ORCID Profile
0000-0001-7135-7662
Current Organisations
Sydney Neuroimaging Analysis Centre
,
University of Sydney
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Publisher: SAGE Publications
Date: 2012
DOI: 10.1255/JNIRS.975
Abstract: Optical coherence tomography (OCT) is a technique that is able to provide cross section views of tissue layers. This fast and non-invasive method is widely used in clinical applications for the diagnosis and treatment of certain diseases. Although conventional OCT is derived from the theory of interferometric imaging, emerging developments, including spectroscopic OCT and related techniques such as dual-band OCT and Raman spectroscopy–OCT, have resulted in significantly improved clinical capabilities for observing the tissue layers through enhanced tissue definition, image resolution, image contrast and scanning speed. This paper reviews the state-of-the-art developments of OCT. It starts with a general introduction of conventional interferometric OCT imaging methods including the time-domain and frequency-domain techniques. The second section explores the advances introduced from spectroscopy techniques in OCT, especially with spectroscopic OCT, dual-band OCT and Raman spectroscopy combined OCT. The final section discusses the current challenges in the application of approaches based on computer-aided diagnosis (CAD) for retinal imaging, for ex le automated segmentation of tissue layers and tracking disease progression. This task is currently limited by the quality of the recorded data from OCT systems but will be improved by adopting spectroscopic techniques. Finally, we analyse and discuss the improvements that are expected in retinal CAD from the adoption of newly emerging near infrared spectroscopy OCT at multiple wavelengths.
Publisher: Elsevier BV
Date: 2018
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-09-2014
Abstract: To investigate the topographic relationship between glaucomatous retinal ganglion cell loss and changes in the optic radiation (OR) using diffusion tensor imaging (DTI). A cross-sectional study was completed on nine patients with primary open angle glaucoma and nine age- and sex-matched controls. Glaucoma patients with binocular, symmetrical superior, or inferior visual hemifield defects were selected. A comparative DTI analysis was conducted between OR fibers connected to the affected and unaffected visual hemifield in the glaucoma group and corresponding OR in the control group. There was a significantly lower number of fiber bundles in the affected OR compared with unaffected OR and controls (P < 0.01). Radial diffusivity was similar between the affected and unaffected OR (P = 0.39), but higher in both groups compared with controls (P < 0.01). There was no difference in axial diffusivity among all groups. As a consequence, fractional anisotropy was lower and mean diffusivity was higher in the affected and unaffected OR compared with controls. A significant loss of OR fibers connected to the severely damaged part of the optic nerve head, but not the fibers connected to the relatively spared retinal hemifield shows a direct relationship between retinal neuronal damage and functionally connected OR fibers in glaucoma. However, OR fibers connected to the relatively preserved visual hemifield in the glaucoma subjects still showed changes in radial diffusivity compared with controls, suggesting possible early dysfunction. Our results support the notion that glaucoma is a neurodegenerative disease involving the posterior visual pathway.
Publisher: Frontiers Media SA
Date: 03-08-2023
DOI: 10.3389/FNEUR.2023.1177723
Abstract: Intracranial hemorrhage (ICH) is a potentially life-threatening medical event that requires expedited diagnosis with computed tomography (CT). Automated medical imaging triaging tools can rapidly bring scans containing critical abnormalities, such as ICH, to the attention of radiologists and clinicians. Here, we retrospectively investigated the real-world performance of VeriScout ™ , an artificial intelligence-based CT hemorrhage detection and triage tool. Ground truth for the presence or absence of ICH was iteratively determined by expert consensus in an unselected dataset of 527 consecutively acquired non-contrast head CT scans, which were sub-grouped according to the presence of artefact, post-operative features and referral source. The performance of VeriScout ™ was compared with the ground truths for all groups. VeriScout ™ detected hemorrhage with a sensitivity of 0.92 (CI 0.84–0.96) and a specificity of 0.96 (CI 0.94–0.98) in the global dataset, exceeding the sensitivity of general radiologists (0.88) with only a minor relative decrement in specificity (0.98). Crucially, the AI tool detected 13/14 cases of subarachnoid hemorrhage, a potentially fatal condition that is often missed in emergency department settings. There was no decrement in the performance of VeriScout ™ in scans containing artefact or postoperative change. Using an integrated informatics platform, VeriScout ™ was deployed into the existing radiology workflow. Detected hemorrhage cases were flagged in the hospital radiology information system (RIS) and relevant, annotated, preview images made available in the picture archiving and communications system (PACS) within 10 min. AI-based radiology worklist prioritization for critical abnormalities, such as ICH, may enhance patient care without adding to radiologist or clinician burden.
Publisher: Cambridge University Press (CUP)
Date: 15-07-2016
DOI: 10.1017/CJN.2016.253
Publisher: Springer Science and Business Media LLC
Date: 12-11-2020
DOI: 10.1007/S12035-019-01792-6
Abstract: We and others have previously demonstrated the potential for circulating exosome microRNAs to aid in disease diagnosis. In this study, we sought the possible utility of serum exosome microRNAs as biomarkers for disease activity in multiple sclerosis patients in response to fingolimod therapy. We studied patients with relapsing-remitting multiple sclerosis prior to and 6 months after treatment with fingolimod. Disease activity was determined using gadolinium-enhanced magnetic resonance imaging. Serum exosome microRNAs were profiled using next-generation sequencing. Data were analysed using univariate/multivariate modelling and machine learning to determine microRNA signatures with predictive utility. Accordingly, we identified 15 in idual miRNAs that were differentially expressed in serum exosomes from post-treatment patients with active versus quiescent disease. The targets of these microRNAs clustered in ontologies related to the immune and nervous systems and signal transduction. While the power of in idual microRNAs to predict disease status post-fingolimod was modest (average 77%, range 65 to 91%), several combinations of 2 or 3 miRNAs were able to distinguish active from quiescent disease with greater than 90% accuracy. Further stratification of patients identified additional microRNAs associated with stable remission, and a positive response to fingolimod in patients with active disease prior to treatment. Overall, these data underscore the value of serum exosome microRNA signatures as non-invasive biomarkers of disease in multiple sclerosis and suggest they may be used to predict response to fingolimod in future clinical practice. Additionally, these data suggest that fingolimod may have mechanisms of action beyond its known functions.
