Littérature scientifique sur le sujet « GlucoCEST »

Uptake of administered D-glucose (Glc) or 2-deoxy-D-glucose (2DG) has been indirectly mapped through the chemical exchange (CE) between glucose hydroxyl and water protons using CE-dependent saturation transfer (glucoCEST) magnetic resonance imaging (MRI). We propose an alternative technique—on-resonance CE-sensitive spin-lock (CESL) MRI—to enhance responses to glucose changes. Phantom data and simulations suggest higher sensitivity for this ‘glucoCESL’ technique (versus glucoCEST) in the intermediate CE regime relevant to glucose. Simulations of CESL signals also show insensitivity to B0-fluctuations. Several findings are apparent from in vivo glucoCESL studies of rat brain at 9.4 Tesla with intravenous injections. First, dose-dependent responses are nearly linearly for 0.25-, 0.5-, and 1-g/kg Glc administration (obtained with 12-second temporal resolution), with changes robustly detected for all doses. Second, responses at a matched dose of 1 g/kg are much larger and persist for a longer duration for 2DG versus Glc administration, and are minimal for mannitol as an osmolality control. And third, with similar increases in steady-state blood glucose levels, glucoCESL responses are ~2.2 times higher for 2DG versus Glc, consistent with their different metabolic properties. Overall, we show that glucoCESL MRI could be a highly sensitive and quantifiable tool for glucose transport and metabolism studies.

Abstract Objective Clinical relevance of dynamic glucose enhanced (DGE) chemical exchange saturation transfer (CEST) imaging has mostly been demonstrated at ultra-high field (UHF) due to low effect size. Results of a cohort study at clinical field strength are shown herein. Materials and methods Motion and field inhomogeneity corrected T1ρ‐based DGE (DGE⍴) images were acquired before, during and after a d-glucose injection with 6.3 s temporal resolution to detect accumulation in the brain. Six glioma patients with clear blood–brain barrier (BBB) leakage, two glioma patients with suspected BBB leakage, and three glioma patients without BBB leakage were scanned at 3 T. Results In high-grade gliomas with BBB leakage, d-glucose uptake could be detected in the gadolinium (Gd) enhancing region as well as in the tumor necrosis with a maximum increase of ∆DGE⍴ around 0.25%, whereas unaffected white matter did not show any significant DGE⍴ increase. Glioma patients without Gd enhancement showed no detectable DGE⍴ effect within the tumor. Conclusion First application of DGE⍴ in a patient cohort shows an association between BBB leakage and DGE signal irrespective of the tumor grade. This indicates that glucoCEST corresponds more to the disruptions of BBB with Gd uptake than to the molecular tumor profile or tumor grading.

AbstractCancer is one of the most devastating diseases that the world is currently facing, accounting for 10 million deaths in 2020 (WHO). In the last two decades, advanced medical imaging has played an ever more important role in the early detection of the disease, as it increases the chances of survival and the potential for full recovery. To date, dynamic glucose-enhanced (DGE) MRI using glucose-based chemical exchange saturation transfer (glucoCEST) has demonstrated the sensitivity to detect both d-glucose and glucose analogs, such as 3-oxy-methyl-d-glucose (3OMG) uptake in tumors. As one of the recent international efforts aiming at pushing the boundaries of translation of the DGE MRI technique into clinical practice, a multidisciplinary team of eight partners came together to form the “glucoCEST Imaging of Neoplastic Tumors (GLINT)” consortium, funded by the Horizon 2020 European Commission. This paper summarizes the progress made to date both by these groups and others in increasing our knowledge of the underlying mechanisms related to this technique as well as translating it into clinical practice.

2-Deoxy-D-glucose (2DG) is a known surrogate molecule that is useful for inferring glucose uptake and metabolism. Although 13C-labeled 2DG can be detected by nuclear magnetic resonance (NMR), its low sensitivity for detection prohibits imaging to be performed. Using chemical exchange saturation transfer (CEST) as a signal-amplification mechanism, 2DG and the phosphorylated 2DG-6-phosphate (2DG6P) can be indirectly detected in 1H magnetic resonance imaging (MRI). We showed that the CEST signal changed with 2DG concentration, and was reduced by suppressing cerebral metabolism with increased general anesthetic. The signal changes were not affected by cerebral or plasma pH, and were not correlated with altered cerebral blood flow as demonstrated by hypercapnia; neither were they related to the extracellular glucose amounts as compared with injection of D- and L-glucose. In vivo31P NMR revealed similar changes in 2DG6P concentration, suggesting that the CEST signal reflected the rate of glucose assimilation. This method provides a new way to use widely available MRI techniques to image deoxyglucose/glucose uptake and metabolism in vivo without the need for isotopic labeling of the molecules.

