Calibration-free whole-brain CEST imaging at 7T with parallel transmit pulse design for saturation homogeneity utilizing universal pulses (PUSHUP).

PURPOSE: Chemical exchange saturation transfer (CEST) measurements at ultra-high field (UHF) suffer from strong saturation inhomogeneity. Retrospective correction of this inhomogeneity is possible to some extent, but requires a time-consuming repetition of the measurement. Here, we propose a calibration-free parallel transmit (pTx)-based saturation scheme that homogenizes the saturation over the imaging volume, which we call PUlse design for Saturation Homogeneity utilizing Universal Pulses (PUSHUP). THEORY: Magnetization transfer effects depend on the saturation B 1 rms $$ {\mathrm{B}}_1^{\mathrm{rms}} $$ . PUSHUP homogenizes the saturation B 1 rms $$ {\mathrm{B}}_1^{\mathrm{rms}} $$ by using multiple saturation pulses with alternating B 1 $$ {\mathrm{B}}_1 $$ -shims. Using a database of B 1 $$ {\mathrm{B}}_1 $$ maps, universal pulses are calculated that remove the necessity of time-consuming, subject-based pulse calculation during the measurement. METHODS: PUSHUP was combined with a whole-brain three-dimensional-echo planar imaging (3D-EPI) readout. Two PUSHUP saturation modules were calculated by either applying whole-brain or cerebellum masks to the database maps. The saturation homogeneity and the group mean CEST amplitudes were calculated for different B 1 $$ {\mathrm{B}}_1 $$ -correction methods and were compared to circular polarized (CP) saturation in five healthy volunteers using an eight-channel transmit coil at 7 Tesla. RESULTS: In contrast to CP saturation, where accurate CEST maps were impossible to obtain in the cerebellum, even with extensive B 1 $$ {\mathrm{B}}_1 $$ -correction, PUSHUP CEST maps were artifact-free throughout the whole brain. A 1-point retrospective B 1 $$ {\mathrm{B}}_1 $$ -correction, that does not need repeated measurements, sufficiently removed the effect of residual saturation inhomogeneity. CONCLUSION: The presented method allows for homogeneous whole-brain CEST imaging at 7 Tesla without the need of a repetition-based B 1 $$ {\mathrm{B}}_1 $$ -correction or online pulse calculation. With the fast 3D-EPI readout, whole-brain CEST imaging with 45 saturation offsets is possible at 1.6 mm resolution in under 4 min.

Improved quantification in CEST-MRI by joint spatial total generalized variation.

PURPOSE: In this work, the use of joint Total Generalized Variation (TGV) regularization to improve Multipool-Lorentzian fitting of chemical exchange saturation transfer (CEST) Spectra in terms of stability and parameter signal-to-noise ratio (SNR) was investigated. THEORY AND METHODS: The joint TGV term was integrated into the nonlinear parameter fitting problem. To increase convergence and weight the gradients, preconditioning using a voxel-wise singular value decomposition was applied to the problem, which was then solved using the iteratively regularized Gauss-Newton method combined with a Primal-Dual splitting algorithm. The TGV method was evaluated on simulated numerical phantoms, 3T phantom data and 7T in vivo data with respect to systematic errors and robustness. Three reference methods were also implemented: The standard nonlinear fitting, a method using a nonlocal-means filter for denoising and the pyramid scheme, which uses downsampled images to acquire accurate start values. RESULTS: The proposed regularized fitting method showed significantly improved robustness (compared to the reference methods). In testing, over a range of SNR values the TGV fit outperformed the other methods and showed accurate results even for large amounts of added noise. Parameter values found were closer or comparable to the ground truth. For in vivo datasets, the added regularization increased the parameter map SNR and prevented instabilities. CONCLUSION: The proposed fitting method using TGV regularization leads to improved results over a range of different data-sets and noise levels. Furthermore, it can be applied to all Z-spectrum data, with different amounts of pools, where the improved SNR and stability can increase diagnostic confidence.

