It has been previously shown that intrinsic metabolites can be imaged based on their water proton exchange rates using saturation transfer techniques. The goal of this study was to identify an appropriate chemical exchange site that could be developed for use as an exogenous chemical exchange dependent saturation transfer (CEST) contrast agent under physiological conditions. These agents would function by reducing the water proton signal through a chemical exchange site on the agent via saturation transfer. The ideal chemical exchange site would have a large chemical shift from water. This permits a high exchange rate without approaching the fast exchange limit at physiological pH (6.5-7.6) and temperature (37 degrees C), as well as minimizing problems associated with magnetic field susceptibility. Numerous candidate chemicals (amino acids, sugars, nucleotides, heterocyclic ring chemicals) were evaluated in this preliminary study. Of these, barbituric acid and 5, 6-dihydrouracil were more fully characterized with regard to pH, temperature, and concentration CEST effects. The best chemical exchange site found was the 5.33-ppm indole ring -NH site of 5-hydroxytryptophan. These data demonstrate that a CEST-based exogenous contrast agent for MRI is feasible.

目前常用的分子影像技术主要有正电子发射型断层显像（PET）、质子磁共振波谱（¹H MRS）及成像（¹H MRSI）、化学交换饱和转移（CEST）、超极化¹³C MRSI等.近4年来，氘代谢波谱（DMS）及成像（DMI）作为一种新兴的分子影像技术获得了越来越多的关注，其通过采集注射或口服氘代葡萄糖后的目标组织与正常组织间氘代谢产物的磁共振信号进行组织区分.相比于其他分子影像方法，该影像技术具有无辐射、稳定性好、扫描操作相对简单等优点.本文综述了近年来DMS/DMI技术的研究进展及其意义，归纳总结了其临床应用价值，并对该技术未来的发展和改进方向，以及应用前景进行了展望.

Solution pH was measured using water proton NMR via chemical exchange dependent saturation transfer (CEST) with selected chemical exchange sites. Several useful pH-sensitive proton chemical exchange agents were found: 5,6-dihydrouracil, 5-hydroxytryptophan, and a combination of 5-hydroxytryptophan and 2-imidazolidinethione. A ratiometric approach was developed that permitted pH determinations that were independent of water T(1) or exchange site concentration.

In the past decade, it has become possible to use the nuclear (proton, 1H) signal of the hydrogen atoms in water for noninvasive assessment of functional and physiological parameters with magnetic resonance imaging (MRI). Here we show that it is possible to produce pH-sensitive MRI contrast by exploiting the exchange between the hydrogen atoms of water and the amide hydrogen atoms of endogenous mobile cellular proteins and peptides. Although amide proton concentrations are in the millimolar range, we achieved a detection sensitivity of several percent on the water signal (molar concentration). The pH dependence of the signal was calibrated in situ, using phosphorus spectroscopy to determine pH, and proton exchange spectroscopy to measure the amide proton transfer rate. To show the potential of amide proton transfer (APT) contrast for detecting acute stroke, pH effects were noninvasively imaged in ischemic rat brain. This observation opens the possibility of using intrinsic pH contrast, as well as protein- and/or peptide-content contrast, as diagnostic tools in clinical imaging.

化学交换饱和转移（Chemical Exchange Saturation Transfer，CEST）技术作为一种新型的磁共振成像（Magnetic Resonance Imaging，MRI）技术.它的原理为溶质池中被激发饱和的质子与游离水中未被饱和的质子间的化学交换，能够引起水质子磁共振信号的下降，从而获得组织内生物分子的相关信息.由于质子间的交换速率k_ex与组织微环境的pH值之间存在直接联系，因而可以通过溶质质子的CEST信号对活体组织进行pH成像.目前用于pH成像的溶质分子既包括内源性游离的蛋白质、多肽分子，还包括一系列的外源性小分子和金属螯合物.通过不同类型的比率法、内源性胺和酰胺浓度-独立检测（Amine and Amide Concentration-independent Detection，AACID）等成像方法，能够获得肾脏、中风脑组织以及肿瘤组织的pH图谱.本文详细总结了2000年以来利用CEST技术进行pH成像方面的研究进展，包括对比剂、成像方法和相关应用，展望了活体组织pH成像的发展趋势和应用前景.

