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PurposeAntiangiogenic therapies are known to cause high radiographic response rates due to reduction in vascular permeability resulting in a lower degree of contrast extravasation. In this study, we investigate the prognostic ability for model-derived parameters describing enhancing tumor volumetric dynamics to predict survival in recurrent glioblastoma treated with antiangiogenic therapy.Experimental designN = 276 patients in two phase II trials were used as training data, including bevacizumab ± irinotecan (NCT00345163) and cabozantinib (NCT00704288), and N = 74 patients in the bevacizumab arm of a phase III trial (NCT02511405) were used for validation. Enhancing volumes were estimated using T1 subtraction maps, and a biexponential model was used to estimate regrowth (g) and regression (d) rates, time to tumor regrowth (TTG), and the depth of response (DpR). Response characteristics were compared to diffusion MR phenotypes previously shown to predict survival.ResultsOptimized thresholds occurred at g = 0.07 months-1 (phase II: HR = 0.2579, P = 5 × 10-20; phase III: HR = 0.2197, P = 5 × 10-5); d = 0.11 months-1 (HR = 0.3365, P < 0.0001; HR = 0.3675, P = 0.0113); TTG = 3.8 months (HR = 0.2702, P = 6 × 10-17; HR = 0.2061, P = 2 × 10-5); and DpR = 11.3% (HR = 0.6326, P = 0.0028; HR = 0.4785, P = 0.0206). Multivariable Cox regression controlling for age and baseline tumor volume confirmed these factors as significant predictors of survival. Patients with a favorable pretreatment diffusion MRI phenotype had a significantly longer TTG and slower regrowth.ConclusionsRecurrent glioblastoma patients with a large, durable radiographic response to antiangiogenic agents have significantly longer survival. This information is useful for interpreting activity of antiangiogenic agents in recurrent glioblastoma.

PurposeThere is limited knowledge about the associations between sodium and proton MRI measurements in brain tumors. The purpose of this study was to quantify intra- and intertumoral correlations between sodium, diffusion, and perfusion MRI in human gliomas.MethodsTwenty glioma patients were prospectively studied on a 3T MRI system with multinuclear capabilities. Three mutually exclusive tumor volumes of interest (VOIs) were segmented: contrast-enhancing tumor (CET), T2/FLAIR hyperintense non-enhancing tumor (NET), and necrosis. Median and voxel-wise associations between apparent diffusion coefficient (ADC), normalized relative cerebral blood volume (nrCBV), and normalized sodium measurements were quantified for each VOI.ResultsBoth relative sodium concentration and ADC were significantly higher in areas of necrosis compared to NET (P = 0.003 and P = 0.008, respectively) and CET (P = 0.02 and P = 0.02). Sodium concentration was higher in CET compared to NET (P = 0.04). Sodium and ADC were higher in treated compared to treatment-naïve gliomas within NET (P = 0.006 and P = 0.01, respectively), and ADC was elevated in CET (P = 0.03). Median ADC and sodium concentration were positively correlated across patients in NET (r = 0.77, P

BackgroundAlterations in tumor growth rate (TGR) in recurrent glioblastoma (rGBM) after treatment may be useful for identifying therapeutic activity. The aim of this study was to assess the impact of volumetric TGR alterations on overall survival (OS) in rGBM treated with chemotherapy with or without radiation therapy (RT).MethodsSixty-one rGBM patients treated with chemotherapy with or without concomitant radiation therapy (RT) at 1st or 2nd recurrence were retrospectively examined. Pre- and post-treatment contrast enhancing volumes were computed. Patients were considered "responders" if they reached progression-free survival at 6 months (PFS6) and showed a decrease in TGR after treatment and "non-responders" if they didn't reach PFS6 or if TGR increased.ResultsStratification by PFS6 and based on TGR resulted in significant differences in OS both for all patients and for patients without RT (P < 0.05). A decrease of TGR (P = 0.009), smaller baseline tumor volume (P = 0.02), O6-methylguanine-DNA methyltransferase promoter methylation (P = 0.048) and fewer number of recurrences (P = 0.048) were significantly associated with longer OS after controlling for age, sex and concomitant RT.ConclusionA decrease in TGR in patients with PFS6, along with smaller baseline tumor volume, were associated with a significantly longer OS in rGBM treated with chemotherapy with or without radiation. Importantly, all patients that exhibited PFS6 also showed a measurable decrease in TGR.