Publisher: IEEE
Date: 10-2011
Publisher: BMJ
Date: 12-04-2016
Publisher: Springer International Publishing
Date: 2021
Publisher: Springer International Publishing
Date: 2020
Publisher: IEEE
Date: 12-2018
Publisher: Frontiers Media SA
Date: 19-12-2016
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-03-2012
DOI: 10.1167/IOVS.11-8732
Abstract: Recently demonstrated neuronal loss in the inner nuclear layer of the retina in multiple sclerosis (MS) and glaucoma raises the question of a primary (possibly immune-mediated) or secondary (transsynaptic) mechanism of retinal damage in these diseases. In the present study we used optical coherence tomography to investigate retrograde retinal transsynaptic degeneration in patients with long-standing and severe loss of ganglion cells due to optic neuropathy. Fifteen eyes of glaucoma patients with visual field defect limited to upper hemifield and 15 eyes of MS patients with previous episode of optic neuritis (ON) and extensive loss of ganglion cells were imaged using spectral-domain optical coherence tomography and compared with two groups of age-matched controls. Combined retinal ganglion cell layer/inner plexiform layer (GCL/IPL) thickness and inner nuclear layer (INL) thickness were analyzed. In the glaucoma group there was a significant (P = 0.0005) reduction of GCL/IPL thickness in the lower (affected) retina compared with normal controls however INL thickness was not statistically reduced (P = 0.49). In the MS group reduction of GCL/IPL thickness in both hemifields of ON eyes was also significant (P = 0.0001 and P < 0.0001 for inferior and superior retina respectively). However, similar to the glaucomatous eyes, there was no significant reduction of INL thickness in both hemifields (P = 0.25 and P = 0.45). This study demonstrates no significant loss of INL thickness in parts of the retina with long-standing and severe loss of retinal ganglion cells.
Publisher: Frontiers Media SA
Date: 25-04-2023
DOI: 10.3389/FNEUR.2023.1129430
Abstract: Magnetic resonance-guided focussed ultrasound (MRgFUS) is an incisionless ablative procedure, widely used for treatment of Parkinsonian and Essential Tremor (ET). Enhanced understanding of the patient- and treatment-specific factors that influence sustained long-term tremor suppression could help clinicians achieve superior outcomes via improved patient screening and treatment strategy. We retrospectively analysed data from 31 subjects with ET, treated with MRgFUS at a single centre. Tremor severity was assessed with parts A, B and C of the Clinical Rating Scale for Tremor (CRST) as well as the combined CRST. Tremor in the dominant and non-dominant hand was assessed with Hand Tremor Scores (HTS), derived from the CRST. Pre- and post-treatment imaging data were analysed to determine ablation volume overlap with automated thalamic segmentations, and the dentatorubrothalamic tract (DRTT) and compared with percentage change in CRST and HTS following treatment. Tremor symptoms were significantly reduced following treatment. Combined pre-treatment CRST (mean: 60.7 ± 17.3) and HTS (mean: 19.2 ± 5.7) improved by an average of 45.5 and 62.6%, respectively. Percentage change in CRST was found to be significantly negatively associated with age (β = −0.375, p = 0.015), and SDR standard deviation (SDR SD β = −0.324, p = 0.006), and positively associated with ablation overlap with the posterior DRTT (β = 0.535, p & 0.001). Percentage HTS improvement in the dominant hand decreased significantly with older age (β = −0.576, p & 0.01). Our results suggest that increased lesioning of the posterior region of the DRTT could result in greater improvements in combined CRST and non-dominant hand HTS, and that subjects with lower SDR standard deviation tended to experience greater improvement in combined CRST.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.OPHTHA.2018.06.022
Abstract: To assess differential patterns of axonal loss and demyelination in the optic nerve in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Cross-sectional study. One hundred ninety-two participants, including 136 MS patients (272 eyes), 19 NMOSD patients (38 eyes), and 37 healthy control participants (74 eyes). All participants underwent spectral-domain OCT scans and multifocal visual evoked potential (mfVEP) recordings. High-resolution magnetic resonance imaging (MRI) with the diffusion protocol also was performed in all patients. Ganglion cell-inner plexiform layer (GCIPL) thickness and mfVEP litude and latency at 5 eccentricities global and temporal retinal nerve fiber layer thickness. In optic neuritis (ON) eyes, the NMOSD patients had more severe GCIPL loss (P < 0.001) and mfVEP litude reduction (P < 0.001) compared with MS patients, whereas in contrast, mfVEP latency delay was more evident in MS patients (P < 0.001). The NMOSD patients showed more morphologic and functional loss at the foveal to parafoveal region, whereas the MS patients showed evenly distributed damage at the macula. Correlation analysis demonstrated a strong structure-function (OCT-mfVEP) association in the NMOSD patients, which was only moderate in the MS patients. In non-ON (NON) eyes, the MS patients showed significantly thinner GCIPL than controls (P < 0.001), whereas no GCIPL loss was observed in NON eyes in NMOSD. In addition, a significant correlation was found between all OCT and mfVEP measures in MS patients, but not in NMOSD patients. MRI demonstrated significant lesional load in the optic radiation in MS compared to NMOSD eyes (P = 0.002), which was related to the above OCT and mfVEP changes in NON eyes. Our study demonstrated different patterns of ON damage in NMOSD and MS. In MS, the ON damage was less severe, with demyelination as the main pathologic component, whereas in NMOSD, axonal loss was more severe compared with myelin loss. The disproportional mfVEP litude and latency changes suggested predominant axonal damage within the anterior visual pathway as the main clinical feature of NMOSD, in contrast to MS, where demyelination spreads along the entire visual pathway.