Paramagnetic Ln-DOTAMGly complexes (Ln not equal La, Lu, and Gd) are the prototypes of a novel class of contrast agents for magnetic resonance imaging based on chemical exchange saturation transfer (CEST). Their ability to reduce the water signal intensity depends on the interplay of several physico-chemical properties of the agent and instrumental parameters. This study aims to identify possible routes for their optimizationSaturation transfer (ST) has been measured in vitro at 7.05 T as a function of pH, temperature, and concentration of the agent.Large saturation transfer effects have been observed upon irradiating the coordinated water protons (for Ln = Pr, Nd, Eu, and Tb). The comparison of the results obtained by irradiating water versus amide protons allows the set-up of ratiometric methods through which the ST response can be made independent on the concentration of the agent.The modulation of the magnetic properties along the lanthanide series allows an in-depth understanding of the determinants of ST effect and provides useful insights for the design of more efficient agents.

Amide proton transfer (APT) imaging is capable of detecting mobile cellular proteins and peptides in tumor and monitoring pH effects in stroke, through the saturation transfer between irradiated amide protons and water protons. In this work, four healthy subjects, eight brain tumor patients (four with high-grade glioma, one with lung cancer metastasis, and three with meningioma), and four stroke patients (average 4.3 ± 2.5 days after the onset of the stroke) were scanned at 3 T, using different radiofrequency saturation powers. The APT effect was quantified using the magnetization transfer ratio (MTR) asymmetry at 3.5 ppm with respect to the water resonance. At a saturation power of 2 μT, the measured APT-MRI signal of the normal brain tissue was almost zero, due to the contamination of the negative conventional magnetization transfer ratio asymmetry. This irradiation power caused an optimal hyperintense APT-MRI signal in the tumor and an optimal hypointense signal in the stroke, compared to the normal brain tissue. The results suggest that the saturation power of 2 μT is ideal for APT imaging of these two pathologies at 3 T with the existing clinical hardware.Copyright © 2011 Wiley-Liss, Inc.

Accurately quantifying the amide proton transfer (APT) effect and the underlying exchange parameters is crucial for its applications, but previous studies have reported conflicting results. In these quantifications, the CEST effect from the fast exchange amine was always ignored because it was considered weak with low saturation powers. This paper aims to evaluate the influence of the fast exchange amine CEST on the quantification of APT at low saturation powers.A quantification method with low and high saturation powers was used to distinguish APT from the fast exchange amine CEST effect. Simulations were conducted to assess the method's capability to separate APT from the fast exchange amine CEST effect. Animal experiments were performed to assess the relative contributions from the fast exchange amine and amide to CEST signals at 3.5 ppm. Three APT quantification methods, each with varying degrees of contamination from the fast exchange amine, were employed to process the animal data to assess the influence of the amine on the quantification of APT effect and the exchange parameters.The relative size of the fast exchange amine CEST effect to APT effect gradually increases with increasing saturation power. At 9.4 T, it increases from approximately 20% to 40% of APT effect with a saturation power increase from 0.25 to 1 μT.The fast exchange amine CEST effect leads overestimation of APT effect, fitted amide concentration, and amide-water exchange rate, potentially contributing to the conflicting results reported in previous studies.© 2023 International Society for Magnetic Resonance in Medicine.

Amide proton transfer (APT) imaging is a type of chemical exchange-dependent saturation transfer (CEST) magnetic resonance imaging (MRI) in which amide protons of endogenous mobile proteins and peptides in tissue are detected. Initial studies have shown promising results for distinguishing tumor from surrounding brain in patients, but these data were hampered by magnetic field inhomogeneity and a low signal-to-noise ratio (SNR). Here a practical six-offset APT data acquisition scheme is presented that, together with a separately acquired CEST spectrum, can provide B(0)-inhomogeneity corrected human brain APT images of sufficient SNR within a clinically relevant time frame. Data from nine brain tumor patients at 3T shows that APT intensities were significantly higher in the tumor core, as assigned by gadolinium-enhancement, than in contralateral normal-appearing white matter (CNAWM) in patients with high-grade tumors. Conversely, APT intensities in tumor were indistinguishable from CNAWM in patients with low-grade tumors. In high-grade tumors, regions of increased APT extended outside of the core into peripheral zones, indicating the potential of this technique for more accurate delineation of the heterogeneous areas of brain cancers.(c) 2008 Wiley-Liss, Inc.

