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In fibroglandular breast tissue, conventional dynamic contrast-enhanced MR-mammography is known to be affected by water content changes during the menstrual cycle. Likewise, amide proton transfer (APT) chemical exchange saturation transfer (CEST)-MRI might be inherently prone to the menstrual cycle, as CEST signals are indirectly detected via the water signal. The purpose of this study was to investigate the influence of the menstrual cycle on APT CEST-MRI in fibroglandular breast tissue.Ten healthy premenopausal women (19-34 years) were included in this IRB approved prospective study and examined twice during their menstrual cycle. Examination one and two were performed during the first half (day 2-8) and the second half (day 15-21) of the menstrual cycle, respectively. As a reference for the APT signal in malignant breast tumor tissue, previously reported data of nine breast cancer patients were included in this study. CEST-MRI (BThe APT signal showed no significant difference in the fibroglandular breast tissue of healthy premenopausal volunteers throughout the menstrual cycle (p = 1.00) (examination 1 vs. examination 2: mean and standard deviation = 3.24 ± 0.68%Hz vs. 3.30 ± 0.73%Hz, median and IQR = 3.36%Hz and 0.87%Hz vs. 3.38%Hz and 0.71%Hz).The present study provides an important basis for the clinical application of APT CEST-MRI as an additional contrast mechanism in MR-mammography, as menstrual cycle-related APT signal fluctuations seem to be negligible compared to the APT signal increase in breast cancer tissue.

Purpose A phantom is presented in this study that allows for an experimental evaluation of QSM reconstruction algorithms. The phantom contains susceptibility producing particles with dia- and paramagnetic properties embedded in an MRI visible medium and is suitable to assess the performance of algorithms that attempt to separate isotropic dia- and paramagnetic susceptibility at the sub-voxel level. Methods The phantom was built from calcium carbonate (diamagnetic) and tungsten carbide particles (paramagnetic) embedded in gelatin and surrounded by agarose gel. Different mass fractions and mixing ratios of both susceptibility sources were used. Gradient echo data were acquired at 1.5 T, 3 T and 7 T. Susceptibility maps were calculated using the MEDI toolbox and relaxation rates Δ R 2 ∗ were determined using exponential fitting. Results Relaxation rates as well as susceptibility values generally coincide with the theoretical values for particles fulfilling the assumptions of the the static dephasing regime with stronger deviations for relaxation rates at higher field strength and for high susceptibility values. MRI raw data are available for free academic use as supplementary material. Conclusions In this study, a susceptibility phantom is presented that might find its application in the development and quantitative validation of current and future QSM reconstruction algorithms which aim to separate the influence of isotropic dia- and paramagnetic substructure in quantitative susceptibility mapping.

Purpose To develop a framework for 3D sodium (23 Na) MR fingerprinting (MRF), based on irreducible spherical tensor operators with tailored flip angle (FA) pattern and time-efficient data acquisition for simultaneous quantification of T1 , T 2 l ∗ , T 2 s ∗ , and T 2 ∗ in addition to ΔB0 . Methods 23 Na-MRF was implemented in a 3D sequence and irreducible spherical tensor operators were exploited in the simulations. Furthermore, the Cramer Rao lower bound was used to optimize the flip angle pattern. A combination of single and double echo readouts was implemented to increase the readout efficiency. A study was conducted to compare results in a multicompartment phantom acquired with MRF and reference methods. Finally, the relaxation times in the human brain were measured in four healthy volunteers. Results Phantom experiments revealed a mean difference of 1.0% between relaxation times acquired with MRF and results determined with the reference methods. Simultaneous quantification of the longitudinal and transverse relaxation times in the human brain was possible within 32 min using 3D 23 Na-MRF with a nominal resolution of (5 mm)3 . In vivo measurements in four volunteers yielded average relaxation times of: T1,brain = (35.0 ± 3.2) ms, T 2 l , brain ∗ = (29.3 ± 3.8) ms and T 2 s , brain ∗ = (5.5 ± 1.3) ms in brain tissue, whereas T1,CSF = (61.9 ± 2.8) ms and T 2 , CSF ∗ = (46.3 ± 4.5) ms was found in cerebrospinal fluid. Conclusion The feasibility of in vivo 3D relaxometric sodium mapping within roughly ½ h is demonstrated using MRF in the human brain, moving sodium relaxometric mapping toward clinically relevant measurement times.

Purpose Hybrid MRI-linear accelerator systems (MR-linacs) allow for the incorporation of MR images with high soft-tissue contrast into the radiation therapy procedure prior to, during, or post irradiation. This allows not only for the optimization of the treatment planning, but also for real-time monitoring of the tumor position using cine MRI, from which intrafractional motion can be compensated. Fast imaging and accurate tumor tracking are crucial for effective compensation. This study investigates the application of cine MRI with a radial acquisition scheme on a low-field MR-linac to accelerate the acquisition rate and evaluates the effect on tracking accuracy. Methods An MR sequence using tiny golden-angle radial k-space sampling was developed and applied to cine imaging on patients with liver tumors on a 0.35 T MR-linac. Tumor tracking was assessed for accuracy and stability from the cine images with increasing k-space undersampling factors. Tracking was achieved using two different auto-segmentation algorithms: a deformable image registration B-spline similar to that implemented on the MR-linac and a convolutional neural network approach known as U-Net. Results Radial imaging allows for increased temporal resolution with reliable tumor tracking, although tracking robustness decreases as temporal resolution increases. Additional acquisition-based artifacts can be avoided by reducing the angle increment using tiny golden-angles. The U-net algorithm was found to have superior auto-segmentation metrics compared to B-spline. U-net was able to track two well-defined tumors, imaged with just 30 spokes per image (10.6 frames per second), with an average Dice coefficient ≥ 83%, Hausdorff distance ≤ 1.4 pixel, and mean contour distance ≤ 0.5 pixel. Conclusions Radial acquisitions are commonplace in dynamic imaging; however, in MR-guided radiotherapy, robust tumor tracking is also required. This study demonstrates the in vivo feasibility of tumor tracking from radially acquired images on a low-field MR-linac. Radial imaging allows for decreased image acquisition times while maintaining robust tracking. The U-net algorithm can track a tumor with higher accuracy in images with undersampling artifacts than a conventional deformable B-spline algorithm and is a promising tool for tracking in MR-guided radiation therapy.

