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@ARTICLE{KarimianJazi:294843,
      author       = {K. Karimian-Jazi and N. Enbergs and E. Golubtsov and K.
                      Schregel and J. Ungermann and H. Fels-Palesandro and D.
                      Schwarz and V. Sturm and J. M. Kernbach and D. Batra and F.
                      Ippen$^*$ and I. Pflüger and N. von Knebel Doeberitz$^*$
                      and S. Heiland and L. Bunse$^*$ and M. Platten$^*$ and F.
                      Winkler$^*$ and W. Wick$^*$ and D. Paech$^*$ and M. Bendszus
                      and M. Breckwoldt$^*$},
      title        = {{D}ifferentiating {G}lioma {R}ecurrence and
                      {P}seudoprogression by {APT}w {CEST} {MRI}.},
      journal      = {Investigative radiology},
      volume       = {60},
      number       = {6},
      issn         = {0020-9996},
      address      = {[Erscheinungsort nicht ermittelbar]},
      publisher    = {Ovid},
      reportid     = {DKFZ-2024-02553},
      pages        = {414-422},
      year         = {2025},
      note         = {#EA:B320#LA:D170# / 2025 Jun 1;60(6):414-422},
      abstract     = {Recurrent glioma is highly treatment resistant due to its
                      metabolic, cellular, and molecular heterogeneity and
                      invasiveness. Tumor monitoring by conventional MRI has
                      shortcomings to assess these key glioma characteristics.
                      Recent studies introduced chemical exchange saturation
                      transfer for metabolic imaging in oncology and assessed its
                      diagnostic value for newly diagnosed glioma. This
                      prospective study investigates amide proton
                      transfer-weighted (APTw) MRI at 3 T as an imaging biomarker
                      to elucidate the molecular heterogeneity and invasion
                      patterns of recurrent glioma in comparison to
                      pseudoprogression (PsPD).We performed a monocenter,
                      prospective trial and screened 371 glioma patients who
                      received tumor monitoring between August 2021 and March 2024
                      at our institution. The study included IDH wildtype
                      astrocytoma and IDH mutant astrocytoma and
                      oligodendroglioma, graded according to the WHO 2021
                      classification. Patients had received clinical standard of
                      care treatment including surgical resection and
                      radiochemotherapy prior to study inclusion. Patients were
                      monitored by 3 monthly MRI follow-up imaging, and response
                      assessment was performed according to the RANO criteria.
                      Within this cohort, we identified 30 patients who presented
                      with recurrent glioma and 12 patients with PsPD. In addition
                      to standard anatomical sequences (FLAIR and T1-w Gd-enhanced
                      sequences), MRI included APTw imaging. After sequence
                      co-registration, semiautomated segmentation was performed of
                      the FLAIR lesion, CE lesion, resection cavity, and the
                      contralateral normal-appearing white matter, and APTw
                      signals were quantified in these regions of interest.APTw
                      values were highest in solid, Gd-enhancing tumor parts as
                      compared with the nonenhancing FLAIR lesion (APTw: $1.99\%$
                      vs $1.36\%,$ P = 0.001), whereas there were no detectable
                      APTw alterations in the normal-appearing white matter (APTw:
                      $0.005\%,$ P < 0.001 compared with FLAIR). Patients with
                      progressive disease had higher APTw levels compared with
                      patients with PsPD (APTw: $1.99\%$ vs $1.26\%,$ P = 0.008).
                      Chemical exchange saturation transfer identified
                      heterogeneity within the FLAIR lesion that was not
                      detectable by conventional sequences. There were also focal
                      APTw signal peaks within contrast enhancing lesions as
                      putative metabolic hotspots within recurrent glioma. The
                      resection cavity developed an APTw increase at recurrence
                      that was not detectable prior to recurrence nor in patients
                      with PsPD (APTw before recurrence: $0.6\%$ vs $2.68\%$ at
                      recurrence, P = 0.03).Our study shows that APTw imaging can
                      differentiate PD and PsPD. We identify previously
                      undetectable imaging patterns during glioma recurrence,
                      which include alterations within resection cavity associated
                      with disease progression. Our work highlights the clinical
                      potential of APTw imaging for glioma monitoring and further
                      establishes it as an imaging biomarker in neuro-oncology.},
      cin          = {B320 / HD01 / B300 / E010 / D170},
      ddc          = {610},
      cid          = {I:(DE-He78)B320-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B300-20160331 / I:(DE-He78)E010-20160331 /
                      I:(DE-He78)D170-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39644107},
      doi          = {10.1097/RLI.0000000000001145},
      url          = {https://inrepo02.dkfz.de/record/294843},
}