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@ARTICLE{Michallek:307247,
      author       = {F. Michallek and M. Dewey and B. Hero and K. Hauptmann and
                      S. Veldhoen and V. Paulsen and K. Astrahantseff and H. E.
                      Deubzer and T. Simon and A. Eggert$^*$ and T. M.
                      Thole-Kliesch},
      title        = {{F}ractal {D}imension of {H}igh-{R}isk {N}euroblastoma
                      {V}ascularity in {MRI} {I}s {A}ssociated with {C}hemotherapy
                      {R}esponse and {E}vent-{F}ree {S}urvival.},
      journal      = {Radiology / Imaging cancer},
      volume       = {8},
      number       = {1},
      issn         = {2638-616X},
      address      = {Oak Brook, IL},
      publisher    = {RSNA, Radiological Society of North America},
      reportid     = {DKFZ-2025-02940},
      pages        = {e250070},
      year         = {2026},
      abstract     = {Purpose To assess therapeutic and prognostic implications
                      of perfusion characterization by fractal analysis using
                      routine MRI in high-risk primary neuroblastomas and to
                      establish a pathophysiologic connection between vascularity
                      phenotype, perfusion imaging characteristics, and treatment
                      response. Materials and Methods In a retrospective cohort
                      study across 30 centers, MRI data of patients with high-risk
                      neuroblastoma (June 2005-February 2021) were collected at
                      the time point of diagnosis (TP1) and after induction
                      chemotherapy before surgery (TP2), with data split into
                      separate discovery (single-center) and validation cohorts
                      (29 centers). Fractal analysis was performed on
                      contrast-enhanced, fat-saturated, T1-weighted sequences at
                      both time points to obtain voxel-wise local fractal
                      dimension (FD) maps for predicting volumetric tumor
                      response. The association of global FD with event-free
                      survival (EFS) was assessed using a Cox proportional hazards
                      model. Additionally, FD was calculated from CD34-stained
                      endothelium in selected histologic tumor samples. Accuracy
                      of response prediction, prognostic value for EFS, and
                      correlation between FD of immunohistochemical vascularity
                      and MRI-derived perfusion were also evaluated. Results In 73
                      patients (median age, 3 years [IQR, 3]; 39 male patients;
                      discovery cohort, n = 36; validation cohort, n = 37), local
                      FD maps helped predict volumetric tumor response to
                      induction chemotherapy between TP1 and TP2 with good
                      accuracy (root mean squared error, 47.78 mL; R2 = 0.94; P <
                      .001), visualizing intratumor high perfusion complexity in
                      areas with low response potential. In multivariate Cox
                      proportional hazards modeling, MYCN status (hazard ratio,
                      2.30; $95\%$ CI: 1.16, 4.55; P = .017) and global FD at TP2
                      (hazard ratio, 0.65; $95\%$ CI: 0.47, 0.88; P = .006) were
                      significantly associated with EFS. Complexity of both
                      CD34-immunohistochemical microvascularity (1.23 ± 0.09 [SD]
                      to 1.44 ± 0.07, P < .001) and MRI perfusion (3.40 ± 0.04
                      to 3.53 ± 0.07, P < .001) increased throughout induction
                      chemotherapy. Conclusion Fractal analysis of MRI-derived
                      perfusion complexity was associated with spatial
                      heterogeneity of chemotherapy response and stratified
                      prognosis in MYCN nonamplified high-risk neuroblastoma,
                      supporting its potential as an imaging biomarker linked to
                      microvascular architecture. German Clinical Trial Registry:
                      DRKS00023442 Keywords: Pediatrics, MR-Imaging,
                      Nervous-Peripheral, Fractal Analysis, Tissue
                      Characterization, Tumor Response Supplemental material is
                      available for this article. © RSNA, 2025.},
      keywords     = {Humans / Neuroblastoma: drug therapy / Neuroblastoma:
                      diagnostic imaging / Neuroblastoma: blood supply /
                      Neuroblastoma: pathology / Male / Female / Magnetic
                      Resonance Imaging: methods / Fractals / Retrospective
                      Studies / Child, Preschool / Child / Infant / Prognosis /
                      Induction Chemotherapy / Disease-Free Survival /
                      Neovascularization, Pathologic: diagnostic imaging / Fractal
                      Analysis (Other) / MR-Imaging (Other) / Nervous-Peripheral
                      (Other) / Pediatrics (Other) / Tissue Characterization
                      (Other) / Tumor Response (Other)},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41384821},
      doi          = {10.1148/rycan.250070},
      url          = {https://inrepo02.dkfz.de/record/307247},
}