Pulse sequences for measuring exchange rates between proton species: From unlocalised NMR spectroscopy to chemical exchange saturation transfer imaging

Demetriou, Eleni; Kujawa, Aaron; Golay, Xavier

doi:10.1016/j.pnmrs.2020.06.001

Cited by 8 publications

(6 citation statements)

References 138 publications

(172 reference statements)

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“…Although single slice readout was adopted in early clinical CEST imaging, recent CEST development includes substantially improved spatial coverage, including fast multislice 186–188 and 3D readout 142,189–191 . Demetriou et al recently provided a comprehensive review of CEST MRI pulse sequences 192 …”

Section: Practical Considerations Of Cest Mri Experimentsmentioning

confidence: 99%

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Detection of tissue pH with quantitative chemical exchange saturation transfer magnetic resonance imaging

2022

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Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as a novel means for sensitive detection of dilute labile protons and chemical exchange rates. By sensitizing to pH-dependent chemical exchange, CEST MRI has shown promising results in monitoring tissue statuses such as pH changes in disorders like acute stroke, tumor, and acute kidney injury. This article briefly reviews the basic principles for CEST imaging and quantitative measures, from the simplistic asymmetry analysis to multipool Lorentzian decoupling and quasi-steady-state reconstruction. In particular, the advantages and limitations of commonly used quantitative approaches for CEST applications are discussed.acute stroke, amide proton transfer, chemical exchange saturation transfer, pH, pH-weighted, tumor | INTRODUCTIONpH is a physiological index tightly regulated in healthy tissue. 1,2 A notable pH change often signals altered tissue states, such as those following acute ischemia [3][4][5][6][7][8] and the development of cancer. 9-15 For example, tissue acidosis is associated with anaerobic glycolysis following acute stroke. [16][17][18][19] The pH drop compromises essential adenosine triphosphate (ATP)-dependent functions, often leading to cell death and ultimately tissue infarction. [20][21][22][23][24] In the case of cancers, excessive amounts of lactate are produced, disrupting pH homeostasis, a hallmark of the Warburg effect. [25][26][27] It has been recognized that pH change profoundly affects tumor growth and metastasis. 28 As such, pH measurement may provide novel insights into tissue microenvironment and response to therapy, and potentially facilitate the development of new therapeutics. pH measurement in vivo, however, is not straightforward because common strategies such as pH immunohistology, fluorescence microscopy, or phosphorus magnetic resonance approaches are either invasive, [29][30][31][32][33] of limited penetration depth, 34,35 or insensitive. [36][37][38] To address such an unmet biomedical need, Balaban and coworkers introduced chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) as a new sensitive means of imaging pH and dilute labile protons, [39][40][41][42] laying the groundwork for CEST MRI research over the following Abbreviations used: APT, amide proton transfer; CEST, chemical exchange saturation transfer; CESTR, CEST ratio; CNR, contrast-to-noise ratio; MMTR, mean magnetization transfer ratio; MRAPT, MT and relaxation normalized APT; MT, magnetization transfer; MTR, magnetization transfer ratio; MTR asym , MTR asymmetry; NOE, nuclear Overhauser enhancement; pHw, pHweighted; QUASS, quasi-steady-state; rCESTR, ratiometric CESTR; rCNR, relative CNR; ΔMRAPTR, delta MRAPT ratio.

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Section: Practical Considerations Of Cest Mri Experimentsmentioning

confidence: 99%

“…142,[189][190][191] Demetriou et al recently provided a comprehensive review of CEST MRI pulse sequences 192. …”

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confidence: 99%

Detection of tissue pH with quantitative chemical exchange saturation transfer magnetic resonance imaging