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

PURPOSE: To employ optimal control for the numerical design of Chemical Exchange Saturation Transfer (CEST) saturation pulses to maximize contrast and stability against B 0 $$ {\mathrm{B}}_0 $$ inhomogeneities. THEORY AND METHODS: 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. RESULTS: 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 B 0 $$ {\mathrm{B}}_0 $$ robustness of the optimized pulses. CONCLUSION: 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.

Phase distribution graphs for fast, differentiable, and spatially encoded Bloch simulations of arbitrary MRI sequences.

PURPOSE: An analytical approach to Bloch simulations for MRI sequences is introduced that enables time efficient calculations of signals free of Monte-Carlo noise, while providing full flexibility and differentiability in RF flip angles, RF phases, magnetic field gradients and time, as well as insights into image formation. THEORY AND METHODS: We present an implementation of the extended phase graph (EPG) concept implemented in PyTorch, including an efficient state selection algorithm. This simulation is compared with an isochromat-based Bloch simulation with random isochromat distribution as well as with in vivo measurements using the Pulseq standard. Additionally, different sequences are tested and analyzed using this novel simulation approach. RESULTS: Our simulation outperforms isochromat-based simulations in terms of computation time as well as signal quality, without exhibiting any kind of Monte-Carlo noise. The novel approach allows extracting useful information about the magnetization evolution not available otherwise. Our approach extends the common state-tensor-based EPG simulation approach for the contribution of dephased states including spatial encoding and T 2 ' $$ {T}_2^{\prime } $$ effects, and arbitrary timing. This allows calculation of echo shapes in addition to echo amplitudes only. Our implementation provides full differentiability in all input parameters allowing gradient descent optimization. Simulation of non-instantaneous pulses via hard-pulse approximation is left for future work, as the performance and accuracy characteristics are not yet analyzed. CONCLUSIONS: Phase distribution graphs provide fast, differentiable, and spatially encoded Bloch simulations for most MRI sequences. It allows efficient simulation and optimization of arbitrary MRI sequences, which was previously only possible via high isochromat counts.

Comprehensive 7 T CEST: A clinical MRI protocol covering multiple exchange rate regimes.

Chemical exchange saturation transfer (CEST) is a magnetic resonance (MR) imaging method providing molecular image contrasts based on indirect detection of low concentrated solutes. Previous CEST studies focused predominantly on the imaging of single CEST exchange regimes (e.g., slow, intermediate or fast exchanging groups). In this work, we aim to establish a so-called comprehensive CEST protocol for 7 T, covering the different exchange regimes by three saturation B1 amplitude regimes: low, intermediate and high. We used the results of previous publications and our own simulations in pulseq-CEST to produce a 7 T CEST protocol that has sensitivity to these three B1 regimes. With postprocessing optimization (simultaneous mapping of water shift and B1, B0-fitting, multiple interleaved mode saturation B1 correction, neural network employment (deepCEST) and analytical input feature reduction), we are able to shorten our initially 40 min protocol to 15 min and generate six CEST contrast maps simultaneously. With this protocol, we measured four healthy subjects and one patient with a brain tumor. We established a comprehensive CEST protocol for clinical 7 T MRI, covering three different B1 amplitude regimes. We were able to reduce the acquisition time significantly by more than 50%, while still maintaining decent image quality and contrast in healthy subjects and one patient with a tumor. Our protocol paves the way to perform comprehensive CEST studies in clinical scan times for hypothesis generation regarding molecular properties of certain pathologies, for example, ischemic stroke or high-grade brain tumours.

Sidebands in CEST MR-How to recognize and avoid them.

