Publication List

zaiss moritz

• MR-zero meets FLASH - controlling the transient signal decay in gradient- and RF-spoiled gradient echo sequences
  CONCLUSION: Individual flip angle and RF phase optimization improves the transient signal decay of FLASH MRI sequences.
• Motion and magnetic field inhomogeneity correction techniques for chemical exchange saturation transfer (CEST) MRI: A contemporary review
  Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) has emerged as a powerful imaging technique sensitive to tissue molecular composition, pH, and metabolic processes in situ. CEST MRI uniquely probes the physical exchange of protons between water and specific molecules within tissues, providing a window into physiological phenomena that remain invisible to standard MRI. However, given the very low concentration (millimolar range) of CEST compounds, the effects measured...
• Calibration-free whole-brain CEST imaging at 7T with parallel transmit pulse design for saturation homogeneity utilizing universal pulses (PUSHUP)
  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.
• Enhanced and robust contrast in CEST MRI: Saturation pulse shape design via optimal control
  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.
• Improved quantification in CEST-MRI by joint spatial total generalized variation
  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.
• Phase distribution graphs for fast, differentiable, and spatially encoded Bloch simulations of arbitrary MRI sequences
  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,...
• Sidebands in CEST MR-How to recognize and avoid them
  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
  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...
• Multi-parametric optimization of magnetic resonance imaging sequences for magnetic resonance-guided radiotherapy
  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.
• Multi-echo-based fat artifact correction for CEST MRI at 7 T
  CONCLUSION: Our work demonstrates the feasibility of multi-echo-based fat-water separation with an adaptive fat model for fat artifact correction for CEST MRI at 7 T. Our approach provided better fat artifact correction throughout the entire spectrum and image than the fat saturation pulse or Z-spectrum-based correction method for both phantom and knee imaging results.
• MR-zero meets RARE MRI: Joint optimization of refocusing flip angles and neural networks to minimize T₂ -induced blurring in spin echo sequences
  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 T(2) -induced blurring can be found. This allows faster single- or multi-shot RARE MRI with longer echo trains.
• 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 B(0) and radiofrequency B(1) field inhomogeneities that degrade their contrast. For this reason, the correction of B(0) field-induced artefacts is essential, whereas accounting for B(1) field inhomogeneities have shown significant improvements in image...
• 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.
• 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 B(1,rms) of 2 μT. After optimization of the snapshot CEST approach for APTw imaging regarding flip angle, voxel size and frequency...
• 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...
• Accelerated and quantitative three-dimensional molecular MRI using a generative adversarial network
  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 ^(13)C labeling and are is easily translatable to the clinics. The main principle of DGE is clear. However, what...
• DeepCEST 7 T: Fast and homogeneous mapping of 7 T CEST MRI parameters and their uncertainty quantification
  CONCLUSION: The proposed deepCEST 7 T approach reduces scan time by 50% to now 6:42 min, but still delivers both B(0) - and B(1) -corrected homogeneous CEST contrasts along with an uncertainty map, which can increase diagnostic confidence. Multiple accurate 7 T CEST contrasts are delivered within seconds.
• 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
  CONCLUSION: This clinically compatible implementation of dynamic pTx pulses improved the fat suppression homogeneity at 7T taking into account the subject-specific B(0) heterogeneities online. This study highlights the lipid-induced biases on the CEST z-spectrum. The results are promising for body applications where B(0) heterogeneities and fat are more substantial.
• MR-double-zero - Proof-of-concept for a framework to autonomously discover MRI contrasts
  CONCLUSIONS: New MR contrasts for mapping a given target can be discovered by derivative-free optimization of parametrized sequences that are directly executed on a real MRI scanner. This is demonstrated by 're-discovery' of a chemical exchange weighted sequence. The proposed method is considered to be a paradigm shift towards autonomous, model-free and target-driven sequence design.
• Theory of chemical exchange saturation transfer MRI in the context of different magnetic fields
  Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a versatile MRI method that provides contrast based on the level of molecular and metabolic activity. This contrast arises from indirect measurement of protons in low concentration molecules that are exchanging with the abundant water proton pool. The indirect measurement is based on magnetization transfer of radio frequency (rf)-prepared magnetization from the small pool to the water pool. The signal can be modeled...
