CEST imaging of fast exchanging amine pools with corrections for competing effects at 9.4 T

Zhang, Xiao‐Yong; Wang, Feng; Li, Hua; Xu, Junzhong; Gochberg, Daniel F.; Gore, John C.; Zu, Zhongliang

doi:10.1002/nbm.3715

Cited by 32 publications

(66 citation statements)

References 57 publications

(167 reference statements)

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“…Various types of pathology can alter tissue properties, particularly, water relaxation times, water content, and semi-solid MTC content. Previous studies showed that APT signal apparently increases with T 1w , but the relationship is not linear (42, 65). Notably, the positive correlation no longer exists at the high RF saturation power level, and it seems that the APT signal is not associated with T 1w at 2 μT, as was used in this study.…”

Section: Discussionmentioning

confidence: 93%

Improving the detection sensitivity of pH‐weighted amide proton transfer MRI in acute stroke patients using extrapolated semisolid magnetization transfer reference signals

Heo

Zhang

Burton

et al. 2017

Magnetic Resonance in Med

138

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Purpose To quantify APT effects in acidic ischemic lesions and assess the spatial-temporal relationship between diffusion, perfusion, and pH deficits in acute stroke patients. Methods Thirty acute stroke patients were scanned at 3 T. Quantitative APT (APT#) effects in acidic ischemic lesions were measured using an extrapolated semisolid magnetization transfer reference signal (EMR) technique and compared with commonly used MTRasym(3.5ppm) or APT-weighted parameters. Results APT# images showed clear pH deficits in the ischemic lesion, whereas MTRasym(3.5ppm) signals were slightly hypointense. The APT# contrast between acidic ischemic lesions and normal tissue in acute stroke patients was more than 3 times larger than MTRasym(3.5ppm) contrast (−1.45 ± 0.40 % for APT# vs. −0.39 ± 0.52 % for MTRasym(3.5ppm), p < 4.6 × 10-4). Hypoperfused and acidic areas without an apparent diffusion coefficient abnormality were observed and assigned to an ischemic acidosis penumbra. Hypoperfused areas at normal pH were also observed and assigned to benign oligemia. Hyperintense APT signals were observed in a hemorrhage area in one case. Conclusion The quantitative APT study using the EMR approach enhances APT MRI sensitivity to pH compared to conventional APT-weighted MRI, allowing more reliable delineation of an ischemic acidosis in the penumbra.

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Section: Discussionmentioning

confidence: 93%

Improving the detection sensitivity of pH‐weighted amide proton transfer MRI in acute stroke patients using extrapolated semisolid magnetization transfer reference signals

Heo

Zhang

Burton

et al. 2017

Magnetic Resonance in Med

138

View full text Add to dashboard Cite

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“…Specifically for EMR, CEST data with Δ ω from –6500 to –3500 Hz and 3500 to 6500 Hz and ω 1 of 3.6 μT, and with Δ ω from –4000 to –2500 Hz and 2500 to 4000–Hz and ω 1 of 1.0 μT, were fitted to a two‐pool MT model (see Appendix). The reference signals in an offset range from –5 to 5 ppm were then estimated using the fitted parameters, and used for the calculation of the above metrics. As a result of the relatively homogeneous B 1 field in rat brain, ω 1 used to calculate tan θ was from nominal values.…”

Section: Methodsmentioning

confidence: 99%

“…In CEST imaging of fast‐exchanging amines, which is usually performed at relatively high irradiation powers (e.g. >3 μT), the CEST peak shifts, which makes it difficult to identify specific CEST effects …”

Section: Introductionmentioning

confidence: 99%

Increased CEST specificity for amide and fast‐exchanging amine protons using exchange‐dependent relaxation rate

