Quasi-steady-state (QUASS) reconstruction enhances T1 normalization in apparent exchange-dependent relaxation (AREX) analysis: A reevaluation of T1 correction in quantitative CEST MRI of rodent brain tumor models.

PURPOSE: The apparent exchange-dependent relaxation (AREX) analysis has been proposed as an effective means to correct T1 contribution in CEST quantification. However, it has been recognized that AREX T1 correction is not straightforward if CEST scans are not performed under the equilibrium condition. Our study aimed to test if quasi-steady-state (QUASS) reconstruction could boost the accuracy of the AREX metric under common non-equilibrium scan conditions. THEORY AND METHODS: Numerical simulation and in vivo scans were performed to assess the AREX metric accuracy. The CEST signal was simulated under different relaxation delays, RF saturation amplitudes, and durations. The AREX was evaluated as a function of the bulk water T1 and labile proton concentration using the multiple linear regression model. AREX MRI was also assessed in brain tumor rodent models, with both apparent CEST scans and QUASS reconstruction. RESULTS: Simulation showed that the AREX calculation from apparent CEST scans, under non-equilibrium conditions, had significant dependence on labile proton fraction ratio, RF saturation time, and T1. In comparison, QUASS-boosted AREX depended on the labile proton fraction ratio without significant dependence on T1 and RF saturation time. Whereas the apparent (2.7 ± 0.8%) and QUASS MTR asymmetry (2.8 ± 0.8%) contrast between normal and tumor regions of interest (ROIs) were significant, the difference was small. In comparison, AREX contrast between normal and tumor ROIs calculated from the apparent CEST scan and QUASS reconstruction was 3.8 ± 1.1%/s and 4.4 ± 1.2%/s, respectively, statistically different from each other. CONCLUSIONS: AREX analysis benefits from the QUASS-reconstructed equilibrium CEST effect for improved T1 correction and quantitative CEST analysis.

Specific and rapid guanidinium CEST imaging using double saturation power and QUASS analysis in a rodent model of global ischemia.

PURPOSE: Guanidinium CEST is sensitive to metabolic changes and pH variation in ischemia, and it can offer advantages over conventional pH-sensitive amide proton transfer (APT) imaging by providing hyperintense contrast in stroke lesions. However, quantifying guanidinium CEST is challenging due to multiple overlapping components and a close frequency offset from water. This study aims to evaluate the applicability of a new rapid and model-free CEST quantification method using double saturation power, termed DSP-CEST, for isolating the guanidinium CEST effect from confounding factors in ischemia. To further reduce acquisition time, the DSP-CEST was combined with a quasi-steady state (QUASS) CEST technique to process non-steady-state CEST signals. METHODS: The specificity and accuracy of the DSP-CEST method in quantifying the guanidinium CEST effect were assessed by comparing simulated CEST signals with/without the contribution from confounding factors. The feasibility of this method for quantifying guanidinium CEST was evaluated in a rat model of global ischemia induced by cardiac arrest and compared to a conventional multiple-pool Lorentzian fit method. RESULTS: The DSP-CEST method was successful in removing all confounding components and quantifying the guanidinium CEST signal increase in ischemia. This suggests that the DSP-CEST has the potential to provide hyperintense contrast in stroke lesions. Additionally, the DSP-CEST was shown to be a rapid method that does not require the acquisition of the entire or a portion of the CEST Z-spectrum that is required in conventional model-based fitting approaches. CONCLUSION: This study highlights the potential of DSP-CEST as a valuable tool for rapid and specific detection of viable tissues.

A Pilot Study of Ratiometric Creatine CEST MRI Assessment of Rabbit Skeletal Muscle Energy Metabolism at 3 T.

