A Neuroradiologist's Guide to Operationalizing the Response Assessment in Neuro-Oncology (RANO) Criteria Version 2.0 for Gliomas in Adults.

Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults. This article provides an overview of significant updates to the criteria including (1) the use of a unified set of criteria for high and low grade gliomas in adults; (2) the use of the post-radiotherapy MRI scan as the baseline for evaluation in newly diagnosed high-grade gliomas; (3) the option for the trial to mandate a confirmation scan to more reliably distinguish pseudoprogression from tumor progression; (4) the option of using volumetric tumor measurements; and (5) the removal of subjective non-enhancing tumor evaluations in predominantly enhancing gliomas (except for specific therapeutic modalities). Step-by-step pragmatic guidance is hereby provided for the neuroradiologist and imaging core lab involved in operationalization and technical execution of RANO 2.0 in clinical trials, including the display of representative cases and in-depth discussion of challenging scenarios.

RANO 2.0: Update to the Response Assessment in Neuro-Oncology Criteria for High- and Low-Grade Gliomas in Adults.

PURPOSE: The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time, some limitations of these criteria were identified, and challenges emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria. METHODS: Informed by data from studies evaluating the different criteria, updates to the RANO criteria are proposed (RANO 2.0). RESULTS: We recommend a standard set of criteria for both high- and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the postradiotherapy magnetic resonance imaging (MRI), rather than the postsurgical MRI, will be used as the baseline for comparison with subsequent scans. Since the incidence of pseudoprogression is high in the 12 weeks after radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, are required to define tumor progression. However, confirmation scans are not mandatory after this period nor for the evaluation of treatment for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is highly recommended. The primary measurement remains the maximum cross-sectional area of tumor (two-dimensional) but volumetric measurements are an option. For IDH wild-type glioblastoma, the nonenhancing disease will no longer be evaluated except when assessing response to antiangiogenic agents. In IDH-mutated tumors with a significant nonenhancing component, clinical trials may require evaluating both the enhancing and nonenhancing tumor components for response assessment. CONCLUSION: The revised RANO 2.0 criteria refine response assessment in gliomas.

Longitudinal Assessment of Posttreatment Diffuse Glioma Tissue Volumes with Three-dimensional Convolutional Neural Networks.

Neural networks were trained for segmentation and longitudinal assessment of posttreatment diffuse glioma. A retrospective cohort (from January 2018 to December 2019) of 298 patients with diffuse glioma (mean age, 52 years ± 14 [SD]; 177 men; 152 patients with glioblastoma, 72 patients with astrocytoma, and 74 patients with oligodendroglioma) who underwent two consecutive multimodal MRI examinations were randomly selected into training (n = 198) and testing (n = 100) samples. A posttreatment tumor segmentation three-dimensional nnU-Net convolutional neural network with multichannel inputs (T1, T2, and T1 postcontrast and fluid-attenuated inversion recovery [FLAIR]) was trained to segment three multiclass tissue types (peritumoral edematous, infiltrated, or treatment-changed tissue [ED]; active tumor or enhancing tissue [AT]; and necrotic core). Separate longitudinal change nnU-Nets were trained on registered and subtracted FLAIR and T1 postlongitudinal images to localize and better quantify and classify changes in ED and AT. Segmentation Dice scores, volume similarities, and 95th percentile Hausdorff distances ranged from 0.72 to 0.89, 0.90 to 0.96, and 2.5 to 3.6 mm, respectively. Accuracy rates of the posttreatment tumor segmentation and longitudinal change networks being able to classify longitudinal changes in ED and AT as increased, decreased, or unchanged were 76%-79% and 90%-91%, respectively. The accuracy levels of the longitudinal change networks were not significantly different from those of three neuroradiologists (accuracy, 90%-92%; κ, 0.58-0.63; P > .05). The results of this study support the potential clinical value of artificial intelligence-based automated longitudinal assessment of posttreatment diffuse glioma. Keywords: MR Imaging, Neuro-Oncology, Neural Networks, CNS, Brain/Brain Stem, Segmentation, Quantification, Convolutional Neural Network (CNN) Supplemental material is available for this article. © RSNA, 2022.

