product for clinical use, and showing measurable antiviral activity) and safety in all patients. The safety monitoring period was 28 days after each infusion. Patients were followed up with serial MRI for up to 12 months after the final infusion. This trial is registered at ClinicalTrials.gov, NCT02694783. FINDINGS: Between April 7, 2016, and Oct 19, 2018, 26 patients were screened, of whom 12 were confirmed eligible and received treatment derived from 14 matched donors. All administered polyomavirus-specific T cells met the release criteria and recognised cognate antigens in vitro. 12 patients received at least one infusion, ten received at least two, and seven received a total of three infusions. The median on-study follow-up was 109·5 days (range 23-699). All infusions were tolerated well, and no serious treatment-related adverse events were observed. Seven patients survived progressive multifocal leukoencephalopathy for longer than 1 year after the first infusion, whereas five died of progressive multifocal leukoencephalopathy within 3 months. INTERPRETATION: We showed that generation of polyomavirus-specific T cells from healthy related donors is feasible, and these cells can be safely used as an infusion for adoptive immunotherapy of progressive multifocal leukoencephalopathy. Although not powered to assess efficacy, our data provide additional support for this strategy as a potential life-saving therapy for some patients. FUNDING: Intramural Research Program of the National Institute of Neurological Disorders and Stroke of the NIH.

Navigator-Guided Motion and B0 Correction of T2*-Weighted Magnetic Resonance Imaging Improves Multiple Sclerosis Cortical Lesion Detection.

BACKGROUND: Cortical lesions are common in multiple sclerosis (MS). T2*-weighted (T2*w) imaging at 7 T is relatively sensitive for cortical lesions, but quality is often compromised by motion and main magnetic field (B0) fluctuations. PURPOSE: The aim of this study was to determine whether motion and B0 correction with a navigator-guided gradient-recalled echo sequence can improve cortical lesion detection in T2*w magnetic resonance imaging. MATERIALS AND METHODS: In this prospective study, a gradient-recalled echo sequence incorporating a navigator allowing for motion and B0 field correction was applied to collect T2*w images at 7 T from adults with MS between August 2019 and March 2020. T2*-weighted images were acquired in 1 to 3 partially overlapping scans per individual and were reconstructed using global average B0 correction ("uncorrected") or motion correction and spatially linear B0 correction ("corrected"). Image quality rating and manual segmentation of cortical lesions were performed on uncorrected and corrected images. Lesions seen on a single scan were retrospectively evaluated on the complementary scan. The association of cortical lesions with clinical disability was assessed. Mixed models were used to determine the effect of correction on lesion detection as well as on the relationship between disability and lesion count. RESULTS: A total of 22 T2*w scans were performed on 11 adults with MS (mean [SD] age, 49 [11] years; 8 women). Quality improved for 20 of 22 scans (91%) after correction. A total of 69 cortical lesions were identified on uncorrected images (median per scan, 2; range, 0-11) versus 148 on corrected images (median per scan, 4.5; range, 0-25; rate ratio [RR], 2.1; P < 0.0001). For low-quality uncorrected scans with moderate to severe motion artifact (18/22, 82%), there was an improvement in cortical lesion detection with correction (RR, 2.5; P < 0.0001), whereas there was no significant change in cortical lesion detection for high-quality scans (RR, 1.3; P = 0.43). CONCLUSIONS: Navigator-guided motion and B0 correction substantially improves the overall image quality of T2*w magnetic resonance imaging at 7 T and increases its sensitivity for cortical lesions.

Progressive multifocal leukoencephalopathy lesion and brain parenchymal segmentation from MRI using serial deep convolutional neural networks.

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic brain infection caused by the JC virus and associated with substantial morbidity and mortality. Accurate MRI assessment of PML lesion burden and brain parenchymal atrophy is of decisive value in monitoring the disease course and response to therapy. However, there are currently no validated automatic methods for quantification of PML lesion burden or associated parenchymal volume loss. Furthermore, manual brain or lesion delineations can be tedious, require the use of valuable time resources by radiologists or trained experts, and are often subjective. In this work, we introduce JCnet (named after the causative viral agent), an end-to-end, fully automated method for brain parenchymal and lesion segmentation in PML using consecutive 3D patch-based convolutional neural networks. The network architecture consists of multi-view feature pyramid networks with hierarchical residual learning blocks containing embedded batch normalization and nonlinear activation functions. The feature maps across the bottom-up and top-down pathways of the feature pyramids are merged, and an output probability membership generated through convolutional pathways, thus rendering the method fully convolutional. Our results show that this approach outperforms and improves longitudinal consistency compared to conventional, state-of-the-art methods of healthy brain and multiple sclerosis lesion segmentation, utilized here as comparators given the lack of available methods validated for use in PML. The ability to produce robust and accurate automated measures of brain atrophy and lesion segmentation in PML is not only valuable clinically but holds promise toward including standardized quantitative MRI measures in clinical trials of targeted therapies. Code is available at: https://github.com/omarallouz/JCnet.

