Accurate DCE-MRI Measurement of Glioblastoma Using Point-of-care Portable Perfusion Phantom

Glioblastoma is the most common primary malignant type of brain tumor in adults. Surgical tumor resection followed by chemoradiation therapy is the standard of care for patients with glioblastoma, but its prognosis is still fairly dismal (median survival time = 15 months). One major concern that prevents effective treatment management is the difficulty of differentiating between pseudo-progression and true-progression. Pseudo-progression occurs in about 20-30% of glioblastoma patients typically within 3 months after chemoradiation therapy has been completed. Pseudo-progression is a local inflammatory reaction caused by irradiation and enhanced by concurrent chemotherapy, which leads to a transient increase of blood brain barrier (BBB) permeability. The BBB, however, is also disrupted by new cancer occurrence. Therefore, both pseudo- and true-progressions appear with an increased contrast enhancement in MRI, and there are currently no established techniques to differentiate between them. Pseudo-progression is typically known to be associated with better clinical outcomes, so pseudo-progression mistaken for true-progression results in the discontinuation of an effective therapy, while true-progression mistaken for pseudo-progression leads to the continuation of an ineffective therapy that may induce adverse side effects. DCE-MRI has potential to differentiate between pseudo- and true-progressions of glioblastoma. The enhancing lesions of pseudo-progression are due to inflammation, whereas those of true-progression are caused by cancer growing. Thus, true-progression typically presents higher perfusion than pseudo-progression does. DCE-MRI can quantitatively assess the tissue perfusion by monitoring the dynamic change of MRI contrast agent concentration. Several investigators have demonstrated the potential of quantitative DCE-MRI to differentiate between pseudo- and true-progressions. However, the variability in quantitative DCE-MRI measurement across different MRI scanners remains a major concern, as it hinders data comparison among institutes to retrieve a reliable threshold for accurate prognosis and subsequent treatment optimization. A point-of-care perfusion phantom may allow high reproducibility and accurate comparison of quantitative DCE-MRI data across MRI platforms. The UAB radiological research team recently developed the P4 phantom, which is small enough to be imaged concurrently with a patient for real-time quality assurance, but large enough not to suffer from the partial volume effect. The P4 phantom creates constant contrast enhancement curves with very robust repeatability, and thus the contrast agent concentration time-course in a tumor, which is a major source of error in quantitating DCE-MRI parameters, can be accurately calculated in reference to the values observed in the phantom. In our previous study, the variability in quantitating the volume transfer constant of various human tissues across two different MRI scanners was reduced fivefold after P4-based error correction. The investigators hypothesize that the variability in quantitative DCE-MRI measurement of glioblastoma across different scanners will be significantly reduced when the P4 is used for error correction, leading to better differentiation between pseudo- and true-progressions. The goal of this study is to test this hypothesis.