For clinical implementation, a chemical exchange saturation transfer (CEST) imaging sequence must be fast, with high signal-to-noise ratio (SNR), 3D coverage, and produce robust contrast. However, spectrally selective CEST contrast requires dense sampling of the Z-spectrum, which increases scan duration. This article proposes a compromise: using a 3D snapshot gradient echo (GRE) readout with optimized CEST presaturation, sampling, and postprocessing, highly resolved Z-spectroscopy at 3T is made possible with 3D coverage at almost no extra time cost.A 3D snapshot CEST sequence was optimized for low-power CEST MRI at 3T. Pulsed saturation was optimized for saturation power and saturation duration. Spectral sampling and postprocessing (B correction, denoising) was optimized for spectrally selective Lorentzian CEST effect extraction. Reproducibility was demonstrated in 3 healthy volunteers and feasibility was shown in 1 tumor patient.Low-power saturation was achieved by a train of 80 pulses of duration t  = 20 ms (total saturation time t = 3.2 seconds at 50% duty cycle) with B = 0.6 μT at 54 irradiation frequency offsets. With the 3D snapshot CEST sequence, a 180 × 220 × 54 mm field of view was acquired in 7 seconds per offset. Spectrally selective CEST effects at +3.5 and -3.5 ppm were quantified using multi-Lorentzian fitting. Reproducibility was high with an intersubject coefficient of variation below 10% in CEST contrasts. Amide and nuclear overhauser effect CEST effects showed similar correlations in tumor and necrosis as show in previous ultra-high field work.A sophisticated CEST tool ready for clinical application was developed and tested for feasibility.© 2018 International Society for Magnetic Resonance in Medicine.

To develop a new faster and higher quality three-dimensional (3D) gagCEST MRI technique for reliable quantification of glycosaminoglycan (GAG) present in the human knee cartilages.A new magnetization-prepared 3D gradient echo-based MRI pulse sequence has been designed to obtain the B inhomogeneity, B inhomogeneity, and CEST Z-spectra images.The gagCEST values of different compartments of knee cartilage are calculated using a newly developed technique for healthy subjects and a symptomatic knee cartilage degenerated subject. The effect of the acquired CEST saturation frequency offset step-size was investigated to establish the optimal step-size to obtain reproducible gagCEST maps. Our novel 3D gagCEST technique demonstrates markedly higher gagCEST contrast value than the previously reported 3D gagCEST studies. This study demonstrates the need for separate B and B inhomogeneity estimation and correction.The new technique provided high quality gagCEST maps with clearer visualization of different layers of knee cartilage with reproducible results. Magn Reson Med 77:1866-1873, 2017. © 2016 International Society for Magnetic Resonance in Medicine.© 2016 International Society for Magnetic Resonance in Medicine.

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.Copyright © 2011 Wiley Periodicals, Inc.

Chemical exchange saturation transfer (CEST) imaging depends on the performance of radiofrequency saturation during the experiment. Scanner specifications, in particular limited pulse width and duty-cycle, and specific absorption rate guidelines restrict the full exploitation of CEST effects in clinical MR systems. The purpose of this study was to optimize techniques for effective pulse train presaturation for CEST imaging in a whole-body MR scanner. Theoretical analysis and simulations of the spectral properties of radiofrequency pulse trains demonstrated the significance of pulse width τ(P) and interpulse delay τ(D) for effective and selective labeling of a chemically exchanging proton pool. CEST experiments with model solutions, e.g., creatine dissolved in water, showed best performance of pulse trains with τ(P) = τ(D) = 100 msec, regarding minimum direct water saturation in z-spectra and distinct magnetization transfer ratio asymmetry that can be determined quantitatively. Saturation efficiency of trains of Gaussian-shaped radiofrequency pulses using this timing was evaluated in MR imagers with field strengths of 1.5, 3, and 7 T. The proposed saturation pulse train does not require hardware modifications, offers low specific absorption rate, and can be used in a standard clinical setup.Copyright © 2011 Wiley-Liss, Inc.

