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Author(s):  
Laura Mancini ◽  
Stefano Casagranda ◽  
Guillaume Gautier ◽  
Philippe Peter ◽  
Bruno Lopez ◽  
...  

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.


Author(s):  
Yulun Wu ◽  
Tobias Charles Wood ◽  
Fatemeh Arzanforoosh ◽  
Juan Antonio Hernandez-Tamames ◽  
Gareth John Barker ◽  
...  

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.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Ken Ohno ◽  
Masaki Ohkubo ◽  
Bingwen Zheng ◽  
Masaki Watanabe ◽  
Tsuyoshi Matsuda ◽  
...  

The glycine level in the brain is known to be altered in neuropsychiatric disorders, such as schizophrenia and Alzheimer’s disease (AD). Several studies have reported the in vivo measurement of glycine concentrations in the brain using proton magnetic resonance spectroscopy (1H-MRS), but 1H-MRS is not capable of imaging the distribution of glycine concentration with high spatial resolution. Chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) is a new technology that can detect specific molecules, including amino acids, in tissues. To validate the measurements of glycine concentrations in living tissues using CEST from glycine to water (GlyCEST), we extracted the brain tissues from mice and performed biochemical tests. In wild-type C57BL/6 mice, GlyCEST effects were found to be higher in the thalamus than in the cerebral cortex ( P < 0.0001 , paired t-test), and this result was in good agreement with the biochemical results. In 5xFAD mice, an animal model of AD, GlyCEST measurements demonstrated that glycine concentrations in the cerebral cortex ( P < 0.05 , unpaired t-test) and thalamus ( P < 0.0001 , unpaired t-test), but not in the hippocampus, were decreased compared to those in wild-type mice. These findings suggest that we have successfully applied the CEST-MRI technique to map the distribution of glycine concentrations in the murine brain. The present method also captured the changes in cerebral glycine concentrations in mice with AD. Imaging the distribution of glycine concentrations in the brain can be useful in investigating and elucidating the pathological mechanisms of neuropsychiatric disorders.


Author(s):  
Philip S. Boyd ◽  
Johannes Breitling ◽  
Andreas Korzowski ◽  
Moritz Zaiss ◽  
Vanessa L. Franke ◽  
...  
Keyword(s):  

2021 ◽  
Author(s):  
Eleni Demetriou ◽  
Mohamed Tachrount ◽  
Matthew Ellis ◽  
Jacqueline Linehan ◽  
Sebastian Brandner ◽  
...  

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


ACS Sensors ◽  
2021 ◽  
Author(s):  
Chathuri J. Kombala ◽  
Sanjaya D. Lokugama ◽  
Aikaterini Kotrotsou ◽  
Tianzhe Li ◽  
Alyssa C. Pollard ◽  
...  

2021 ◽  
Author(s):  
Zheng Han ◽  
Chuheng Chen ◽  
Xiang Xu ◽  
Renyuan Bai ◽  
Verena Staedtke ◽  
...  

2021 ◽  
Author(s):  
Laura Mancini ◽  
Stefano Casagranda ◽  
Guillaume Gautier ◽  
Philippe Peter ◽  
Bruno Lopez ◽  
...  

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.


Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4278
Author(s):  
Chloé Buyse ◽  
Nicolas Joudiou ◽  
Cyril Corbet ◽  
Olivier Feron ◽  
Lionel Mignion ◽  
...  

(1) Background: The acidosis of the tumor micro-environment may have profound impact on cancer progression and on the efficacy of treatments. In the present study, we evaluated the impact of a treatment with UK-5099, a mitochondrial pyruvate carrier (MPC) inhibitor on tumor extracellular pH (pHe); (2) Methods: glucose consumption, lactate secretion and extracellular acidification rate (ECAR) were measured in vitro after exposure of cervix cancer SiHa cells and breast cancer 4T1 cells to UK-5099 (10 µM). Mice bearing the 4T1 tumor model were treated daily during four days with UK-5099 (3 mg/kg). The pHe was evaluated in vivo using either chemical exchange saturation transfer (CEST)-MRI with iopamidol as pHe reporter probe or 31P-NMR spectroscopy with 3-aminopropylphosphonate (3-APP). MR protocols were applied before and after 4 days of treatment; (3) Results: glucose consumption, lactate release and ECAR were increased in both cell lines after UK-5099 exposure. CEST-MRI showed a significant decrease in tumor pHe of 0.22 units in UK-5099-treated mice while there was no change over time for mice treated with the vehicle. Parametric images showed a large heterogeneity in response with 16% of voxels shifting to pHe values under 7.0. In contrast, 31P-NMR spectroscopy was unable to detect any significant variation in pHe; (4) Conclusions: MPC inhibition led to a moderate acidification of the extracellular medium in vivo. CEST-MRI provided high resolution parametric images (0.44 µL/voxel) of pHe highlighting the heterogeneity of response within the tumor when exposed to UK-5099.


Author(s):  
Xiongqi Han ◽  
Joseph Ho Chi Lai ◽  
Jianpan Huang ◽  
Se Weon Park ◽  
Yang Liu ◽  
...  
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