Purpose Tissue microstructure can influence quantitative magnetic resonance imaging such as relaxation rate measurements. Consequently, relaxation rate mapping can provide useful information on tissue microstructure. In this work, the theory on relaxation mechanisms of the change of the relaxation rate ∆R2⁎ in the presence of spherical susceptibility sources in a spin bearing medium is validated in simulations and phantom experiments for the coexistence of two species of susceptibility sources. Methods The influence of coexisting spherical perturbers with magnetic susceptibilitys of different signs was evaluated in Monte Carlo simulations including diffusion effects in the surrounding medium. Simulations were compared with relaxometry measurements at 1.5 Tesla and at 3 Tesla. The phantoms used to validate the simulations were built from agarose gel containing calcium carbonate and tungsten carbide particles of different size and concentration. Results The Monte Carlo simulations showed, that the change in relaxation rate only depends on the overall amount of susceptibility producing structures in the simulation volume and no difference was found, if mixtures of positive and negative particles were simulated. Phantom measurements within the static dephasing regime showed linear additivity of the effects from positive and negative susceptibility sources that were present within the same voxel. Conclusions In summary, both the simulations and the phantom measurements showed that changes in the relaxation rate ΔR2⁎ add up linearly for spherical particles with different susceptibilities within the same voxel if the conditions for the static dephasing regime are fulfilled. If particles with different susceptibilities have both different sizes and violate the conditions of the static dephasing regime, effects on relaxation rates might no longer be linear.

PURPOSE To evaluate the feasibility of 23 Na MR fingerprinting (MRF) for simultaneous quantification of T1 , T2l∗ , T2s∗ , T2∗ in addition to ΔB0 . METHODS A framework for sodium relaxometry using MRF at 7T was developed, allowing simultaneous measurement of relaxation times and inhomogeneities in the static field. The technique distinguishes between bi- and monoexponential transverse relaxation and was validated in simulations with respect to the ground truth. In phantom measurements, a resolution of 2 × 2 × 12 mm3 was achieved within 1 h acquisition time, and the resulting parameter maps were compared to results from reference methods. Relaxation times in five healthy volunteers were measured with a resolution of 4 × 4 × 12 mm3 . RESULTS Phantom experiments revealed an agreement between the relaxation times obtained via 23 Na-MRF and the reference methods. In white matter, a longitudinal relaxation constant of T1 = 38.9 ± 4.8 ms was found, while values of T2l∗ = 29.2 ± 4.9 ms and T2s∗ = 4.7 ± 1.2 ms were found for the long and short component of the transverse relaxation. In cerebrospinal fluid, T1 was 67.7 ± 6.3 ms and T2∗ = 41.5 ± 3.4 ms. CONCLUSION This work demonstrates the feasibility of 23 Na-MRF for relaxometry in sodium MRI in both phantom and in vivo studies. Simultaneous quantification of T1 , T2l∗ , T2s∗ , T2∗ and ΔB0 was possible within a 1 h measurement time.

Purpose: In vivo 31 P MRSI enables noninvasive mapping of absolute pH values via the pH-dependent chemical shifts of inorganic phosphates (Pi ). A particular challenge is the quantification of extracellular Pi with low SNR in vivo. The purpose of this study was to demonstrate feasibility of assessing both intra- and extracellular pH across the whole human brain via volumetric 31 P MRSI at 7T.Methods: 3D 31 P MRSI data sets of the brain were acquired from three healthy volunteers and three glioma patients. Low-rank denoising was applied to enhance the SNR of 31 P MRSI data sets that enables detection of extracellular Pi at high spatial resolutions. A robust two-compartment quantification model for intra- and extracellular Pi signals was implemented.Results: In particular low-rank denoising enabled volumetric mapping of intra- and extracellular pH in the human brain with voxel sizes of 5.7 mL. The average intra- and extracellular pH measured in white matter of healthy volunteers were 7.00 ± 0.00 and 7.33 ± 0.03, respectively. In tumor tissue of glioma patients, both the average intra- and extracellular pH increased to 7.12 ± 0.01 and 7.44 ± 0.01, respectively, compared to normal appearing tissue.Conclusion: Mapping of pH values via 31 P MRSI at 7T using the proposed two-compartment quantification model improves reliability of pH values obtained in vivo, and has the potential to provide novel insights into the pH heterogeneity of various tissues.

Purpose To investigate velocity encoded and velocity compensated variants of multi-spoke RF pulses that can be used for flip-angle homogenization at ultra-high fields (UHF). Attention is paid to the velocity encoding for each individual spoke pulse and to displacement artifacts that arise in Fourier transform imaging in the presence of flow. Theory and methods A gradient waveform design for multi-spoke excitation providing an algorithm for minimal TE was proposed that allows two different encodings. Such schemes were compared to an encoding approach that applies an established scheme to multi-spoke excitations. The impact on image quality and quantitative velocity maps was evaluated in phantoms using single- and two-spoke excitations. Additional validation measurements were obtained in-vivo at 7 T. Results Phantom experiments showed that keeping the first gradient moment constant for all k-space lines eliminates any displacements in phase-encoding and slice-selection direction for all spoke pulses but leads to artifacts for non-zero velocity components along readout direction. Introducing variable but well-defined first gradient moments in the phase-encoding direction creates displacements along the velocity vector and thus minimizes velocity-induced geometrical distortions. Phase-resolved mean volume flow in the ascending and descending aorta obtained from two-spoke excitation showed excellent agreement with single-spoke excitation over the cardiac cycle (mean difference 0.8 ± 16.2 ml/s). Conclusions The use of single- and multi-spoke RF pulses for flow quantification at 7 T with controlled displacement artifacts has been successfully demonstrated. The presented techniques form the basis for correct velocity quantification and compensation not only for conventional but also for multi-spoke RF pulses allowing in-plane B1+ homogenization using parallel transmission at UHF.

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.

