Determination of multipool contributions to endogenous amide proton transfer effects in global ischemia with high spectral resolution in vivo chemical exchange saturation transfer <scp>MRI</scp>

Zhou, Iris Yuwen; Lu, Dongshuang; Ji, Yang; Wu, Limin; Wang, Enfeng; Cheung, J. T.; Zhang, Xiaoan; Sun, Phillip Zhe

doi:10.1002/mrm.27385

Cited by 51 publications

(79 citation statements)

References 50 publications

(65 reference statements)

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“…Thus, the stronger correlation between T 1 -normalized MTR asym and AREX compared with T 1 -normalized MTR asym and MTR asym suggests that it is not necessary to correct for MT, but necessary to compensate for T 1 in cases of acute stroke. This finding was in agreement with previous studies that reported nearly no changes in MT, 45 but significant changes in T 1 in cases of acute stroke. 36,39 It is also worth noting that previous studies have found that APT effect does not linearly depend on T 1 .…”

Section: F I G U R Esupporting

confidence: 94%

Study of common quantification methods of amide proton transfer magnetic resonance imaging for ischemic stroke detection

Foo

Larkin

Sutherland

et al. 2020

Magnetic Resonance in Med

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To assess the correlation and differences between common amide proton transfer (APT) quantification methods in the diagnosis of ischemic stroke. Methods: Five APT quantification methods, including asymmetry analysis and its variants as well as two Lorentzian model-based methods, were applied to data acquired from six rats that underwent middle cerebral artery occlusion scanned at 9.4T. Diffusion and perfusion-weighted images, and water relaxation time maps were also acquired to study the relationship of these conventional imaging modalities with the different APT quantification methods. Results: The APT ischemic area estimates had varying sizes (Jaccard index: 0.544 ≤ J ≤ 0.971) and had varying correlations in their distributions (Pearson correlation coefficient: 0.104 ≤ r ≤ 0.995), revealing discrepancies in the quantified ischemic areas. The Lorentzian methods produced the highest contrast-to-noise ratios (CNRs; 1.427 ≤ CNR ≤ 2.002), but generated APT ischemic areas that were comparable in size to the cerebral blood flow (CBF) deficit areas; asymmetry analysis and its variants produced APT ischemic areas that were smaller than the CBF deficit areas but larger than the apparent diffusion coefficient deficit areas, though having lower CNRs (0.561 ≤ CNR ≤ 1.083). Conclusion: There is a need to further investigate the accuracy and correlation of each quantification method with the pathophysiology using a larger scale | 2189 FOO et al.

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Section: F I G U R Esupporting

confidence: 94%

Study of common quantification methods of amide proton transfer magnetic resonance imaging for ischemic stroke detection

Foo

Larkin

Sutherland

et al. 2020

Magnetic Resonance in Med

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“…Concerning the APTw signal of WMH, pH may play a decisive role. In ischemic lesions, the exchange rate of amide protons is affected due to its sensitivity by pH changes (21,22). In acute ischemic stroke, elevated APTw signal intensity values are attributed to intracellular acidosis (22,(35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

“…In ischemic lesions, the exchange rate of amide protons is affected due to its sensitivity by pH changes (21,22). In acute ischemic stroke, elevated APTw signal intensity values are attributed to intracellular acidosis (22,(35)(36)(37)(38). This intracellular tissue acidification will alleviate in the follow up if clinical symptom improvement occurs after ischemic stroke (with or without treatment) (38,39).…”

Section: Discussionmentioning

confidence: 99%

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Amide Proton Transfer Weighted Imaging Shows Differences in Multiple Sclerosis Lesions and White Matter Hyperintensities of Presumed Vascular Origin

Sartoretti

Wyss

et al. 2019

Front. Neurol.

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Objectives: To assess the ability of 3D amide proton transfer weighted (APTw) imaging based on magnetization transfer analysis to discriminate between multiple sclerosis lesions (MSL) and white matter hyperintensities of presumed vascular origin (WMH) and to compare APTw signal intensity of healthy white matter (healthy WM) with APTw signal intensity of MSL and WHM. Materials and Methods: A total of 27 patients (16 female, 11 males, mean age 39.6 years) with multiple sclerosis, 35 patients (17 females, 18 males, mean age 66.6 years) with small vessel disease (SVD) and 20 healthy young volunteers (9 females, 11 males, mean age 29 years) were included in the MSL, the WMH, and the healthy WM group. MSL and WMH were segmented on fluid attenuated inversion recovery (FLAIR) images underlaid onto APTw images. Histogram parameters (mean, median, 10th, 25th, 75th, 90th percentile) were calculated. Mean APTw signal intensity values in healthy WM were defined by "Region of interest" (ROI) measurements. Wilcoxon rank sum tests and receiver operating characteristics (ROC) curve analyses of clustered data were applied. Results: All histogram parameters except the 75 and 90th percentile were significantly different between MSL and WMH (p = 0.018-p = 0.034). MSL presented with higher median values in all parameters. The histogram parameters offered only low diagnostic performance in discriminating between MSL and WMH. The 10th percentile yielded the highest diagnostic performance with an AUC of 0.6245 (95% CI: [0.532, 0.717]). Mean APTw signal intensity values of MSL were significantly higher than mean values of healthy WM (p = 0.005). The mean values of WMH did not differ significantly from the values of healthy WM (p = 0.345). Sartoretti et al. APTw of White Matter Lesions Conclusions: We found significant differences in APTw signal intensity, based on straightforward magnetization transfer analysis, between MSL and WMH and between MSL and healthy WM. Low AUC values from ROC analyses, however, suggest that it may be challenging to determine type of lesion with APTw imaging. More advanced analysis of the APT CEST signal may be helpful for further differentiation of MSL and WMH.

