Pulsed Chemical Exchange Saturation Transfer Research Articles

Enhanced and robust contrast in CEST MRI: Saturation pulse shape design via optimal control.

To employ optimal control for the numerical design of Chemical Exchange Saturation Transfer (CEST) saturation pulses to maximize contrast and stability against inhomogeneities. We applied an optimal control framework for the design pulse shapes for CEST saturation pulse trains. The cost functional minimized both the pulse energy and the discrepancy between the corresponding CEST spectrum and the target spectrum based on a continuous radiofrequency (RF) pulse. The optimization is subject to hardware limitations. In measurements on a 7 T preclinical scanner, the optimal control pulses were compared to continuous-wave and Gaussian saturation methods. We conducted a comparison of the optimal control pulses with Gaussian, block pulse trains, and adiabatic spin-lock pulses. The optimal control pulse train demonstrated saturation levels comparable to continuous-wave saturation and surpassed Gaussian saturation by up to 50 % in phantom measurements. In phantom measurements at 3 T the optimized pulses not only showcased the highest CEST contrast, but also the highest stability against field inhomogeneities. In contrast, block pulse saturation resulted in severe artifacts. Dynamic Bloch-McConnell simulations were employed to identify the source of these artifacts, and underscore the robustness of the optimized pulses. In this work, it was shown that a substantial improvement in pulsed saturation CEST imaging can be achieved by using Optimal Control design principles. It is possible to overcome the sensitivity of saturation to B0 inhomogeneities while achieving CEST contrast close to continuous wave saturation.

Scan-specific Unsupervised Highly Accelerated Non-Cartesian CEST Imaging using Implicit Neural Representation and Explicit Sparse Prior.

Chemical exchange saturation transfer (CEST) is a promising magnetic resonance imaging (MRI) technique. CEST imaging usually requires a long scan time, and reducing acquisition time is highly desirable for clinical applications. A novel scan-specific unsupervised deep learning algorithm is proposed to accelerate steady-state pulsed CEST imaging with golden-angle stack-of-stars trajectory using hybrid-feature hash encoding implicit neural representation. Additionally, imaging quality is further improved by using the explicit prior knowledge of low rank and weighted joint sparsity in the spatial and Z-spectral domain of CEST data. In the retrospective acceleration experiment, the proposed method outperforms other state-of-the-art algorithms (TDDIP, LRTES, kt-SLR, NeRP, CRNN, and PBCS) for the in vivo human brain dataset under various acceleration rates. In the prospective acceleration experiment, the proposed algorithm can still obtain results close to the fully-sampled images. The hybrid-feature hash encoding implicit neural representation combined with explicit sparse prior (INRESP) can efficiently accelerate CEST imaging. The proposed algorithm achieves reduced error and improved image quality compared to several state-of-the-art algorithms at relatively high acceleration factors. The superior performance and the training database-free characteristic make the proposed algorithm promising for accelerating CEST imaging in various applications.

Mapping tumour heterogeneity with pulsed 3D CEST MRI in non-enhancing glioma at 3\xa0T

ObjectiveAmide proton transfer (APT) weighted chemical exchange saturation transfer (CEST) imaging is increasingly used to investigate high-grade, enhancing brain tumours. Non-enhancing glioma is currently less studied, but shows heterogeneous pathophysiology with subtypes having equally poor prognosis as enhancing glioma. Here, we investigate the use of CEST MRI to best differentiate non-enhancing glioma from healthy tissue and image tumour heterogeneity.Materials & MethodsA 3D pulsed CEST sequence was applied at 3 Tesla with whole tumour coverage and 31 off-resonance frequencies (+6 to -6 ppm) in 18 patients with non-enhancing glioma. Magnetisation transfer ratio asymmetry (MTRasym) and Lorentzian difference (LD) maps at 3.5 ppm were compared for differentiation of tumour versus normal appearing white matter. Heterogeneity was mapped by calculating volume percentages of the tumour showing hyperintense APT-weighted signal.ResultsLDamide gave greater effect sizes than MTRasym to differentiate non-enhancing glioma from normal appearing white matter. On average, 17.9 % ± 13.3 % (min–max: 2.4 %–54.5 %) of the tumour volume showed hyperintense LDamide in non-enhancing glioma.ConclusionThis works illustrates the need for whole tumour coverage to investigate heterogeneity in increased APT-weighted CEST signal in non-enhancing glioma. Future work should investigate whether targeting hyperintense LDamide regions for biopsies improves diagnosis of non-enhancing glioma.