In principle, non-invasive mapping of the intracellular pH (pHCompensation of the concomitant effects was achieved by a ratiometric approach (i.e. the ratio of one CEST signal at different BIn porcine brain lysates, measurement of pH was feasible over a broad range of physiologically relevant pH values of 6.2 to 8.0, while being independent of changes in concentration. A median pHThe presented method enables non-invasive mapping of absolute pH

In chemical exchange saturation transfer (CEST) MRI, motion correction is compromised by the drastically changing image contrast at different frequency offsets, particularly at the direct water saturation. In this study, a simple extension for conventional image registration algorithms is proposed, enabling robust and accurate motion correction of CEST-MRI data. The proposed method uses weighted averaging of motion parameters from a conventional rigid image registration to identify and mitigate erroneously misaligned images. Functionality of the proposed method was verified by ground truth datasets generated from 10 three-dimensional in vivo measurements at 3 T with simulated realistic random rigid motion patterns and noise. Performance was assessed using two different criteria: the maximum image misalignment as a measure for the robustness against direct water saturation artifacts, and the spectral error as a measure of the overall accuracy. For both criteria, the proposed method achieved the best scores compared with two motion-correction algorithms specifically developed to handle the varying contrasts in CEST-MRI. Compared with a straightforward linear interpolation of the motion parameters at frequency offsets close to the direct water saturation, the proposed method offers better performance in the absence of artifacts. The proposed method for motion correction in CEST-MRI allows identification and mitigation of direct water saturation artifacts that occur with conventional image registration algorithms. The resulting improved robustness and accuracy enable reliable motion correction, which is particularly crucial for an automated and carefree evaluation of spectral CEST-MRI data, e.g., for large patient cohorts or in clinical routines.

Purpose The value of relaxation-compensated amide proton transfer (APT) and relayed nuclear Overhauser effect (rNOE) chemical exchange saturation transfer (CEST)-MRI has already been demonstrated in various neuro-oncological clinical applications. Recently, we translated the approach from 7T to a clinically relevant magnetic field strength of 3T. However, the overall acquisition time was still too long for a broad application in the clinical setting. The aim of this study was to establish a shorter acquisition protocol whilst maintaining the contrast behavior and reproducibility. Methods Ten patients with glioblastoma were examined using the previous state-of-the-art acquisition protocol at 3T. The acquired spectral data were retrospectively reduced to find the minimal amount of required information that allows obtaining the same contrast behavior. To further reduce the acquisition time, also the image readout was accelerated and the pre-saturation parameters were further optimized. Results In total, the overall acquisition time could be reduced from 19 min to under 7 min. One key finding was that, when evaluated by the relaxation-compensated inverse metric, a contrast correction for B1 -field inhomogeneities at 3T can also be achieved reliably with CEST data at only one B1 value. In contrast, a 1-point B1 -correction was not sufficient for the common linear difference evaluation. The reproducibility of the new clinical routine acquisition protocol was similar to the previous state-of-the-art protocol with limits of agreement below 20%. Conclusions The substantial reduction in acquisition time by about 64% now allows the application of 3D relaxation-compensated APT and rNOE CEST-MRI for examinations of the human brain at 3T in clinical routine.

Purpose: The application of amide proton transfer (APT) CEST MRI for diagnosis of breast cancer is of emerging interest. However, APT imaging in the human breast is affected by the ubiquitous fat signal preventing a straightforward application of existing acquisition protocols. Although the spectral region of the APT signal does not coincide with fat resonances, the fat signal leads to an incorrect normalization of the Z‐spectrum, and therefore to distorted APT effects. In this study, we propose a novel normalization for APT‐CEST MRI that corrects for fat signal–induced artifacts in the postprocessing without the need for application of fat saturation schemes or water–fat separation approaches. Methods The novel normalization uses the residual signal at the spectral position of the direct water saturation to estimate the fat contribution. A comprehensive theoretical description of the normalization for an arbitrary phase relation of the water and fat signal is provided. Functionality and applicability of the proposed normalization was demonstrated by in vitro and in vivo experiments. Results In vitro, an underestimation of the conventional APT contrast of approximately −1.2% per 1% fat fraction was observed. The novel normalization yielded an APT contrast independent of the fat contribution, which was also independent of the water‐fat phase relation. This allowed APT imaging in patients with mamma carcinoma corrected for fat signal contribution, field inhomogeneities, spillover dilution, and water relaxation effects. Conclusion The proposed normalization increases the specificity of APT imaging in tissues with varying fat content and represents a time‐efficient and specific absorption rate–efficient alternative to fat saturation and water–fat separation approaches.

Purpose To quantify the tissue sodium concentration (TSC) in cardiac 23 Na MRI. To evaluate the influence of different correction methods on the measured myocardial TSC. Methods 23 Na MRI of four healthy subjects was conducted at a whole-body 7T MRI system using an oval-shaped 23 Na birdcage coil. Data acquisition was performed with a density-adapted 3D radial pulse sequence using a golden angle projection scheme. 1 H MRI data were acquired at a 3T MRI system to generate a myocardial mask. Retrospective cardiac and respiratory gating were used to reconstruct 23 Na MRI data in the diastolic phase and exhaled state. B0 and B1 inhomogeneity and partial volume (PV) effects were corrected. Relaxation times and TSC of ex vivo blood samples and calf muscle were determined. These values were used in the PV correction to estimate myocardial TSC, which was compared with the measured TSC of calf muscle. Results Without any correction the measured myocardial TSC was (54 ± 5) mM. The applied correction methods reduced these values by (48 ± 5)% to (29 ± 3) mM, where PV correction had the largest effect (reduction of (34 ± 1)%). Respiratory and cardiac motion gating decreased the concentrations by (11 ± 1)%. With the applied setup, the corrections of B0 and B1 inhomogeneity (reduction of (3 ± 2)%) had negligible influences on TSC values. The resulting myocardial TSC was approximately 1.4-fold higher than the measured TSC of calf muscle tissue of the same healthy subjects ((20 ± 3) mM). Conclusion For quantitative human cardiac 23 Na MRI several corrections are needed and ranked for our setup: PV correction, respiratory and cardiac gating, correction for B1 inhomogeneity effects.