Quantitative vibratory sensation measurement is related to sensory cortical thickness in MS.

Objective: Vibratory sensation is a quantifiable measure of physical dysfunction and is often related to spinal cord pathology; however, its association with relevant brain areas has not been fully explored. Our objective was to establish a cortical structural substrate for vibration sensation. Methods: Eighty-four individuals with multiple sclerosis (MS) (n = 54 relapsing, n = 30 progressive) and 28 controls participated in vibratory sensation threshold quantification at the great toe and a 3T MRI evaluating volume of the thalamus and cortical thickness primary and secondary sensory cortices. Results: After controlling for age, sex, and disability level, vibratory sensation thresholds were significantly related to cortical thickness of the anterior cingulate (P = 0.041), parietal operculum (P = 0.022), and inferior frontal gyrus pars operculum (P = 0.044), pars orbitalis (P = 0.007), and pars triangularis (P = 0.029). Within the progressive disease subtype, there were significant relationships between vibratory sensation and thalamic volume (P = 0.039) as well as reduced inferior frontal gyrus pars operculum (P = 0.014) and pars orbitalis (P = 0.005) cortical thickness. Conclusions: The data show significant independent relationships between quantitative vibratory sensation and measures of primary and secondary sensory cortices. Quantitative clinical measurement of vibratory sensation reflects pathological changes in spatially distinct brain areas and may supplement information captured by brain atrophy measures. Without overt relapses, monitoring decline in progressive forms of MS has proved challenging; quantitative clinical assessment may provide a tool to examine pathological decline in this cohort. These data suggest that quantitative clinical assessment may be a reliable way to examine pathological decline and have broader relevance to progressive forms of MS.

Characteristics of morphologic macular abnormalities in neuroimmunology practice.

BACKGROUND: Morphologic macular abnormalities (MMAs) are frequently seen on macular optical coherence tomography (OCT) imaging in neuroimmunology practice, yet studies pragmatically assessing prevalence and risk factors of MMAs to date are limited. OBJECTIVE: To describe the characteristics of MMAs in a neuroimmunology-based academic practice. METHODS: Cross-sectional study of 1450 patients (2900 eyes) who underwent spectral-domain macular OCT between June 2010 and June 2012. The association between MMAs and demographic variables was analyzed using mixed-effects logistic regression. Odds ratios (ORs) were calculated per 5-year age increments. RESULTS: MMAs were observed in 338/2872 eyes (11.7%) of 232/1445 participants (16.1%). The most common abnormalities identified, included drusen (6.0%), epiretinal membrane (ERM; 5.5%), and microcystoid macular pathology (MMP; 1.9%). Overall, patients with MMAs were older (OR: 1.79, p = 5 × 10-5) and more likely to be males (OR: 2.45, p = 0.014). In particular, advancing age was associated with higher risk of drusen and ERM (OR: 1.80 and 4.26, p = 2 × 10-5 and 7 × 10-3, respectively). MMP prevalence declined with age (OR: 0.73, p = 0.015) and was associated with African-American ethnicity (OR: 15.0, p = 5 × 10-5). CONCLUSION: Unexpected or incidental MMAs are common in patients assessed with OCT in neuroimmunology practice, emphasizing the importance of comprehensive OCT image review for risk stratification and appropriate ophthalmology referral.

Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis: a longitudinal study.

On average, African Americans with multiple sclerosis demonstrate higher inflammatory disease activity, faster disability accumulation, greater visual dysfunction, more pronounced brain tissue damage and higher lesion volume loads compared to Caucasian Americans with multiple sclerosis. Neurodegeneration is an important component of multiple sclerosis, which in part accounts for the clinical heterogeneity of the disease. Brain atrophy appears to be widespread, although it is becoming increasingly recognized that regional substructure atrophy may be of greater clinical relevance. Patient race (within the limitations of self-identified ancestry) is regarded as an important contributing factor. However, there is a paucity of studies examining differences in neurodegeneration and brain substructure volumes over time in African Americans relative to Caucasian American patients. Optical coherence tomography is a non-invasive and reliable tool for measuring structural retinal changes. Recent studies support its utility for tracking neurodegeneration and disease progression in vivo in multiple sclerosis. Relative to Caucasian Americans, African American patients have been found to have greater retinal structural injury in the inner retinal layers. Increased thickness of the inner nuclear layer and the presence of microcystoid macular pathology at baseline predict clinical and radiological inflammatory activity, although whether race plays a role in these changes has not been investigated. Similarly, assessment of outer retinal changes according to race in multiple sclerosis remains incompletely characterized. Twenty-two African Americans and 60 matched Caucasian Americans with multiple sclerosis were evaluated with brain MRI, and 116 African Americans and 116 matched Caucasian Americans with multiple sclerosis were monitored with optical coherence tomography over a mean duration of 4.5 years. Mixed-effects linear regression models were used in statistical analyses. Grey matter (-0.9%/year versus -0.5%: P =0.02), white matter (-0.7%/year versus -0.3%: P =0.04) and nuclear thalamic (-1.5%/year versus -0.7%/year: P =0.02) atrophy rates were approximately twice as fast in African Americans. African Americans also exhibited higher proportions of microcystoid macular pathology (12.1% versus 0.9%, P =0.001). Retinal nerve fibre layer (-1.1% versus -0.8%: P =0.02) and ganglion cell+ inner plexiform layer (-0.7%/year versus -0.4%/year: P =0.01) atrophy rates were faster in African versus Caucasian Americans. African Americans on average exhibited more rapid neurodegeneration than Caucasian Americans and had significantly faster brain and retinal tissue loss. These results corroborate the more rapid clinical progression reported to occur, in general, in African Americans with multiple sclerosis and support the need for future studies involving African Americans in order to identify individual differences in treatment responses in multiple sclerosis.

