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

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.

scholarly journals Mapping tumour heterogeneity with pulsed 3D CEST MRI in non-enhancing glioma at 3 T

2021 ◽  
Author(s):  
Esther A. H. Warnert ◽  
Tobias C. Wood ◽  
Fatih Incekara ◽  
Gareth J. Barker ◽  
Arnaud J. P. Vincent ◽  
...  
Keyword(s):  
White Matter ◽  
Chemical Exchange ◽  
Tumour Volume ◽  
Chemical Exchange Saturation Transfer ◽  
Amide Proton ◽  
Tumour Heterogeneity ◽  
Normal Appearing White Matter ◽  
Cest Imaging ◽  
Resonance Frequencies ◽  
Cest Mri

Abstract Objective Amide proton transfer (APT) weighted chemical exchange saturation transfer (CEST) imaging is increasingly used to investigate high-grade, enhancing brain tumours. Non-enhancing glioma is currently less studied, but shows heterogeneous pathophysiology with subtypes having equally poor prognosis as enhancing glioma. Here, we investigate the use of CEST MRI to best differentiate non-enhancing glioma from healthy tissue and image tumour heterogeneity. Materials & Methods A 3D pulsed CEST sequence was applied at 3 Tesla with whole tumour coverage and 31 off-resonance frequencies (+6 to -6 ppm) in 18 patients with non-enhancing glioma. Magnetisation transfer ratio asymmetry (MTRasym) and Lorentzian difference (LD) maps at 3.5 ppm were compared for differentiation of tumour versus normal appearing white matter. Heterogeneity was mapped by calculating volume percentages of the tumour showing hyperintense APT-weighted signal. Results LDamide gave greater effect sizes than MTRasym to differentiate non-enhancing glioma from normal appearing white matter. On average, 17.9 % ± 13.3 % (min–max: 2.4 %–54.5 %) of the tumour volume showed hyperintense LDamide in non-enhancing glioma. Conclusion This works illustrates the need for whole tumour coverage to investigate heterogeneity in increased APT-weighted CEST signal in non-enhancing glioma. Future work should investigate whether targeting hyperintense LDamide regions for biopsies improves diagnosis of non-enhancing glioma.

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

2022 ◽  
Author(s):  
Laura Mancini ◽  
Stefano Casagranda ◽  
Guillaume Gautier ◽  
Philippe Peter ◽  
Bruno Lopez ◽  
...  
Keyword(s):  
Chemical Exchange ◽  
Magnetization Transfer ◽  
Chemical Exchange Saturation Transfer ◽  
Magnetization Transfer Ratio ◽  
Saturation Transfer ◽  
Wild Type ◽  
Clinical Value ◽  
Cest Mri ◽  
Treatment Naïve ◽  
Glioma Classification

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.

scholarly journals Can Chemical Exchange Saturation Transfer (CEST MRI) be used as biomarker of disease progression in Prion Disease?

2021 ◽  
Author(s):  
Eleni Demetriou ◽  
Mohamed Tachrount ◽  
Matthew Ellis ◽  
Jacqueline Linehan ◽  
Sebastian Brandner ◽  
...  
Keyword(s):  
Disease Progression ◽  
Prion Protein ◽  
Prion Disease ◽  
Neurodegenerative Disorders ◽  
Chemical Exchange ◽  
Chemical Exchange Saturation Transfer ◽  
Amide Proton ◽  
Saturation Transfer ◽  
Protein Deposition ◽  
Cest Mri

Human prion diseases are fatal neurodegenerative disorders that may have prolonged asymptomatic incubation periods. However, the underlying mechanism by which prions cause brain damage remains unclear. In turn, characterization of early pathological aspects would be of benefit for the diagnosis and potential treatment of these progressive neurodegenerative disorders. We investigated chemical exchange saturation transfer (CEST) MRI based on its exquisite sensitivity to cytosol protein content as a surrogate for prion disease pathology. Three groups of prion-infected mice at different stages of the disease underwent conventional magnetic resonance imaging and CEST MRI at 9.4T. For each mouse, chemical exchange contrasts were measured by applying five RF powers at various frequency offsets using magnetization transfer asymmetries. Relayed Nuclear Overhauser effects (NOE*) and amide proton transfer (APT*) were also assessed. For comparison, CEST MRI measurements were also made in healthy control mice brains. Here we show that alterations in CEST signal were detected before structural modifications or any clinical signs of prion disease. The detected CEST signal displayed different patterns at different stages of the disease indicating its potential for use as a longitudinal marker of disease progression. Highly significant correlations were found between CEST metrics and histopathological findings. A decline in NOE signal was positively correlated with abnormal prion protein deposition (R2 = 0.91) in the thalami of prion infected mice. Moreover, the NOE signal was negatively correlated with astrogliosis (R2 = 0.71) in the thalamus. No significant correlations were detected between NOE signals and spongiosis. MTR asymmetry at 3.5 ppm was also correlated with astrogliosis (R2 = 0.59), and prion protein deposition (R2 = 0.63) in thalamus. No significant changes were detected in APT* between prion-infected and control mice at all stages of the disease. Finally, MTR asymmetry between 2.8 and 3.2 ppm was correlated with prion protein deposition (R2 = 0.47) in the thalamus of prion -infected mice. To conclude, CEST MRI has potential utility as a biomarker of neurodegenerative processes in prion disease

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

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.

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

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.

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

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.

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

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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