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Purpose: To evaluate the performance of different chemical exchange saturation transfer (CEST) metrics for grading gliomas with semiautomatically defined regions of interest (ROIs)., Methods: Thirty-eight adult subjects were included, including 23 high-grade gliomas and 15 low-grade gliomas confirmed by histopathology. The B0-corrected CEST z-spectra were first calculated with magnetization transfer ratio asymmetry (MTR asym ) analysis at frequency offsets of 3.5, 3, 2.5, 2, 1.5, and 1 ppm to obtain the fit-free metrics and subsequently fitted with three Lorentzian functions denoting direct water saturation (DS), amide proton transfer (APT), and combined semisolid magnetization transfer and nuclear Overhauser enhancement (MT & NOE) effects to derive the fit-based metrics. Wilcoxon rank-sum test was performed to determine if a statistically significant difference was present in the CEST metrics between low- and high-grade gliomas. Receiver operating characteristic (ROC) curves were used to evaluate the differentiation of CEST metrics between low- and high-grade gliomas. Pearson correlation coefficients were employed to evaluate the correlations of CEST metrics., Results: For the fit-free metrics, the highest areas under the curve (AUCs) of 0.85, 0.88, and 0.88, corresponding to MTR asym , MTR normref (normalization by the reference scan), and MTR Rex (subtraction of inverse z-spectra), respectively, were obtained at 3 ppm across various frequency offsets. In addition, the AUCs generated from the fit-based metrics (0.88-0.90) were higher than those generated from the fit-free metrics at 3 ppm., Conclusion: The results of this preliminary study indicate that fit-free CEST metrics at 3 ppm are superior to the other frequency offsets for grading human brain gliomas. The fit-based metrics manifested improved differentiation between low- and high-grade gliomas compared to the fit-free CEST metrics., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the performance of velocity-selective (VS) ASL among patients with untreated gliomas by comparing with both pseudo-continuous (PC) ASL and dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI)., Methods: Forty-four consecutive patients with newly diagnosed glioma who underwent preoperative perfusion MRI including VSASL, PCASL, and DSC-PWI between 2017 and 2019 were retrospectively evaluated. Visual inspection was performed to evaluate the tumor signal intensity relative to gray matter based on 1-5 score criteria and weighted kappa was used to evaluate the pair-wise concordance between VSASL or PCASL and DSC-PWI. The relative tumor blood flow (rTBF) was measured from sampling intra-tumoral areas of hot-spot on the blood flow map and normalized against the contralateral normal gray matter blood flow. Linear regression and Bland-Altman analyses were performed to evaluate the correlation and agreement of rTBF measurements between ASL methods and DSC-PWI. The ROC analysis was constructed to determine the diagnostic performance of three perfusion methods for grading gliomas., Results: TBF maps derived from VSASL were more comparable with DSC-PWI than PCASL on visual inspection (weighted kappa of 0.90 vs 0.68). In quantitative analysis, VSASL-rTBF yielded higher correlation with the values from DSC-PWI than PCASL-rTBF (R 2  = 80% vs 47%, p < 0.001 for both). Both ASL and DSC-derived rTBF showed good distinction between low-grade and high-grade gliomas (p < 0.001). Compared to PCASL, VSASL yielded superior diagnostic sensitivity, specificity, and accuracy in glioma grading., Conclusions: VSASL showed great promise for accurate quantification of TBF and could potentially improve the diagnostic performance of ASL in preoperative grading of gliomas., Key Points: • VSASL demonstrated a greater agreement with DSC-PWI than with PCASL on visual inspection and perfusion quantification. • VSASL showed a higher diagnostic sensitivity, negative predictive value, and accuracy than PCASL for glioma grading. • With the advantages of insensitivity to transit delay and no need of prescribing a labeling plane, VSASL could potentially improve the diagnostic performance of ASL for a more accurate, noninvasive quantification of TBF in patients with glioma., (© 2021. The Author(s), under exclusive licence to European Society of Radiology.)

Objectives: To explore the feasibility of using amide proton transfer-weighted (APTw) MRI metrics as surrogate biomarkers to identify the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in glioblastoma (GBM)., Methods: Eighteen newly diagnosed GBM patients, who were previously scanned at 3T and had a confirmed MGMT methylation status, were retrospectively analysed. For each case, a histogram analysis in the tumour mass was performed to evaluate several quantitative APTw MRI metrics. The Mann-Whitney test was used to evaluate the difference in APTw parameters between MGMT methylated and unmethylated GBMs, and the receiver-operator-characteristic analysis was further used to assess diagnostic performance., Results: Ten GBMs were found to harbour a methylated MGMT promoter, and eight GBMs were unmethylated. The mean, variance, 50th percentile, 90th percentile and Width 10-90 APTw values were significantly higher in the MGMT unmethylated GBMs than in the MGMT methylated GBMs, with areas under the receiver-operator-characteristic curves of 0.825, 0.837, 0.850, 0856 and 0.763, respectively, for the discrimination of MGMT promoter methylation status., Conclusions: APTw signal metrics have the potential to serve as valuable imaging biomarkers for identifying MGMT methylation status in the GBM population., Key Points: • APTw-MRI is applied to predict MGMT promoter methylation status in GBMs. • GBMs with unmethylated MGMT promoter present higher APTw-MRI than methylated GBMs. • Multiple APTw histogram metrics can identify MGMT methylation status. • Mean APTw values showed the highest diagnostic accuracy (AUC = 0.825).