L'imagerie par résonance magnétique du transfert de saturation par échange chimique (IRM CEST) représente un outil puissant pour l'étude du métabolisme, offrant une résolution temporelle et spatiale supérieure ainsi qu'une sensibilité accrue par rapport à la spectroscopie par résonance magnétique. L'IRM CEST permet la détection indirecte de certains métabolites grâce à l'interaction entre leurs protons et ceux de l'eau. Le CEST peut cartographier le glucose, le glutamate et la créatine, qui sont des métabolites importants impliqués dans les cancers et les maladies neurodégénératives et musculosquelettiques, ce qui en fait un outil de bio-imagerie prometteur. Le développement rapide de l'IRM à haut champ magnétique (≥7 T) au cours des dernières décennies a grandement bénéficié au CEST, ouvrant la voie à de nouvelles applications et suscitant ainsi un intérêt croissant.L'objectif de cette thèse est de développer l'IRM CEST dans un contexte clinique, en tirant pleinement parti des champs magnétiques élevés pour augmenter la robustesse et la vitesse des acquisitions CEST. Pour ce faire, nous nous concentrons sur deux objectifs principaux. Le premier est de développer la méthode d'imagerie CEST dans un environnement clinique, en surmontant les limitations pratiques associées aux scanners IRM cliniques à haut champ, notamment les contraintes strictes du débit d'absorption spécifique (DAS) et des hétérogénéités de champ (B1) des RadioFréquences (RF).Pour atteindre ce premier objectif, une séquence CEST en transmission parallèle a été mise au point. La transmission parallèle utilise une antenne d'émission RF multicanal, qui peut être contrôlée indépendamment pour réduire l'hétérogénéité B1. En utilisant la transmission parallèle, nous avons mis en œuvre une stratégie d'acquisition qui nous a permis de produire des images CEST avec trois fois moins d'hétérogénéité B1, et deux fois plus rapidement que l'état de l'art de la littérature.Le deuxième objectif est d'évaluer la performance du CEST, pondérée en glucose et glutamate, dans la détection et la caractérisation du vieillissement normal et pathologique. Une étude clinique a été réalisée, impliquant des volontaires sains jeunes et âgés ainsi que des patients atteints de la maladie d'Alzheimer. Les résultats ont montré que le CEST peut détecter les variations globales de glutamate et de glucose dans le cerveau associées au vieillissement. L'acquisition et l'exploitation de données provenant de patients atteints de la maladie d'Alzheimer sont, eux, toujours en cours.En conclusion, cette thèse a permis de développer des méthodes CEST à haut champ et d'évaluer leurs performances dans l'étude du vieillissement. Ces résultats ouvrent des perspectives encourageantes pour l'utilisation du CEST comme biomarqueur de la maladie d'Alzheimer et d'autres maladies neurodégénératives
Chemical Exchange Saturation Transfer Magnetic Resonance Imaging (CEST MRI) represents a powerful tool for the study of metabolism, offering superior temporal and spatial resolution as well as increased sensitivity compared to Magnetic Resonance Spectroscopy (MRS). CEST MRI enables the indirect detection of certain metabolites through the interaction between their labile protons and those of bulk water. CEST can map glucose, glutamate, creatine, which are important metabolites involved in cancers, and neurodegenerative and musculoskeletal diseases, representing therefore a promising bioimaging tool. The rapid development of high magnetic field MRI ((≥7 T) in recent decades greatly benefits CEST, opening up new applications and generating growing interest.The aim of this thesis is to develop CEST MRI in a clinical context, taking full advantage of high magnetic fields to increase the robustness and speed of CEST acquisitions. To this end, we focus on two main objectives. The first is to develop the CEST imaging method in a clinical environment, overcoming the practical limitations associated with high-field clinical MRI scanners, notably the strict constraints of Specific Absorption Rate (SAR) and RadioFrequency (RF) field heterogeneities (B1).To achieve this first objective, a parallel transmission CEST sequence was developed. Parallel transmission uses a multi-channel RF transmit antenna, which can be controlled independently to reduce B1 heterogeneity. Moreover, parallel transmission also allows optimized energy management using virtual observation points (a strategy developed in the laboratory) By making use of parallel transmission we have implemented an acquisition strategy which allowed us to produce CEST images with three times less B1 heterogeneity, and two times faster than compared to the state of the art literature reports.The second objective is to evaluate the performance of CEST, glucose, and glutamate weighted, in detecting and characterizing normal and pathological aging. A clinical study was carried out, involving young and elderly healthy volunteers as well as Alzheimer’s disease (AD) patients. The results showed that CEST can detect global variations in glutamate and glucose in the brain associated with aging. The acquisition and exploitation of data from AD patients is still in progress.In conclusion, this thesis has enabled the development of high-field CEST methods and the evaluation of their performance in the study of aging. These results open up encouraging prospects for the use of CEST as a biomarker of AD and other neurodegenerative diseases