To introduce an unsupervised deep-learning method for fast and effective correction of susceptibility artifacts in reversed phase-encode (PE) image pairs acquired with echo planar imaging (EPI).Recent learning-based correction approaches in EPI estimate a displacement field, unwarp the reversed-PE image pair with the estimated field, and average the unwarped pair to yield a corrected image. Unsupervised learning in these unwarping-based methods is commonly attained via a similarity constraint between the unwarped images in reversed-PE directions, neglecting consistency to the acquired EPI images. This work introduces a novel unsupervised deep Forward-Distortion Network (FD-Net) that predicts both the susceptibility-induced displacement field and the underlying anatomically correct image. Unlike previous methods, FD-Net enforces the forward-distortions of the correct image in both PE directions to be consistent with the acquired reversed-PE image pair. FD-Net further leverages a multiresolution architecture to maintain high local and global performance.FD-Net performs competitively with a gold-standard reference method (TOPUP) in image quality, while enabling a leap in computational efficiency. Furthermore, FD-Net outperforms recent unwarping-based methods for unsupervised correction in terms of both image and field quality.The unsupervised FD-Net method introduces a deep forward-distortion approach to enable fast, high-fidelity correction of susceptibility artifacts in EPI by maintaining consistency to measured data. Therefore, it holds great promise for improving the anatomical accuracy of EPI imaging.© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.

Echo Planar Imaging (EPI) is a neuroimaging tool for clinical practice and research investigation. Due to odd-even echo phase inconsistencies, however, EPI suffers from Nyquist N/2 ghost artifacts. In standard neuroimaging protocols, EPI artifacts are suppressed using phase correction techniques that require reference data collected from a reference scan. Because reference-scan based techniques are sensitive to subject motion, EPI performance is sub-optimal in neuroimaging applications. In this technical note, we present a novel EPI data processing technique which we call Parallel EPI Artifact Correction (PEAC). By introducing an implicit data constraint associated with multi-coil sensitivity in parallel imaging, PEAC converts phase correction into a constrained problem that can be resolved using an iterative algorithm. This enables "reference-less" EPI that can improve neuroimaging performance. In the presented work, PEAC is investigated using a standard functional magnetic resonance imaging (fMRI) protocol with multi-slice 2D EPI. It is demonstrated that PEAC can suppress ghost artifacts as effectively as the standard reference-scan based phase correction technique used on a clinical MRI system. We also found that PEAC can achieve dynamic phase correction when motion occurs.Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical exchange saturation transfer (CEST) MRI is a versatile imaging technique for measuring microenvironment properties via dilute CEST labile groups. Conventionally, CEST MRI is implemented with a long radiofrequency irradiation module, followed by fast image acquisition to obtain the steady state CEST contrast. Nevertheless, the sensitivity, scan time, and spatial coverage of the conventional CEST MRI method may not be optimal. Our study proposed a segmented radiofrequency labeling scheme that includes a long primary radiofrequency irradiation module to generate the steady state CEST contrast and repetitive short secondary radiofrequency irradiation module immediately after the image acquisition so as to maintain the steady state CEST contrast for multislice acquisition and signal averaging. The proposed CEST MRI method was validated experimentally with a tissue-like pH phantom and optimized for the maximal contrast-to-noise ratio. In addition, the proposed sequence was evaluated for imaging ischemic acidosis via pH-weighted endogenous amide proton transfer MRI, which showed similar contrast as conventional amide proton transfer MRI. In sum, a fast multislice relaxation self-compensated CEST MRI sequence was developed, with significantly improved sensitivity and suitable for in vivo applications.Copyright © 2010 Wiley-Liss, Inc.

To integrate 3D CEST EPI with an unevenly segmented RF irradiation module and preliminarily demonstrate it in the clinical setting.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.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 k 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.It is feasible to implement a highly accelerated 3D EPI CEST imaging with unevenly segmented RF irradiation.© 2023 International Society for Magnetic Resonance in Medicine.

