Association of cerebral blood flow with myelin content in cognitively unimpaired adults

Bouhrara, Mustapha; Alisch, Joseph S R; Khattar, Nikkita; Kim, Richard W.; Rejimon, Abinand C.; Cortina, Luis E.; Qian, Wenshu; Ferrucci, Luigi; Resnick, Susan M.; Spencer, Richard G.

doi:10.1136/bmjno-2020-000053

Cited by 26 publications

(27 citation statements)

References 38 publications

(60 reference statements)

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“…To address these limitations, we studied a larger cohort, with an improved age distribution, of cognitively unimpaired subjects (N = 140) across the extended age range of 21-94 years. Our main objectives are: First, building on Lambert et al and our previous work [10,15], we sought to characterize age-and sex-related microstructural correlates by determining the diffusion tensor imaging (DTI) indices of fractional anisotropy (FA) and mean, radial, and axial diffusivities (MD, RD, and AxD), as well as longitudinal and transverse relaxation rates (R1, R2), and myelin water fraction (MWF) quantification using our recently-introduced method [16][17][18][19][20][21], within selected brainstem substructures. Second, we compared MWF estimates with widely used markers of myelin content (RD, R1, R2), axonal damage (AxD), and tissue composition (FA, MD) to determine whether the information provided by these biomarkers is complimentary or is redundant to MWF.…”

Section: Introductionmentioning

confidence: 99%

Maturation and degeneration of the human brainstem across the adult lifespan

Bouhrara¹,

Cortina²,

Khattar³

et al. 2021

aging

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Brainstem tissue microstructural properties change across the adult lifespan. However, studies elucidating the biological processes that govern brainstem maturation and degeneration in-vivo are lacking. In the present work, conducted on a large cohort of 140 cognitively unimpaired subjects spanning a wide age range of 21 to 94 years, we implemented a multi-parameter approach to characterize the sex-and age differences. In addition, we examined regional correlations between myelin water fraction (MWF), a direct measure of myelin content, and diffusion tensor imaging indices, and transverse and longitudinal relaxation rates to evaluate whether these metrics provide information complementary to MWF. We observed region-dependent differences in myelin content and axonal density with age and found that both exhibit an inverted U-shape association with age in several brainstem substructures. We emphasize that the microstructural differences captured by our distinct MRI metrics, along with their weak associations with MWF, strongly indicate the potential of using these outcome measures in a multi-parametric approach. Furthermore, our results support the gain-predictsloss hypothesis of tissue maturation and degeneration in the brainstem. Indeed, our results indicate that myelination follows a temporally symmetric time course across the adult life span, while axons appear to degenerate significantly more rapidly than they mature. AGINGTable 2. The slopes and standard error (SE) of the maturation and degeneration phases of the standardized MWF, R1, R2, and DTI indices for six brainstem substructures. Maturation and degeneration slopes ± SE Slope of maturation Slope of degeneration p-value Slope of maturation Slope of degeneration p-value MWF Cerebral peduncle

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Section: Introductionmentioning

confidence: 99%

Maturation and degeneration of the human brainstem across the adult lifespan

Bouhrara¹,

Cortina²,

Khattar³

et al. 2021

aging

Self Cite

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“…All of the aforementioned pathophysiological alterations resulted in cerebral hypoperfusion. Cerebral hypoperfusion produced pathological myelin loss and axonal injury, altered nerve cell metabolism, promoted neurodegeneration, caused white matter bundle ischemia, disrupted subcortical circuits, and eventually resulted in abnormalities in brain tissue microstructure ( 20 , 52 , 53 ).…”