BACKGROUND: pH MRI may provide useful information to evaluate metabolic disruption following ischemia. Radiofrequency amplitude-based creatine chemical exchange saturation transfer (CrCEST) ratiometric MRI is pH-sensitive, which could but has not been explored to examine muscle ischemia. PURPOSE: To investigate skeletal muscle energy metabolism alterations with CrCEST ratiometric MRI. STUDY TYPE: Prospective. ANIMAL MODEL: Seven adult New Zealand rabbits with ipsilateral hindlimb muscle ischemia. FIELD STRENGTH/SEQUENCE: 3 T/two MRI scans, including MRA and CEST imaging, were performed under two B1 amplitudes of 0.5 and 1.25 µT after 2 hours of hindlimb muscle ischemia and 1 hour of reperfusion recovery, respectively. ASSESSMENT: CEST effects of two energy metabolites of creatine and phosphocreatine (PCrCEST) were resolved with the multipool Lorentzian fitting approach. The pixel-wise CrCEST ratio was quantified by calculating the ratio of the resolved CrCEST peaks under a B1 amplitude of 1.25 µT to those under 0.5 µT in the entire muscle. STATISTICAL TESTS: One-way ANOVA and Pearson's correlation. P < 0.05 was considered statistically significant. RESULTS: MRA images confirmed the blood flow loss and restoration in the ischemic hindlimb at the ischemia and recovery phases, respectively. Ischemic muscles exhibited a significant decrease of PCr at the ischemia (under both B1 amplitudes) and recovery phases (under B1 amplitude of 0.5 µT) and significantly increased CrCEST from normal tissues at both phases (under both B1 levels). Specifically, CrCEST decreased, and PCrCEST increased with the CrCEST ratio. Significantly strong correlations were observed among the CrCEST ratio, and CrCEST and PCrCEST under both B1 levels (r > 0.80). DATA CONCLUSION: The CrCEST ratio altered substantially with muscle pathological states and was closely related to CEST effects of energy metabolites of Cr and PCr, suggesting that the pH-sensitive CrCEST ratiometric MRI is feasible to evaluate muscle injuries at the metabolic level. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1.

Generalization of quasi-steady-state reconstruction to CEST MRI with two-tiered RF saturation and gradient-echo readout-Synergistic nuclear Overhauser enhancement contribution to brain tumor amide proton transfer-weighted MRI.

PURPOSE: While amide proton transfer-weighted (APTw) MRI has been adopted in tumor imaging, there are concurrent APT, magnetization transfer, and nuclear Overhauser enhancement changes. Also, the APTw image is confounded by relaxation changes, particularly when the relaxation delay and saturation time are not sufficiently long. Our study aimed to extend a quasi-steady-state (QUASS) solution to determine the contribution of the multipool CEST signals to the observed tumor APTw contrast. METHODS: Our study derived the QUASS solution for a multislice CEST-MRI sequence with an interleaved RF saturation and gradient-echo readout between signal averaging. Multiparametric MRI scans were obtained in rat brain tumor models, including T1 , T2 , diffusion, and CEST scans. Finally, we performed spinlock model-based multipool fitting to determine multiple concurrent CEST signal changes in the tumor. RESULTS: The QUASS APTw MRI showed small but significant differences in normal and tumor tissues and their contrast from the acquired asymmetry calculation. The spinlock model-based fitting showed significant differences in semisolid magnetization transfer, amide, and nuclear Overhauser enhancement effects between the apparent and QUASS CEST MRI. In addition, we determined that the tumor APTw contrast is due to synergistic APT increase (+3.5 ppm) and NOE decrease (-3.5 ppm), with their relative contribution being about one third and two thirds under a moderate B1 of 0.75 µT at 4.7 T. CONCLUSION: Our study generalized QUASS analysis to gradient-echo image readout and quantified the underlying tumor CEST signal changes, providing an improved elucidation of the commonly used APTw MRI.

Comparison of model-free Lorentzian and spinlock model-based fittings in quantitative CEST imaging of acute stroke.

PURPOSE: CEST MRI detects complex tissue changes following acute stroke. Our study aimed to test if spinlock model-based fitting of the quasi-steady-state (QUASS)-reconstructed equilibrium CEST MRI improves the determination of multi-pool signal changes over the commonly-used model-free Lorentzian fitting in acute stroke. THEORY AND METHODS: Multiple three-pool CEST Z-spectra were simulated using Bloch-McConnell equations for a range of T1 , relaxation delay, and saturation times. The multi-pool CEST signals were solved from the simulated Z-spectra to test the accuracy of routine Lorentzian (model-free) and spinlock (model-based) fittings without and with QUASS reconstruction. In addition, multiparametric MRI scans were obtained in rat models of acute stroke, including relaxation, diffusion, and CEST Z-spectrum. Finally, we compared model-free and model-based per-pixel CEST quantification in vivo. RESULTS: The spinlock model-based fitting of QUASS CEST MRI provided a nearly T1 -independent determination of multi-pool CEST signals, advantageous over the fittings of apparent CEST MRI (model-free and model-based). In vivo data also demonstrated that the spinlock model-based QUASS fitting captured significantly different changes in semisolid magnetization transfer (-0.9 ± 0.8 vs. 0.3 ± 0.8%), amide (-1.1 ± 0.4 vs. -0.5 ± 0.2%), and guanidyl (1.0 ± 0.4 vs. 0.7 ± 0.3%) signals over the model-free Lorentzian analysis. CONCLUSION: Our study demonstrated that spinlock model-based fitting of QUASS CEST MRI improved the determination of the underlying tissue changes following acute stroke, promising further clinical translation of quantitative CEST imaging.

