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T2-weighted images are superior to other MR image types for the determination of diffuse intrinsic pontine glioma intratumoral heterogeneity

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Abstract

Purpose

Diffuse intrinsic pontine glioma (DIPG) remains the main cause of death in children with brain tumors. Given the inefficacy of numerous peripherally delivered agents to treat DIPG, convection enhanced delivery (CED) of therapeutic agents is a promising treatment modality. The purpose of this study was to determine which MR imaging type provides the best discrimination of intratumoral heterogeneity to guide future stereotactic implantation of CED catheters into the most cellular tumor regions.

Methods

Patients ages 18 years or younger with a diagnosis of DIPG from 2000 to 2015 were included. Radiographic heterogeneity index (HI) of the tumor was calculated by measuring the standard deviation of signal intensity of the tumor (SDTumor) normalized to the genu of the corpus callosum (SDCorpus Callosum). Four MR image types (T2-weighted, contrast-enhanced T1-weighted, FLAIR, and ADC) were analyzed at several time points both before and after radiotherapy and chemotherapy. HI values across these MR image types were compared and correlated with patient survival.

Results

MR images from 18 patients with DIPG were evaluated. The mean survival ± standard deviation was 13.8 ± 13.7 months. T2-weighted images had the highest HI (mean ± SD, 5.1 ± 2.5) followed by contrast-enhanced T1-weighted images (3.7 ± 1.5), FLAIR images (3.0 ± 1.1), and ADC maps (1.6 ± 0.4). ANOVA demonstrated that HI values were significantly higher for T2-weighted images than FLAIR (p < 0.01) and ADC (p < 0.0001). Following radiotherapy, T2-weighted and contrast-enhanced T1-weighted image HI values increased, while FLAIR and ADC HI values decreased. Univariate and multivariate analyses did not reveal a relationship between HI values and patient survival (p > 0.05).

Conclusions

For children with DIPG, T2-weighted MRI demonstrates the greatest signal intensity variance suggesting tumor heterogeneity. Within this heterogeneity, T2-weighted signal hypointensity is known to correlate with increased cellularity and thus may represent a putative target for CED catheter placement in future clinical trials.

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Acknowledgements

The authors wish to thank Kristy Averette, RN, for assistance with the IRB submission.

Funding

This study was supported by the Southeastern Brain Tumor Foundation (EMT), Rory David Deutsch Foundation (OJB).

Author information

Author notes

  1. Stephen Harward and S. Harrison Farber contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Duke University Medical Center, Box 3272, Durham, NC, 27710, USA

    Stephen Harward, S. Harrison Farber & Eric M. Thompson

  2. Department of Radiology, Duke University Medical Center, Durham, NC, USA

    Michael Malinzak

  3. Department of Pediatrics, Division of Hematology/Oncology, Northwestern University, Chicago, IL, USA

    Oren Becher

  4. Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Box 3272, Durham, NC, 27710, USA

    Eric M. Thompson

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  1. Stephen Harward
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Contributions

Concept and design: Farber, Harward, Becher, Thompson. Acquisition of data: Farber and Harward. Analysis and interpretation of data: all authors. Drafting the article: Farber, Harward, Malinzak, Thompson. Critically revising the article: all authors. Statistical analysis: Farber, Harward, Thompson. Final manuscript approval on behalf of all authors: Thompson.

Corresponding author

Correspondence to Eric M. Thompson.

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Conflict of interest

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Additional information

Portions of this work were presented as proceedings at the AANS Annual Scientific Meeting, American Association of Neurological Surgeons, Los Angeles, CA, USA, April 23, 2017.

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Harward, S., Harrison Farber, S., Malinzak, M. et al. T2-weighted images are superior to other MR image types for the determination of diffuse intrinsic pontine glioma intratumoral heterogeneity. Childs Nerv Syst 34, 449–455 (2018). https://doi.org/10.1007/s00381-017-3659-8

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  • DOI: https://doi.org/10.1007/s00381-017-3659-8

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