• Direct Detection of Lithium Exchange across the Solid Electrolyte Interphase by ⁷Li Chemical Exchange Saturation Transfer
  Lithium metal anodes offer a huge leap in the energy density of batteries, yet their implementation is limited by solid electrolyte interphase (SEI) formation and dendrite deposition. A key challenge in developing electrolytes leading to the SEI with beneficial properties is the lack of experimental approaches for directly probing the ionic permeability of the SEI. Here, we introduce lithium chemical exchange saturation transfer (Li-CEST) as an efficient nuclear magnetic resonance (NMR) approach...
• Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T: Application to brain tumors
  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...
• Breast cancer imaging with glucosamine CEST (chemical exchange saturation transfer) MRI: first human experience
  CONCLUSION: The results of this initial feasibility study indicate the potential of GlcN CEST MRI to diagnose breast cancer in a clinical setup.
• 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...
• An end-to-end AI-based framework for automated discovery of rapid CEST/MT MRI acquisition protocols and molecular parameter quantification (AutoCEST)
  CONCLUSION: AutoCEST can automatically generate optimized CEST/MT acquisition protocols that can be rapidly reconstructed into quantitative exchange parameter maps.
• 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 B(0) and B(1) 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...
• What do we know about dynamic glucose-enhanced (DGE) MRI and how close is it to the clinics? Horizon 2020 GLINT consortium report
  Cancer is one of the most devastating diseases that the world is currently facing, accounting for 10 million deaths in 2020 (WHO). In the last two decades, advanced medical imaging has played an ever more important role in the early detection of the disease, as it increases the chances of survival and the potential for full recovery. To date, dynamic glucose-enhanced (DGE) MRI using glucose-based chemical exchange saturation transfer (glucoCEST) has demonstrated the sensitivity to detect both...
• Mapping intracellular pH in tumors using amide and guanidyl CEST-MRI at 9.4 T
  CONCLUSION: The presented method enables non-invasive mapping of absolute pH(i) values in tumors using CEST-MRI, which was so far prevented by concomitant effects. Consequently, pre-clinical studies on pH(i) changes in tumors are possible allowing the assessment of pH(i) in vivo as a biomarker for cancer diagnosis or treatment monitoring.
• GLINT: GlucoCEST in neoplastic tumors at 3 T-clinical results of GlucoCEST in gliomas
  CONCLUSION: First application of DGE⍴ in a patient cohort shows an association between BBB leakage and DGE signal irrespective of the tumor grade. This indicates that glucoCEST corresponds more to the disruptions of BBB with Gd uptake than to the molecular tumor profile or tumor grading.
• Quantitative imaging of apoptosis following oncolytic virotherapy by magnetic resonance fingerprinting aided by deep learning
  Non-invasive imaging methods for detecting intratumoural viral spread and host responses to oncolytic virotherapy are either slow, lack specificity or require the use of radioactive or metal-based contrast agents. Here we show that in mice with glioblastoma multiforme, the early apoptotic responses to oncolytic virotherapy (characterized by decreased cytosolic pH and reduced protein synthesis) can be rapidly detected via chemical-exchange-saturation-transfer magnetic resonance fingerprinting...
• Pulseq-CEST: Towards multi-site multi-vendor compatibility and reproducibility of CEST experiments using an open-source sequence standard
  CONCLUSION: With Pulseq-CEST, we provide a straightforward approach to standardize, share, simulate, and measure different CEST preparation schemes, which are inherently completely defined.
• Brain tissues have single-voxel signatures in multi-spectral MRI
  Since the seminal works by Brodmann and contemporaries, it is well-known that different brain regions exhibit unique cytoarchitectonic and myeloarchitectonic features. Transferring the approach of classifying brain tissues - and other tissues - based on their intrinsic features to the realm of magnetic resonance (MR) is a longstanding endeavor. In the 1990s, atlas-based segmentation replaced earlier multi-spectral classification approaches because of the large overlap between the class...
• The traveling heads 2.0: Multicenter reproducibility of quantitative imaging methods at 7 Tesla
  CONCLUSION: Our results show that quantitative brain imaging can be performed with high reproducibility at 7 T and with similar reliability as found at 3 T for multicenter studies of the supratentorial brain.
• Whole-brain quantitative CEST MRI at 7T using parallel transmission methods and B1+ correction
  CONCLUSION: A combination of MIMOSA FOCUS with a single-point B1+ correction can be used to achieve quantitative CEST measurements at ultra-high magnetic field strengths. Compared to previous B1+ correction methods, acquisition time can be reduced as additional scans required for B1+ correction can be omitted.