3D CEST MRI with an unevenly segmented RF irradiation scheme: A feasibility study in brain tumor imaging.

PURPOSE: To integrate 3D CEST EPI with an unevenly segmented RF irradiation module and preliminarily demonstrate it in the clinical setting. METHODS: A CEST MRI with unevenly segmented RF saturation was implemented, including a long primary RF saturation to induce the steady-state CEST effect, maintained with repetitive short secondary RF irradiation between readouts. This configuration reduces relaxation-induced blur artifacts during acquisition, allowing fast 3D spatial coverage. Numerical simulations were performed to select parameters such as flip angle (FA), short RF saturation duration (Ts2), and the number of readout segments. The sequence was validated experimentally with data from a phantom, healthy volunteers, and a brain tumor patient. RESULTS: Based on the numerical simulation and l-carnosine gel phantom experiment, FA, Ts2, and the number of segments were set to 20°, 0.3 s, and the range from 4 to 8, respectively. The proposed method minimized signal modulation in the human brain images in the kz direction during the acquisition and provided the blur artifacts-free CEST contrast over the whole volume. Additionally, the CEST contrast in the tumor tissue region is higher than in the contralateral normal tissue region. CONCLUSIONS: It is feasible to implement a highly accelerated 3D EPI CEST imaging with unevenly segmented RF irradiation.

In vivo pH mapping with omega plot-based quantitative chemical exchange saturation transfer MRI.

PURPOSE: Chemical exchange saturation transfer (CEST) MRI is promising for detecting dilute metabolites and microenvironment properties, which has been increasingly adopted in imaging disorders such as acute stroke and cancer. However, in vivo CEST MRI quantification remains challenging because routine asymmetry analysis (MTRasym ) or Lorentzian decoupling measures a combined effect of the labile proton concentration and its exchange rate. Therefore, our study aimed to quantify amide proton concentration and exchange rate independently in a cardiac arrest-induced global ischemia rat model. METHODS: The amide proton CEST (APT) effect was decoupled from tissue water, macromolecular magnetization transfer, nuclear Overhauser enhancement, guanidinium, and amine protons using the image downsampling expedited adaptive least-squares (IDEAL) fitting algorithm on Z-spectra obtained under multiple RF saturation power levels, before and after global ischemia. Omega plot analysis was applied to determine amide proton concentration and exchange rate simultaneously. RESULTS: Global ischemia induces a significant APT signal drop from intact tissue. Using the modified omega plot analysis, we found that the amide proton exchange rate decreased from 29.6 ± 5.6 to 12.1 ± 1.3 s-1 (P < 0.001), whereas the amide proton concentration showed little change (0.241 ± 0.035% vs. 0.202 ± 0.034%, P = 0.074) following global ischemia. CONCLUSION: Our study determined the labile proton concentration and exchange rate underlying the in vivo APT MRI. The significant change in the exchange rate, but not the concentration of amide proton demonstrated that the pH effect dominates the APT contrast during tissue ischemia.

Numerical simulation-based assessment of pH-sensitive chemical exchange saturation transfer MRI quantification accuracy across field strengths.

