Publications by authors named "Irene M Vavasour"

46 Publications

Elevated levels of serum CD5 antigen-like protein distinguish secondary progressive multiple sclerosis from other disease subtypes.

Mult Scler Relat Disord 2021 Sep 20;56:103269. Epub 2021 Sep 20.

Department of Pathology & Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada; International Collaboration on Repair Discoveries (ICORD), Faculty of Medicine, University of British Columbia, Vancouver, Canada. Electronic address:

CD5 antigen-like (CD5L) protein is a macrophage-secreted protein with roles in immunomodulation and lipid homeostasis. We compared serum CD5L levels in healthy controls to individuals diagnosed with clinically isolated syndrome, relapsing remitting (RR), secondary progressive (SP), and primary progressive (PP) multiple sclerosis (MS). CD5L was increased in SPMS relative to controls, RRMS, and PPMS. SPMS CD5L was associated with longer disease duration independent of age, sex, or disease severity. The positive relationship between CD5L and disease duration in SPMS suggests a chronic peripheral inflammatory profile compared to other subtypes, particularly PPMS, warranting investigation of functional roles for CD5L in MS.
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http://dx.doi.org/10.1016/j.msard.2021.103269DOI Listing
September 2021

Water content changes in new multiple sclerosis lesions have a minimal effect on the determination of myelin water fraction values.

J Neuroimaging 2021 Jul 26. Epub 2021 Jul 26.

Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada.

Background And Purpose: Myelin water fraction (MWF) is a histopathologically validated in vivo myelin marker. As MWF is the proportion of water with a short T relative to the total water, increases in water from edema and inflammation may confound MWF determination in multiple sclerosis (MS) lesions. Total water content (TWC) measurement enables calculation of absolute myelin water content (MWC) and can be used to distinguish edema/inflammation from demyelination. We assessed what influence changes in total water might have on MWF by calculating MWC values in new MS lesions.

Methods: 3T 32-echo T relaxation data were collected monthly for 6 months from six relapsing-remitting MS participants. TWC was determined and multiplied with MWF images to calculate corrected MWC images. The effect of this water content correction was examined in 20 new lesions by comparing mean MWF and MWC over time.

Results: On average, at lesion first appearance, lesion TWC increased by 6.4% (p = .003; range: -1% to +21%), MWF decreased by 24% (p = .006; range: -70% to +12%), and MWC decreased by 20% (p = .026; range: -68% to +21%), relative to prelesion values. Average TWC in lesions then gradually decreased, whereas MWF and MWC remained low. The shape of the MWF and MWC lesion evolution curves was nearly identical, differing only by an offset.

Conclusion: MWF mirrors MWC and is able to monitor myelin in new lesions. Even after taking into account water content increases, MWC still decreased at lesion first appearance attributed to demyelination.
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http://dx.doi.org/10.1111/jon.12908DOI Listing
July 2021

Characterization of multiple sclerosis neuroinflammation and neurodegeneration with relaxation and diffusion basis spectrum imaging.

Mult Scler 2021 Jun 16:13524585211023345. Epub 2021 Jun 16.

Department of Radiology, The University of British Columbia, Vancouver, BC, Canada/International Collaboration on Repair Discoveries (ICORD), The University of British Columbia, Vancouver, BC, Canada/Department of Physics & Astronomy, The University of British Columbia, Vancouver, BC, Canada/Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada.

Background: Advanced magnetic resonance imaging (MRI) methods can provide more specific information about various microstructural tissue changes in multiple sclerosis (MS) brain. Quantitative measurement of T and T relaxation, and diffusion basis spectrum imaging (DBSI) yield metrics related to the pathology of neuroinflammation and neurodegeneration that occurs across the spectrum of MS.

Objective: To use relaxation and DBSI MRI metrics to describe measures of neuroinflammation, myelin and axons in different MS subtypes.

Methods: 103 participants (20 clinically isolated syndrome (CIS), 33 relapsing-remitting MS (RRMS), 30 secondary progressive MS and 20 primary progressive MS) underwent quantitative T, T, DBSI and conventional 3T MRI. Whole brain, normal-appearing white matter, lesion and corpus callosum MRI metrics were compared across MS subtypes.

Results: A gradation of MRI metric values was seen from CIS to RRMS to progressive MS. RRMS demonstrated large oedema-related differences, while progressive MS had the most extensive abnormalities in myelin and axonal measures.

Conclusion: Relaxation and DBSI-derived MRI measures show differences between MS subtypes related to the severity and composition of underlying tissue damage. RRMS showed oedema, demyelination and axonal loss compared with CIS. Progressive MS had even more evidence of increased oedema, demyelination and axonal loss compared with CIS and RRMS.
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http://dx.doi.org/10.1177/13524585211023345DOI Listing
June 2021

Nonlesional diffusely abnormal appearing white matter in clinically isolated syndrome: Prevalence, association with clinical and MRI features, and risk for conversion to multiple sclerosis.

J Neuroimaging 2021 09 15;31(5):981-994. Epub 2021 Jun 15.

Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada.

Background And Purpose: While diffusely abnormal white matter (DAWM) is a nonlesional MRI abnormality identified in ∼25% of patients with multiple sclerosis (MS), it has yet to be investigated in patients at an earlier disease stage, namely clinically isolated syndrome (CIS). The goals of this study were to (1) determine the prevalence of DAWM in patients with a CIS suggestive of MS, (2) evaluate the association between DAWM and demographic, clinical, and MRI features, and (3) evaluate the prognostic significance of DAWM on conversion from CIS to MS.

Methods: One hundred and forty-two CIS participants were categorized into DAWM and non-DAWM groups at baseline and followed for up to 24 months or until MS diagnosis. The primary outcome was conversion to MS (2005 McDonald criteria) within 6 months.

Results: DAWM was present in 27.5% of participants, and was positively associated with brainstem symptom onset, receiving corticosteroids, dissemination in space, and T lesion volume. DAWM was associated with an increased risk of conversion to MS over 6 months after adjustment for age and disability (hazard ratio [HR] = 2.24, p = 0.004). This association remained at a trend-level after adjustment for high-risk imaging features (HR = 1.68, p = 0.10).