• Clinical routine acquisition protocol for 3D relaxation-compensated APT and rNOE CEST-MRI of the human brain at 3T
  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.
• A fast multislice sequence for 3D MRI-CEST pH imaging
  CONCLUSION: The proposed fast multislice CEST-MRI sequence allows volumetric acquisitions with good pH sensitivity, accuracy, and spatial resolution for several in vivo pH imaging applications.
• On the interference from agar in chemical exchange saturation transfer MRI parameter optimization in model solutions
  Chemical exchange saturation transfer (CEST) MRI is currently set to become part of clinical routine as it enables indirect detection of low concentrated molecules and proteins. Recently, intermediate to fast exchanging functional groups of glucose and its derivatives, glutamate and dextran, have gained attention as promising CEST contrast agents. To increase the specificity of CEST MRI for certain functional groups, the presaturation module is commonly optimized. At an early stage, this is...
• Association between tissue hypoxia, perfusion restrictions, and microvascular architecture alterations with lesion-induced impairment of neurovascular coupling
  Functional magnetic resonance imaging (fMRI) has been mainly utilized for the preoperative localization of eloquent cortical areas. However, lesion-induced impairment of neurovascular coupling (NVC) in the lesion border zone may lead to false-negative fMRI results. The purpose of this study was to determine physiological factors impacting the NVC. Twenty patients suffering from brain lesions were preoperatively examined using multimodal neuroimaging including fMRI, magnetoencephalography (MEG)...
• The cellular heat shock response monitored by chemical exchange saturation transfer MRI
  CEST-MRI of the rNOE signal has been demonstrated in vitro to be closely linked to the protein conformational state. As the detectability of denaturation and aggregation processes on a physiologically relevant scale in living organisms has yet to be verified, the aim of this study was to perform heat-shock experiments with living cells to monitor the cellular heat-shock response of the rNOE CEST signal. Cancer cells (HepG2) were dynamically investigated after a mild, non-lethal heat-shock of 42...
• Whole brain snapshot CEST at 3T using 3D-EPI: Aiming for speed, volume, and homogeneity
  CONCLUSION: The suggested protocol enables whole brain coverage at 1.8 mm isotropic resolution and fast acquisition of 4.3 s per presaturation offset. For the fitted CEST amplitudes, high reproducibility was proven, increasing the opportunities of quantitative CEST investigations at 3T significantly.
• Optimized dualCEST-MRI for imaging of endogenous bulk mobile proteins in the human brain
  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...
• Structure or Exchange? On the Feasibility of Chemical Exchange Detection with Balanced Steady-State Free Precession in Tissue - An In Vitro Study
  Balanced steady-state free precession imaging has recently been suggested for chemical exchange detection (bSSFPX). The objective of this work is to investigate the contributions of microstructural, chemical shift and chemical exchange effects to the asymmetry of the bSSFP profile at field strengths of 3 T and 9.4 T. To this end, in vitro bSSFPX experiments are performed for a range of repetition times and flip angles in glucose water solutions with different MnCl(2) concentrations and tissue...
• DeepCEST 3T: Robust MRI parameter determination and uncertainty quantification with neural networks-application to CEST imaging of the human brain at 3T
  CONCLUSIONS: The deepCEST 3T neural network provides fast and robust estimation of CEST parameters, enabling online reconstruction of sophisticated CEST contrast images without the typical computational cost. Moreover, the uncertainty quantification indicates if the predictions are trustworthy, enabling confident interpretation of contrast changes.
• Dynamic glucose-enhanced (DGE) MRI in the human brain at 7 T with reduced motion-induced artifacts based on quantitative R_1ρ mapping
  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.
• A novel normalization for amide proton transfer CEST MRI to correct for fat signal-induced artifacts: application to human breast cancer imaging
  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.
• CEST MR-Fingerprinting: Practical considerations and insights for acquisition schedule design and improved reconstruction
  CONCLUSIONS: Optimization of the CEST-MRF acquisition schedule is critical for obtaining the best exchange parameter accuracy. The use of Euclidean distance-based matching of signal trajectories simultaneously improved the discrimination ability and reduced the scan time and maximal saturation power required.
• Adaptive denoising for chemical exchange saturation transfer MR imaging
  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...