Chemical exchange saturation transfer (CEST) MRI detects dilute labile protons via their exchange with bulk water, conferring pH sensitivity. Based on published exchange and relaxation properties, a 19-pool simulation was used to model the brain pH-dependent CEST effect and assess the accuracy of quantitative CEST (qCEST) analysis across magnetic field strengths under typical scan conditions. First, the optimal B1 amplitude was determined by maximizing pH-sensitive amide proton transfer (APT) contrast under the equilibrium condition. Apparent and quasi-steady-state (QUASS) CEST effects were then derived under the optimal B1 amplitude as functions of pH, RF saturation duration, relaxation delay, Ernst flip angle, and field strength. Finally, CEST effects, particularly the APT signal, were isolated with spinlock model-based Z-spectral fitting to evaluate the accuracy and consistency of CEST quantification. Our data showed that QUASS reconstruction significantly improved the consistency between simulated and equilibrium Z-spectra. The residual difference between QUASS and equilibrium CEST Z-spectra was, on average, 30 times less than that of the apparent CEST Z-spectra across field strengths, saturation, and repetition times. Also, the spinlock fitting of the QUASS CEST effect significantly reduced the residual errors 9-fold. Furthermore, the isolated APT amplitude from QUASS reconstruction was consistent and higher than the apparent CEST analysis under nonequilibrium conditions. To summarize, this study confirmed that QUASS reconstruction facilitates accurate determination of the CEST system under different scan protocols across field strengths, with the potential to help standardize CEST quantification.

Demonstration of pH imaging in acute stroke with endogenous ratiometric chemical exchange saturation transfer magnetic resonance imaging at 2 ppm.

pH change is often considered a hallmark of metabolic disruption in diseases such as ischemic stroke and cancer. Chemical exchange saturation transfer (CEST) MRI, particularly amide proton transfer (APT), has emerged as a noninvasive pH imaging approach. However, there are changes in multipool CEST effects besides APT MRI. Our study investigated radiofrequency (RF) amplitude-based ratiometric CEST pH imaging in acute stroke. Briefly, adult male Wistar rats underwent CEST MRI under two RF saturation (B1 ) levels of 0.75 and 1.5 µT following middle cerebral artery occlusion. Magnetization transfer (MT), direct water saturation, CEST at 2 ppm (CEST@2 ppm), amine (2.75 ppm), and APT (3.5 ppm) effects were resolved with the multipool Lorentzian fitting approach. The ratiometric analysis was measured in the ischemic lesion and the contralateral normal area, which was also correlated with pH-specific MT and the relaxation normalized APT (MRAPT) index. MT, amine CEST effect, and their respective ratiometric indices did not show significant changes in ischemic regions (p > 0.05), as expected. Whereas APT decreased in the ischemic lesion for B1 of 1.5 µT (p < 0.01), the correlation between the amide ratio with MRAPT index was moderate (r = 0.52, p = 0.02). By comparison, the ischemic tissue showed a significantly increased CEST@2 ppm for both saturation levels from the contralateral normal area (p ≤ 0.01). Importantly, the CEST@2 ppm ratio decreased in the ischemic lesion (p < 0.01), which highly correlated with the MRAPT index (r = 0.93, p < 0.001). To summarize, our study demonstrated the feasibility of endogenous CEST@2 ppm ratiometric imaging of pH upon acute stroke, promising to detect pH changes in metabolic diseases.

Detection of tissue pH with quantitative chemical exchange saturation transfer magnetic resonance imaging.

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.

Tissue perfusion of the kurtosis/diffusion mismatch differs from the central core and peripheral regions in acute cerebral infarction patients.

BACKGROUND: Despite its wide adoption in stroke imaging, the diffusion-weighted imaging (DWI) lesion is heterogeneous. The emerging diffusion kurtosis imaging (DKI) has been postulated to resolve the graded DWI lesion. PURPOSE: To determine the perfusion characteristics of the central infarction core, kurtosis/diffusion mismatch, and peripheral regions. MATERIAL AND METHODS: Patients with acute ischemic stroke underwent DWI, DKI, and perfusion-weighted imaging (PWI) scans. The patients were divided into mean kurtosis (MK)/mean diffusivity (MD) match and mismatch groups. Perfusion parameters were measured in the MK/MD lesion and peripheral areas in the MK/MD match group. We also analyzed perfusion status in the MK/MD lesion mismatch area for the mismatch group. RESULTS: A total of 40 eligible patients (24 MK/MD match and 16 MK/MD mismatch) were enrolled in the final data analysis. The MTT and TTP progressively decreased, while the cerebral blood flow (CBF) and cerebral blood volume (CBV) increased from the central to peripheral areas. In addition, CBF in the MK/MD mismatch region was significantly higher than that in the central region (P < 0.05), but similar to the peripheral region. Furthermore, CBV in the MK/MD mismatch region did not differ significantly from that of the central region, but both were significantly lower than that of the peripheral area (P < 0.05). CONCLUSION: The MK/MD mismatch region had blood flow similar to the peripheral region but with a reduced blood volume, indicating that it was less ischemic from the infarction core, albeit insufficient collateral circulation.

