Brain Tumor Imaging without Gadolinium-based Contrast Agents: Feasible or Fantasy?

Gadolinium-based contrast agents (GBCAs) form the cornerstone of current primary brain tumor MRI protocols at all stages of the patient journey. Though an imperfect measure of tumor grade, GBCAs are repeatedly used for diagnosis and monitoring. In practice, however, radiologists will encounter situations where GBCA injection is not needed or of doubtful benefit. Reducing GBCA administration could improve the patient burden of (repeated) imaging (especially in vulnerable patient groups, such as children), minimize risks of putative side effects, and benefit costs, logistics, and the environmental footprint. On the basis of the current literature, imaging strategies to reduce GBCA exposure for pediatric and adult patients with primary brain tumors will be reviewed. Early postoperative MRI and fixed-interval imaging of gliomas are examples of GBCA exposure with uncertain survival benefits. Half-dose GBCAs for gliomas and T2-weighted imaging alone for meningiomas are among options to reduce GBCA use. While most imaging guidelines recommend using GBCAs at all stages of diagnosis and treatment, non-contrast-enhanced sequences, such as the arterial spin labeling, have shown a great potential. Artificial intelligence methods to generate synthetic postcontrast images from decreased-dose or non-GBCA scans have shown promise to replace GBCA-dependent approaches. This review is focused on pediatric and adult gliomas and meningiomas. Special attention is paid to the quality and real-life applicability of the reviewed literature.

Performance of amide proton transfer imaging to differentiate true progression from therapy-related changes in gliomas and metastases.

OBJECTIVES: Differentiating true progression or recurrence (TP/TR) from therapy-related changes (TRC) is complex in brain tumours. Amide proton transfer-weighted (APT) imaging is a chemical exchange saturation transfer (CEST) MRI technique that may improve diagnostic accuracy during radiological follow-up. This systematic review and meta-analysis elucidated the level of evidence and details of state-of-the-art imaging for APT-CEST in glioma and brain metastasis surveillance. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for original articles about glioma and metastasis patients who received APT-CEST imaging for suspected TP/TR within 2 years after (chemo)radiotherapy completion. Modified Quality Assessment of Diagnostic Accuracy Studies-2 criteria were applied. A meta-analysis was performed to pool results and to compare subgroups. RESULTS: Fifteen studies were included for a narrative synthesis, twelve of which (500 patients) were deemed sufficiently homogeneous for a meta-analysis. Magnetisation transfer ratio asymmetry performed well in gliomas (sensitivity 0.88 [0.82-0.92], specificity 0.84 [0.72-0.91]) but not in metastases (sensitivity 0.64 [0.38-0.84], specificity 0.56 [0.33-0.77]). APT-CEST combined with conventional/advanced MRI rendered 0.92 [0.86-0.96] and 0.88 [0.72-0.95] in gliomas. Tumour type, TR prevalence, sex, and acquisition protocol were sources of significant inter-study heterogeneity in sensitivity (I2 = 62.25%; p < 0.01) and specificity (I2 = 66.31%; p < 0.001). CONCLUSION: A growing body of literature suggests that APT-CEST is a promising technique for improving the discrimination of TP/TR from TRC in gliomas, with limited data on metastases. CLINICAL RELEVANCE STATEMENT: This meta-analysis identified a utility for APT-CEST imaging regarding the non-invasive discrimination of brain tumour progression from therapy-related changes, providing a critical evaluation of sequence parameters and cut-off values, which can be used to improve response assessment and patient outcome. KEY POINTS: Therapy-related changes mimicking progression complicate brain tumour treatment. Amide proton imaging improves the non-invasive discrimination of glioma progression from therapy-related changes. Magnetisation transfer ratio asymmetry measurement seems not to have added value in brain metastases.

Ten Years of VASARI Glioma Features: Systematic Review and Meta-Analysis of Their Impact and Performance.

