Abstract
ObjectiveAmide 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 & MethodsA 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.ResultsLDamide 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.ConclusionThis 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.
Highlights
Chemical exchange saturation transfer (CEST) is a technique to create magnetic resonance imaging (MRI) contrasts by selective targeting of labile protons in endogenous and patients with non-enhancing gliomas are often included in studies investigating amide proton transfer (APT)-weighted CEST MRI, the main aim is often differentiation of glioma grade based on the classic histological classification of low to high-grade tumours, where high-grade tumours often show enhancement and form the majority of the studied population
Patients with non-enhancing gliomas are often included in studies investigating APT-weighted CEST MRI, the main aim is often differentiation of glioma grade based on the classic histological classification of low to high-grade tumours, where high-grade tumours often show enhancement and form the majority of the studied population
For Magnetisation transfer ratio asymmetry (MTRasym), LDamide, and LDNOE the mixed-effects linear regression showed a significant effect of regions of interest (ROI) (p < 0.05, Bonferroni corrected), indicating significant differences found between normal-appearing white matter (NAWM) and tumour tissue
Summary
Chemical exchange saturation transfer (CEST) is a technique to create magnetic resonance imaging (MRI) contrasts by selective targeting of labile protons in endogenous and patients with non-enhancing gliomas are often included in studies investigating APT-weighted CEST MRI, the main aim is often differentiation of glioma grade based on the classic histological classification of low to high-grade tumours, where high-grade tumours often show enhancement and form the majority of the studied population. Magnetic Resonance Materials in Physics, Biology and Medicine like glioblastomas, have spatially varying pathophysiology and underlying molecular signatures [5]. The latter is of particular importance in light of the recently updated molecular classification of tumours as published by the World Health Organisation [6]. Whereas non-enhancing glioma used to be classified based on histology only, two molecular parameters (IDH mutation and 1p/19q codeletion) are of interest that lead to three distinct classes of non-enhancing glioma [7] These three classes differ widely in prognosis, ranging from a median overall survival of more than 10 years to just over 1 year, similar to enhancing glioblastoma (grade IV). Each of these classes warrants a different treatment regime, which stresses the need for accurate diagnosis
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