Quasi-steady-state amide proton transfer (QUASS APT) MRI enhances pH-weighted imaging of acute stroke.

PURPOSE: Chemical exchange saturation transfer (CEST) imaging measurement depends not only on the labile proton concentration and pH-dependent exchange rate but also on experimental conditions, including the relaxation delay and radiofrequency (RF) saturation time. Our study aimed to extend a quasi-steady-state (QUASS) solution to a modified multi-slice CEST MRI sequence and test if it provides enhanced pH imaging after acute stroke. METHODS: Our study derived the QUASS solution for a modified multislice CEST MRI sequence with an unevenly segmented RF saturation between image readout and signal averaging. Numerical simulation was performed to test if the generalized QUASS solution corrects the impact of insufficiently long relaxation delay, primary and secondary saturation times, and multi-slice readout. In addition, multiparametric MRI scans were obtained after middle cerebral artery occlusion, including relaxation and CEST Z-spectrum, to evaluate the performance of QUASS CEST MRI in a rodent acute stroke model. We also performed Lorentzian fitting to isolate multi-pool CEST contributions. RESULTS: The QUASS analysis enhanced pH-weighted magnetization transfer asymmetry contrast over the routine apparent CEST measurements in both contralateral normal (-3.46% ± 0.62% (apparent) vs. -3.67% ± 0.66% (QUASS), P < 0.05) and ischemic tissue (-5.53% ± 0.68% (apparent) vs. -5.94% ± 0.73% (QUASS), P < 0.05). Lorentzian fitting also showed significant differences between routine and QUASS analysis of ischemia-induced changes in magnetization transfer, amide, amine, guanidyl CEST, and nuclear Overhauser enhancement (-1.6 parts per million) effects. CONCLUSION: Our study demonstrated that generalized QUASS analysis enhanced pH MRI contrast and improved quantification of the underlying CEST contrast mechanism, promising for further in vivo applications.

Consistent depiction of the acidic ischemic lesion with APT MRI-Dual RF power evaluation of pH-sensitive image in acute stroke.

PURPOSE: Amide proton transfer-weighted (APTw) MRI provides a non-invasive pH-sensitive image, complementing perfusion and diffusion imaging for refined stratification of ischemic tissue. Although the commonly used magnetization transfer (MT) asymmetry (MTRasym ) calculation reasonably corrects the direct RF saturation effect, it is susceptible to the concomitant semisolid macromolecular MT contribution. Therefore, this study aimed to compare the performance of MTRasym and magnetization transfer and relaxation-normalized APT (MRAPT) analyses under 2 representative experimental conditions. METHODS: Multiparametric MRI scans were performed in a rodent model of acute stroke, including relaxation, diffusion, and Z spectral images under 2 representative RF levels of 0.75 and 1.5 µT. Both MTRasym and MRAPT values in the ischemic diffusion lesion and the contralateral normal areas were compared using correlation and Bland-Altman tests. In addition, the acidic lesion volumes were compared. RESULTS: MRAPT measurements from the diffusion lesion under the 2 conditions were highly correlated (R2 = 0.97) versus MTRasym measures (R2 = 0.58). The pH lesion sizes determined from MRAPT analysis were in good agreement (178 ± 43 mm3 vs. 186 ± 55 mm3 for B1 of 0.75 and 1.5 µT, respectively). CONCLUSIONS: The study demonstrated that MRAPT analysis could be generalized to moderately different RF amplitudes, providing a more consistent depiction of acidic lesions than the MTRasym analysis.

Demonstration of fast multi-slice quasi-steady-state chemical exchange saturation transfer (QUASS CEST) human brain imaging at 3T.

PURPOSE: 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 (Ts ) and longitudinal relaxation during the relaxation delay time (Td ) 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 Ts , Td, and PLD. RESULTS: The numerical simulation showed that the apparent CEST effect strongly depends on Ts , Td , 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 PLD-corrected 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.

