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Evaluation of low-grade glioma structural changes after chemotherapy using DTI-based histogram analysis and functional diffusion maps

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Abstract

Objectives

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/mm2, 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 (R2 = 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.

Key Points

• 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.

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Abbreviations

DTI:

diffusion tensor imaging

MRI:

magnetic resonance imaging

fDM:

functional diffusion maps

LGGs:

low-grade gliomas

HGGs:

high-grade gliomas

WM:

white matter

RANO:

Response Assessment in Neuro-Oncology

FLAIR:

fluid-attenuated inversion recovery

TMZ:

Temozolomide

PCV:

Procarbazine, Lomustine, and Vincristine

PR:

partial response

mR:

minor response

SD:

stable disease

PD:

progressive disease

vPR:

volumetric partial response

vmR:

volumetric minor response

vSD:

volumetric stable disease

vPD:

volumetric progression of disease

ADC:

apparent diffusion coefficient

FA:

fractional anisotropy

MD:

mean diffusivity

p :

pure isotropic diffusion

q :

pure anisotropic diffusion

IQR:

interquartile range

ROC:

receiver operating characteristic

AUC:

area under the ROC curve

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Acknowledgments

The scientific guarantor of this publication is Andrea Falini. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. This study has received funding by the Italian Ministry of Health (RF-2009-1530888) and by the Italian Ministry of Education, University, and Research (MIUR PON 254/Ric “Ricerca e competitività 2007-2013”, upgrading of the “Centro ricerche per la salute dell'uomo e dell'ambiente” PONa3_00334). M.R. has received funding by the Fellowship for Abroad 2013 of the Fondazione Italiana per la Ricerca sul Cancro (FIRC). Antonella Castellano conducted this study as partial fulfillment of her PhD in Molecular Medicine, Program in Experimental Neurology, Vita-Salute San Raffaele University, Milan, Italy.

The authors are grateful to Prof. Alessandro Ambrosi that kindly provided statistical advice for this manuscript and Kesshi M. Jordan for English editing. Institutional review board approval was obtained.

Written informed consent was obtained from all patients in this study. Methodology: retrospective, diagnostic study, observational.

Author information

Authors and Affiliations

  1. Neuroradiology Unit and CERMAC, San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Via Olgettina 60, 20132, Milano, Italy

    Antonella Castellano, Antonella Iadanza & Andrea Falini

  2. Department of Mathematics and Physics “Ennio De Giorgi” and A.D.A.M. (Advanced Data Analysis in Medicine), University of Salento, Lecce, Italy

    Marina Donativi & Giorgio De Nunzio

  3. Department of Neuro-oncology, University of Torino, Turin, Italy

    Roberta Rudà, Luca Bertero & Riccardo Soffietti

  4. INFN (National Institute of Nuclear Physics), Lecce, Italy

    Giorgio De Nunzio

  5. Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, and Humanitas Research Hospital, Rozzano, MI, Italy

    Marco Riva & Lorenzo Bello

  6. School of Science and Technology, Computer Science Division, University of Camerino, Camerino, MC, Italy

    Matteo Rucco

Authors
  1. Antonella Castellano
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  2. Marina Donativi
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Correspondence to Andrea Falini.

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Castellano, A., Donativi, M., Rudà, R. et al. Evaluation of low-grade glioma structural changes after chemotherapy using DTI-based histogram analysis and functional diffusion maps. Eur Radiol 26, 1263–1273 (2016). https://doi.org/10.1007/s00330-015-3934-6

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  • DOI: https://doi.org/10.1007/s00330-015-3934-6

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