Spatiotemporal characterisation of ischaemic lesions in transient stroke animal models using diffusion free water elimination and mapping MRI with echo time dependence

Farrher, Ezequiel; Chiang, Chia‐Wen; Cho, Kuan-Hung; Grinberg, Farida; Buschbeck, Richard P.; Chen, Ming-Jye; Wu, Kuo‐Jen; Wang, Yun; Huang, Sheng-Min; Abbas, Zaheer; Choi, C.; Shah, N. Jon; Li, Kuo

doi:10.1016/j.neuroimage.2021.118605

Cited by 6 publications

(11 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…47,48,29 These free-water increases seem to diminish in the surrounding tissue within the first month, suggesting the regredience of edema in this time period. On the other hand, consistent with previous imaging and preclinical histopathological studies 15,27,46,22 , we observed free-water increases 3 and 12 months after stroke that are most likely explained by secondary mechanisms of neurodegeneration at the microscopic level such as fluid-filled cavitation and axonal loss (i.e., atrophy) leading to larger extracellular spaces. Intriguingly, these changes were also observed in the normal appearing white matter surrounding the stroke lesion.…”

Section: Free-water Alterationssupporting

confidence: 91%

“…44 The free-water metric measures the amount of freely diffusing water molecules in the extracellular space and may thus be a sensitive marker of vasogenic edema due to upregulated immune responses and consecutive blood-brain-barrier leakage. 23,25,45,46 It is therefore conceivable that the early increases in extracellular diffusivity, which we observe in and beyond the lesion 3-5 days after stroke, are attributable to vasogenic edema and inflammatory processes. 47,48,29 These free-water increases seem to diminish in the surrounding tissue within the first month, suggesting the regredience of edema in this time period.…”

Section: Free-water Alterationsmentioning

confidence: 89%

See 1 more Smart Citation

Longitudinal alterations in brain microstructure surrounding subcortical ischemic stroke lesions detected by free-water imaging

Nägele

Petersen

Mayer

et al. 2023

Preprint

View full text Add to dashboard Cite

BackgroundFree-water imaging identifies subtle changes in white matter microstructure indicative of cellular and extracellular pathologies not visible on conventional stroke MRI. We explore the spatial extent and temporal trajectory of free-water changes in patients with subcortical stroke and their relationship to symptoms, as well as lesion evolution.MethodsTwenty-seven patients with isolated subcortical infarct with mean age of 66.73 (SD 11.57) and median initial NIHSS score of 4 (IQR 4) received MRI 3-5 days, 1 month, 3 months and 12 months after symptom-onset. After lesion segmentation, 8 unique tissue shells (2 mm distance) surrounding stroke lesions were created. Extracellular free-water and fractional anisotropy of the tissue (FAT), derived from diffusion-weighted MRI, were averaged within tissue shells/stroke lesions, and normalized to corresponding contralateral regions. Linear mixed-effects models and t-tests were used for statistics. Baseline imaging measures were correlated with clinical outcomes 3 months after stroke.ResultsWe found increased free-water and decreased FATin the stroke lesion, as well as the surrounding tissue with a characteristic spatio-temporal distribution. Free-water and FATchanges were most prominent within the lesion and gradually became less with increasing distance from the lesion. Free-water elevations continuously in-creased over time and peaked after 12 months. In contrast, FATdecreases were most pronounced 1 month after stroke, after which there was a steady increase leading to similarly reduced FATlevels 12 months compared to 3-5 days after stroke. Higher perilesional free-water and higher lesional FATat baseline were correlated with greater reductions in lesion size, while there were no associations with clinical measures.ConclusionsBoth free-water and FATare altered beyond isolated subcortical stroke lesions. The spatial extent of these extracellular and cellular changes varies differentially over time indicating a dynamic parenchymal response to the initial insult characterized by vasogenic edema, cellular damage and white matter atrophy

show abstract

Section: Free-water Alterationssupporting

confidence: 91%

Section: Free-water Alterationsmentioning

confidence: 89%

Longitudinal alterations in brain microstructure surrounding subcortical ischemic stroke lesions detected by free-water imaging

Nägele

Petersen

Mayer

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…21 FW fraction is a novel measure inferring on unrestricted extracellular water and is associated with ischemic vasogenic edema. 20 FW fraction is elevated in patients with MCI and dementia 22 and associated with poorer cognitive function and dementia progression. 23 To our knowledge, only 1 previous study explored the association between longitudinal changes in sleep duration over time and multiple ATV(N) neuroimaging biomarkers.…”

Section: Discussionmentioning

confidence: 98%

“…19 FW corresponds to the fraction of unrestricted extracellular water in white matter, where a higher value is associated with ischemic vasogenic edema. 20…”