Artifacts caused by strong lipid signals pose challenges in body chemical exchange saturation transfer (CEST) imaging. This study aimed to develop an accurate water-fat reconstruction method based on the multi-echo Dixon technique to remove lipid artifacts in CEST imaging.It is well known that fat has multiple spectral peaks. Furthermore, RF pulses in CEST preparation saturate each fat peak at different levels, complicating fat modeling. Therefore, a self-adapting multi-peak model (SMPM) is proposed to update relative amplitudes of fat peaks using numerical calculation. With the SMPM-based updating, nonlinear least-squares fitting combined with IDEAL (Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation) algorithms was used for water-fat reconstruction and B mapping. The proposed method was compared with the reported 3-point Dixon method and the fixed multi-peak model in a phantom study using a fat-free Z-spectrum obtained from MR spectroscopy acquisition as the ground truth. This method was also validated by in vivo experiments on human breast.In the phantom experiments, the Z-spectrum from the SMPM-based method agreed well with the fat-free Z-spectrum from CEST-PRESS (point-resolved spectroscopy), validating the effective removal of lipid artifacts, while a decrease or a rise that appeared at -3.5 ppm was observed in the Z-spectrum from the 3-point method and the FMPM-based method, respectively. In the in vivo experiments, no lipid artifacts were observed in the Z-spectrum or the amide CEST map from the SMPM-based method in the fibro-glandular region of the breast with high fat fractions.The SMPM-based method successfully removes lipid artifacts and significantly improves the accuracy of CEST contrast.© 2019 International Society for Magnetic Resonance in Medicine.

Active contour segmentation and its robust implementation using level set methods are well-established theoretical approaches that have been studied thoroughly in the image analysis literature. Despite the existence of these powerful segmentation methods, the needs of clinical research continue to be fulfilled, to a large extent, using slice-by-slice manual tracing. To bridge the gap between methodological advances and clinical routine, we developed an open source application called ITK-SNAP, which is intended to make level set segmentation easily accessible to a wide range of users, including those with little or no mathematical expertise. This paper describes the methods and software engineering philosophy behind this new tool and provides the results of validation experiments performed in the context of an ongoing child autism neuroimaging study. The validation establishes SNAP intrarater and interrater reliability and overlap error statistics for the caudate nucleus and finds that SNAP is a highly reliable and efficient alternative to manual tracing. Analogous results for lateral ventricle segmentation are provided.

Chemical exchange saturation transfer (CEST) is a contrast mechanism that exploits exchange-based magnetization transfer (MT) between solute and water protons. CEST effects compete with direct water saturation and conventional MT processes, and generally can only be quantified through an asymmetry analysis of the water saturation spectrum (Z-spectrum) with respect to the water frequency, a process that is exquisitely sensitive to magnetic field inhomogeneities. Here it is shown that direct water saturation imaging allows measurement of the absolute water frequency in each voxel, allowing proper centering of Z-spectra on a voxel-by-voxel basis independently of spatial B(0) field variations. Optimal acquisition parameters for this "water saturation shift referencing" (WASSR) approach were estimated using Monte Carlo simulations and later confirmed experimentally. The optimal ratio of the WASSR sweep width to the linewidth of the direct saturation curve was found to be 3.3-4.0, requiring a sampling of 16-32 points. The frequency error was smaller than 1 Hz at signal-to-noise ratios of 40 or higher. The WASSR method was applied to study glycogen, where the chemical shift difference between the hydroxyl (OH) protons and bulk water protons at 3T is so small (0.75-1.25 ppm) that the CEST spectrum is inconclusive without proper referencing.

The purpose of the study is to demonstrate the value of quantitative amide proton transfer (APT) imaging for differentiating glioma grades and detecting tumor proliferation.This study included 32 subjects with 16 low-grade gliomas (LGG) and 16 high-grade gliomas (HGG) confirmed by histopathology. Chemical exchange saturation transfer (CEST) magnetic resonance imaging with APT weighting was performed on a 3 T scanner. After B correction, Z-spectra were fitted with Lorentzian functions corresponding to the upfield semi-solid magnetization transfer and nuclear overhauser enhancement (MT&NOE) effect, the direct saturation (DS) effect, and the downfield APT effect centered at around - 1.5, 0, and + 3.5 ppm, respectively. To compute the Z-spectral fitted APT (fitted_APT) in solid tumor tissue, double-peak histogram fitting of pixel MT&NOE effect from the whole tumor was used to remove necrosis regions. The fitted APT was then compared with the conventional APT based on magnetization transfer ratio asymmetry. Receiver operating characteristic (ROC) analysis was used to compare the performance between Z-spectral fitted contrasts and the con_APT for LGG versus HGG differentiation. Additionally, the correlations between the imaging contrasts (fitted_APT, con_APT, and fitted_MT&NOE) and Ki-67 labeling index for tumor proliferation were also evaluated.Z-spectral fitted_APT shows improved statistical power for differentiating HGG and LGG (7.58 ± 0.99 vs. 6.79 ± 1.05 %, p < 0.05) than con_APT (4.34 ± 0.95 vs. 4.05 ± 2.02 %, p > 0.05) in solid tumor tissues. Analyses of whole tumor, on the other hand, have less differentiating power for both fitted_APT (p from 0.032 to 0.08) and con_APT (p from 0.696 to 0.809). Similarly, based on ROC analyses, fitted_APT shows larger area under the curve (AUC = 0.723) than con_APT (AUC = 0.543). The combination of fitted APT, DS, and MT&NOE further improved the specificity (75 %), diagnostic accuracy (78.2 %), and area under the curve (0.758) in differentiating LGG and HGG. Consistently, fitted_APT (r = 0.451, p = 0.018) is better correlated with Ki-67 than con_APT (r = 0.331, p = 0.092).Fitted APT from Z-spectrum improves differentiation of low- and high-grade gliomas and better correlated with tumor proliferation than conventional APT.