Objectives: To assess the accuracy, repeatability, and reproducibility of T1 and T2 relaxation time measurements by three-dimensional magnetic resonance fingerprinting (3D MRF) using various dictionary resolutions. Methods: The ISMRM/NIST phantom was scanned daily for 10 days in two 3 T MR scanners using a 3D MRF sequence reconstructed using four dictionaries with varying step sizes and one dictionary with wider ranges. Thirty-nine healthy volunteers were enrolled: 20 subjects underwent whole-brain MRF scans in both scanners and the rest in one scanner. ROI/VOI analyses were performed on phantom and brain MRF maps. Accuracy, repeatability, and reproducibility metrics were calculated. Results: In the phantom study, all dictionaries showed high T1 linearity to the reference values (R2 > 0.99), repeatability (CV < 3%), and reproducibility (CV < 3%) with lower linearity (R2 > 0.98), repeatability (CV < 6%), and reproducibility (CV ≤ 4%) for T2 measurement. The volunteer study demonstrated high T1 reproducibility of within-subject CV (wCV) < 4% by all dictionaries with the same ranges, both in the brain parenchyma and CSF. Yet, reproducibility was moderate for T2 measurement (wCV < 8%). In CSF measurement, dictionaries with a smaller range showed a seemingly better reproducibility (T1, wCV 3%; T2, wCV 8%) than the much wider range dictionary (T1, wCV 5%; T2, wCV 13%). Truncated CSF relaxometry values were evident in smaller range dictionaries. Conclusions: The accuracy, repeatability, and reproducibility of 3D MRF across various dictionary resolutions were high for T1 and moderate for T2 measurements. A lower-resolution dictionary with a well-defined range may be adequate, thus significantly reducing the computational load. Key Points: • A lower-resolution dictionary with a well-defined range may be sufficient for 3D MRF reconstruction. • CSF relaxation times might be underestimated due to truncation by the upper dictionary range. • Dictionary with a higher upper range might be advisable, especially for CSF evaluation and elderly subjects whose perivascular spaces are more prominent. [ABSTRACT FROM AUTHOR]

Background: Neuromelanin‐sensitive magnetic resonance imaging techniques have been developed but currently require relatively long scan times. The aim of this study was to assess the ability of black‐blood delay alternating with nutation for tailored excitation‐prepared T1‐weighted variable flip angle turbo spin echo (DANTE T1‐SPACE), which provides relatively high resolution with a short scan time, to visualize neuromelanin in the substantia nigra pars compacta (SNpc). Methods: Participants comprised 49 healthy controls and 25 patients with Parkinson's disease (PD). Contrast ratios of SNpc and hyperintense SNpc areas, which show pixels brighter than thresholds, were assessed between DANTE T1‐SPACE and T1‐SPACE in healthy controls. To evaluate the diagnostic ability of DANTE T1‐SPACE, the contrast ratios and hyperintense areas were compared between healthy and PD groups, and receiver operating characteristic analyses were performed. We also compared areas under the curve (AUCs) between DANTE T1‐SPACE and the previously reported gradient echo neuromelanin (GRE‐NM) imaging. Each analysis was performed using original images in native space and images transformed into Montreal Neurological Institute space. Values of P < 0.05 were considered significant. Results: DANTE T1‐SPACE showed significantly higher contrast ratios and larger hyperintense areas than T1‐SPACE. On DANTE T1‐SPACE, healthy controls showed significantly higher contrast ratios and larger hyperintense areas than patients with PD. Hyperintense areas in native space analysis achieved the best AUC (0.94). DANTE T1‐SPACE showed AUCs as high as those of GRE‐NM. Conclusions: DANTE T1‐SPACE successfully visualized neuromelanin of the SNpc and showed potential for evaluating PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background: Hypothalamic–pituitary–thyroid (HPT) maturation has not been extensively evaluated using neonatal MRI, even though both structures are visualized on MRI. Hypothesis: That signal intensity and volume of pituitary and thyroid (T) glands on MRI in neonates may be interrelated. Study Type: Retrospective. Subjects: In all, 102 participants. Field Strength/Sequence: 3.0T, T1‐weighted pointwise encoding time reduction with radial acquisition (PETRA). Assessment: The volume of interest of the anterior pituitary (AP), posterior pituitary (PP), and T on MRI were defined on T1‐PETRA by two radiologists, and volumes of AP (AP_vol) and thyroid (T_vol) were calculated. Gestational