BACKGROUND Rapid volumetric imaging protocols could better utilize limited scanner resources. PURPOSE To develop and validate an optimized 6-minute high-resolution volumetric brain MRI examination using Wave-CAIPI encoding. STUDY TYPE Prospective. POPULATION/SUBJECTS Ten healthy subjects and 20 patients with a variety of intracranial pathologies. FIELD STRENGTH/SEQUENCE At 3 T, MPRAGE, T2 -weighted SPACE, SPACE FLAIR, and SWI were acquired at 9-fold acceleration using Wave-CAIPI and for comparison at 2-4-fold acceleration using conventional GRAPPA. ASSESSMENT Extensive simulations were performed to optimize the Wave-CAIPI protocol and minimize both g-factor noise amplification and potential T1 /T2 blurring artifacts. Moreover, refinements in the autocalibrated reconstruction of Wave-CAIPI were developed to ensure high-quality reconstructions in the presence of gradient imperfections. In a randomized and blinded fashion, three neuroradiologists assessed the diagnostic quality of the optimized 6-minute Wave-CAIPI exam and compared it to the roughly 3× slower GRAPPA accelerated protocol using both an individual and head-to-head analysis. STATISTICAL TEST A noninferiority test was used to test whether the diagnostic quality of Wave-CAIPI was noninferior to the GRAPPA acquisition, with a 15% noninferiority margin. RESULTS Among all sequences, Wave-CAIPI achieved negligible g-factor noise amplification (gavg ≤ 1.04) and burring artifacts from T1 /T2 relaxation. Improvements of our autocalibration approach for gradient imperfections enabled increased robustness to gradient mixing imperfections in tilted-field of view (FOV) prescriptions as well as variations in gradient and analog-to-digital converter (ADC) sampling rates. In the clinical evaluation, Wave-CAIPI achieved similar mean scores when compared with GRAPPA (MPRAGE: OW = 4.03, OG = 3.97; T2 w SPACE: OW = 4.00, OG = 4.00; SPACE FLAIR: OW = 3.97, OG = 3.97; SWI: OW = 3.93, OG = 3.83) and was statistically noninferior (N = 30, P

Magnetic resonance imaging and spectroscopic techniques are widely used in humans both for clinical diagnostic applications and in basic research areas such as cognitive neuroimaging. In recent years, new human MR systems have become available operating at static magnetic fields of 7 T or higher (≥300 MHz proton frequency). Imaging human-sized objects at such high frequencies presents several challenges including non-uniform radiofrequency fields, enhanced susceptibility artifacts, and higher radiofrequency energy deposition in the tissue. On the other side of the scale are gains in signal-to-noise or contrast-to-noise ratio that allow finer structures to be visualized and smaller physiological effects to be detected. This review presents an overview of some of the latest methodological developments in human ultra-high field MRI/MRS as well as associated clinical and scientific applications. Emphasis is given to techniques that particularly benefit from the changing physical characteristics at high magnetic fields, including susceptibility-weighted imaging and phase-contrast techniques, imaging with X-nuclei, MR spectroscopy, CEST imaging, as well as functional MRI. In addition, more general methodological developments such as parallel transmission and motion correction will be discussed that are required to leverage the full potential of higher magnetic fields, and an overview of relevant physiological considerations of human high magnetic field exposure is provided.

To develop a framework for 3D sodium (Phantom experiments revealed a mean difference of 1.0% between relaxation times acquired with MRF and results determined with the reference methods. Simultaneous quantification of the longitudinal and transverse relaxation times in the human brain was possible within 32 min using 3DThe feasibility of in vivo 3D relaxometric sodium mapping within roughly ½ h is demonstrated using MRF in the human brain, moving sodium relaxometric mapping toward clinically relevant measurement times.

Purpose Water exchange between the intracellular and extracellular space can be measured using apparent exchange rate (AXR) imaging. The aim of this study was to investigate the relationship between the measured AXR and the geometry of diffusion restrictions, membrane permeability, and the real exchange rate, as well as to explore the applicability of AXR for typical human measurement settings. Methods The AXR measurements and the underlying exchange rates were simulated using the Monte Carlo method with different geometries, size distributions, packing densities, and a broad range of membrane permeabilities. Furthermore, the influence of SNR and sequence parameters was analyzed. Results The estimated AXR values correspond to the simulated values and show the expected proportionality to membrane permeability, except for fast exchange (ie, AXR>20‐30s‐1) and small packing densities. Moreover, it was found that the duration of the filter gradient must be shorter than 2·AXR‐1. In cell size and permeability distributions, AXR depends on the average surface‐to‐volume ratio, permeability, and the packing density. Finally, AXR can be reliably determined in the presence of orientation dispersion in axon‐like structures with sufficient gradient sampling (ie, 30 gradient directions). Conclusion Currently used experimental settings for in vivo human measurements are well suited for determining AXR, with the exception of single‐voxel analysis, due to limited SNR. The detection of changes in membrane permeability in diseased tissue is nonetheless challenging because of the AXR dependence on further factors, such as packing density and geometry, which cannot be disentangled without further knowledge of the underlying cell structure.

We propose Nonlinear Dipole Inversion (NDI) for high-quality Quantitative Susceptibility Mapping (QSM) without regularization tuning, while matching the image quality of state-of-the-art reconstruction techniques. In addition to avoiding over-smoothing that these techniques often suffer from, we also obviate the need for parameter selection. NDI is flexible enough to allow for reconstruction from an arbitrary number of head orientations and outperforms COSMOS even when using as few as 1-direction data. This is made possible by a nonlinear forward-model that uses the magnitude as an effective prior, for which we derived a simple gradient descent update rule. We synergistically combine this physics-model with a Variational Network (VN) to leverage the power of deep learning in the VaNDI algorithm. This technique adopts the simple gradient descent rule from NDI and learns the network parameters during training, hence requires no additional parameter tuning. Further, we evaluate NDI at 7 T using highly accelerated Wave-CAIPI acquisitions at 0.5 mm isotropic resolution and demonstrate high-quality QSM from as few as 2-direction data., National Institutes of Health (U.S.) (Grants R01EB020613, R01EB019437, P41EB015896, U01EB025162, S10RR023401, S10RR019307, S10RR019254, S10RR023043))

Purpose Dynamic glucose-enhanced (DGE)-MRI based on chemical exchange-sensitive MRI, that is, glucoCEST and gluco-chemical exchange-sensitive spin-lock (glucoCESL), is intrinsically prone to motion-induced artifacts because the final DGE contrast relies on the difference of images, which were acquired with a time gap of several mins. In this study, identification of different types of motion-induced artifacts led to the development of a 3D acquisition protocol for DGE examinations in the human brain at 7 T with improved robustness in the presence of subject motion. Methods DGE-MRI was realized by the chemical exchange-sensitive spin-lock approach based either on relaxation rate in the rotating frame (R1ρ )-weighted or quantitative R1ρ imaging. A 3D image readout was implemented at 7 T, enabling retrospective volumetric coregistration of the image series and quantification of subject motion. An examination of a healthy volunteer without administration of glucose allowed for the identification of isolated motion-induced artifacts. Results Even after coregistration, significant motion-induced artifacts remained in the DGE contrast based on R1ρ -weighted images. This is due to the spatially varying sensitivity of the coil and was found to be compensated by a quantitative R1ρ approach. The coregistered quantitative approach allowed the observation of a clear increase of the DGE contrast in a patient with glioblastoma, which did not correlate with subject motion. Conclusion The presented 3D acquisition protocol enables DGE-MRI examinations in the human brain with improved robustness against motion-induced artifacts. Correction of motion-induced artifacts is of high importance for DGE-MRI in clinical studies where an unambiguous assignment of contrast changes due to an actual change in local glucose concentration is a prerequisite.