Section: Methodsmentioning

confidence: 99%

Association of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology

Baril,

Kojis,

Himali

et al. 2024

Neurology

View full text Add to dashboard Cite

Background and Objectives Both short and long sleep duration were previously associated with incident dementia, but underlying mechanisms remain unclear. We evaluated how self-reported sleep duration and its change over time associate with (A)myloid, (T)au, (N)eurodegeneration, and (V)ascular neuroimaging markers of Alzheimer disease. Methods Two Framingham Heart Study overlapping samples were studied: participants who underwent 11C-Pittsburg Compound B amyloid and 18F-flortaucipir tau PET imaging and participants who underwent an MRI. MRI metrics estimated neurodegeneration (total brain volume) and cerebrovascular injuries (white matter hyperintensities [WMHs] volume, covert brain infarcts, free-water [FW] fraction). Self-reported sleep duration was assessed and split into categories both at the time of neuroimaging testing and approximately 13 years before: short ≤6 hours. average 7–8 hours, and long ≥9 hours. Logistic and linear regression models were used to examine sleep duration and neuroimaging metrics. Results The tested cohort was composed of 271 participants (age 53.6 ± 8.0 years; 51% male) in the PET imaging sample and 2,165 participants (age 61.3 ± 11.1 years; 45% male) in the MRI sample. No fully adjusted association was observed between cross-sectional sleep duration and neuroimaging metrics. In fully adjusted models compared with consistently sleeping 7–8 hours, groups transitioning to a longer sleep duration category over time had higher FW fraction (short to average β [SE] 0.0062 [0.0024], p = 0.009; short to long β [SE] 0.0164 [0.0076], p = 0.031; average to long β [SE] 0.0083 [0.0022], p = 0.002), and those specifically going from average to long sleep duration also had higher WMH burden (β [SE] 0.29 [0.11], p = 0.007). The opposite associations (lower WMH and FW) were observed in participants consistently sleeping ≥9 hours as compared with people consistently sleeping 7–8 hours in fully adjusted models (β [SE] −0.43 [0.20], p = 0.028; β [SE] −0.019 [0.004], p = 0.020). Each hour of increasing sleep (continuous, β [SE] 0.12 [0.04], p = 0.003; β [SE] 0.002 [0.001], p = 0.021) and extensive increase in sleep duration (≥2 hours vs 0 ± 1 hour change; β [SE] 0.24 [0.10], p = 0.019; β [SE] 0.0081 [0.0025], p = 0.001) over time was associated with higher WMH burden and FW fraction in fully adjusted models. Sleep duration change was not associated with PET amyloid or tau outcomes. Discussion Longer self-reported sleep duration over time was associated with neuroimaging biomarkers of cerebrovascular pathology as evidenced by higher WMH burden and FW fraction. A longer sleep duration extending over time may be an early change in the neurodegenerative trajectory.

show abstract

“…Although occasionally an adjustment for T1 and/or T2 is made (Pasternak et al 2009, Jerome et al 2016, Veraart et al 2018, Farrher et al 2021, in the majority of dMRI studies that use multicompartment models, the correct accounting for all three (PD, T1, T2) terms, as recently done by Abbas et al (2014), Rydhög et al(2019) or Grussu et al (2020), is the exception rather than the rule. Specifically for the free water model, the PD, T1, T2 terms are usually assumed to be the same across the compartments; although, the studies that use such models often acknowledge potential differences in compartment specific T1, T2 and PD, and that experiment choices for TR and TE would alter the relative weight of these terms (Afzali et al 2021).…”

Section: Introductionmentioning

confidence: 99%

The distortions of the free water model for diffusion MRI data when assuming single compartment relaxometry and proton density

et al. 2023

View full text Add to dashboard Cite

Objective: To document the bias of the simplified free water model of diffusion MRI (dMRI) signal vis-a-vis a specific model which, in addition to diffusion, incorporates compartment-specific proton density (PD), T1 recovery during repetition time (TR), and T2 decay during echo time (TE). Approach: Both models assume that volume fraction f of the total signal in any voxel arises from the free water compartment (fw) such as cerebrospinal fluid (CSF) or edema, and the remainder (1-f) from hindered water (hw) which is constrained by cellular structures such as white matter (WM). The specific and simplified models are compared on a synthetic dataset, using a range of PD, T1 and T2 values. We then fit the models to an in vivo healthy brain dMRI dataset. For both synthetic and in vivo data we use experimentally feasible TR, TE, signal-to-noise ratio (SNR) and physiologically plausible diffusion profiles. Main Results: From the simulations we see that the difference between the estimated simplified f and specific f is largest for mid-range ground-truth f, and it increases as SNR increases. The estimation of volume fraction f is sensitive to the choice of model, simplified or specific, but the estimated diffusion parameters are robust. Specific f is more accurate and precise than simplified f. In the white matter (WM) regions of the in vivo images, specific f is lower than simplified f. Significance: In dMRI models for free water, accounting for compartment specific PD, T1 and T2, in addition to diffusion, improves the estimation of model parameters. This extra model specification attenuates the estimation bias of compartmental volume fraction without affecting the estimation of other diffusion parameters.

show abstract

Spatiotemporal characterisation of ischaemic lesions in transient stroke animal models using diffusion free water elimination and mapping MRI with echo time dependence

Cited by 6 publications

References 71 publications

Longitudinal alterations in brain microstructure surrounding subcortical ischemic stroke lesions detected by free-water imaging

Longitudinal alterations in brain microstructure surrounding subcortical ischemic stroke lesions detected by free-water imaging

Association of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology

The distortions of the free water model for diffusion MRI data when assuming single compartment relaxometry and proton density

Contact Info

Product

Resources

About