Chemical exchange saturation transfer (CEST)-derived, pH-weighted, amide proton transfer (APT) MRI has shown promise in animal studies for the prediction of infarction risk in ischemic tissue. Here, APT MRI was translated to patients with acute stroke (1-24 h post-symptom onset), and assessments of APT contrast, perfusion, diffusion, disability and final infarct volume (23-92 days post-stroke) are reported. Healthy volunteers (n = 5) and patients (n = 10) with acute onset of symptoms (0-4 h, n = 7; uncertain onset <24 h, n = 3) were scanned with diffusion- and perfusion-weighted MRI, fluid-attenuated inversion recovery (FLAIR) and CEST. Traditional asymmetry and a Lorentzian-based APT index were calculated in the infarct core, at-risk tissue (time-to-peak, TTP; lengthening) and final infarct volume. On average (mean ± standard deviation), control white matter APT values (asymmetry, 0.019 ± 0.005; Lorentzian, 0.045 ± 0.006) were not significantly different (p > 0.05) from APT values in normal-appearing white matter (NAWM) of patients (asymmetry, 0.022 ± 0.003; Lorentzian, 0.048 ± 0.003); however, ischemic regions in patients showed reduced (p = 0.03) APT effects compared with NAWM. Representative cases are presented, whereby the APT contrast is compared quantitatively with contrast from other imaging modalities. The findings vary between patients; in some patients, a trend for a reduction in the APT signal in the final infarct region compared with at-risk tissue was observed, consistent with tissue acidosis. However, in other patients, no relationship was observed in the infarct core and final infarct volume. Larger clinical studies, in combination with focused efforts on sequence development at clinically available field strengths (e.g. 3.0 T), are necessary to fully understand the potential of APT imaging for guiding the hyperacute management of patients.Copyright © 2013 John Wiley & Sons, Ltd.

Chemical exchange saturation transfer magnetic resonance imaging can detect low-concentration compounds with exchangeable protons through saturation transfer to water. This technique is generally slow, as it requires acquisition of saturation images at multiple frequencies. In addition, multislice imaging is complicated by saturation effects differing from slice to slice because of relaxation losses. In this study, a fast three-dimensional chemical exchange saturation transfer imaging sequence is presented that allows whole-brain coverage for a frequency-dependent saturation spectrum (z-spectrum, 26 frequencies) in less than 10 min. The approach employs a three-dimensional gradient- and spin-echo readout using a prototype 32-channel phased-array coil, combined with two-dimensional sensitivity encoding accelerations. Results from a homogenous protein-containing phantom at 3T show that the sequence produced a uniform contrast across all slices. To show translational feasibility, scans were also performed on five healthy human subjects. Results for chemical exchange saturation transfer images at 3.5 ppm downfield of the water resonance, so-called amide proton transfer images, show that lipid signals are sufficiently suppressed and artifacts caused by B(0) inhomogeneity can be removed in postprocessing. The scan time and image quality of these in vivo results show that three-dimensional chemical exchange saturation transfer MRI using gradient- and spin-echo acquisition is feasible for whole-brain chemical exchange saturation transfer studies at 3T in a clinical time frame.2010 Wiley-Liss, Inc.

