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@ARTICLE{Farrher:902165,
      author       = {Farrher, Ezequiel and Chiang, Chia-Wen and Cho, Kuan-Hung
                      and Grinberg, Farida and Buschbeck, Richard P. and Chen,
                      Ming-Jye and Wu, Kuo-Jen and Wang, Yun and Huang, Sheng-Min
                      and Abbas, Zaheer and Choi, Chang-Hoon and Shah, N. Jon and
                      Kuo, Li-Wei},
      title        = {{S}patiotemporal characterisation of ischaemic lesions in
                      transient stroke animal models using diffusion free water
                      elimination and mapping {MRI} with echo time dependence},
      journal      = {NeuroImage},
      volume       = {244},
      issn         = {1053-8119},
      address      = {Orlando, Fla.},
      publisher    = {Academic Press},
      reportid     = {FZJ-2021-04074},
      pages        = {118605 -},
      year         = {2021},
      abstract     = {Background and purposeThe excess fluid as a result of
                      vasogenic oedema and the subsequent tissue cavitation
                      obscure the microstructural characterisation of ischaemic
                      tissue by conventional diffusion and relaxometry MRI. They
                      lead to a pseudo-normalisation of the water diffusivity and
                      transverse relaxation time maps in the subacute and chronic
                      phases of stroke. Within the context of diffusion MRI, the
                      free water elimination and mapping method (FWE) with echo
                      time dependence has been proposed as a promising approach to
                      measure the amount of free fluid in brain tissue robustly
                      and to eliminate its biasing effect on other biomarkers. In
                      this longitudinal study of transient middle cerebral artery
                      occlusion (MCAo) in the rat brain, we investigated the use
                      of FWE MRI with echo time dependence for the
                      characterisation of the tissue microstructure and explored
                      the potential of the free water fraction as a novel
                      biomarker of ischaemic tissue condition.MethodsAdult rats
                      received a transient MCAo. Diffusion- and transverse
                      relaxation-weighted MRI experiments were performed
                      longitudinally, pre-occlusion and on days 1, 3, 4, 5, 6, 7
                      and 10 after MCAo on four rats. Histology was performed for
                      non-stroke and 1, 3 and 10 days after MCAo on three
                      different rats at each time point.ResultsThe free water
                      fraction was homogeneously increased in the ischaemic cortex
                      one day after stroke. Between three and ten days after
                      stroke, the core of the ischaemic tissue showed a
                      progressive normalisation in the amount of free water,
                      whereas the inner and outer border zones of the ischaemic
                      cortex depicted a large, monotonous increase with time. The
                      specific lesions in brain sections were verified by $H\&E$
                      and immunostaining. The tissue-specific diffusion and
                      relaxometry MRI metrics in the ischaemic cortex were
                      significantly different compared to their conventional
                      counterpart.ConclusionsOur results demonstrate that the free
                      water fraction in FWE MRI with echo time dependence is a
                      valuable biomarker, sensitive to the progressive
                      degeneration in ischaemic tissue. We showed that part of the
                      heterogeneity previously observed in conventional parameter
                      maps can be accounted for by a heterogeneous distribution of
                      free water in the tissue. Our results suggest that the
                      temporal evolution of the free fluid fraction map at the
                      core and inner border zone can be associated with the
                      pathological changes linked to the evolution of vasogenic
                      oedema. Namely, the homogeneous increase in free water one
                      day after stroke and its tendency to normalise in the core
                      of the ischaemic cortex starting three days after stroke,
                      followed by a progressive increase in free water at the
                      inner border zone from three to ten days after stroke.
                      Finally, the monotonous increase in free fluid in the outer
                      border zone of the cortex reflects the formation of
                      fluid-filled cysts.},
      cin          = {INM-4 / INM-11 / JARA-BRAIN},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-4-20090406 / I:(DE-Juel1)INM-11-20170113 /
                      I:(DE-Juel1)VDB1046},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {34592438},
      UT           = {WOS:000710098200001},
      doi          = {10.1016/j.neuroimage.2021.118605},
      url          = {https://juser.fz-juelich.de/record/902165},
}