Section: Discussionmentioning

confidence: 99%

Assessment of cognitive impairment after acute cerebral infarction with T1 relaxation time measured by MP2RAGE sequence and cerebral hemodynamic by transcranial Doppler

et al. 2022

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ObjectiveThis study aimed to investigate early brain microstructural changes discovered using magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) sequence and cerebral hemodynamic using TCD for cognitive impairment after acute cerebral infarction.MethodsWe enrolled 43 patients with acute cerebral infarction and 21 healthy people in the study, who were subjected to cognitive assessments, the MP2RAGE sequence, and a cerebral hemodynamic examination. A total of 26 brain regions of interest were investigated. Furthermore, we used cerebral hemodynamics to explain brain microstructural changes, which helped us better understand the pathophysiology of cognitive impairment after acute cerebral infarction and guide treatment.ResultsT1 relaxation times in the left frontal lobe, right frontal lobe, right temporal lobe, left precuneus, left thalamus, right hippocampus, right head of caudate nucleus, and splenium of corpus callosum were substantially different across the three groups, which were significantly correlated with neuropsychological test scores. CI group patients had significantly lower cerebral blood flow velocity than those in the N-CI and Normal groups. The receiver operating curve analysis revealed that most T1 relaxation times had high sensitivity and specificity, especially on the right temporal lobe and right frontal lobe. There was a potential correlation between T1 relaxation times and MMSE scores through TCD parameters.ConclusionThe MP2RAGE sequence can detect alterations in whole brain microstructure in patients with cognitive impairment after acute cerebral infarction. Brain microstructural changes could influence cognitive function through cerebral hemodynamics. T1 relaxation times on the right temporal lobe and the right frontal lobe are expected to be a prospective biomarker of cognitive impairment after acute cerebral infarction.

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“…Active demyelination is associated with a complex pro-inflammatory cascade that has been shown to correlate negatively with CBF alterations. 28 A recent study in healthy cognitively unimpaired adults showed a correlation between CBF and myelin water fraction (MWF) 29 such that as WM microstructural integrity decreased, concomitant decreases in CBF were observed. We found a correlation between capillary-sized cerebral perfusion metrics and WM microstructural integrity assessed using sT 1 w/T 2 w ratios.…”

Section: Discussionmentioning

confidence: 99%

Investigating the relationship between multi-scale perfusion and white matter microstructural integrity in patients with relapsing-remitting MS

Sisco

Borazanci

Dortch

et al. 2021

Multiple Sclerosis Journal - Experimental, Translational and Cl

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Background Multiple sclerosis is characterized by the formation of central nervous system demyelinating lesions with microvasculature inflammation. Objective Evaluate how lesion cerebral perfusion relates to white matter microstructural integrity in patients with RRMS using perfusion MRI and myelin-related T1-weighted to T2-weighted (T1w/T2w) ratios. Methods Forty-eight patients with RRMS were imaged with dynamic susceptibility contrast imaging using SAGE (spin- and gradient-echo) to calculate global and capillary-sized perfusion parameters, including cerebral blood flow (CBF), volume (CBV), and mean transit time (MTT). T1w/T2w ratios were used to indirectly assess white matter microstructural integrity. Results For global perfusion metrics, CBF was reduced 28.4% in lesion regions of interest (ROIs) compared to normal appearing white matter (NAWM), CBV was reduced 25.9% in lesion ROIs compared to NAWM, and MTT increased 12.9%. For capillary perfusion metrics (via spin-echo (SE)), CBF-SE was reduced 35.7% in lesion ROIs compared to NAWM, CBV-SE was reduced 35.2% in lesion ROIs compared to NAWM, and MTT-SE increased 9.1%. Capillary-level CBF was correlated (ρ = 0.34, p = 0.024) with white matter microstructural integrity in lesion ROIs. Conclusion This study demonstrates that lesion perfusion is reduced at both the global and capillary level and capillary-associated hypoperfusion is associated with reduced white matter microstructural integrity in RRMS.

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Association of cerebral blood flow with myelin content in cognitively unimpaired adults

Cited by 26 publications

References 38 publications

Maturation and degeneration of the human brainstem across the adult lifespan

Maturation and degeneration of the human brainstem across the adult lifespan

Assessment of cognitive impairment after acute cerebral infarction with T1 relaxation time measured by MP2RAGE sequence and cerebral hemodynamic by transcranial Doppler

Investigating the relationship between multi-scale perfusion and white matter microstructural integrity in patients with relapsing-remitting MS

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