scholarly journals GLINT: GlucoCEST in neoplastic tumors at 3 T—clinical results of GlucoCEST in gliomas

2021 ◽  
Author(s):  
Benjamin Bender ◽  
Kai Herz ◽  
Anagha Deshmane ◽  
Vivien Richter ◽  
Ghazaleh Tabatabai ◽  
...  
Keyword(s):  
Chemical Exchange ◽  
Tumor Grade ◽  
Clinical Results ◽  
Chemical Exchange Saturation Transfer ◽  
Ultra High Field ◽  
Tumor Grading ◽  
Maximum Increase ◽  
Glucose Injection ◽  
Cest Imaging ◽  
The Brain

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.

scholarly journals Novel nanomedicine with a chemical-exchange saturation transfer effect for breast cancer treatment in vivo

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Yanlong Jia ◽  
Chaochao Wang ◽  
Jiehua Zheng ◽  
Guisen Lin ◽  
Dalong Ni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Chemical Exchange ◽  
Raft Polymerization ◽  
Animal Experiments ◽  
Chemical Exchange Saturation Transfer ◽  
Saturation Transfer ◽  
Cest Imaging

Abstract Background Nanomedicine is a promising new approach to cancer treatment that avoids the disadvantages of traditional chemotherapy and improves therapeutic indices. However, the lack of a real-time visualization imaging technology to monitor drug distribution greatly limits its clinical application. Image-tracked drug delivery is of great clinical interest; it is useful for identifying those patients for whom the therapy is more likely to be beneficial. This paper discusses a novel nanomedicine that displays features of nanoparticles and facilitates functional magnetic resonance imaging but is challenging to prepare. Results To achieve this goal, we synthesized an acylamino-containing amphiphilic block copolymer (polyethylene glycol-polyacrylamide-polyacetonitrile, PEG-b-P(AM-co-AN)) by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PEG-b-P(AM-co-AN) has chemical exchange saturation transfer (CEST) effects, which enable the use of CEST imaging for monitoring nanocarrier accumulation and providing molecular information of pathological tissues. Based on PEG-b-P(AM-co-AN), a new nanomedicine PEG-PAM-PAN@DOX was constructed by nano-precipitation. The self-assembling nature of PEG-PAM-PAN@DOX made the synthesis effective, straightforward, and biocompatible. In vitro studies demonstrate decreased cytotoxicity of PEG-PAM-PAN@DOX compared to free doxorubicin (half-maximal inhibitory concentration (IC50), mean ~ 0.62 μg/mL vs. ~ 5 μg/mL), and the nanomedicine more efficiently entered the cytoplasm and nucleus of cancer cells to kill them. Further, in vivo animal experiments showed that the nanomedicine developed was not only effective against breast cancer, but also displayed an excellent sensitive CEST effect for monitoring drug accumulation (at about 0.5 ppm) in tumor areas. The CEST signal of post-injection 2 h was significantly higher than that of pre-injection (2.17 ± 0.88% vs. 0. 09 ± 0.75%, p < 0.01). Conclusions The nanomedicine with CEST imaging reflects the characterization of tumors and therapeutic functions has great potential medical applications.

scholarly journals Whole brain mapping of glutamate in adult and old primates at 11.7T

2021 ◽  
Author(s):  
Clement M Garin ◽  
Nachiket A. Nadkarni ◽  
Jeremy Pepin ◽  
Julien Flament ◽  
Marc Dhenain
Keyword(s):  
Magnetic Field ◽  
Nucleus Accumbens ◽  
High Magnetic Field ◽  
Basal Forebrain ◽  
Chemical Exchange ◽  
Chemical Exchange Saturation Transfer ◽  
Whole Brain ◽  
Cortical Areas ◽  
Age Related ◽  
The Brain

