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Cornelia Laule

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7 papers

1 author row

YNICL Journal 2022 Journal Article

Myelin water imaging in relapsing multiple sclerosis treated with ocrelizumab and interferon beta-1a

Shannon Kolind
Shawna Abel
Carolyn Taylor
Roger Tam
Cornelia Laule
David K.B. Li
Hideki Garren
Laura Gaetano

BACKGROUND: Myelin water imaging is a magnetic resonance imaging (MRI) technique that quantifies myelin damage and repair in multiple sclerosis (MS) via the myelin water fraction (MWF). OBJECTIVE: In this substudy of a phase 3 therapeutic trial, OPERA II, MWF was assessed in relapsing MS participants assigned to interferon beta-1a (IFNb-1a) or ocrelizumab (OCR) during a two-year double-blind period (DBP) followed by a two-year open label extension (OLE) with ocrelizumab treatment. METHODS: MWF in normal appearing white matter (NAWM), including both whole brain NAWM and 5 white matter structures, and chronic lesions, was assessed in 29 OCR and 26 IFNb-1a treated participants at weeks 0, 24, 48 and 96 (DBP), and weeks 144 and 192 (OLE), and in white matter for 23 healthy control participants at weeks 0, 48 and 96. RESULTS: Linear mixed-effects models of data from baseline to week 96 showed a difference in the change in MWF over time favouring ocrelizumab in all NAWM regions. At week 192, lesion MWF was lower for participants originally randomised to IFNb-1a compared to those originally randomised to OCR. Controls showed no change in MWF over 96 weeks in any region. CONCLUSION: Ocrelizumab appears to protect against demyelination in MS NAWM and chronic lesions and may allow for a more permissive micro environment for remyelination to occur in focal and diffusely damaged tissue.

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YNIMG Journal 2021 Journal Article

Temperature dependence and histological correlation of inhomogeneous magnetization transfer and myelin water imaging in ex vivo brain

Valentin H. Prevost
Andrew Yung
Sarah R. Morris
Irene M. Vavasour
Zahra Samadi-Bahrami
G.R. Wayne Moore
Cornelia Laule
Alex MacKay

PURPOSE: . METHODS: ihMT ratio (ihMTR) and MWF maps were acquired at 7 T from formalin-fixed human brain samples at 22.5 °C, 30 °C and 37 °C. The impact of temperature on unfiltered ihMTR, filtered ihMTR and MWF was investigated and compared to myelin basic protein staining. RESULTS: C, filtered ihMTR was more strongly correlated with myelin staining and had increased dynamic range compared to unfiltered ihMTR. CONCLUSIONS: components. Ex vivo myelin water imaging should be performed at room temperature, to avoid fitting issues found at higher temperatures.

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YNIMG Journal 2020 Journal Article

Myelin water imaging data analysis in less than one minute

Hanwen Liu
Qing-San Xiang
Roger Tam
Adam V. Dvorak
Alex L. MacKay
Shannon H. Kolind
Anthony Traboulsee
Irene M. Vavasour

Purpose Based on a deep learning neural network (NN) algorithm, a super fast and easy to implement data analysis method was proposed for myelin water imaging (MWI) to calculate the myelin water fraction (MWF). Methods A NN was constructed and trained on MWI data acquired by a 32-echo 3D gradient and spin echo (GRASE) sequence. Ground truth labels were created by regularized non-negative least squares (NNLS) with stimulated echo corrections. Voxel-wise GRASE data from 5 brains (4 healthy, 1 multiple sclerosis (MS)) were used for NN training. The trained NN was tested on 2 healthy brains, 1 MS brain with segmented lesions, 1 healthy spinal cord, and 1 healthy brain acquired from a different scanner. Results Production of whole brain MWF maps in approximately 33 s can be achieved by a trained NN without graphics card acceleration. For all testing regions, no visual differences between NN and NNLS MWF maps were observed, and no obvious regional biases were found. Quantitatively, all voxels exhibited excellent agreement between NN and NNLS (all R2>0. 98, p < 0. 001, mean absolute error <0. 01). Conclusion The time for accurate MWF calculation can be dramatically reduced to less than 1 min by the proposed NN, addressing one of the barriers facing future clinical feasibility of MWI.

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YNICL Journal 2019 Journal Article

Rapid myelin water imaging for the assessment of cervical spinal cord myelin damage

Adam V. Dvorak
Emil Ljungberg
Irene M. Vavasour
Hanwen Liu
Poljanka Johnson
Alexander Rauscher
John L.K. Kramer
Roger Tam

BACKGROUND: ). OBJECTIVE: metrics. METHODS: data were acquired in 2 PLS, 1 relapsing-remitting MS (RRMS), 1 primary-progressive MS (PPMS) and 2 NMO subjects, as well as 6 age (±3 yrs) and sex matched healthy controls (HC). Internal cord structure guided template registrations, used for region of interest (ROI) analysis. Z score maps were calculated for the difference between disease subject and mean HC metric values. RESULTS: metrics showed similar trends, corroborating the MWF results and providing complementary information. CONCLUSION: measures.

