High-Grade Glioma Treatment Response Monitoring Biomarkers: A Position Statement on the Evidence Supporting the Use of Advanced MRI Techniques in the Clinic, and the Latest Bench-to-Bedside Developments. Part 1: Perfusion and Diffusion Techniques

Abstract

ObjectiveSummarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and highlight the latest bench-to-bedside developments.MethodsExperts in advanced MRI techniques applied to high-grade glioma treatment response assessment convened through a European framework. Current evidence regarding the potential for monitoring biomarkers in adult high-grade glioma is reviewed, and individual modalities of perfusion, permeability, and microstructure imaging are discussed (in Part 1 of two). In Part 2, we discuss modalities related to metabolism and/or chemical composition, appraise the clinic readiness of the individual modalities, and consider post-processing methodologies involving the combination of MRI approaches (multiparametric imaging) or machine learning (radiomics).ResultsHigh-grade glioma vasculature exhibits increased perfusion, blood volume, and permeability compared with normal brain tissue. Measures of cerebral blood volume derived from dynamic susceptibility contrast-enhanced MRI have consistently provided information about brain tumor growth and response to treatment; it is the most clinically validated advanced technique. Clinical studies have proven the potential of dynamic contrast-enhanced MRI for distinguishing post-treatment related effects from recurrence, but the optimal acquisition protocol, mode of analysis, parameter of highest diagnostic value, and optimal cut-off points remain to be established. Arterial spin labeling techniques do not require the injection of a contrast agent, and repeated measurements of cerebral blood flow can be performed. The absence of potential gadolinium deposition effects allows widespread use in pediatric patients and those with impaired renal function. More data are necessary to establish clinical validity as monitoring biomarkers. Diffusion-weighted imaging, apparent diffusion coefficient analysis, diffusion tensor or kurtosis imaging, intravoxel incoherent motion, and other microstructural modeling approaches also allow treatment response assessment; more robust data are required to validate these alone or when applied to post-processing methodologies.ConclusionConsiderable progress has been made in the development of these monitoring biomarkers. Many techniques are in their infancy, whereas others have generated a larger body of evidence for clinical application.

Advanced Neuroimaging Approaches to Pediatric Brain Tumors

“…ASL is promising in distinguishing choroid plexus carcinoma from papilloma, with carcinoma exhibiting significantly higher relative CBF ratio [98,101] (Figure 5). Of note, studies evaluating post-treatment changes in pa tients with high-grade glioma using ASL are sparse and have small number of subjects but more evidence is slowly emerging [106]. There is also elevation of lactate (Lac).…”

Radiomics for pseudoprogression prediction in high grade gliomas: added value of MR contrast agent

“…Due to the increased perfusion and higher blood volume of gliomas, clinically best validated technique on brain tumor growth and response to treatment is CBV measurement derived from DSC-MRI [ 26 ]. Radiomics is ready to contribute to the imaging arsenal.…”

“…Thus, our results further provide evidence, that the administration of contrast agent in patients with suspicion of tumor progression is decisive and should not be omitted [ 33 , 34 ]. In pediatric patients and patients with impaired renal function due to rapidly repeated measurements, ASL techniques are discussed as an alternative [ 26 ].…”

Mathematical modelling of the dynamics of image-informed tumor habitats in a murine model of glioma

“…Decreased ADC values have been associated with poorer survival 15 , while increased ADC values have been associated with positive response to chemotherapy [15][16][17] .…”