Evaluation of Glioblastoma Response to Therapy With Chemical Exchange Saturation Transfer

Purpose: To monitor cellular and metabolic characteristics of glioblastoma (GBM) over the course of standard 6-week chemoradiation treatment with chemical exchange saturation transfer (CEST)-MRI; and to identify the earliest time point CEST could determine subsequent therapeutic response.

Methods And Materials: Nineteen patients with newly diagnosed GBM were recruited, and CEST-MRI was acquired immediately before (Day), 2 weeks (Day) and 4 weeks (Day) into treatment, and 1 month after the end of treatment (Day). Several CEST metrics, including magnetization transfer ratio and area under the curve of CEST peaks corresponding to nuclear Overhauser effect (NOE) and amide protons (MTR, MTR, CEST, and CEST respectively), magnetization transfer (MT), and direct water effect were investigated. Lack of early progression was determined as no increase in tumor size or worsening of clinical symptoms according to routine post-chemoradiation serial structural MRI.

Results: Changes in MTR (nonprogressors = 1.35 ± 0.18, progressors = 0.97 ± 0.22, P = .006) and MTR (nonprogressors = 1.25 ± 0.17, progressors = 0.99 ± 0.10, P = .017) between baseline (Day) and Day resulted in the best separation of nonprogressors from progressors. Moreover, the baseline (Day) MTR (nonprogressors = 6.5% ± 1.6%, progressors = 9.1% ± 2.1%, P = .015), MTR (nonprogressors = 6.7% ± 1.7%, progressors = 8.9% ± 1.9%, P = .028), MT (nonprogressors = 3.8% ± 0.9%, progressors = 5.4% ± 1.4%, P = .019), and CEST (nonprogressors = 4.1%ċHz ± 1.7%ċHz, progressors = 6.1%ċHz ± 1.9%ċHz, P = .044) were able to identify progressors even before the start of the treatment.

Conclusions: Chemical exchange saturation transfer (CEST) provides imaging-based biomarkers of GBM response as early as 2 weeks into the treatment. Certain CEST metrics can characterize tumor aggressiveness and identify early progressors even before beginning the treatment. Such an early biomarker of response may allow for adjusting the GBM treatment plan for adaptive radiation therapy in early progressors and more confidently continuing standard adjuvant treatment for nonprogressors.