Mapping tumour heterogeneity with pulsed 3D CEST MRI in non-enhancing glioma at 3 T

Esther A H Warnert; Tobias C Wood; Fatih Incekara; Gareth J Barker; Arnaud J P Vincent; Joost Schouten; Johan M Kros; Martin van den Bent; Marion Smits; Juan A Hernandez Tamames

doi:10.1007/s10334-021-00911-6

Mapping tumour heterogeneity with pulsed 3D CEST MRI in non-enhancing glioma at 3 T

Esther A H Warnert, Tobias C Wood, Fatih Incekara, Gareth J Barker, Arnaud J P Vincent, Joost Schouten, Johan M Kros, Martin van den Bent, Marion Smits, Juan A Hernandez Tamames

Department of Radiology and Nuclear Medicine
Psychology and Neuroscience
King's College London
Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK; Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK.
Department of Pathology, University of California San Diego, La Jolla, CA, USA; Department of Pathology, VA San Diego Healthcare System, San Diego, CA, USA.
National Hospital for Neurology and Neurosurgery and the University Department of Clinical Neurology

Research output: Contribution to journal › Article › peer-review

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Abstract

OBJECTIVE: Amide proton transfer (APT) weighted chemical exchange saturation transfer (CEST) imaging is increasingly used to investigate high-grade, enhancing brain tumours. Non-enhancing glioma is currently less studied, but shows heterogeneous pathophysiology with subtypes having equally poor prognosis as enhancing glioma. Here, we investigate the use of CEST MRI to best differentiate non-enhancing glioma from healthy tissue and image tumour heterogeneity.

MATERIALS & METHODS: A 3D pulsed CEST sequence was applied at 3 Tesla with whole tumour coverage and 31 off-resonance frequencies (+6 to -6 ppm) in 18 patients with non-enhancing glioma. Magnetisation transfer ratio asymmetry (MTRasym) and Lorentzian difference (LD) maps at 3.5 ppm were compared for differentiation of tumour versus normal appearing white matter. Heterogeneity was mapped by calculating volume percentages of the tumour showing hyperintense APT-weighted signal.

RESULTS: LDamide gave greater effect sizes than MTRasym to differentiate non-enhancing glioma from normal appearing white matter. On average, 17.9 % ± 13.3 % (min-max: 2.4 %-54.5 %) of the tumour volume showed hyperintense LDamide in non-enhancing glioma.

CONCLUSION: This works illustrates the need for whole tumour coverage to investigate heterogeneity in increased APT-weighted CEST signal in non-enhancing glioma. Future work should investigate whether targeting hyperintense LDamide regions for biopsies improves diagnosis of non-enhancing glioma.

Original language	English
Journal	Magma: Magnetic Resonance Materials in Physics, Biology and Medicine
DOIs	https://doi.org/10.1007/s10334-021-00911-6
Publication status	E-pub ahead of print - 19 Feb 2021

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10.1007/s10334-021-00911-6

Warnert2021_Article_MappingTumourHeterogeneityWith
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Warnert, E. A. H., Wood, T. C., Incekara, F., Barker, G. J., Vincent, A. J. P., Schouten, J., Kros, J. M., van den Bent, M., Smits, M., & Tamames, J. A. H. (2021). Mapping tumour heterogeneity with pulsed 3D CEST MRI in non-enhancing glioma at 3 T. Magma: Magnetic Resonance Materials in Physics, Biology and Medicine. Advance online publication. https://doi.org/10.1007/s10334-021-00911-6

@article{77208a900eb24db09929be04443a9f61,

title = "Mapping tumour heterogeneity with pulsed 3D CEST MRI in non-enhancing glioma at 3 T",

abstract = "OBJECTIVE: Amide proton transfer (APT) weighted chemical exchange saturation transfer (CEST) imaging is increasingly used to investigate high-grade, enhancing brain tumours. Non-enhancing glioma is currently less studied, but shows heterogeneous pathophysiology with subtypes having equally poor prognosis as enhancing glioma. Here, we investigate the use of CEST MRI to best differentiate non-enhancing glioma from healthy tissue and image tumour heterogeneity.MATERIALS & METHODS: A 3D pulsed CEST sequence was applied at 3 Tesla with whole tumour coverage and 31 off-resonance frequencies (+6 to -6 ppm) in 18 patients with non-enhancing glioma. Magnetisation transfer ratio asymmetry (MTRasym) and Lorentzian difference (LD) maps at 3.5 ppm were compared for differentiation of tumour versus normal appearing white matter. Heterogeneity was mapped by calculating volume percentages of the tumour showing hyperintense APT-weighted signal.RESULTS: LDamide gave greater effect sizes than MTRasym to differentiate non-enhancing glioma from normal appearing white matter. On average, 17.9 % ± 13.3 % (min-max: 2.4 %-54.5 %) of the tumour volume showed hyperintense LDamide in non-enhancing glioma.CONCLUSION: This works illustrates the need for whole tumour coverage to investigate heterogeneity in increased APT-weighted CEST signal in non-enhancing glioma. Future work should investigate whether targeting hyperintense LDamide regions for biopsies improves diagnosis of non-enhancing glioma.",

author = "Warnert, {Esther A H} and Wood, {Tobias C} and Fatih Incekara and Barker, {Gareth J} and Vincent, {Arnaud J P} and Joost Schouten and Kros, {Johan M} and {van den Bent}, Martin and Marion Smits and Tamames, {Juan A Hernandez}",