Conclusions: DAWM is present in a similar proportion of patients with CIS and clinically definite MS, and it is associated with increased risk of conversion to MS over 6 months.
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http://dx.doi.org/10.1111/jon.12900DOI Listing
September 2021

Cortical N-acetylaspartate concentrations are impacted in chronic stroke but do not relate to motor impairment: A magnetic resonance spectroscopy study.

Hum Brain Mapp 2021 Jul 3;42(10):3119-3130. Epub 2021 May 3.

Department of Physical Therapy, University of British Columbia, Vancouver, British Columbia, Canada.

Magnetic resonance spectroscopy (MRS) measures cerebral metabolite concentrations, which can inform our understanding of the neurobiological processes associated with stroke recovery. Here, we investigated whether metabolite concentrations in primary motor and somatosensory cortices (sensorimotor cortex) are impacted by stroke and relate to upper-extremity motor impairment in 45 individuals with chronic stroke. Cerebral metabolite estimates were adjusted for cerebrospinal fluid and brain tissue composition in the MRS voxel. Upper-extremity motor impairment was indexed with the Fugl-Meyer (FM) scale. N-acetylaspartate (NAA) concentration was reduced bilaterally in stroke participants with right hemisphere lesions (n = 23), relative to right-handed healthy older adults (n = 15; p = .006). Within the entire stroke sample (n = 45) NAA and glutamate/glutamine (GLX) were lower in the ipsilesional sensorimotor cortex, relative to the contralesional cortex (NAA: p < .001; GLX: p = .003). Lower ipsilesional NAA was related to greater extent of corticospinal tract (CST) injury, quantified by a weighted CST lesion load (p = .006). Cortical NAA and GLX concentrations did not relate to the severity of chronic upper-extremity impairment (p > .05), including after a sensitivity analysis imputing missing metabolite data for individuals with large cortical lesions (n = 5). Our results suggest that NAA, a marker of neuronal integrity, is sensitive to stroke-related cortical damage and may provide mechanistic insights into cellular processes of cortical adaptation to stroke. However, cortical MRS metabolites may have limited clinical utility as prospective biomarkers of upper-extremity outcomes in chronic stroke.
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http://dx.doi.org/10.1002/hbm.25421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193507PMC
July 2021

Myelin water fraction decrease in individuals with chronic mild traumatic brain injury and persistent symptoms.

Heliyon 2021 Apr 6;7(4):e06709. Epub 2021 Apr 6.

Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.

The diffuse and continually evolving secondary changes after mild traumatic brain injury (mTBI) make it challenging to assess alterations in brain-behaviour relationships. In this study we used myelin water imaging to evaluate changes in myelin water fraction (MWF) in individuals with chronic mTBI and persistent symptoms and measured their cognitive status using the NIH Toolbox Cognitive Battery. Fifteen adults with mTBI with persistent symptoms and twelve age, gender and education matched healthy controls took part in this study. We found a significant decrease in global white matter MWF in patients compared to the healthy controls. Significantly lower MWF was evident in most white matter region of interest (ROIs) examined including the corpus callosum (separated into genu, body and splenium), minor forceps, right anterior thalamic radiation, left inferior longitudinal fasciculus; and right and left superior longitudinal fasciculus and corticospinal tract. Although patients showed lower cognitive functioning, no significant correlations were found between MWF and cognitive measures. These results suggest that individuals with chronic mTBI who have persistent symptoms have reduced MWF.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056430PMC
April 2021

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

Neuroimage 2021 08 20;236:118046. Epub 2021 Apr 20.

University of British Columbia MRI Research Centre, 2221 Wesbrook Mall, M10 Purdy Pavilion, Vancouver, BC V6T 2B5, Canada; Radiology, University of British Columbia, 2775 Laurel Street, 11th Floor, Vancouver, BC V5Z 1M9, Canada; ICORD (International Collaboration on Repair Discoveries), 818 W. 10th Ave., Vancouver, BC V5Z 1M9, Canada. Electronic address:

Purpose: The promise of inhomogeneous magnetization transfer (ihMT) as a new myelin imaging method was studied in ex vivo human brain tissue and in relation to myelin water fraction (MWF). The temperature dependence of both methods was characterized, as well as their correspondence with a histological measure of myelin content. Unfiltered and filtered ihMT protocols were studied by adjusting the saturation scheme to preserve or attenuate signal from tissue with short dipolar relaxation time T.

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: Unfiltered ihMTR exhibited no temperature dependence, whereas filtered ihMTR increased with increasing temperature. MWF decreased at higher temperature, with an increasing prevalence of areas where the myelin water signal was unreliably determined, likely related to a reduction in T peak separability at higher temperatures ex vivo. MWF and ihMTR showed similar per-sample correlation with myelin staining at room temperature. At 37 C, filtered ihMTR was more strongly correlated with myelin staining and had increased dynamic range compared to unfiltered ihMTR.

Conclusions: Given the temperature dependence of filtered ihMT, increased dynamic range, and strong myelin specificity that persists at higher temperatures, we recommend carefully controlled temperatures close to 37 °C for filtered ihMT acquisitions. Unfiltered ihMT may also be useful, due to its independence from temperature, higher amplitude values, and sensitivity to short T components. Ex vivo myelin water imaging should be performed at room temperature, to avoid fitting issues found at higher temperatures.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118046DOI Listing
August 2021

Cervical cord myelin abnormality is associated with clinical disability in multiple sclerosis.

Mult Scler 2021 Mar 22:13524585211001780. Epub 2021 Mar 22.

Division of Neurology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada; Department of Radiology, The University of British Columbia, Vancouver, BC, Canada/Department of Physics and Astronomy, The University of British Columbia, Vancouver, BC, Canada; International Collaboration on Repair and Discoveries, Vancouver, BC, Canada.

Background: Myelin water imaging (MWI) was recently optimized to provide quantitative in vivo measurement of spinal cord myelin, which is critically involved in multiple sclerosis (MS) disability.

Objective: To assess cervical cord myelin measurements in relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis (ProgMS) participants and evaluate the correlation between myelin measures and clinical disability.

Methods: We used MWI data from 35 RRMS, 30 ProgMS, and 28 healthy control (HC) participants collected at cord level C2/C3 on a 3 T magnetic resonance imaging (MRI) scanner. Myelin heterogeneity index (MHI), a measurement of myelin variability, was calculated for whole cervical cord, global white matter, dorsal column, lateral and ventral funiculi. Correlations were assessed between MHI and Expanded Disability Status Scale (EDSS), 9-Hole Peg Test (9HPT), timed 25-foot walk, and disease duration.

