Fast and equilibrium CEST imaging of brain tumor patients at 3T

Wu, Yin; Liu, Zhou; Yang, Qian; Zou, Lihui; Zhang, Fan; Qian, Long; Liu, Xin; Zheng, Hairong; Luo, Dingcun; Sun, Phillip Zhe

doi:10.1016/j.nicl.2021.102890

Cited by 23 publications

(28 citation statements)

References 49 publications

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“…Briefly, a quasi‐steady‐state (QUASS) algorithm was recently proposed to reconstruct the equilibrium CEST effect from experimental measurements, 24 permitting accurate determination of the underlying CEST effects despite the use of different Ts and Td, advantageous over routine CEST effect calculation 25 . Furthermore, the QUASS solution has been shown to provide robust and accurate quantification of saturation transfer effects, such as amide proton transfer (APT) and combined MT and NOE (MT & NOE), in experimental tumor models and brain tumor patients 26,27 . Capitalizing on the recent progress of QUASS‐CEST MRI, the current study aimed to preliminarily investigate and establish QUASS CrCEST MRI in human muscles at 3 T. Both creatine phantom and healthy volunteers were imaged to evaluate the accuracy and robustness of QUASS CrCEST MRI, laying the groundwork for future multicenter trials.…”

Section: Introductionmentioning

confidence: 99%

Demonstration of fast and equilibrium human muscle creatine CEST imaging at 3 T

Liu

Yang

Luo

et al. 2022

Magnetic Resonance in Med

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Purpose Creatine chemical exchange saturation transfer (CrCEST) MRI is used increasingly in muscle imaging. However, the CrCEST measurement depends on the RF saturation duration (Ts) and relaxation delay (Td), and it is challenging to compare the results of different scan parameters. Therefore, this study aims to evaluate the quasi‐steady‐state (QUASS) CrCEST MRI on clinical 3T scanners. Methods T1 and CEST MRI scans of Ts/Td of 1 s/1 s and 2 s/2 s were obtained from a multi‐compartment creatine phantom and 5 healthy volunteers. The CrCEST effect was quantified with asymmetry analysis in the phantom, whereas 5‐pool Lorentzian fitting was applied to isolate creatine from phosphocreatine, amide proton transfer, combined magnetization transfer and nuclear Overhauser enhancement effects, and direct water saturation in four major muscle groups of the lower leg. The routine and QUASS CrCEST measurements were compared under two different imaging conditions. Paired Student's t‐test was performed with p‐values less than 0.05 considered statistically significant. Results The phantom study showed a substantial influence of Ts/Td on the routine CrCEST quantification (p = 0.02), and such impact was mitigated with the QUASS algorithm (p = 0.20). The volunteer experiment showed that the routine CrCEST, amide proton transfer, and combined magnetization transfer and nuclear Overhauser enhancement effects increased significantly with Ts and Td (p < 0.05) and were significantly smaller than the corresponding QUASS indices (p < 0.01). In comparison, the QUASS CrCEST MRI showed little dependence on Ts and Td, indicating its robustness and accuracy. Conclusion The QUASS CrCEST MRI is feasible to provide fast and accurate muscle creatine imaging.

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Section: Introductionmentioning

confidence: 99%

Demonstration of fast and equilibrium human muscle creatine CEST imaging at 3 T

Liu

Yang

Luo

et al. 2022

Magnetic Resonance in Med

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“…These changes further validated that CEST contrast at 3.5 ppm sensitively detects molecular changes in GBM related to its aggressiveness. Meanwhile, CEST at 3.5 ppm showed an increased signal in brain tumors with other analyses such as direct saturation-corrected (DISC-CEST) [26,92], threeoffset analysis [26], and quasi-steady-state (QUASS) [10]. More neuropathologies could be revealed when combining T1 and diffusion findings in APT interpretation.…”

Section: Glioblastoma and Gliomas (Grade II Iii)mentioning

confidence: 94%

“…GBM, also known as a grade IV astrocytoma, defined by World Health Organization (WHO), is the most common and aggressive brain tumor. Generally, hyperintensities in APT/APTw images were reported in GBM when compared with contralateral regions [10,11,16,22,25,33,34,36,39,42,60,98]. In human GBM, the increased signals were found to correlate positively to cell proliferation (Ki-67) and cell density, validated by histology [27,39].…”

