Статті в журналах: "Myelin Content"

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Kim, Joo-won, Thomas P. Naidich, Benjamin A. Ely, Essa Yacoub, Federico De Martino, Mary E. Fowkes, Wayne K. Goodman, and Junqian Xu. "Human habenula segmentation using myelin content." NeuroImage 130 (April 2016): 145–56. http://dx.doi.org/10.1016/j.neuroimage.2016.01.048.

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Weickenmeier, J., R. de Rooij, S. Budday, P. Steinmann, T. C. Ovaert, and E. Kuhl. "Brain stiffness increases with myelin content." Acta Biomaterialia 42 (September 2016): 265–72. http://dx.doi.org/10.1016/j.actbio.2016.07.040.

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Bouhrara, Mustapha, Joseph S. R. Alisch, Nikkita Khattar, Richard W. Kim, Abinand C. Rejimon, Luis E. Cortina, Wenshu Qian, Luigi Ferrucci, Susan M. Resnick, and Richard G. Spencer. "Association of cerebral blood flow with myelin content in cognitively unimpaired adults." BMJ Neurology Open 2, no. 1 (July 2020): e000053. http://dx.doi.org/10.1136/bmjno-2020-000053.

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BackgroundMyelin loss and cerebral blood flow (CBF) decline are central features of several neurodegenerative diseases. Myelin maintenance through oligodendrocyte metabolism is an energy-demanding process, so that myelin homeostasis is particularly sensitive to hypoxia, hypoperfusion or ischaemia. However, in spite of its central importance, little is known about the association between blood supply and myelin integrity.ObjectiveTo assess associations between cortical and subcortical CBF, and subcortical myelin content, in critical brain white matter regions.Materials and methodsMRI was performed on a cohort of 67 cognitively unimpaired adults. Using advanced MRI methodology, we measured whole-brain longitudinal and transverse relaxation rates (R1 and R2), sensitive but non-specific markers of myelin content, and myelin water fraction (MWF), a direct surrogate of myelin content, as well as regional CBF, from each of these participants.ResultsAll quantitative relaxometry metrics were positively associated with CBF in all brain regions evaluated. These associations between MWF or R1 and CBF, and, to a lesser extent, between R2 and CBF, were statistically significant in most brain regions examined, indicating that lower regional cortical or subcortical CBF corresponds to a decrease in local subcortical myelin content. Finally, all relaxometry metrics exhibited a quadratic, inverted U-shaped, association with age; this is attributed to the development of myelination from young to middle age, followed by progressive loss of myelin in later years.ConclusionsIn this first study examining the association between local blood supply and myelin integrity, we found that myelin content declines with CBF across a wide age range of cognitively normal subjects.

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Laporte, John P., Mary E. Faulkner, Zhaoyuan Gong, Mohammad A. B. S. Akhonda, Luigi Ferrucci, Josephine M. Egan, and Mustapha Bouhrara. "Hypertensive Adults Exhibit Lower Myelin Content: A Multicomponent Relaxometry and Diffusion Magnetic Resonance Imaging Study." Hypertension 80, no. 8 (August 2023): 1728–38. http://dx.doi.org/10.1161/hypertensionaha.123.21012.

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BACKGROUND: It is unknown whether hypertension plays any role in cerebral myelination. To fill this knowledge gap, we studied 90 cognitively unimpaired adults, age range 40 to 94 years, who are participants in the Baltimore Longitudinal Study of Aging and the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing to look for potential associations between hypertension and cerebral myelin content across 14 white matter brain regions. METHODS: Myelin content was probed using our advanced multicomponent magnetic resonance relaxometry method of myelin water fraction, a direct and specific magnetic resonance imaging measure of myelin content, and longitudinal and transverse relaxation rates ( R 1 and R 2 ), 2 highly sensitive magnetic resonance imaging metrics of myelin content. We also applied diffusion tensor imaging magnetic resonance imaging to measure fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity values, which are metrics of cerebral microstructural tissue integrity, to provide context with previous magnetic resonance imaging findings. RESULTS: After adjustment of age, sex, systolic blood pressure, smoking status, diabetes status, and cholesterol level, our results indicated that participants with hypertension exhibited lower myelin water fraction, fractional anisotropy, R 1 and R 2 values and higher mean diffusivity, radial diffusivity, and axial diffusivity values, indicating lower myelin content and higher impairment to the brain microstructure. These associations were significant across several white matter regions, particularly in the corpus callosum, fronto-occipital fasciculus, temporal lobes, internal capsules, and corona radiata. CONCLUSIONS: These original findings suggest a direct association between myelin content and hypertension and form the basis for further investigations including longitudinal assessments of this relationship.

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Kozko, Volodymyr, Maryna Hvozdetska-Shaar, Anton Sokhan, Kateryna Yurko, and Ganna Solomennyk. "Myelin basic protein and its diagnostic value in HIV-infected individuals with 4th clinical stage and neuroinfections." ScienceRise: Medical Science, no. 2(41) (April 5, 2021): 28–32. http://dx.doi.org/10.15587/2519-4798.2021.228189.

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It was shown that in HIV-infected patients, pathomorphological changes in the white matter in the form of demyelinization are already observed in the early stages of the disease. The most studied marker of this process is myelin basic protein that can be detected in cerebrospinal fluid or serum immediately after acute myelin breakdown. The aim. To assess the diagnostic value of myelin basic protein content in serum and cerebrospinal fluid of HIV-infected individuals with 4th clinical stage and central nervous system opportunistic infections. Materials and methods. Using ELISA with diagnostic kit “MBP ELISA” (Ansh Labs, USA), we studied the myelin basic protein content in serum and cerebrospinal fluid of 53 HIV-infected patients with 4th clinical stage and central nervous system opportunistic infections depending on its etiology, the outcome of the diseases and according to Glasgow coma scale score. As well correlation analysis with some laboratory and clinical indicators was performed. Results. We found significantly increased myelin basic protein content in both cerebrospinal fluid and serum of HIV-infected patients 4th clinical stage with central nervous system opportunistic infections compared to control (p˂0.01), which indicate the presence of active demyelinization in central nervous system. The highest cerebrospinal fluid myelin basic protein was registered in patients with an unfavourable outcome of the disease, as death or residual neurologic deficit, and patients with cerebral toxoplasmosis. The cerebrospinal fluid myelin basic protein had an association with the size of white matter lesions on magnetic resonance imaging and serum myelin basic protein content. Conclusions. Myelin basic protein detection in cerebrospinal fluid as well as in serum can serve as an additional quantitative marker of myelin disruption, which can be used along with magnetic resonance imaging for the diagnosis improvement and prognosis of central nervous system opportunistic infections in HIV-infected individuals with 4th clinical stage

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Träger, Jennica, Katharina Widder, Andreas Kerth, George Harauz, and Dariush Hinderberger. "Effect of Cholesterol and Myelin Basic Protein (MBP) Content on Lipid Monolayers Mimicking the Cytoplasmic Membrane of Myelin." Cells 9, no. 3 (February 25, 2020): 529. http://dx.doi.org/10.3390/cells9030529.