The purpose of this work was to investigate the diagnostic performance of amide proton transfer-weighted (APTW) and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in the preoperative grading of gliomas. Fifty-one patients with suspected gliomas were recruited and underwent a preoperative MRI examination that included APTW and IVIM sequences. All cases were confirmed by postsurgical histopathology. APTW signal intensity, true diffusion coefficient (D), perfusion fraction (f) and pseudo-diffusion coefficient (D*) were applied to assess the solid tumor component and contralateral normal-appearing white matter. The relative APTW signal intensity (rAPTW) was also used. Independent-sample and paired-sample t-tests were used to compare differences in MRI parameters between low-grade glioma (LGG) and high-grade glioma (HGG) groups. The diagnostic performance was assessed with the receiver operating characteristic curve. Twenty-six patients were pathologically diagnosed with LGG and 25 were diagnosed with HGG. APTW, rAPTW and f values were significantly higher (all p < 0.001), whereas D values were significantly lower (p < 0.001) in the HGG group than in the LGG group. There was no significant difference between D* values for the two groups. rAPTW had an area under the curve (AUC) of 0.957, with a sensitivity of 100% and a specificity of 84.6%, followed by APTW, f, D and D*. The combined use of APTW and IVIM showed the best diagnostic performance, with an AUC of 0.986. In conclusion, APTW and IVIM, as two promising supplementary sequences for routine MRI, could be valuable in differentiating LGGs from HGGs., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objectives: To determine the utility of amide proton transfer-weighted (APTw) MR imaging in distinguishing solitary brain metastases (SBMs) from glioblastomas (GBMs)., Methods: Forty-five patients with SBMs and 43 patients with GBMs underwent conventional and APT-weighted sequences before clinical intervention. The APTw parameters and relative APTw (rAPTw) parameters in the tumour core and the peritumoral brain zone (PBZ) were obtained and compared between SBMs and GBMs. The receiver-operating characteristic (ROC) curve was used to assess the best parameter for distinguishing between the two groups., Results: The APTw max , APTw min , APTw mean , rAPTw max , rAPTw min or rAPTw mean values in the tumour core were not significantly different between the SBM and GBM groups (P = 0.141, 0.361, 0.221, 0.305, 0.578 and 0.448, respectively). However, the APTw max , APTw min , APTw mean , rAPTw max , rAPTw min or rAPTw mean values in the PBZ were significantly lower in the SBM group than in the GBM group (P < 0.001). The APTw min values had the highest area under the ROC curve 0.905 and accuracy 85.2% in discriminating between the two neoplasms., Conclusion: As a noninvasive imaging method, APT-weighted MR imaging can be used to distinguish SBMs from GBMs., Key Points: • APTw values in the tumour core were not different between SBMs and GBMs. • APTw values in peritumoral brain zone were lower in SBMs than in GBMs. • The APTw min was the best parameter to distinguish SBMs from GBMs.

Purpose: To assess the amide proton transfer-weighted (APTw) MRI features of isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant grade II gliomas and to test the hypothesis that the APTw signal is a surrogate imaging marker for identifying IDH mutation status preoperatively., Methods: Twenty-seven patients with pathologically confirmed low-grade glioma, who were previously scanned at 3T, were retrospectively analyzed. The Mann-Whitney test was used to evaluate relationships between APTw intensities for IDH-mutant and IDH-wildtype groups, and receiver operator characteristic (ROC) analysis was used to assess the diagnostic performance of APTw., Results: Based on histopathology and molecular analysis, seven cases were diagnosed as IDH-wildtype grade II gliomas and 20 cases as IDH-mutant grade II gliomas. The maximum and minimum APTw values, based on multiple regions of interest, as well as the whole-tumor histogram-based mean and 50th percentile APTw values, were significantly higher in the IDH-wildtype gliomas than in the IDH-mutant groups. This corresponded to the areas under the ROC curves of 0.89, 0.76, 0.75, and 0.75, respectively, for the prediction of the IDH mutation status., Conclusion: IDH-wildtype lesions typically were associated with relatively high APTw signal intensities as compared with IDH-mutant lesions. The APTw signal could be a valuable imaging biomarker by which to identify IDH1 mutation status in grade II gliomas. Magn Reson Med 78:1100-1109, 2017. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Objectives: To show the ability of using the amide proton transfer-weighted (APTW) MRI signals as imaging biomarkers to differentiate primary central nervous system lymphomas (PCNSLs) from high-grade gliomas (HGGs)., Methods: Eleven patients with lymphomas and 21 patients with HGGs were examined. Magnetization-transfer (MT) spectra over an offset range of ± 6 ppm and the conventional MT ratio (MTR) at 15.6 ppm were acquired. The APTW signals, total chemical-exchange-saturation-transfer signal (integral between 0 and 5 ppm, CEST total), and MTR signal were obtained and compared between PCNSLs and HGGs. The diagnostic performance was assessed with the receiver operating characteristic (ROC) curve analysis., Results: The PCNSLs usually showed more homogeneous APTW hyperintensity (spatially compared to normal brain tissue) than the HGGs. The APTW max, APTW max-min and CEST total signal intensities were significantly lower (P < 0.05, 0.001 and 0.05, respectively), while the APTW min and MTR were significantly higher (both P < 0.01) in PCNSL lesions than in HGG lesions. The APTW values in peritumoral oedema were significantly lower for PCNSLs than for HGGs (P < 0.01). APTW max-min had the highest area under the ROC curve (0.963) and accuracy (94.1 %) in differentiating PCNSLs from HGGs., Conclusions: The protein-based APTW signal would be a valuable MRI biomarker by which to identify PCNSLs and HGGs presurgically., Key Points: PCNSLs overall showed more homogeneous APTW hyperintensity than HGGs. Maximum APTW signals were lower in PCNSL lesions than in HGG lesions. MTR signals were higher in PCNSLs than in HGGs. APTW heterogeneity had the highest accuracy in differentiating PCNSLs from HGGs.