Results: In various regions of the cervical cord, ProgMS MHI was higher compared to HC (between 9.5% and 31%,  ⩽ 0.04) and RRMS (between 13% and 26%,  ⩽ 0.02), and ProgMS MHI was associated with EDSS ( = 0.42-0.52) and 9HPT ( = 0.45-0.52).

Conclusion: Myelin abnormalities within clinically eloquent areas are related to clinical disability. MWI metrics have a potential role for monitoring subclinical disease progression and adjudicating treatment efficacy for new therapies targeting ProgMS.
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http://dx.doi.org/10.1177/13524585211001780DOI Listing
March 2021

Comparison of multi echo T relaxation and steady state approaches for myelin imaging in the central nervous system.

Sci Rep 2021 01 14;11(1):1369. Epub 2021 Jan 14.

Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada.

The traditional approach for measuring myelin-associated water with quantitative magnetic resonance imaging (MRI) uses multi-echo T relaxation data to calculate the myelin water fraction (MWF). A fundamentally different approach, abbreviated "mcDESPOT", uses a more efficient steady-state acquisition to generate an equivalent metric (f). Although previous studies have demonstrated inherent instability and bias in the complex mcDESPOT analysis procedure, f has often been used as a surrogate for MWF. We produced and compared multivariate atlases of MWF and f in healthy human brain and cervical spinal cord (available online) and compared their ability to detect multiple sclerosis pathology. A significant bias was found in all regions (p < 10), albeit reversed for spinal cord (f-MWF =  - 3.4%) compared to brain (+ 6.2%). MWF and f followed an approximately linear relationship for regions with MWF <  ~ 10%. For MWF >  ~ 10%, the relationship broke down and f no longer increased in tandem with MWF. For multiple sclerosis patients, MWF and f Z score maps showed overlapping areas of low Z score and similar trends between patients and brain regions, although those of f generally had greater spatial extent and magnitude of severity. These results will guide future choice of myelin-sensitive quantitative MRI and improve interpretation of studies using either myelin imaging approach.
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http://dx.doi.org/10.1038/s41598-020-80585-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809349PMC
January 2021

An atlas for human brain myelin content throughout the adult life span.

Sci Rep 2021 01 11;11(1):269. Epub 2021 Jan 11.

Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada.

Myelin water imaging is a quantitative neuroimaging technique that provides the myelin water fraction (MWF), a metric highly specific to myelin content, and the intra-/extra-cellular T (IET2), which is related to water and iron content. We coupled high-resolution data from 100 adults with gold-standard methodology to create an optimized anatomical brain template and accompanying MWF and IET2 atlases. We then used the MWF atlas to characterize how myelin content relates to demographic factors. In most brain regions, myelin content followed a quadratic pattern of increase during the third decade of life, plateau at a maximum around the fifth decade, then decrease during later decades. The ranking of mean myelin content between brain regions remained consistent across age groups. These openly available normative atlases can facilitate evaluation of myelin imaging results on an individual basis and elucidate the distribution of myelin content between brain regions and in the context of aging.
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http://dx.doi.org/10.1038/s41598-020-79540-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801525PMC
January 2021

Multi-spin echo T relaxation imaging with compressed sensing (METRICS) for rapid myelin water imaging.

Magn Reson Med 2020 09 17;84(3):1264-1279. Epub 2020 Feb 17.

Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada.

Purpose: Myelin water imaging (MWI) provides a valuable biomarker for myelin, but clinical application has been restricted by long acquisition times. Accelerating the standard multi-echo T acquisition with gradient echoes (GRASE) or by 2D multi-slice data collection results in image blurring, contrast changes, and other issues. Compressed sensing (CS) can vastly accelerate conventional MRI. In this work, we assessed the use of CS for in vivo human MWI, using a 3D multi spin-echo sequence.

Methods: We implemented multi-echo T relaxation imaging with compressed sensing (METRICS) and METRICS with partial Fourier acceleration (METRICS-PF). Scan-rescan data were acquired from 12 healthy controls for assessment of repeatability. MWI data were acquired for METRICS in 9 m:58 s and for METRICS-PF in 7 m:25 s, both with 1.5 × 2 × 3 mm voxels, 56 echoes, 7 ms ΔTE, and 240 × 240 × 170 mm FOV. METRICS was compared with a novel multi-echo spin-echo gold-standard (MSE-GS) MWI acquisition, acquired for a single additional subject in 2 h:2 m:40 s.

Results: METRICS/METRICS-PF myelin water fraction had mean: repeatability coefficient 1.5/1.1, coefficient of variation 6.2/4.5%, and intra-class correlation coefficient 0.79/0.84. Repeatability metrics comparing METRICS with METRICS-PF were similar, and both sequences agreed with reference values from literature. METRICS images and quantitative maps showed excellent qualitative agreement with those of MSE-GS.

Conclusion: METRICS and METRICS-PF provided highly repeatable MWI data without the inherent disadvantages of GRASE or 2D multi-slice acquisition. CS acceleration allows MWI data to be acquired rapidly with larger FOV, higher estimated SNR, more isotropic voxels and more echoes than with previous techniques. The approach introduced here generalizes to any multi-component T mapping application.
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http://dx.doi.org/10.1002/mrm.28199DOI Listing
September 2020

Brain Myelin Water Fraction and Diffusion Tensor Imaging Atlases for 9-10 Year-Old Children.

J Neuroimaging 2020 03 16;30(2):150-160. Epub 2020 Feb 16.

Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada.

Background And Purpose: Myelin water imaging (MWI) and diffusion tensor imaging (DTI) provide information about myelin and axon-related brain microstructure, which can be useful for investigating normal brain development and many childhood brain disorders. While pediatric DTI atlases exist, there are no pediatric MWI atlases available for the 9-10 years old age group. As myelination and structural development occurs throughout childhood and adolescence, studies of pediatric brain pathologies must use age-specific MWI and DTI healthy control data. We created atlases of myelin water fraction (MWF) and DTI metrics for healthy children aged 9-10 years for use as normative data in pediatric neuroimaging studies.