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Myelin basic protein (MBP) is located in the insulating covers of nerve cells in the brain and spinal cord. By interacting with lipid membranes, it is responsible for compaction of the myelin sheath in the central nervous system, which is weakened in demyelinating diseases. The lipid composition of the myelin leaflet has a high impact on the interaction between the membrane and MBP. Cholesterol is present in the cytoplasmic leaflet with a rather high amount of 44% (mol%). In this study, the focus is on the effect of cholesterol, mainly by varying its content, on the interaction of MBP with a lipid monolayer. Therefore, Langmuir lipid monolayers mimicking the cytoplasmic membrane of myelin and monolayers with variations of cholesterol content between 0% and 100% were measured at the air/water interface with additional imaging by fluorescence microscopy. All experiments were performed with and without bovine MBP to study the dependence of the interaction of the protein with the monolayers on the cholesterol content. The native amount of 44% cholesterol in the monolayer combines optima in the order of the monolayer (presumably correlating to compaction and thermodynamic stability) and protein interaction and shows unique features in comparison to lower or higher cholesterol contents.

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Qiu, Yidan, Shenglin She, Shufei Zhang, Fengchun Wu, Qunjun Liang, Yongjun Peng, Haishan Yuan, Yuping Ning, Huawang Wu, and Ruiwang Huang. "Cortical myelin content mediates differences in affective temperaments." Journal of Affective Disorders 282 (March 2021): 1263–71. http://dx.doi.org/10.1016/j.jad.2021.01.038.

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Dao, Elizabeth, Roger Tam, Ging-Yuek R. Hsiung, Lisanne ten Brinke, Rachel Crockett, Cindy K. Barha, Youngjin Yoo, et al. "Exploring the Contribution of Myelin Content in Normal Appearing White Matter to Cognitive Outcomes in Cerebral Small Vessel Disease." Journal of Alzheimer's Disease 80, no. 1 (March 9, 2021): 91–101. http://dx.doi.org/10.3233/jad-201134.

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Background: Myelin damage is a salient feature in cerebral small vessel disease (cSVD). Of note, myelin damage extends into the normal appearing white matter (NAWM). Currently, the specific role of myelin content in cognition is poorly understood. Objective: The objective of this exploratory study was to investigate the association between NAWM myelin and cognitive function in older adults with cSVD. Methods: This exploratory study included 55 participants with cSVD. NAWM myelin was measured using myelin water imaging and was quantified as myelin water fraction (MWF). Assessment of cognitive function included processing speed (Trail Making Test Part A), set shifting (Trail Making Test Part B minus A), working memory (Verbal Digit Span Backwards Test), and inhibition (Stroop Test). Multiple linear regression analyses assessed the contribution of NAWM MWF on cognitive outcomes controlling for age, education, and total white matter hyperintensity volume. The overall alpha was set at ≤0.05. Results: After accounting for age, education, and total white matter hyperintensity volume, lower NAWM MWF was significantly associated with slower processing speed (β = –0.29, p = 0.037) and poorer working memory (β= 0.30, p = 0.048). NAWM MWF was not significantly associated with set shifting or inhibitory control (p > 0.132). Conclusion: Myelin loss in NAWM may play a role in the evolution of impaired processing speed and working memory in people with cSVD. Future studies, with a longitudinal design and larger sample sizes, are needed to fully elucidate the role of myelin as a potential biomarker for cognitive function.

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Huynh, Thao N., Matthew C. Havrda, George J. Zanazzi, Catherine C. Y. Chang, and Ta Yuan Chang. "Inhibiting the Cholesterol Storage Enzyme ACAT1/SOAT1 in Myelin Debris-Treated Microglial Cell Lines Activates the Gene Expression of Cholesterol Efflux Transporter ABCA1." Biomolecules 14, no. 10 (October 14, 2024): 1301. http://dx.doi.org/10.3390/biom14101301.

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Aging is the major risk factor for Alzheimer’s disease (AD). In the aged brain, myelin debris accumulates and is cleared by microglia. Phagocytosed myelin debris increases neutral lipid droplet content in microglia. Neutral lipids include cholesteryl esters (CE) and triacylglycerol (TAG). To examine the effects of myelin debris on neutral lipid content in microglia, we added myelin debris to human HMC3 and mouse N9 cells. The results obtained when using 3H-oleate as a precursor in intact cells reveal that myelin debris significantly increases the biosynthesis of CE but not TAG. Mass analyses have shown that myelin debris increases both CE and TAG. The increase in CE biosynthesis was abolished using inhibitors of the cholesterol storage enzyme acyl-CoA:cholesterol acyltransferase 1 (ACAT1/SOAT1). ACAT1 inhibitors are promising drug candidates for AD treatment. In myelin debris-loaded microglia, treatment with two different ACAT1 inhibitors, K604 and F12511, increased the mRNA and protein content of ATP-binding cassette subfamily A1 (ABCA1), a protein that is located at the plasma membrane and which controls cellular cholesterol disposal. The effect of the ACAT1 inhibitor on ABCA1 was abolished by preincubating cells with the liver X receptor (LXR) antagonist GSK2033. We conclude that ACAT1 inhibitors prevent the accumulation of cholesterol and CE in myelin debris-treated microglia by activating ABCA1 gene expression via the LXR pathway.

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Walker, Keenan. "COMBINED USE OF NOVEL MR IMAGING AND FLUID BIOMARKERS REVEAL DETERMINANTS OF MYELIN AND AXONAL LOSS WITH AGING." Innovation in Aging 7, Supplement_1 (December 1, 2023): 386. http://dx.doi.org/10.1093/geroni/igad104.1279.

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Abstract Cerebral white matter damage is a feature of Alzheimer’s disease, vascular dementia, and other neurodegenerative conditions, yet little is known about the molecular underpinnings of key features of white matter pathology. In a series of studies we have used targeted assays and large-scale proteomics platforms to determine how biomarkers of Alzheimer’s disease pathology (Aß42/40 ratio; pTau181), neuronal injury (NfL), reactive astrogliosis (GFAP), and other disease processes relate to state-of-the-art diffusion-based MRI measures of brain myelin content and axonal density in cognitively unimpaired older adults. Using data from the Baltimore Longitudinal Study of Aging (BLSA) and the GESTALT study, we measured plasma biomarkers using the Quanterix Simoa assay (targeted measurement of 4 proteins) and the SomaScan proteomic platform (untargeted measurement of 7000 proteins). Additionally, participants underwent 3T MRI, from which measure of myelin content (defined by myelin water fraction [MWF]) and axonal density (defined by neurite density index [NDI]) were derived. We found an association between higher plasma GFAP and lower myelin content in temporal brain regions. Additionally, higher levels of NfL and GFAP were associated with lower total brain axonal density. Using untargeted proteomics, we identified a set of 155 plasma proteins that were associations with myelin content (P <0.05). Using these findings, we applied machine learning to construct a plasma protein-based predictor of brain myelin content, which we plan to validate in a cohort of individuals with multiple sclerosis: a condition characterized by demyelination.