Demonstration of fast and equilibrium human muscle creatine CEST imaging at 3 T.

PURPOSE: Creatine chemical exchange saturation transfer (CrCEST) MRI is used increasingly in muscle imaging. However, the CrCEST measurement depends on the RF saturation duration (Ts) and relaxation delay (Td), and it is challenging to compare the results of different scan parameters. Therefore, this study aims to evaluate the quasi-steady-state (QUASS) CrCEST MRI on clinical 3T scanners. METHODS: T1 and CEST MRI scans of Ts/Td of 1 s/1 s and 2 s/2 s were obtained from a multi-compartment creatine phantom and 5 healthy volunteers. The CrCEST effect was quantified with asymmetry analysis in the phantom, whereas 5-pool Lorentzian fitting was applied to isolate creatine from phosphocreatine, amide proton transfer, combined magnetization transfer and nuclear Overhauser enhancement effects, and direct water saturation in four major muscle groups of the lower leg. The routine and QUASS CrCEST measurements were compared under two different imaging conditions. Paired Student's t-test was performed with p-values less than 0.05 considered statistically significant. RESULTS: The phantom study showed a substantial influence of Ts/Td on the routine CrCEST quantification (p = 0.02), and such impact was mitigated with the QUASS algorithm (p = 0.20). The volunteer experiment showed that the routine CrCEST, amide proton transfer, and combined magnetization transfer and nuclear Overhauser enhancement effects increased significantly with Ts and Td (p < 0.05) and were significantly smaller than the corresponding QUASS indices (p < 0.01). In comparison, the QUASS CrCEST MRI showed little dependence on Ts and Td, indicating its robustness and accuracy. CONCLUSION: The QUASS CrCEST MRI is feasible to provide fast and accurate muscle creatine imaging.

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

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.

Quasi-steady state chemical exchange saturation transfer (QUASS CEST) analysis-correction of the finite relaxation delay and saturation time for robust CEST measurement.

PURPOSE: CEST provides a MR contrast mechanism sensitizing to the exchange between dilute labile and bulk water protons. However, the CEST effect depends on the RF saturation duration and relaxation delay, which need to be long to reach its steady state. Our study aims to estimate the QUAsi-Steady State (QUASS) CEST signal from experiments with shorter saturation and relaxation delay times. METHODS: The evolution of the CEST signal was modeled as a function of the bulk water longitudinal relaxation rate during the relaxation delay (Td) and spin-lock relaxation rate during the RF saturation (Ts), from which the QUASS CEST effect is solved. Numeric simulations were programmed to compare the apparent CEST and QUASS CEST effects as a function of Ts and Td times. We also performed CEST MRI experiments from a creatine-gel pH phantom under serially varied Ts and Td times. RESULTS: The numeric simulation showed that although the apparent CEST effect depends on Td and Ts, the QUASS CEST solution has little dependence. Phantom results showed that the routine CEST pH contrast could be described by a nonlinear regression model (ie, ΔCESTR=ΔCESTReqapp1-e-R1ρapp·t ). We had ΔCESTReqapp = 3.90±0.03% (P < 5e-8) and R1ρapp=0.62±0.02s-1 (P < 5e-6). For the QUASS CEST analysis, we modeled the pH contrast as ΔCESTR=ΔCESTReqQUASS+s·t , using a linear regression model. We had ΔCESTReqQUASS=3.63±0.01% (P < 5e-9) and s=-0.02±0.00%/s (P < 0.01), the slope of which is minimal. CONCLUSIONS: The QUASS CEST algorithm provides a post-processing solution that facilitates robust CEST measurement.

Quasi-steady-state CEST (QUASS CEST) solution improves the accuracy of CEST quantification: QUASS CEST MRI-based omega plot analysis.