Publisher: Springer Science and Business Media LLC
Date: 28-06-2022
DOI: 10.1038/S41380-022-01641-4
Abstract: White matter lesions (WMLs) are common in older adults and represent an important predictor of negative long-term outcomes. Rest-activity rhythm disturbance is also common, however, few studies have investigated associations between these factors. We employed a novel AI-based automatic WML segmentation tool and diffusion-weighted tractography to investigate associations between tract specific WML volumes and non-parametric actigraphy measures in older adults at risk for cognitive decline. The primary non-parametric measures of interest were inter-daily stability (IS), intra-daily variability and relative litude, with the anterior thalamic radiation (ATR), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF) selected as tracts of interest. One hundred and eight participants at risk for cognitive decline (classified as experiencing subjective or objective cognitive decline) were included (mean age = 68.85 years, SD = 8.91). Of the primary non-parametric measures of interest, results showed that lower IS was associated with a greater likelihood of higher WML burden in the ATR (OR = 1.82, 95% CI [1.12,3.15]). Analysis of secondary non-parametric measures revealed later onset of the least active period to be associated with greater likelihood of high WML burden in the SLF (OR = 1.55, 95% CI [1.00,2.53]) and increased activity during the least active 5-h period to be associated with a greater likelihood of high whole-brain WML burden (OR = 1.83, 95% CI [1.06,3.47]). This study shows integrity of the ATR and SLF, and overall WML burden is linked to altered rest-activity rhythms in older adults at risk for cognitive decline, with those demonstrating altered rest-activity rhythms showing 50%-80% higher odds of having high WML burden.
Publisher: Public Library of Science (PLoS)
Date: 17-01-2018
Publisher: Springer International Publishing
Date: 2018
Publisher: Wiley
Date: 27-12-2022
DOI: 10.1111/JNS.12478
Abstract: Diffusion‐weighted imaging has been used to quantify peripheral nerve properties however, traditional post‐processing techniques have several limitations. Advanced neuroimaging techniques, which overcome many of these limitations, have not been applied to peripheral nerves. Here, we use state‐of‐the‐art diffusion analysis tools to reconstruct the median and ulnar nerves and quantify their diffusion properties. Diffusion‐weighted MRI scans were obtained from eight healthy adult subjects. Constrained spherical deconvolution was combined with probabilistic fibre tracking to compute track‐weighted fibre orientation distribution (TW‐FOD). The tensor was computed and used along with the tracks to estimate TW apparent diffusion coefficient (TW‐ADC), TW fractional anisotropy (TW‐FA), TW axial diffusivity (TW‐AD), and TW radial diffusivity (TW‐RD). Variability of TW measurements was used to estimate power size information. The population intersession mean (± SD) measurements for the median nerve were TW‐FOD 1.30 (±0.17), TW‐ADC 1.16 (±0.13) × 10 −3 mm 2 /s, TW‐FA 0.60 (±0.05), TW‐AD 2.05 (±0.16) × 10 −3 mm 2 /s, and TW‐RD 0.72 (±0.12) × 10 −3 mm 2 /s. The corresponding measurements for the ulnar nerve were TW‐FOD 1.25 (±0.14), TW‐ADC 1.13 (±0.10) × 10 −3 mm 2 /s, TW‐FA 0.56 (±0.06), TW‐AD 1.93 (±0.01) × 10 −3 mm 2 /s, and TW‐RD 0.74 (±0.12) × 10 −3 mm 2 /s. Based on these measurements, a s le size of 37 would be sufficient to detect a 10% difference in any of the measured TW metrics. A s le size of 20 would be large enough to detect within‐subject differences as small as 2.9% (TW‐AD, ulnar nerve) and between‐subject differences as small as 3.8% (TW‐AD, ulnar nerve).
Publisher: SAGE Publications
Date: 07-2020
Abstract: Treatment of MS often begins with low-efficacy injectable disease-modifying therapy (iDMT). To compare the effect of fingolimod 0.5 mg/day on clinical, MRI, patient-reported, and safety outcomes, in treatment-naïve and previously treated (≥1 iDMT) patients with early MS. EARLIMS was a multicentre, open-label, non-randomized, parallel-group phase 3 b/4 study in Australia and Spain. Patients with relapsing–remitting MS, Expanded Disability Status Scale (EDSS) score .0, and ≥1–5 years since diagnosis, received daily fingolimod for 48 weeks. The primary endpoint was annualized relapse rate (ARR). Of 347 patients enrolled at 51 sites (treatment-naïve, 200 [57.6%] previously treated, 147 [42.4%]), 320 completed the study (treatment-naïve, 184 [92.0%] previously treated, 136 [92.5%]), but the study remained underpowered (planned enrolment, n = 432). Fingolimod reduced ARR to similar levels in both treatment-naïve (mean ARR [95% confidence interval], 0.21 [0.14, 0.29]) and previously treated groups (0.30 [0.20, 0.41] p = 0.1668). There were no new safety signals. Fingolimod appeared equally effective as first- or second-line therapy in relapsing MS. There was a trend for better outcomes with fingolimod in treatment-naïve patients than in those previously treated with iDMT.