2022

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“…Those pulses were applied at 71 frequency offsets to collect an evenly sampled Z spectrum between -5.0 and 5.0ppm. To obtain optimal saturation efficiency of slow and fast exchanging species, five different radiofrequency field amplitudes (B 1 ) were applied (11), (12): 0.6μT (n=80, pulse length=50ms, flip angle=360°, 90% duty cycle), 1.2 μT (n=80, pulse length=50ms, flip angle=900°, 90% duty cycle), 2.0 μT (n=60, pulse length=50ms, flip angle=1200°, 90% duty cycle), 3.6 μT (n=40, pulse length=50ms, flip angle=2100°, 90% duty cycle) and 10 μT (n=30, pulse length=50ms, flip angle=6000°, 99% duty cycle). In addition, to improve image SNR and to reduce the physiological noise during MRI acquisition, each Z-spectrum was collected three times and then averaged for each mouse.…”

Section: Cest Protocolmentioning

confidence: 99%

Can Chemical Exchange Saturation Transfer (CEST MRI) be used as biomarker of disease progression in Prion Disease?

Demetriou

Tachrount

Ellis

et al. 2021

Preprint

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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.

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“…CEST MRI confers a sensitive imaging mechanism to measure dilute labile groups and properties such as pH. 1,2 Amide proton transfer-weighted (APTw) CEST imaging probes pH-dependent amide proton exchange. [3][4][5] Notably, pH MRI complements perfusion, diffusion, and kurtosis MRI to demarcate graded ischemic tissue injury for guiding treatment, [6][7][8][9] with promising results from experimental [10][11][12] and translational stroke research.…”

Section: Introductionmentioning

confidence: 99%

“…CEST MRI confers a sensitive imaging mechanism to measure dilute labile groups and properties such as pH 1,2 . Amide proton transfer‐weighted (APTw) CEST imaging probes pH‐dependent amide proton exchange 3–5 .…”

Section: Introductionmentioning

confidence: 99%

Comparison of model‐free Lorentzian and spinlock model‐based fittings in quantitative CEST imaging of acute stroke

Sun

2023

Magnetic Resonance in Med

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PurposeCEST MRI detects complex tissue changes following acute stroke. Our study aimed to test if spinlock model‐based fitting of the quasi‐steady‐state (QUASS)‐reconstructed equilibrium CEST MRI improves the determination of multi‐pool signal changes over the commonly‐used model‐free Lorentzian fitting in acute stroke.Theory and MethodsMultiple three‐pool CEST Z‐spectra were simulated using Bloch‐McConnell equations for a range of T1, relaxation delay, and saturation times. The multi‐pool CEST signals were solved from the simulated Z‐spectra to test the accuracy of routine Lorentzian (model‐free) and spinlock (model‐based) fittings without and with QUASS reconstruction. In addition, multiparametric MRI scans were obtained in rat models of acute stroke, including relaxation, diffusion, and CEST Z‐spectrum. Finally, we compared model‐free and model‐based per‐pixel CEST quantification in vivo.ResultsThe spinlock model‐based fitting of QUASS CEST MRI provided a nearly T1‐independent determination of multi‐pool CEST signals, advantageous over the fittings of apparent CEST MRI (model‐free and model‐based). In vivo data also demonstrated that the spinlock model‐based QUASS fitting captured significantly different changes in semisolid magnetization transfer (−0.9 ± 0.8 vs. 0.3 ± 0.8%), amide (−1.1 ± 0.4 vs. −0.5 ± 0.2%), and guanidyl (1.0 ± 0.4 vs. 0.7 ± 0.3%) signals over the model‐free Lorentzian analysis.ConclusionOur study demonstrated that spinlock model‐based fitting of QUASS CEST MRI improved the determination of the underlying tissue changes following acute stroke, promising further clinical translation of quantitative CEST imaging.

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Pulse sequences for measuring exchange rates between proton species: From unlocalised NMR spectroscopy to chemical exchange saturation transfer imaging

Cited by 8 publications

References 138 publications

Detection of tissue pH with quantitative chemical exchange saturation transfer magnetic resonance imaging

Detection of tissue pH with quantitative chemical exchange saturation transfer magnetic resonance imaging

Can Chemical Exchange Saturation Transfer (CEST MRI) be used as biomarker of disease progression in Prion Disease?

Comparison of model‐free Lorentzian and spinlock model‐based fittings in quantitative CEST imaging of acute stroke

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