Methods: 3D-T , DTI, and MWI scans were acquired from 20 healthy children (mean age: 9.6 years, range: 9.2-10.3 years, 4 females). ANTs and FSL registration were used to create quantitative MWF and DTI atlases. Region of interest (ROI) analysis in nine white matter regions was used to compare pediatric MWF with adult MWF values from a recent study and to investigate the correlation between pediatric MWF and DTI metrics.

Results: Adults had significantly higher MWF than the pediatric cohort in seven of the nine white matter ROIs, but not in the genu of the corpus callosum or the cingulum. In the pediatric data, MWF correlated significantly with mean diffusivity, but not with axial diffusivity, radial diffusivity, or fractional anisotropy.

Conclusions: Normative MWF and DTI metrics from a group of 9-10 year old healthy children provide a resource for comparison to pathologies. The age-specific atlases are ready for use in pediatric neuroimaging research and can be accessed: https://sourceforge.net/projects/pediatric-mri-myelin-diffusion/.
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http://dx.doi.org/10.1111/jon.12689DOI Listing
March 2020

Myelin water imaging data analysis in less than one minute.

Neuroimage 2020 04 21;210:116551. Epub 2020 Jan 21.

Physics & Astronomy, University of British Columbia, Canada; International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Canada; Radiology, University of British Columbia, Canada; Pathology & Laboratory Medicine, University of British Columbia, Canada. Electronic address:

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 R>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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http://dx.doi.org/10.1016/j.neuroimage.2020.116551DOI Listing
April 2020

Magnetic resonance spectroscopy evidence for declining gliosis in MS patients treated with ocrelizumab versus interferon beta-1a.

Mult Scler J Exp Transl Clin 2019 Oct-Dec;5(4):2055217319879952. Epub 2019 Oct 15.

Department of Medicine, University of British Columbia.

Background: Magnetic resonance spectroscopy quantitatively monitors biomarkers of neuron-myelin coupling (N-acetylaspartate (NAA)), and inflammation (total creatine (tCr), total choline (tCho), myo-inositol (mI)) in the brain.

Objective: This study aims to investigate how ocrelizumab and interferon beta-1a differentially affects imaging biomarkers of neuronal-myelin coupling and inflammation in patients with relapsing multiple sclerosis (MS).

Methods: Forty patients with relapsing MS randomized to either treatment were scanned at 3T at baseline and weeks 24, 48, and 96 follow-up. Twenty-four healthy controls were scanned at weeks 0, 48, and 96. NAA, tCr, tCho, mI, and NAA/tCr were measured in a single large supra-ventricular voxel.

Results: There was a time × treatment interaction in NAA/tCr ( = 0.04), primarily driven by opposing tCr trends between treatment groups after 48 weeks of treatment. Patients treated with ocrelizumab showed a possible decline in mI after week 48 week, and stable tCr and tCho levels. Conversely, the interferon beta-1a treated group showed possible increases in mI, tCr, and tCho over 96 weeks.

Conclusions: Results from this exploratory study suggest that over 2 years, ocrelizumab reduces gliosis compared with interferon beta-1a, demonstrated by declining ml, and stable tCr and tCho. Ocrelizumab may improve the physiologic milieu by decreasing neurotoxic factors that are generated by inflammatory processes.
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http://dx.doi.org/10.1177/2055217319879952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796216PMC
October 2019

Myelin Water Atlas: A Template for Myelin Distribution in the Brain.

J Neuroimaging 2019 11 25;29(6):699-706. Epub 2019 Jul 25.

Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, Canada.

Background And Purpose: Myelin water imaging (MWI) is a magnetic resonance imaging technique that quantifies myelin in-vivo. Although MWI has been extensively applied to study myelin-related diseases in groups, clinical use in individual patients is challenging mainly due to population heterogeneity. The purpose of this study was twofold: (1) create a normative brain myelin water atlas depicting the population mean and regional variability of myelin content; and (2) apply the myelin atlas to assess the degree of demyelination in individuals with multiple sclerosis (MS).

Methods: 3T MWI was performed on 50 healthy adults (25 M/25 F, mean age 25 years [range 17-42 years]). The myelin water atlas was created by averaging coregistered myelin water fraction (MWF) maps from all healthy individuals. To illustrate the preliminary utility of the atlas, white matter (WM) regional MWF variations were evaluated and voxel-wise z-score maps (z < -1.96) from the MWI of three MS participants were produced to assess individually the degree of demyelination.

Results: The myelin water atlas demonstrated significant MWF variation across control WM. No significant MWF differences were found between male and female healthy participants. MS z-score maps revealed diffuse regions of demyelination in the two participants with Expanded Disability Status Scale (EDSS) = 2.0 but not in the participant with EDSS = 0.

Conclusions: The myelin water atlas can be used as a reference (URL: https://sourceforge.net/projects/myelin-water-atlas/) to demonstrate areas of demyelination in individual MS participants. Future studies will expand the atlas age range, account for education, and other variables that may affect myelination.
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http://dx.doi.org/10.1111/jon.12657DOI Listing
November 2019

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

Neuroimage Clin 2019 17;23:101896. Epub 2019 Jun 17.

Physics and Astronomy, University of British Columbia, 6224 Agricultural Road, Vancouver, BC V6T 1Z1, Canada; Radiology, University of British Columbia, 2775 Laurel Street, Vancouver, BC V5Z 1M9, Canada; International Collaboration on Repair Discoveries, University of British Columbia, 818 West 10th Avenue, Vancouver, BC V5Z 1M9, Canada; Medicine (Neurology), University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.

Background: Rapid myelin water imaging (MWI) using a combined gradient and spin echo (GRASE) sequence can produce myelin specific metrics for the human brain. Spinal cord MWI could be similarly useful, but technical challenges have hindered routine application. GRASE rapid MWI was recently successfully implemented for imaging of healthy cervical spinal cord and may complement other advanced imaging methods, such as diffusion tensor imaging (DTI) and quantitative T (qT).

Objective: To demonstrate the feasibility of cervical cord GRASE rapid MWI in multiple sclerosis (MS), primary lateral sclerosis (PLS) and neuromyelitis optica spectrum disorder (NMO), with comparison to DTI and qT metrics.