Publisher: SAGE Publications
Date: 2019
Abstract: Whole brain atrophy (WBA) estimates in multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. We compare Structural Image Evaluation using Normalisation of Atrophy (SIENA) with the icobrain longitudinal pipeline (icobrain long), for assessment of longitudinal WBA in MS patients. Magnetic resonance imaging (MRI) scan pairs [1.05 (±0.15) year separation] from 102 MS patients were acquired on the same 3T scanner. Three-dimensional (3D) T1-weighted and two-dimensional (2D)/3D fluid-attenuated inversion-recovery sequences were analysed. Percentage brain volume change (PBVC) measurements were calculated using SIENA and icobrain long. Statistical correlation, agreement and consistency between methods was evaluated MRI brain volumetric and clinical data were compared. The proportion of the cohort with annualized brain volume loss (aBVL) rates ⩾ 0.4%, ⩾0.8% and ⩾0.94% were calculated. No evidence of disease activity (NEDA) 3 and NEDA 4 were also determined. Mean annualized PBVC was −0.59 (±0.65)% and −0.64 (±0.73)% as measured by icobrain long and SIENA. icobrain long and SIENA-measured annualized PBVC correlated strongly, r = 0.805 ( p 0.001), and the agreement [intraclass correlation coefficient (ICC) 0.800] and consistency (ICC 0.801) were excellent. Weak correlations were found between MRI metrics and Expanded Disability Status Scale scores. Over half the cohort had aBVL ⩾ 0.4%, approximately a third ⩾0.8%, and aBVL was ⩾0.94% in 28.43% and 23.53% using SIENA and icobrain long, respectively. NEDA 3 was achieved in 35.29%, and NEDA 4 in 15.69% and 16.67% of the cohort, using SIENA and icobrain long to derive PBVC, respectively. icobrain long quantified longitudinal WBA with a strong level of statistical agreement and consistency compared to SIENA in this real-world MS population. Utility of WBA measures in in iduals remains challenging, but show promise as biomarkers of neurodegeneration in MS clinical practice. Optimization of MRI analysis algorithms/techniques are needed to allow reliable use in in iduals. Increased levels of automation will enable more rapid clinical translation.
Publisher: SAGE Publications
Date: 18-06-2019
Abstract: Alemtuzumab is a highly effective treatment for relapsing-remitting multiple sclerosis (MS) but requires ongoing pathology monitoring for autoimmune adverse effects. The Alemtuzumab in MS Safety Systems (AMS3) study evaluated the implementation of an automated pathology-monitoring system. To develop an efficient automated clinical decision support system (CDSS) to electronically prompt and track pathology collection and to provide prescribers and patients with customised alerts of abnormal results for identified risks. A total of 10 patients with relapsing-remitting MS treated with alemtuzumab were enrolled to test the system. Standard care laboratory monitoring was performed and compared to the performance of the CDSS. The automated CDSS, an integrated patient smartphone application and an additional pre-screening tool were all successfully developed. Compliance with pathology monitoring was 96.7%. The automated analysis of pathology results was significantly faster than standard care neurologist review ( p 0.001). The system correctly identified and alerted abnormalities, including one case of immune thrombocytopenia (ITP) while the treating neurologist was on leave, enabling prompt treatment of serious adverse events. During the course of the study, the CDSS was deployed throughout Australia. We successfully developed automated pathology monitoring with a CDSS, demonstrating real-world benefits of high compliance and timely alerting of important results.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2023
Publisher: SAGE Publications
Date: 12-11-2015
Abstract: The objective of this paper is to inform the pathophysiology of medial longitudinal fasciculus (MLF) axonal dysfunction in patients with internuclear ophthalmoplegia (INO) due to multiple sclerosis (MS), and develop a composite structural-functional biomarker of axonal and myelin integrity in this tract. Eighteen patients with definite MS and clinically suspected INO underwent electrical vestibular stimulation and search-coil eye movement recording. Components of the electrically evoked vestibulo-ocular reflex (eVOR) were analyzed to probe the latency and fidelity of MLF axonal conduction. The MLF and T 2 -visible brainstem lesions were defined by high-resolution MRI. White matter integrity was determined by diffusion-weighted imaging metrics. eVOR onset latency was positively correlated with MLF lesion length (left: r = 0.66, p = 0.004 right: r = 0.75, p = 0.001). The mean conduction velocity (±SD) within MLF lesions was estimated at 2.72 (±0.87) m/s. eVOR onset latency correlated with normalized axial diffusivity ( r = 0.66, p 0.001) and fractional anisotropy ( r = 0.44, p = 0.02) after exclusion of cases with ipsilateral vestibular root entry zone lesions. Axonal conduction velocity through lesions involving the MLF was reduced below levels predicted for natively myelinated and remyelinated axons. Composite in vivo biomarkers enable delineation of axonal from myelin processes and may provide a crucial role in assessing efficacy of novel reparative therapies in MS.
Publisher: Oxford University Press (OUP)
Date: 19-01-2019
DOI: 10.1093/BRAIN/AWY338
Abstract: The spread of neurodegeneration through the human brain network is reported as underlying the progression of neurodegenerative disorders. However, the exact mechanisms remain unknown. The human visual pathway is characterized by its unique hierarchical architecture and, therefore, represents an ideal model to study trans-synaptic degeneration, in contrast to the complexity in neural connectivity of the whole brain. Here we show in two specifically selected patient cohorts, including (i) glaucoma patients with symmetrical bilateral hemifield defects respecting the horizontal meridian (n = 25, 14 females, 64.8 ± 10.1 years versus 13 normal controls with similar age/sex distributions) and (ii) multiple sclerosis patients without optic radiation lesions (to avoid potential effects of lesions on diffusivity measures) (n = 30, 25 females, 37.9 ± 10.8 years versus 20 controls), that there are measurable topographic changes in the posterior visual pathways corresponding to the primary optic nerve defects. A significant anisotropic increase of water diffusion was detected in both patient cohorts in the optic radiations, characterized by changes in perpendicular (radial) diffusivity (a measure of myelin integrity) that extended more posteriorly than those observed in parallel (axial) diffusivity (reflecting axonal integrity). In glaucoma, which is not considered a demyelinating disease, the observed increase in radial diffusivity within the optic radiations was validated by topographically linked delay of visual evoked potential latency, a functional measure of demyelination. Radial diffusivity change in the optic radiations was also associated with an asymmetrical reduction in the thickness of the calcarine cortex in glaucoma. In addition, 3 years longitudinal observation of the multiple sclerosis patient cohort revealed an anterograde increase of radial diffusivity in the anterior part of optic radiations which again was retinotopically associated with the primary damage caused by optic neuritis. Finally, in an animal model of optic nerve injury, we observed early glial activation and demyelination in the posterior visual projections, evidenced by the presence of myelin-laden macrophages. This occurred prior to the appearance of amyloid precursor protein accumulation, an indicator of disrupted fast axonal transport. This study demonstrated strong topographical spread of neurodegeneration along recognized neural projections and showed that myelin and glial pathology precedes axonal loss in the process, suggesting that the mechanism of trans-synaptic damage may be at least partially mediated by glial components at the cellular level. The findings may have broad biological and therapeutic implications for other neurodegenerative disorders.