• Quantification of hydroxyl exchange of D-Glucose at physiological conditions for optimization of glucoCEST MRI at 3, 7 and 9.4 Tesla
  CONCLUSION: For the determined fast exchange regime, presaturation pulses in the spin-lock regime (long recover time, short yet strong saturation) were found to be optimal. This study gives an estimation for optimization of the glucoCEST signal in vivo on the basis of glucose exchange rate at physiological conditions.
• T1ρ-based dynamic glucose-enhanced (DGEρ) MRI at 3 T: method development and early clinical experience in the human brain
  CONCLUSION: DGEρ imaging was optimized for clinical field strengths of 3 T, and a robust protocol was established for broader application. Early experience shows that DGEρ seems possible at 3 T and could not only be attributed to motion artifacts. Observed DGEρ maps showed unique patterns, partly matching with the T(1) -ce tumor ring enhancement. However, effect sizes are small and careful clinical application is necessary.
• Whole-brain snapshot CEST imaging at 7 T using 3D-EPI
  CONCLUSIONS: The proposed sequence enables robust acquisition of 2 mm isotropic whole-brain CEST maps at 7 Tesla within a total scan time of 16 minutes.
• Multiple interleaved mode saturation (MIMOSA) for B₁⁺ inhomogeneity mitigation in chemical exchange saturation transfer
  CONCLUSION: Multiple interleaved mode saturation can be used as a simple method to mitigate B1+ inhomogeneity effects in CEST MRI at ultra-high magnetic field strengths. Compared to previous B1+ correction methods, acquisition time can be reduced because an additional scan, usually required for B1+ correction, can be omitted.
• Relaxation-compensated APT and rNOE CEST-MRI of human brain tumors at 3 T
  CONCLUSION: The presented acquisition protocol allows relaxation-compensated CEST-MRI at 3 T with a 3D coverage of the human brain. Translation to a clinically relevant magnetic field strength of 3 T opens the door to trials with a large number of participants, thus enabling a comprehensive assessment of the clinical relevance of relaxation compensation in CEST-MRI.
• Relaxation-compensated amide proton transfer (APT) MRI signal intensity is associated with survival and progression in high-grade glioma patients
  CONCLUSION: 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.
• DeepCEST: 9.4 T Chemical exchange saturation transfer MRI contrast predicted from 3 T data - a proof of concept study
  CONCLUSION: The 9.4 T CEST signals acquired at low saturation power can be accurately estimated from CEST imaging at 3 T using a neural network trained with coregistered 3 T and 9.4 T data of healthy subjects. The deepCEST approach generalizes to Z-spectra of tumor areas and might indicate whether additional ultrahigh-field (UHF) scans will be beneficial.
• Assessment of a clinically feasible Bayesian fitting algorithm using a simplified description of Chemical Exchange Saturation Transfer (CEST) imaging
  Fitting a model based on the Bloch-McConnell (BM) equations to Chemical Exchange Saturation Transfer (CEST) spectra allows for the quantification of metabolite concentration and exchange rate as well as simultaneous correction of field inhomogeneity, direct water saturation and magnetization transfer. Employing a Bayesian fitting approach permits the integration of prior information into the analysis to incorporate expected parameter distributions and to prevent over-fitting. However, the...
• Dynamic Interactions in Synthetic Receptors: A Guest Exchange Saturation Transfer Study
  The accumulated knowledge regarding molecular architectures is based on established, reliable, and accessible analytical tools that provide robust structural and functional information on assemblies. However, both the dynamicity and low population of noncovalently interacting moieties within studied molecular systems limit the efficiency and accuracy of traditional methods. Herein, the use of a saturation transfer-based NMR approach to study the dynamic binding characteristics of an anion to a...
• Pros and cons of ultra-high-field MRI/MRS for human application
  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...
• Possible artifacts in dynamic CEST MRI due to motion and field alterations
  CONCLUSION: Correction or mitigation for small motions is crucial for dynamic CEST imaging, especially in subjects with lesions. Concomitant B(0) alterations can as well induce pseudo CEST effects at 3 T.
• 3D gradient echo snapshot CEST MRI with low power saturation for human studies at 3T
  CONCLUSION: A sophisticated CEST tool ready for clinical application was developed and tested for feasibility.
• CEST imaging at 9.4 T using adjusted adiabatic spin-lock pulses for on- and off-resonant T1⍴-dominated Z-spectrum acquisition
  CONCLUSION: By adapting a pulse shape for low-power SL experiments, we were able to acquire robust on- and off-resonant adiabatic SL prepared images in vivo at 9.4 T. This development leads directly to SL Z-spectrum acquisition, beneficial for chemical-exchange-weighted MRI.
