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@ARTICLE{Iordanishvili:864417,
      author       = {Iordanishvili, Elene and Schall, Melissa and Loução,
                      Ricardo and Zimmermann, Markus and Kotetishvili, Ketevan and
                      Shah, N. Jon and Oros-Peusquens, Ana-Maria},
      title        = {{Q}uantitative {MRI} of cerebral white matter
                      hyperintensities: {A} new approach towards understanding the
                      underlying pathology},
      journal      = {NeuroImage},
      volume       = {202},
      issn         = {1053-8119},
      address      = {Orlando, Fla.},
      publisher    = {Academic Press},
      reportid     = {FZJ-2019-04201},
      pages        = {116077 -},
      year         = {2019},
      abstract     = {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.},
      cin          = {INM-11 / INM-4 / JARA-BRAIN},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-11-20170113 / I:(DE-Juel1)INM-4-20090406 /
                      $I:(DE-82)080010_20140620$},
      pnm          = {573 - Neuroimaging (POF3-573)},
      pid          = {G:(DE-HGF)POF3-573},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31398433},
      UT           = {WOS:000491861000081},
      doi          = {10.1016/j.neuroimage.2019.116077},
      url          = {https://juser.fz-juelich.de/record/864417},
}