Advanced MRI Techniques in the Monitoring of Treatment of Gliomas

Abstract

With advances in treatments and survival of patients with glioblastoma (GBM), it has become apparent that conventional imaging sequences have significant limitations both in terms of assessing response to treatment and monitoring disease progression. Both 'pseudoprogression' after chemoradiation for newly diagnosed GBM and 'pseudoresponse' after anti-angiogenesis treatment for relapsed GBM are well-recognised radiological entities. This in turn has led to revision of response criteria away from the standard MacDonald criteria, which depend on the two-dimensional measurement of contrast-enhancing tumour, and which have been the primary measure of radiological response for over three decades. A working party of experts published RANO (Response Assessment in Neuro-oncology Working Group) criteria in 2010 which take into account signal change on T2/FLAIR sequences as well as the contrast-enhancing component of the tumour. These have recently been modified for immune therapies, which are associated with specific issues related to the timing of radiological response. There has been increasing interest in quantification and validation of physiological and metabolic parameters in GBM over the last 10 years utilising the wide range of advanced imaging techniques available on standard MRI platforms. Previously, MRI would provide structural information only on the anatomical location of the tumour and the presence or absence of a disrupted blood-brain barrier. Advanced MRI sequences include proton magnetic resonance spectroscopy (MRS), vascular imaging (perfusion/permeability) and diffusion imaging (diffusion weighted imaging/diffusion tensor imaging) and are now routinely available. They provide biologically relevant functional, haemodynamic, cellular, metabolic and cytoarchitectural information and are being evaluated in clinical trials to determine whether they offer superior biomarkers of early treatment response than conventional imaging, when correlated with hard survival endpoints. Multiparametric imaging, incorporating different combinations of these modalities, improves accuracy over single imaging modalities but has not been widely adopted due to the amount of post-processing analysis required, lack of clinical trial data, lack of radiology training and wide variations in threshold values. New techniques including diffusion kurtosis and radiomics will offer a higher level of quantification but will require validation in clinical trial settings. Given all these considerations, it is clear that there is an urgent need to incorporate advanced techniques into clinical trial design to avoid the problems of under or over assessment of treatment response.

Quantitative T1 mapping indicates tumor infiltration beyond the enhancing part of glioblastomas

“…A combination of the presented method with qMRI techniques measuring further parameters (DTI, CBV, T2, PD, perfusion) and more novel MRI techniques (diffusion kurtosis imaging, chemical exchange saturation transfer) might provide a more precise characterization of the area beyond the enhancing tumor and emerge as a useful tool for initial tumor characterization and for treatment monitoring …”

The biology and mathematical modelling of glioma invasion: a review

“…MRS uses the proton signals to determine relative concentrations of target metabolites rather than an anatomical image. In various studies, MRS has been shown capable of identifying regions of tissue enriched with stem-like cell-enriched foci [131], detecting tumours with mutations in the isocitrate dehydrogenase (IDH) genes [132,133], and assessing response to various therapies such as radiation and PI3K/mTOR inhibitors [134,135]. Further, the use of hyperpolarized (HP) contrast agents can significantly increase the sensitivity of MRS by enhancing the signal-to-noise ratio [136,137].…”

Conventional and advanced magnetic resonance imaging in patients with high-grade glioma

“…CEST creates imaging contrast based on sensitivity to chemical exchange of protons on functional metabolic groups rather than exogenously administered contrast. 23 The CEST technique which has primarily been applied to brain tumor imaging is the exchange of amide protons of endogenous tissue proteins and peptides, known as amide proton transfer (APT). Early studies have shown a potential use of APT in the differentiation of tumor from edema and true progression versus pseudoprogression, although these techniques have yet to be widely applied clinically.…”