• Chemical exchange saturation transfer (CEST) signal intensity at 7T MRI of WHO IV° gliomas is dependent on the anatomic location
  BACKGROUND: Chemical exchange saturation transfer (CEST) is a novel MRI technique applied to brain tumor patients.
• Chemical exchange saturation transfer MRI serves as predictor of early progression in glioblastoma patients
  CONCLUSIONS: CEST derived contrasts, particularly NOE-weighted imaging and dns-APT, yielded significant predictors of early progression after fist-line therapy in glioblastoma. Therefore, CEST MRI might be considered as non-invasive tool for customization of treatment in the future.
• Amide chemical exchange saturation transfer at 7 T: a possible biomarker for detecting early response to neoadjuvant chemotherapy in breast cancer patients
  CONCLUSIONS: This preliminary study shows the feasibility of using APT CEST magnetic resonance imaging as a noninvasive biomarker to assess the effect of NAC in an early stage of NAC treatment of breast cancer patients.
• Chemical exchange saturation transfer MRI contrast in the human brain at 9.4 T
  CONCLUSION: High spectral resolution chemical exchange saturation transfer at 9.4 T allows deeper insights into the Z-spectrum structure of the human brain, and provides many different contrasts showing different correlations in healthy tissue and in tumor-affected areas of the brain, generating hypotheses for future investigations of in-vivo-CEST at UHF.
• Assessment of frequency drift on CEST MRI and dynamic correction: application to gagCEST at 7 T
  CONCLUSION: Prospective or retrospective correction of the frequency drift of the MRI scanner is essential for reproducible gagCEST measurements. The proposed retrospective correction method fulfills this requirement without the need of additional measurements.
• Comparison of B₀ versus B₀ and B₁ field inhomogeneity correction for glycosaminoglycan chemical exchange saturation transfer imaging
  CONCLUSION: The B(0) and B(1) field inhomogeneity correction method leads to an improved quality of gagCEST imaging in IVDs compared with only B(0) correction.
• Assessing the predictability of IDH mutation and MGMT methylation status in glioma patients using relaxation-compensated multipool CEST MRI at 7.0 T
  CONCLUSIONS: Relaxation-compensated multipool CEST MRI, particularly dns-APT imaging, enabled prediction of IDH mutation status and differentiation of LGG versus HGG and should therefore be considered as a non-invasive MR biomarker in the diagnostic workup.
• Dual-frequency irradiation CEST-MRI of endogenous bulk mobile proteins
  A novel MRI contrast is proposed which enables the selective detection of endogenous bulk mobile proteins in vivo. Such a non-invasive imaging technique may be of particular interest for many diseases associated with pathological alterations of protein expression, such as cancer and neurodegenerative disorders. Specificity to mobile proteins was achieved by the selective measurement of intramolecular spin diffusion and the removal of semi-solid macromolecular signal components by a correction...
• PRO-QUEST: a rapid assessment method based on progressive saturation for quantifying exchange rates using saturation times in CEST
  CONCLUSION: Because of the reduced scan time and insensitivity to nonchemical exchange factors such as direct water saturation, PRO-QUEST can serve as an excellent alternative for researchers and clinicians interested to map pH changes in vivo.
• Snapshot-CEST: Optimizing spiral-centric-reordered gradient echo acquisition for fast and robust 3D CEST MRI at 9.4 T
  Gradient echo (GRE)-based acquisition provides a robust readout method for chemical exchange saturation transfer (CEST) at ultrahigh field (UHF). To develop a snapshot-CEST approach, the transient GRE signal and point spread function were investigated in detail, leading to optimized measurement parameters and reordering schemes for fast and robust volumetric CEST imaging. Simulation of the transient GRE signal was used to determine the optimal sequence parameters and the maximum feasible number...
• Flip-angle based ratiometric approach for pulsed CEST-MRI pH imaging
  Several molecules have been exploited for developing MRI pH sensors based on the chemical exchange saturation transfer (CEST) technique. A ratiometric approach, based on the saturation of two exchanging pools at the same saturation power, or by varying the saturation power levels on the same pool, is usually needed to rule out the concentration term from the pH measurement. However, all these methods have been demonstrated by using a continuous wave saturation scheme that limits its translation...
