Figure 6 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
B0 maps (A) and resulting MTR asym images (B) generated by different methods. IDE-LF: iterative down-sampling (k-means clustering) estimation with Lorentzian fitting; LF-Poly: two stage Lorentzian estimation with 4D polynomial fitting. Black arrow: MTR asym (at 3.0 ppm) contrast in tumor area; white arrow: region with severe B 0 inhomogeneity.
Source publication
Amine chemical exchange saturation transfer (CEST) echoplanar imaging (EPI) provides unique pH and amino acid MRI contrast, enabling sensitive detection of altered microenvironment properties in various diseases. However, CEST contrast is sensitive to static magnetic field (B0) inhomogeneities. Here we propose 2 new B0 correction algorithms for use...
Contexts in source publication
Context 1
... example slice of estimated B 0 map and resulting MTR asym image generated by different correction methods is illustrated in Figure 6. The quantitative assessments of B 0 estimation methods for 7 patients are plotted in Figure 7, in- cluding image quality metrics PSNR and SSIM of B 0 maps and MTR asym images, computation time, and standard deviation of NAWM MTR asym . ...
Context 2
... all methods except for multiecho-phase method, the proposed IDE-LF method and the LF-Poly method perform the best in terms of having the highest PSNR and SSIM values and lowest NAWM MTR asym standard deviations, while the ninth-order polynomial and the smoothing-spline fittings of Z-spectra have the worst performance. Consistent with the quantitative metrics, the proposed IDE-LF method and the LF-Poly method generated MTR asym images that are visually less noisy in Figure 6, while compared, the proposed IDE-LF method and the LF-Poly method show significantly higher intertissue consistency (lower stan- dard deviation of NAWM MTR asym at 3.0 ppm) than the conven- tional CSC method and the multiecho-phase method (IDE-LF: P 2.03 10 18 compared with the CSC method and P 1.10 10 4 compared with the the multiecho-phase method; LF-Poly(a): P 9.02 10 19 compared with the CSC method and P 3.03 10 4 compared with the multiecho-phase method). There is no significant difference in the standard de- viation of NAWM MTR asym at 3.0 ppm between IDE-LF method and the LF-Poly methods (P .402/.939). ...
Context 3
... the mul- tiecho-phase method shifted the distribution noticeably in some of the patients. The proposed IDE-LF and LF-Poly methods shifted the distribution slightly toward the negative direction, which could be explained by the better B 0 estimation close to the sinus regions, alleviating the overestimation of MTR asym (at 3.0 ppm) in areas with very high B 0 ( Figure 6). No difference of whole-brain MTR asym distribution has been observed between the IDE-LF and LF-Poly methods. ...
Context 4
... uneven sampling of the Z-spectrum particularly impairs the fitting accuracy of the polynomial method when B 0 inhomogeneity is large (outside the range of central spectral points). This can be observed in Figure 6. Although voxel- by-voxel single-pool LF performs better, as it uses the global information of Z-spectra; this method requires unrealistic compu- tation time for whole-brain analysis (40 minutes to 1 hour per patient) and may still suffer from corrupt Z-spectral data. ...
Citations
... All CEST-SAGE-EPI and CEST-EPI images were motion corrected using an affine transformation (mcflirt; FSL, FMRIB, Oxford, United Kingdom) and B 0 correction via a z-spectra based k-means clustering and Lorentzian fitting algorithm [46]. Following motion and B 0 correction, the integral of width of 0.4 ppm was quantified around both the − 3.0 and + 3.0 ppm (− 3.2 to − 2.8 ppm and + 2.8 to + 3.2 ppm, respectively) spectral points. ...
Introduction
Hypoxia inducible factor 2-alpha (HIF2α) mediates cellular responses to hypoxia and is over-expressed in glioblastoma (GBM). PT2385 is an oral HIF2α inhibitor with in vivo activity against GBM.
Methods
A two-stage single-arm open-label phase II study of adults with GBM at first recurrence following chemoradiation with measurable disease was conducted through the Adult Brain Tumor Consortium. PT2385 was administered at the phase II dose (800 mg b.i.d.). The primary outcome was objective radiographic response (ORR = complete response + partial response, CR + PR); secondary outcomes were safety, overall survival (OS), and progression free survival (PFS). Exploratory objectives included pharmacokinetics (day 15 Cmin), pharmacodynamics (erythropoietin, vascular endothelial growth factor), and pH-weighted amine- chemical exchange saturation transfer (CEST) MRI to quantify tumor acidity at baseline and explore associations with drug response. Stage 1 enrolled 24 patients with early stoppage for ≤ 1 ORR.