Dual-frequency irradiation chemical exchange saturation transfer (dualCEST) allows imaging of endogenous bulk mobile proteins by selectively measuring the intramolecular spin diffusion. The resulting specificity to changes in the concentration, molecular size, and folding state of mobile proteins is of particular interest as a marker for neurodegenerative diseases and cancer. Until now, application of dualCEST in clinical trials was prevented by the inherently small signal-to-noise ratio and the resulting comparatively long examination time. In this study, we present an optimized acquisition protocol allowing 3D dualCEST-MRI examinations in a clinically relevant time frame. The optimization comprised the extension of the image readout to 3D, allowing a retrospective co-registration and application of denoising strategies. In addition, cosine-modulated dual-frequency presaturation pulses were implemented with a weighted acquisition scheme of the necessary frequency offsets. The optimization resulted in a signal-to-noise ratio gain by a factor of approximately 8. In particular, the application of denoising and the motion correction were the most crucial improvement steps. In vitro experiments verified the preservation of specificity of the dualCEST signal to proteins. Good-to-excellent intra-session and good inter-session repeatability was achieved, allowing reliable detection of relative signal differences of about 16% or higher. Applicability in a clinical setting was demonstrated by examining a patient with glioblastoma. The optimized acquisition protocol for dualCEST-MRI at 3 T enables selective imaging of endogenous bulk mobile proteins under clinically relevant conditions.

Tissue microstructure can influence quantitative magnetic resonance imaging such as relaxation rate measurements. Consequently, relaxation rate mapping can provide useful information on tissue microstructure. In this work, the theory on relaxation mechanisms of the change of the relaxation rate ∆RThe influence of coexisting spherical perturbers with magnetic susceptibilitys of different signs was evaluated in Monte Carlo simulations including diffusion effects in the surrounding medium. Simulations were compared with relaxometry measurements at 1.5 Tesla and at 3 Tesla. The phantoms used to validate the simulations were built from agarose gel containing calcium carbonate and tungsten carbide particles of different size and concentration.The Monte Carlo simulations showed, that the change in relaxation rate only depends on the overall amount of susceptibility producing structures in the simulation volume and no difference was found, if mixtures of positive and negative particles were simulated. Phantom measurements within the static dephasing regime showed linear additivity of the effects from positive and negative susceptibility sources that were present within the same voxel.In summary, both the simulations and the phantom measurements showed that changes in the relaxation rate ΔR

BACKGROUND Using lower refocusing flip angles in multi-echo turbo spin echo (ME-TSE) sequences at ultra-high magnetic field leads to non-monoexponential signal decay and overestimation of T2 values due to stimulated and secondary echoes. PURPOSE To investigate the feasibility of a fast and accurate reconstruction of quantitative T2 values using an ME-TSE sequence with reduced refocusing flip angles at 7 Tesla, a dictionary-based reconstruction method was developed and is presented in this work. STUDY TYPE Prospective. SUBJECTS Phantom measurements with relaxation phantom, four healthy volunteers. FIELD STRENGTH/SEQUENCE 7 Tesla MRI, multi-echo turbo spin echo (ME-TSE), spin echo (SE), and B1 mapping. ASSESSMENT Based on Bloch simulations and the extended phase graph model, signal decay curves were calculated to account for nonrectangular slice profile, B1 inhomogeneity, and reduced refocusing flip angles and stored in a dictionary. Data obtained with an ME-TSE sequence at 7 Tesla were matched to this dictionary to obtain T2 values. To compare the proposed method to reference T2 values, a spin echo sequence with different echo times was used. STATISTICAL TESTS Welch's t-test was used to compare T2 values in phantom measurements. RESULTS T2 values obtained with the proposed ME-TSE method coincided with the T2 values from the spin echo experiment in phantom measurements (P = 0.89 for 120° flip angle, P = 0.75 for 180° flip angle). Only for very low B1 transmit fields, a slight overestimation of T2 values was observed. In vivo measurements showed lower T2 values in gray matter (55 ± 2 millisecond) and white matter (39 ± 5 millisecond) compared with literature values of 3 Tesla data. DATA CONCLUSIONS The proposed dictionary-based ME-TSE approach provided accurate T2 values in short measurement time at 7 Tesla with low specific absorption rate burden due to the reduction of refocusing flip angles. Therefore, it can provide new opportunities in clinical high-field MRI to further improve radiographic diagnosis by using quantitative imaging. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1253-1262.

Background Chemical exchange saturation transfer (CEST) is a novel MRI technique applied to brain tumor patients. Purpose To investigate the anatomic location dependence of CEST MRI obtained at 7T and histopathological/molecular parameters in WHO IV° glioma patients. Study type Analytic prospective study. Population Twenty-one patients with newly diagnosed WHO IV° gliomas were studied prior to surgery; 11 healthy volunteers were investigated. Field strength/sequence Conventional MRI (contrast-enhanced, T2 w and diffusion-weighted imaging) at 3T and T2 w and CEST MRI at 7T was performed for patients and both patients and volunteers. Assessment Mean CEST signal intensities (nuclear-Overhauser-enhancement [NOE], amide-proton-transfer [APT], downfield NOE-suppressed APT [dns-APT]), ADC values, and histopathological/molecular parameters were evaluated with regard to hemisphere location and contact with the subventricular zone. CEST signal intensities of cerebral tissue of healthy volunteers were evaluated with regard to hemisphere discrimination. Statistical tests Spearman correlation, Mann-Whitney U-test, Wilcoxon signed-rank-test, Fisher's exact test, and area under the receiver operating curve. Results Maximum APT and dns-APT signal intensities were significantly different in right vs. left hemisphere gliomas (P = 0.037 and P = 0.007), but not in right vs. left hemisphere cerebral tissue of healthy subjects (P = 0.062-0.859). Mean ADC values were significantly decreased in right vs. left hemisphere gliomas (P = 0.044). Mean NOE signal intensity did not differ significantly between gliomas of either hemisphere (P = 0.820), but in case of subventricular zone contact (P = 0.047). A significant correlation was observed between APT and dns-APT and ADC signal intensities (rs = -0.627, P = 0.004 and rs = -0.534, P = 0.019), but not between NOE and ADC (rs = -0.341, P = 0.154). Histopathological/molecular parameters were not significantly different concerning the tumor location (P = 0.104-1.000, P = 0.286-0.696). Data conclusion APT, dns-APT, and ADC were inversely correlated and depended on the gliomas' hemisphere location. NOE showed significant dependence on subventricular zone contact. Location dependency of APT- and NOE-mediated CEST effects should be considered in clinical investigations of CEST MRI. Level of evidence 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:777-785.

