CEST MRI provides amide/amine surrogate biomarkers for treatment-naïve glioma sub-typing

Abstract 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-mutant_1p/19qret (p < 0.021). IDH-mutant_1p/19qret had higher amides and amines than IDH-mutant_1p/19qcodel (p < 0.035). IDH-mutant_1p/19qret with AB/FS mismatch had higher amines than IDH-mutant_1p/19qret without AB/FS mismatch ( < 0.016). In IDH-mutant_1p/19qret, the presence of AB/FS mismatch was closely related to the presence of T2/FLAIR mismatch (p = 0.014). Conclusions CEST-derived biomarkers for amides, amines, and their ratio can help with histomolecular staging in gliomas without intense contrast enhancement. T2/FLAIR mismatch is reflected in the presence of AB/FS CEST mismatch. The AB/FS CEST mismatch identifies glioma subgroups that may have prognostic and clinical relevance.

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CEST MRI Provides Amides/amines Surrogate Biomarkers for Treatment-naïve Glioma Sub-typing

10.21203/rs.3.rs-887227/v1 ◽

2021 ◽

Author(s):

Laura Mancini ◽

Stefano Casagranda ◽

Guillaume Gautier ◽

Philippe Peter ◽

Bruno Lopez ◽

...

Keyword(s):

Patient Management ◽

Chemical Exchange ◽

Chemical Exchange Saturation Transfer ◽

Idh Mutation ◽

Saturation Transfer ◽

Magnetisation Transfer Ratio ◽

Clinical Value ◽

Cest Mri ◽

Treatment Naïve ◽

Glioma Classification

Abstract PurposeAccurate gliomas 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 gliomas subpopulations.MethodsForty-five treatment-naïve glioma patients with known isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status received CEST MRI at 3T. Magnetisation transfer ratio asymmetry and CEST metrics (amides: offset range 3-4ppm, amines: 1.5-2.5ppm, amides/amines ratio) were calculated with two models: ‘asymmetry-based’ (AB) and ‘fluid-suppressed’ (FS). Presence of T2/FLAIR mismatch was noted.ResultsIDH-wildtype had higher amides/amines ratio than IDH-mutant_1p/19qcodel (p<0.022). Amides/amines ratio and amines levels differentiated IDH-wildtype from IDH-mutant (p<0.0045) and from IDH-mutant_1p/19qret (p<0.021). IDH-mutant_1p/19qret had higher amides and amines than IDH-mutant_1p/19qcodel (p<0.035). IDH-mutant_1p/19qret with AB/FS mismatch had higher amines than IDH-mutant_1p/19qret without AB/FS mismatch (p<0.016). In IDH-mutant_1p/19qret, the presence of AB/FS mismatch was closely related to the presence of T2/FLAIR mismatch (p=0.014).ConclusionsCEST-derived biomarkers for amides, amines and their ratio can help with histomolecular staging in gliomas without intense contrast enhancement. T2/FLAIR mismatch is reflected in the presence of AB/FS CEST mismatch. The AB/FS CEST mismatch identifies glioma sub-groups that may have prognostic and clinical relevance.

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Supercharged green fluorescent proteins as bimodal reporter genes for CEST MRI and optical imaging

Chemical Communications ◽

10.1039/c4cc10195b ◽

2015 ◽

Vol 51 (23) ◽

pp. 4869-4871 ◽

Cited By ~ 26

Author(s):

Amnon Bar-Shir ◽

Yajie Liang ◽

Kannie W. Y. Chan ◽

Assaf A. Gilad ◽

Jeff W. M. Bulte

Keyword(s):

Fluorescent Proteins ◽

Chemical Exchange ◽

Reporter Genes ◽

Chemical Exchange Saturation Transfer ◽

Green Fluorescent Proteins ◽

Saturation Transfer ◽

Wild Type ◽

Mri Contrast ◽

Cest Mri ◽

Green Fluorescent

Superpositively charged GFP mutants demonstrate dramatically improved chemical exchange saturation transfer (CEST) MRI contrast compared to their wild type counterparts.

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3D APT and NOE CEST-MRI of healthy volunteers and patients with non-enhancing glioma at 3 T

Magnetic Resonance Materials in Physics Biology and Medicine ◽

10.1007/s10334-021-00996-z ◽

2022 ◽

Author(s):

Yulun Wu ◽

Tobias Charles Wood ◽

Fatemeh Arzanforoosh ◽

Juan Antonio Hernandez-Tamames ◽

Gareth John Barker ◽

...