BACKGROUND: Visually Accessible Rembrandt (Repository for Molecular Brain Neoplasia Data) Images (VASARI) features, a vocabulary to establish reproducible terminology for glioma reporting, have been applied for a decade, but a systematic performance evaluation is lacking. PURPOSE: Our aim was to conduct a systematic review and meta-analysis of the performance of the VASARI features set for glioma assessment. DATA SOURCES: MEDLINE, Web of Science, EMBASE, and the Cochrane Library were systematically searched until September 26, 2023. STUDY SELECTION: Original articles predicting diagnosis, progression, and survival in patients with glioma were included. DATA ANALYSIS: The modified Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was applied to evaluate the risk-of-bias. The meta-analysis used a random effects model and forest plot visualizations, if ≥5 comparable studies with a low or medium risk of bias were provided. DATA SYNTHESIS: Thirty-five studies (3304 patients) were included. Risk-of-bias scores were medium (n = 33) and low (n = 2). Recurring objectives were overall survival (n = 18) and isocitrate dehydrogenase mutation (IDH; n = 12) prediction. Progression-free survival was examined in 7 studies. In 4 studies (glioblastoma n = 2, grade 2/3 glioma n = 1, grade 3 glioma n = 1), a significant association was found between progression-free survival and single VASARI features. The single features predicting overall survival with the highest pooled hazard ratios were multifocality (hazard ratio = 1.80; 95%-CI, 1.21-2.67; I2 = 53%), ependymal invasion (hazard ratio = 1.73; 95% CI, 1.45-2.05; I2 = 0%), and enhancing tumor crossing the midline (hazard ratio = 2.08; 95% CI, 1.35-3.18; I2 = 52%). IDH mutation-predicting models combining VASARI features rendered a pooled area under the receiver operating characteristic curve of 0.82 (95% CI, 0.76-0.88) at considerable heterogeneity (I2 = 100%). Combined input models using VASARI plus clinical and/or radiomics features outperformed single data-type models in all relevant studies (n = 17). LIMITATIONS: Studies were heterogeneously designed and often with a small sample size. Several studies used The Cancer Imaging Archive database, with likely overlapping cohorts. The meta-analysis for IDH was limited due to a high study heterogeneity. CONCLUSIONS: Some VASARI features perform well in predicting overall survival and IDH mutation status, but combined models outperform single features. More studies with less heterogeneity are needed to increase the evidence level.

Rasmussen's encephalitis: structural, functional, and clinical correlates of contralesional epileptiform activity.

Progressive inflammation of one hemisphere characterises Rasmussen's encephalitis (RE), but contralesional epileptiform activity has been repeatedly reported. We aimed to quantify contralesional epileptiform activity in RE and uncover its functional and structural underpinnings. We retrospectively ascertained people with RE treated between 2000 and 2018 at a tertiary centre (Centre 1) and reviewed all available EEG datasets. The temporal occurrence of preoperative contralesional epileptiform activity (interictal/ictal) was evaluated using mixed-effects logistic regression. Cases with/without contralesional epileptiform activity were compared for cognition, inflammation (ipsilesional brain biopsies), and MRI (cortical and fixel-based morphometry). EEG findings were validated in a second cohort treated at another tertiary centre (Centre 2) between 1995 and 2020. We included 127 people with RE and 687 EEG samples. Preoperatively, contralesional epileptiform activity was seen in 30/68 (44%, Centre 1) and 8/59 (14%, Centre 2). In both cohorts, this activity was associated with younger onset age (OR = 0.9; 95% CI 0.83-0.97; P = 0.006). At centre 1, contralesional epileptiform activity was associated with contralesional MRI alterations, lower intelligence (OR = 5.19; 95% CI 1.28-21.08; P = 0.021), and impaired verbal memory (OR = 10.29; 95% CI 1.97-53.85; P = 0.006). After hemispherotomy, 11/17 (65%, Centre 1) and 28/37 (76%, Centre 2) were seizure-free. Contralesional epileptiform activity was persistent postoperatively in 6/12 (50%, Centre 1) and 2/34 (6%, Centre 2). Preoperative contralesional epileptiform activity reduced the chance of postoperative seizure freedom in both cohorts (OR = 0.69; 95% CI 0.50-0.95; P = 0.029). Our findings question the concept of strict unilaterality of RE and provide the evidence of contralesional epileptiform activity as a possible EEG predictor for persisting postoperative seizures.