Assessment of higher-order singular value decomposition denoising methods on dynamic hyperpolarized [1-13C]pyruvate MRI data from patients with glioma.

BACKGROUND: Real-time metabolic conversion of intravenously-injected hyperpolarized [1-13C]pyruvate to [1-13C]lactate and [13C]bicarbonate in the brain can be measured using dynamic hyperpolarized carbon-13 (HP-13C) MRI. However, voxel-wise evaluation of metabolism in patients with glioma is challenged by the limited signal-to-noise ratio (SNR) of downstream 13C metabolites, especially within lesions. The purpose of this study was to evaluate the ability of higher-order singular value decomposition (HOSVD) denoising methods to enhance dynamic HP [1-13C]pyruvate MRI data acquired from patients with glioma. METHODS: Dynamic HP-13C MRI were acquired from 14 patients with glioma. The effects of two HOSVD denoising techniques, tensor rank truncation-image enhancement (TRI) and global-local HOSVD (GL-HOSVD), on the SNR and kinetic modeling were analyzed in [1-13C]lactate data with simulated noise that matched the levels of [13C]bicarbonate signals. Both methods were then evaluated in patient data based on their ability to improve [1-13C]pyruvate, [1-13C]lactate and [13C]bicarbonate SNR. The effects of denoising on voxel-wise kinetic modeling of kPL and kPB was also evaluated. The number of voxels with reliable kinetic modeling of pyruvate-to-lactate (kPL) and pyruvate-to-bicarbonate (kPB) conversion rates within regions of interest (ROIs) before and after denoising was then compared. RESULTS: Both denoising methods improved metabolite SNR and regional signal coverage. In patient data, the average increase in peak dynamic metabolite SNR was 2-fold using TRI and 4-5 folds using GL-HOSVD denoising compared to acquired data. Denoising reduced kPL modeling errors from a native average of 23% to 16% (TRI) and 15% (GL-HOSVD); and kPB error from 42% to 34% (TRI) and 37% (GL-HOSVD) (values were averaged voxelwise over all datasets). In contrast-enhancing lesions, the average number of voxels demonstrating within-tolerance kPL modeling error relative to the total voxels increased from 48% in the original data to 84% (TRI) and 90% (GL-HOSVD), while the number of voxels showing within-tolerance kPB modeling error increased from 0% to 15% (TRI) and 8% (GL-HOSVD). CONCLUSION: Post-processing denoising methods significantly improved the SNR of dynamic HP-13C imaging data, resulting in a greater number of voxels satisfying minimum SNR criteria and maximum kinetic modeling errors in tumor lesions. This enhancement can aid in the voxel-wise analysis of HP-13C data and thereby improve monitoring of metabolic changes in patients with glioma following treatment.

Clinical Assessment of Deep Learning-based Super-Resolution for 3D Volumetric Brain MRI.

Artificial intelligence (AI)-based image enhancement has the potential to reduce scan times while improving signal-to-noise ratio (SNR) and maintaining spatial resolution. This study prospectively evaluated AI-based image enhancement in 32 consecutive patients undergoing clinical brain MRI. Standard-of-care (SOC) three-dimensional (3D) T1 precontrast, 3D T2 fluid-attenuated inversion recovery, and 3D T1 postcontrast sequences were performed along with 45% faster versions of these sequences using half the number of phase-encoding steps. Images from the faster sequences were processed by a Food and Drug Administration-cleared AI-based image enhancement software for resolution enhancement. Four board-certified neuroradiologists scored the SOC and AI-enhanced image series independently on a five-point Likert scale for image SNR, anatomic conspicuity, overall image quality, imaging artifacts, and diagnostic confidence. While interrater κ was low to fair, the AI-enhanced scans were noninferior for all metrics and actually demonstrated a qualitative SNR improvement. Quantitative analyses showed that the AI software restored the high spatial resolution of small structures, such as the septum pellucidum. In conclusion, AI-based software can achieve noninferior image quality for 3D brain MRI sequences with a 45% scan time reduction, potentially improving the patient experience and scanner efficiency without sacrificing diagnostic quality. Keywords: MR Imaging, CNS, Brain/Brain Stem, Reconstruction Algorithms © RSNA, 2022.

