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

Warnert, Esther; Wood, Tobias C.; Incekara, Fatih; Barker, Gareth J.; Vincent, Arnaud; Schouten, Joost W.; Kros, Johan M.; Bent, Martin van den; Smits, Marion; Tamames, Juan Antonio Hernández

doi:10.1007/s10334-021-00911-6

Cited by 18 publications

(30 citation statements)

References 31 publications

(50 reference statements)

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“…To evaluate the extent of hyper/hypointensity of LD APT/ NOE and MTR REX APT/NOE within the tumor per patient, a patient-specific threshold was determined as reported in [17] (3)…”

Section: And 4 Based On Ldmentioning

confidence: 99%

“…In addition, MTR asym cannot evaluate saturation pools on opposite sides of the main resonance frequency individually, i.e., the effect of APT (3.5 ppm) and nuclear Overhauser enhancement (NOE, at − 3.5 ppm) are both reflected in MTR asym at 3.5 ppm. Advanced metrics were proposed for separation of the APT and NOE signal, via multi-pool Lorentzian fitting [28] and the isolation of individual CEST effects by the Lorentzian difference (LD) [17,[28][29][30][31][32][33]. In addition, relaxation-compensated inverse magnetization transfer ratio (MTR Rex [34,35]) combined with Lorentzian fitting was proposed in glioma imaging at clinical field strength (3 T) to account for spillover effects that cannot be compensated by LD analysis [13,28,30,[36][37][38].…”

Section: Introductionmentioning

confidence: 99%

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

Wood

Arzanforoosh

et al. 2022

Magn Reson Mater Phy

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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.

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“…To evaluate the extent of hyper/hypointensity of LD APT/ NOE and MTR REX APT/NOE within the tumor per patient, a patient-specific threshold was determined as reported in [17] (3)…”

Section: And 4 Based On Ldmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Wood

Arzanforoosh

et al. 2022

Magn Reson Mater Phy

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“…In human patients, hyperintensities of APTw were found in tumors when compared with the contralateral regions [11,23,25,26,33,36,39,[42][43][44]60,70,[87][88][89][90][91][92] (Table 1). These increased APTw signals were positively correlated to high cellularity [39,70] and were validated by histology.…”

Section: Apt-weighted (Aptw) Contrastmentioning

confidence: 99%

“…In general, NOE signals consistently decrease among different analyses in both human and animal studies. Among these studies, there is one study that showed unchanged NOE in a non-enhancing glioma, while APTw signal consistently increased in both enhancing and non-enhancing gliomas [11]. Nevertheless, NOE could be an additional CEST contrast to indicate molecular changes in brain tumors.…”

Section: Noe Contrastmentioning

confidence: 99%

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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“…In the case of glioma imaging, amide proton transfer (APT) CEST is the most common application of CEST, although not as widely available or commonly used as MRS. Elevated concentrations of proteins in glioma compared to surrounding tissues and the high rates of intracellular proton exchanges leads to an increased APT level. APT CEST can be used to differentiate between LGGs and HGGs ( Choi et al, 2017 ), differentiation between regions of tumor and peritumoral edema ( Wen et al, 2010 ), and is gaining interest as a method of investigating intratumoral heterogeneity ( Warnert et al, 2021 ). One notable advantage of MRS over CEST is that MRS is able to simultaneously quantify multiple compounds, while CEST is only able to acquire one or two compounds at a time.…”

Section: Preoperative Imaging and Surgical Planningmentioning

confidence: 99%

Advanced Imaging Techniques for Newly Diagnosed and Recurrent Gliomas

Carrete

Young

2022

Front. Neurosci.

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Management of gliomas following initial diagnosis requires thoughtful presurgical planning followed by regular imaging to monitor treatment response and survey for new tumor growth. Traditional MR imaging modalities such as T1 post-contrast and T2-weighted sequences have long been a staple of tumor diagnosis, surgical planning, and post-treatment surveillance. While these sequences remain integral in the management of gliomas, advances in imaging techniques have allowed for a more detailed characterization of tumor characteristics. Advanced MR sequences such as perfusion, diffusion, and susceptibility weighted imaging, as well as PET scans have emerged as valuable tools to inform clinical decision making and provide a non-invasive way to help distinguish between tumor recurrence and pseudoprogression. Furthermore, these advances in imaging have extended to the operating room and assist in making surgical resections safer. Nevertheless, surgery, chemotherapy, and radiation treatment continue to make the interpretation of MR changes difficult for glioma patients. As analytics and machine learning techniques improve, radiomics offers the potential to be more quantitative and personalized in the interpretation of imaging data for gliomas. In this review, we describe the role of these newer imaging modalities during the different stages of management for patients with gliomas, focusing on the pre-operative, post-operative, and surveillance periods. Finally, we discuss radiomics as a means of promoting personalized patient care in the future.

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

Cited by 18 publications

References 31 publications

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

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

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

Advanced Imaging Techniques for Newly Diagnosed and Recurrent Gliomas

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