Methods: GRASE MWI, DTI and qT 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: PLS subjects had low myelin water fraction (MWF) in the lateral funiculi compared to HC. RRMS subject MWF was heterogeneous within the cord. The PPMS subject showed no trends in ROI results but had a region of low MWF Z score corresponding to a focal lesion. The NMO subject with a longitudinally extensive transverse myelitis lesion had low values for whole cord mean MWF of 12.8% compared to 24.3% (standard deviation 2.2%) for HC. The NMO subject without lesions also had low MWF compared to HC. DTI and qT metrics showed similar trends, corroborating the MWF results and providing complementary information.

Conclusion: GRASE is sufficiently sensitive to detect decreased myelin within MS spinal cord plaques, NMO lesions, and PLS diffuse spinal cord injury. Decreased MWF in PLS is consistent with demyelination secondary to motor neuron degeneration. GRASE MWI is a feasible method for rapid assessment of myelin content in the cervical spinal cord and provides complementary information to that of DTI and qT measures.
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http://dx.doi.org/10.1016/j.nicl.2019.101896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611998PMC
June 2020

Intra- and inter-site reproducibility of human brain single-voxel proton MRS at 3 T.

NMR Biomed 2019 06 19;32(6):e4083. Epub 2019 Mar 19.

Physics & Astronomy, University of British Columbia, Vancouver, British Columbia, Canada.

Introduction: Clinical trials that involve participants from multiple sites necessitate standardized and reliable quantitative MRI outcomes to detect significant group differences over time. Metabolite concentrations measured by proton MRS ( H-MRS) provide valuable information about in vivo metabolism of the central nervous system, but can vary based on the acquisition and quantitation methods used by different MR sites. Therefore, we investigated the intra- and inter-site reproducibility of metabolite concentrations measured by H-MRS on MRI scanners from a single manufacturer across six sites.

Methods: Five healthy controls were scanned twice within 24 h at six participating 3 T MR sites with large single-voxel PRESS (TE/TR/NSA = 36 ms/4000 ms/56) and anatomical images for voxel positioning and correction of partial volume relaxation. Absolute metabolite concentrations were calculated relative to the T and T relaxation corrected signal from water. Intra- and inter-site reproducibility was assessed using Bland-Altman plots and intra- and inter-site coefficient of variation (CoV) as well as intra- and inter-site intra-class correlation coefficient.

Results: The median intra-site CoVs for the five major metabolite concentrations ([NAA], [tCr], [Glu], [tCho] and [Ins]) were between 2.5 and 5.3%. Inter-site CoVs were also low, with the median CoVs for all metabolites between 3.7 and 6.4%. Metabolite concentrations were robust to small inconsistencies in voxel placement and site was not the driving factor in the variance of the measurement of any metabolite concentration. Between-subject differences accounted for the majority of the concentration variability for creatine, choline and myo-inositol (42-65% of the variance).

Conclusion: A large single-voxel H-MRS acquisition from a single manufacturer's MRI scanner is highly reproducible and reliable for multi-site clinical trials.
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http://dx.doi.org/10.1002/nbm.4083DOI Listing
June 2019

Longitudinal advanced MRI case report of white matter radiation necrosis.

Ann Clin Transl Neurol 2019 02 10;6(2):379-385. Epub 2018 Dec 10.

Department of Medicine Division of Neurology University of British Columbia Vancouver British Columbia Canada.

Radiation necrosis mostly occurs in and near the radiation field. We used magnetic resonance imaging to study radiation-induced necrosis of atypical onset, severity, and extent following stereotactic radiosurgery for a symptomatic arteriovenous malformation. Susceptibility-sensitive imaging, T-relaxation, myelin water imaging, and magnetic resonance spectroscopy were acquired three times up to 52 months postradiosurgery. Increasing water content outside the radiation field, contralateral neuronal loss, and gliosis were detected over time. Our findings suggest that radiation-induced vasculopathic changes spread more diffusely than previously described. An autoimmune response to brain antigens could underlie white matter changes outside the initial radiation field.
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http://dx.doi.org/10.1002/acn3.704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389755PMC
February 2019

Advanced imaging findings in progressive solitary sclerosis: a single lesion or a global disease?

Mult Scler J Exp Transl Clin 2019 Jan-Mar;5(1):2055217318824612. Epub 2019 Jan 16.

Department of Medicine (Neurology), University of British Columbia, CanadaThe first two and final two authors contributed equally to the manuscript.

Background: Progressive solitary sclerosis is a unifocal demyelinating disease recently proposed as a possible multiple sclerosis variant.

Objective: To compare myelin content and brain metabolite ratio qualitatively in the normal-appearing white matter of progressive solitary sclerosis cases compared to multiple sclerosis and healthy control participants.

Methods: Case report.

Results: Progressive solitary sclerosis cases showed abnormal myelin in normal-appearing white matter tracts and global normal-appearing white matter as well as lower N-acetyl-aspartate to total creatine ratio compared to multiple sclerosis and healthy control groups.

Conclusion: Despite a single demyelinating lesion along the corticospinal tract in progressive solitary sclerosis, we showed evidence of more extensive abnormality within the normal-appearing white matter.
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http://dx.doi.org/10.1177/2055217318824612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350151PMC
January 2019

Inter-Vendor Reproducibility of Myelin Water Imaging Using a 3D Gradient and Spin Echo Sequence.

Front Neurosci 2018 21;12:854. Epub 2018 Nov 21.

Department of Medicine, The University of British Columbia, Vancouver, BC, Canada.