PURPOSE: Clinical scanners require pulsed CEST sequences to maintain amplifier and specific absorption rate limits. During off-resonant RF irradiation and interpulse delay, the magnetization can accumulate specific relative phases within the pulse train. In this work, we show that these phases are important to consider, as they can lead to unexpected artifacts when no interpulse gradient spoiling is performed during the saturation train. METHODS: We investigated sideband artifacts using a CEST-3D snapshot gradient-echo sequence at 3 T. Initially, Bloch-McConnell simulations were carried out with Pulseq-CEST, while measurements were performed in vitro and in vivo. RESULTS: Sidebands can be hidden in Z-spectra, and their structure becomes clearly visible only at high sampling. Sidebands are further influenced by B0 inhomogeneities and the RF phase cycling within the pulse train. In vivo, sidebands are mostly visible in liquid compartments such as CSF. Multi-pulse sidebands can be suppressed by interpulse gradient spoiling. CONCLUSION: We provide new insights into sidebands occurring in pulsed CEST experiments and show that, similar as in imaging sequences, gradient and RF spoiling play an important role. Gradient spoiling avoids misinterpretations of sidebands as CEST effects especially in liquid environments including pathological tissue or for CEST resonances close to water. It is recommended to simulate pulsed CEST sequences in advance to avoid artifacts.

Fluid suppression in amide proton transfer-weighted (APTw) CEST imaging: New theoretical insights and clinical benefits.

PURPOSE: Amide proton transfer-weighted (APTw) MRI at 3T provides a unique contrast for brain tumor imaging. However, APTw imaging suffers from hyperintensities in liquid compartments such as cystic or necrotic structures and provides a distorted APTw signal intensity. Recently, it has been shown that heuristically motivated fluid suppression can remove such artifacts and significantly improve the readability of APTw imaging. THEORY AND METHODS: In this work, we show that the fluid suppression can actually be understood by the known concept of spillover dilution, which itself can be derived from the Bloch-McConnell equations in comparison to the heuristic approach. Therefore, we derive a novel post-processing formula that efficiently removes fluid artifact, and explains previous approaches. We demonstrate the utility of this APTw assessment in silico, in vitro, and in vivo in brain tumor patients acquired at MR scanners from different vendors. RESULTS: Our results show a reduction of the CEST signals from fluid environments while keeping the APTw-CEST signal intensity almost unchanged for semi-solid tissue structures such as the contralateral normal appearing white matter. This further allows us to use the same color bar settings as for conventional APTw imaging. CONCLUSION: Fluid suppression has considerable value in improving the readability of APTw maps in the neuro-oncological field. In this work, we derive a novel post-processing formula from the underlying Bloch-McConnell equations that efficiently removes fluid artifact, and explains previous approaches which justify the derivation of this metric from a theoretical point of view, to reassure the scientific and medical field about its use.

APT weighted imaging in diffuse gliomas.

Amide proton transfer-weighted (APTw) imaging is a non-invasive molecular MRI technique with a wide range of applications in neuroradiology and particularly neuro-oncology imaging. More than 15 years of pre-clinical experiments and clinical studies have demonstrated that APTw metrics are reproducible and reliable, leading to large-scale clinical acceptance. At present, major vendors of MRI scanners provide APTw sequences upon request. However, most neuroradiologists are unfamiliar with this advanced MRI contrast, its related metrics, and its established added value to patient care. In this manuscript, we present the APTw contrast and illustrate its clinical potential for glioma patients, before and after tumor therapy. We also show common artifacts of APTw imaging and discuss potential limitations and future refinements. Our goal is to suggest how this emerging technique can aid in diffuse gliomas work-up.

Multi-parametric optimization of magnetic resonance imaging sequences for magnetic resonance-guided radiotherapy.

Background and purpose: Magnetic Resonance Imaging (MRI) is widely used in oncology for tumor staging, treatment response assessment, and radiation therapy (RT) planning. This study proposes a framework for automatic optimization of MRI sequences based on pulse sequence parameter sets (SPS) that are directly applied on the scanner, for application in RT planning. Materials and methods: A phantom with seven in-house fabricated contrasts was used for measurements. The proposed framework employed a derivative-free optimization algorithm to repeatedly update and execute a parametrized sequence on the MR scanner to acquire new data. In each iteration, the mean-square error was calculated based on the clinical application. Two clinically relevant optimization goals were pursued: achieving the same signal and therefore contrast as in a target image, and maximizing the signal difference (contrast) between specified tissue types. The framework was evaluated using two optimization methods: a covariance matrix adaptation evolution strategy (CMA-ES) and a genetic algorithm (GA). Results: The obtained results demonstrated the potential of the proposed framework for automatic optimization of MRI sequences. Both CMA-ES and GA methods showed promising results in achieving the two optimization goals, however, CMA-ES converged much faster as compared to GA. Conclusions: The proposed framework enables for automatic optimization of MRI sequences based on SPS that are directly applied on the scanner and it may be used to enhance the quality of MRI images for dedicated applications in MR-guided RT.