Publisher: Wiley
Date: 13-09-2017
DOI: 10.1111/ENE.13404
Abstract: The mechanism of retinal ganglion cell and retinal nerve fiber layer loss in multiple sclerosis (MS) remains unknown. This study aimed to investigate the association between temporal retinal nerve fiber layer (tRNFL) thinning and disease activity in the brain determined by T2 lesions on magnetic resonance imaging (MRI). Fifty-five consecutive patients with relapsing-remitting MS and 25 controls were enrolled. All patients underwent annual optical coherence tomography and high-resolution MRI scans for tRNFL thickness and brain lesion volume analysis, respectively. Significant tRNFL thickness reduction was observed over the 3-year follow-up period at a relatively constant rate (1.02 μm/year). Thinning of tRNFL fibers was more prominent in younger patients (P = 0.01). The tRNFL loss was associated with new MRI lesions in the optic radiations (ORs). There was significantly greater tRNFL thinning in patients with new lesional activity in the ORs compared with patients with new lesions outside the ORs (P = 0.009). This study supports the notion that retrograde transneuronal degeneration caused by OR lesions might play a role in progressive retinal nerve fiber layer loss. In addition, the results of the study also indicate that the disease-related neurodegenerative changes in the retina start much earlier than the clinical diagnosis of MS.
Publisher: Public Library of Science (PLoS)
Date: 28-08-2014
Publisher: Cold Spring Harbor Laboratory
Date: 09-02-2022
DOI: 10.1101/2022.02.07.22270654
Abstract: The expansion of long-standing multiple sclerosis (MS) lesions and an enlargement of choroid plexus are linked to chronic inflammation and microglial activation. In the current study, we investigated the association between plexus volume and subsequent lesion expansion in patients with relapsing remitting MS. Pre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 49 patients with relapsing-remitting MS. Choroid plexus volume and lesion activity were analysed between baseline and 48 months. Plexus volume remained stable during follow-up period. There was a strong correlation between baseline plexus volume and subsequent rate of chronic lesion expansion (r=0.77, p .001), which was stronger in close proximity to CSF. Furthermore, baseline plexus volume was also associated with change of Mean Diffusivity (MD) inside expanding area (r=0.55, p .001). There was, however, no correlation between baseline plexus volume and volume of new lesions. A cut-off of 98 × 10 −5 plexus/TIV ratio predicted future lesion expansion with a sensitivity of 85% and specificity of 76%. Plexus volume larger than a cut-off was associated with -fold increased risk of chronic lesion expansion. Furthermore, baseline plexus volume significantly correlated with change of MD in lesional core during the study period (r=0.67, p .001) and with central brain atrophy (r=0.57, p .001). Our data demonstrate that baseline plexus volume predicts subsequent expansion of chronic periventricular MS lesions and associated tissue damage.
Publisher: Springer International Publishing
Date: 2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2019
Publisher: Cold Spring Harbor Laboratory
Date: 21-12-2021
DOI: 10.1101/2021.12.20.21268136
Abstract: Expansion of chronic lesions in MS patients and recently described CSF-related gradient of tissue damage are linked to microglial activation. The aim of the current study was to investigate whether lesion expansion is associated with proximity to ventricular CSF spaces. Pre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 36 RRMS patients. Lesional activity was analysed between baseline and 48 months at different distances from the CSF using successive 1-mm thick concentric rings radiating from the ventricles. Voxel-based analysis of the rate of lesion expansion demonstrated a clear periventricular gradient decreasing away from the ventricles. This was particularly apparent when lesions of equal diameter were analysed. Periventricular lesional tissue showed higher degree of tissue distraction at baseline that significantly increased during follow-up in rings close to CSF. This longitudinal change was proportional to degree of lesion expansion. Lesion-wise analysis revealed a gradual, centrifugal decrease in the proportion of expanding lesions from the immediate periventricular zone. Our data suggest that chronic white matter lesions in close proximity to the ventricles are more destructive, show a higher degree of expansion at the lesion border and accelerated tissue loss in the lesion core.
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 2017
Publisher: BMJ
Date: 29-06-2021
Abstract: To investigate potential neuroprotective and pro-remyelinating effects of alemtuzumab in multiple sclerosis (MS), using the visual pathway as a model. We monitored clinical, multifocal visual evoked potential (mfVEP) and MRI outcomes in 30 patients commencing alemtuzumab for relapsing MS, and a reference group of 20 healthy controls (HCs), over 24 months. Change in mfVEP latency was the primary endpoint change in optic radiation (OR) lesion diffusion metrics and Mars letter contrast sensitivity over the course of the study were secondary endpoints. In patients, we observed a mean shortening of mfVEP latency of 1.21 ms over the course of the study (95% CI 0.21 to 2.21, p=0.013), not altered by correction for age, gender, disease duration or change in OR T2 lesion volume. Mean mfVEP latency in the HC group increased over the course of the study by 0.72 ms (not significant). Analysis of chronic OR T2 lesions (patients) showed an increase in normalised fractional anisotropy and axial diffusivity between baseline and 24 months (both p .01). Mean Mars letter contrast sensitivity was improved at 24 months vs baseline (p .001), and driven by an early improvement, in both patients and HC. We found evidence of partial lesion remyelination after alemtuzumab therapy, indicating either natural restoration in the context of a ‘permissive’ local milieu or potentially an independent, pro-reparative mechanism of action. The visual system presents a unique opportunity to study function-structure specific effects of therapy and inform the design of future phase 2 MS remyelination trials.