Glutamate is the amino acid with the highest cerebral concentration. It plays a central role in brain metabolism. It is also the principal excitatory neurotransmitter in the brain and is involved in multiple cognitive functions. Alterations of the glutamatergic system may contribute to the pathophysiology of many neurological disorders. For example, changes of glutamate availability are reported in rodents and humans during Alzheimer's and Huntington's diseases, epilepsy as well as during aging. Most studies evaluating cerebral glutamate have used invasive or spectroscopy approaches focusing on specific brain areas. Chemical Exchange Saturation Transfer imaging of glutamate (gluCEST) is a recently developed imaging technique that can map glutamate distribution in the entire brain with higher sensitivity and at higher resolution than previous techniques. It thus has strong potential clinical applications to assess glutamate changes in the brain. High field is a key condition to perform gluCEST images with a meaningful signal to noise ratio. Thus, even if some studies started to evaluate gluCEST in humans, most studies focused on rodent models that can be imaged at high magnetic field. In particular, systematic characterization of gluCEST contrast distribution throughout the whole brain has never been performed in humans or non-human primates. Here, we characterized for the first time the distribution of the glutamate index in the whole brain and in large-scale networks of mouse lemur primates at 11.7 Tesla. Because of its small size, this primate can be imaged in high magnetic field systems. It is widely studied as a model of cerebral aging or Alzheimer's disease. We observed high gluCEST contrast in cerebral regions such as the nucleus accumbens, septum, basal forebrain, cortical areas 24 and 25. Age-related alterations of this biomarker were detected in the nucleus accumbens, septum, basal forebrain, globus pallidus, hypophysis, cortical areas 24, 21, 6 and in olfactory bulbs. An age-related gluCEST contrast decrease was also detected in specific neuronal networks, such as fronto-temporal and evaluative limbic networks. These results outline regional differences of gluCEST contrast and strengthen its potential to provide new biomarkers of cerebral function in primates.

scholarly journals NIMG-70. A LABEL-FREE APPROACH TO ASSESS CHEMOTHERAPY DRUG CONCENTRATION USING CHEMICAL EXCHANGE SATURATION TRANSFER MRI – A FEASIBILITY STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi177-vi177
Author(s):  
David Kamson ◽  
Stuart Grossman ◽  
Zheng Han ◽  
Xiang Xu ◽  
Peter van Zijl ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Chemical Exchange ◽  
Detection Threshold ◽  
Chemical Exchange Saturation Transfer ◽  
High Dose ◽  
Label Free ◽  
Saturation Transfer ◽  
Synthetic Urine ◽  
Drug Concentrations ◽  
The Brain

Abstract BACKGROUND Drug delivery is one of the most pressing problems in neuro-oncology as the blood-brain barrier (BBB) uniquely limits penetration of substances into the brain parenchyma. Plasma and CSF drug concentrations are relatively easy to measure, but do not necessarily reflect concentrations in the brain. Furthermore, invasive measurements may be inaccurate in regions of heterogeneous BBB integrity. Advanced non-invasive imaging approaches may help bridge this information gap without the added risk. Chemical exchange saturation transfer (CEST) is an MRI technique that allows in vivo detection of molecules with a suitable hydrogen exchange rate, such as methotrexate (MTX). High-dose MTX is commonly used in oncology and its concentrations in urine (>2000µM), plasma (>1000µM) and enhancing brain tumors (>350µM) are well above the theoretical threshold of CEST. AIM: We aimed to confirm the CEST detectability of MTX in vitro, and to estimate the currently lowest measurable concentrations in solutions mimicking bodily fluids. METHODS We used a 9.4T MRI to assess the spectra of MTX at 37°C at various concentrations (0.1–10.0 mM) in a phosphate-buffered saline (PBS) solution at various pH (6.0–8.0), as well as in synthetic urine at pH 6.2. RESULTS CEST signals attributable to MTX at 1.5 and 2.7ppm were successfully detected in PBS at concentrations as low as 500µM. The optimal field strength was 3.6µT. While increasing pH increased the detection threshold of the 2.7ppm signal, the 1.5ppm signal was minimally affected by pH within physiologic ranges. In synthetic urine, the MTX CEST signal was well-detectable even at concentrations as low as 200µM. CONCLUSIONS These preliminary results suggest that MTX-CEST may be feasible at field strengths achievable in clinical scanners and at MTX concentrations previously measured in enhancing brain tumors treated with high-dose MTX. Further optimization of the technique for in human use is under way.

scholarly journals pH Mapping of Skeletal Muscle by Chemical Exchange Saturation Transfer (CEST) Imaging

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2610
Author(s):  
Yu-Wen Chen ◽  
Hong-Qing Liu ◽  
Qi-Xuan Wu ◽  
Yu-Han Huang ◽  
Yu-Ying Tung ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Magnetic Resonance ◽  
Ph Value ◽  
Chemical Exchange ◽  
Chemical Exchange Saturation Transfer ◽  
Resonance Spectroscopy ◽  
Saturation Transfer ◽  
Ph Changes ◽  
Cest Imaging

