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

Interest in white matter hyperintensities (WMH), a radiological biomarker of small vessel disease, is continuously increasing. This is, in most part, due to our better understanding of their association with various clinical disorders, such as stroke and Alzheimer's disease, and the overlapping pathology of WMH with these afflictions. Although post-mortem histological studies have reported various underlying pathophysiological substrates, in vivo research has not been specific enough to fully corroborate these findings. Furthermore, post-mortem studies are not able to capture which pathological processes are the driving force of the WMH severity. The current study attempts to fill this gap by non-invasively investigating the influence of WMH on brain tissue using quantitative MRI (qMRI) measurements of the water content (H2O), the longitudinal (T1) and effective transverse relaxation times (T2∗), as well as the semi-quantitative magnetization transfer ratio (MTR), and bound proton fraction (ƒbound). In total, seventy subjects (age range 50-80 years) were selected from a population-based aging cohort study, 1000BRAINS. Normal appearing grey (NAGM) and white matter (NAWM), as well as deep (DWMH) and periventricular (PWMH) white matter hyperintensities, were segmented and characterized in terms of their quantitative properties. The subjects were then further divided into four grades according to the Fazekas rating scale of severity. Groupwise analyses of the qMRI values in each tissue class were performed. All five qMRI parameters showed significant differences between WMH and NAWM (p < 0.001). Importantly, the parameters differed between DWMH and PWMH, the latter having higher H2O, T1, T2∗ and lower MTR and ƒbound values (p < 0.001). Following grading according to the Fazekas scale, DWMH showed an increase in the water content, T1 and a decrease in bound proton fraction corresponding to severity, exhibiting significant changes in grade 3 (p < 0.001), while NAWM revealed significantly higher H2O values in grade 3 compared to grade 0 (p < 0.001). PWMH demonstrated an increase in T2∗ values (significant in grade 3, P < 0.001). These results are in agreement with previous histopathological studies and support the interpretation that both edema and myelin loss due to a possible breakdown of the blood-brain barrier and inflammation are the major pathological substrates turning white matter into DWMH. Edema being an earlier contributing factor to the pathology, as expressed in the elevated water content values in NAWM with increasing severity. In the case of PWMH, an altered fluid dynamic and cerebrospinal fluid leakage exacerbate the changes. It was also found that the pathology, as monitored by qMRI, evolves faster in DWMH than in the PWMH following the severity.

Iordanishvili E ，Schall M ，Loução R ，Zimmermann M ，Kotetishvili K ，Shah NJ ，Oros-Peusquens AM ... -  《-》

Amide Proton Transfer MRI Could Be Used to Evaluate the Pathophysiological Status of White Matter Hyperintensities.

The pathophysiology of white matter hyperintensities (WMH) remains unclear, investigations of amide proton transfer (APT) signals in WMH disease may provide relevant pathophysiological information. To evaluate the APT signals differences and heterogeneity of WMH and adjacent normal-appearing white matter (NAWM) at different Fazekas grades and different locations. Prospective. In all, 180 WMH patients (age, 40-76; male/female, 77/103) and 59 healthy controls (age, 42-70; male/female, 23/36). A 3 T; 3D fluid-attenuated inversion recovery (FLAIR), 3D APT-weighted (APTw). The mean APTw values (APTwmean ) and the APTw signals heterogeneity (APTwmax-min ) among different grades WMH and NAWM and the APTwmean of the same grade deep WMH (DWMH) and paraventricular WMH (PWMH) were calculated and compared. Regions of interests were delineated on WMH lesions, NAWM and healthy white matter. One-way analysis of variance (ANOVA); independent sample t test; Chi-square test. Significance level: P < 0.05. APTwmean among different grade WMH (from grade 0 to 3, 0.58 ± 0.14% vs. 0.29 ± 0.23% vs. 0.37 ± 0.24% vs. 0.61 ± 0.22%, respectively) were significantly different except between grade 1 and 2 (P = 0.27) and between grade 0 and 3 (P = 0.97). The differences in APTwmean between WMH and NAWM were significant (WMH vs. NAWM from grade 1 to 3, 0.29% ± 0.23% vs. 0.55% ± 0.27%; 0.37% ± 0.24% vs. 0.59% ± 0.22%; 0.61% ± 0.22% vs. 0.42% ± 0.24%, respectively). Lower APTwmean values were found only in grade 3 NAWM than other grades NAWM and controls. The APTwmax-min values of grade 1-3 WMH (0.38% ± 0.27% vs. 0.51% ± 0.31% vs. 0.67% ± 0.34%, respectively) were significantly different. Higher APTmean values were found only in grade 2 PWMH (0.47% ± 0.22% vs. 0.32% ± 0.24%). Significant differences of APT signals were found in WMH of different Fazekas grades and different locations. 2 TECHNICAL EFFICACY: Stage 3.

Guo Z ，Meng Z ，Mu R ，Qin X ，Zhuang Z ，Zheng W ，Liu F ，Zhu X ... -  《-》

Heterogeneity of white matter hyperintensities in Alzheimer's disease: post-mortem quantitative MRI and neuropathology.

Gouw AA ，Seewann A ，Vrenken H ，van der Flier WM ，Rozemuller JM ，Barkhof F ，Scheltens P ，Geurts JJ ... -  《-》

Can white matter hyperintensities based Fazekas visual assessment scales inform about Alzheimer's disease pathology in the population?

Pradeep A ，Raghavan S ，Przybelski SA ，Preboske GM ，Schwarz CG ，Lowe VJ ，Knopman DS ，Petersen RC ，Jack CR Jr ，Graff-Radford J ，Cogswell PM ，Vemuri P ... -  《Alzheimers Research & Therapy》

Multi-parametric quantitative MRI of normal appearing white matter in multiple sclerosis, and the effect of disease activity on T2.

Reitz SC ，Hof SM ，Fleischer V ，Brodski A ，Gröger A ，Gracien RM ，Droby A ，Steinmetz H ，Ziemann U ，Zipp F ，Deichmann R ，Klein JC ... -  《-》