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King, EM, MJ Sabatier, M. Hoque, TM Kesar, D. Backus, and MR Borich. "Myelin status is associated with change in functional mobility following slope walking in people with multiple sclerosis." Multiple Sclerosis Journal - Experimental, Translational and Clinical 4, no. 2 (April 2018): 205521731877354. http://dx.doi.org/10.1177/2055217318773540.

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Background The level of myelin disruption in multiple sclerosis patients may impact the capacity for training-induced neuroplasticity and the magnitude of therapeutic response to rehabilitation interventions. Downslope walking has been shown to increase functional mobility in individuals with multiple sclerosis, but it is unclear if myelin status influences therapeutic response. Objective The current study aimed to examine the relationship between baseline myelin status and change in functional mobility after a walking intervention. Methods The Timed Up and Go test was used to measure functional mobility before and after completion of a repeated, six-session slope walking intervention in 16 participants with relapsing–remitting multiple sclerosis. Multi-component T2 relaxation imaging was used to index myelin water fraction of overall water content in brain tissue compartments. Results Results demonstrated that the ratio of the myelin water fraction in lesion to normal-appearing white matter (myelin water fraction ratio) significantly predicted 31% of the variance in change in Timed Up and Go score after the downslope walking intervention, where less myelin disruption was associated with greater intervention response. Conclusions Myelin water content fraction ratio may offer a neural biomarker of myelin to identify potential responders to interventions targeting functional impairments in multiple sclerosis.

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POKOŠOVÁ, P., D. KALA, J. ŠANDA, P. JEŽDÍK, Y. PRYSIAZHNIUK, A. FARIDOVÁ, A. JAHODOVÁ, et al. "Magnetic Resonance Imaging Techniques for Indirect Assessment of Myelin Content in the Brain Using Standard T1w and T2w MRI Sequences and Postprocessing Analysis." Physiological Days, Suppl. 5 (December 31, 2023): S573—S585. http://dx.doi.org/10.33549/physiolres.935250.

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Magnetic Resonance Imaging (MRI) has revolutionized our ability to non-invasively study the brain's structural and functional properties. However, detecting myelin, a crucial component of white matter, remains challenging due to its indirect visibility on conventional MRI scans. Myelin plays a vital role in neural signal transmission and is associated with various neurological conditions. Understanding myelin distribution and content is crucial for insights into brain development, aging, and neurological disorders. Although specialized MRI sequences can estimate myelin content, these are time-consuming. Also, many patients sent to specialized neurological centers have an MRI of the brain already scanned. In this study, we focused on techniques utilizing standard MRI T1-weighted (T1w) and T2 weighted (T2w) sequences commonly used in brain imaging protocols. We evaluated the applicability of the T1w/T2w ratio in assessing myelin content by comparing it to quantitative T1 mapping (qT1). Our study included 1 healthy adult control and 7 neurologic patients (comprising both pediatric and adult populations) with epilepsy originating from focal epileptogenic lesions visible on MRI structural scans. Following image acquisition on a 3T Siemens Vida scanner, datasets were co registered, and segmented into anatomical regions using the Fastsurfer toolbox, and T1w/T2w ratio maps were calculated in Matlab software. We further assessed interhemispheric differences in volumes of individual structures, their signal intensity, and the correlation of the T1w/T2w ratio to qT1. Our data demonstrate that in situations where a dedicated myelin-sensing sequence such as qT1 is not available, the T1w/T2w ratio provides significantly better information than T1w alone. By providing indirect information about myelin content, this technique offers a valuable tool for understanding the neurobiology of myelin-related conditions using basic brain scans.

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Irimia, Andrei, Nahian Chowdhury, Shania Wang, Sean Mahoney, Van Ngo, Kenneth Rostowsky, Benjamin Hacker, and Nikhil Chaudhari. "Widespread Cortical Demyelination in Geriatric Cases of Mild Traumatic Brain Injury and in Alzheimer’s Disease." Innovation in Aging 5, Supplement_1 (December 1, 2021): 673–74. http://dx.doi.org/10.1093/geroni/igab046.2538.

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Abstract Cortical demyelination is related to neurodegeneration after mild traumatic brain injury (mTBI) and Alzheimer’s disease (AD). The ratio R of T1-to-T2-weighted magnetic resonance image (MRI) intensities is proportional to myelin content, and allows myelin changes to be mapped in vivo. T1 and T2 MRIs were acquired from mTBI patients (N = 97, age μ = 41 y; σ = 19 y, range: 21-79) both acutely and chronically (~1 week and ~6 months post-injury, respectively), from AD patients (N = 80, age μ = 76 y; σ = 8 y, range: 55-88), and from cognitively normal (CN) adults (N = 78, age μ = 75 y; σ = 5 y, range: 12-90). AD and CN subjects’ data were acquired less than a year apart. MRIs were analyzed using 3DSlicer’s BRAINSfit (registration), FreeSurfer (segmentation), SPM12 (bias field correction) and custom MATLAB scripts to calculate myelin content and demyelination. The null hypothesis of no myelin change was tested at each cortical location for each pair of groups (α = 0.05), after accounting for age, sex and interscan interval. Compared to HCs, AD subjects featured significantly greater myelin loss in dorsolateral prefrontal cortex, lateral and medial temporal lobes (~52% of the cortex, p < 0.05). mTBI participants experienced significantly greater myelin loss across ~96% of the cortex (p < 0.05), suggesting that mTBI has dramatic impact upon cortical myelin content. Myelin loss magnitude was comparable across mTBI and AD, particularly within temporal lobes. Future research should study whether post-traumatic demyelination increases the AD risk.

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Tardif, Christine L., Barry J. Bedell, Simon F. Eskildsen, D. Louis Collins, and G. Bruce Pike. "Quantitative Magnetic Resonance Imaging of Cortical Multiple Sclerosis Pathology." Multiple Sclerosis International 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/742018.

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Although significant improvements have been made regarding the visualization and characterization of cortical multiple sclerosis (MS) lesions using magnetic resonance imaging (MRI), cortical lesions (CL) continue to be under-detectedin vivo, and we have a limited understanding of the causes of GM pathology. The objective of this study was to characterize the MRI signature of CLs to help interpret the changes seenin vivoand elucidate the factors limiting their visualization. A quantitative 3D high-resolution (350 μm isotropic) MRI study at 3 Tesla of a fixedpost mortemcerebral hemisphere from a patient with MS is presented in combination with matched immunohistochemistry. Type III subpial lesions are characterized by an increase in T1, T2 and M0, and a decrease in MTR in comparison to the normal appearing cortex (NAC). All quantitative MR parameters were associated with cortical GM myelin content, while T1 showed the strongest correlation. The histogram analysis showed extensive overlap between CL and NAC for all MR parameters and myelin content. This is due to the poor contrast in myelin content between CL and NAC in comparison to the variability in myelo-architecture throughout the healthy cortex. This latter comparison is highlighted by the representation of T1 times on cortical surfaces at several laminar depths.