Myelin water imaging can be achieved using multicomponent T relaxation analysis to quantify measurement of myelin content, termed the myelin water fraction (MWF). Therefore, myelin water imaging can be a valuable tool to better understand the underlying white matter pathology in demyelinating diseases, such as multiple sclerosis. To apply myelin water imaging in multisite studies and clinical applications, it must be acquired in a clinically feasible scan time (less than 15 min) and be reproducible across sites and scanner vendors. Here, we assessed the reproducibility of MWF measurements in regional and global white matter in 10 healthy human brains across two sites with two different 3 T magnetic resonance imaging scanner vendors (Philips and Siemens), using a 32-echo gradient and spin echo (GRASE) sequence. A strong correlation was found between the MWF measurements in the global white matter (Pearson's = 0.91; < 0.001) for all participants across the two sites. The mean intersite MWF coefficient of variation across participants was 2.77% in the global white matter and ranged from 4.47% (splenium of the corpus callosum) to 17.89% (genu of the corpus callosum) in white matter regions of interest. Bland-Altman analysis showed a good agreement in MWF measurements between the two sites with small bias of 0.002. Overall, MWF estimates were in good agreement across the two sites and scanner vendors. Our findings support the use of quantitative multi-echo T relaxation metrics, such as the MWF, in multicenter studies and clinical trials to gain deeper understanding about the pathological processes resulting from the underlying disease progression in neurodegenerative diseases.
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http://dx.doi.org/10.3389/fnins.2018.00854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258882PMC
November 2018

Diffusely Abnormal White Matter, T Burden of Disease, and Brain Volume in Relapsing-Remitting Multiple Sclerosis.

J Neuroimaging 2019 01 30;29(1):151-159. Epub 2018 Oct 30.

Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada.

Background And Purpose: Multiple sclerosis (MS) diffusely abnormal white matter (DAWM) is a mildly hyperintense magnetic resonance imaging abnormality distinct from typical lesions. Our goal was to investigate the prevalence and natural history of DAWM in a large cohort (n = 348) of relapsing-remitting MS (RRMS) patients.

Methods: The presence of DAWM and relationship to changes in T burden of disease (BOD), brain volume (brain fractional ratio, BFR), and disability (Expanded Disability Status Scale, EDSS) were investigated at baseline and year 7-8 (long-term follow-up, LTF).

Results: DAWM was present in 25.3% (88 of 348) of patients at baseline. At LTF, DAWM was unchanged in 69.3% (61 of 88), decreased in 28.4% (25 of 88), and increased in 2.3% (2 of 88) of patients. Baseline BOD and change in BOD did not significantly differ between patients with and without DAWM. DAWM was associated with greater reduction in BFR at LTF (P = .038). DAWM and DAWM change did not predict EDSS or EDSS progression.

Conclusions: DAWM is present in a quarter of RRMS patients, and rarely increases or develops de novo. DAWM predicts brain atrophy but does not predict physical disability. Because of its posterior periventricular location, further investigation is warranted to evaluate its relationship to other measures of disability, including visual spatial processing and cognitive function.
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http://dx.doi.org/10.1111/jon.12574DOI Listing
January 2019

Multicenter Measurements of T Relaxation and Diffusion Tensor Imaging: Intra and Intersite Reproducibility.

J Neuroimaging 2019 01 19;29(1):42-51. Epub 2018 Sep 19.

Department of Radiology, University of British Columbia, UBC MRI Research Centre, Vancouver, British Columbia, Canada.

Background And Purpose: Quantitative T and diffusion tensor imaging (DTI) may provide information about pathological changes underlying disability and progression in diseases like multiple sclerosis (MS). Imaging the corpus callosum (CC), a primary site of damage in MS with a critical role in interhemispheric connectivity, may be useful for assessing overall brain health, prognosis, and therapy efficacy. We assessed the feasibility of multisite clinical trials using advanced MRI by examining the intra and intersite reproducibility of T and DTI measurements in the CC and segmented white matter (WM).

Methods: Five healthy volunteers were scanned twice within 24 hours at six 3T sites. Coefficients of variation (COVs) and intraclass correlation coefficients (ICCs) for CC and WM T , fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (D ), and radial diffusivity (D ) assessed intrasite and intersite reliability.

Results: CC and WM T showed excellent intrasite reproducibility with low COVs (mean = .90% and .89%, respectively) and good ICCs (CC = .78, WM = .90). T also demonstrated intersite reliability (low COVs: CC = 2.4%, WM = 1.8%; moderate ICCs: CC = .43, WM = .69). DTI had low intrasite COVs (CC: FA = 1.3%, MD = 1.5%, D = 1.4%, D = 2.2%; WM: FA = .9%, MD = .9%, D = .7%, D = 1.2%) and high intrasite ICCs (CC: FA = .95, MD = .97, D = .94, D = .97; CC: FA = .9, MD = .66, D = .88, D = .63), indicating excellent intrasite reproducibility. DTI also showed excellent intersite reliability with low COVs (CC: FA = 2.1%, MD = 4.1%, D = 3.4%, D = 5.3%, WM: FA = 1.3%, MD = 1.9%, D = 1.8%, D = 2.1%,) and good ICCs (CC: FA = .90, MD = .84, D = .72, D = .90; WM: FA = .83, MD = .34, D = .62, D = .41).

Conclusions: T and DTI measures are reproducible using equivalent MRI scanners and sequence protocols. Using a similar MR system, it is feasible to carry out multicenter studies using T and DTI to evaluate changes within the CC and WM.
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http://dx.doi.org/10.1111/jon.12559DOI Listing
January 2019

A 24-month advanced magnetic resonance imaging study of multiple sclerosis patients treated with alemtuzumab.

Mult Scler 2019 05 17;25(6):811-818. Epub 2018 Apr 17.

Division of Neurology, Department of Medicine, The University of British Columbia, Vancouver, BC, Canada.

Background: Tissue damage in both multiple sclerosis (MS) lesions and normal-appearing white matter (NAWM) are important contributors to disability and progression. Specific aspects of MS pathology can be measured using advanced imaging. Alemtuzumab is a humanised monoclonal antibody targeting CD52 developed for MS treatment.

Objective: To investigate changes over 2 years of advanced magnetic resonance (MR) metrics in lesions and NAWM of MS patients treated with alemtuzumab.

Methods: A total of 42 relapsing-remitting alemtuzumab-treated MS subjects were scanned for 2 years at 3 T. T relaxation, T relaxation, diffusion tensor, MR spectroscopy and volumetric sequences were performed. Mean T and myelin water fraction (MWF) were determined for stable lesions, new lesions and NAWM. Fractional anisotropy was calculated for the corpus callosum (CC) and N-acetylaspartate (NAA) concentration was determined from a large NAWM voxel. Brain parenchymal fraction (BPF), cortical thickness and CC area were also calculated.

Results: No change in any MR measurement was found in lesions or NAWM over 24 months. BPF, cortical thickness and CC area all showed decreases in the first year followed by stability in the second year.

