Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast‐enhanced MRI, arterial spin labeling, diffusion‐weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility‐weighted imaging, MRI‐PET, MR elastography, and MR‐based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2

Purpose Current challenges of in vivo CEST imaging include overlapping signals from different pools. The overlap arises from closely resonating pools and/or the broad magnetization transfer contrast (MTC) from macromolecules. This study aimed to evaluate the feasibility of variable delay multipulse (VDMP) CEST to separately assess solute pools with different chemical exchange rates in the human brain in vivo, while mitigating the MTC. Methods VDMP saturation buildup curves were simulated for amines, amides, and relayed nuclear Overhauser effect. VDMP data were acquired from glutamate and bovine serum albumin phantoms, and from six healthy volunteers at 7T. For the in vivo data, MTC removal was performed via a three‐pool Lorentzian fitting. Different B1 amplitudes and mixing times were used to evaluate CEST pools with different exchange rates. Results The results show the importance of removing MTC when applying VDMP in vivo and the influence of B1 for distinguishing different pools. Finally, the optimal B1 and mixing times to effectively saturate slow‐ and fast‐exchanging components are also reported. Slow‐exchanging amides and rNOE components could be distinguished when using B1 = 1 μT and tmix = 10 ms and 40 ms, respectively. Fast‐exchanging components reached the highest saturation when using a B1 = 2.8 μT and tmix = 0 ms. Conclusion VDMP is a powerful CEST‐editing tool, exploiting chemical exchange‐rate differences. After MTC removal, it allows separate assessment of slow‐ and fast‐exchanging solute pools in in vivo human brain.

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Background Perfusion MRI by Arterial Spin Labeling (ASL) and Dynamic Susceptibility Contrast (DSC) has shown its potential for differentiating tumor progression from pseudo-progression in glioblastoma patients. The ASL scans can be affected by arterial transit time (ATT) delays, which could be caused by treatment effects due to concomitant radiochemotherapy. A prolonged ATT is present as apparent signal increase in the large arteries due to labeled spins still residing within the vasculature, leading to underestimation of tissue perfusion and thus potentially affecting clinical decision-making. The research questions were: 1) Do delayed ATTs lead to a difference in the visual assessment of ASL perfusion (normal/increased) maps compared to DSC-MRI?; 2) Does the radiological evaluation (progression vs. pseudo-progression) of ASL and DSC perfusion maps differ when ATT artifacts are present?; 3) Do delayed ATTs affect the predictive value of ASL-MRI scans 3 months post-radiotherapy for detecting true disease progression? Material and Methods This retrospective, single-center study included 68 adult patients with histologically confirmed glioblastoma who received postoperative radio(chemo)therapy. ASL and DSC scans were acquired 3 months post-radiotherapy as part of routine clinical follow-up. The perfusion data were visually scored by a neuroradiologist who determined presence/absence of ATT artifacts and their severity (%), perfusion of the enhancing tumor lesion and the radiological evaluation of tumor progression versus pseudo-progression. Presence of true disease progression was determined by follow-up of clinical data until 9 months post-radiotherapy available for 49/68 patients. Logistic regression was performed with gender, age, treatment type and tumor genetic status as covariates to assess the predictive value of ASL. Results In 78% of the patients ATT artifacts were present. No statistically significant association between the agreement of the perfusion maps and presence of ATT artifacts was found, but presence of ATT artifacts lowered the agreement between the DSC and ASL radiological evaluation. The logistic regression analysis showed that the ASL-based radiological score could not predict true disease progression, whereas higher age and unmethylated MGMT gene were associated with progression. Presence of ATT artifacts was not associated with tumor progression. Conclusion The presence of delayed ATT in ASL data seems to impact the radiological evaluation of ASL data, steering interpretation towards tumor progression (as compared to the DSC evaluation), whereas in patients without ATT artifacts ASL and DSC provide more similar radiological scores. Therefore, it is highly recommended to consider these artifacts when interpreting ASL perfusion MRI to differentiate between tumor progression and pseudo-progression in glioblastoma patients.

In the clinical follow-up of glioblastoma patients, presence of delayed arterial transit times (ATT) could affect the evaluation of ASL perfusion data. In this retrospective study the influence of the presence and severity of ATT-artifacts on perfusion assessment and differentiation between tumor progression and pseudo-progression were studied. The results show that the presence of ATT-artifacts lowers the agreement between radiological evaluation of DSC-MRI and ASL, although the severity of ATT-artifacts did not have significant influence. In conclusion, detection of ATT-artifacts is important as it could affect radiological evaluation of ASL-data. Future work aims to include additional quantitative perfusion measures.