Fast WASABI post-processing: Access to rapid B0 and B1 correction in clinical routine for CEST MRI.

CEST MRI methods, such as APT and NOE imaging reveal biomarkers with significant diagnostic potential due to their ability to access molecular tissue information. Regardless of the technique used, CEST MRI data are affected by static magnetic B0 and radiofrequency B1 field inhomogeneities that degrade their contrast. For this reason, the correction of B0 field-induced artefacts is essential, whereas accounting for B1 field inhomogeneities have shown significant improvements in image readability. In a previous work, an MRI protocol called WASABI was presented, which can map simultaneously B0 and B1 field inhomogeneities, while maintaining the same sequence and readout types as used for CEST MRI. Despite the highly satisfactory quality of B0 and B1 maps computed from the WASABI data, the post-processing method is based on an exhaustive search of a four-parameter space and an additional four-parameter non-linear model fitting step. This leads to long post-processing times that are prohibitive in clinical practice. This work provides a new method for fast post-processing of WASABI data with outstanding acceleration of the parameter estimation procedure and without compromising its stability. The resulting computational acceleration makes the WASABI technique suitable for clinical use. The stability of the method is demonstrated on phantom data and clinical 3 Tesla in vivo data.

MR-zero meets RARE MRI: Joint optimization of refocusing flip angles and neural networks to minimize T2 -induced blurring in spin echo sequences.

PURPOSE: An end-to-end differentiable 2D Bloch simulation is used to reduce T2 induced blurring in single-shot turbo spin echo sequences, also called rapid imaging with refocused echoes (RARE) sequences, by using a joint optimization of refocusing flip angles and a convolutional neural network. METHODS: Simulation and optimization were performed in the MR-zero framework. Variable flip angle train and DenseNet parameters were optimized jointly using the instantaneous transverse magnetization, available in our simulation, at a certain echo time, which serves as ideal blurring-free target. Final optimized sequences were exported for in vivo measurements at a real system (3 T Siemens, PRISMA) using the Pulseq standard. RESULTS: The optimized RARE was able to successfully lower T2 -induced blurring for single-shot RARE sequences in proton density-weighted and T2 -weighted images. In addition to an increased sharpness, the neural network allowed correction of the contrast changes to match the theoretical transversal magnetization. The optimization found flip angle design strategies similar to existing literature, however, visual inspection of the images and evaluation of the respective point spread function demonstrated an improved performance. CONCLUSIONS: This work demonstrates that when variable flip angles and a convolutional neural network are optimized jointly in an end-to-end approach, sequences with more efficient minimization of T2 -induced blurring can be found. This allows faster single- or multi-shot RARE MRI with longer echo trains.

Theory of chemical exchange saturation transfer MRI in the context of different magnetic fields.

The article from this special issue was previously published in NMR In Biomedicine , Volume 35, Issue 11, 2022. For completeness we are including the title page of the article below. The full text of the article can be read in Issue 35:11 on Wiley Online Library: https://doi.org/10.1002/nbm.4789.

Germany's journey toward 14 Tesla human magnetic resonance.