Results
Of the 24 enrolled patients, median age was 62.1 (38.7–76.7) years, median KPS 80, MGMT promoter was methylated in 46% of tumors. PT2385 was well tolerated. Grade ≥ 3 drug-related adverse events were hypoxia (n = 2), hyponatremia (2), lymphopenia (1), anemia (1), and hyperglycemia (1). No objective radiographic responses were observed; median PFS was 1.8 months (95% CI 1.6–2.5) and OS was 7.7 months (95% CI 4.9–12.6). Drug exposure varied widely and did not differ by corticosteroid use (p = 0.12), antiepileptics (p = 0.09), or sex (p = 0.37). Patients with high systemic exposure had significantly longer PFS (6.7 vs 1.8 months, p = 0.009). Baseline acidity by pH-weighted CEST MRI correlated significantly with treatment duration (R² = 0.49, p = 0.017). Non-enhancing infiltrative disease with high acidity gave rise to recurrence.
Conclusions
PT2385 monotherapy had limited activity in first recurrent GBM. Drug exposure was variable. Signals of activity were observed in GBM patients with high systemic exposure and acidic lesions on CEST imaging. A second-generation HIF2α inhibitor is being studied.
... Despite its improved denoising performance, IDEAL used a fixed-square subgroup downsampling strategy, resulting in intensity dilution and loss of detailed structure information in the contrast map. Later, another study used a similar voxel grouping idea to IDEAL but further integrated K-means for voxel clustering (36). Since K-means can intelligently group voxels according to the image structure, this study significantly improved B 0 correction using 1-pool LF. ...
... To determine the proper R S and R N values, the structural similarity index (SSIM) (41) and peak signal-to-noise ratio (PSNR) (36) were calculated between the groupwise Lorentzian estimation of the whole image and the raw input saturated data at −10 to −6.25 ppm, −2 to 2 ppm and 6.25 to 10 ppm: ...
Background:
Quantification of in vivo chemical exchange saturation transfer (CEST) magnetic resonance signals is challenging due to contamination from coexisting effects, including the direct water effect and asymmetric magnetization transfer. Fitting-based analysis allows the calculation of multiple types of signals from the line shape of Z-spectra. However, the conventional voxelwise method has several drawbacks, including its long computation time and its susceptibility to image noise and Z-spectra oscillations, and it is difficult to determine the initial fitting parameters.
Methods:
Herein, we propose a K-means clustering method for accelerated Lorentzian estimation (KALE) in CEST quantification. Briefly, voxels in CEST images are clustered into K groups according to their Z-spectra characteristics. A 'groupwise' fitting process is then performed with preset initial values, yielding a set of fitted spectra and fitted parameters for each group. With the updated initial values, each group is further clustered into subgroups, and groupwise fitting is performed again. This hierarchical K-means clustering and parameter updating process continues until the pixel number or intensity error meets the termination criteria. Voxelwise fitting could be further conducted to improve the quantification images (termed voxel-K) by utilizing the previous groupwise KALE results as the initial values (termed group-K).
Results:
Incorporated with Lorentzian difference (LD) quantification, KALE was first optimized and evaluated on 5 healthy human brain datasets at 3 Tesla. Compared with traditional voxel-by-voxel LD quantification, the computation times of group-K and voxel-K were significantly reduced by ~85% and ~70%, respectively (P<0.001). Furthermore, the group-K images exhibited better denoising performance than traditional LD and voxel-K. KALE was further validated on six ischemic rat brains acquired at 7 Tesla, with both LD_group-K and LD_voxel-K displaying almost identical contrast maps with traditional voxelwise maps. When incorporated with the five-pool Lorentzian fitting (LF), KALE exhibited an improved contrast-to-noise ratio (CNR) for amplitude maps of each pool [P=0.003, 0.015, 0.047, and 0.047 for amide, nuclear Overhauser effect (NOE), magnetic transfer (MT) and guanidine amine, respectively] and improved fitting goodness (P=0.033).