Direct radiofrequency saturation corrected amide proton transfer tumor MRI at 3T.

Amide proton transfer (APT) imaging has been increasingly applied in tumor characterization that complements diffusion and dynamic contrast-enhanced MRI. However, quantification of in vivo APT effect is challenging because of concomitant semisolid magnetization transfer (MT) and nuclear overhauser enhancement effects. A direct saturation corrected (DISC) chemical exchange saturation transfer (CEST) analysis has been recently proposed that simplifies the determination of in vivo CEST effects. Our present study aimed to extend the DISC analysis to pulsed radiofrequency CEST MRI and evaluate it at 3T. Nine adult male Sprague-Dawley rats implanted C6 gliomas underwent multiparametric MRI of T1 , T2 , CEST, and T1 -weighted gadolinium-enhanced imaging 1 day before and 3 days after chemoradiotherapy. The routine MT asymmetry, 3-point method, and the extended DISC analysis were compared in tumor characterization with histology as a reference. Regional variations were assessed by 1-way analysis of variance. T1 , T2 , and MT asymmetry and the DISC CEST effects showed significant alterations in tumor/necrosis with respect to the contralateral reference (P < 0.05). The resolved APT effect revealed a significant difference among the contralateral reference (2.42 ± 0.24%), necrosis (2.86 ± 0.19%), and tumor (3.25 ± 0.15%) regions after chemoradiotherapy (P < 0.05), consistent with histological observations. Conversely, the MT asymmetry did not show tumor regional variation post-treatment (P > 0.05), whereas the 3-point method detected no regional alteration at both time points (P > 0.05). Our study translated DISC CEST MRI to 3T, evaluated it in glioma rat models, and confirmed its advantages in resolving tumor heterogeneity over the routine asymmetry and 3-point analyses.

Towards an analytic solution for pulsed CEST.

Chemical exchange saturation transfer (CEST) is an imaging method based on magnetization exchange between solutes and water. This exchange generates changes in the measured signal after off-resonance radiofrequency irradiation. Although the analytic solution for CEST with continuous wave (CW) irradiation has been determined, most studies are performed using pulsed irradiation. In this work, we derive an analytic solution for the CEST signal after pulsed irradiation that includes both short-time rotation effects and long-time saturation effects in a two-pool system corresponding to water and a low-concentration exchanging solute pool. Several approximations are made to balance the accuracy and simplicity of the resulting analytic form, which is tested against numerical solutions of the coupled Bloch equations and is found to be largely accurate for amides at high fields, but less accurate at the higher exchange rates, lower offsets and typically higher irradiation powers of amines.

Presaturation Power Adjusted Pulsed CEST: A Method to Increase Independence of Target CEST Signals.

Chemical exchange saturation transfer (CEST) imaging has been demonstrated to discuss the concentration changes of amide proton, glutamate, creatine, or glucose measured at 3.5, 3.0, 2.0, and 1.0–1.2 ppm. However, these peaks in z-spectra are quite broad and overlap with each other, and thus, the independence of a CEST signal on any specific metabolite is still open to question. Here, we described whether there was interference among the CEST signals and how these CEST signals behave when the power of the presaturation pulse was changed. Based on these results, further experiments were designed to investigate a method to increase the independence of the CEST signal in both phantoms and animals. The result illustrates a clear interference among CEST signals. A presaturation power adjusted pulsed- (PPAP-) CEST method which was designed based on the exchange rates of the metabolites can be used to remove contributions from other exchanging species in the same sample. Further, the method was shown to improve the independence of the glutamate signal in vivo in the renal medulla in mice. The PPAP-CEST method has the potential to increase the independence of any target CEST signals in vivo by choosing the appropriate combination of pulse amplitudes and durations.

