Our study demonstrates that 2HG-MRS can be linked with routine MR imaging to provide quantitative measurements of 2HG in glioma and may be useful as an imaging biomarker to monitor the abundance of IDH-mutant tumor cells noninvasively during glioma therapy and disease monitoring.

Pseudoprogression may present as transient new or increasing enhancing lesions that mimic recurrent tumors in treated glioblastoma. The purpose of this study was to examine the utility of dynamic contrast enhanced T1 magnetic resonance imaging (DCE MRI) in differentiating between pseudoprogression and tumor progression and devise a cut-off value sensitive for pseudoprogression. We retrospectively examined 37 patients with glioblastoma treated with radiation and temozolomide after surgical resection that then developed new or increasing enhancing lesion(s) indeterminate for pseudoprogression versus progression. Volumetric plasma volume (Vp) and time-dependent leakage constant (Ktrans) maps were measured for the enhancing lesion and the mean and ninetieth percentile histogram values recorded. Lesion outcome was determined by clinical follow up with pseudoprogression defined as stable disease not requiring new treatment. Statistical analysis was performed with Wilcoxon rank-sum tests. Patients with pseudoprogression (n = 13) had Vp (mean) = 2.4 and Vp (90 %tile) = 3.2; and Ktrans (mean) = 3.5 and Ktrans (90 %tile) = 4.2. Patients with tumor progression (n = 24) had Vp (mean) = 5.3 and Vp (90 %tile) = 6.6; and Ktrans (mean) = 7.4 and Ktrans (90 %tile) = 9.1. Compared with tumor progression, pseudoprogression demonstrated lower Vp perfusion values (p = 0.0002) with a Vp (mean) cutoff <3.7 yielding 85 % sensitivity and 79 % specificity for pseudoprogression. Ktrans (mean) of >3.6 had a 69 % sensitivity and 79 % specificity for disease progression. DCE MRI shows lower plasma volume and time dependent leakage constant values in pseudoprogression than in tumor progression. A cut-off value with high sensitivity for pseudoprogression can be applied to aid in interpretation of DCE MRI.

Purpose Accurate glioma grading is crucial for treatment planning and predicting prognosis. We performed a quantitative volumetric analysis to assess the diagnostic accuracy of histogram analysis of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) T1-weighted perfusion imaging in the preoperative evaluation of gliomas. Methods Sixty-three consecutive patients with pathologically-confirmed gliomas who underwent baseline DWI and DCE-MRI were enrolled. The patients were classified by histopathology according to tumor grade: 20 low-grade gliomas (grade II) and 43 high-grade gliomas (grades III and IV). Volumes-of-interest were calculated and transferred to DCE perfusion and ADC maps. Histogram analysis was performed to determine mean and maximum values for Vp and Ktrans, and mean and minimum values for ADC. Comparisons between high-grade and low-grade gliomas, and between grades II, III and IV, were performed. A Mann-Whitney U test at a significance level of corrected p≤0.01 was used to assess differences. Results All perfusion parameters could differentiate between high-grade and low-grade gliomas (p<0.001) and between grades II and IV, grades II and III and grades III and IV. Significant differences in minimum ADC were also found (p<0.01). Mean ADC only differed significantly between high and low grades and grades II and IV (p<0.01). There were no differences between grades II and III (p=0.1) and grades III and IV (p=0.71). Conclusion When derived from whole-tumor histogram analysis, DCE-MRI perfusion parameters performed better than ADC in non-invasively discriminating low- from high-grade gliomas.

Background Glioblastoma and primary CNS lymphoma (PCNSL) dictate different neurosurgical strategies; it is critical to distinguish between them preoperatively. However, current imaging modalities do not effectively differentiate them. We aim to examine the use of DWI and T1-weighted dynamic contrast-enhanced (DCE)-MRI as potential discriminative tools. Methods We retrospectively reviewed 18 PCNSL and 36 matched glioblastoma patients with pretreatment DWI- and DCE-MRI. VOIs were drawn around the tumor on contrast-enhanced T1WI and FLAIR images; these images were transferred onto coregistered ADC maps to obtain ADC, and onto DCE perfusion maps to obtain plasma volume (Vp) and permeability transfer constant (Ktrans). Histogram analysis was performed to determine mean (ADCmean) and relative ADCmean (rADCmean), and relative 90th percentile values for plasma volume (rVp90%tile) and permeability transfer constant (rKtrans90%tile). Non-parametric tests were used to assess differences and ROC analysis was performed for optimal threshold calculations. Results The enhancing component of PCNSL was found to have significantly lower ADCmean (1.1 × 103 vs 1.4 × 103; p<0.001) and rADCmean (1.5 vs 1.9; p<0.001) and rVp90%tile (3.7 vs 5.0; p<0.05) than the enhancing component of glioblastoma, but not significantly different rKtrans90%tile (5.4 vs 4.4; p=0.83). The non-enhancing portions of GBM and PCNSL did not differ in these parameters. Based on ROC analysis, mean ADC provided the best threshold (AUC 0.83) to distinguish primary CNS lymphoma from glioblastoma, which was not improved with normalized ADC or addition of perfusion parameters. Conclusion ADC was superior to DCE-MRI perfusion alone or in combination in differentiating PCNSL from glioblastoma.

Background Context Recent advances in image guidance and stereotactic body radiotherapy (SBRT) have resulted in unprecedented local control for spinal metastases of all histologies. However, little is known about early imaging biomarkers of local control. Purpose To identify early MRI biomarkers to predict local control after SBRT for patients with sarcoma spine metastases. Study Design/Setting Retrospective case series at a large tertiary cancer center. Patient Sample From 2011 to 2014, nine consecutive patients with 12 metastatic sarcoma lesions to the spine were treated with SBRT and underwent evaluation with DCE-MRI both pre- and post-SBRT. Outcome Measure Changes in perfusion metrics, including the wash-in rate constant (Ktrans), plasma volume (Vp), composite multi-parametric MRI (mpMRI) score, bi-dimensional tumor size, and a graded response assessment were performed and correlated to local control. Methods All measurements were independent and blinded by two neuroradiologists. R2 statistics were performed to document correlation, and two-tailed t-tests were used to compare groups. P<0.05 was deemed statistically significant. Results The median time from SBRT until post-treatment MRI was 57 days. Local failure developed in one lesion (8.3%) 10 months after SBRT. Vp mean, Ktrans mean, Vp max, and Ktrans max were significantly decreased post-SBRT as compared to pre-SBRT (58.7%, 63.2%, 59.0%, and 55.2%; all p-values <0.05). Bi-dimensional tumor measurements demonstrated an average increase in size across the cohort, and 50%, 25%, and 25% of the treated lesions demonstrated features of “worsening,” “no change,” or “improvement,” respectively, by both radiologists’ graded impressions. There was good inter-reader reliability for both size and subjective disease response scores (R2 = 0.84). The mpMRI score had 100% accuracy in predicting local control at time of last follow-up. There was no apparent correlation with size changes compared to the mpMRI score change post-SBRT (R2 = 0.026). Conclusions We report the first analysis on the utility of DCE-MRI for metastatic sarcoma spine metastases treated with SBRT. We demonstrate that early assessment at two months post-SBRT using size and subjective neuroradiology impressions is insufficient to judge ultimate disease progression, and that a combination of perfusion parameters provides excellent correlation to local control.