• QUESP and QUEST revisited - fast and accurate quantitative CEST experiments
  CONCLUSIONS: The refined formulas yield improved exchange rate estimation. General convergence intervals of the methods that would apply for smaller shift agents are also discussed. Magn Reson Med 79:1708-1721, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
• Spectrally Undiscerned Isomers Might Lead to Erroneous Determination of Water Exchange Rates of paraCEST Eu(III) Agents
  We report a detailed study of the solution structure and water exchange rate of a Eu(III) complex with the cyclen-based ligand L¹, containing (S)-2-(2-acetamido)-3-(4-(trifluoromethyl)phenyl)propanoate pendant arms at positions 1 and 7 of the cyclen ring and acetylglycinate pendants at positions 4 and 10. The EuL¹ complex was characterized by a combination of NMR and luminescence spectroscopy and density functional theory (DFT) calculations. The chemical exchange saturation transfer (CEST)...
• Exploiting sequence and stability information for directing nanobody stability engineering
  CONCLUSIONS: The results reveal a mutational strategy to improve the biophysical behavior of nanobody binders and indicate a species-specificity of nanobody architecture.
• T1ρ-weighted Dynamic Glucose-enhanced MR Imaging in the Human Brain
  Purpose To evaluate the ability to detect intracerebral regions of increased glucose concentration at T1ρ-weighted dynamic glucose-enhanced (DGE) magnetic resonance (MR) imaging at 7.0 T. Materials and Methods This prospective study was approved by the institutional review board. Nine patients with newly diagnosed glioblastoma and four healthy volunteers were included in this study from October 2015 to July 2016. Adiabatically prepared chemical exchange-sensitive spin-lock imaging was performed...
• Measurement of APT using a combined CERT-AREX approach with varying duty cycles
  The goal is to develop an imaging method where contrast reflects amide-water magnetization exchange, with minimal signal contributions from other sources. Conventional chemical exchange saturation transfer (CEST) imaging of amides (often called amide proton transfer, or APT, and quantified by the metric MTR(asym)) is confounded by several factors unrelated to amides, such as aliphatic protons, water relaxation, and macromolecular magnetization transfer. In this work, we examined the effects of...
• Fast and Quantitative T1ρ-weighted Dynamic Glucose Enhanced MRI
  Common medical imaging techniques usually employ contrast agents that are chemically labeled, e.g. with radioisotopes in the case of PET, iodine in the case of CT or paramagnetic metals in the case of MRI to visualize the heterogeneity of the tumor microenvironment. Recently, it was shown that natural unlabeled D-glucose can be used as a nontoxic biodegradable contrast agent in Chemical Exchange sensitive Spin-Lock (CESL) magnetic resonance imaging (MRI) to detect the glucose uptake and...
• On the transmit field inhomogeneity correction of relaxation-compensated amide and NOE CEST effects at 7 T
  High field MRI is beneficial for chemical exchange saturation transfer (CEST) in terms of high SNR, CNR, and chemical shift dispersion. These advantages may, however, be counter-balanced by the increased transmit field inhomogeneity normally associated with high field MRI. The relatively high sensitivity of the CEST contrast to B(1) inhomogeneity necessitates the development of correction methods, which is essential for the clinical translation of CEST. In this work, two B(1) correction...
• Aggregation-induced changes in the chemical exchange saturation transfer (CEST) signals of proteins
  Chemical exchange saturation transfer (CEST) is an MRI technique that allows mapping of biomolecules (small metabolites, proteins) with nearly the sensitivity of conventional water proton MRI. In living organisms, several tissue-specific CEST effects have been observed and successfully applied to diagnostic imaging. In these studies, particularly the signals of proteins showed a distinct correlation with pathological changes. However, as CEST effects depend on various properties that determine...
• Adiabatically prepared spin-lock approach for T1ρ-based dynamic glucose enhanced MRI at ultrahigh fields
  CONCLUSION: An adiabatically prepared spin-lock preparation was presented that enables a homogeneous and chemical exchange sensitive T(1ρ) -based imaging at ultra-high field whole-body scanners, e.g., for T(1ρ) -based dynamic glucose enhanced MRI. Magn Reson Med 78:215-225, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
• Comparison of glycosaminoglycan chemical exchange saturation transfer using Gaussian-shaped and off-resonant spin-lock radiofrequency pulses in intervertebral disks
  CONCLUSION: CESL does not improve the chemical exchange asymmetry effect compared with conventional CEST, but leads to comparable results. Magn Reson Med 78:280-284, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
• Simultaneous mapping of water shift and B₁ (WASABI)-Application to field-Inhomogeneity correction of CEST MRI data
  CONCLUSION: The proposed WASABI method yields a novel simultaneous B(0) and B(1) mapping within 1 min that is robust and easy to implement. Magn Reson Med 77:571-580, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
• Downfield-NOE-suppressed amide-CEST-MRI at 7 Tesla provides a unique contrast in human glioblastoma
  CONCLUSION: Thus, suppression of the downfield rNOE contribution might be the important step to yield the amide proton CEST contrast originally aimed at. Magn Reson Med 77:196-208, 2017. © 2016 Wiley Periodicals, Inc.