Conclusions:
KALE quantification provides comparable or even superior contrast maps to traditional voxelwise fitting, with significantly reduced computation time. The 'smart' and hierarchical voxel-clustering and parameter updating process of KALE may facilitate more preclinical and clinical CEST applications.
... All CEST-SAGE-EPI and CEST-EPI images were motion corrected using affine transformation (mcflirt, FSL; FMRIB) and B 0 correction via a z-spectra-based k-means clustering and Lorentzian-fitting algorithm 90 is the amount of bulk water signal available after the saturation pulse with offset frequency ω and S 0 is the signal available without application of radiofrequency (RF) saturation. For the CEST-SAGE-EPI data, the average MTRasym at 3.0 ppm was calculated by averaging the first (echo time = 14.0 ms) and second (echo time = 34.1 ms) gradient echoes to increase the available signal-to-noise ratio. ...
Glioblastoma (GBM) is characterized by exceptionally high intratumoral heterogeneity. However, the molecular mechanisms underlying the origin of different GBM cell populations remain unclear. Here, we found that the compositions of ribosomes of GBM cells in the tumour core and edge differ due to alternative RNA splicing. The acidic pH in the core switches before messenger RNA splicing of the ribosomal gene RPL22L1 towards the RPL22L1b isoform. This allows cells to survive acidosis, increases stemness and correlates with worse patient outcome. Mechanistically, RPL22L1b promotes RNA splicing by interacting with lncMALAT1 in the nucleus and inducing its degradation. Contrarily, in the tumour edge region, RPL22L1a interacts with ribosomes in the cytoplasm and upregulates the translation of multiple messenger RNAs including TP53. We found that the RPL22L1 isoform switch is regulated by SRSF4 and identified a compound that inhibits this process and decreases tumour growth. These findings demonstrate how distinct GBM cell populations arise during tumour growth. Targeting this mechanism may decrease GBM heterogeneity and facilitate therapy.
... First, densely sampled signals with intervals of 0.1 ppm are interpolated from sparsely acquired signals using spline or other interpolated methods [14][15][16][17][18]. Second, the B 0 inhomogeneity is corrected through a B 0 inhomogeneity (∆B 0 ) map of the same image geometry. A ∆B 0 map can be obtained using water saturation shift referencing (WASSR) [19,20], Dixon [21], or Lorentzian-based methods [22]. ...
... Fortunately, some studies have focused on accelerating Lorentzian fitting. For example, Yao et al. classified voxels into several clusters, and only conducted Lorentzian fitting once for a cluster to reduce the fitting time [22]. Zaiss et al. employed neural networks to predict the parameters of Lorentzian function, and accelerated Lorentzian fitting to several seconds [37]. ...
Amide proton transfer (APT)-weighted MRI is a promising molecular imaging technique that has been employed in clinic for detection and grading of brain tumors. MTRasym, the quantification method of APT, is easily influenced by B0 inhomogeneity and causes artifacts. Current model-free interpolation methods have enabled moderate B0 correction for middle offsets, but have performed poorly at limbic offsets. To address this shortcoming, we proposed a practical B0 correction approach that is suitable under time-limited sparse acquisition scenarios and for B1 ≥ 1 μT under 3T. In this study, this approach employed a simplified Lorentzian model containing only two pools of symmetric water and asymmetric solutes, to describe the Z-spectral shape with wide and 'invisible' CEST peaks. The B0 correction was then performed on the basis of the fitted two-pool Lorentzian lines, instead of using conventional model-free interpolation. The approach was firstly evaluated on densely sampled Z-spectra data by using the spline interpolation of all acquired 16 offsets as the gold standard. When only six offsets were available for B0 correction, our method outperformed conventional methods. In particular, the errors at limbic offsets were significantly reduced (n = 8, p < 0.01). Secondly, our method was assessed on the six-offset APT data of nine brain tumor patients. Our MTRasym (3.5 ppm), using the two-pool model, displayed a similar contrast to the vendor-provided B0-orrected MTRasym (3.5 ppm). While the vendor failed in correcting B0 at 4.3 and 2.7 ppm for a large portion of voxels, our method enabled well differentiation of B0 artifacts from tumors. In conclusion, the proposed approach could alleviate analysis errors caused by B0 inhomogeneity, which is useful for facilitating the comprehensive metabolic analysis of brain tumors.
... Scanning parameters along with B 0 and B 1 inhomogeneities are known to influence the amine-weighted CEST signal. 40,89,90 Yao et al. ...
