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Radiogenomics of diffuse intrinsic pontine gliomas (DIPGs): correlation of histological and biological characteristics with multimodal MRI features

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Abstract

Objectives

The diffuse intrinsic pontine gliomas (DIPGs) are now defined by the type of histone H3 mutated at lysine 27. We aimed to correlate the multimodal MRI features of DIPGs, H3K27M mutant, with their histological and molecular characteristics.

Methods

Twenty-seven treatment-naïve children with histopathologically confirmed DIPG H3K27M mutant were prospectively included. MRI performed prior to biopsy included multi-b-value diffusion-weighted imaging, ASL, and dynamic susceptibility contrast (DSC) perfusion imaging. The ADC and cerebral blood flow (CBF) and blood volume (CBV) were measured at the biopsy site. We assessed quantitative histological data, including microvascular density, nuclear density, and H3K27M-positive nuclear density. Gene expression profiling was also assessed in the samples. We compared imaging and histopathological data according to histone subgroup. We correlated MRI quantitative data with histological data and gene expression.

Results

H3.1K27M mutated tumors showed higher ADC values (median 3151 μm2/s vs 1741 μm2/s, p = 0.003), and lower perfusion values (DSC-rCBF median 0.71 vs 1.43, p = 0.002, and DSC-rCBV median 1.00 vs 1.71, p = 0.02) than H3.3K27M ones. They had similar microvascular and nuclear density, but lower H3K27M-positive nuclear density (p = 0.007). The DSC-rCBV was positively correlated to the H3K27M-positive nuclear density (rho = 0.74, p = 0.02). ADC values were not correlated with nuclear density nor perfusion values with microvascular density. The expression of gated channel activity–related genes tended to be inversely correlated with ADC values and positively correlated with DSC perfusion.

Conclusions

H3.1K27M mutated tumors have higher ADC and lower perfusion values than H3.3K27M ones, without direct correlation with microvascular or nuclear density. This may be due to tissular edema possibly related to gated channel activity–related gene expression.

Key Points

• H3.1K27M mutant DIPG had higher apparent diffusion coefficient (p = 0.003), lower α (p = 0.048), and lower relative cerebral blood volume (p = 0.02) than H3.3K27M mutant DIPG at their biopsy sites.

• Biopsy samples obtained within the tumor’s enhancing portion showed higher microvascular density (p = 0.03) than samples obtained outside the tumor’s enhancing portion, but similar H3K27M-positive nuclear density (p = 0.84).

• Relative cerebral blood volume measured at the biopsy site was significantly correlated with H3K27M-positive nuclear density (rho = 0.74, p = 0.02).

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Abbreviations

CBF:

Cerebral blood flow

CBV:

Cerebral blood volume

DIPG:

Diffuse intrinsic pontine glioma

DSC:

Dynamic susceptibility contrast

FLAIR:

Fluid-attenuated inversion recovery

WHO:

Word Health Organization

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Funding

The authors state that this work has not received any funding.

Author information

Author notes

  1. Raphaël Calmon and Volodia Dangouloff-Ros contributed equally to this work.

Authors and Affiliations

  1. Pediatric Radiology Department, AP-HP, Hôpital Universitaire Necker-Enfants Malades, 149 rue de Sèvres, F-75015, Paris, France

    Raphaël Calmon, Volodia Dangouloff-Ros, David Grevent, Raphael Levy, Charles-Joris Roux & Nathalie Boddaert

  2. Université de Paris, INSERM ERL UA10, F-75015, Paris, France

    Raphaël Calmon, Volodia Dangouloff-Ros, David Grevent, Raphael Levy, Charles-Joris Roux, Ana Saitovitch, Monica Zilbovicius & Nathalie Boddaert

  3. Université de Paris, UMR 1163, Institut Imagine, F-75015, Paris, France

    Raphaël Calmon, Volodia Dangouloff-Ros, David Grevent, Raphael Levy, Charles-Joris Roux, Ana Saitovitch, Monica Zilbovicius & Nathalie Boddaert

  4. Neuropathology Department, Sainte-Anne Hospital, F-75014, Paris, France

    Pascale Varlet

  5. Université de Paris, INSERM U894, IMA BRAIN, F-75014, Paris, France

    Pascale Varlet

  6. Université Paris-Saclay, CNRS/IN2P3, IJCLab, F-91405, Orsay, France

    Christophe Deroulers

  7. Université Paris-Saclay, Neurospin, Institut Joliot, CEA, Gif-sur-Yvette, France

    Cathy Philippe

  8. Université Paris-Saclay, UMR8203, CNRS, F-94805, Villejuif, France

    Marie-Anne Debily, David Castel, Christelle Dufour & Jacques Grill

  9. Pediatric Neurosurgery Department, AP-HP, Hôpital Universitaire Necker-Enfants Malades, F-75015, Paris, France

    Kevin Beccaria, Thomas Blauwblomme & Stéphanie Puget

  10. Université de Paris, F-75015, Paris, France

    Kevin Beccaria, Thomas Blauwblomme & Stéphanie Puget

  11. Radiology Department, Fondation Rothschild, F-75019, Paris, France

    Yvonne Purcell

  12. Department of Pediatric and Adolescent Oncology, Institut Gustave Roussy, F-94805, Villejuif, France

    Christelle Dufour & Jacques Grill

Authors
  1. Raphaël Calmon
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  2. Volodia Dangouloff-Ros
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  3. Pascale Varlet
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Corresponding author

Correspondence to Volodia Dangouloff-Ros.

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Guarantor

The scientific guarantor of this publication is Nathalie Boddaert.

Conflict of interest

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.

Statistics and biometry

One of the authors has significant statistical expertise.

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Written informed consent was obtained from all subjects (patients) in this study.

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Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Some study subjects (17/27) or cohorts have been previously reported in a molecular analysis study (Castel et al Acta Neuropathol 2015).

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• prospective

• observational

• performed at one institution

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Calmon, R., Dangouloff-Ros, V., Varlet, P. et al. Radiogenomics of diffuse intrinsic pontine gliomas (DIPGs): correlation of histological and biological characteristics with multimodal MRI features. Eur Radiol 31, 8913–8924 (2021). https://doi.org/10.1007/s00330-021-07991-x

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