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Galazka, Grazyna, Marcin P. Mycko, Igor Selmaj, Cedric S. Raine, and Krzysztof W. Selmaj. "Multiple sclerosis: Serum-derived exosomes express myelin proteins." Multiple Sclerosis Journal 24, no. 4 (February 1, 2017): 449–58. http://dx.doi.org/10.1177/1352458517696597.

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Background: Exosomes are small extracellular vesicles that provide cell-to-cell communication and are involved in immunoregulation. Objective: To investigate serum exosomes for the presence of myelin proteins outside the central nervous system (CNS) and their role in multiple sclerosis (MS). Methods: Serum, cerebrospinal fluid (CSF), and peripheral blood mononuclear cell (PBMC) samples were collected from 45 patients with relapsing–remitting MS (RRMS), 30 patients with secondary progressive MS (SPMS), and 45 healthy controls. Exosomes were isolated using a polymer formulation method, and their size, concentration, and CNS myelin protein contents were measured by a nanoparticle tracking analysis, enzyme-linked immunosorbent assays, and Western blot. Results: We found that exosomes expressed three major myelin proteins, myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein (MOG). Exosomal content of MOG strongly correlated with disease activity and was highest in RRMS patients in relapse and in SPMS patients. Serum-derived exosomes induced proliferation of MOG-T cell receptor transgenic T cells confirming that serum exosomes maintained MOG immunogenicity. Conclusion: Exosomes isolated outside CNS tissue expressed myelin proteins, and the presence of MOG correlated strongly with disease activity. We conclude that exosomes might enhance and/or perpetuate anti-myelin immune reactions in MS and may provide novel markers of disease activity.

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Tonkova, Vyara, Volker Arhelger, Jochen Schenk, and Heiko Neeb. "Rapid myelin water content mapping on clinical MR systems." Zeitschrift für Medizinische Physik 22, no. 2 (June 2012): 133–42. http://dx.doi.org/10.1016/j.zemedi.2011.09.005.

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Meyer, Jerrold S., and Kenneth R. Fairman. "Early adrenalectomy increases myelin content of the rat brain." Developmental Brain Research 17, no. 1-2 (January 1985): 1–9. http://dx.doi.org/10.1016/0165-3806(85)90126-9.

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Laule, C., I. M. Vavasour, G. R. W. Moore, J. Oger, D. K. B. Li, D. W. Paty, and A. L. MacKay. "Water content and myelin water fraction in multiple sclerosis." Journal of Neurology 251, no. 3 (March 1, 2004): 284–93. http://dx.doi.org/10.1007/s00415-004-0306-6.

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Viquez, Olga M., Barry Lai, Jae Hee Ahn, Mark D. Does, Holly L. Valentine, and William M. Valentine. "N,N-diethyldithiocarbamate promotes oxidative stress prior to myelin structural changes and increases myelin copper content." Toxicology and Applied Pharmacology 239, no. 1 (August 2009): 71–79. http://dx.doi.org/10.1016/j.taap.2009.05.017.

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Cirone, Victoria, Nárlon Cássio Boa Sorte Silva, Cindy Barha, Todd Handy, Ryan Stein, Sarah Heath, and Teresa Liu-Ambrose. "FEASIBILITY AND EFFECTS OF HIGH-INTENSITY INTERVAL TRAINING ON COGNITIVE FUNCTION AND BRAIN HEALTH IN PERIMENOPAUSE." Innovation in Aging 8, Supplement_1 (December 2024): 1084. https://doi.org/10.1093/geroni/igae098.3482.

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Abstract Neuroendocrine changes during perimenopause negatively impact cognitive function and brain health (e.g., reduced verbal episodic memory and myelin catabolism in the brain). Exercise promotes cognitive performance and mitigates vascular risk factors for cognitive impairment. High-intensity interval training (HIIT) involves short bursts of high-intensity exercise interspersed with active recovery; it improves cardiovascular fitness and vascular risk profile. HIIT addresses the “lack of time” barrier to exercise that perimenopausal females report. This pre-post pilot study assessed the feasibility and potential effects of 12-weeks of HIIT on cardiovascular fitness, verbal episodic memory, hippocampal volume, and myelin content. Feasibility metrics included recruitment rate (i.e., 1/month), withdrawal rate (i.e., < 15%), adherence (i.e., >60%). Training fidelity was assessed by cardiovascular fitness (VO2max.) Verbal episodic memory was assessed by Rey Auditory Verbal Learning Test delayed recall. Hippocampal volume was measured by T1-weighted magnetic resonance imaging. Myelin content was measured by myelin water fraction. Cohen’s d and one-tailed paired t-tests assessed effect sizes and potential changes. Recruitment rate was 0.35 participants/month (six participants in 17 months). Withdrawal rate was 16.67% and adherence was 88.2%. The intervention had a negligible effect on VO2max (Cohen’s d=0.06, p=0.35), large and significant effect on delayed recall (Cohen’s d=0.94, p=0.04), negligible effect on hippocampal volume (Cohen’s d=0.06, p=0.18), and medium to large effect on sagittal stratum myelin content (Cohen’s d=0.68, p=0.06). Future studies should consider home-based exercise and tailored recruitment methods (e.g. social media) to meet recruitment targets. HIIT may be beneficial for cognitive function and myelin content.

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Pridham, Glen, Shahnewaz Hossain, Khalil S. Rawji, and Yunyan Zhang. "A metric learning method for estimating myelin content based on T2-weighted MRI from a de- and re-myelination model of multiple sclerosis." PLOS ONE 16, no. 4 (April 5, 2021): e0249460. http://dx.doi.org/10.1371/journal.pone.0249460.

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Myelin plays a critical role in the pathogenesis of neurological disorders but is difficult to characterize in vivo using standard analysis methods. Our goal was to develop a novel analytical framework for estimating myelin content using T2-weighted magnetic resonance imaging (MRI) based on a de- and re-myelination model of multiple sclerosis. We examined 18 mice with lysolecithin induced demyelination and spontaneous remyelination in the ventral white matter of thoracic spinal cord. Cohorts of 6 mice underwent 9.4T MRI at days 7 (peak demyelination), 14 (ongoing recovery), and 28 (near complete recovery), as well as histological analysis of myelin and the associated cellularity at corresponding timepoints. Our MRI framework took an unsupervised learning approach, including tissue segmentation using a Gaussian Markov random field (GMRF), and myelin and cellularity feature estimation based on the Mahalanobis distance. For comparison, we also investigated 2 regression-based supervised learning approaches, one using our GMRF results, and another using a freely available generalized additive model (GAM). Results showed that GMRF segmentation was 73.2% accurate, and our unsupervised learning method achieved a correlation coefficient of 0.67 (top quartile: 0.78) with histological myelin, similar to 0.70 (top quartile: 0.78) obtained using supervised analyses. Further, the area under the receiver operator characteristic curve of our unsupervised myelin feature (0.883, 95% CI: 0.874–0.891) was significantly better than any of the supervised models in detecting white matter myelin as compared to histology. Collectively, metric learning using standard MRI may prove to be a new alternative method for estimating myelin content, which ultimately can improve our disease monitoring ability in a clinical setting.