Utility of optical coherence tomography in the evaluation of sellar and parasellar mass lesions.

PURPOSE OF REVIEW: Anterior visual pathway compression is a common feature of sellar region masses. We review the visual pathway neuroanatomy pertaining to sellar and parasellar lesions and describe recent advances in optical coherence tomography (OCT) imaging that have provided a novel quantitative perspective in the evaluation and management of such patients. RECENT FINDINGS: Ultrastructural measurements of optic nerve integrity using OCT, namely peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell and inner plexiform layer (GCIPL) thicknesses, have been shown to correlate with visual acuity and visual field deficits on perimetry in patients with compressive sellar region masses. In some cases, OCT can visualize early signs of anterior visual pathway involvement in the absence of clinically evident visual field loss or optic disc pallor. OCT is particularly useful when assessing patients who demonstrate less reliable visual field testing. Furthermore, there is growing awareness that pRNFL and GCIPL thinning preoperatively correlate with worse visual recovery following chiasmal decompression, highlighting the prognostic utility of OCT in this patient population. SUMMARY: OCT provides a complimentary, yet critical, role in quantitatively assessing ultrastructural retinal injury in patients with sellar and parasellar lesions compressing the anterior visual pathway and should be incorporated into routine evaluation.

Retrograde trans-synaptic visual pathway degeneration in multiple sclerosis: A case series.

BACKGROUND: Trans-synaptic degeneration (TSD) describes the propagation of neuronal injury through synaptic pathways in the human nervous system and may be linked to the accelerated retinal atrophy seen in multiple sclerosis (MS). RESULTS: We report six cases where homonymous, hemi-macular ganglion cell + inner plexiform (GCIP) thickness reduction was seen in conjunction with posterior visual pathway lesions. Macular microcystoid changes of the inner nuclear layer (INL) were seen in a subset of three subjects. CONCLUSION: Our findings highlight the utility of assessing regional GCIP changes to identify potential retrograde TSD in MS and demonstrate that INL changes may be an accompaniment in such instances.

Disease-modifying therapies modulate retinal atrophy in multiple sclerosis: A retrospective study.

OBJECTIVE: To retrospectively investigate whether disease-modifying therapies (DMTs) exert differential effects on rates of retinal atrophy in relapsing-remitting multiple sclerosis (RRMS), as assessed using optical coherence tomography (OCT). METHODS: A total of 402 patients with RRMS followed at the Johns Hopkins MS Center who underwent Cirrus-HD OCT were assessed for eligibility. Inclusion criteria included at least 1 year of OCT follow-up and adherence to a single DMT during the period of follow-up. Combined thickness of the ganglion cell + inner plexiform (GCIP) and other retinal layers was computed utilizing automated macular segmentation. Retinal thickness changes were analyzed using mixed-effects linear regression. RESULTS: The effects of glatiramer acetate (GA; n = 48), natalizumab (NAT; n = 46), and interferon-ß-1a subcutaneously (IFNSC; n = 35) and intramuscularly (IFNIM; n = 28) were assessed. Baseline analyses revealed no significant differences between groups in terms of age, sex, optic neuritis history, or follow-up duration. During follow-up, relative to NAT-treated patients, IFNSC- and GA-treated patients exhibited 0.37 µm/y (p < 0.001) and 0.14 µm/y (p = 0.035) faster rates of GCIP thinning, respectively, adjusting for the interval between initiation of DMT and OCT monitoring (gap time), age, sex, relapses, and disease duration. In the IFNSC group, GCIP thinning was 1.53 µm/y faster during the first year of therapy vs during the time interval afterwards (p < 0.001). CONCLUSIONS: Rates of GCIP atrophy in patients with RRMS vary according to DMT utilization. Our findings support OCT for monitoring neurodegenerative treatment effects in the retina, an easily accessible tissue, and as a practical outcome measure in RRMS clinical trials.

