PROJECT SUMMARY / ABSTRACT
Glioblastoma (GBM) is the most aggressive and inevitably recurrent brain tumor with a dismal prognosis and
highly heterogeneous profiles. While front-line chemoradiotherapy (CRT) improves survival, it also complicates
the assessment of early tumor progression (TP). Pseudoprogression (PsP), presenting as increased
enhancement indistinguishable from TP by conventional MRI, occurs in about 36% of GBM patients. The
current RANO criteria require longitudinal follow-up imaging exams and occasionally biopsy to make the
ultimate distinction, often 6 or more months after the completion of CRT, precluding the possibility of timely and
potentially more effective interventions. Despite advances in sophisticated physiological and metabolic MRI
techniques, response assessment remains a prevailing challenge in the clinical management of GBM.
Encouraged by recent findings in murine GBM xenografts that are corroborated further by a patient case, this
proposal aims to validate the underlying histopathological basis and assess the ability of MR elastography
(MRE) in the early differentiation of TP by spatially mapping the heterogenous response in GBM patients. MRE
is an MRI technique that provides noninvasive, quantitative, and direct 3D maps of tissue viscoelastic
properties in vivo. These biomechanical factors of tumors have been increasingly recognized to have profound
implications for malignant progression, tumor heterogeneity, and treatment resistance. The central hypothesis
of this project is that MRE can accurately differentiate between early TP and PsP by mapping the spatial
distribution of active tumor and treatment-related changes (TRCs) within the known heterogeneous tumor
response. Two independent specific aims are outlined to test this hypothesis. MRE features distinctive of active
tumors and TRCs will be validated in Aim 1 in a pre-operative cohort with gold-standard tissue confirmation.
The approach takes advantage of high-precision sampling during neuro-navigational surgeries to obtain co-
localized tissue and imaging volumes for quantitative correlation analysis. This much-needed but never studied
correlation in human GBM is crucial to help elucidate the pathophysiologic basis of the heterogenous MRE
contrast. The ability of viscoelastic imaging markers to differentiate early TP from PsP will be determined in a
longitudinal post-CRT imaging study in Aim 2. The approach leverages a robust high-sensitivity MRE
methodology developed by the study team originally for mapping rapid functional changes in human brains to
provide a high-resolution mapping of tissue viscoelastic properties. This enables full utilization of the diagnostic
features in the heterogeneous biomechanical response of tumors for more accurate distinction. This innovative
project will establish the first evidence on the role of MRE in the clinical evaluation of the treatment response of
GBM. It is significant as the accurate and early understanding of the true underlying tumor burden following
CRT is critical for guiding subsequent treatment planning to improve patient outcomes.