IMG-132. Voxel-wise prediction of tumor burden in glioblastoma using BOLD fMRI and structural MRI

Abstract BACKGROUND Glioblastoma (GBM) is a highly infiltrative brain tumor in which standard MRI sequences often fail to accurately reflect histologic tumor burden. Structural MRI remains the foundation for surgical and radiotherapy planning, but its ability to define true tumor extent is limited. We hypothesized that combining resting-state BOLD fMRI with structural MRI could provide a more accurate estimate of tumor burden. METHODS Twenty-one treatment-naïve patients with IDH-wildtype GBM underwent preoperative MRI including T1 post-contrast, T2, FLAIR, ADC, and resting-state BOLD fMRI. BOLD asynchrony (BA) maps were generated by identifying voxels with time series more similar to the contrast-enhancing lesion than to contralateral normal brain. A total of 56 MRI-localized stereotactic biopsies were acquired and analyzed for cellularity (H&E), tumor burden (Sox2), and neuronal density (NeuN). RESULTS BA was positively associated with H&E (R2 = 0.54, p = 2.6x10-9) and Sox2 (R2 = 0.45, p = 1.6x10-7) and negatively associated with NeuN (R2 = 0.28, p = 4.4x10-5). Conversely, ADC was negatively associated with H&E (R2 = 0.45, p = 6.3x10-8) and Sox2 (R2 = 0.48, p = 1.3x10-8) and not associated with NeuN (p = 0.48). Stepwise linear regression demonstrated that BA and ADC remained independently associated with both H&E and Sox2 after controlling for each other, with 65 percent of tumor burden variance explained by the combined model. T1, T2, and FLAIR values were not correlated with tumor burden or neuronal density (p > 0.05). Within FLAIR-positive, non-enhancing regions, tumor burden was heterogeneous but predicted well by the BA-ADC model. CONCLUSIONS BOLD asynchrony is a non-invasive, functional biomarker that offers a robust voxel-wise estimate of tumor burden when combined with ADC. These findings support the integration of BOLD fMRI with structural imaging in surgical and radiation planning for primary GBM. Ongoing studies will assess its prognostic value for recurrence and survival.