Brain pH Imaging and its Applications

Kim, Hahnsung; Krishnamurthy, Lisa C.; Sun, Phillip Zhe

doi:10.1016/j.neuroscience.2021.01.026

Cited by 16 publications

(22 citation statements)

References 134 publications

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“…The basics of APTw imaging have been explained in several previous review articles. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Briefly, APTw imaging is generally obtained by RF saturation labeling of the water-exchangeable backbone amide proton pool of proteins and peptides, followed by a physical transfer (chemical exchange) of these saturated amide protons to bulk water protons, resulting in a decrease in their magnetization. Theoretically, the CEST effect of amide protons can be expressed in terms of a so-called amide proton transfer ratio (APTR), a formulation that describes the different parameters on which the CEST effect depends.…”

Section: Background and Theorymentioning

confidence: 99%

Review and consensus recommendations on clinical APT‐weighted imaging approaches at 3T: Application to brain tumors

Zhou

Zaiß

Knutsson

et al. 2022

Magnetic Resonance in Med

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119

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Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use. K E Y W O R D APTw standardization, APT-weighted imaging, brain tumor, CEST imaging How to cite this article: Zhou J, Zaiss M, Knutsson L, et al. Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T: Application to brain tumors.

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Section: Background and Theorymentioning

confidence: 99%

Review and consensus recommendations on clinical APT‐weighted imaging approaches at 3T: Application to brain tumors

Zhou

Zaiß

Knutsson

et al. 2022

Magnetic Resonance in Med

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119

138

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“…Glutamate chemical exchange saturation transfer (GluCEST) has emerged as a new and powerful molecular imaging technique for imaging glutamate distribution on the basis of its chemical exchange saturation transfer effect 9 . In particular, using GluCEST technique could determine the level of glutamate through the chemical exchange and magnetization transfer effects between the amine protons of glutamate and bulk water 10 . CEST contrast is generally computed using magnetization transfer ratio asymmetry (MTR asym ) analysis, and GluCEST asymmetry is observed ~3 ppm downfield from bulk water.…”

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confidence: 99%

Glutamate Chemical Exchange Saturation Transfer Imaging and Functional Alterations of Hippocampus in Rat Depression Model: A Pilot Study

Luo

Ren

Luo

et al. 2021

Magnetic Resonance Imaging

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Background Adjusting abnormal glutamate neurotransmission is a crucial mechanism in the treatment of depression. However, few non‐invasive techniques could effectively detect changes in glutamate neurotransmitters, and no consensus exists on whether glutamate could affect resting‐state function changes in depression. Purpose To study the changes in glutamate chemical exchange saturation transfer (GluCEST) value in the hippocampus of rat model exposed to chronic unpredictable mild stress (CUMS), and to explore the effect of this change on the activity of hippocampal glutamatergic neurons. Study Type Prospective animal study. Animal Model Twenty male Sprague–Dawley rats (200–300 g). Field Strength/Sequence 7.0 T scanner. Fat rapid acquisition relaxation enhancement sequence for GluCEST, and echo planner imaging sequence for resting‐state functional magnetic resonance imaging (rs_fMRI). Assessment Rats were divided into two groups: CUMS group (N = 10) and control group (CTRL, N = 10). The magnetization transfer ratio asymmetry analysis was used to quantify the GluCEST data, and evaluate the rs_fMRI data through the amplitude of low‐frequency fluctuation (ALFF) and regional homogeneity (ReHo) analysis. Statistical Tests A t‐test was used to compare the difference in GluCEST or rs_fMRI between CUMS and CTRL groups. Spearman's correlation was applied to explore the correlation between GluCEST values and abnormal fMRI values in hippocampus. Statistical significance was set at P < 0.05. Results The GluCEST value in the left hippocampus has changed significantly (3.3 ± 0.3 [CUMS] vs. 3.9 ± 0.4 [CTRL], P < 0.05). In addition, the GluCEST value was significantly positively correlated with the ALFF values (r = 0.5, P < 0. 05, df = 7) and negatively correlated with the ReHo values (r = −0.6, P < 0.05, df = 7). Data Conclusion GluCEST technique has the feasibility of mapping glutamate changes in rat depression. Glutamate neurotransmitters are important factors affecting the abnormal function of neural activity. Level of Evidence 2 Technical Efficacy Stage 1

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“…Tissue acidosis may subsequently induce cellular damage through the production of free radicals, impaired protein synthesis, mitochondrial failure, DNA damage, and accumulation of calcium ions (Durukan and Tatlisumak, 2007;Radak et al, 2017). Thus, having real-time spatial pH information could provide clinically useful information in the diagnosis and treatment of ischemic stroke, such as the estimation of the "real" penumbra (Harston et al, 2015) or potential targeted delivery of neuroprotective agents (Tóth et al, 2020a), leading some to suggest penumbra may be better estimated through pH imaging instead of spatial mismatch of CT and CT perfusion or diffusion and perfusion MRI (Heo et al, 2017;Kim et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…This means that the chemical shift for the Pi peak is sensitive to pH (Moon and Richards, 1973), whereas the peaks corresponding to other phosphate-containing species such as PCr are relatively insensitive to pH changes. Thus, through the measurement of the chemical shift difference between Pi and PCr, intracellular pH can be estimated through the modified Henderson-Hasselbalch equation (Seo et al, 1983;Kim et al, 2021):…”

Section: Introductionmentioning

confidence: 99%

“…In this perspective, we used pK a = 6.77, δ acid = 3.29 and δ base = 5.68. Due to its specificity, reliability, and extensive validation with microelectrode measurements, 31 P MRS has long been regarded as the gold standard for in vivo and non-invasive pH measurement (Kim et al, 2021) although pH can also be evaluated with 1 H MRS via tissue lactate concentration which has a linear correlation with pH (Jokivarsi et al, 2007). Unfortunately, 31 P has several key limitations that prevent its widespread clinical use.…”

Section: Introductionmentioning

confidence: 99%

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Magnetic Resonance pH Imaging in Stroke – Combining the Old With the New

et al. 2022

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The study of stroke has historically made use of traditional spectroscopy techniques to provide the ground truth for parameters like pH. However, techniques like 31P spectroscopy have limitations, in particular poor temporal and spatial resolution, coupled with a need for a high field strength and specialized coils. More modern magnetic resonance spectroscopy (MRS)-based imaging techniques like chemical exchange saturation transfer (CEST) have been developed to counter some of these limitations but lack the definitive gold standard for pH that 31P spectroscopy provides. In this perspective, both the traditional (31P spectroscopy) and emerging (CEST) techniques in the measurement of pH for ischemic imaging will be discussed. Although each has its own advantages and limitations, it is likely that CEST may be preferable simply due to the hardware, acquisition time and image resolution advantages. However, more experiments on CEST are needed to determine the specificity of endogenous CEST to absolute pH, and 31P MRS can be used to calibrate CEST for pH measurement in the preclinical model to enhance our understanding of the relationship between CEST and pH. Combining the two imaging techniques, one old and one new, we may be able to obtain new insights into stroke physiology that would not be possible otherwise with either alone.

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Brain pH Imaging and its Applications

Cited by 16 publications

References 134 publications

Review and consensus recommendations on clinical APT‐weighted imaging approaches at 3T: Application to brain tumors

Review and consensus recommendations on clinical APT‐weighted imaging approaches at 3T: Application to brain tumors

Glutamate Chemical Exchange Saturation Transfer Imaging and Functional Alterations of Hippocampus in Rat Depression Model: A Pilot Study

Magnetic Resonance pH Imaging in Stroke – Combining the Old With the New

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