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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › 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
Pages (from-to)	53-62
Number of pages	10
Journal	Magnetic Resonance Materials in Physics Biology and Medicine
Volume	35
Issue number	1
Early online date	19 Feb 2021
DOIs	https://doi.org/10.1007/s10334-021-00911-6
Publication status	Published - Feb 2022

Bibliographical note

Funding
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.

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@article{71ec7dece7264992b21c5ec916d64e2c,

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 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.",

year = "2022",

month = feb,

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

language = "English",

volume = "35",

pages = "53--62",

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

issn = "0968-5243",

publisher = "Springer-Verlag",

number = "1",

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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 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.

PY - 2022/2

Y1 - 2022/2

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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U2 - 10.1007/s10334-021-00911-6

DO - 10.1007/s10334-021-00911-6

M3 - Article

C2 - 33606114

VL - 35

SP - 53

EP - 62

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

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

SN - 0968-5243

IS - 1

ER -

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

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