Feasibility of Simulated Postcontrast MRI of Glioblastomas and Lower-Grade Gliomas by Using Three-dimensional Fully Convolutional Neural Networks.

PURPOSE: To evaluate the feasibility and accuracy of simulated postcontrast T1-weighted brain MR images generated by using precontrast MR images in patients with brain glioma. MATERIALS AND METHODS: In this retrospective study, a three-dimensional deep convolutional neural network was developed to simulate T1-weighted postcontrast images from eight precontrast sequences in 400 patients (mean age, 57 years; 239 men; from 2015 to 2020), including 332 with glioblastoma and 68 with lower-grade gliomas. Performance was evaluated by using quantitative image similarity and error metrics and enhancing tumor overlap analysis. Performance was also assessed on a multicenter external dataset (n = 286 from the 2019 Multimodal Brain Tumor Segmentation Challenge; mean age, 60 years; ratio of men to women unknown) by using transfer learning. A subset of cases was reviewed by neuroradiologist readers to assess whether simulated images affected the ability to determine the tumor grade. RESULTS: Simulated whole-brain postcontrast images were both qualitatively and quantitatively similar to the real postcontrast images in terms of quantitative image similarity (structural similarity index of 0.84 ± 0.05), pixelwise error (symmetric mean absolute percent error of 3.65%), and enhancing tumor compartment overlap (Dice coefficient, 0.65 ± 0.25). Similar results were achieved with the external dataset (Dice coefficient, 0.62 ± 0.27). There was no difference in the ability of the neuroradiologist readers to determine the tumor grade in real versus simulated images (accuracy, 87.7% vs 90.6%; P = .87). CONCLUSION: The developed model was capable of producing simulated postcontrast T1-weighted MR images that were similar to real acquired images as determined by both quantitative analysis and radiologist assessment.Keywords: MR-Contrast Agent, MR-Imaging, CNS, Brain/Brain Stem, Contrast Agents-Intravenous, Neoplasms-Primary, Experimental Investigations, Technology Assessment, Supervised Learning, Transfer Learning, Convolutional Neural Network, Deep Learning Algorithms, Machine Learning Algorithms Supplemental material is available for this article. © RSNA, 2021.

Pairwise comparison versus Likert scale for biomedical image assessment.

OBJECTIVE: Biomedical imaging research relies heavily on the subjective and semi-quantitative reader analysis of images. Current methods are limited by interreader variability and fixed upper and lower limits. The purpose of this study was to compare the performance of two assessment methods, pairwise comparison and Likert scale, for improved analysis of biomedical images. MATERIALS AND METHODS: A set of 10 images with varying degrees of image sharpness was created by digitally blurring a normal clinical chest radiograph. Readers assessed the degree of image sharpness using two different methods: pairwise comparison and a 10-point Likert scale. Reader agreement with actual chest radiograph sharpness was calculated for each method by use of the Lin concordance correlation coefficient (CCC). RESULTS: Reader accuracy was highest for pairwise comparison (CCC, 1.0) and ranked Likert (CCC, 0.99) scores and lowest for nonranked Likert scores (CCC, 0.83). Accuracy improved slightly when readers repeated their assessments (CCC, 0.87) or had reference images available (CCC, 0.91). CONCLUSION: Pairwise comparison and ranked Likert scores yield more accurate reader assessments than nonranked Likert scores.