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@ARTICLE{Lindig:165324,
      author       = {Lindig, Tobias and Ruff, Christer and Rattay, Tim W and
                      König, Stephan and Schöls, Ludger and Schüle, Rebecca and
                      Nägele, Thomas and Ernemann, Ulrike and Klose, Uwe and
                      Bender, Benjamin},
      title        = {{D}etection of spinal long fiber tract degeneration in
                      {HSP}: {I}mproved diffusion tensor imaging.},
      journal      = {NeuroImage: Clinical},
      volume       = {36},
      issn         = {2213-1582},
      address      = {[Amsterdam u.a.]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2022-01602},
      pages        = {103213},
      year         = {2022},
      abstract     = {Spinal diffusion tensor imaging (sDTI) is still a
                      challenging technique for selectively evaluating anatomical
                      areas like the pyramidal tracts (PT), dorsal columns (DC),
                      and anterior horns (AH) in clinical routine and for reliably
                      quantifying white matter anisotropy and diffusivity. In
                      neurodegenerative diseases, the value of sDTI is promising
                      but not yet well understood. The objective of this
                      prospective, single-center study was to evaluate the long
                      fiber tract degeneration within the spinal cord in normal
                      aging (n = 125) and to prove its applicability in pathologic
                      conditions as in patients with molecular genetically
                      confirmed hereditary spastic paraplegias (HSP; n = 40), a
                      prototypical disease of the first motor neuron and in some
                      genetic variants with affection of the dorsal columns. An
                      optimized monopolar Stejskal-Tanner sequence for
                      high-resolution, axial sDTI of the cervical spinal cord at
                      3.0 T with advanced standardized evaluation methods was
                      developed for a robust DTI value estimation of PT, DC, and
                      AH in both groups. After sDTI measurement at C2, an
                      automatic motion correction and an advanced semi-automatic
                      ROI-based, standardized evaluation of white matter
                      anisotropy and diffusivity was performed to obtain regional
                      diffusivity measures for PT, DC, and AH. Reliable and stable
                      sDTI values were acquired in a healthy population without
                      significant decline between age 20 and 65. Reference values
                      for PT, DC, and AH for fractional anisotropy (FA), mean
                      diffusivity (MD), and radial diffusivity (RD) were
                      established. In HSP patients, the decline of the long spinal
                      fiber tracts could be demonstrated by diffusivity
                      abnormalities in the pyramidal tracts with significantly
                      reduced PTFA (p < 0.001), elevated PTRD (p = 0.002) and
                      reduced PTMD (p = 0.003) compared to healthy controls.
                      Furthermore, FA was significantly reduced in DCFA (p <
                      0.001) with no differences in AH. In a genetically
                      homogeneous subgroup of SPG4 patients (n = 12) with
                      affection of the dorsal columns, DCRD significantly
                      correlated with the overall disease severity as measured by
                      the Spastic Paraplegia Rating Scale (SPRS) (r = - 0.713, p =
                      0.009). With the most extensive sDTI study in vivo to date,
                      we showed that axial sDTI combined with motion correction
                      and advanced data post-processing strategies enables robust
                      measurements and is ready to use, allowing recognition and
                      quantification of disease- and age-related changes of the
                      PT, DC, and AH. These results may also encourage the usage
                      of sDTI in other neurodegenerative diseases with spinal cord
                      involvement to explore its capability as selective
                      biomarkers.},
      keywords     = {Animals / Humans / Young Adult / Adult / Middle Aged / Aged
                      / Diffusion Tensor Imaging: methods / Prospective Studies /
                      White Matter: diagnostic imaging / White Matter: pathology /
                      Anisotropy / Pyramidal Tracts: diagnostic imaging /
                      Fractional anisotropy (Other) / Hereditary spastic
                      paraplegia (Other) / Pyramidal degeneration (Other) / Radial
                      diffusivity (Other) / Spinal diffusion tensor imaging
                      (Other)},
      cin          = {Core ICRU / AG Gasser 1 / AG Maetzler},
      ddc          = {610},
      cid          = {I:(DE-2719)1240005 / I:(DE-2719)1210000 /
                      I:(DE-2719)5000024},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9668628},
      pubmed       = {pmid:36270162},
      doi          = {10.1016/j.nicl.2022.103213},
      url          = {https://pub.dzne.de/record/165324},
}