Rudolf Stollberger

Purpose: To evaluate the repeatability of an extended multiparametric 7 T MRI protocol for voxel‐wise tissue characterization combining morphological, CEST, QSM, QTI, and Sodium contrasts. Methods: A repeatability study was performed in 12 volunteers without diagnosed neurological disease on a 7 T MRI system, using a comprehensive acquisition protocol with a combined acquisition time of 45:24 min, from which 45 contrast maps were derived. Quantitative repeatability was assessed using region‐based and voxel‐wise analyses. Precision and reliability were evaluated using the coefficient of variation (CV), repeatability coefficient (%RC), and intraclass correlation coefficient (ICC). Voxel‐wise agreement between scan–rescan images was assessed using Pearson correlation coefficients. Results: Across contrasts spanning morphological, CEST, QSM, QTI, and ²³ Na imaging, %RC was below 20% for 20 contrasts, with mean CV below 5% for most. Repeatability was highest for MP2RAGE T ₁ maps and QTI MD (CV ≈ 1%–2%; ICC up to 0.86) and lowest for ²³ Na imaging (ICC < 0.6). CEST contrasts were highly repeatable at low saturation power but more variable at higher power (CV up to ≈8%). QSM contrasts showed moderate ICC (0.46–0.82). Voxel‐wise correlations exceeded r = 0.8 for most contrasts, confirming preserved spatial patterns across repeated scans. Conclusion: Multiparametric 7 T MRI enables reproducible voxel‐wise characterization of brain tissue across a wide range of contrasts. Despite variability in specific contrasts, the overall high repeatability and strong voxel‐wise agreement support the feasibility of voxel‐wise imaging approaches for quantitative brain imaging and provide a foundation for future applications in clinical research and neuroscience.

Purpose: This work proposes a method for the simultaneous estimation of the exchange‐dependent relaxation rate and the longitudinal relaxation time from a single acquisition. Methods: A novel acquisition scheme was developed that combines CEST saturation with an inversion pulse and a Look‐Locker readout to capture the magnetization evolution starting from the inverse transient Z‐spectrum. The corresponding signal model, derived from the Bloch‐McConnell equations, describes both the transient Z‐spectrum and the Look‐Locker dynamics. A model‐based reconstruction approach is employed to jointly estimate and . The proposed method was validated using a numerical phantom and benchmarked against conventional CEST and Look‐Locker mapping in a phantom and in vivo on a clinical 3T scanner. Results: The joint estimation approach demonstrated strong agreement with ground truth and conventional methods across a wide range of and CEST parameters. The acquisition time was reduced by 20%–30% compared to standard CEST protocols, while providing a higher signal‐to‐noise ratio (SNR) in parameter maps. Conclusion: The proposed technique enables robust and efficient simultaneous quantification of CEST and in a single acquisition. It improves parameter map quality and reduces scan time, making it suitable for both phantom and in vivo imaging across a wide range of physiological conditions.

Purpose: Optimal control (OC) chemical exchange saturation transfer (CEST) pulse design for singular pulses that can be used flexibly and robustly with high saturation at different duty cycles, saturation durations, and magnetic field strengths. Theory and Methods: An OC framework was developed to design a single‐pulse shape that can be flexibly applied for arbitrary pulse train parameters and outperform typically used CEST saturation pulse shapes. The pulse design was developed primarily with a continuous‐wave (CW) spectrum as the optimization target, but can be easily adapted to specific scenarios. The generalized OC pulse was evaluated through simulations, a phantom, and in vivo measurements on a 3 T clinical scanner. Performance was assessed in terms of contrast, robustness to field inhomogeneities, and resilience against artifacts such as Rabi oscillations and sidebands, compared to established saturation techniques. Results: Investigations showed that the generalized OC pulse achieved a contrast matching CW saturation and also functioned well under field inhomogeneities. Low‐pass filtering of the optimized pulse shape effectively suppressed artifacts outside the initial optimization frequency range, enabling generalization across different field strengths. Phantom experiments consistently showed higher contrast than Gaussian, Fermi, and adiabatic spin‐lock (aSL) pulses for various CEST agents covering most clinically relevant regimes. In vivo imaging demonstrated substantially enhanced CEST contrast for both creatine/phosphocreatine in muscle and amide proton transfer (APT) in the brain compared to Gaussian saturation. Conclusion: The generalized OC pulse provides a robust and flexible alternative to conventional CEST saturation strategies. Its integration into the open‐source Pulseq‐CEST framework supports simple reproducibility and a vendor‐independent implementation.