Conclusion: Advanced MR biomarkers of myelin (MWF) and neuron/axons (NAA) show no change in NAWM over 24 months in alemtuzumab-treated MS participants.
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http://dx.doi.org/10.1177/1352458518770085DOI Listing
May 2019

Hematopoietic Stem Cell Transplantation in Late-Onset Krabbe Disease: No Evidence of Worsening Demyelination and Axonal Loss 4 Years Post-allograft.

J Neuroimaging 2018 05 26;28(3):252-255. Epub 2018 Feb 26.

Department of Medicine (Endocrinology), University of British Columbia, Vancouver, Canada.

Background And Purpose: Late-onset adult Krabbe disease is a very rare demyelinating leukodystrophy, affecting less than 1 in a million people. Hematopoietic stem cell transplantation (HSCT) strategies can stop the accumulation of toxic metabolites that damage myelin-producing cells. We used quantitative advanced imaging metrics to longitudinally assess the impact of HSCT on brain abnormalities in adult-onset Krabbe disease.

Methods: A 42-year-old female with late-onset Krabbe disease and an age/sex-matched healthy control underwent annual 3T MRI (baseline was immediately prior to HSCT for the Krabbe subject). Imaging included conventional scans, myelin water imaging, diffusion tensor imaging, and magnetic resonance spectroscopy.

Results: Brain abnormalities far beyond those visible on conventional imaging were detected, suggesting a global pathological process occurs in Krabbe disease with adult-onset etiology, with myelin being more affected than axons, and evidence of wide-spread gliosis. After HSCT, our patient showed clinical stability in all measures, as well as improvement in gait, dysarthria, and pseudobulbar affect at 7.5 years post-transplant. No MRI evidence of worsening demyelination and axonal loss was observed up to 4 years post-allograft.

Conclusions: Clinical evidence and stability of advanced MR measures related to myelin and axons supports HSCT as an effective treatment strategy for stopping progression associated with late-onset Krabbe disease.
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http://dx.doi.org/10.1111/jon.12502DOI Listing
May 2018

Characterization of brain tumours with spin-spin relaxation: pilot case study reveals unique T distribution profiles of glioblastoma, oligodendroglioma and meningioma.

J Neurol 2017 Nov 11;264(11):2205-2214. Epub 2017 Sep 11.

Radiology, University of British Columbia, Vancouver, Canada.

Prolonged spin-spin relaxation times in tumour tissue have been observed since some of the earliest nuclear magnetic resonance investigations of the brain. Over the last three decades, numerous studies have sought to characterize tumour morphology and malignancy using quantitative assessment of T relaxation times, although attempts to categorize and differentiate tumours have had limited success. However, previous work must be interpreted with caution as relaxation data were typically acquired using a variety of multiple echo sequences with a range of echoes and T decay curves and were frequently fit with monoexponential analysis. We defined the distribution of T components in three different human brain tumours (glioblastoma, oligodendroglioma, meningioma) using a multi-echo sequence with a greater number of echoes and a longer acquisition window than previously used (48 echoes, data collection out to 1120 ms) with no a priori assumptions about the number of exponential components contributing to the T decay. T relaxation times were increased in tumour tissue and each tumour showed a distinct T distribution profile. Tumours have complex and unique compartmentalization characteristics. Quantitative assessment of T relaxation in brain cancer may be useful in evaluating different grades of brain tumours on the basis of their T distribution profile, and has the potential to be a non-invasive diagnostic tool which may also be useful in monitoring therapy. Further study with a larger sample size and varying grades of tumours is warranted.
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http://dx.doi.org/10.1007/s00415-017-8609-6DOI Listing
November 2017

Global loss of myelin water over 5 years in multiple sclerosis normal-appearing white matter.

Mult Scler 2018 10 7;24(12):1557-1568. Epub 2017 Aug 7.

Department of Radiology, The University of British Columbia, Vancouver, BC, Canada/Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada/International Collaboration on Repair Discoveries (ICORD), The University of British Columbia, Vancouver, BC, Canada.

Background: Reduced myelin water fraction (MWF, a marker for myelin), increased geometric mean T (ieGMT, reflecting intra/extracellular water properties), and increased T (related to total water content) have been observed in cross-sectional studies of multiple sclerosis (MS) normal-appearing white matter (NAWM).

Objective: To assess longitudinal changes of magnetic resonance (MR) measures in relapsing-remitting MS (RRMS) brain NAWM.

Methods: A total of 11 subjects with RRMS and 4 controls were scanned on a 3T MRI at baseline and long-term follow-up (LTFU; 3.2-5.8 years) with a 32-echo T relaxation and an inversion recovery T sequence. For every voxel, MWF, ieGMT, and T were obtained. Mean, peak height, and peak location from NAWM mask-based histograms were determined.

Results: In MS subjects, NAWM MWF mean decreased by 8% ( p = 0.0016). No longitudinal changes were measured in T or ieGMT. There was no relationship between change in any MR metric and change in EDSS. Control white matter showed no differences over time in any metric.

Conclusion: The decreases we observed in MWF suggest that changes in myelin integrity and loss of myelin may be occurring diffusely and over long time periods in the MS brain. The timescale of these changes indicates that chronic, progressive myelin damage is an evolving process occurring over many years.
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http://dx.doi.org/10.1177/1352458517723717DOI Listing
October 2018

Quantifying visual pathway axonal and myelin loss in multiple sclerosis and neuromyelitis optica.

Neuroimage Clin 2016 26;11:743-750. Epub 2016 May 26.

Department of Medicine, University of British Columbia, Vancouver, Canada. Electronic address:

Background: The optic nerve is frequently injured in multiple sclerosis and neuromyelitis optica, resulting in visual dysfunction, which may be reflected by measures distant from the site of injury.

Objective: To determine how retinal nerve fiber layer as a measure of axonal health, and macular volume as a measure of neuronal health are related to changes in myelin water fraction in the optic radiations of multiple sclerosis and neuromyelitis optica participants with and without optic neuritis and compared to healthy controls.

Methods: 12 healthy controls, 42 multiple sclerosis (16 with optic neuritis), and 10 neuromyelitis optica participants (8 with optic neuritis) were included in this study. Optical coherence tomography assessment involved measurements of the segmented macular layers (total macular, ganglion cell layer, inner plexiform layer, and inner nuclear layer volume) and paripapillary retinal nerve fiber layer thickness. The MRI protocol included a 32-echo T2-relaxation GRASE sequence. Average myelin water fraction values were calculated within the optic radiations as a measure of myelin density.

