Harbo, Frederik Severin Gråe

Abstract Glioblastoma progression is spatially heterogeneous, but conventional imaging provides limited information about where subsequent tumor progression is likely to occur. We developed a directional magnetic resonance elastography (MRE) framework to test whether local post-treatment tumor–brain interface mechanics are associated with later spatial tumor progression. In a secondary analysis of a prospectively acquired glioblastoma cohort, wedge-level viscoelastic instability features were extracted from the first post-treatment MRE scan and related to novel tumor burden on the second post-treatment scan after excluding tumor already present on pretreatment or first post-treatment imaging. Nine patients had longitudinal imaging suitable for spatial comparison; six lesions showed net interval growth and were included in the primary wedge-level directional analysis, while three non-growing lesions were retained for descriptive comparison. In growing lesions, several directional mechanical features were descriptively associated with later novel tumor burden. In cluster-aware models accounting for within-patient dependence among wedges, mean Δtanδ showed the most consistent association with later wedge-level novel tumor fraction across mixed-effects and generalized estimating equation analyses. Associations were directionally stable across wedge-width sensitivity analyses. These findings provide proof of principle that post-treatment glioblastoma interface mechanics contain spatially resolved information related to where later tumor emergence occurs, supporting further validation of directional MRE as a framework for longitudinal mapping of progression geometry.

ABSTRACT Background Magnetic resonance elastography (MRE) has demonstrated potential in characterizing intracranial tumors, including glioblastoma. The influence of pathology on measurement consistency and interobserver agreement needs evaluation to promote MRE implementation as a quantitative biomarker. Purpose To assess repeatability and interobserver agreement of absolute and normalized magnitude of the complex shear modulus (| G *|), storage modulus ( G ′), and loss modulus ( G ″) in glioblastoma. Study Type Prospective. Population Thirteen adults (5 male, 8 female, mean age 66.23 years) with histopathologically confirmed glioblastoma. Field Strength/Sequence 3 T MRI, modified single‐shot spin‐echo echo‐planar imaging. Assessment Two same‐session MRE acquisitions were performed with patient repositioning. The solid tumor component was independently segmented by 2 observers on contrast‐enhanced T1‐weighted images co‐registered to MRE maps. Statistical Tests Repeatability was assessed using the repeatability coefficient, coefficient of variation, and Bland–Altman plots, and interobserver agreement by the intraclass correlation coefficient. The Wilcoxon signed‐rank test compared parameters and coefficients of variation between tumor‐normal‐appearing white matter and absolute and normalized measurements. Significance was set at 0.05. Results Tumor | G *| and G ′ showed repeatability coefficients of 0.07–0.08 kPa and 0.05 kPa, compared with 0.13 kPa (| G *|) and 0.15–0.16 kPa ( G ′) for normalized measurements. Coefficients of variation in tumor regions were 1.42% ± 1.12%–1.60% ± 1.41% for | G *| and 1.19% ± 0.96%–2.08% ± 2.22% for G ′, significantly lower than normalized values (4.82% ± 4.49%–4.21% ± 4.27% for | G *|; 5.12% ± 5.04%–5.45% ± 4.53% for G ′). Tumor | G *| and G ′ showed excellent interobserver agreement (intraclass correlation coefficients 0.97 and 0.95). Tumor G ″ demonstrated higher variability than | G *| and G ′ (coefficients of variation 8.58% ± 7.69%–7.51% ± 6.73%), with no significant difference between absolute and normalized measurements ( p = 0.14). Data Conclusion Tumor | G *| and G ′ are the most repeatable metrics in glioblastoma. Normalization reduces measurement repeatability due to normal‐appearing white matter variability. The small sample size ( n = 13) limits generalizability. Evidence Level 2. Technical Efficacy Stage 2.