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Laule, C., E. Leung, D. KB Li, A. L. Traboulsee, D. W. Paty, A. L. MacKay, and G. RW Moore. "Myelin water imaging in multiple sclerosis: quantitative correlations with histopathology." Multiple Sclerosis Journal 12, no. 6 (November 2006): 747–53. http://dx.doi.org/10.1177/1352458506070928.

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Various magnetic resonance (MR) techniques are used to study the pathological evolution of demyelinating diseases, such as multiple sclerosis (MS). However, few studies have validated MR derived measurements with histopathology. Here, we determine the correlation of myelin water imaging, an MR measure of myelin content, with quantitative histopathologic measures of myelin density. The multi-component T2 distribution of water was determined from 25 formalin-fixed MS brain samples using a multi-echo T2 relaxation MR experiment. The myelin water fraction (MWF), defined as T2 signal below 30 milliseconds divided by the total signal, was determined for various regions of interest and compared to Luxol fast blue (myelin stain) mean optical density (OD) for each sample. MWF had a strong correlation with myelin stain [mean (range) R2-/0.67 (0.45+ 0.92)], validating MWF as a measure of myelin density. This quantitative technique has many practical applications for the in vivo monitoring of demyelination and remyelination in a variety of disorders of myelin.

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Kisel, A., M. Khodanovich, D. Atochin, L. Mustafina, and V. Yarnykh. "Dynamics of myelin content decrease in the rat stroke model." Journal of Physics: Conference Series 886 (August 2017): 012008. http://dx.doi.org/10.1088/1742-6596/886/1/012008.

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Bock, Nicholas A., Eyesha Hashim, Rafal Janik, Norman B. Konyer, Marcel Weiss, Greg J. Stanisz, Robert Turner, and Stefan Geyer. "Optimizing T1-weighted imaging of cortical myelin content at 3.0T." NeuroImage 65 (January 2013): 1–12. http://dx.doi.org/10.1016/j.neuroimage.2012.09.051.

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Merkler, Doron, Florian Klinker, Tanja Jürgens, Raoul Glaser, Walter Paulus, Bastian G. Brinkmann, Michael W. Sereda, et al. "Propagation of spreading depression inversely correlates with cortical myelin content." Annals of Neurology 66, no. 3 (September 2009): 355–65. http://dx.doi.org/10.1002/ana.21746.

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Matthieu, J. M., J. M. Roch, F. X. Omlin, I. Rambaldi, G. Almazan, and P. E. Braun. "Myelin instability and oligodendrocyte metabolism in myelin-deficient mutant mice." Journal of Cell Biology 103, no. 6 (December 1, 1986): 2673–82. http://dx.doi.org/10.1083/jcb.103.6.2673.

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During the active phase of myelination in myelin-deficient mutant mice (mld), myelin basic protein (MBP) synthesis is defective and the myelin lamellae are uncompacted. In these mutants, we found a fast metabolism of the myelin-associated glycoprotein (MAG) and of sulfatides, and the presence of cholesterol esters and a degradation product of MAG, dMAG, indicating that mld myelin was unstable. The increased synthesis of MAG and Wolfgram protein, two proteins present in uncompacted myelin sheath and paranodal loops, was demonstrated by high levels of messengers. Simultaneously, we found an accumulation of inclusion bodies, vacuoles, and rough endoplasmic reticulum in mld oligodendrocytes. This material was heavily immunostained for MAG. Furthermore, the developmental change between the two molecular forms of MAG (p72MAG/p67MAG) was delayed in mld mice. In 85-d-old mld mice, the MBP content increased and myelin lamellae became better compacted. In these mutants, dMAG was absent and MAG mRNAs were found in normal amounts. Furthermore, the fine structure of mld oligodendrocytes was normal and the MAG immunostaining was similar to age-matched controls. These results support a functional role for MBP in maintaining the metabolic stability and the compact structure of myelin. Furthermore, in the absence of MBP and myelin compaction, the regulation of the synthesis of at least two membrane proteins related to myelin cannot proceed.

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Bondarenko, V. P., D. A. Kupriyanov, A. V. Artemov, and G. V. Tereshchenko. "Multiparametric Quantitative MRI Evaluation of Changes in Brain Myelin Content after the First Course of Chemotherapy." Radiology - Practice, no. 2 (February 27, 2024): 73–89. http://dx.doi.org/10.52560/2713-0118-2024-2-73-89.

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Objective. Quantitative assessment of changes in brain myelin content after the first course of chemotherapyMaterials and Methods. T1 and T2 maps as well as myelin water fraction (MWF) and macromolecular proton fraction (MPF) maps, reflecting myelin content, were acquired in 6 patients (mean age — 13.7 ± 2.4 years) before and after the first course of chemotherapy. The study was carried out using on 3T MRI scanner. Statistical data processing was carried out using the GraphPad Prism.Results. MPF and T2 values showed an increase in the thalamus and white matter of the occipital lobes of the brain, while MWF values showed an increase in the cerebellum and a decline in the white matter of the frontal lobes. Significant changes were not found for T1 values.Discussion. According to MWF the structures of the brain which are primarily affected by treatment with toxic drugs — the white matter of the frontal lobes and the cerebellum, were revealed. MWF values decreasing in the white matter of the frontal lobes may indicate the process of demyelination in this area, while increased MWF values in the cerebellum could be caused either by remyelination processes or by incomplete cleansing of myelin residues accumulation by macrophages at the site of degeneration. Conclusion. The results obtained demonstrated high potential of MWF values serve as early changes biomarker of neurotoxicity after the chemotherapy treatment. Along with this, the MPF index, which is more sensitive to cerebral edema, may be a predictor of demyelination.

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Poitelon, Yannick, Ashley M. Kopec, and Sophie Belin. "Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism." Cells 9, no. 4 (March 27, 2020): 812. http://dx.doi.org/10.3390/cells9040812.

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Myelin is critical for the proper function of the nervous system and one of the most complex cell–cell interactions of the body. Myelination allows for the rapid conduction of action potentials along axonal fibers and provides physical and trophic support to neurons. Myelin contains a high content of lipids, and the formation of the myelin sheath requires high levels of fatty acid and lipid synthesis, together with uptake of extracellular fatty acids. Recent studies have further advanced our understanding of the metabolism and functions of myelin fatty acids and lipids. In this review, we present an overview of the basic biology of myelin lipids and recent insights on the regulation of fatty acid metabolism and functions in myelinating cells. In addition, this review may serve to provide a foundation for future research characterizing the role of fatty acids and lipids in myelin biology and metabolic disorders affecting the central and peripheral nervous system.