Keyword(s):

Healthy Volunteers ◽

Tumor Heterogeneity ◽

Chemical Exchange ◽

Magnetization Transfer ◽

Chemical Exchange Saturation Transfer ◽

Amide Proton ◽

Magnetization Transfer Ratio ◽

Normal Appearing White Matter ◽

Saturation Power ◽

Cest Mri

Abstract Objective Clinical application of chemical exchange saturation transfer (CEST) can be performed with investigation of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) effects. Here, we investigated APT- and NOE-weighted imaging based on advanced CEST metrics to map tumor heterogeneity of non-enhancing glioma at 3 T. Materials and methods APT- and NOE-weighted maps based on Lorentzian difference (LD) and inverse magnetization transfer ratio (MTRREX) were acquired with a 3D snapshot CEST acquisition at 3 T. Saturation power was investigated first by varying B1 (0.5–2 µT) in 5 healthy volunteers then by applying B1 of 0.5 and 1.5 µT in 10 patients with non-enhancing glioma. Tissue contrast (TC) and contrast-to-noise ratios (CNR) were calculated between glioma and normal appearing white matter (NAWM) and grey matter, in APT- and NOE-weighted images. Volume percentages of the tumor showing hypo/hyperintensity (VPhypo/hyper,CEST) in APT/NOE-weighted images were calculated for each patient. Results LD APT resulting from using a B1 of 1.5 µT was found to provide significant positive TCtumor,NAWM and MTRREX NOE (B1 of 1.5 µT) provided significant negative TCtumor,NAWM in tissue differentiation. MTRREX-based NOE imaging under 1.5 µT provided significantly larger VPhypo,CEST than MTRREX APT under 1.5 µT. Conclusion This work showed that with a rapid CEST acquisition using a B1 saturation power of 1.5 µT and covering the whole tumor, analysis of both LD APT and MTRREX NOE allows for observing tumor heterogeneity, which will be beneficial in future studies using CEST-MRI to improve imaging diagnostics for non-enhancing glioma.

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Chemical exchange saturation transfer for detection of antiretroviral drugs in brain tissue

10.1101/2021.02.25.432765 ◽

2021 ◽

Author(s):

Aditya N. Bade ◽

Howard E. Gendelman ◽

JoEllyn McMillan ◽

Yutong Liu

Keyword(s):

Chemical Exchange ◽

Magnetization Transfer ◽

Antiretroviral Drugs ◽

Chemical Exchange Saturation Transfer ◽

Magnetization Transfer Ratio ◽

Saturation Transfer ◽

Viral Reservoirs ◽

Drug Concentrations ◽

Imaging Results ◽

Magnetic Resonance Imaging Mri

AbstractHuman immunodeficiency virus type-1 (HIV-1) antiretroviral drug (ARV) theranostics facilitates biodistribution and efficacy of therapies designed to target viral reservoirs. To this end, we have now deployed intrinsic drug chemical exchange saturation transfer (CEST) contrast to detect ARV distribution within the central nervous system (CNS).MethodsCEST effects for lamivudine (3TC) and emtricitabine (FTC) were measured by asymmetric magnetization transfer ratio analyses in solutions. CEST magnetic resonance imaging (MRI) was performed on 3TC-treated mice with analysis made by Lorentzian fitting.ResultsCEST effects of 3TC and FTC hydroxyl and amino protons linearly correlated to drug concentrations. 3TC was successfully detected in brain sub-regions by MRI. The imaging results were validated by measurements of CNS drug concentrations.ConclusionCEST contrasts can be used to detect ARVs using MRI. Such detection can be used to assess spatial-temporal drug biodistribution. This is most notable within the CNS where drug biodistribution may be more limited with the final goal of better understanding ARV-associated efficacy and potential toxicity.

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Saturation transfer MRI is sensitive to neurochemical changes in the rat brain due to chronic unpredictable mild stress

Scientific Reports ◽

10.1038/s41598-021-97991-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anna Pankowska ◽

Agata Chudzik ◽

Tymoteusz Słowik ◽

Artur Łazorczyk ◽

Katarzyna Kochalska ◽

...

Keyword(s):

Chemical Exchange ◽

Nuclear Overhauser Effect ◽

Magnetization Transfer ◽

Brain Regions ◽

Chemical Exchange Saturation Transfer ◽

Magnetization Transfer Ratio ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Saturation Transfer ◽

Neurochemical Changes

AbstractChemical exchange saturation transfer (CEST) MRI was performed for the evaluation of cerebral metabolic changes in a rat model of depressive-like disease induced by chronic unpredictable mild stress (CUMS). CEST Z-spectra were acquired on a 7 T MRI with two saturation B1 amplitudes (0.5 and 0.75 µT) to measure the magnetization transfer ratio (MTR), CEST and relayed nuclear Overhauser effect (rNOE). Cerebral cortex and hippocampus were examined in two groups of animals: healthy control (n = 10) and stressed (n = 14), the latter of which was exposed to eight weeks of the CUMS protocol. The stressed group Z-spectrum parameters, primarily MTRs, were significantly lower than in controls, at all selected frequency offsets (3.5, 3.0, 2.0, − 3.2, − 3.6 ppm) in the cortex (the largest difference of ~ 3.5% at − 3.6 ppm, p = 0.0005) and the hippocampus (MTRs measured with a B1 = 0.5 µT). The hippocampal rNOE contributions decreased significantly in the stressed brains. Glutamate concentration (assessed using ELISA) and MTR at 3 ppm correlated positively in both brain regions. GABA concentration also correlated positively with CEST contributions in both cerebral areas, while such correlation with MTR was positive in hippocampus, and nonsignificant in cortex. Results indicate that CEST is sensitive to neurometabolic changes following chronic stress exposure.