Amine‐weighted chemical exchange saturation transfer (CEST) MRI is particularly valuable as an amine‐ and pH‐sensitive imaging technique in brain tumors, targeting the intrinsically high concentration of amino acids with exchangeable amine protons and reduced extracellular pH in brain tumors. Amine‐weighted CEST MRI contrast is dependent on the glioma genotype, likely related to differences in degree of malignancy and metabolic behavior. Amine‐weighted CEST MRI may provide complementary value to anatomic imaging in conventional and exploratory therapies in brain tumors, including chemoradiation, anti‐angiogenic therapies, and immunotherapies. Continual improvement and clinical testing of amine‐weighted CEST MRI has the potential to greatly impact patients with brain tumors by understanding vulnerabilities in the tumor microenvironment that may be therapeutically exploited.
... Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/cancers14102520/s1, Supplementary Methods; Figure S1: Tissue type differentiation based on MRI features; Table S1: Cox proportional-hazards model analysis of glioma patient residual overall survival using clinical variables and MRI features (treatment-naïve patients); Table S2: Cox proportional-hazards model analysis of glioma patient residual progressionfree survival using clinical variables and MRI features (treatment-naïve patients) [7,18,19,[44][45][46][47]. Funding: This research was funded by the American Cancer Society (ACS) Research Scholar Grant (RSG-15-003-01-CCE) (BME); University of California Research Coordinating Committee (BME); UCLA Jonsson Comprehensive Cancer Center Seed Grant (BME); UCLA SPORE in Brain Cancer (NIH/NCI 1P50CA211015-01A1) (BME, LML, PLN, AL, WBP, TFC); and NIH/NCI 1R21CA223757-01 (BME). ...
Simple Summary
Gliomas are known to present with an altered metabolic phenotype that contributes to the abnormal tumor microenvironment detectable on MRI. The aim of this study was to quantify metabolic statuses of glioma using pH- and oxygen-sensitive MRI and associate the measurements with genetic mutation and prognosis. Using the data of 159 adult glioma patients, we revealed that isocitrate dehydrogenase mutation, 1p/19q co-deletion, and epidermal growth factor receptor amplification statuses were associated with the MRI measurements revealing tissue acidosis and hypoxia, and these measurements were also associated with progression-free survival and overall survival, independent of patient age, treatment status, and isocitrate dehydrogenase mutation status. In conclusion, the pH- and oxygen-sensitive MRI is clinically feasible and potentially valuable for distinguishing glioma genotypes and provides additional prognostic value to clinical practice.
Abstract
Characterization of hypoxia and tissue acidosis could advance the understanding of glioma biology and improve patient management. In this study, we evaluated the ability of a pH- and oxygen-sensitive magnetic resonance imaging (MRI) technique to differentiate glioma genotypes, including isocitrate dehydrogenase (IDH) mutation, 1p/19q co-deletion, and epidermal growth factor receptor (EGFR) amplification, and investigated its prognostic value. A total of 159 adult glioma patients were scanned with pH- and oxygen-sensitive MRI at 3T. We quantified the pH-sensitive measure of magnetization transfer ratio asymmetry (MTRasym) and oxygen-sensitive measure of R2’ within the tumor region-of-interest. IDH mutant gliomas showed significantly lower MTRasym × R2’ (p < 0.001), which differentiated IDH mutation status with sensitivity and specificity of 90.0% and 71.9%. Within IDH mutants, 1p/19q codeletion was associated with lower tumor acidity (p < 0.0001, sensitivity 76.9%, specificity 91.3%), while IDH wild-type, EGFR-amplified gliomas were more hypoxic (R2’ p = 0.024, sensitivity 66.7%, specificity 76.9%). Both R2’ and MTRasym × R2’ were significantly associated with patient overall survival (R2’: p = 0.045; MTRasym × R2’: p = 0.002) and progression-free survival (R2’: p = 0.010; MTRasym × R2’: p < 0.0001), independent of patient age, treatment status, and IDH status. The pH- and oxygen-sensitive MRI is a clinically feasible and potentially valuable imaging technique for distinguishing glioma subtypes and providing additional prognostic value to clinical practice.