Flip-angle based ratiometric approach for pulsed CEST-MRI pH imaging

Several molecules have been exploited for developing MRI pH sensors based on the chemical exchange saturation transfer (CEST) technique. A ratiometric approach, based on the saturation of two exchanging pools at the same saturation power, or by varying the saturation power levels on the same pool, is usually needed to rule out the concentration term from the pH measurement. However, all these methods have been demonstrated by using a continuous wave saturation scheme that limits its translation to clinical scanners. This study shows a new ratiometric CEST-MRI pH-mapping approach based on a pulsed CEST saturation scheme for a radiographic contrast agent (iodixanol) possessing a single chemical exchange site. This approach is based on the ratio of the CEST contrast effects at two different flip angles combinations (180°/360° and 180°/720°), keeping constant the mean irradiation RF power (Bavg power). The proposed ratiometric approach index is concentration independent and it showed good pH sensitivity and accuracy in the physiological range between 6.0 and 7.4.

B1+ inhomogeneity mitigation in CEST using parallel transmission.

In order to benefit from the increased spectral bandwidth at ultrahigh field (UHF), the use of parallel transmission (pTx) to mitigate flip-angle inhomogeneity in chemical exchange saturation transfer (CEST) imaging is investigated. A pTx basis pulse is homogenised by magnitude least-squares (MLS) optimization and expanded to form a frequency-selective saturation pulse for CEST. The pTx saturation pulse was simulated with a three-pool Bloch-McConnell equation to evaluate the impact of pTx on CEST contrast. In vivo CEST imaging performance (7 T) of the pTx saturation pulse and the standard Gaussian saturation in circularly polarized mode were compared. Two-spokes pTx homogeneous excitation was used in all in vivo experiments to ensure fair comparison of the two saturation pulses. Magnetization transfer ratio and inverse Z-spectrum analyses were used as metrics in evaluating the data from 3 healthy volunteers. Bloch-McConnell simulations showed that side bands of the pTx saturation pulse at ±20 ppm did not affect any CEST contrast. Improved homogeneity in contrasts and relaxation-compensated CEST metrics were observed in our in vivo data when the pTx saturation pulse was used. A pTx-based pulsed CEST presaturation scheme is proposed and validated by simulations and 7T in vivo imaging. Magn Reson Med 78:2216-2225, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Design and optimization of pulsed Chemical Exchange Saturation Transfer MRI using a multiobjective genetic algorithm

Pulsed Chemical Exchange Saturation Transfer (CEST) MRI experimental parameters and RF saturation pulse shapes were optimized using a multiobjective genetic algorithm. The optimization was carried out for RF saturation duty cycles of 50% and 90%, and results were compared to continuous wave saturation and Gaussian waveform. In both simulation and phantom experiments, continuous wave saturation performed the best, followed by parameters and shapes optimized by the genetic algorithm and then followed by Gaussian waveform. We have successfully demonstrated that the genetic algorithm is able to optimize pulse CEST parameters and that the results are translatable to clinical scanners.

Association between obstructive pulmonary function abnormalities and brain cortical thickness