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Preliminary application of 3.0T magnetic resonance chemical exchange saturation transfer imaging in brain metastasis of lung cancer

10.21203/rs.2.11304/v2 ◽

2019 ◽

Author(s):

Yonggui Yang ◽

Xiaobo QU ◽

Yihui HUANG ◽

Afsar Khan ◽

Gen Yan ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Chemical Exchange ◽

Magnetization Transfer ◽

Metastatic Tumor ◽

Chemical Exchange Saturation Transfer ◽

Magnetization Transfer Ratio ◽

Saturation Transfer ◽

Tumor Group ◽

Significant Difference

Abstract Background: Lung cancer brain metastases are very common and one of the common causes of treatment failure. We aimed to examine the clinical use of chemical exchange saturation transfer(CEST) technology in the evaluation of brain metastases for lung cancer diagnosis and prognosis. Methods: We included26 cases of lung cancer brain metastases, 15 cases of gliomas, and 20 cases with normal tests. The magnetization transfer ratio (MTR;3.5ppm) image from the GRE-EPI-CEST sequence was analyzed using the ASSET technique and APT technology. The MTR values were measured in the lesion-parenchymal, edema, and non-focus regions, and the MTR image was compared with the conventional MRI. ANOVA and t-test were used for statistical analysis. Results: The lesion-parenchymal, edema, and non-focus areas in the metastatic-tumor-group were red-yellow, yellow-green, and green-blue, and the MTR values were 3.29±1.14%,1.28±0.36%,and 1.26±0.31%, respectively. However, in the glioma-group, the corresponding areas were red, red-yellow, and green-blue, and the MTR values were 6.29±1.58%, 2.87±0.65%, and 1.03±0.30%, respectively. The MTR values of the corresponding areas in the normal-group were 1.07±0.22%,1.04±0.23%, and 1.06±0.24%, respectively. Traditional MR images are in black-white contrast and no metabolic information is displayed. The MTRvalues of the three regions were significantly different among the three groups. The values were also significantly different between the parenchymal and edema areas in the metastatic-tumor-group. There were significant differences in the MTR values between the non-lesion and edema regions, but there was no significant difference between the edema and non-focus areas. In the glioma-group, there were significant differences in the MTR values between the parenchymal and edema areas, between the parenchymal and non-focus areas, and between the edema and non-focus areas. Conclusions: CEST reflects the protein metabolism; therefore, early diagnosis of brain metastases and assessment of the prognosis can be achieved using molecular imaging.

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Temporal Changes in In Vivo Glutamate Signal during Demyelination and Remyelination in the Corpus Callosum: A Glutamate-Weighted Chemical Exchange Saturation Transfer Imaging Study

International Journal of Molecular Sciences ◽

10.3390/ijms21249468 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9468

Author(s):

Do-Wan Lee ◽

Hwon Heo ◽

Chul-Woong Woo ◽

Dong-Cheol Woo ◽

Jeong-Kon Kim ◽

...

Keyword(s):

Corpus Callosum ◽

Chemical Exchange ◽

Magnetization Transfer ◽

Imaging Study ◽

Chemical Exchange Saturation Transfer ◽

Cerebral White Matter ◽

Magnetization Transfer Ratio ◽

Saturation Transfer ◽

Clinical Magnetic Resonance Imaging

Background: Glutamate-weighted chemical exchange saturation transfer (GluCEST) is a useful imaging tool that can be used to detect changes in glutamate levels in vivo and could also be helpful in the diagnosis of brain myelin changes. We investigated glutamate level changes in the cerebral white matter of a rat model of cuprizone-administered demyelination and remyelination using GluCEST. Method: We used a 7 T pre-clinical magnetic resonance imaging (MRI) system. The rats were divided into the normal control (CTRL), cuprizone-administered demyelination (CPZDM), and remyelination (CPZRM) groups. GluCEST data were analyzed using the conventional magnetization transfer ratio asymmetry in the corpus callosum. Immunohistochemistry and transmission electron microscopy analyses were also performed to investigate the myelinated axon changes in each group. Results: The quantified GluCEST signals differed significantly between the CPZDM and CTRL groups (−7.25 ± 1.42% vs. −2.84 ± 1.30%; p = 0.001). The increased GluCEST signals in the CPZDM group decreased after remyelination (−6.52 ± 1.95% in CPZRM) to levels that did not differ significantly from those in the CTRL group (p = 0.734). Conclusion: The apparent temporal signal changes in GluCEST imaging during demyelination and remyelination demonstrated the potential usefulness of GluCEST imaging as a tool to monitor the myelination process.

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