Multiple sites within Germany operate human MRI systems with magnetic fields either at 7 Tesla or 9.4 Tesla. In 2013, these sites formed a network to facilitate and harmonize the research being conducted at the different sites and make this technology available to a larger community of researchers and clinicians not only within Germany, but also worldwide. The German Ultrahigh Field Imaging (GUFI) network has defined a strategic goal to establish a 14 Tesla whole-body human MRI system as a national research resource in Germany as the next progression in magnetic field strength. This paper summarizes the history of this initiative, the current status, the motivation for pursuing MR imaging and spectroscopy at such a high magnetic field strength, and the technical and funding challenges involved. It focuses on the scientific and science policy process from the perspective in Germany, and is not intended to be a comprehensive systematic review of the benefits and technical challenges of higher field strengths.

Snapshot CEST++: Advancing rapid whole-brain APTw-CEST MRI at 3 T.

APTw CEST MRI suffers from long preparation times and consequently long acquisition times (~5 min). Recently, a consensus on the preparation module for clinical APTw CEST at 3 T was found in the community, and we present a fast whole-brain APTw CEST MRI sequence following this consensus preparation of pulsed RF irradiation of 2 s duration at 90% RF duty-cycle and a B1,rms of 2 µT. After optimization of the snapshot CEST approach for APTw imaging regarding flip angle, voxel size and frequency offset sampling, we extend it by undersampled GRE acquisition and compressed sensing reconstruction. This allows 2 mm isotropic whole-brain APTw imaging for clinical research at 3 T below 2 min. With this sequence, a fast snapshot APTw imaging method is now available for larger clinical studies of brain tumors.

Accelerated and quantitative three-dimensional molecular MRI using a generative adversarial network.

PURPOSE: To substantially shorten the acquisition time required for quantitative three-dimensional (3D) chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) imaging and allow for rapid chemical exchange parameter map reconstruction. METHODS: Three-dimensional CEST and MT magnetic resonance fingerprinting (MRF) datasets of L-arginine phantoms, whole-brains, and calf muscles from healthy volunteers, cancer patients, and cardiac patients were acquired using 3T clinical scanners at three different sites, using three different scanner models and coils. A saturation transfer-oriented generative adversarial network (GAN-ST) supervised framework was then designed and trained to learn the mapping from a reduced input data space to the quantitative exchange parameter space, while preserving perceptual and quantitative content. RESULTS: The GAN-ST 3D acquisition time was 42-52 s, 70% shorter than CEST-MRF. The quantitative reconstruction of the entire brain took 0.8 s. An excellent agreement was observed between the ground truth and GAN-based L-arginine concentration and pH values (Pearson's r > 0.95, ICC > 0.88, NRMSE < 3%). GAN-ST images from a brain-tumor subject yielded a semi-solid volume fraction and exchange rate NRMSE of 3 . 8 ± 1 . 3 % $$ 3.8\pm 1.3\% $$ and 4 . 6 ± 1 . 3 % $$ 4.6\pm 1.3\% $$ , respectively, and SSIM of 96 . 3 ± 1 . 6 % $$ 96.3\pm 1.6\% $$ and 95 . 0 ± 2 . 4 % $$ 95.0\pm 2.4\% $$ , respectively. The mapping of the calf-muscle exchange parameters in a cardiac patient, yielded NRMSE < 7% and SSIM > 94% for the semi-solid exchange parameters. In regions with large susceptibility artifacts, GAN-ST has demonstrated improved performance and reduced noise compared to MRF. CONCLUSION: GAN-ST can substantially reduce the acquisition time for quantitative semi-solid MT/CEST mapping, while retaining performance even when facing pathologies and scanner models that were not available during training.

Simultaneous dynamic glucose-enhanced (DGE) MRI and fiber photometry measurements of glucose in the healthy mouse brain.