Publisher: Public Library of Science (PLoS)
Date: 22-02-2016
Publisher: Springer Science and Business Media LLC
Date: 19-10-2023
Publisher: MDPI AG
Date: 18-10-2022
DOI: 10.3390/APP122010487
Abstract: The implications of combining structural and functional connectivity to quantify the most active brain regions in seizure onset remain unclear. This study tested a new model that may facilitate the incorporation of diffusion MRI (dMRI) in clinical practice. We obtained structural connectomes from dMRI and functional connectomes from electroencephalography (EEG) to assess whether high structure-function coupling corresponded with the seizure onset region. We mapped in idual electrodes to their nearest cortical region to allow for a one-to-one comparison between the structural and functional connectomes. A seizure laterality score and expected onset zone were defined. The patients with well-lateralised seizures revealed high structure-function coupling consistent with the seizure onset zone. However, a lower seizure lateralisation score translated to reduced alignment between the high structure-function coupling regions and the seizure onset zone. We illustrate that dMRI, in combination with EEG, can improve the identification of the seizure onset zone. Our model may be valuable in enhancing ultra-long-term monitoring by indicating optimal, in idualised electrode placement.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.MSARD.2017.12.016
Abstract: The availability of effective therapies for patients with relapsing-remitting multiple sclerosis (RRMS) has prompted a re-evaluation of the most appropriate way to measure treatment response, both in clinical trials and clinical practice. Traditional parameters of treatment efficacy such as annualized relapse rate, magnetic resonance imaging (MRI) activity, and disability progression have an important place, but their relative merit is uncertain, and the role of other factors such as brain atrophy is still under study. More recently, composite measures such as "no evidence of disease activity" (NEDA) have emerged as new potential treatment targets, but NEDA itself has variable definitions, is not well validated, and may be hard to implement as a treatment goal in a clinical setting. We describe the development of NEDA as an outcome measure in MS, discuss definitions including NEDA-3 and NEDA-4, and review the strengths and limitations of NEDA, indicating where further research is needed.
Publisher: Frontiers Media SA
Date: 06-07-2023
DOI: 10.3389/FNINS.2023.1196087
Abstract: Brain atrophy is a critical biomarker of disease progression and treatment response in neurodegenerative diseases such as multiple sclerosis (MS). Confounding factors such as inconsistent imaging acquisitions h er the accurate measurement of brain atrophy in the clinic. This study aims to develop and validate a robust deep learning model to overcome these challenges and to evaluate its impact on the measurement of disease progression. Voxel-wise pseudo-atrophy labels were generated using SIENA, a widely adopted tool for the measurement of brain atrophy in MS. Deformation maps were produced for 195 pairs of longitudinal 3D T1 scans from patients with MS. A 3D U-Net, namely DeepBVC, was specifically developed overcome common variances in resolution, signal-to-noise ratio and contrast ratio between baseline and follow up scans. The performance of DeepBVC was compared against SIENA using McLaren test-retest dataset and 233 in-house MS subjects with MRI from multiple time points. Clinical evaluation included disability assessment with the Expanded Disability Status Scale (EDSS) and traditional imaging metrics such as lesion burden. For 3 subjects in test-retest experiments, the median percent brain volume change (PBVC) for DeepBVC and SIENA was 0.105 vs. 0.198% (subject 1), 0.061 vs. 0.084% (subject 2), 0.104 vs. 0.408% (subject 3). For testing consistency across multiple time points in in idual MS subjects, the mean (± standard deviation) PBVC difference of DeepBVC and SIENA were 0.028% (± 0.145%) and 0.031% (±0.154%), respectively. The linear correlation with baseline T2 lesion volume were r = −0.288 ( p & 0.05) and r = −0.249 ( p & 0.05) for DeepBVC and SIENA, respectively. There was no significant correlation of disability progression with PBVC as estimated by either method ( p = 0.86, p = 0.84). DeepBVC is a deep learning powered brain volume change estimation method for assessing brain atrophy used T1-weighted images. Compared to SIENA, DeepBVC demonstrates superior performance in reproducibility and in the context of common clinical scan variances such as imaging contrast, voxel resolution, random bias field, and signal-to-noise ratio. Enhanced measurement robustness, automation, and processing speed of DeepBVC indicate its potential for utilisation in both research and clinical environments for monitoring disease progression and, potentially, evaluating treatment effectiveness.
Publisher: Frontiers Media SA
Date: 14-09-2022
DOI: 10.3389/FNEUR.2022.972590
Abstract: We examined the white matter of patients with and without focal to bilateral tonic-clonic seizures (FBTCS), and control participants. A neural network based tract segmentation model (Tractseg) was used to isolate tract-specific, track-weighted tensor-based measurements from the tracts of interest. We compared the group differences in the track-weighted tensor-based measurements derived from whole and hemispheric tracts. We identified several regions that displayed significantly altered white matter in patients with focal epilepsy compared to controls. Furthermore, patients without FBTCS showed significantly increased white matter disruption in the inferior fronto-occipital fascicle and the striato-occipital tract. In contrast, the track-weighted tensor-based measurements from the FBTCS cohort exhibited a stronger resemblance to the healthy controls (compared to the non-FBTCS group). Our findings revealed marked alterations in a range of subcortical tracts considered critical in the genesis of seizures in focal epilepsy. Our novel application of tract-specific, track-weighted tensor-based measurements to a new clinical dataset aided the elucidation of specific tracts that may act as a predictive biomarker to distinguish patients likely to develop FBTCS.
Publisher: Elsevier BV
Date: 02-2016
Publisher: Frontiers Media SA
Date: 11-09-2023
Publisher: Frontiers Media SA
Date: 18-05-2023
DOI: 10.3389/FNINS.2023.1167612
Abstract: Federated learning (FL) has been widely employed for medical image analysis to facilitate multi-client collaborative learning without sharing raw data. Despite great success, FL's applications remain suboptimal in neuroimage analysis tasks such as lesion segmentation in multiple sclerosis (MS), due to variance in lesion characteristics imparted by different scanners and acquisition parameters. In this work, we propose the first FL MS lesion segmentation framework via two effective re-weighting mechanisms. Specifically, a learnable weight is assigned to each local node during the aggregation process, based on its segmentation performance. In addition, the segmentation loss function in each client is also re-weighted according to the lesion volume for the data during training. The proposed method has been validated on two FL MS segmentation scenarios using public and clinical datasets. Specifically, the case-wise and voxel-wise Dice score of the proposed method under the first public dataset is 65.20 and 74.30, respectively. On the second in-house dataset, the case-wise and voxel-wise Dice score is 53.66, and 62.31, respectively. The Comparison experiments on two FL MS segmentation scenarios using public and clinical datasets have demonstrated the effectiveness of the proposed method by significantly outperforming other FL methods. Furthermore, the segmentation performance of FL incorporating our proposed aggregation mechanism can achieve comparable performance to that from centralized training with all the raw data.
