Glioma staging with CEST asymmetry curves and amides/amines ratio (original) (raw)
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CEST MRI provides amide/amine surrogate biomarkers for treatment-naïve glioma sub-typing
European Journal of Nuclear Medicine and Molecular Imaging, 2022
Purpose Accurate glioma classification affects patient management and is challenging on non- or low-enhancing gliomas. This study investigated the clinical value of different chemical exchange saturation transfer (CEST) metrics for glioma classification and assessed the diagnostic effect of the presence of abundant fluid in glioma subpopulations. Methods Forty-five treatment-naïve glioma patients with known isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status received CEST MRI (B1rms = 2μT, Tsat = 3.5 s) at 3 T. Magnetization transfer ratio asymmetry and CEST metrics (amides: offset range 3–4 ppm, amines: 1.5–2.5 ppm, amide/amine ratio) were calculated with two models: ‘asymmetry-based’ (AB) and ‘fluid-suppressed’ (FS). The presence of T2/FLAIR mismatch was noted. Results IDH-wild type had higher amide/amine ratio than IDH-mutant_1p/19qcodel (p < 0.022). Amide/amine ratio and amine levels differentiated IDH-wild type from IDH-mutant (p < 0.0045) and from IDH-mu...
CEST‐MRI for glioma pH quantification in mouse model: Validation by immunohistochemistry
NMR in Biomedicine, 2018
In glioma, the acidification of the extracellular tumor microenvironment drives proliferation, angiogenesis, immunosuppression, invasion and chemoresistance. Therefore, quantification of glioma extracellular pH (pHe) is of crucial importance. This study is focused on the application of the YbHPDO3A (ytterbium 1,4,7‐triscarboxymethyl‐1,4,7,10‐tetraazacyclododecane) probe for in vivo glioma pHe quantification using chemical exchange saturation transfer (CEST)‐MRI and its correlation with tumor metabolism assessed by immunohistochemistry.The U87 glioma mouse model was used (n = 18) and MRI performed at 4.7 T. CEST‐MRI of YbHPDO3A solutions at different pH values showed two resolved CEST spectra at 71 ppm and 99 ppm, both sensitive to pH variations, allowing therefore calculation of the ratiometric curve for in vivo pH quantification. In vivo MRI sequences consisted of T2w for tumor localization, T2w* to assess YbHPDO3A biodistribution by exploiting its magnetic susceptibility effect an...
Oncotarget, 2016
Using noninvasive magnetic resonance imaging techniques to accurately evaluate the grading and cellularity of gliomas is beneficial for improving the patient outcomes. Amide proton transfer imaging is a noninvasive molecular magnetic resonance imaging technique based on chemical exchange saturation transfer mechanism that detects endogenous mobile proteins and peptides in biological tissues. Between August 2012 and November 2015, a total number of 44 patients with pathologically proven gliomas were included in this study. We compared the capability of amide proton transfer magnetic resonance imaging with that of noninvasive diffusion-weighted imaging and noninvasive 3-dimensional pseudo-continuous arterial spin imaging in evaluating the grading and cellularity of gliomas. Our results reveal that amide proton transfer magnetic resonance imaging is a superior imaging technique to diffusion-weighted imaging and 3-dimensional pseudo-continuous arterial spin imaging in the grading of gli...
Scientific Reports, 2020
Co-deletion of 1p/19q is a hallmark of oligodendroglioma and predicts better survival. However, little is understood about its metabolic characteristics. In this study, we aimed to explore the extracellular acidity of WHO grade II and III gliomas associated with 1p/19q co-deletion. We included 76 glioma patients who received amine chemical exchange saturation transfer (CEST) imaging at 3 T. Magnetic transfer ratio asymmetry (MTRasym) at 3.0 ppm was used as the pH-sensitive CEST biomarker, with higher MTRasym indicating lower pH. To control for the confounder factors, T2 relaxometry and l-6-18F-fluoro-3,4-dihydroxyphenylalnine (18F-FDOPA) PET data were collected in a subset of patients. We found a significantly lower MTRasym in 1p/19q co-deleted gliomas (co-deleted, 1.17% ± 0.32%; non-co-deleted, 1.72% ± 0.41%, P = 1.13 × 10−7), while FDOPA (P = 0.92) and T2 (P = 0.61) were not significantly affected. Receiver operating characteristic analysis confirmed that MTRasym could discriminat...
Brain pH Measurement Using AACID CEST MRI Incorporating the 2 ppm Amine Resonance
Tomography, 2022
Many pathological conditions lead to altered intracellular pH (pHi) disrupting normal cellular functions. The chemical exchange saturation transfer (CEST) method, known as Amine and Amide Concentration Independent Detection (AACID), can produce image contrast that is predominantly dependent on tissue intracellular pHi. The AACID value is linearly related to the ratio of the 3.5 ppm amide CEST effect and the 2.75 ppm amine CEST effect in the physiological range. However, the amine CEST effect at 2 ppm is often more clearly defined in vivo, and may provide greater sensitivity to pH changes. The purpose of the current study was to compare AACID measurement precision utilizing the 2.0 and 2.75 ppm amine CEST effects. We hypothesized that the 2.0 ppm amine CEST resonance would produce measurements with greater sensitivity to pH changes. In the current study, we compare the range of the AACID values obtained in 24 mice with brain tumors and in normal tissue using the 2 ppm and 2.75 ppm am...
Cancers
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 ...
Towards longitudinal mapping of extracellular pH in gliomas
NMR in biomedicine, 2016
Biosensor imaging of redundant deviation in shifts (BIRDS), an ultrafast chemical shift imaging technique, requires infusion of paramagnetic probes such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis methylene phosphonate (DOTP(8-) ) complexed with thulium (Tm(3+) ) ion (i.e. TmDOTP(5-) ), where the pH-sensitive resonances of hyperfine-shifted non-exchangeable protons contained within the paramagnetic probe are detected. While imaging extracellular pH (pHe ) with BIRDS meets an important cancer research need by mapping the intratumoral-peritumoral pHe gradient, the surgical intervention used to raise the probe's plasma concentration limits longitudinal scans on the same subject. Here we describe using probenecid (i.e. an organic anion transporter inhibitor) to temporarily restrict renal clearance of TmDOTP(5-) , thereby facilitating molecular imaging by BIRDS without surgical intervention. Co-infusion of probenecid with TmDOTP(5-) increased the probe's distribution into...