PURPOSE To investigate and to reduce influences on the determination of the short and long apparent transverse relaxation times ( T2,s*, T2,l*) of 23 Na in vivo with respect to signal sampling. METHODS The accuracy of T2* determination was analyzed in simulations for five different sampling schemes. The influence of noise in the parameter fit was investigated for three different models. A dedicated sampling scheme was developed for brain parenchyma by numerically optimizing the parameter estimation. This scheme was compared in vivo to linear sampling at 7T. RESULTS For the considered sampling schemes, T2,s* / T2,l* exhibit an average bias of 3% / 4% with a variation of 25% / 15% based on simulations with previously published T2* values. The accuracy could be improved with the optimized sampling scheme by strongly averaging the earliest sample. A fitting model with constant noise floor can increase accuracy while additional fitting of a noise term is only beneficial in case of sampling until late echo time > 80 ms. T2* values in white matter were determined to be T2,s* = 5.1 ± 0.8 / 4.2 ± 0.4 ms and T2,l* = 35.7 ± 2.4 / 34.4 ± 1.5 ms using linear/optimized sampling. CONCLUSION Voxel-wise T2* determination of 23 Na is feasible in vivo. However, sampling and fitting methods have to be chosen carefully to retrieve accurate results. Magn Reson Med 80:571-584, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Purpose In biological tissue, phase contrast is determined by multiple substances such as iron, myelin or calcifications. Often, these substances occur co-located within the same measurement volume. However, quantitative susceptibility mapping can solely measure the average susceptibility per voxel. To provide new insight in disease progression and mechanisms in neurological diseases, where multiple processes such as demyelination and iron accumulation occur simultaneously in the same location, a separation of susceptibility sources is desirable to disentangle the underlying susceptibility proportions. Methods The basic concept of separating the susceptibility effects from sources with different sign within one voxel is to include information on relaxation rate Δ R 2 ∗ in the quantitative susceptibility mapping reconstruction pipeline. The presented reconstruction algorithm is implemented as a constrained minimization problem and solved using conjugate gradients. The algorithm is evaluated using a software phantom and validated in MRI measurements with a phantom containing mixtures of microscopic positive and negative susceptibility sources. Data from three multiple sclerosis patients are used to show in vivo feasibility. Results In numerical simulations, the feasibility of disentangling susceptibility sources within the same voxel was confirmed provided the critera of the static dephasing regime were fulfilled. In phantom experiments, the magnitude decay kernel, which is an essential reconstruction parameter of the algorithm, was determined to be D m = 194.5 T -1 s -1 ppm -1 , and susceptibility sources could be separated in MRI measurement data. Conclusions In conclusion, in this study a detailed description of the implementation of an algorithm for the separation of positive and negative susceptibility sources within the same volume element as well as its limitations is presented and validated quantitatively in both simulation and phantom experiments for the first time. An application to multiple sclerosis lesions shows promising results for in vivo usability.

PURPOSE To assess the reproducibility of 17 O MRI-based determination of the cerebral metabolic rate of oxygen consumption (CMRO2 ) in healthy volunteers. To assess the influence of image acquisition and reconstruction parameters on dynamic quantification of functional parameters such as CMRO2 . METHODS Dynamic 17 O MRI data were simulated and used to investigate influences of temporal resolution (Δt) and partial volume correction (PVC) on the determination of CMRO2 . Three healthy volunteers were examined in two separate examinations. In vivo 17 O MRI measurements were conducted with a nominal spatial resolution of (7.5 mm)3 using a density-adapted radial sequence with golden angle acquisition scheme. In each measurement, 4.0 ± 0.1 L of 70%-enriched 17 O gas were administered using a rebreathing system. Data were corrected with a PVC algorithm, and CMRO2 was determined in gray matter (GM) and white matter (WM) compartments using a three-phase metabolic model (baseline, 17 O inhalation, decay phase). RESULTS Comparison with the ground truth of simulations revealed improved CMRO2 determination after application of PVC and with Δt ≤ 2:00 min. Evaluation of in vivo data yields to CMRO2,GM = 2.31 ± 0.1 μmol/g/min and to CMRO2,WM = 0.69 ± 0.04 μmol/g/min with coefficients of variation (CoV) of 0.3-5.5% and 4.3-5.0% for intra-volunteer and inter-volunteer data, respectively. CONCLUSION This in vivo 17 O inhalation study demonstrated that the proposed experimental setup enables reproducible determination of CMRO2 in healthy volunteers. Magn Reson Med 79:2923-2934, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Purpose Conventional 31P chemical shift imaging is time-consuming and yields only limited spatial resolution. The purpose of this study was to demonstrate feasibility of 31P echo-planar spectroscopic imaging (EPSI) in vivo at 7T. Methods A 3D 31P EPSI sequence with trapezoidal-shaped gradient pulses was implemented on a 7T MR scanner. To increase spectral width with reduced demand on gradient performance, a multishot approach was chosen. Acquisition weighting and 31P–{1H} double resonance for nuclear Overhauser signal enhancement were applied to increase sensitivity. Results 3D 31P–{1H} EPSI data from model solution and from human calf muscle and brain were obtained from voxels with effective sizes of 4.1 to 16.2 cm3 in measurement times of approximately 10 min. Individual spectra showed well-resolved resonances of endogenous 31P-metabolites without artifacts. Volumetric high-resolution 31P-metabolite maps in vivo showed metabolic heterogeneity of different tissues. Conclusion In vivo 31P EPSI at 7T yields high-quality metabolic images. The proposed multishot EPSI technique reduces the measurement times for acquisition of volumetric high-resolution maps of 31P-metabolites or intracellular pH in human studies. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Functional parameters can be measured with the help of quantitative non-proton MRI where exact relaxometry parameters are needed. Investigation of $$T_{2}^{*}$$ is often biased by strong partial volume (PV) effects. Hence, in this work a PV correction algorithm approach was evaluated that uses iteratively adapted $$T_{2}^{*}$$ -values and high-resolution structural 1H data to determine transverse relaxation in non-proton MRI more accurately. Simulations, a phantom study and in vivo 23Na, 17O and 35Cl MRI measurements of five healthy volunteers were performed to evaluate the algorithm. $$T_{2}^{*}$$ values of grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF) were obtained. Data were acquired at B 0 = 7T with nominal spatial resolutions of (4–7 mm)3 using a density-adapted radial sequence. The resulting transverse relaxation times were used for quantification of 17O data. The conducted simulations and phantom study verified the correction performance of the algorithm. For in vivo measured $$T_{2}^{*}$$ values, the correction of PV effects leads to an increase in CSF and to a decrease in GM/WM (23Na MRI: long/short GM, WM $$T_{2}^{*}$$ : 36.4 ± 3.1/5.4 ± 0.2, 23.3 ± 2.6/3.5 ± 0.1 ms; 35Cl MRI: 8.9 ± 1.4/1.0 ± 0.4, 5.9 ± 0.3/0.4 ± 0.1 ms; 17O MRI: 2.5 ± 0.1, 2.8 ± 0.1 ms). Iteratively corrected in vivo $$T_{2}^{*}$$ values of the 17O study resulted in improved water content quantification. The proposed iterative algorithm for PV correction leads to more accurate $$T_{2}^{*}$$ values and, thus, can improve accuracy in quantitative non-proton MRI.