Publisher: Wiley
Date: 07-2019
DOI: 10.1111/JON.12650
Abstract: Quantitative neuroimaging is an important part of multiple sclerosis research and clinical trials, and measures of lesion volume (LV) and brain atrophy are key clinical trial endpoints. However, translation of these endpoints to heterogeneous historical datasets and nonstandardized clinical routine imaging has been difficult. The NeuroSTREAM technique was recently introduced as a robust and broadly applicable surrogate for brain atrophy measurement, but no such surrogate currently exists for conventional T2-LV. Therefore, we sought to develop a fully automated proxy for T2-LV with similar analytic value but increased robustness to common issues arising in clinical routine imaging. We created an algorithm to identify salient central lesion volume (SCLV), comprised of the subset of lesion voxels within a specific distance to the lateral ventricles (centrality) and with intensity at least a quantitatively-derived amount brighter than normal appearing tissue (salience). We evaluated this method on four datasets (clinical, inter-scanner, scan-rescan, and real-world multi-center), including 1.5T, 3T, Philips, Siemens, and GE scanners with heterogeneous protocols, to assess agreement with conventional T2-LV, comparative relationship with disability, reliability across scanners and between scans, and applicability to real-world scans. SCLV correlated strongly with conventional T2-LV in both research-quality (r = .90, P < .001) and real-world (r = 0.87, P < 0.001) datasets. It also showed similar correlations with Expanded Disability Status Scale, as conventional T2-LV (r = 0.48 for T2-LV vs. r = 0.45 for SCLV). Inter-scanner reproducibility (ICC) was 0.86, p < 0.001 for SCLV compared to 0.84, p < 0.001 for conventional T2-LV, whereas scan-rescan ICC was 0.999 for SCLV versus 0.997 for T2-LV. SCLV is a robust, fully-automated proxy for T2-LV in situations where conventional T2-LV is not easily or reliably calculated.
Publisher: Cold Spring Harbor Laboratory
Date: 19-01-2021
DOI: 10.1101/2021.01.17.427042
Abstract: Mapping the human connectome using fiber-tracking permits the study of brain connectivity and yields new insights into neuroscience. However, reliable connectome reconstruction using diffusion magnetic resonance imaging (dMRI) data acquired by widely available clinical protocols remains challenging, thus limiting the connectome / tractography clinical applications. Here we develop fiber orientation distribution (FOD) network (FOD-Net), a deep-learning-based framework for FOD angular super-resolution. Our method enhances the angular resolution of FOD images computed from common clinical-quality dMRI data, to obtain FODs with quality comparable to those produced from advanced research scanners. Super-resolved FOD images enable superior tractography and structural connectome reconstruction from clinical protocols. The method was trained and tested with high-quality data from the Human Connectome Project (HCP) and further validated with a local clinical 3.0T scanner. Using this method, we improve the angular resolution of FOD images acquired with typical single-shell low-angular-resolution dMRI data (e.g., 32 directions, b = 1000 s/mm 2 ) to approximate the quality of FODs derived from time-consuming, multi-shell high-angular-resolution dMRI research protocols. We also demonstrate tractography improvement, removing spurious connections and bridging missing connections. We further demonstrate that connectomes reconstructed by super-resolved FODs achieve comparable results to those obtained with more advanced dMRI acquisition protocols, on both HCP and clinical 3.0T data. Advances in deep-learning approaches used in FOD-Net facilitate the generation of high quality tractography / connectome analysis from existing clinical MRI environments. Our code is freely available at uizengalways/FOD-Net .
Publisher: Public Library of Science (PLoS)
Date: 03-10-2013
Publisher: Springer Nature Switzerland
Date: 2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-05-2014
Publisher: SAGE Publications
Date: 16-03-2022
DOI: 10.1177/13524585221080667
Abstract: Expansion of chronic lesions in multiple sclerosis (MS) patients and recently described cerebrospinal fluid (CSF)-related gradient of tissue damage are linked to microglial activation. The aim of this study was to investigate whether lesion expansion is associated with proximity to ventricular CSF spaces. Pre- and post-gadolinium three-dimensional (3D)-T1, 3D FLAIR and diffusion tensor images were acquired from 36 relapsing-remitting MS (RRMS) patients. Lesional activity was analysed between baseline and 48 months at different distances from the CSF using successive 1 mm thick concentric bands radiating from the ventricles. Voxel-based analysis of the rate of lesion expansion demonstrated a clear periventricular gradient decreasing away from the ventricles. This was particularly apparent when lesions of equal diameter were analysed. Periventricular lesional tissue showed higher degree of tissue destruction at baseline that significantly increased during follow-up in bands close to CSF. This longitudinal change was proportional to degree of lesion expansion. Lesion-wise analysis revealed a gradual, centrifugal decrease in the proportion of expanding lesions from the immediate periventricular zone. Our data suggest that chronic white matter lesions in close proximity to the ventricles are more destructive, show a higher degree of expansion at the lesion border and accelerated tissue loss in the lesion core.