WCN 2013 No: 1860 Topic: 36 — Other Topic A fast method for determination of the parameters of pulsed-CEST MRI G. Xiao, Z. Dai, P.Z. Sun, R. Wu. Department of Mathematics and Applied Mathematics, Hanshan Normal University, Chaozhou, China; Department of Radiology, 2nd Affiliated Hospital of Shantou University Medical College, Shantou, China; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA Objective: The object of the research is to demonstrate a fast method for simultaneous determination of labile proton fraction ratio and exchange rate and other parameters of pulsed chemical exchange saturation transfer (pulsed-CEST) MRI. Methods: Mathematical models have been developed to describe pulsed-CEST contrast. We simulated pulsed-CEST MRI in MatLab (MathWorks, Natick, MA) for Z-spectra and asymmetry spectra using matrix exponential algorithm. The number of repetition of the sequence is 256. Each Gaussian-shaped pulse was divided into 101 steps, and the evolution within each step was modeled assuming a constant amplitude. We also calculated the above spectra by using the fourth/fifth-order RKF(ode45 in MatLab; MathWorks, Natick, MA, USA) with an absolute error tolerance for each integration step of 10−6, and compared with the results obtained by our method. Calculations were performed using MatLab on Pentium® Dual-Core CPU (2.2 GHz) with 2-GB RAM. There was a good agreement between them, and this method was much faster than the RKF method (by a factor of approximately 1000 in this study). We simulated that the error of the labile proton fraction ratio, exchange rate and other parameters less than 5%. Results: This method will be useful for determination of labile proton fraction ratio and exchange rate and other parameters, and for analyzing the pulsed-CEST contrast mechanism and/or investigating the optimal RF pulse parameters such as the RF pulse duration or pulse flip angle. doi:10.1016/j.jns.2013.07.2242 Abstract — WCN 2013 No: 1859 Topic: 36 — Other Topic Association between obstructive pulmonary function abnormalities and brain cortical thickness WCN 2013 No: 1859 Topic: 36 — Other Topic Association between obstructive pulmonary function abnormalities and brain cortical thickness J. Cho, J. Sohn, S.-K. Cho, H. Kim, C. Kim, D.-C. Shin, S. Seo. Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,

Variable delay multi-pulse train for fast chemical exchange saturation transfer and relayed-nuclear overhauser enhancement MRI

Chemical exchange saturation transfer (CEST) imaging is a new MRI technology allowing the detection of low concentration endogenous cellular proteins and metabolites indirectly through their exchangeable protons. A new technique, variable delay multi-pulse CEST (VDMP-CEST), is proposed to eliminate the need for recording full Z-spectra and performing asymmetry analysis to obtain CEST contrast. The VDMP-CEST scheme involves acquiring images with two (or more) delays between radiofrequency saturation pulses in pulsed CEST, producing a series of CEST images sensitive to the speed of saturation transfer. Subtracting two images or fitting a time series produces CEST and relayed-nuclear Overhauser enhancement CEST maps without effects of direct water saturation and, when using low radiofrequency power, minimal magnetization transfer contrast interference. When applied to several model systems (bovine serum albumin, crosslinked bovine serum albumin, l-glutamic acid) and in vivo on healthy rat brain, VDMP-CEST showed sensitivity to slow to intermediate range magnetization transfer processes (rate < 100-150 Hz), such as amide proton transfer and relayed nuclear Overhauser enhancement-CEST. Images for these contrasts could be acquired in short scan times by using a single radiofrequency frequency. VDMP-CEST provides an approach to detect CEST effect by sensitizing saturation experiments to slower exchange processes without interference of direct water saturation and without need to acquire Z-spectra and perform asymmetry analysis.

Nuclear Overhauser enhancement (NOE) imaging in the human brain at 7T

Chemical exchange saturation transfer (CEST) is a magnetization transfer (MT) technique to indirectly detect pools of exchangeable protons through the water signal. CEST MRI has focused predominantly on signals from exchangeable protons downfield (higher frequency) from water in the CEST spectrum. Low power radiofrequency (RF) pulses can slowly saturate protons with minimal interference of conventional semi-solid based MT contrast (MTC). When doing so, saturation-transfer signals are revealed upfield from water, which is the frequency range of non-exchangeable aliphatic and olefinic protons. The visibility of such signals indicates the presence of a relayed transfer mechanism to the water signal, while their finite width reflects that these signals are likely due to mobile solutes. It is shown here in protein phantoms and the human brain that these signals build up slower than conventional CEST, at a rate typical for intramolecular nuclear Overhauser enhancement (NOE) effects in mobile macromolecules such as proteins/peptides and lipids. These NOE-based saturation transfer signals show a pH dependence, suggesting that this process is the inverse of the well-known exchange-relayed NOEs in high resolution NMR protein studies, thus a relayed-NOE CEST process. When studying 6 normal volunteers with a low-power pulsed CEST approach, the relayed-NOE CEST effect was about twice as large as the CEST effects downfield and larger in white matter than gray matter. This NOE contrast upfield from water provides a way to study mobile macromolecules in tissue. First data on a tumor patient show reduction in both relayed NOE and CEST amide proton signals leading to an increase in magnetization transfer ratio asymmetry, providing insight into previously reported amide proton transfer (APT) effects in tumors.