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Bouhrara, Mustapha, Nikkita Khattar, Richard Kim, Wenshu Qian, Joseph Alisch, Luigi Ferrucci, Susan Resnick, and Richard Spencer. "Cerebral Microstructure in Aging Using Advanced Quantitative MRI." Innovation in Aging 4, Supplement_1 (December 1, 2020): 767. http://dx.doi.org/10.1093/geroni/igaa057.2771.

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Abstract White matter (WM) maintenance through oligodendrocyte metabolism is an energy-intensive process. Myelin homeostasis is sensitive to hypoxia, ischemia, or hypoperfusion. Besides substrate delivery, adequate cerebral blood flow (CBF) is crucial for removal of metabolic byproducts such as iron. While some data show decreased myelin content and CBF with aging, the association between CBF and myelination is unknown. Further, breakdown of oligodendrocyte and iron may potentiate myelin loss through oxidative mechanisms. Whether iron deposition is related to myelination is unclear. Using advanced MRI methodology, we investigated associations between CBF deficits, myelin loss, and iron deposition in cognitively normal individuals. We found significant association between i) CBF deficits and myelin loss (N=67,age24-88), ii) myelin loss and iron accumulation (N=92,age21-94), and iii) CBF deficits and iron accumulation (N=35,age22-88) in critical brain structures. This work may lay the foundation for further investigations of age-related WM degeneration and markers to differentiate normal from abnormal alterations.

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ROTH, ALEJANDRO D., ANNA IVANOVA, and DAVID R. COLMAN. "New observations on the compact myelin proteome." Neuron Glia Biology 2, no. 1 (December 16, 2005): 15–21. http://dx.doi.org/10.1017/s1740925x06000068.

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Myelin formation and maintenance depends on the establishment of two structurally and biochemically discernible domains: (a) compact myelin, that is multilamellar stacks of plasma membrane sheets; and (b) cytoplasmic channels that border the compact myelin domains, attach them to the cell body and anchor the myelin sheath to the axonal membrane. To identify proteins involved in the organization of these domains we took advantage of the high lipid content of compact myelin to separate it cleanly from other neural membranes and then used reverse-phase HPLC coupled to Electro-Spray Double Mass Spectrometry (‘MudPIT’) to characterize the proteome of this sample. MudPIT allowed us to sidestep the bias of 2D-PAGE against either highly charged or transmembrane proteins. Thus, of 97 proteins that presented at least two, fully tryptic peptides (a stringent threshold), seven were well known myelin markers, including the mayor CNS myelin proteins: proteolipid protein and myelin basic protein, which are not resolvable by 2D-PAGE. Furthermore, we have confirmed and extended the known compact myelin proteome by 22 proteins and confirmed that CNS and PNS myelinated tracts present Sirtuin 2, a tubulin deacetylase, and Septin 7, a small GTPase that is likely to be involved in membrane and cytoplasm partitioning.

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Drenthen, Gerhard S., Walter H. Backes, and Jacobus F. A. Jansen. "Estimating myelin-water content from anatomical and diffusion images using spatially undersampled myelin-water imaging through machine learning." NeuroImage 226 (February 2021): 117626. http://dx.doi.org/10.1016/j.neuroimage.2020.117626.

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Spader, Heather S., Anna Ellermeier, Jonathan O'Muircheartaigh, Douglas C. Dean, Holly Dirks, Jerrold L. Boxerman, G. Rees Cosgrove, and Sean C. L. Deoni. "Advances in myelin imaging with potential clinical application to pediatric imaging." Neurosurgical Focus 34, no. 4 (April 2013): E9. http://dx.doi.org/10.3171/2013.1.focus12426.

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White matter development and myelination are critical processes in neurodevelopment. Myelinated white matter facilitates the rapid and coordinated brain messaging required for higher-order cognitive and behavioral processing. Whereas several neurological disorders such as multiple sclerosis are associated with gross white matter damage and demyelination, other disorders such as epilepsy may involve altered myelination in the efferent or afferent white matter pathways adjoining epileptic foci. Current MRI techniques including T1 weighting, T2 weighting, FLAIR, diffusion tensor imaging, and MR spectroscopy permit visualization of gross white matter abnormalities and evaluation of underlying white matter fiber architecture and integrity, but they provide only qualitative information regarding myelin content. Quantification of these myelin changes could provide new insight into disease severity and prognosis, reveal information regarding spatial location of foci or lesions and the associated affected neural systems, and create a metric to evaluate treatment efficacy. Multicomponent analysis of T1 and T2 relaxation data, or multicomponent relaxometry (MCR), is a quantitative imaging technique that is sensitive and specific to myelin content alteration. In the past, MCR has been associated with lengthy imaging times, but a new, faster MCR technique (mcDESPOT) has made quantitative analysis of myelin content more accessible for clinical research applications. The authors briefly summarize traditional white matter imaging techniques, describe MCR and mcDESPOT, and discuss current and future clinical applications of MCR, with a particular focus on pediatric epilepsy.

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Proescholdt, Martin, Amer Haj, Karl-Michael Schebesch, Markus Riemenschneider, Atik Baborie, and Nils-Ole Schmidt. "CSIG-13. DIELECTRIC PROPERTIES OF INTRACRANIAL TUMORS – ROLE OF MYELIN CONTENT." Neuro-Oncology 25, Supplement_5 (November 1, 2023): v42—v43. http://dx.doi.org/10.1093/neuonc/noad179.0169.

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Abstract INTRODUCTION Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed glioblastoma (GBM). One of the most crucial parameters defining the treatment efficacy of TTFields is the electric field intensity, which depends on the dielectric properties of the tumor tissue. In this study we determined the dieclectric properties of brain tumors by analyzing resected tissue. In GBM patients, histological analysis for cellularity, vascularization and myelin content was performed. In addition, sensitivity analyses for specific parameters were conducted. METHODS A cohort of 130 patients with tumors of different histology and malignancy grade have been recruited. Tissue samples were placed into a cylindrical cell with a known diameter. The impedance was recorded at frequencies 20Hz-1MHz. The measured impedance was translated into dielectric properties (conductivity and relative permittivity) based on the parallel plate model. Myelin, which is the most powerful electric isolator in the brain, was assessed in GBM samples by luxol fast blue staining, and quantified in a three-tier scale. To assess the impact of tissue conditions on the measurements, probes were warmed to 35 degree Celsius, dehydrated or irrigated with 0.9% saline solution. RESULTS We found significant differences between the conductivity of different types of tumors with meningiomas showing the lowest and GBM tissue exhibiting the highest conductivity values. GBM samples with very high median conductivity values displayed a consistently lower myelin content. In addition, GBM patients with particularly high conductivity had a significantly shorter overall survival (log rank analysis, p = 0.024). While tissue temperature had no detectable effects on the dielectric properties in GBM, saline irrigation tissue hydration significantly affected the results. CONCLUSION The dielectric properties of intracranial tumors depend on histological class and malignancy grade. GBM patients with high conductivity values showed a significantly poorer prognosis, indicating this parameter as potential marker for TTF efficacy.