Section: Glioblastoma and Gliomas (Grade II Iii)mentioning

confidence: 94%

“…Most of the studies focused on the offset at around −3.5 ppm as it is more detectable, especially at 3 T [81,97]. NOE at −3.2 to −3.7 ppm, extracted using Lorentzian fitting, showed decreased signals in brain tumors in both animal and human studies [10,33,34,44,90,[98][99][100]. NOE analyzed by AREX showed hypointensity in brain tumors as compared to contralateral regions which correlated to the macromolecular content in tumors [96].…”

Section: Noe Contrastmentioning

confidence: 99%

“…CEST contrast is dependent on acquisitions and post-processing methods. In brain tumors, careful interpretation is needed since other contributions, such as MT and T1, could be quite different from normal brain tissues [10,21,25,34,89,90,96,99,100,104,168,169]. In this section, we will explain the principle of CEST acquisition, the common methods in analyzing the Z-spectrum, and recent developments in using deep-learning to assist CEST post-processing.…”

Section: Technical Partmentioning

confidence: 99%

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Molecular Imaging of Brain Tumors and Drug Delivery Using CEST MRI: Promises and Challenges

et al. 2022

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Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) detects molecules in their natural forms in a sensitive and non-invasive manner. This makes it a robust approach to assess brain tumors and related molecular alterations using endogenous molecules, such as proteins/peptides, and drugs approved for clinical use. In this review, we will discuss the promises of CEST MRI in the identification of tumors, tumor grading, detecting molecular alterations related to isocitrate dehydrogenase (IDH) and O-6-methylguanine-DNA methyltransferase (MGMT), assessment of treatment effects, and using multiple contrasts of CEST to develop theranostic approaches for cancer treatments. Promising applications include (i) using the CEST contrast of amide protons of proteins/peptides to detect brain tumors, such as glioblastoma multiforme (GBM) and low-grade gliomas; (ii) using multiple CEST contrasts for tumor stratification, and (iii) evaluation of the efficacy of drug delivery without the need of metallic or radioactive labels. These promising applications have raised enthusiasm, however, the use of CEST MRI is not trivial. CEST contrast depends on the pulse sequences, saturation parameters, methods used to analyze the CEST spectrum (i.e., Z-spectrum), and, importantly, how to interpret changes in CEST contrast and related molecular alterations in the brain. Emerging pulse sequence designs and data analysis approaches, including those assisted with deep learning, have enhanced the capability of CEST MRI in detecting molecules in brain tumors. CEST has become a specific marker for tumor grading and has the potential for prognosis and theranostics in brain tumors. With increasing understanding of the technical aspects and associated molecular alterations detected by CEST MRI, this young field is expected to have wide clinical applications in the near future.

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A Magnetic Resonance Imaging‐Chemical Exchange Saturation Transfer (MRI‐CEST) Method for the Detection of Water Cycling across Cellular Membranes

Di Gregorio,

Papi,

Conti

et al. 2024

Angewandte Chemie

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Water cycling across the membrane transporters is considered a hallmark of cellular metabolism and it could be of high diagnostic relevance in the characterization of tumors and other diseases. The method relies on the response of intracellular proton exchanging molecules to the presence of extracellular Gd‐based contrast agents (GBCAs). Paramagnetic GBCAs enhances the relaxation rate of water molecules in the extracellular compartment and, through membrane exchange, the relaxation enhancement is transferred to intracellular molecules. The effect is detected at the MRI‐CEST (Magnetic Resonance Imaging ‐ Chemical Exchange Saturation Transfer) signal of intracellular proton exchanging molecules. The magnitude of the change in the CEST response reports on water cycling across the membrane. The method has been tested on RBC and on orthotopic murine models of breast cancer with different degree of malignancy (4T1, TS/A and 168FARN). The distribution of voxels reporting on membrane permeability fits well with the cells’ aggressiveness and act as an early reporter to monitor therapeutic treatments.

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Fast and equilibrium CEST imaging of brain tumor patients at 3T

Abstract: Highlights CEST MRI under non-equilibrium conditions is prone to measurement variabilities. The QUASS algorithm reconstructs the equilibrium CEST effect from measurements. The QUASS CEST algorithm enables fast and equilibrium tumor imaging at 3 T.

Cited by 23 publications

References 49 publications

Demonstration of fast and equilibrium human muscle creatine CEST imaging at 3 T

Demonstration of fast and equilibrium human muscle creatine CEST imaging at 3 T

Molecular Imaging of Brain Tumors and Drug Delivery Using CEST MRI: Promises and Challenges

A Magnetic Resonance Imaging‐Chemical Exchange Saturation Transfer (MRI‐CEST) Method for the Detection of Water Cycling across Cellular Membranes

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