PURPOSE: CEST MRI omega plot quantifies the labile proton fraction ratio (fr ) and exchange rate (ksw ), yet it assumes long RF saturation time (Ts) and relaxation delay (Td). Our study aimed to test if a quasi-steady-state (QUASS) CEST analysis that accounts for the effect of finite Ts and Td could improve the accuracy of CEST MRI quantification. METHODS: We modeled the MRI signal evolution using a typical CEST EPI sequence. The signal relaxes toward its thermal equilibrium following the bulk water relaxation rate during Td, and then toward its CEST steady state following the spin-lock relaxation rate during Ts from which the QUASS CEST effect is derived. Both fr and ksw were solved from simulated conventional apparent CEST and QUASS CEST MRI. We also performed MRI experiments from a Cr-gel phantom under serially varied Ts and Td times from 1.5 to 7.5 s. RESULTS: Simulation showed that, although ksw could be slightly overestimated (3%-15%) for the range of Ts and Td, fr could be substantially underestimated by as much as 67%. In contrast, the QUASS solution provided accurate ksw and fr determination within 2%. The CEST MRI experiments confirmed that the QUASS solution enabled robust quantification of ksw and fr , superior over the omega plot analysis based on the conventional apparent CEST MRI measurements. CONCLUSIONS: The QUASS CEST MRI algorithm corrects the effect of finite Ts and Td times on CEST measurements, thereby allowing robust and accurate CEST quantification.

Preliminary demonstration of in vivo quasi-steady-state CEST postprocessing-Correction of saturation time and relaxation delay for robust quantification of tumor MT and APT effects.

PURPOSE: Chemical exchange saturation transfer (CEST) MRI is versatile for measuring the dilute labile protons and microenvironment properties. However, the use of insufficiently long RF saturation duration (Ts) and relaxation delay (Td) may underestimate the CEST measurement. This study proposed a quasi-steady-state (QUASS) CEST analysis for robust CEST quantification. METHODS: The CEST signal evolution was modeled as a function of the longitudinal relaxation rate during Td and spin-lock relaxation rate during Ts, from which the QUASS-CEST effect is derived. Numerical simulation and in vivo rat glioma MRI experiments were conducted at 11.7 T to compare the apparent and QUASS-CEST results obtained under different Ts/Td of 2 seconds/2 seconds and 4 seconds/4 seconds. Magnetization transfer and amide proton transfer effects were resolved using a multipool Lorentzian fitting and evaluated in contralateral normal tissue and tumor regions. RESULTS: The simulation showed the dependence of the apparent CEST effect on Ts and Td, and such reliance was mitigated with the QUASS algorithm. Animal experiment results showed that the apparent magnetization transfer and amide proton transfer effects and their contrast between contralateral normal tissue and tumor regions increased substantially with Ts and Td. In comparison, the QUASS magnetization transfer and amide proton transfer effects and their difference between contralateral normal tissue and tumor exhibited little dependence on Ts and Td. In addition, the apparent magnetization transfer and amide proton transfer were significantly smaller than the corresponding QUASS indices (P < .05). CONCLUSION: The QUASS-CEST algorithm enables robust CEST quantification and offers a straightforward approach to standardize CEST experiments.

Development of fast multi-slice apparent T1 mapping for improved arterial spin labeling MRI measurement of cerebral blood flow.

PURPOSE: To develop fast multi-slice apparent T1 (T1app ) mapping for accurate cerebral blood flow (CBF) quantification with arterial spin labeling (ASL) MRI. METHODS: Fast multi-slice T1app was measured using a modified inversion recovery echo planar imaging (EPI) sequence with simultaneous application of ASL tagging radiofrequency (RF) and gradient pulses. The fast multi-slice T1app measurement was compared with the single-slice T1app imaging approach, repeated per slice. CBF was assessed in healthy adult Wistar rats (N = 5) and rats with acute stroke 24 hours after a transient middle cerebral artery occlusion (N = 5). RESULTS: The fast multi-slice T1app measurement was in good agreement with that of a single-slice T1app imaging approach (Lin's concordance correlation coefficient = 0.92). CBF calculated using T1app reasonably accounted for the finite labeling RF duration, whereas the routine T1 -normalized ASL MRI underestimated the CBF, particularly at short labeling durations. In acute stroke rats, the labeling time and the CBF difference (ΔCBF) between the contralateral normal area and the ischemic lesion were significantly correlated when using T1 -normalized perfusion calculation (R = 0.844, P = .035). In comparison, T1app -normalized ΔCBF had little labeling time dependence based on the linear regression equation of ΔCBF = -0.0247*τ + 1.579 mL/g/min (R = -0.352, P = .494). CONCLUSIONS: Our study found fast multi-slice T1app imaging improves the accuracy and reproducibility of CBF measurement.