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VERSTRAETEN, Sandra V., Carl L. KEEN, Mari S. GOLUB, and Patricia I. OTEIZA. "Membrane composition can influence the rate of Al3+-mediated lipid oxidation: effect of galactolipids." Biochemical Journal 333, no. 3 (August 1, 1998): 833–38. http://dx.doi.org/10.1042/bj3330833.

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In the first part of the present study we investigated the effects of pre-natal and early postnatal exposure of mice to high levels of dietary Al3+ on myelin lipid composition and lipid oxidation. We found: (1) a significantly higher (104%; P< 0.01) content of brain myelin galactolipids in the high-Al3+ group than in controls, and, (2) a significant correlation (r2 = 0.70; P< 0.01) between the concentration of myelin galactolipids and TBARS (2-thiobarbituric acid-reactive substances) content, a parameter of lipid oxidation. Based on these results, we evaluated in an in vitro model (liposomes) whether galactolipids could affect the capacity of Al3+ to stimulate Fe2+-initiated lipid oxidation, and whether this effect could be due to the promotion of changes in membrane physical properties (membrane phase separation and rigidification). The presence of galactolipids (10–40 mol%) in the liposomes caused a concentration-dependent increase in the stimulatory effect of Al3+ on Fe2+-induced TBARS production, and on the ability of Al3+ to induce phase separation and membrane rigidification. The capacity of Al3+ (10–100 µM) to induce lateral phase separation in liposomes composed of phosphatidylcholine/phosphatidylserine/galactolipid (36:24:40, molar ratio) was correlated significantly (r2 = 0.99; P< 0.001) with the stimulatory action of Al3+ on Fe2+-induced TBARS production. We propose that the high content of galactolipids found in myelin from Al3+-intoxicated mice could favour Al3+-induced changes in membrane physical properties, with the subsequent acceleration of lipid oxidation rates.

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Miskimins, R., H. Ebato, T. N. Seyfried, and R. K. Yu. "Molecular basis for heterosis for myelin basic protein content in mice." Proceedings of the National Academy of Sciences 83, no. 5 (March 1, 1986): 1532–35. http://dx.doi.org/10.1073/pnas.83.5.1532.

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36

Bartzokis, George. "Quadratic trajectories of brain myelin content: unifying construct for neuropsychiatric disorders." Neurobiology of Aging 25, no. 1 (January 2004): 49–62. http://dx.doi.org/10.1016/j.neurobiolaging.2003.08.001.

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37

Dean, Douglas C., Jitka Sojkova, Samuel Hurley, Patrick O'Grady, Christybelle-Marie Canda, Katie-Grace Burke, Nancy J. Davenport, et al. "P3-156: Elevated cardiovascular risk is associated with altered myelin content." Alzheimer's & Dementia 11, no. 7S_Part_15 (July 2015): P688. http://dx.doi.org/10.1016/j.jalz.2015.06.1527.

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38

Webb, Stephanie, Catherine A. Munro, Rajiv Midha, and Greg J. Stanisz. "Is multicomponentT2 a good measure of myelin content in peripheral nerve?" Magnetic Resonance in Medicine 49, no. 4 (March 18, 2003): 638–45. http://dx.doi.org/10.1002/mrm.10411.

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39

Kim, Joo-Won, Thomas P. Naidich, Joshmi Joseph, Divya Nair, Matthew F. Glasser, Rafael O'halloran, Gaelle E. Doucet, et al. "Reproducibility of myelin content-based human habenula segmentation at 3 Tesla." Human Brain Mapping 39, no. 7 (March 26, 2018): 3058–71. http://dx.doi.org/10.1002/hbm.24060.

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40

Miskimins, R., and R. K. Yu. "Heterosis for myelin content is limited to the central nervous system." Journal of Neuroscience Research 19, no. 3 (March 1988): 364–66. http://dx.doi.org/10.1002/jnr.490190312.

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41

Piredda, Gian Franco, Tom Hilbert, Jean‐Philippe Thiran, and Tobias Kober. "Probing myelin content of the human brain with MRI: A review." Magnetic Resonance in Medicine 85, no. 2 (September 16, 2020): 627–52. http://dx.doi.org/10.1002/mrm.28509.

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42

Laule, Cornelia, Irene M. Vavasour, Esther Leung, David KB Li, Piotr Kozlowski, Anthony L. Traboulsee, Joel Oger, Alex L. MacKay, and GR Wayne Moore. "Pathological basis of diffusely abnormal white matter: insights from magnetic resonance imaging and histology." Multiple Sclerosis Journal 17, no. 2 (October 21, 2010): 144–50. http://dx.doi.org/10.1177/1352458510384008.

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Background: The pathological basis of diffusely abnormal white matter (DAWM) in multiple sclerosis (MS) has not been elucidated in detail, but may be an important element in disability and clinical progression. Methods: Fifty-three subjects with MS were examined with T1, multi-echo T2 and magnetization transfer (MT). Twenty-three samples of formalin-fixed MS brain tissue were examined with multi-echo T2 and subsequently stained for myelin phospholipids using luxol fast blue, for axons using Bielschowsky, immunohistochemically for the myelin proteins myelin basic protein (MBP) and 2′,3′-cyclic nucleotide 3′ phosphohydrolase (CNP) and for astrocytes using glial fibrillary acidic protein (GFAP). Regions of interest in DAWM were compared with normal appearing white matter. Results: Fourteen of 53 subjects with MS in the in vivo study showed the presence of DAWM. Subjects with DAWM were found to have a significantly lower Expanded Disability Status Scale (EDSS) and shorter disease duration (DD) when compared with subjects without DAWM (EDSS: 1.5 versus 3.0, p = 0.031; DD: 5.4 versus 10.3 years, p = 0.045). DAWM in vivo had reduced myelin water and MT ratio, and increased T2 and water content. Histological analysis suggests DAWM, which shows a reduction of the myelin water fraction, is characterized by selective reduction of myelin phospholipids, but with a relative preservation of myelin proteins and axons. Conclusions: These findings suggest that the primary abnormality in DAWM is a reduction or perturbation of myelin phospholipids that correlates with a reduction of the myelin water fraction.

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43

Stanley, Jeffrey, Jennifer Losiowski, Phil Easter, Dalal Khatib, Pamela Szura, Rebecca Neill, Usha Rajan, Julia Bellamy, David Rosenberg, and Vaibhav Diwadkar. "403. Evidence of Lower Myelin Content in Selective White Matter Tracts of OCD Children/Adolescents Utilizing Myelin Water Imaging." Biological Psychiatry 97, no. 9 (May 2025): S263. https://doi.org/10.1016/j.biopsych.2025.02.641.