age (GA), chronological age (CA), GA+CA, birth weight (BW), and thyroid function were recorded. Mean and maximum signal intensities of AP, PP, and T were normalized using signals from the pons and spinal cord as follows: signal ratio of anterior pituitary/pons (AP/pons), signal ratio of posterior pituitary/pons (PP/pons), and signal ratio of thyroid/cord (T/cord) T/cord, respectively. Statistical Tests: Correlations between signal intensity and volume measures and GA, CA, GA+CA, and BW were assessed using Pearson's correlation coefficient or Spearman's rank correlation coefficient. Thyroid function analysis and Tmean/cord, Tmax/cord, and T_vol were evaluated using the Steel–Dwass test. Results: APmean/pons correlated positively with GA (ρ = 0.62, P < 0.001) and BW (ρ = 0.74, P < 0.001), and negatively with CA (ρ = −0.86, P < 0.001) and GA+CA (ρ = −0.46, P < 0.001). PPmean/pons correlated positively with GA (ρ = 0.49, P < 0.001) and BW (ρ = 0.63, P < 0.001), and negatively with CA (ρ = −0.70, P < 0.001) and GA+CA (r = −0.38, P < 0.001). Tmean/cord correlated positively with GA (ρ = 0.48, P < 0.001) and BW (ρ = 0.55, P < 0.001), and negatively with CA (ρ = −0.59, P < 0.001) and GA+CA (ρ = −0.22, P = 0.03). AP_vol correlated positively with GA (ρ = 0.68, P < 0.001) and BW (ρ = 0.73, P < 0.001), and negatively with CA (ρ = −0.72, P < 0.001). T_vol correlated positively with GA (ρ = 0.50, P < 0.001) and BW (ρ = 0.61, P < 0.001), and negatively with CA (ρ = −0.54, P < 0.001). APmean/pons correlated positively with Tmean/cord (ρ = 0.61, P < 0.001). Data Conclusion: Signal and volume of pituitary and thyroid glands correlated positively with GA and BW, and negatively with CA in neonates. Level of Evidence: 4 Technical Efficacy Stage: 5 [ABSTRACT FROM AUTHOR]

Background and Purpose: Resting-state functional MRI (rs-fMRI) can be used to estimate functional connectivity (FC) between different brain regions, which may be of value for identifying cognitive impairment in patients with brain tumors. Unfortunately, neither rs-fMRI nor neurocognitive assessments are routinely assessed clinically, mostly due to limitations in examination time and cost. Since DSC perfusion MRI is often used clinically to assess tumor vascularity and similarly uses a gradient-echo-EPI sequence for T2*-sensitivity, we theorized a "pseudo-rs-fMRI" signal could be derived from DSC perfusion to simultaneously quantify FC and perfusion metrics, and these metrics can be used to estimate cognitive impairment in patients with brain tumors., Materials and Methods: Twenty-four consecutive patients with gliomas were enrolled in a prospective study that included DSC perfusion MRI, resting-sate functional MRI (rs-fMRI), and neurocognitive assessment. Voxelwise modeling of contrast bolus dynamics during DSC acquisition was performed and then subtracted from the original signal to generate a residual "pseudo-rs-fMRI" signal. Following the preprocessing of pseudo-rs-fMRI, full rs-fMRI, and a truncated version of the full rs-fMRI (first 100 timepoints) data, the default mode, motor, and language network maps were generated with atlas-based ROIs, Dice scores were calculated for the resting-state network maps from pseudo-rs-fMRI and truncated rs-fMRI using the full rs-fMRI maps as reference. Seed-to-voxel and ROI-to-ROI analyses were performed to assess FC differences between cognitively impaired and nonimpaired patients., Results: Dice scores for the group-level and patient-level (mean±SD) default mode, motor, and language network maps using pseudo-rs-fMRI were 0.905/0.689 ± 0.118 (group/patient), 0.973/0.730 ± 0.124, and 0.935/0.665 ± 0.142, respectively. There was no significant difference in Dice scores between pseudo-rs-fMRI and the truncated rs-fMRI default mode ( P = .97) or language networks ( P = .30), but there was a difference in motor networks ( P = .02). A multiple logistic regression classifier applied to ROI-to-ROI FC networks using pseudo-rs-fMRI could identify cognitively impaired patients (sensitivity = 84.6%, specificity = 63.6%, receiver operating characteristic area under the curve (AUC) = 0.7762 ± 0.0954 (standard error), P = .0221) and performance was not significantly different from full rs-fMRI predictions (AUC = 0.8881 ± 0.0733 (standard error), P = .0013, P = .29 compared with pseudo-rs-fMRI)., Conclusions: DSC perfusion MRI-derived pseudo-rs-fMRI data can be used to perform typical rs-fMRI FC analyses that may identify cognitive decline in patients with brain tumors while still simultaneously performing perfusion analyses., (© 2024 by American Journal of Neuroradiology.)

