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@ARTICLE{Voorter:274062,
      author       = {Voorter, Paulien H M and Stringer, Michael S and van
                      Dinther, Maud and Kerkhofs, Daniëlle and Dewenter, Anna and
                      Blair, Gordon W and Thrippleton, Michael J and Jaime Garcia,
                      Daniela and Chappell, Francesca M and Janssen, Esther and
                      Kopczak, Anna and Staals, Julie and Ingrisch, Michael and
                      Duering, Marco and Doubal, Fergus N and Dichgans, Martin and
                      van Oostenbrugge, Robert J and Jansen, Jacobus F A and
                      Wardlaw, Joanna M and Backes, Walter H},
      collaboration = {Consortium, SVDs@target},
      title        = {{H}eterogeneity and {P}enumbra of {W}hite {M}atter
                      {H}yperintensities in {S}mall {V}essel {D}iseases
                      {D}etermined by {Q}uantitative {MRI}.},
      journal      = {Stroke},
      volume       = {56},
      number       = {1},
      issn         = {0039-2499},
      address      = {Philadelphia, Pa.},
      publisher    = {Lippincott Williams $\&$ Wilkins},
      reportid     = {DZNE-2025-00043},
      pages        = {128 - 137},
      year         = {2025},
      abstract     = {White matter hyperintensities (WMHs) are established
                      structural imaging markers of cerebral small vessel disease.
                      The pathophysiologic condition of brain tissue varies over
                      the core, the vicinity, and the subtypes of WMH and cannot
                      be interpreted from conventional magnetic resonance imaging.
                      We aim to improve our pathophysiologic understanding of WMHs
                      and the adjacently injured normal-appearing white matter in
                      terms of microstructural and microvascular alterations using
                      quantitative magnetic resonance imaging in patients with
                      sporadic and genetic cerebral small vessel
                      disease.Structural T2-weighted imaging, multishell diffusion
                      imaging, and dynamic contrast-enhanced magnetic resonance
                      imaging were performed at 3T in 44 participants with
                      sporadic cerebral small vessel disease and 32 participants
                      with monogenic cerebral small vessel disease (cerebral
                      autosomal dominant arteriopathy with subcortical infarcts
                      and leukoencephalopathy; 59±12 years, 41 males) between
                      June 2017 and May 2020 as part of the prospective,
                      multicenter (Edinburgh, the United Kingdom; Maastricht, the
                      Netherlands; and Munich, Germany), observational
                      INVESTIGATE-SVDs study (Imaging Neurovascular, Endothelial
                      and Structural Integrity in Preparation to Treat Small
                      Vessel Diseases). The mean diffusivity, free water content,
                      and perfusion (all derived from multishell diffusion
                      imaging), as well as the blood-brain barrier leakage and
                      plasma volume fraction (derived from dynamic
                      contrast-enhanced magnetic resonance imaging), were compared
                      between deep and periventricular WMH types using paired t
                      tests. Additional spatial analyses were performed inside and
                      outside the WMH types to determine the internal
                      heterogeneity and the extent of the penumbras, that is,
                      adjacent white matter at risk for conversion to
                      WMH.Periventricular WMH had higher mean diffusivity, higher
                      free water content, and more plasma volume compared with
                      deep WMH (P<0.001, P=0.01, and P<0.001, respectively). No
                      differences were observed in perfusion (P=0.94) and
                      blood-brain barrier leakage (P=0.65) between periventricular
                      and deep WMHs. The spatial analyses inside WMH and the
                      adjacent white matter revealed a gradual gradient in white
                      matter microstructure, free water content, perfusion, and
                      plasma volume but not in blood-brain barrier leakage.We
                      showed different pathophysiological heterogeneity of the 2
                      WMH types. Periventricular WMHs display more severe damage
                      and fluid accumulation compared with deep WMH, whereas deep
                      WMHs reflect stronger hypoperfusion in the lesion's
                      core.URL: https://www.isrctn.com; Unique identifier:
                      ISRCTN10514229.},
      keywords     = {Humans / White Matter: diagnostic imaging / White Matter:
                      pathology / Middle Aged / Male / Female / Cerebral Small
                      Vessel Diseases: diagnostic imaging / Cerebral Small Vessel
                      Diseases: pathology / Aged / Magnetic Resonance Imaging:
                      methods / Prospective Studies / Blood-Brain Barrier:
                      diagnostic imaging / Blood-Brain Barrier: pathology /
                      Diffusion Magnetic Resonance Imaging: methods / blood-brain
                      barrier (Other) / cerebral small vessel diseases (Other) /
                      diffusion (Other) / magnetic resonance imaging (Other) /
                      perfusion (Other)},
      cin          = {AG Dichgans},
      ddc          = {610},
      cid          = {I:(DE-2719)5000022},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39648904},
      doi          = {10.1161/STROKEAHA.124.047910},
      url          = {https://pub.dzne.de/record/274062},
}