Zhang

Wang

et al. 2017

NMR in Biomedicine

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Chemical exchange saturation transfer (CEST) imaging of amides at 3.5 ppm and fast-exchanging amines at 3 ppm provides a unique means to enhance the sensitivity of detection of, for example, proteins/peptides and neurotransmitters, respectively, and hence can provide important information on molecular composition. However, despite the high sensitivity relative to conventional magnetic resonance spectroscopy (MRS), in practice, CEST often has relatively poor specificity. For example, CEST signals are typically influenced by several confounding effects, including direct water saturation (DS), semi-solid non-specific magnetization transfer (MT), the influence of water relaxation times (T ) and nearby overlapping CEST signals. Although several editing techniques have been developed to increase the specificity by removing DS, semi-solid MT and T influences, it is still challenging to remove overlapping CEST signals from different exchanging sites. For instance, the amide proton transfer (APT) signal could be contaminated by CEST effects from fast-exchanging amines at 3 ppm and intermediate-exchanging amines at 2 ppm. The current work applies an exchange-dependent relaxation rate (R ) to address this problem. Simulations demonstrate that: (1) slowly exchanging amides and fast-exchanging amines have distinct dependences on irradiation powers; and (2) R serves as a resonance frequency high-pass filter to selectively reduce CEST signals with resonance frequencies closer to water. These characteristics of R provide a means to isolate the APT signal from amines. In addition, previous studies have shown that CEST signals from fast-exchanging amines have no distinct features around their resonance frequencies. However, R gives Lorentzian lineshapes centered at their resonance frequencies for fast-exchanging amines and thus can significantly increase the specificity of CEST imaging for amides and fast-exchanging amines.

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“…However, distinct from the narrow and specific peaks prevalent in MRS, CEST peaks, especially those from fast‐exchanging pools (e.g. glutamate at 3 ppm 2 ), are broad and often overlap . Therefore, the CEST signal at 2 ppm may contain contributions from both intermediate‐exchanging amines at 2 ppm and other nearby fast‐exchanging pools.…”

Section: Introductionmentioning

confidence: 99%

Chemical exchange rotation transfer imaging of intermediate‐exchanging amines at 2 ppm

Louie

Lin

et al. 2017

NMR in Biomedicine

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Chemical exchange saturation transfer (CEST) imaging of amine protons exchanging at intermediate rates and whose chemical shift is around 2 ppm may provide a means of mapping creatine. However, quantification of this effect may be compromised by the influence of overlapping CEST signals from fast exchanging amines and hydroxyls. We aimed to investigate the exchange rate filtering effect of a variation of CEST, named chemical exchange rotation transfer (CERT), as a means of isolating creatine contributions at around 2 ppm from other overlapping signals. Simulations were performed to study the filtering effects of CERT for selecting transfer effects from protons of specific exchange rates. Control samples containing the main metabolites in brain, bovine serum albumin (BSA), and egg white albumen (EWA) at their physiological concentrations and pH were used to study the ability of CERT to isolate molecules with amines at 2 ppm that exchange at intermediate rates, and corresponding methods were used for in vivo rat brain imaging. Simulations showed that exchange rate filtering can be combined with conventional filtering based on chemical shift. Studies on samples showed that signal contributions from creatine can be separated from those of other metabolites by using this combined filter, but contributions from protein amines may still be significant. This exchange filtering can also be used for in vivo imaging. CERT provides more specific quantification of amines at 2 ppm that exchange at intermediate rates compared to conventional CEST imaging.

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CEST imaging of fast exchanging amine pools with corrections for competing effects at 9.4 T

Cited by 32 publications

References 57 publications

Improving the detection sensitivity of pH‐weighted amide proton transfer MRI in acute stroke patients using extrapolated semisolid magnetization transfer reference signals

Improving the detection sensitivity of pH‐weighted amide proton transfer MRI in acute stroke patients using extrapolated semisolid magnetization transfer reference signals

Increased CEST specificity for amide and fast‐exchanging amine protons using exchange‐dependent relaxation rate

Chemical exchange rotation transfer imaging of intermediate‐exchanging amines at 2 ppm

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