Quantitative MRI of cerebral white matter hyperintensities: A new approach towards understanding the underlying pathology

Iordanishvili, Elene; Schall, Melissa; Loução, Ricardo; Zimmermann, Markus; Kotetishvili, K.V.; Shah, N. Jon; Oros-Peusquens, Ana-Maria

doi:10.1016/j.neuroimage.2019.116077

Cited by 25 publications

(24 citation statements)

References 44 publications

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“…The observation points to the importance of vascular barrier integrity in protecting the brain from edema formation. Latest research identified both edema and demyelination, possibly caused by breakdown of the blood-brain barrier and inflammation, as the major pathological substrates of WMHI (Iordanishvili et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

An Observational Cerebral Magnetic Resonance Imaging Study Following 7 Days at 4554 m

Kühn

Gerlach

Noblé

et al. 2019

High Altitude Medicine & Biology

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Background: In human beings exposed to high altitude, cerebral magnetic resonance imaging (cMRI) revealed alterations ranging from subclinical cerebral edema formation to subtle brain abnormalities. Yet, brain structure after adaptation to high altitude and their recovery after return to lowlands have been rarely investigated. We, therefore, examined 10 healthy individuals by cMRI before, 12 hours after descent (R + 12h), and again 3.5 months (R + 3.5m) after a 7-day high altitude exposure at 4554 m. Results: After their 3-day lasting, stepwise ascent to 4554 m, all subjects suffered acute mountain sickness with a mean Lake Louise score of 5.8-1.7 after the first night at that altitude. Acute mountain sickness completely resolved after 4 days at 4554 m. While 12 hours after descent mean white and gray matter volumes were increased compared with before altitude exposure (p = 0.045 and p = 0.002), these volumes were normalized on R + 3.5m. Moreover, we observed significant focal volume alterations likely attributed to either vasogenic or cytotoxic edema formation. Two subjects presented new brain findings after altitude exposure. In one individual the number of preexisting white matter hyperintensities (WMHI) transiently increased, in the other individual a reversible splenial lesion syndrome (RESLES) emerged. Both findings had resolved 15 and 8 days after descent, respectively. None developed structural lesions like brain atrophy, cerebral infarcts, microbleeds, or highaltitude cerebral edema. Discussion: Three days after complete recovery from acute mountain sickness and after return to low altitude, subclinical vasogenic and cytotoxic edema, RESLES and WMHI are present in high-altitude acclimatized individuals. However, these cerebral alterations are reversible within months at lowland.

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Section: Discussionmentioning

confidence: 99%

An Observational Cerebral Magnetic Resonance Imaging Study Following 7 Days at 4554 m

Kühn

Gerlach

Noblé

et al. 2019

High Altitude Medicine & Biology

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“…Periventricular hyperintensities had lower MPF than deep WM ones. A decrease in MPF corresponds to lesion severity according to Fazekas scale (Iordanishvili et al, 2019).…”

Section: Schizophreniamentioning

confidence: 99%

Macromolecular Proton Fraction as a Myelin Biomarker: Principles, Validation, and Applications

2022

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Macromolecular proton fraction (MPF) is a quantitative MRI parameter describing the magnetization transfer (MT) effect and defined as a relative amount of protons bound to biological macromolecules with restricted molecular motion, which participate in magnetic cross-relaxation with water protons. MPF attracted significant interest during past decade as a biomarker of myelin. The purpose of this mini review is to provide a brief but comprehensive summary of MPF mapping methods, histological validation studies, and MPF applications in neuroscience. Technically, MPF maps can be obtained using a variety of quantitative MT methods. Some of them enable clinically reasonable scan time and resolution. Recent studies demonstrated the feasibility of MPF mapping using standard clinical MRI pulse sequences, thus substantially enhancing the method availability. A number of studies in animal models demonstrated strong correlations between MPF and histological markers of myelin with a minor influence of potential confounders. Histological studies validated the capability of MPF to monitor both demyelination and re-myelination. Clinical applications of MPF have been mainly focused on multiple sclerosis where this method provided new insights into both white and gray matter pathology. Besides, several studies used MPF to investigate myelin role in other neurological and psychiatric conditions. Another promising area of MPF applications is the brain development studies. MPF demonstrated the capabilities to quantitatively characterize the earliest stage of myelination during prenatal brain maturation and protracted myelin development in adolescence. In summary, MPF mapping provides a technically mature and comprehensively validated myelin imaging technology for various preclinical and clinical neuroscience applications.

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“…18 Interestingly, some studies utilizing quantitative parametric mapping and new microstructural modeling methods suggest that increased ISF might be a dominating factor of WMH existence. [19][20][21] Taken together, we hypothesize that increased ISF might be the key link between PVS dilation and WMH.…”

Section: Introductionmentioning

confidence: 99%

Deep white matter hyperintensity is associated with the dilation of perivascular space

Huang

Zhang

Jiaerken

et al. 2021

J Cereb Blood Flow Metab

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Understanding the pathophysiology of white matter hyperintensity (WMH) is necessary to reduce its harmfulness. Dilated perivascular space (PVS) had been found related to WMH. In the present study, we aimed to examine the topological connections between WMH and PVS, and to investigate whether increased interstitial fluid mediates the correlation between PVS and WMH volumes. One hundred and thirty-six healthy elder subjects were retrospectively included from a prospectively collected community cohort. Sub-millimeter T2 weighted and FLAIR images were acquired for assessing the association between PVS and WMH. Diffusion tensor imaging and free-water (FW) analytical methods were used to quantify white matter free water content, and to explore whether it mediates the PVS-WMH association. We found that most (89%) of the deep WMH lesions were spatially connected with PVS, exhibiting several interesting topological types. PVS and WMH volumes were also significantly correlated (r = 0.222, p < 0.001). FW mediated this association in the whole sample (β = 0.069, p = 0.037) and in subjects with relatively high WMH load (β = 0.118, p = 0.006). These findings suggest a tight association between PVS dilation and WMH formation, which might be linked by the impaired glymphatic drainage function and accumulated local interstitial fluid.

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Quantitative MRI of cerebral white matter hyperintensities: A new approach towards understanding the underlying pathology

Cited by 25 publications

References 44 publications

An Observational Cerebral Magnetic Resonance Imaging Study Following 7 Days at 4554 m

An Observational Cerebral Magnetic Resonance Imaging Study Following 7 Days at 4554 m

Macromolecular Proton Fraction as a Myelin Biomarker: Principles, Validation, and Applications

Deep white matter hyperintensity is associated with the dilation of perivascular space

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