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YNICL Journal 2014 Journal Article

48 echo T2 myelin imaging of white matter in first-episode schizophrenia: Evidence for aberrant myelination

Donna J.M. Lang
Eugene Yip
Alexander L. MacKay
Allen E. Thornton
Fidel Vila-Rodriguez
G. William MacEwan
Lili C. Kopala
Geoffrey N. Smith

Myelin water imaging provides a novel strategy to assess myelin integrity and corresponding clinical relationships in psychosis, of particular relevance in frontal white matter regions. In the current study, T2 myelin water imaging was used to assess the myelin water fraction (MWF) signal from frontal areas in a sample of 58 individuals experiencing first-episode psychosis (FEP) and 44 healthy volunteers. No differences in frontal MWF were observed between FEP subjects and healthy volunteers; however, differences in normal patterns of associations between frontal MWF and age, education and IQ were seen. Significant positive relationships between frontal MWF and age, North American Adult Reading Test (NAART) IQ, and years of completed education were observed in healthy volunteers. In contrast, only the relationship between frontal MWF and NAART IQ was significant after Bonferroni correction in the FEP group. Additionally, significant positive relationships between age and MWF in the anterior and posterior internal capsules, the genu, and the splenium were observed in healthy volunteers. In FEP subjects, only the relationship between age and MWF in the splenium was statistically significant. Frontal MWF was not associated with local white matter volume. Altered patterns of association between age, years of education, and MWF in FEP suggest that subtle disturbances in myelination may be present early in the course of psychosis.

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YNIMG Journal 2008 Journal Article

Complementary information from multi-exponential T2 relaxation and diffusion tensor imaging reveals differences between multiple sclerosis lesions

Shannon H. Kolind
Cornelia Laule
Irene M. Vavasour
David K.B. Li
Anthony L. Traboulsee
Burkhard Mädler
G.R. Wayne Moore
Alex L. MacKay

While conventional magnetic resonance imaging (MRI) has long been used to study multiple sclerosis (MS), more sensitive and specific approaches to studying both MS lesions and normal appearing white matter (NAWM) are needed to gain a better understanding of the pathogenesis of the disease. Two MRI techniques thought to offer insight regarding myelin and axonal integrity are T 2 relaxation and diffusion tensor imaging (DTI). In this study, metrics obtained from T 2 relaxation (specifically myelin water content (MWC) and long-T 2 fraction) and DTI experiments (in particular the fractional anisotropy, mean diffusivity <D>, parallel diffusivity λ ||, and perpendicular diffusivity λ ⊥) were compared for 19 MS patients within both lesion and contralateral NAWM with the goal of better understanding how each of the measures are affected by pathology. In particular, it was successfully determined that the detection of a long-T 2 signal within an MS lesion is indicative of a different underlying pathology than is present in lesions without long-T 2 signal. All of the diffusion metrics were significantly different in lesions with a long-T 2 signal than in those without. While no significant correlations were found between MWC and <D>, λ || or λ ⊥ in NAWM (R 2 =0. 02–0. 04, p >0. 07), and only weak correlations were found in lesions without long-T 2 signal (R 2 =0. 05–0. 14, p <0. 04), strong correlations were observed in lesions exhibiting long-T 2 signal (R 2 =0. 54–0. 61, p <0. 0001).

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YNIMG Journal 2008 Journal Article

Myelin water imaging of multiple sclerosis at 7 T: Correlations with histopathology

Cornelia Laule
Piotr Kozlowski
Esther Leung
David K.B. Li
Alex L. MacKay
G.R. Wayne Moore

Myelin water imaging (MWI) promises to be invaluable in understanding neurological diseases like MS. However, a limitation of MWI is signal to noise ratio. Recently, a number of investigators have performed MWI at field strengths higher than 1. 5 T. Our goal was to determine if myelin water imaging at increased SNR, arising from the use of a small bore 7 T MR system with optimized coil geometry, enables the production of superior myelin water maps with increased spatial detail and enables better correlations with histology. Ten formalin-fixed MS brain samples underwent a 32-echo T 2 relaxation experiment which measured myelin water fraction (MWF) on a 7-T animal MRI scanner. MWF correlated strongly qualitatively and quantitatively with luxol fast blue staining for myelin [mean (range): R 2 =0. 78 (0. 56–0. 95), p <0. 0001]. The quality and detail of 7 T myelin water maps were far superior to that previously seen at 1. 5 T, allowing for visualization of fine structures such as the normal prominent myelination of the deeper cortical layers, the alveus of the hippocampus and rings of preserved myelin in a concentric Balo's lesion. 7 T imaging will allow detailed assessment of myelin pathology to a degree not possible with lower field strengths.

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