note = "Funding Information: This research was conducted with support from the Dutch Cancer Society (KWF): “Non-invasive phenotypying of molecular brain tumour profiles using novel advanced MR imaging and analysis”, EMCR 2015–7859, and from the Brain Tumour Charity; “Making the invisible visible: In vivo mapping of molecular biomarkers in adult diffuse glioma with CEST MRI”, GN-000540. EW is funded by a “Veni Vernieuwingsimpuls” from the Dutch Association entitled “Food for thought: Oxygen delivery to the brain”, Grant number 91619121. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = feb,

day = "19",

doi = "10.1007/s10334-021-00911-6",

language = "English",

journal = "Magma: Magnetic Resonance Materials in Physics, Biology and Medicine",

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T1 - Mapping tumour heterogeneity with pulsed 3D CEST MRI in non-enhancing glioma at 3 T

AU - Warnert, Esther A H

AU - Wood, Tobias C

AU - Incekara, Fatih

AU - Barker, Gareth J

AU - Vincent, Arnaud J P

AU - Schouten, Joost

AU - Kros, Johan M

AU - van den Bent, Martin

AU - Smits, Marion

AU - Tamames, Juan A Hernandez

N1 - Funding Information: This research was conducted with support from the Dutch Cancer Society (KWF): “Non-invasive phenotypying of molecular brain tumour profiles using novel advanced MR imaging and analysis”, EMCR 2015–7859, and from the Brain Tumour Charity; “Making the invisible visible: In vivo mapping of molecular biomarkers in adult diffuse glioma with CEST MRI”, GN-000540. EW is funded by a “Veni Vernieuwingsimpuls” from the Dutch Association entitled “Food for thought: Oxygen delivery to the brain”, Grant number 91619121. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2/19

Y1 - 2021/2/19

N2 - OBJECTIVE: Amide proton transfer (APT) weighted chemical exchange saturation transfer (CEST) imaging is increasingly used to investigate high-grade, enhancing brain tumours. Non-enhancing glioma is currently less studied, but shows heterogeneous pathophysiology with subtypes having equally poor prognosis as enhancing glioma. Here, we investigate the use of CEST MRI to best differentiate non-enhancing glioma from healthy tissue and image tumour heterogeneity.MATERIALS & METHODS: A 3D pulsed CEST sequence was applied at 3 Tesla with whole tumour coverage and 31 off-resonance frequencies (+6 to -6 ppm) in 18 patients with non-enhancing glioma. Magnetisation transfer ratio asymmetry (MTRasym) and Lorentzian difference (LD) maps at 3.5 ppm were compared for differentiation of tumour versus normal appearing white matter. Heterogeneity was mapped by calculating volume percentages of the tumour showing hyperintense APT-weighted signal.RESULTS: LDamide gave greater effect sizes than MTRasym to differentiate non-enhancing glioma from normal appearing white matter. On average, 17.9 % ± 13.3 % (min-max: 2.4 %-54.5 %) of the tumour volume showed hyperintense LDamide in non-enhancing glioma.CONCLUSION: This works illustrates the need for whole tumour coverage to investigate heterogeneity in increased APT-weighted CEST signal in non-enhancing glioma. Future work should investigate whether targeting hyperintense LDamide regions for biopsies improves diagnosis of non-enhancing glioma.

AB - OBJECTIVE: Amide proton transfer (APT) weighted chemical exchange saturation transfer (CEST) imaging is increasingly used to investigate high-grade, enhancing brain tumours. Non-enhancing glioma is currently less studied, but shows heterogeneous pathophysiology with subtypes having equally poor prognosis as enhancing glioma. Here, we investigate the use of CEST MRI to best differentiate non-enhancing glioma from healthy tissue and image tumour heterogeneity.MATERIALS & METHODS: A 3D pulsed CEST sequence was applied at 3 Tesla with whole tumour coverage and 31 off-resonance frequencies (+6 to -6 ppm) in 18 patients with non-enhancing glioma. Magnetisation transfer ratio asymmetry (MTRasym) and Lorentzian difference (LD) maps at 3.5 ppm were compared for differentiation of tumour versus normal appearing white matter. Heterogeneity was mapped by calculating volume percentages of the tumour showing hyperintense APT-weighted signal.RESULTS: LDamide gave greater effect sizes than MTRasym to differentiate non-enhancing glioma from normal appearing white matter. On average, 17.9 % ± 13.3 % (min-max: 2.4 %-54.5 %) of the tumour volume showed hyperintense LDamide in non-enhancing glioma.CONCLUSION: This works illustrates the need for whole tumour coverage to investigate heterogeneity in increased APT-weighted CEST signal in non-enhancing glioma. Future work should investigate whether targeting hyperintense LDamide regions for biopsies improves diagnosis of non-enhancing glioma.

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DO - 10.1007/s10334-021-00911-6

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C2 - 33606114

SN - 0968-5243

JO - Magma: Magnetic Resonance Materials in Physics, Biology and Medicine

JF - Magma: Magnetic Resonance Materials in Physics, Biology and Medicine

ER -

Mapping tumour heterogeneity with pulsed 3D CEST MRI in non-enhancing glioma at 3 T

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