Combined registration and motion correction of longitudinal retinal OCT data.

Optical coherence tomography (OCT) has become an important modality for examination of the eye. To measure layer thicknesses in the retina, automated segmentation algorithms are often used, producing accurate and reliable measurements. However, subtle changes over time are difficult to detect since the magnitude of the change can be very small. Thus, tracking disease progression over short periods of time is difficult. Additionally, unstable eye position and motion alter the consistency of these measurements, even in healthy eyes. Thus, both registration and motion correction are important for processing longitudinal data of a specific patient. In this work, we propose a method to jointly do registration and motion correction. Given two scans of the same patient, we initially extract blood vessel points from a fundus projection image generated on the OCT data and estimate point correspondences. Due to saccadic eye movements during the scan, motion is often very abrupt, producing a sparse set of large displacements between successive B-scan images. Thus, we use lasso regression to estimate the movement of each image. By iterating between this regression and a rigid point-based registration, we are able to simultaneously align and correct the data. With longitudinal data from 39 healthy control subjects, our method improves the registration accuracy by 50% compared to simple alignment to the fovea and 22% when using point-based registration only. We also show improved consistency of repeated total retina thickness measurements.

Simultaneous Segmentation of Retinal Surfaces and Microcystic Macular Edema in SDOCT Volumes.

Optical coherence tomography (OCT) is a noninvasive imaging modality that has begun to find widespread use in retinal imaging for the detection of a variety of ocular diseases. In addition to structural changes in the form of altered retinal layer thicknesses, pathological conditions may also cause the formation of edema within the retina. In multiple sclerosis, for instance, the nerve fiber and ganglion cell layers are known to thin. Additionally, the formation of pseudocysts called microcystic macular edema (MME) have also been observed in the eyes of about 5% of MS patients, and its presence has been shown to be correlated with disease severity. Previously, we proposed separate algorithms for the segmentation of retinal layers and MME, but since MME mainly occurs within specific regions of the retina, a simultaneous approach is advantageous. In this work, we propose an automated globally optimal graph-theoretic approach that simultaneously segments the retinal layers and the MME in volumetric OCT scans. SD-OCT scans from one eye of 12 MS patients with known MME and 8 healthy controls were acquired and the pseudocysts manually traced. The overall precision and recall of the pseudocyst detection was found to be 86.0% and 79.5%, respectively.

Voxel Based Morphometry in Optical Coherence Tomography: Validation & Core Findings.

Optical coherence tomography (OCT) of the human retina is now becoming established as an important modality for the detection and tracking of various ocular diseases. Voxel based morphometry (VBM) is a long standing neuroimaging analysis technique that allows for the exploration of the regional differences in the brain. There has been limited work done in developing registration based methods for OCT, which has hampered the advancement of VBM analyses in OCT based population studies. Following on from our recent development of an OCT registration method, we explore the potential benefits of VBM analysis in cohorts of healthy controls (HCs) and multiple sclerosis (MS) patients. Specifically, we validate the stability of VBM analysis in two pools of HCs showing no significant difference between the two populations. Additionally, we also present a retrospective study of age and sex matched HCs and relapsing remitting MS patients, demonstrating results consistent with the reported literature while providing insight into the retinal changes associated with this MS subtype.

Outer retinal changes following acute optic neuritis.

BACKGROUND: Retinal nerve fiber and ganglion cell+inner plexiform (GCIP) layer thinning following multiple sclerosis-related acute optic neuritis (AON) is well described. However, whether AON results in changes in the inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL) and/or photoreceptor segment (PS) layers remains undetermined. OBJECTIVES: The objective of this paper is to determine if INL+OPL and/or ONL+PS changes occur following AON. METHODS: Thirty-three AON patients underwent serial optical coherence tomography (OCT) and visual function testing (mean follow-up: 25 months). Longitudinal changes in retinal layer thickness were analyzed using mixed-effects linear regression. RESULTS: Four months following AON, the mean decrease in GCIP thickness relative to baseline was 11.4% (p < 0.001). At four months, a concomitant 3.4% increase in average ONL+PS thickness was observed (p < 0.001). The percentage decrease in GCIP thickness and increase in ONL+PS thickness were strongly correlated (r = -0.70; p < 0.001). Between months 4 to 12, ONL+PS thickness declined and, at 12 months, was no longer significantly different from baseline (mean change: 0.5%; p = 0.37). Similar, albeit less robust, changes in the INL+OPL were observed. CONCLUSIONS: Following AON, dynamic changes occur in the deep retinal layers, which are proportional to GCIP thinning. These novel findings help further our understanding of the biological and/or anatomical sequelae resulting from AON.