Enhancing sensitivity of pH-weighted MRI with combination of amide and guanidyl CEST

Jin, Tao; Wang, Ping; Hitchens, T. Kevin; Kim, Seong‐Gi

doi:10.1016/j.neuroimage.2017.06.007

Cited by 70 publications

(124 citation statements)

References 57 publications

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“…These data confirmed the presence of a hypoperfused area with a decrease in pH without an ADC abnormality, corresponding to an ischemic acidosis penumbra, as well as a hypoperfused region at normal pH, corresponding with benign oligemia. APTw imaging of permanent and reversible brain ischemic models has been intensively studied over the past 12 years, confirming these early established principles …”

Section: Current Applicationsmentioning

confidence: 63%

APT‐weighted MRI: Techniques, current neuro applications, and challenging issues

Zhou

Heo

Knutsson

et al. 2019

Magnetic Resonance Imaging

245

329

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Amide proton transfer‐weighted (APTw) imaging is a molecular MRI technique that generates image contrast based predominantly on the amide protons in mobile cellular proteins and peptides that are endogenous in tissue. This technique, the most studied type of chemical exchange saturation transfer imaging, has been used successfully for imaging of protein content and pH, the latter being possible due to the strong dependence of the amide proton exchange rate on pH. In this article we briefly review the basic principles and recent technical advances of APTw imaging, which is showing promise clinically, especially for characterizing brain tumors and distinguishing recurrent tumor from treatment effects. Early applications of this approach to stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and traumatic brain injury are also illustrated. Finally, we outline the technical challenges for clinical APT‐based imaging and discuss several controversies regarding the origin of APTw imaging signals in vivo. Level of Evidence: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:347–364.

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Section: Current Applicationsmentioning

confidence: 63%

APT‐weighted MRI: Techniques, current neuro applications, and challenging issues

Zhou

Heo

Knutsson

et al. 2019

Magnetic Resonance Imaging

245

329

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“…Estimating from our phantom data at pH 7.0 and pH 6.4, we would expect only a 16% decrease in PCrCEST from pH, with the rest of the drop being a result of phosphorylative changes. The 90.6% increase in the Cr peak as seen in CEST is due to the shift toward slower exchange from the drop in pH as well as the conversion of PCr to Cr from dephosphorylation. Due to both phosphorylative changes and pH differences, changes detected by PCrCEST were expected to be exaggerated in comparison to 31 P‐MRS, due to the drop in pH postmortem.…”

Section: Discussionmentioning

confidence: 96%

“…Thus, a number of groups have held interest in imaging creatine (Cr) using CEST methods, as creatine has labile protons in its guanidyl group. However, a portion of this CEST signal will come from the guanidyl groups of mobile proteins . Conversely, targeting PCr in this phosphorylation process may be crucial for obtaining more specific information about this metabolic process.…”

Section: Introductionmentioning

confidence: 99%

Chemical exchange saturation transfer imaging of phosphocreatine in the muscle

Chung

Jin

Lee

et al. 2019

Magnetic Resonance in Med

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Purpose To determine the exchange parameters for the CEST of phosphocreatine (PCrCEST) in phantoms and to characterize PCrCEST in vivo in the muscle at different saturation powers and magnetic fields. Methods Exchange parameters were measured in PCr solutions using varying saturation power at 15.2 T. Z‐spectra were analyzed using multipool Lorentzian fitting in the hindlimb using various powers at 2 different fields: 9.4 T and 15.2 T. Modulation of PCr signal in PCrCEST and phosphorus MRS was observed in the mouse hindlimb before and after euthanasia. Results The exchange rate of PCr at physiological pH in phantoms was confirmed to be in a much slower exchange regime compared with Cr: kex at pH 7.3 and below was less than 400 s–1. There was insufficient signal for detection of PCrCEST in the brain, but PCrCEST in the hindlimb was measured to be 2.98% ± 0.43 at a B1 of 0.47 μT at 15.2 T, which is 29% higher than 9.4T values. The value of PCrCEST at a B1 of 0.71 μT was not significantly different than that measured at a B1 of 0.47 μT. After euthanasia, PCrCEST signal dropped by 82.3% compared with an 85% decrease in PCr in phosphorus MRS, whereas CrCEST signal increased by 90.6%. Conclusion The PCrCEST technique has viable sensitivity in the muscle at high fields and shows promise for the study of metabolic dysfunction and cardiac systems.

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“…Previously, several variations of CEST, such as amide proton transfer (APT), glutamate CEST, creatine CEST, CEST imaging of glucose and its derivatives, paramagnetic agent CEST, and acidoCEST, have been developed to detect endogenous and exogenous agents. To further quantify the exchange rate, which is relevant to the intracellular or extracellular pH, a ratiometric approach, using the ratio of two CEST signals that have different dependences on the exchange rate but the same dependences on other non‐specific factors (e.g., solute pool concentration), was also developed .…”

Section: Introductionmentioning

confidence: 99%

Ratiometric NOE(−1.6) contrast in brain tumors

2018

NMR in Biomedicine

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Recently, a new nuclear Overhauser enhancement (NOE)‐mediated saturation transfer effect at around −1.6 ppm from water, termed NOE(−1.6), was reported to show hypointense signals in brain tumors. Similar to chemical exchange saturation transfer or magnetization transfer (MT) effects, which depend on the solute pool concentration, the exchange/coupling rate, the solute transverse relaxation rate, etc., the NOE(−1.6) effect should also depend on these factors. Since the exchange rate is relevant to tissue pH, and the coupling rate and the solute transverse relaxation rate are relevant to the motional property of the coupled molecules, further studies to quantify the contribution from only the exchange/coupling rate and the solute transverse relaxation rate are always interesting. The purpose of this paper is to apply a ratiometric approach to the NOE(−1.6) effect to obtain a metric that is more specific to the NOE coupling rate and the solute transverse relaxation rate than the NOE(−1.6) signal amplitude. Simulations indicate that the ratiometric approach allows us to rule out nearly all of the non‐specific factors including the solute pool concentration, solute and water longitudinal relaxation rates, direct water saturation, and semi‐solid MT effects, and provides a more specific NOE coupling rate‐ and solute transverse relaxation rate‐weighted signal. Animal studies show that the ratiometric NOE(−1.6) decreases dramatically in brain tumors, which suggests that the change in the NOE(−1.6) coupling rate and/or the solute transverse relaxation rate are major contributors to the previously observed hypointense NOE(−1.6) signal in tumors.

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Enhancing sensitivity of pH-weighted MRI with combination of amide and guanidyl CEST

Cited by 70 publications

References 57 publications

APT‐weighted MRI: Techniques, current neuro applications, and challenging issues

APT‐weighted MRI: Techniques, current neuro applications, and challenging issues

Chemical exchange saturation transfer imaging of phosphocreatine in the muscle

Ratiometric NOE(−1.6) contrast in brain tumors

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