The ability to measure proton exchange rates in tissue using MRI would be very useful for quantitative assessment of magnetization transfer properties, both in conventional MT imaging and in the more recent chemical exchange saturation transfer (CEST) approach. CEST is a new MR contrast mechanism that depends on several factors, including the exchange rate of labile protons in the agent in a pH-dependent manner. Two new methods to monitor local exchange rate based on CEST are introduced. The two MRI-compatible approaches to measure exchange are quantifying exchange using saturation time (QUEST) dependence and quantifying exchange using saturation power (QUESP) dependence. These techniques were applied to poly-L-lysine (PLL) and a generation-5 polyamidoamine dendrimer (SPD-5) to measure the pH dependence of amide proton exchange rates in the physiologic range. Data were fit both to an analytical expression and to numerical solutions to the Bloch equations. Results were validated by comparison with exchange rates determined by two established spectroscopic methods. The exchange rates determined using the four methods were pooled for the pH-calibration curve of the agents consisting of contributions from spontaneous (k0) acid catalyzed (ka), and base catalyzed (kb) exchange rate constants. These constants were k0 = 68.9 Hz, ka = 1.21 Hz, kb = 1.92 x 10(9) Hz, and k0 = 106.4 Hz, ka = 25.8 Hz, kb = 5.45 x 10(8) Hz for PLL and SPD-5, respectively, showing the expected predominance of base-catalyzed exchange for these amide protons.(c) 2006 Wiley-Liss, Inc.

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.Copyright © 2011 Wiley-Liss, Inc.

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.© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.

Calculation of sophisticated MR contrasts often requires complex mathematical modeling. Data evaluation is computationally expensive, vulnerable to artifacts, and often sensitive to fit algorithm parameters. In this work, we investigate whether neural networks can provide not only fast model fitting results, but also a quality metric for the predicted values, so called uncertainty quantification, investigated here in the context of multi-pool Lorentzian fitting of CEST MRI spectra at 3T.A deep feed-forward neural network including a probabilistic output layer allowing for uncertainty quantification was set up to take uncorrected CEST-spectra as input and predict 3T Lorentzian parameters of a 4-pool model (water, semisolid MT, amide CEST, NOE CEST), including the B inhomogeneity. Networks were trained on data from 3 subjects with and without data augmentation, and applied to untrained data from 1 additional subject and 1 brain tumor patient. Comparison to conventional Lorentzian fitting was performed on different perturbations of input data.The deepCEST 3T networks provided fast and accurate predictions of all Lorentzian parameters and were robust to input perturbations because of noise or B artifacts. The uncertainty quantification detected fluctuations in input data by increase of the uncertainty intervals. The method generalized to unseen brain tumor patient CEST data.The deepCEST 3T neural network provides fast and robust estimation of CEST parameters, enabling online reconstruction of sophisticated CEST contrast images without the typical computational cost. Moreover, the uncertainty quantification indicates if the predictions are trustworthy, enabling confident interpretation of contrast changes.© 2019 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

磁共振成像（Magnetic Resonance Imaging，MRI）化学交换饱和转移（Chemical Exchange Saturation Transfer，CEST）技术在临床诊断中展现了巨大的潜力，但在腹部成像中受到主磁场偏移量大的挑战，而且利用传统的非对称性分析法得到的酰胺质子转移（Amide Proton Transfer，APT）成像对比度受到核奥氏增强（Nuclear Overhauser Enhancement，NOE）效应的干扰.本文提出了一种基于神经网络拟合的CEST后处理方法，对每个像素采集得到的Z谱特征进行识别，不需要额外序列扫描即可得到背景参考Z谱与主磁场偏移量，用以校正和获得理想的Z谱，并进一步分离得到源自APT效应与NOE效应的信号.鸡蛋清和健康志愿者腹部成像结果显示，本文提出的基于神经网络的CEST后处理方法效果较好.