The purpose of this study is to improve direct phosphorus (31P) MR imaging. Therefore, 3D density-adapted radially-sampled balanced steady-state free precession (bSSFP) sequences were developed and an iterative approach exploiting additional anatomical information from hydrogen (1H) data was evaluated. Three healthy volunteers were examined at B0=7T in order to obtain the spatial distribution of the phosphocreatine (PCr) intensities in the human calf muscle with a nominal isotropic resolution of 10mm in an acquisition time of 10min. Three different bSSFP gradient schemes were investigated. The highest signal-to-noise ratio (SNR) was obtained for a scheme with two point-reflected density-adapted gradients. Furthermore, the conventional reconstruction based on a gridding algorithm was compared to an iterative method using an 1H MRI constraint in terms of a segmented binary mask, which comprises prior knowledge. The parameters of the iterative approach were optimized and evaluated by simulations featuring 31P MRI parameters. Thereby, partial volume effects as well as Gibbs ringing artifacts could be reduced. In conclusion, the iterative reconstruction of 31P bSSFP data using an 1H MRI constraint is appropriate for investigating regions where sharp tissue boundaries occur and leads to images that represent the real PCr distributions better than conventionally reconstructed images.

High image signal-to-noise ratio (SNR) is required to reliably detect the inherently small chemical exchange saturation transfer (CEST) effects in vivo. In this study, it was demonstrated that identifying spectral redundancies of CEST data by principal component analysis (PCA) in combination with an appropriate data-driven extraction of relevant information can be used for an effective and robust denoising of CEST spectra. The relationship between the number of relevant principal components and SNR was studied on fitted in vivo Z-spectra with artificially introduced noise. Three different data-driven criteria to automatically determine the optimal number of necessary components were investigated. In addition, these criteria facilitate straightforward assessment of data quality that could provide guidance for CEST MR protocols in terms of SNR. Insights were applied to achieve a robust denoising of highly sampled low power Z-spectra of the human brain at 3 and 7 T. The median criterion provided the best estimation for the optimal number of components consistently for all three investigated artificial noise levels. Application of the denoising technique to in vivo data revealed a considerable increase in image quality for the amide and rNOE contrast with a considerable SNR gain. At 7 T the denoising capability was quantified to be comparable or even superior to an averaging of six measurements. The proposed denoising algorithm enables an efficient and robust denoising of CEST data by combining PCA with appropriate data-driven truncation criteria. With this generally applicable technique at hand, small CEST effects can be reliably detected without the need for repeated measurements.

To evaluate the feasibility ofA framework for sodium relaxometry using MRF at 7T was developed, allowing simultaneous measurement of relaxation times and inhomogeneities in the static field. The technique distinguishes between bi- and monoexponential transverse relaxation and was validated in simulations with respect to the ground truth. In phantom measurements, a resolution of 2 × 2 × 12 mmPhantom experiments revealed an agreement between the relaxation times obtained viaThis work demonstrates the feasibility of

PURPOSE: To improve the image quality of highly accelerated multi-channel MRI data by learning a joint variational network that reconstructs multiple clinical contrasts jointly. METHODS: Data from our multi-contrast acquisition was embedded into the variational network architecture where shared anatomical information is exchanged by mixing the input contrasts. Complementary k-space sampling across imaging contrasts and Bunch-Phase/Wave-Encoding were used for data acquisition to improve the reconstruction at high accelerations. At 3T, our joint variational network approach across T1w, T2w and T2-FLAIR-weighted brain scans was tested for retrospective under-sampling at R=6 (2D) and R=4×4 (3D) acceleration. Prospective acceleration was also performed for 3D data where the combined acquisition time for whole brain coverage at 1 mm isotropic resolution across three contrasts was less than three minutes. RESULTS: Across all test datasets, our joint multi-contrast network better preserved fine anatomical details with reduced image-blurring when compared to the corresponding single-contrast reconstructions. Improvement in image quality was also obtained through complementary k-space sampling and Bunch-Phase/Wave-Encoding where the synergistic combination yielded the overall best performance as evidenced by exemplarily slices and quantitative error metrics. CONCLUSION: By leveraging shared anatomical structures across the jointly reconstructed scans, our joint multi-contrast approach learnt more efficient regularizers which helped to retain natural image appearance and avoid over-smoothing. When synergistically combined with advanced encoding techniques, the performance was further improved, enabling up to R=16-fold acceleration with good image quality. This should help pave the way to very rapid high-resolution brain exams.

