Role of chemical exchange on the relayed nuclear Overhauser enhancement signal in saturation transfer MRI

Jin, Tao; Kim, Seong‐Gi

doi:10.1002/mrm.28961

Cited by 21 publications

(39 citation statements)

References 49 publications

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“…A recent study shows the presence of downfield aromatic NOE which overlaps with APT 69 . Based on our simulations in Figure 3D, if the T 2s of aromatic protons is as long as that of amide protons, the low‐duty‐cycle 2π‐CEST can also reduce its contribution.…”

Section: Discussionmentioning

confidence: 49%

NOE‐weighted imaging in tumors using low‐duty‐cycle2π‐CEST

Cui

Sun

2022

Magnetic Resonance in Med

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Purpose: Nuclear Overhauser enhancement (NOE)-mediated CEST imaging at −3.5 ppm has shown clinical interest in diagnosing tumors. Multiple-pool Lorentzian fit has been used to quantify NOE, which, however, requires a long scan time. Asymmetric analysis of CEST signals could be a simple and fast method to quantify this NOE, but it has contamination from the amide proton transfer (APT) at 3.5 ppm. This work proposes a new method using an asymmetric analysis of a low-duty-cycle pulsed-CEST sequence with a flip angle of 360 • , termed 2π-CEST, to reduce the contribution from APT.Methods: Simulations were used to evaluate the capability of the 2π-CEST to reduce APT. Experiments on animal tumor models were performed to show its advantages compared with the conventional asymmetric analysis. Samples of reconstituted phospholipids and proteins were used to evaluate the molecular origin of this NOE. Results:The 2π-CEST has reduced contribution from APT. In tumors where we show that the NOE is comparable to the APT effect, reducing the contamination from APT is crucial. The results show that the NOE signal obtained with 2π-CEST in tumor regions appears more homogeneous than that obtained with the conventional method. The phantom study showed that both phospholipids and proteins contribute to the NOE at −3.5 ppm. Conclusion:The NOE at −3.5 ppm has a different contrast mechanism from APT and other CEST/NOE effects. The proposed 2π-CEST is more accurate than the conventional asymmetric analysis in detecting NOE, and requires much less scan time than the multiple-pool Lorentzian fit. K E Y W O R D S chemical exchange saturation transfer (CEST), magnetization transfer (MT), nuclear Overhauser enhancement (NOE), tumor

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Section: Discussionmentioning

confidence: 49%

NOE‐weighted imaging in tumors using low‐duty‐cycle2π‐CEST

Cui

Sun

2022

Magnetic Resonance in Med

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“…Further studies on ghost membranes and reconstituted phospholipids reveal that the NOE(-3.5 ppm) signals are independent on pH and dependent on the chemical composition of lipids. The independence of lipid-sourced effect on pH along with the similar property of protein-sourced NOE(-3.5 ppm) demonstrated in a recent study (49) can be explained by the mechanism of relayed NOE that NOE is relayed by chemical exchange to achieve saturation transfer from protons on aliphatic chains to the water proton pool (16). Specifically, NOE mediated magnetization transfer is much slower than chemical exchange from relay sites to the water proton pool.…”

Section: Discussionmentioning

confidence: 70%

Assignment of molecular origins of NOE signal at −3.5 ppm in the brain

Zhao

2023

Preprint

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Purpose: Nuclear Overhauser Enhancement mediated saturation transfer effect, termed NOE(-3.5 ppm), is a major source of chemical exchange saturation transfer (CEST) MRI contrasts at 3.5 ppm in the brain. Previous phantom experiments have demonstrated that both proteins and lipids, two major components in tissues, have substantial contributions to NOE(-3.5 ppm) signals. Their relative contributions in tissues are informative for the interpretation of NOE(-3.5 ppm) contrasts that could provide potential imaging biomarkers for relevant diseases, which remain incompletely understood. Methods: Experiments on homogenates and supernatants of brain tissues collected from healthy rats, that could isolate proteins from lipids, were performed to evaluate the relative contribution of lipids to NOE(-3.5 ppm) signals. On the other hand, experiments on ghost membranes with varied pH, and reconstituted phospholipids with different chemical compositions were conducted to study the dependence of NOE(-3.5 ppm) on physiological conditions. Besides, CEST imaging on rat brains bearing 9L tumors and healthy rat brains was performed to analyze the causes of the NOE(-3.5 ppm) contrast variations between tumors and normal tissues, and between gray matter and white matter. Results: Our experiments reveal that lipids have dominant contributions to the NOE (-3.5 ppm) signals. Further analysis suggests that decreased NOE(-3.5 ppm) signals in tumors and higher NOE(-3.5 ppm) signals in white matter than in gray matter are mainly explained by changes in membrane lipids, rather than proteins. Conclusion: NOE(-3.5 ppm) could be exploited as a highly sensitive MRI contrast for imaging membrane lipids in the brain.

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“…31 Note that the signal for 2.6 ppm (∼1.9% in the contralateral tissue) reported here is higher than what we might expect from brain PCr alone (<1%), indicating there may be other sources of contrast in ASEFR 2.6 ppm , such as the amide from protein sidechains, amine protons with a close resonance frequency, and slow nuclear Overhauser enhancement signal from aromatic protons. 48 Besides B 1,avg , the DC of the pulse train may also be adjusted to improve the sensitivity of these CEST signals. However, because the MT mismatch and the matching coefficients are highly sensitive to B 1,avg and the DC of the pulse train (Figure 3B,C), a lower B 1,avg and higher DC low would be preferred to reduce the MT mismatch.…”

Section: Discussionmentioning

confidence: 99%

Average saturation efficiency filter ASEF‐CEST MRI of stroke rodents

Chung

Jin

2022

Magnetic Resonance in Med

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The average saturation efficiency filter (ASEF) is a novel method of improving the specificity of CEST; however, there is a mismatch between the magnetization transfer (MT) effect under high-duty cycle and low-duty cycle pulse trains. We explore measures of mitigation and the sensitivity and potential of ASEF imaging in phantoms and stroke rats.Methods: Simulation and nicotinamide phantoms in denatured protein were used to investigate the effect of different average saturation powers and MT pool parameters on matching coefficients used for correction as well as the ASEF ratio signal and baseline. Then, in vivo studies were performed in stroke rodents to further investigate the sensitivity and fidelity of ASEF ratio spectra.Results: Simulation and studies of nicotinamide phantoms show that the matching coefficient needed to correct the baseline MT mismatch is strongly dependent on the average saturation power. In vivo studies in stroke rodents show that the matching coefficient required to correct the baseline MT mismatch is different for normal versus ischemic tissue. Thus, a baseline correction was performed to further suppress the residue MT mismatch. After correction of the mismatch, ASEF ratio achieved comparable contrast at 3.6 ppm between normal and ischemic tissue when compared to the apparent amide proton transfer (APT*) approach. Moreover, contrasts for 2.0 and 2.6 ppm were also ascertainable from the same spectra. Conclusion:ASEF can improve the CEST signal specificity of slow exchange labile protons such as amide and guanidyl, with small loss to sensitivity. It has strong potential in the CEST imaging of various diseases.

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Role of chemical exchange on the relayed nuclear Overhauser enhancement signal in saturation transfer MRI

Cited by 21 publications

References 49 publications

NOE‐weighted imaging in tumors using low‐duty‐cycle2π‐CEST

NOE‐weighted imaging in tumors using low‐duty‐cycle2π‐CEST

Assignment of molecular origins of NOE signal at −3.5 ppm in the brain

Average saturation efficiency filter ASEF‐CEST MRI of stroke rodents

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