Objective Isocitrate dehydrogenase (IDH) mutations are key prognostic factors in gliomas. IDH-wildtype (IDH-wt) glioblastomas are high-grade tumors, which often exhibit blood–brain barrier (BBB) breakdown. Blood–brain barrier arterial spin labeling (BBB-ASL) is a novel MRI technique that provides information on cerebral blood flow (CBF) and water exchange time (Tex) across the BBB. The aim of this study was to evaluate the feasibility of using BBB-ASL to measure CBF and Tex for distinguishing IDH mutational subgroups in gliomas, while accounting for region-specific T2 relaxation time variations. Methods Twenty-five histopathologically confirmed gliomas (15 IDH-wt and 10 IDH-mutant (IDH-mut); mean age <InlineEquation ID="IEq1"> <EquationSource Format="TEX">$53.6 \pm 14$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mn>53.6</mn> <mo>±</mo> <mn>14</mn> </mrow> </math></EquationSource> </InlineEquation> years; F/M = 11/14) were scanned. Hadamard-4 and Hadamard-8 pseudo-continuous arterial spin labeling (pCASL) MRI data were preprocessed in ExploreASL using the BBB-ASL model. CBF and Tex maps were generated using fixed T2 values (tissue: 85 ms; blood: 165 ms), and recomputed with a tissue T2 of 116.2 ms (CBF_116ms and Tex_116ms) and patient specific regional median T2 (CBF_corr and Tex_corr). Relative CBF and Tex maps (rCBF_116ms, rTex_116ms; rCBF_corr, rTex_corr) were calculated by normalizing to median normal-appearing gray matter (NAGM) values. Group comparisons of rCBF and rTex values between IDH mutational subgroups were performed using Mann–Whitney U tests with Holm-Bonferroni correction for multiple comparisons. Results rTex_116ms maps showed significantly lower energy in IDH-wt tumors (<InlineEquation ID="IEq2"> <EquationSource Format="TEX">$P=0.010$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mi>P</mi> <mo>=</mo> <mn>0.010</mn> </mrow> </math></EquationSource> </InlineEquation>) and a higher <InlineEquation ID="IEq3"> <EquationSource Format="TEX">$95^{\text {th}}$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <msup> <mn>95</mn> <mrow> <mi mathvariant="italic">th</mi> </mrow> </msup> </mrow> </math></EquationSource> </InlineEquation> percentile (<InlineEquation ID="IEq4"> <EquationSource Format="TEX">$P=0.049$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mi>P</mi> <mo>=</mo> <mn>0.049</mn> </mrow> </math></EquationSource> </InlineEquation>) in IDH-mut tumors. In addition, IDH-wt gliomas demonstrated a trend toward higher <InlineEquation ID="IEq5"> <EquationSource Format="TEX">$5^{\text {th}}$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <msup> <mn>5</mn> <mrow> <mi mathvariant="italic">th</mi> </mrow> </msup> </mrow> </math></EquationSource> </InlineEquation> percentile rCBF_116ms and rCBF_corr (<InlineEquation ID="IEq6"> <EquationSource Format="TEX">$P=0.033$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mi>P</mi> <mo>=</mo> <mn>0.033</mn> </mrow> </math></EquationSource> </InlineEquation>, <InlineEquation ID="IEq7"> <EquationSource Format="TEX">$P=0.014$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mi>P</mi> <mo>=</mo> <mn>0.014</mn> </mrow> </math></EquationSource> </InlineEquation>, respectively). Conclusion Multi-TE BBB-ASL provides noninvasive insight into perfusion and water exchange characteristics in gliomas, with T2 relaxation time assumptions strongly influencing CBF and Tex estimates.

Cerebral blood flow and time of exchange measurements using multi-TE blood–brain barrier arterial spin labeling MRI in IDH mutational subgroups of gliomas

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2026年4月21日

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Gülce Turhan,
Ayse Irem Cetin,
Beatriz E. Padrela,
Amnah Mahroo,
Omer-Yasin Cur,
Simon Konstandin,
Daniel Christopher Hoinkiss,
Nora-Josefin Breutigam,
Henk J. M. M. Mutsaerts,
Ayca Ersen Danyeli,
Koray Ozduman,
Klaus Eickel,
Vera C. Keil,
Matthias Günther,
Jan Petr,
Alp Dincer,
Esin Ozturk-Isik

摘要

Objective

Isocitrate dehydrogenase (IDH) mutations are key prognostic factors in gliomas. IDH-wildtype (IDH-wt) glioblastomas are high-grade tumors, which often exhibit blood–brain barrier (BBB) breakdown. Blood–brain barrier arterial spin labeling (BBB-ASL) is a novel MRI technique that provides information on cerebral blood flow (CBF) and water exchange time (Tex) across the BBB. The aim of this study was to evaluate the feasibility of using BBB-ASL to measure CBF and Tex for distinguishing IDH mutational subgroups in gliomas, while accounting for region-specific T2 relaxation time variations.

Methods

Twenty-five histopathologically confirmed gliomas (15 IDH-wt and 10 IDH-mutant (IDH-mut); mean age $53.6 \pm 14$ $53.6 \pm 14$ years; F/M = 11/14) were scanned. Hadamard-4 and Hadamard-8 pseudo-continuous arterial spin labeling (pCASL) MRI data were preprocessed in ExploreASL using the BBB-ASL model. CBF and Tex maps were generated using fixed T2 values (tissue: 85 ms; blood: 165 ms), and recomputed with a tissue T2 of 116.2 ms (CBF_116ms and Tex_116ms) and patient specific regional median T2 (CBF_corr and Tex_corr). Relative CBF and Tex maps (rCBF_116ms, rTex_116ms; rCBF_corr, rTex_corr) were calculated by normalizing to median normal-appearing gray matter (NAGM) values. Group comparisons of rCBF and rTex values between IDH mutational subgroups were performed using Mann–Whitney U tests with Holm-Bonferroni correction for multiple comparisons.

Results

rTex_116ms maps showed significantly lower energy in IDH-wt tumors ( $P=0.010$ $P = 0.010$ ) and a higher $95^{\text {th}}$ $95^{th}$ percentile ( $P=0.049$ $P = 0.049$ ) in IDH-mut tumors. In addition, IDH-wt gliomas demonstrated a trend toward higher $5^{\text {th}}$ $5^{th}$ percentile rCBF_116ms and rCBF_corr ( $P=0.033$ $P = 0.033$ , $P=0.014$ $P = 0.014$ , respectively).

Conclusion

Multi-TE BBB-ASL provides noninvasive insight into perfusion and water exchange characteristics in gliomas, with T2 relaxation time assumptions strongly influencing CBF and Tex estimates.