Publisher: Cold Spring Harbor Laboratory
Date: 26-10-2021
DOI: 10.1101/2021.10.21.21265249
Abstract: We sought to examine the microstructural white matter differences in patients with focal to bilateral tonic-clonic seizures (FBTCS), compared to those with focal epilepsy without FBTCS, and control participants. Using a superior tract segmentation model, we obtained track-weighted tensor-metrics (TW-TM), implemented through an automated pipeline for image analysis and tract reconstruction. Analysis of covariance was used to compare group differences in the TW-TM for whole-tract and hemispheric tract measurements. We identified several white matter regions that displayed significantly altered white matter in patients with focal epilepsy compared to controls. Further, patients without FBTCS had significantly increased white matter disruption in the inferior fronto-occipital fascicle and the striato-occipital tract. In contrast, patients with FBTCS were more similar to healthy controls in most regions, except for distinct alterations in the inferior cerebellar region compared to the non-FBTCS group and controls. Our study revealed marked alterations in a range of subcortical tracts widely considered critical in the genesis of seizures in focal epilepsy. Our application of TW-TM in a new clinical dataset enabled the identification of specific tracts that may act as a predictive biomarker to distinguish patients who are likely to develop FBTCS.
Publisher: SAGE Publications
Date: 13-05-2015
Abstract: Emotional processing has been reported to effect sensory gating as measured by the event-related potential known as P50. Because both P50 and emotional processing are dysfunctional in bipolar disorder (BD), we sought to investigate the impact that concurrent emotional processing has on sensory gating in this psychiatric population. P50 was recorded using a paired-click paradigm. Peak-to-peak litudes for stimulus 1 (S1) and stimulus 2 (S2) were acquired during the presentation of disgust and neutral faces to young adults with BD (n = 19) and controls (n = 20). Social functioning and quality-of-life self-reported measures were also obtained. The BD group had significantly larger P50 litudes elicited by the S2-disgust response compared with controls, but no significant difference in overall P50 sensory gating was found between the groups. There were also no differences between groups in S1-disgust or in either of the neutral P50 litudes. The BD group showed significant associations between sensory gating to disgust and measures of social functioning. Importantly, BD showed impaired filtering of auditory information when paired with an emotionally salient image. Thus, it appears that patients with the greatest impairment in sensory gating also have the most difficulty engaging in social situations.
Publisher: Springer Nature Switzerland
Date: 2022
Publisher: Public Library of Science (PLoS)
Date: 25-03-2015
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.MEDIA.2022.102431
Abstract: Mapping the human connectome using fiber-tracking permits the study of brain connectivity and yields new insights into neuroscience. However, reliable connectome reconstruction using diffusion magnetic resonance imaging (dMRI) data acquired by widely available clinical protocols remains challenging, thus limiting the connectome/tractography clinical applications. Here we develop fiber orientation distribution (FOD) network (FOD-Net), a deep-learning-based framework for FOD angular super-resolution. Our method enhances the angular resolution of FOD images computed from common clinical-quality dMRI data, to obtain FODs with quality comparable to those produced from advanced research scanners. Super-resolved FOD images enable superior tractography and structural connectome reconstruction from clinical protocols. The method was trained and tested with high-quality data from the Human Connectome Project (HCP) and further validated with a local clinical 3.0T scanner as well as with another public available multicenter-multiscanner dataset. Using this method, we improve the angular resolution of FOD images acquired with typical single-shell low-angular-resolution dMRI data (e.g., 32 directions, b=1000s/mm
Publisher: The Royal Society
Date: 05-2023
DOI: 10.1098/RSOS.230022
Abstract: Epilepsy is a prevalent condition characterized by recurrent, unpredictable seizures. Monitoring with surface electroencephalography (EEG) is the gold standard for diagnosing epilepsy, but a time-consuming, uncomfortable and sometimes ineffective process for patients. Further, using EEG over a brief monitoring period has variable success, dependent on patient tolerance and seizure frequency. The availability of hospital resources and hardware and software specifications inherently restrict the options for comfortable, long-term data collection, resulting in limited data for training machine-learning models. This mini-review examines the current patient journey, providing an overview of the current state of EEG monitoring with reduced electrodes and automated channel reduction methods. Opportunities for improving data reliability through multi-modal data fusion are suggested. We assert the need for further research in electrode reduction to advance brain monitoring solutions towards portable, reliable devices that simultaneously offer patient comfort, perform ultra-long-term monitoring and expedite the diagnosis process.
Publisher: Informa UK Limited
Date: 28-02-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-07-2019
DOI: 10.1212/NXI.0000000000000593
Abstract: To evaluate the combined effect of lesion activity and pathologic processes occurring in both chronically demyelinated lesions and normal-appearing white matter (NAWM) on brain atrophy in MS. Pre- and post-gadolinium T1, fluid attenuation inversion recovery, and diffusion tensor imaging images were acquired from 50 consecutive patients with relapsing-remitting MS (all, but one, on disease-modifying therapy) at baseline and 5 years. Brain atrophy was measured using structural image evaluation, using normalization of atrophy percent brain volume change (PBVC) analysis. During follow-up, brain volume diminished by 2.0% ± 1.1%. PBVC was not associated with patient age, disease duration, sex, or type of treatment. PBVC moderately correlated with baseline lesion load ( r = −0.38, p = 0.016), but demonstrated strong association with new lesion activity ( r = −0.63, p 0.001). Brain atrophy was also strongly linked to the increase of water diffusion within chronic MS lesions ( r = −0.62, p 0.001). In normal-appearing white matter (NAWM), PBVC demonstrated a significant correlation with both baseline and longitudinal increase of demyelination as measured by radial diffusivity (RD, r = −0.44, p = 0.005 and r = −0.35, p = 0.026, respectively). Linear regression analysis explained 62% of the variance in PBVC. It confirmed the major role of new lesion activity ( p = 0.002, standardized beta-coefficient −0.42), whereas change in diffusivity inside chronic lesions and NAWM RD at baseline also contributed significantly ( p = 0.04 and 0.02, standardized beta-coefficient −0.31 and −0.29, respectively), increasing predictive power of the model by 55%. In addition to new lesion activity, progressive loss of demyelinated axons in chronic lesions and the degree of demyelination in NAWM significantly contribute to accelerated loss of brain tissue in patients with MS receiving immunomodulatory therapy.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 06-2014
Publisher: Public Library of Science (PLoS)
Date: 25-04-2018
No related grants have been discovered for Chenyu Wang.