Purpose: Amide proton transfer (APT) imaging is able to extend the achievable magnetic resonance imaging (MRI) contrast to the protein level. In this study, we demonstrate the feasibility of applying a turbo-spin-echo (TSE)-based, three-dimensional (3D) APT sequence into routine clinical practice for patients with brain tumors., Procedures: Experiments were performed on a Philips 3-Tesla (3-T) MRI scanner using an eight-channel phased-array coil for reception. A fast 3D APT sequence with a TSE acquisition was proposed (saturation power, 2 μT; saturation time, 500 ms; 8 slices). The gradient echo (GRE)-based field-mapping technique or water-saturation-shift-referencing (WASSR) technique was used to acquire B(0) maps to correct for B(0)-induced artifacts in APT images. The test was performed on a box of homogenous protein solution, four healthy volunteers, and eight patients with high-grade gliomas., Results: The experimental data from a homogenous, protein-containing phantom and healthy volunteers show that the sequence produced a uniform contrast across all slices. The average MTR(asym)(3.5 ppm) values with GRE B(0)-corrected 3D APT imaging and WASSR-corrected 3D APT imaging were both comparable to the values obtained using the undemanding single-slice acquisition. The average APT image intensity was consistently higher in the tumor core than in the peripheral edema and in the contralateral normal-appearing white matter (both P < 0.001)., Conclusion: 3D APT imaging of brain tumors can be performed in about 5 min at 3-T using a routine, commercial eight-channel SENSE coil.

Amide proton transfer (APT) imaging is capable of detecting mobile cellular proteins and peptides in tumor and monitoring pH effects in stroke, through the saturation transfer between irradiated amide protons and water protons. In this work, four healthy subjects, eight brain tumor patients (four with high-grade glioma, one with lung cancer metastasis, and three with meningioma), and four stroke patients (average 4.3 ± 2.5 days after the onset of the stroke) were scanned at 3 T, using different radiofrequency saturation powers. The APT effect was quantified using the magnetization transfer ratio (MTR) asymmetry at 3.5 ppm with respect to the water resonance. At a saturation power of 2 μT, the measured APT-MRI signal of the normal brain tissue was almost zero, due to the contamination of the negative conventional magnetization transfer ratio asymmetry. This irradiation power caused an optimal hyperintense APT-MRI signal in the tumor and an optimal hypointense signal in the stroke, compared to the normal brain tissue. The results suggest that the saturation power of 2 μT is ideal for APT imaging of these two pathologies at 3 T with the existing clinical hardware., (Copyright © 2011 Wiley-Liss, Inc.)

Amide proton transfer (APT) imaging is a novel MRI technique, in which the amide protons of endogenous proteins and peptides are irradiated to accomplish indirect detection using the bulk water signal. In this paper, the APT approach was added to a standard brain MRI protocol at 3T, and twelve patients with high-grade gliomas confirmed by histopathology were scanned. It is shown that all tumors, including one with minor gadolinium enhancement, showed heterogeneous hyperintensity on the APT images. The average APT signal intensities of the viable tumor cores were significantly higher than those of peritumoral edema and normal-appearing white matter (P<0.001). The average APT signal intensities were significantly lower in the necrotic regions than in the viable tumor cores (P=0.004). The APT signal intensities of the cystic cavities were similar to those of the viable tumor cores (P>0.2). The initial results show that APT imaging at the protein and peptide level may enhance non-invasive identification of tissue heterogeneity in high-grade brain tumors., (Copyright 2010 Elsevier Inc. All rights reserved.)