Evaluating the use of a continuous approximation for model-based quantification of pulsed chemical exchange saturation transfer (CEST)

Many potential clinical applications of chemical exchange saturation transfer (CEST) have been studied in recent years. However, due to various limitations such as specific absorption rate guidelines and scanner hardware constraints, most of the proposed applications have yet to be translated into routine diagnostic tools. Currently, pulsed CEST which uses multiple short pulses to perform the saturation is the only viable irradiation scheme for clinical translation. However, performing quantitative model-based analysis on pulsed CEST is time consuming because it is necessary to account for the time dependent amplitude of the saturation pulses. As a result, pulsed CEST is generally treated as continuous CEST by finding its equivalent average field or power. Nevertheless, theoretical analysis and simulations reveal that the resulting magnetization is different when the different irradiation schemes are applied. In this study, the quantification of important model parameters such as the amine proton exchange rate from a pulsed CEST experiment using quantitative model-based analyses were examined. Two model-based approaches were considered – discretized and continuous approximation to the time dependent RF irradiation pulses. The results showed that the discretized method was able to fit the experimental data substantially better than its continuous counterpart, but the smaller fitted error of the former did not translate to significantly better fit for the important model parameters. For quantification of the endogenous CEST effect, such as in amide proton transfer imaging, a model-based approach using the average power equivalent saturation can thus be used in place of the discretized approximation.

In vivo three‐dimensional whole‐brain pulsed steady‐state chemical exchange saturation transfer at 7 T

Chemical exchange saturation transfer (CEST) is a technique to indirectly detect pools of exchangeable protons through the water signal. To increase its applicability to human studies, it is needed to develop sensitive pulse sequences for rapidly acquiring whole-organ images while adhering to stringent amplifier duty cycle limitations and specific absorption rate restrictions. In addition, the interfering effects of direct water saturation and conventional magnetization transfer contrast complicate CEST quantification and need to be reduced as much as possible. It is shown that for protons exchanging with rates of less than 50-100 Hz, such as imaged in amide proton transfer experiments, these problems can be addressed by using a three-dimensional steady state pulsed acquisition of limited B(1) strength (≈ 1 μT). Such an approach exploits the fact that the direct water saturation width, magnetization transfer contrast magnitude, and specific absorption rate increase strongly with B(1) , while the size of the CEST effect for such protons depends minimally on B(1) . A short repetition time (65 ms) steady-state sequence consisting of a brief saturation pulse (25 ms) and a segmented echo-planar imaging train allowed acquisition of a three-dimensional whole-brain volume in approximately 11 s per saturation frequency, while remaining well within specific absorption rate and duty cycle limits. Magnetization transfer contrast was strongly reduced, but substantial saturation effects were found at frequencies upfield from water, which still confound the use of magnetization transfer asymmetry analysis. Fortunately, the limited width of the direct water saturation signal could be exploited to fit it with a Lorentzian function allowing CEST quantification. Amide proton transfer effects ranged between 1.5% and 2.5% in selected white and grey matter regions. This power and time-efficient 3D pulsed CEST acquisition scheme should aid endogenous CEST quantification at both high and low fields.

Understanding quantitative pulsed CEST in the presence of MT

Phantom experiments in agar and ammonium chloride were performed to evaluate a three-pool model of magnetization transfer and chemical exchange saturation transfer (CEST) in a pulsed saturation transfer experiment. The utility of the pulsed CEST method was demonstrated by varying the pH of the phantoms and observing the effect upon the CEST spectra both with and without the solid agar (the magnetization transfer pool), while fitting the spectra to the Bloch equation model with exchange. Pulsed CEST could be used to robustly quantify parameters related to CEST, including the exchange rate constant describing proton exchange with free water and the concentration of exchanging protons. Furthermore, the exchange rate constant and the CEST pool offset frequency of the ammonium chloride remained unchanged in the presence of a magnetization transfer pool. The logarithm of the fitted exchange rate constant was linearly related to pH: this relationship was maintained in the presence of magnetization transfer.