... ac. uk/ fsl/) and corrected for B 0 inhomogeneities by using a z-spectra-based k-means clustering and Lorentzian fitting algorithm 37 . Then, an integral with a width of 0.4 ppm was calculated around both the − 3.0 and + 3.0 ppm spectral points (− 3.2 to − 2.8 ppm and + 2.8 to + 3.2 ppm, respectively). ...
This study aimed to differentiate isocitrate dehydrogenase (IDH) mutation status with the voxel-wise clustering method of multiparametric magnetic resonance imaging (MRI) and to discover biological underpinnings of the clusters. A total of 69 patients with treatment-naïve diffuse glioma were scanned with pH-sensitive amine chemical exchange saturation transfer MRI, diffusion-weighted imaging, fluid-attenuated inversion recovery, and contrast-enhanced T1-weighted imaging at 3 T. An unsupervised two-level clustering approach was used for feature extraction from acquired images. The logarithmic ratio of the labels in each class within tumor regions was applied to a support vector machine to differentiate IDH status. The highest performance to predict IDH mutation status was found for 10-class clustering, with a mean area under the curve, accuracy, sensitivity, and specificity of 0.94, 0.91, 0.90, and 0.91, respectively. Targeted biopsies revealed that the tissues with labels 7–10 showed high expression levels of hypoxia-inducible factor 1-alpha, glucose transporter 3, and hexokinase 2, which are typical of IDH wild-type glioma, whereas those with labels 1 showed low expression of these proteins. In conclusion, A machine learning model successfully predicted the IDH mutation status of gliomas, and the resulting clusters properly reflected the metabolic status of the tumors.
... ac. uk/ fsl/ fslwi ki/ MCFLI RT) and B0 correction via a z-spectra-based K-means clustering and Lorentzian fitting algorithm 36 . An integral of the width of 0.4 ppm was then obtained around both the − 3.0 and + 3.0 ppm (− 3.2 to − 2.8 and + 2.8 to + 3.2 ppm, respectively) spectral points of the inhomogeneity-corrected data. ...
Glioblastoma (GBM) has high metabolic demands, which can lead to acidification of the tumor microenvironment. We hypothesize that a machine learning model built on temporal principal component analysis (PCA) of dynamic susceptibility contrast-enhanced (DSC) perfusion MRI can be used to estimate tumor acidity in GBM, as estimated by pH-sensitive amine chemical exchange saturation transfer echo-planar imaging (CEST-EPI). We analyzed 78 MRI scans in 32 treatment naïve and post-treatment GBM patients. All patients were imaged with DSC-MRI, and pH-weighting that was quantified from CEST-EPI estimation of the magnetization transfer ratio asymmetry (MTRasym) at 3 ppm. Enhancing tumor (ET), non-enhancing core (NC), and peritumoral T2 hyperintensity (namely, edema, ED) were used to extract principal components (PCs) and to build support vector machines regression (SVR) models to predict MTRasym values using PCs. Our predicted map correlated with MTRasym values with Spearman’s r equal to 0.66, 0.47, 0.67, 0.71, in NC, ET, ED, and overall, respectively (p < 0.006). The results of this study demonstrates that PCA analysis of DSC imaging data can provide information about tumor pH in GBM patients, with the strongest association within the peritumoral regions.
... Clinical postprocessing of CEST-EPI consisted of affine motion correction (MCFLIRT; FSL, https://fsl.fmrib.ox.ac.uk/fsl/ fslwiki/MCFLIRT) and B 0 correction via a z-spectra-based K-means clustering and Lorentzian fitting algorithm. 18 An integral of the width of 0.4 ppm was then obtained around both the Ϫ3.0 and ϩ3.0 ppm (Ϫ3.2 to Ϫ2.8 and ϩ2.8 to ϩ3.2 ppm, respectively) spectral points of the inhomogeneity-corrected data. These data points were combined with the S 0 image to calculate the asymmetry in the magnetization transfer ratio (MTR asym ) at 3.0 ppm as defined ...
Background and purpose:
Acidification of the tumor microenvironment from abnormal metabolism along with angiogenesis to meet metabolic demands are both hallmarks of malignant brain tumors; however, the interdependency of tumor acidity and vascularity has not been explored. Therefore, our aim was to investigate the association between pH-sensitive amine chemical exchange saturation transfer echoplanar imaging (CEST-EPI) and relative cerebral blood volume (CBV) measurements obtained from dynamic susceptibility contrast (DSC) perfusion MRI in patients with gliomas.