Glucose is the main energy source in the brain and its regulated uptake and utilization are important biomarkers of pathological brain function. Glucose Chemical Exchange Saturation Transfer (GlucoCEST) and its time-resolved version Dynamic Glucose-Enhanced MRI (DGE) are promising approaches to monitor glucose and detect tumors, since they are radioactivity-free, do not require 13C labeling and are is easily translatable to the clinics. The main principle of DGE is clear. However, what remains to be established is to which extent the signal reflects vascular, extracellular or intracellular glucose. To elucidate the compartmental contributions to the DGE signal, we coupled it with FRET-based fiber photometry of genetically encoded sensors, a technique that combines quantitative glucose readout with cellular specificity. The glucose sensor FLIIP was used with fiber photometry to measure astrocytic and neuronal glucose changes upon injection of D-glucose, 3OMG and L-glucose, in the anaesthetized murine brain. By correlating the kinetic profiles of the techniques, we demonstrate the presence of a vascular contribution to the signal, especially at early time points after injection. Furthermore, we show that, in the case of the commonly used contrast agent 3OMG, the DGE signal actually anticorrelates with the glucose concentration in neurons and astrocytes.

DeepCEST 7 T: Fast and homogeneous mapping of 7 T CEST MRI parameters and their uncertainty quantification.

PURPOSE: In this work, we investigated the ability of neural networks to rapidly and robustly predict Lorentzian parameters of multi-pool CEST MRI spectra at 7 T with corresponding uncertainty maps to make them quickly and easily available for routine clinical use. METHODS: We developed a deepCEST 7 T approach that generates CEST contrasts from just 1 scan with robustness against B1 inhomogeneities. The input data for a neural feed-forward network consisted of 7 T in vivo uncorrected Z-spectra of a single B1 level, and a B1 map. The 7 T raw data were acquired using a 3D snapshot gradient echo multiple interleaved mode saturation CEST sequence. These inputs were mapped voxel-wise to target data consisting of Lorentzian amplitudes generated conventionally by 5-pool Lorentzian fitting of normalized, denoised, B0 - and B1 -corrected Z-spectra. The deepCEST network was trained with Gaussian negative log-likelihood loss, providing an uncertainty quantification in addition to the Lorentzian amplitudes. RESULTS: The deepCEST 7 T network provides fast and accurate prediction of all Lorentzian parameters also when only a single B1 level is used. The prediction was highly accurate with respect to the Lorentzian fit amplitudes, and both healthy tissues and hyperintensities in tumor areas are predicted with a low uncertainty. In corrupted cases, high uncertainty indicated wrong predictions reliably. CONCLUSION: The proposed deepCEST 7 T approach reduces scan time by 50% to now 6:42 min, but still delivers both B0 - and B1 -corrected homogeneous CEST contrasts along with an uncertainty map, which can increase diagnostic confidence. Multiple accurate 7 T CEST contrasts are delivered within seconds.

Linear projection-based chemical exchange saturation transfer parameter estimation.

Isolated evaluation of multiparametric in vivo chemical exchange saturation transfer (CEST) MRI often requires complex computational processing for both correction of B0 and B1 inhomogeneity and contrast generation. For that, sufficiently densely sampled Z-spectra need to be acquired. The list of acquired frequency offsets largely determines the total CEST acquisition time, while potentially representing redundant information. In this work, a linear projection-based multiparametric CEST evaluation method is introduced that offers fast B0 and B1 inhomogeneity correction, contrast generation and feature selection for CEST data, enabling reduction of the overall measurement time. To that end, CEST data acquired at 7 T in six healthy subjects and in one brain tumor patient were conventionally evaluated by interpolation-based inhomogeneity correction and Lorentzian curve fitting. Linear regression was used to obtain coefficient vectors that directly map uncorrected data to corrected Lorentzian target parameters. L1-regularization was applied to find subsets of the originally acquired CEST measurements that still allow for such a linear projection mapping. The linear projection method allows fast and interpretable mapping from acquired raw data to contrast parameters of interest, generalizing from healthy subject training data to unseen healthy test data and to the tumor patient dataset. The L1-regularization method shows that a fraction of the acquired CEST measurements is sufficient to preserve tissue contrasts, offering up to a 2.8-fold reduction of scan time. Similar observations as for the 7-T data can be made for data from a clinical 3-T scanner. Being a fast and interpretable computation step, the proposed method is complementary to neural networks that have recently been employed for similar purposes. The scan time acceleration offered by the L1-regularization ("CEST-LASSO") constitutes a step towards better applicability of multiparametric CEST protocols in a clinical context.