Purpose: This work proposes a method for the simultaneous estimation of the exchange-dependent relaxation rate Rex and the longitudinal relaxation time T1 from a single acquisition. Methods: A novel acquisition scheme was developed that combines CEST saturation with an inversion pulse and a Look-Locker readout to capture the magnetization evolution starting from the inverse transient Z-spectrum. The corresponding signal model, derived from the Bloch-McConnell equations, describes both the transient Z-spectrum and the Look-Locker dynamics. A model-based reconstruction approach is employed to jointly estimate Rex and T1. The proposed method was validated using a numerical phantom and benchmarked against conventional CEST and Look-Locker T1 mapping in phantom and in vivo on a clinical 3T scanner. Results: The joint estimation approach demonstrated strong agreement with ground truth and conventional methods across a wide range of T1 and CEST parameters. The acquisition time was reduced by 20-30% compared to standard CEST protocols, while providing higher signal-to-noise ratio (SNR) in parameter maps. Conclusion: The proposed technique enables robust and efficient simultaneous quantification of CEST Rex and T1 in a single acquisition. It improves parameter map quality and reduces scan time, making it suitable for both phantom and in vivo imaging across a wide range of physiological conditions.

Purpose: Optimal Control (OC) CEST pulse design for singular pulses that can be used flexibly and robustly with high saturation at different duty cycles, saturation durations and magnetic field strengths. Theory and Methods: An OC framework was developed to design a single pulse shape that can be flexibly applied for arbitrary pulse train parameters and outperform typically used CEST saturation pulses shapes. The pulse design was developed primarily with a continuous wave spectrum (CW) as the optimization target, but can be easily adapted to specific scenarios. The generalized OC pulse was evaluated through simulations, phantom, and in vivo measurements on a 3 T clinical scanner. Performance was assessed in terms of contrast, robustness to field inhomogeneities, and resilience against artifacts such as Rabi oscillations and sidebands, compared to established saturation techniques. Results: Investigations showed that the generalized OC pulse achieved a contrast matching CW saturation and also functioned well under field inhomogeneities. Low-pass filtering of the optimized pulse shape effectively suppressed artifacts outside the initial optimization frequency range, enabling generalization across different field strengths. Phantom experiments consistently showed higher contrast than Gaussian, Fermi, and adiabatic spin-lock pulses for various CEST agents covering most clinically relevant regimes. In vivo imaging demonstrated substantially enhanced CEST contrast for both creatine/phosphocreatine in muscle and Amide Proton Transfer (APT) in brain compared to Gaussian saturation. Conclusion: The generalized OC pulse provides a robust and flexible alternative to conventional CEST saturation strategies. Its integration into the open-source Pulseq-CEST framework supports simple reproducibility and a vendor-independent implementation.

Purpose: The complex signal decay during the transient FLASH MRI readout can lead to artifacts in magnitude and phase images. We show that target‐driven optimization of individual RF flip angles and phases can realize near‐ideal signal behavior and mitigate artifacts.Methods: The differentiable end‐to‐end optimization framework MR‐zero is used to optimize RF trains of the FLASH sequence. We focus herein on minimizing deviations from the ideally spoiled signal by using a mono‐exponential Look–Locker target. We first obtain the transient FLASH signal decay substructure, and then minimize the deviation to the Look–Locker decay by optimizing the individual (i) flip angles, (ii) RF phases, and (iii) flip angles and RF phases. Comparison between measurement and simulation is performed using Pulseq in 1D and 2D.Results: We were able to reproduce the complex substructure of the transient FLASH signal decay. All three optimization objectives can bring the real FLASH signal closer to the ideal case, with best results when both flip angles and RF phases are adjusted jointly. This solution outperformed all tested conventional quadratic RF cyclings in terms of (i) matching the Look–Locker target signal, (ii) phase stability, (iii) point spread functions ideality, (iv) robustness against parameter changes, and (v) magnitude and phase image quality. Other target functions for the signal could as well be realized, yet their response is not as general as for the Look–Locker target and needs to be optimized for a specific context.Conclusion: Individual flip angle and RF phase optimization improves the transient signal decay of FLASH MRI sequences.

Purpose: To employ optimal control for the numerical design of Chemical Exchange Saturation Transfer (CEST) saturation pulses to maximize contrast and stability against 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 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.

PurposeIn 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 MethodsThe 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.ResultsThe 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.ConclusionThe 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.