title: Evaluation of low-grade glioma structural changes after chemotherapy using DTI-based histogram analysis and functional diffusion maps.
abstract: OBJECTIVE
  To explore the role of diffusion tensor imaging (DTI)-based histogram analysis and functional diffusion maps (fDMs) in evaluating structural changes of low-grade gliomas (LGGs) receiving temozolomide (TMZ) chemotherapy.
  
  
  METHODS
  Twenty-one LGG patients underwent 3T-MR examinations before and after three and six cycles of dose-dense TMZ, including 3D-fluid-attenuated inversion recovery (FLAIR) sequences and DTI (b = 1000 s/mm(2), 32 directions). Mean diffusivity (MD), fractional anisotropy (FA), and tensor-decomposition DTI maps (p and q) were obtained. Histogram and fDM analyses were performed on co-registered baseline and post-chemotherapy maps. DTI changes were compared with modifications of tumour area and volume [according to Response Assessment in Neuro-Oncology (RANO) criteria], and seizure response.
  
  
  RESULTS
  After three cycles of TMZ, 20/21 patients were stable according to RANO criteria, but DTI changes were observed in all patients (Wilcoxon test, P ≤ 0.03). After six cycles, DTI changes were more pronounced (P ≤ 0.005). Seventy-five percent of patients had early seizure response with significant improvement of DTI values, maintaining stability on FLAIR. Early changes of the 25th percentiles of p and MD predicted final volume change (R(2) = 0.614 and 0.561, P < 0.0005, respectively). TMZ-related changes were located mainly at tumour borders on p and MD fDMs.
  
  
  CONCLUSIONS
  DTI-based histogram and fDM analyses are useful techniques to evaluate the early effects of TMZ chemotherapy in LGG patients.
  
  
  CONCLUSIONS
  • DTI helps to assess the efficacy of chemotherapy in low-grade gliomas. • Histogram analysis of DTI metrics quantifies structural changes in tumour tissue. • Functional diffusion maps (fDMs) spatially localize the changes of DTI metrics. • Changes in DTI histograms and fDMs precede changes in conventional MRI. • Early changes in DTI histograms and fDMs correlate with seizure response.
authors: Neuroradiology Unit and CERMAC, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milano, Italy.
authors: Antonella
authors: A
authors: Castellano
authors: Department of Mathematics and Physics "Ennio De Giorgi" and A.D.A.M. (Advanced Data Analysis in Medicine), University of Salento, Lecce, Italy.
authors: Marina
authors: M
authors: Donativi
authors: Department of Neuro-oncology, University of Torino, Turin, Italy.
authors: Roberta
authors: R
authors: Rudà
authors: Department of Mathematics and Physics "Ennio De Giorgi" and A.D.A.M. (Advanced Data Analysis in Medicine), University of Salento, Lecce, Italy.|INFN (National Institute of Nuclear Physics), Lecce, Italy.
authors: Giorgio
authors: G
authors: De Nunzio
authors: Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, and Humanitas Research Hospital, Rozzano, MI, Italy.
authors: Marco
authors: M
authors: Riva
authors: Neuroradiology Unit and CERMAC, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milano, Italy.
authors: Antonella
authors: A
authors: Iadanza
authors: Department of Neuro-oncology, University of Torino, Turin, Italy.
authors: Luca
authors: L
authors: Bertero
authors: School of Science and Technology, Computer Science Division, University of Camerino, Camerino, MC, Italy.
authors: Matteo
authors: M
authors: Rucco
authors: Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, and Humanitas Research Hospital, Rozzano, MI, Italy.
authors: Lorenzo
authors: L
authors: Bello
authors: Department of Neuro-oncology, University of Torino, Turin, Italy.
authors: Riccardo
authors: R
authors: Soffietti
authors: Neuroradiology Unit and CERMAC, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milano, Italy. falini.andrea@hsr.it.
authors: Andrea
authors: A
authors: Falini
mesh_terms: D000328:Adult; D016880:Anisotropy; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000188:drug therapy; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D005910:Glioma / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D000970:Antineoplastic Agents
keywords: Chemotherapy; Diffusion Tensor Imaging; Glioma; Magnetic Resonance Imaging; Response Evaluation Criteria