Background and Purpose: The T2-FLAIR mismatch sign on MR imaging is a highly specific imaging biomarker of isocitrate dehydrogenase ( IDH )-mutant astrocytomas, which lack 1p/19q codeletion. However, most studies using the T2-FLAIR mismatch sign have used visual assessment. This study quantified the degree of T2-FLAIR mismatch using digital subtraction of fluid-nulled T2-weighted FLAIR images from non-fluid-nulled T2-weighted images in human nonenhancing diffuse gliomas and then used this information to assess improvements in diagnostic performance and investigate subregion characteristics within these lesions., Materials and Methods: Two cohorts of treatment-naïve, nonenhancing gliomas with known IDH and 1p/19q status were studied ( n  = 71 from The Cancer Imaging Archive (TCIA) and n  = 34 in the institutional cohort). 3D volumes of interest corresponding to the tumor were segmented, and digital subtraction maps of T2-weighted MR imaging minus T2-weighted FLAIR MR imaging were used to partition each volume of interest into a T2-FLAIR mismatched subregion (T2-FLAIR mismatch, corresponding to voxels with positive values on the subtraction maps) and nonmismatched subregion (T2-FLAIR nonmismatch corresponding to voxels with negative values on the subtraction maps). Tumor subregion volumes, percentage of T2-FLAIR mismatch volume, and T2-FLAIR nonmismatch subregion thickness were calculated, and 2 radiologists assessed the T2-FLAIR mismatch sign with and without the aid of T2-FLAIR subtraction maps., Results: Thresholds of ≥42% T2-FLAIR mismatch volume classified IDH -mutant astrocytoma with a specificity/sensitivity of 100%/19.6% (TCIA) and 100%/31.6% (institutional); ≥25% T2-FLAIR mismatch volume showed 92.0%/32.6% and 100%/63.2% specificity/sensitivity, and ≥15% T2-FLAIR mismatch volume showed 88.0%/39.1% and 93.3%/79.0% specificity/sensitivity. In IDH -mutant astrocytomas with ≥15% T2-FLAIR mismatch volume, T2-FLAIR nonmismatch subregion thickness was negatively correlated with the percentage T2-FLAIR mismatch volume ( P  < .0001) across both cohorts. The percentage T2-FLAIR mismatch volume was higher in grades 3-4 compared with grade 2 IDH -mutant astrocytomas ( P  < .05), and ≥15% T2-FLAIR mismatch volume IDH- mutant astrocytomas were significantly larger than <15% T2-FLAIR mismatch volume IDH -mutant astrocytoma ( P  < .05) across both cohorts. When evaluated by 2 radiologists, the additional use of T2-FLAIR subtraction maps did not show a significant difference in interreader agreement, sensitivity, or specificity compared with a separate evaluation of T2-FLAIR and T2-weighted MR imaging alone., Conclusions: T2-FLAIR digital subtraction maps may be a useful, automated tool to obtain objective segmentations of tumor subregions based on quantitative thresholds for classifying IDH -mutant astrocytomas using the percentage T2 FLAIR mismatch volume with 100% specificity and exploring T2-FLAIR mismatch/T2-FLAIR nonmismatch subregion characteristics. Conversely, the addition of T2-FLAIR subtraction maps did not enhance the sensitivity or specificity of the visual T2-FLAIR mismatch sign assessment by experienced radiologists., (© 2024 by American Journal of Neuroradiology.)