Glioblastoma states are defined by cohabitating cellular populations with progression-, imaging- and sex-distinct patterns

Bond, K. M.; Curtin, L.; Hawkins-Daarud, A.; Urcuyo, J. C.; De Leon, G.; Sereduk, C.; Singleton, K. W.; Langworthy, J. M.; Jackson, P. R.; Krishna, C.; Zimmerman, R. S.; Patra, D. P.; Bendok, B. R.; Smith, K.; Nakaji, P.; Donev, K.; Baxter, L. C.; Mrugala, M. M.; Al-Dalahmah, O.; Hu, L. S.; Tran, N. L.; Rubin, J. B.; Canoll, P.; Swanson, K. R.

doi:10.1101/2022.03.23.485500

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bioRxiv · 10.1101/2022.03.23.485500

Glioblastoma states are defined by cohabitating cellular populations with progression-, imaging- and sex-distinct patterns

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Abstract

Background: Magnetic Resonance Imaging (MRI) is the mainstay for neurosurgical oncology but not for informing us about glioma biology. An obstacle to developing MR-based glioma biomarkers is the absence of rigorous correlation between MRI features and glioma biology as assessed in multi-regional biopsies, within and across patients. Methods: We directly addressed this obstacle by collating a unique cohort of 202 MRI-localized biopsies from 58 patients. We define a low-dimensional transcriptional pseudotime continuum along which heterogeneous high-grade glioma (HGG) samples organize both within and across patients. Results: We observe three polarized transcriptional tissue states: infiltrated brain, immune/inflammatory, and proliferative associated with patterns of cohabitation of cellular subpopulations. The states and deconvolved populations show correlation with enhancement status on T1Gd MRI. Moreover, discrete MRI habitats, regions sharing common imaging features, defined as combinations of high or low signal intensity across multiparametric MRI revealed 14 MRI habitats. We order the MRI habitats according to the average pseudotime on the transcriptional continuum. We find that MRI habitats with low pseudotime (associated with early tumor development and diffusely invaded brain tissue) localized at the periphery of the tumor whilst high pseudotime either proliferative or immune/inflammatory states were towards the core of the lesion. We find that composition of MRI habitats is impacted by MGMT status. Conclusion: This suggests that ongoing aggregation of MRI-localized biopsies may augment our projection of biology onto MRI habitats to support the noninvasive identification of cellular ecologies within and across each patient's tumor.

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Bond, K. M., Curtin, L., Hawkins-Daarud, A., Urcuyo, J. C., De Leon, G., Sereduk, C., Singleton, K. W., Langworthy, J. M., Jackson, P. R., Krishna, C., Zimmerman, R. S., Patra, D. P., Bendok, B. R., Smith, K., Nakaji, P., Donev, K., Baxter, L. C., Mrugala, M. M., Al-Dalahmah, O., Hu, L. S., Tran, N. L., Rubin, J. B., Canoll, P., Swanson, K. R.. 2022-03-26. Glioblastoma states are defined by cohabitating cellular populations with progression-, imaging- and sex-distinct patterns. https://doi.org/10.1101/2022.03.23.485500

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