Results: Multiple sclerosis and neuromyelitis optica eyes with optic neuritis history had lower retinal nerve fiber layer thickness, total macular, ganglion cell and inner plexiform layer volumes compared to eyes without optic neuritis history and controls. Inner nuclear layer volume increased in multiple sclerosis with optic neuritis history (mean = 0.99 mm(3), SD = 0.06) compared to those without (mean = 0.97 mm(3), SD = 0.06; p = 0.003). Mean myelin water fraction in the optic radiations was significantly lower in demyelinating diseases (neuromyelitis optica: mean = 0.098, SD = 0.01, multiple sclerosis with optic neuritis history: mean = 0.096, SD = 0.01, multiple sclerosis without optic neuritis history: mean = 0.098, SD = 0.02; F3,55 = 3.35, p = 0.03) compared to controls. Positive correlations between MRI and optical coherence tomography measures were also apparent (retinal nerve fiber layer thickness and ganglion cell layer thickness: r = 0.25, p = 0.05, total macular volume and inner plexiform layer volume: r = 0.27, p = 0.04).

Conclusions: The relationship between reductions in OCT measures of neuro-axonal health in the anterior visual pathway and MRI-based measures of myelin health in the posterior visual pathway suggests that these measures may be linked through bidirectional axonal degeneration.
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http://dx.doi.org/10.1016/j.nicl.2016.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908282PMC
October 2017

Motor Skill Acquisition Promotes Human Brain Myelin Plasticity.

Neural Plast 2016 16;2016:7526135. Epub 2016 May 16.

Department of Physical Therapy, University of British Columbia, Vancouver, BC, Canada V6T 1Z3; Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.

Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI), the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements) using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus). In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults.
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http://dx.doi.org/10.1155/2016/7526135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884808PMC
September 2017

Does hydration status affect MRI measures of brain volume or water content?

J Magn Reson Imaging 2016 08 29;44(2):296-304. Epub 2016 Jan 29.

Medicine, University of British Columbia, Vancouver, BC, Canada.

Purpose: To determine whether differences in hydration state, which could arise from routine clinical procedures such as overnight fasting, affect brain total water content (TWC) and brain volume measured with magnetic resonance imaging (MRI).

Materials And Methods: Twenty healthy volunteers were scanned with a 3T MR scanner four times: day 1, baseline scan; day 2, hydrated scan after consuming 3L of water over 12 hours; day 3, dehydrated scan after overnight fasting of 9 hours, followed by another scan 1 hour later for reproducibility. The following MRI data were collected: T2 relaxation (for TWC measurement), inversion recovery (for T1 measurement), and 3D T1 -weighted (for brain volumes). Body weight and urine specific gravity were also measured. TWC was calculated by fitting the T2 relaxation data with a nonnegative least-squares algorithm, with corrections for T1 relaxation and image signal inhomogeneity and normalization to ventricular cerebrospinal fluid. Brain volume changes were measured using SIENA. TWC means were calculated within 14 tissue regions.

Results: Despite indications of dehydration as demonstrated by increases in urine specific gravity (P = 0.03) and decreases in body weight (P = 0.001) between hydrated and dehydrated scans, there was no measurable change in TWC (within any brain region) or brain volume between hydration states.

Conclusion: We demonstrate that within a range of physiologic conditions commonly encountered in routine clinical scans (no pretreatment with hydration, well hydrated before MRI, and overnight fasting), brain TWC and brain volumes are not substantially affected in a healthy control cohort. J. Magn. Reson. Imaging 2016;44:296-304.
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http://dx.doi.org/10.1002/jmri.25168DOI Listing
August 2016

Increased spinal cord movements in cervical spondylotic myelopathy.

Spine J 2014 Oct 23;14(10):2344-54. Epub 2014 Jan 23.

Spinal Cord Injury Center, Forchstrasse 340, University of Zurich, CH-8008 Zurich, Switzerland; International Collaboration on Repair Discoveries (ICORD), 818 West 10th Ave, University of British Columbia, Vancouver, BC, Canada, V5Z 1M9.

Background Context: Magnetic resonance imaging (MRI) is a very useful diagnostic test for cervical spondylotic myelopathy (CSM) because it can identify degenerative changes within the spinal cord (SC), disclose the extent, localization, and the kind of SC compression, and help rule out other SC disorders. However, the relationships between changes in cerebrospinal fluid (CSF) flow, cord motion, the extent and severity of spinal canal stenosis, and the development of CSM symptoms are not well understood.

Purpose: To evaluate if changes in the velocity of CSF and SC movements provide additional insight into the pathophysiological mechanisms underlying CSM beyond MRI observations of cord compression.

Study Design: Prospective radiologic study of recruited patients.

Patient Sample: Thirteen CSM subjects and 15 age and gender matched controls.

Outcome Measures: Magnetic resonance imaging measures included CSF and SC movement. Cervical cord condition was assessed by the Japanese Orthopaedic Association (JOA) score, compression ratio (CR), and somatosensory evoked potentials (SSEPs) of the tibial and ulnar nerves.

Methods: Phase-contrast imaging at the level of stenosis for patients and at C5 for controls and T2-weighted images were compared with clinical findings.

Results: Cerebrospinal fluid velocity was significantly reduced in CSM subjects as compared with controls and was related to cord CR. Changes in CSF velocity and cord compression were not correlated with clinical measures (JOA scores, SSEP) or the presence of T2 hyperintensities. Spinal cord movements, that is, cord displacement and velocity in the craniocaudal axis, were increased in CSM patients. Increased SC movements (ie, total cord displacement) both in the controls and CSM subjects were associated with altered spinal conduction as assessed by SSEP.

Conclusions: This study revealed rather unexpected increased cord movements in the craniocaudal axis in CSM patients that may contribute to myelopathic deteriorations in combination with spinal canal compression. Understanding the relevance of cord movements with respect to supporting the clinical CSM diagnosis or disease monitoring requires further long-term follow-up studies.
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http://dx.doi.org/10.1016/j.spinee.2014.01.036DOI Listing
October 2014
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