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“…MTR asym is heterogeneous across the intact white and gray matter despite their little pH difference . It has been shown that in rats, the T 1w ‐normalized CEST effects for the intact brain WM and GM are 2.08 ± 0.20 vs. 2.00 ± 0.23%/s (APT), −1.79 ± 0.88 vs. −0.89 ± 0.97%/s (MT contrast asymmetry) and 4.42 ± 0.58 vs. 3.38 ± 0.42%/s (nuclear overhauser enhancement, NOE), respectively . Indeed, the noticeable NOE and MT contrast between brain WM and GM despite their little pH difference suggest that NOE and MT effects are not pH specific.…”

Section: Introductionmentioning

confidence: 99%

Demonstration of magnetization transfer and relaxation normalized pH‐specific pulse‐amide proton transfer imaging in an animal model of acute stroke

Sun

2020

Magnetic Resonance in Med

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Purpose: pH-weighted amide proton transfer (APT) MRI is promising to serve as a new surrogate metabolic imaging biomarker for refined ischemic tissue demarcation.APT MRI with pulse-RF irradiation (pulse-APT) is an alternative to the routine continuous wave (CW-) APT MRI that overcomes the RF duty cycle limit. Our study aimed to generalize the recently developed pH-specific magnetization transfer and relaxationnormalized APT (MRAPT) analysis to pulse-APT MRI in acute stroke imaging. Methods: Multiparametric MRI, including CW-and pulse-APT MRI scans, were performed following middle cerebral artery occlusion in rats. We calculated pH-sensitive MTR asym and pH-specific MRAPT contrast between the ipsilateral diffusion lesion and contralateral normal area. Results: An inversion pulse of 10 to 15 ms maximizes the pH-sensitive MRI contrast for pulse-APT MRI. The contrast-to-noise ratio of pH-specific MRAPT effect between the contralateral normal area and ischemic lesion from both methods are comparable (3.25 ± 0.65 vs. 3.59 ± 0.40, P > .05). pH determined from both methods were in good agreement, with their difference within 0.1. Conclusions: Pulse-APT MRI provides highly pH-specific mapping for acute stroke imaging. K E Y W O R D Sacidosis, acute stroke, amide proton transfer (APT), chemical exchange saturation transfer (CEST), pulse-CEST MRI | 1527 SUN mismatch into perfusion/pH lesion mismatch (benign oligemia) and pH/diffusion lesion mismatch (metabolic penumbra), refining the routine mismatch paradigm. 13,14 Indeed, recent clinical trials have shown that response to endovascular reperfusion is not time dependent in patients with salvageable tissue, underscoring the importance of accurate penumbra mapping. [15][16][17] Although CEST MRI has often been implemented with continuous wave (CW) RF irradiation, the irradiation scheme of an RF pulse train is of reduced RF duty cycle and specific absorption rate (SAR), making it amenable to all scanners. 18 For slow exchangeable protons, it has been shown that pulse-CEST MRI with inversion pulses of intermediate durations provides similar contrast to that of CW-CEST MRI. [19][20][21] The routine magnetization transfer (MT) ratio asymmetry (MTR asym ) analysis, despite its pH sensitivity, is susceptible to the slightly asymmetric magnetization transfer (MT) effects. MTR asym is heterogeneous across the intact white and gray matter despite their little pH difference. 22 It has been shown that in rats, the T 1w -normalized CEST effects for the intact brain WM and GM are 2.08 ± 0.20 vs. 2.00 ± 0.23%/s (APT), −1.79 ± 0.88 vs. −0.89 ± 0.97%/s (MT contrast asymmetry) and 4.42 ± 0.58 vs. 3.38 ± 0.42%/s (nuclear overhauser enhancement, NOE), respectively. 23 Indeed, the noticeable NOE and MT contrast between brain WM and GM despite their little pH difference suggest that NOE and MT effects are not pH specific. The recently developed MT and relaxation-normalized APT (MRAPT) analysis minimizes the intrinsic non-pH related heterogeneity in pH-weighted MTR asym image toward pH-specific im...

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Determination of multipool contributions to endogenous amide proton transfer effects in global ischemia with high spectral resolution in vivo chemical exchange saturation transfer MRI

Abstract: Combined amide and amine effects dominated the MTR changes after global ischemia, indicating that MTR is predominantly pH-sensitive and suitable for detecting tissue acidosis following acute stroke.

Cited by 51 publications

References 50 publications

Study of common quantification methods of amide proton transfer magnetic resonance imaging for ischemic stroke detection

Study of common quantification methods of amide proton transfer magnetic resonance imaging for ischemic stroke detection

Amide Proton Transfer Weighted Imaging Shows Differences in Multiple Sclerosis Lesions and White Matter Hyperintensities of Presumed Vascular Origin

Demonstration of magnetization transfer and relaxation normalized pH‐specific pulse‐amide proton transfer imaging in an animal model of acute stroke

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