7 tricks for 7 T CEST: Improving the reproducibility of multipool evaluation provides insights into the effects of age and the early stages of Parkinson's disease.

The objective of the current study was to optimize the postprocessing pipeline of 7 T chemical exchange saturation transfer (CEST) imaging for reproducibility and to prove this optimization for the detection of age differences and differences between patients with Parkinson's disease versus normal subjects. The following 7 T CEST MRI experiments were analyzed: repeated measurements of a healthy subject, subjects of two age cohorts (14 older, seven younger subjects), and measurements of 12 patients with Parkinson's disease. A slab-selective, B 1 + -homogeneous parallel transmit protocol was used. The postprocessing, consisting of motion correction, smoothing, B 0 -correction, normalization, denoising, B 1 + -correction and Lorentzian fitting, was optimized regarding the intrasubject and intersubject coefficient of variation (CoV) of the amplitudes of the amide pool and the aliphatic relayed nuclear Overhauser effect (rNOE) pool within the brain. Seven "tricks" for postprocessing accomplished an improvement of the mean voxel CoV of the amide pool and the aliphatic rNOE pool amplitudes of less than 5% and 3%, respectively. These postprocessing steps are: motion correction with interpolation of the motion of low-signal offsets (1) using the amide pool frequency offset image as reference (2), normalization of the Z-spectrum using the outermost saturated measurements (3), B 0 correction of the Z-spectrum with moderate spline smoothing (4), denoising using principal component analysis preserving the 11 highest intensity components (5), B 1 + correction using a linear fit (6) and Lorentzian fitting using the five-pool fit model (7). With the optimized postprocessing pipeline, a significant age effect in the amide pool can be detected. Additionally, for the first time, an aliphatic rNOE contrast between subjects with Parkinson's disease and age-matched healthy controls in the substantia nigra is detected. We propose an optimized postprocessing pipeline for CEST multipool evaluation. It is shown that by the use of these seven "tricks", the reproducibility and, thus, the statistical power of a CEST measurement, can be greatly improved and subtle changes can be detected.

Clinically compatible subject-specific dynamic parallel transmit pulse design for homogeneous fat saturation and water-excitation at 7T: Proof-of-concept for CEST MRI of the brain.

PURPOSE: To evaluate the benefits and challenges of dynamic parallel transmit (pTx) pulses for fat saturation (FS) and water-excitation (WE), in the context of CEST MRI. METHODS: "Universal" kT -points (for FS) and spiral non-selective (for WE) trajectories were optimized offline for flip angle (FA) homogeneity. Routines to optimize the pulse shape online, based on the subject's fields maps, were implemented (target FA of 110°/0° for FS, 0°/5° for WE at fat/water frequencies). The pulses were inserted in a CEST sequence with a pTx readout. The different fat suppression schemes and their effects on CEST contrasts were compared in 12 volunteers at 7T. RESULTS: With a 25%-shorter pulse duration, pTx FS largely improved the FA homogeneity (root-mean-square-error (RMSE) = 12.3° vs. 53.4° with circularly-polarized mode, at the fat frequency). However, the spectral selectivity was degraded mainly in the cerebellum and close to the sinuses (RMSE = 5.8° vs. 0.2° at the water frequency). Similarly, pTx WE showed a trade-off between FA homogeneity and spectral selectivity compared to pTx non-selective pulses (RMSE = 0.9° and 1.1° at the fat and water frequencies, vs. 4.6° and 0.5°). In the brain, CEST metrics were reduced by up to 31.9% at -3.3 ppm with pTx FS, suggesting a mitigated lipid-induced bias. CONCLUSION: This clinically compatible implementation of dynamic pTx pulses improved the fat suppression homogeneity at 7T taking into account the subject-specific B0 heterogeneities online. This study highlights the lipid-induced biases on the CEST z-spectrum. The results are promising for body applications where B0 heterogeneities and fat are more substantial.