To combine multi-slice chemical exchange saturation transfer (CEST) imaging with quasi-steady-state (QUASS) processing and demonstrate the feasibility of fast QUASS CEST MRI at 3T. Methods:Fast multi-slice echo planar imaging (EPI) CEST imaging was developed with concatenated slice acquisition after single radiofrequency irradiation.The multi-slice CEST signal evolution was described by the spin-lock relaxation during saturation duration (T s ) and longitudinal relaxation during the relaxation delay time (T d ) and post-label delay (PLD), from which the QUASS CEST was generalized to fast multi-slice acquisition. In addition, numerical simulations, phantom, and normal human subjects scans were performed to compare the conventional apparent and QUASS CEST measurements with different T s , T d, and PLD. Results:The numerical simulation showed that the apparent CEST effect strongly depends on T s , T d , and PLD, while the QUASS CEST algorithm minimizes such dependences. In the L-carnosine gel phantom, the proposed QUASS CEST effects (2.68 ± 0.12% [mean ± SD]) were higher than the apparent CEST effects (1.85 ± 0.26%, p < 5e-4). In the human brain imaging, Bland-Altman analysis bias of the proposed QUASS CEST effects was much smaller than the PLDcorrected apparent CEST effects (0.03% vs. −0.54%), indicating the proposed fast multi-slice CEST imaging is robust and accurate. Conclusions:The QUASS processing enables fast multi-slice CEST imaging with minimal loss in the measurement of the CEST effect.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as a novel means for sensitive detection of dilute labile protons and chemical exchange rates. By sensitizing to pH-dependent chemical exchange, CEST MRI has shown promising results in monitoring tissue statuses such as pH changes in disorders like acute stroke, tumor, and acute kidney injury. This article briefly reviews the basic principles for CEST imaging and quantitative measures, from the simplistic asymmetry analysis to multipool Lorentzian decoupling and quasi-steady-state reconstruction. In particular, the advantages and limitations of commonly used quantitative approaches for CEST applications are discussed.acute stroke, amide proton transfer, chemical exchange saturation transfer, pH, pH-weighted, tumor | INTRODUCTIONpH is a physiological index tightly regulated in healthy tissue. 1,2 A notable pH change often signals altered tissue states, such as those following acute ischemia [3][4][5][6][7][8] and the development of cancer. 9-15 For example, tissue acidosis is associated with anaerobic glycolysis following acute stroke. [16][17][18][19] The pH drop compromises essential adenosine triphosphate (ATP)-dependent functions, often leading to cell death and ultimately tissue infarction. [20][21][22][23][24] In the case of cancers, excessive amounts of lactate are produced, disrupting pH homeostasis, a hallmark of the Warburg effect. [25][26][27] It has been recognized that pH change profoundly affects tumor growth and metastasis. 28 As such, pH measurement may provide novel insights into tissue microenvironment and response to therapy, and potentially facilitate the development of new therapeutics. pH measurement in vivo, however, is not straightforward because common strategies such as pH immunohistology, fluorescence microscopy, or phosphorus magnetic resonance approaches are either invasive, [29][30][31][32][33] of limited penetration depth, 34,35 or insensitive. [36][37][38] To address such an unmet biomedical need, Balaban and coworkers introduced chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) as a new sensitive means of imaging pH and dilute labile protons, [39][40][41][42] laying the groundwork for CEST MRI research over the following Abbreviations used: APT, amide proton transfer; CEST, chemical exchange saturation transfer; CESTR, CEST ratio; CNR, contrast-to-noise ratio; MMTR, mean magnetization transfer ratio; MRAPT, MT and relaxation normalized APT; MT, magnetization transfer; MTR, magnetization transfer ratio; MTR asym , MTR asymmetry; NOE, nuclear Overhauser enhancement; pHw, pHweighted; QUASS, quasi-steady-state; rCESTR, ratiometric CESTR; rCNR, relative CNR; ΔMRAPTR, delta MRAPT ratio.

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