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44

Li, C., PP Chu, P. Hung, D. Mikulis, and M. Hodaie. "A.2 Clinical application of T1-w/T2-w ratio images for in vivo comparisons of myelin content in patients with trigeminal neuralgia." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 48, s3 (November 2021): S14. http://dx.doi.org/10.1017/cjn.2021.264.

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Background: Novel magnetic resonance (MR) imaging techniques prompted the emergence of T1-w/T2-w images or “myelin-sensitive maps (MMs)” to measure myelin in vivo. However, acquisition-related variations in MR intensities prevent meaningful quantitative comparisons between MMs. We propose an improved pipeline to standardize MMs that is applied to patients with classic trigeminal neuralgia (CTN) and trigeminal neuralgia secondary to multiple sclerosis (MSTN). Methods: 3T scanner was used to obtain T1-w and T2-w images for 17 CTN and 17 MSTN patients. Template images were obtained from ICBM152 database. MS plaques and normal-appearing white matter (NAWM) were labelled. A Gaussian curve-fit was applied to the histogram of the intensity distribution of each patient image, and transformed to match the Gaussian curve-fit of the template image. Results: MM intensities were decreased within MS plaques, compared to NAWM in MSTN patients (p<0.001) and its corresponding regions in CTN patients (p<0.001). Qualitatively, the standardized patient image and its histogram better resembled the ICBM152 template. Conclusions: MM analysis revealed reduced myelin content in MS plaques compared to corresponding regions in CTN patients and surrounding NAWM in MSTN patients. The standardized MM serves as a non-invasive, clinical tool for quantitative analyses of myelin content between different brain regions and different patients in vivo.

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45

Huitema, Marije J. D., Eva M. M. Strijbis, Antonio Luchicchi, John G. J. M. Bol, Jason R. Plemel, Jeroen J. G. Geurts, and Geert J. Schenk. "Myelin Quantification in White Matter Pathology of Progressive Multiple Sclerosis Post-Mortem Brain Samples: A New Approach for Quantifying Remyelination." International Journal of Molecular Sciences 22, no. 23 (November 23, 2021): 12634. http://dx.doi.org/10.3390/ijms222312634.

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Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS). Repair through remyelination can be extensive, but quantification of remyelination remains challenging. To date, no method for standardized digital quantification of remyelination of MS lesions exists. This methodological study aims to present and validate a novel standardized method for myelin quantification in progressive MS brains to study myelin content more precisely. Fifty-five MS lesions in 32 tissue blocks from 14 progressive MS cases and five tissue blocks from 5 non-neurological controls were sampled. MS lesions were selected by macroscopic investigation of WM by standard histopathological methods. Tissue sections were stained for myelin with luxol fast blue (LFB) and histological assessment of de- or remyelination was performed by light microscopy. The myelin quantity was estimated with a novel myelin quantification method (MQM) in ImageJ. Three independent raters applied the MQM and the inter-rater reliability was calculated. We extended the method to diffusely appearing white matter (DAWM) and encephalitis to test potential wider applicability of the method. Inter-rater agreement was excellent (ICC = 0.96) and there was a high reliability with a lower- and upper limit of agreement up to −5.93% to 18.43% variation in myelin quantity. This study builds on the established concepts of histopathological semi-quantitative assessment of myelin and adds a novel, reliable and accurate quantitative measurement tool for the assessment of myelination in human post-mortem samples.

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46

Smith, R., P. E. Braun, M. A. J. Ferguson, M. G. Low, and W. R. Sherman. "Direct measurement of inositol in bovine myelin basic protein." Biochemical Journal 248, no. 1 (November 15, 1987): 285–88. http://dx.doi.org/10.1042/bj2480285.

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Myelin basic protein has been isolated from bovine central-nervous-system myelin by four methods, none of which exposes the protein to acid. After purification the inositol content of both hydrolysed and unhydrolysed protein was quantified by g.c.-m.s. Basic protein prepared by all methods contained less than 4 mol % of inositol. It is concluded, contrary to a previous proposal, that covalent binding to phosphoinositides does not represent a general mechanism for attachment of this cytoplasmically-oriented protein to its membrane.

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47

Roggenhofer, Elisabeth, Evdokia Toumpouli, Margitta Seeck, Roland Wiest, Antoine Lutti, Ferath Kherif, Jan Novy, Andrea O. Rossetti, and Bogdan Draganski. "Clinical phenotype modulates brain’s myelin and iron content in temporal lobe epilepsy." Brain Structure and Function 227, no. 3 (November 24, 2021): 901–11. http://dx.doi.org/10.1007/s00429-021-02428-z.

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AbstractTemporal lobe epilepsy (TLE) is associated with brain pathology extending beyond temporal lobe structures. We sought to look for informative patterns of brain tissue properties in TLE that go beyond the established morphometry differences. We hypothesised that volume differences, particularly in hippocampus, will be paralleled by changes in brain microstructure. The cross-sectional study included TLE patients (n = 25) from a primary care center and sex-/age-matched healthy controls (n = 55). We acquired quantitative relaxometry-based magnetic resonance imaging (MRI) data yielding whole-brain maps of grey matter volume, magnetization transfer (MT) saturation, and effective transverse relaxation rate R2* indicative for brain tissue myelin and iron content. For statistical analysis, we used the computational anatomy framework of voxel-based morphometry and voxel-based quantification. There was a positive correlation between seizure activity and MT saturation measures in the ipsilateral hippocampus, paralleled by volume differences bilaterally. Disease duration correlated positively with iron content in the mesial temporal lobe, while seizure freedom was associated with a decrease of iron in the very same region. Our findings demonstrate the link between TLE clinical phenotype and brain anatomy beyond morphometry differences to show the impact of disease burden on specific tissue properties. We provide direct evidence for the differential effect of clinical phenotype characteristics on processes involving tissue myelin and iron in mesial temporal lobe structures. This study offers a proof-of-concept for the investigation of novel imaging biomarkers in focal epilepsy.

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48

Maksimov, G. V., V. V. Volkov, E. Yu Parshina, M. Ia Akhalaia, O. V. Kozlova, E. V. Derinskaya, V. V. Revin, and A. B. Rubin. "Investigation of carotenoid conformations in myelin nerve upon changes in oxygen content." Doklady Biochemistry and Biophysics 417, no. 1 (December 2007): 324–26. http://dx.doi.org/10.1134/s1607672907060099.

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49

Glasser, Matthew F., Manu S. Goyal, Todd M. Preuss, Marcus E. Raichle, and David C. Van Essen. "Trends and properties of human cerebral cortex: Correlations with cortical myelin content." NeuroImage 93 (June 2014): 165–75. http://dx.doi.org/10.1016/j.neuroimage.2013.03.060.

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50

Hwang, Dosik, Dong-Hyun Kim, and Yiping P. Du. "In vivo multi-slice mapping of myelin water content using T2* decay." NeuroImage 52, no. 1 (August 2010): 198–204. http://dx.doi.org/10.1016/j.neuroimage.2010.04.023.

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