多通道磁共振成像方法采用多个接收线圈同时欠采样k空间以加快成像速度，并基于后处理算法重建图像，但在较高加速因子时，其图像重建质量仍然较差．本文提出了一种基于PCAU-Net的快速多通道磁共振成像方法，将单通道实数U型卷积神经网络拓展到多通道复数卷积神经网络，设计了一种结构不对称的U型网络结构，通过在解码部分减小网络规模以降低模型的复杂度．PCAU-Net网络在跳跃连接前增加了1×1卷积，以实现跨通道信息交互．输入和输出之间利用残差连接为误差的反向传播提供捷径．实验结果表明，使用规则和随机采样模板，在不同加速因子时，相比常规的GRAPPA重建算法和SPIRiT重建方法，本文提出的PCAU-Net方法可高质量重建出磁共振复数图像，并且相比于PCU-Net方法，PCAU-Net减少了模型参数、缩短了训练时间．

为了提高磁共振图像在欠采样下重建的质量，本文融合注意力机制和多尺度残差卷积构建Unet网络，实现磁共振图像在欠采样下的重建算法．为增强网络特征的表现能力，以及防止网络训练中梯度消失与退化的问题，在Unet网络的编码路径中引入多尺度残差卷积，提取不同尺度的特征信息；为能准确地恢复图像的细节纹理特征，在Unet网络编码和解码路径的跳层拼接部分引入卷积注意力块，对细节纹理等关键信息进行不同程度的响应．实验表明，本文方法可通过欠采样k-空间数据快速重建出细节纹理清晰且无重叠伪影的高质量磁共振图像．

To investigate the effect of a frequency drift of the static magnetic field on 3D CEST MRI based on glycosaminoglycans (GAGs) of articular cartilage at 7 T and to introduce a retrospective correction method that uses the phase images of the gradient-echo readout.Repeated gagCEST and B measurements were performed in a glucose model solution and in vivo in the knee joint of 3 healthy volunteers at 7 T. Phase images of the modified 3D rectangular spiral centric-reordered gradient-echo CEST sequence were used to quantify and compensate the apparent frequency drift in repeated gagCEST measurements.The frequency drift of the MRI scanner strongly influences the gagCEST signal in the articular cartilage of the human knee joint. The gagCEST signal in the articular cartilage is changed by 0.18%/Hz while an average drift of 0.7 ± 0.2 Hz/minute was observed. The proposed correction method can be applied retrospectively without the need of additional measurements and provides improved comparability and reproducibility for gagCEST studies. This correction method may also be of interest for other applications of CEST MRI.Prospective or retrospective correction of the frequency drift of the MRI scanner is essential for reproducible gagCEST measurements. The proposed retrospective correction method fulfills this requirement without the need of additional measurements.© 2018 International Society for Magnetic Resonance in Medicine.

Although spin-echo (SE) sequence has some advantages over gradient-echo sequence in brain imaging, gradient-echo sequence is commonly used for T1-weighted imaging (T1WI) at 3 T because contrast on SE T1WI is widely believed to be poor at 3 T. Recently, gray-white matter contrast on single-slice and multi-slice SE imaging with interslice gap was reported as better at 3 T than at 1.5 T. This study examined the feasibility of interleaved SE T1WI of the brain at 3 T. This study also examined whether presaturation pulse (PP) sufficiently suppresses intra-arterial signals because these signals tend to be hyperintense due to longer T1 at 3 T.Subjects consisted of 18 healthy volunteers. Two sets of T1WI were performed using SE sequence. One set consisted of imaging without PP, and the other consisted of imaging with PP. Each set contained three types of gapless imaging as follows; sequential, 100% interleaved, and 200% interleaved imaging. In each subject, contrast-to-noise ratio between gray-matter and white-matter (CNR(GM-WM)) and intra-arterial signals were evaluated.CNR(GM-WM) was significantly higher on interleaved images than on sequential images, regardless of PP (P <.0001). PP sufficiently suppressed intra-arterial signals (P <.0001).CNR(GM-WM) on SE T1WI at 3 T can be improved by interleaved acquisition, and PP sufficiently suppressed intra-arterial signals. Interleaved SE T1WI with PP appears clinically feasible at 3 T.

Magnetization transfer (MT) imaging provides a unique method of tissue characterization by capitalizing on the interaction between solid-like tissue components and bulk water. We used a continuous-wave (CW) MT pulse sequence with low irradiation power to study healthy human brains in vivo at 3 T and quantified the asymmetry of the MT effects with respect to the water proton frequency. This asymmetry was found to be a difference of approximately a few percent from the water signal intensity, depending on both the RF irradiation power and the frequency offset. The experimental results could be quantitatively described by a modified two-pool MT model extended with a shift contribution for the semisolid pool with respect to water. For white matter, this shift was fitted to be 2.34 +/- 0.17 ppm (N = 5) upfield from the water signal.