Dynamic glucose-enhanced (DGE)-MRI based on chemical exchange-sensitive MRI, that is, glucoCEST and gluco-chemical exchange-sensitive spin-lock (glucoCESL), is intrinsically prone to motion-induced artifacts because the final DGE contrast relies on the difference of images, which were acquired with a time gap of several mins. In this study, identification of different types of motion-induced artifacts led to the development of a 3D acquisition protocol for DGE examinations in the human brain at 7 T with improved robustness in the presence of subject motion.DGE-MRI was realized by the chemical exchange-sensitive spin-lock approach based either on relaxation rate in the rotating frame (REven after coregistration, significant motion-induced artifacts remained in the DGE contrast based on RThe presented 3D acquisition protocol enables DGE-MRI examinations in the human brain with improved robustness against motion-induced artifacts. Correction of motion-induced artifacts is of high importance for DGE-MRI in clinical studies where an unambiguous assignment of contrast changes due to an actual change in local glucose concentration is a prerequisite.

Nuclear magnetic resonance (NMR) diffusion pore imaging has been proposed to study the shape of arbitrary closed pores filled with an NMR-detectable medium by use of nonclassical diffusion encoding schemes. Potential applications can be found in biomedical imaging and porous media research. When studying non-point-symmetric pores, NMR signals with nonvanishing imaginary parts arise containing the pore shape information, which is lost for classical diffusion encoding schemes. Key limitations are the required high magnetic field gradient amplitudes and T2 relaxation while approaching the diffusion long-time limit. To benefit from the slower T1 decay, we demonstrate the feasibility of diffusion pore imaging with stimulated echoes using Monte Carlo simulations and experiments with hyperpolarized xenon-129 gas in well-defined geometries and show that the necessary complex-valued signals can be acquired. Analytical derivation of the stimulated echo double diffusion encoded signal was performed to investigate the effect of the additionally arising undesired terms on the complex phase information. These terms correspond to signals arising for spin-echo sequences with unbalanced gradients. For most possible applications, the unbalanced terms can be neglected. If non-negligible, selection of the appropriate signal component using a phase cycling scheme was demonstrated experimentally. Using stimulated echoes may be a step towards application of diffusion pore imaging to larger pores with gradient amplitudes available today in preclinical systems.

The purpose of this study was to investigate the association of relaxation-compensated chemical exchange saturation transfer (CEST) MRI with overall survival (OS) and progression-free survival (PFS) in newly diagnosed high-grade glioma (HGG) patients. Twenty-six patients with newly diagnosed high-grade glioma (WHO grades III–IV) were included in this prospective IRB-approved study. CEST MRI was performed on a 7.0-T whole-body scanner. Association of patient OS/PFS with relaxation-compensated CEST MRI (amide proton transfer (APT), relayed nuclear Overhauser effect (rNOE)/NOE, downfield-rNOE-suppressed APT (dns-APT)) and diffusion-weighted imaging (apparent diffusion coefficient) were assessed using the univariate Cox proportional hazards regression model. Hazard ratios (HRs) and corresponding 95% confidence intervals were calculated. Furthermore, OS/PFS association with clinical parameters (age, gender, O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation status, and therapy: biopsy + radio-chemotherapy vs. debulking surgery + radio-chemotherapy) were tested accordingly. Relaxation-compensated APT MRI was significantly correlated with patient OS (HR = 3.15, p = 0.02) and PFS (HR = 1.83, p = 0.009). The strongest association with PFS was found for the dns-APT metric (HR = 2.61, p = 0.002). These results still stand for the relaxation-compensated APT contrasts in a homogenous subcohort of n = 22 glioblastoma patients with isocitrate dehydrogenase (IDH) wild-type status. Among the tested clinical parameters, patient age (HR = 1.1, p = 0.001) and therapy (HR = 3.68, p = 0.026) were significant for OS; age additionally for PFS (HR = 1.04, p = 0.048). Relaxation-compensated APT MRI signal intensity is associated with overall survival and progression-free survival in newly diagnosed, previously untreated glioma patients and may, therefore, help to customize treatment and response monitoring in the future. • Amide proton transfer (APT) MRI signal intensity is associated with overall survival and progression in glioma patients. • Relaxation compensation enhances the information value of APT MRI in tumors. • Chemical exchange saturation transfer (CEST) MRI may serve as a non-invasive biomarker to predict prognosis and customize treatment.

Background Patients with newly diagnosed inoperable glioma receive chemoradiotherapy (CRT). Standard Response Assessment in Neuro-Oncology (RANO) takes a minimum of 4 weeks after the end of treatment. Purpose/hypothesis To investigate whether chemical exchange saturation transfer (CEST) MRI enables earlier assessment of response to CRT in glioma patients. Study type Longitudinal prospective study. Population Twelve brain tumor patients who underwent definitive CRT were included in this study. Three longitudinal CEST MRI measurements were performed for each patient at 7T: first before, second immediately after completion of CRT, and a third measurement as a 6-week follow-up. Field strength/sequence Conventional MRI (contrast-enhanced, T2 w and diffusion-weighted imaging) at 3T and T2 w and CEST MRI at 7T was performed for all patients. Assessment The mean relaxation-compensated relayed nuclear-Overhauser-effect CEST signal (rNOE) and the mean downfield-rNOE-suppressed amide proton transfer (dns-APT) CEST signal were investigated. Additionally, choline-to-N-acetyl-aspartate ratios (Cho/NAA) were evaluated using single-voxel 1 H-MRS in six of these patients. Performance of obtained contrasts was analyzed in assessing treatment response as classified according to the updated RANO criteria. Statistical test Unpaired Student's t-test. Results The rNOE signal significantly separated stable and progressive disease directly after the end of therapy (post-treatment normalized to pre-treatment mean ± SD: rNOEresponder = 1.090 ± 0.110, rNOEnon-responder = 0.808 ± 0.155, P = 0.015). In contrast, no significant difference was observed between either group when assessing the normalized dns-APT (dns-APTresponder = 0.953 ± 0.384, dns-APTnon-responder = 0.972 ± 0.477, P = 0.95). In the smaller MRS subcohort, normalized Cho/NAA decreased in therapy responders (Cho/NAAresponder = 0.632 ± 0.007, Cho/NAAnon-responder = 0.946 ± 0.124, P = 0.070). DATA CONCLUSION: rNOE mediated CEST imaging at 7T allowed for discrimination of responders and non-responders immediately after the end of CRT, additionally supported by 1 H-MRS data. This is at least 4 weeks earlier than the standard clinical evaluation according to RANO. Therefore, CEST MRI may enable early response assessment in glioma patients. Level of evidence 1 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:1268-1277.