Materials and methods:
In this retrospective study, 90 patients with histologically confirmed gliomas were scanned between 2015 and 2018 (median age, 50.3 years; male/female ratio = 59:31). pH-weighting was obtained using chemical exchange saturation transfer echo-planar imaging estimation of the magnetization transfer ratio asymmetry at 3 ppm, and CBV was estimated using DSC-MR imaging. The voxelwise correlation and patient-wise median value correlation between the magnetization transfer ratio asymmetry at 3 ppm and CBV within T2-hyperintense lesions and contrast-enhancing lesions were evaluated using the Pearson correlation analysis.
Results:
General colocalization of elevated perfusion and high acidity was observed in tumors, with local intratumor heterogeneity. For patient-wise analysis, median CBV and magnetization transfer ratio asymmetry at 3 ppm within T2-hyperintense lesions were significantly correlated (R = 0.3180, P = .002), but not in areas of contrast enhancement (P = .52). The positive correlation in T2-hyperintense lesions remained within high-grade gliomas (R = 0.4128, P = .001) and in isocitrate dehydrogenase wild-type gliomas (R = 0.4300, P = .002), but not in World Health Organization II or in isocitrate dehydrogenase mutant tumors. Both magnetization transfer ratio asymmetry at 3 ppm and the voxelwise correlation between magnetization transfer ratio asymmetry and CBV were higher in high-grade gliomas compared with low-grade gliomas in T2-hyperintense tumors (magnetization transfer ratio asymmetry, P = .02; Pearson correlation, P = .01). The same trend held when comparing isocitrate dehydrogenase wild-type gliomas and isocitrate dehydrogenase mutant gliomas (magnetization transfer ratio asymmetry, P = .04; Pearson correlation, P = .01).
Conclusions:
A positive linear correlation between CBV and acidity in areas of T2-hyperintense, nonenhancing tumor, but not enhancing tumor, was observed across patients. Local heterogeneity was observed within individual tumors.
... All CEST-SAGE-EPI and CEST-EPI images were motion corrected using an affine transformation (mcflirt; Functional Magnetic Resonance Imaging of the Brain Software Library) and B 0 correction via a z-spectra based k-means clustering and Lorentzian fitting algorithm. 31 Following motion and B 0 correction, the integral of width of 0.4 ppm was quantified around both the −3.0 and +3.0 ppm (−3.2 to −2.8 ppm and +2.8 to +3.2 ppm, respectively) spectral points. These data points were combined with the S 0 image to calculate the asymmetry in the magnetization transfer ratio asymmetry (MTR asym ) at 3.0 ppm, a measure related to pH, 23 as defined using equation: MTR asym (3. ...
Background:
IDH1 mutant gliomas are thought to have distinct metabolic characteristics, including a blunted response to hypoxia and lower glycolytic flux. We hypothesized non-invasive quantification of abnormal metabolic behavior in human IDH1 mutant gliomas could be performed using a new pH- and oxygen-sensitive molecular MRI technique.
Methods:
Simultaneous pH- and oxygen-sensitive MRI was obtained at 3T using amine CEST-SAGE-EPI. The pH-dependent measure of MTRasym at 3ppm and oxygen-sensitive measure of R2' were quantified in 90 patients with gliomas. Additionally, stereotactic, image-guided biopsies were performed in 20 patients for a total of 52 samples. The association between imaging measurements and HIF1α expression were identified using Pearson correlation analysis.
Results:
IDH1 mutant gliomas exhibited significantly lower MTRasym at 3ppm, R2', and MTRasymxR2' (P=0.007, P=0.003, and P=0.001, respectively). MTRasymxR2' could identify IDH1 mutant gliomas with a high sensitivity (81.0%) and specificity (81.3%). HIF1α was positively correlated with MTRasym at 3ppm, R2' and MTRasymxR2' in IDH1 wildtype (r=0.610, P=0.003; r=0.667, P=0.008; r=0.635, P=0.006), but only MTRasymxR2' in IDH1 mutant gliomas (r=0.727, P=0.039).
Conclusions:
IDH1 mutant gliomas have distinct metabolic and microenvironment characteristics compared to wild type gliomas. An imaging biomarker combining tumor acidity and hypoxia (MTRasymxR2') can differentiate IDH1 mutation status and is correlated with tumor acidity and hypoxia.