Magnetic resonance imaging (MRI) is extensively used in clinical and basic biomedical research. However, MRI detection of pH changes still poses a technical challenge. Chemical exchange saturation transfer (CEST) imaging is a possible solution to this problem. Using saturation transfer, alterations in the exchange rates between the solute and water protons because of small pH changes can be detected with greater sensitivity. In this study, we examined a fatigued skeletal muscle model in electrically stimulated mice. The measured CEST signal ratio was between 1.96 ppm and 2.6 ppm in the z-spectrum, and this was associated with pH values based on the ratio between the creatine (Cr) and the phosphocreatine (PCr). The CEST results demonstrated a significant contrast change at the electrical stimulation site. Moreover, the pH value was observed to decrease from 7.23 to 7.15 within 20 h after electrical stimulation. This pH decrease was verified by 31P magnetic resonance spectroscopy and behavioral tests, which showed a consistent variation over time.

scholarly journals Rapid and quantitative chemical exchange saturation transfer (CEST) imaging with magnetic resonance fingerprinting (MRF)

2018 ◽  
Vol 80 (6) ◽  
pp. 2449-2463 ◽  
Author(s):  
Ouri Cohen ◽  
Shuning Huang ◽  
Michael T. McMahon ◽  
Matthew S. Rosen ◽  
Christian T. Farrar
Keyword(s):  
Magnetic Resonance ◽  
Chemical Exchange ◽  
Chemical Exchange Saturation Transfer ◽  
Saturation Transfer ◽  
Cest Imaging ◽  
Quantitative Chemical

Abstract 63: Novel Imaging of Protein Integrity to Better Define Ischemic Injury After Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
George Harston ◽  
Yee Kai Tee ◽  
Nicholas Blockley ◽  
Yunus Msayib ◽  
Fintan Sheerin ◽  
...  
Keyword(s):  
Protein Structure ◽  
Chemical Exchange ◽  
Ischemic Injury ◽  
Chemical Exchange Saturation Transfer ◽  
Imaging Biomarker ◽  
Imaging Protocol ◽  
Patient Level ◽  
Cest Imaging ◽  
Ischemic Core ◽  
Nuclear Overhauser

Introduction: Ischemic injury on MRI is defined acutely by measuring the diffusion of water alone. Chemical exchange saturation transfer imaging (CEST) allows measurement of intracellular pH, and changes in protein structure and mobility using Nuclear Overhauser Enhancement (NOE). When identifying treatment targets, changes to protein integrity have the potential to complement diffusion-weighted imaging (DWI) in distinguishing irreversible from reversible intracellular processes that are amenable to therapeutic intervention. Methods: Patients with non-lacunar ischemic stroke underwent serial MRI over 1 month. The imaging protocol included single slice CEST imaging. NOE was quantified using a 3-pool exchange model relative to the contralateral hemisphere (rNOE*). DWI, ASL perfusion imaging, T1-weighted and FLAIR imaging were used to define the tissue outcome: ischemic core, infarct growth, and oligemic tissue that survived. Infarct growth was classified as early or late (before or after 24 hours). Images and masks were registered to CEST native image space for voxelwise and patient-level serial analyses. Results: 30 patients were included in the analysis. Within 6 hours rNOE* in early infarct growth was significantly lower than ischemic core and late infarct growth (p<0.001 and p<0.001, see Figure). In patient-level analyses, rNOE* dropped over the initial 24 hours in the ischemic core and early infarct growth regions, but not in regions of late infarct growth or oligemia. Conclusion: rNOE* showed a discrete temporal profile in tissue that infarcted by 24 hours in contrast to that which survived or infarcted later. This is additive information to that provided by routine acute stroke MRI at presentation, and demonstrates that the imaging of intracellular protein structure and mobility may have a role alongside DWI in helping to predict tissue fate. Further work is required to understand the potential of NOE as a modifiable imaging biomarker.

scholarly journals Insight into the quantitative metrics of chemical exchange saturation transfer (CEST) imaging

2016 ◽  
Vol 77 (5) ◽  
pp. 1853-1865 ◽  
Author(s):  
Hye‐Young Heo ◽  
Dong‐Hoon Lee ◽  
Yi Zhang ◽  
Xuna Zhao ◽  
Shanshan Jiang ◽  
...  
Keyword(s):  
Chemical Exchange ◽  
Chemical Exchange Saturation Transfer ◽  
Saturation Transfer ◽  
Quantitative Metrics ◽  
Cest Imaging ◽  
Insight Into
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