• R1 correction in amide proton transfer imaging: indication of the influence of transcytolemmal water exchange on CEST measurements
  Amide proton transfer (APT) imaging may potentially detect mobile proteins/peptides non-invasively in vivo, but its specificity may be reduced by contamination from other confounding effects such as asymmetry of non-specific magnetization transfer (MT) effects and spin-lattice relaxation with rate R1 (=1/T1). Previously reported spillover, MT and R1 correction methods were based on a two-pool model, in which the existence of multiple water compartments with heterogeneous relaxation properties in...
• Relaxation-compensated CEST-MRI at 7 T for mapping of creatine content and pH--preliminary application in human muscle tissue in vivo
  The small biomolecule creatine is involved in energy metabolism. Mapping of the total creatine (mostly PCr and Cr) in vivo has been done with chemical shift imaging. Chemical exchange saturation transfer (CEST) allows an alternative detection of creatine via water MRI. Living tissue exhibits CEST effects from different small metabolites, including creatine, with four exchanging protons of its guanidinium group resonating about 2 ppm from the water peak and hence contributing to the amine proton...
• Quantitative pulsed CEST-MRI using Ω-plots
  Chemical exchange saturation transfer (CEST) allows the indirect detection of dilute metabolites in living tissue via MRI of the tissue water signal. Selective radio frequency (RF) with amplitude B1 is used to saturate the magnetization of protons of exchanging groups, which transfer the saturation to the abundant water pool. In a clinical setup, the saturation scheme is limited to a series of short pulses to follow regulation of the specific absorption rate (SAR). Pulsed saturation is difficult...
• Amide proton transfer of carnosine in aqueous solution studied in vitro by WEX and CEST experiments
  Amide protons of peptide bonds induce an important chemical exchange saturation transfer (CEST) contrast in vivo. As a simple in vitro model for a peptide amide proton CEST effect, we suggest herein the dipeptide carnosine. We show that the metabolite carnosine creates a CEST effect and we study the properties of the exchange of the amide proton (-NH) of the carnosine peptide bond (NHCPB) in model solutions for a pH range from 6 to 8.3 and a temperature range from T = 5 °C to 43 °C by means of...
• Signature of protein unfolding in chemical exchange saturation transfer imaging
  Chemical exchange saturation transfer (CEST) allows the detection of metabolites of low concentration in tissue with nearly the sensitivity of MRI with water protons. With this spectroscopic imaging approach, several tissue-specific CEST effects have been observed in vivo. Some of these originate from exchanging sites of proteins, such as backbone amide protons, or from aliphatic protons within the hydrophobic protein core. In this work, we employed CEST experiments to detect global protein...
• Nuclear Overhauser Enhancement imaging of glioblastoma at 7 Tesla: region specific correlation with apparent diffusion coefficient and histology
  OBJECTIVE: To explore the correlation between Nuclear Overhauser Enhancement (NOE)-mediated signals and tumor cellularity in glioblastoma utilizing the apparent diffusion coefficient (ADC) and cell density from histologic specimens. NOE is one type of chemical exchange saturation transfer (CEST) that originates from mobile macromolecules such as proteins and might be associated with tumor cellularity via altered protein synthesis in proliferating cells.
• Correction of B1-inhomogeneities for relaxation-compensated CEST imaging at 7 T
  Chemical exchange saturation transfer (CEST) imaging of endogenous agents in vivo is influenced by direct water proton saturation (spillover) and semi-solid macromolecular magnetization transfer (MT). Lorentzian fit isolation and application of the inverse metric yields the pure CEST contrast AREX, which is less affected by these processes, but still depends on the measurement technique, in particular on the irradiation amplitude B1 of the saturation pulses. This study focuses on two well-known...
• Relaxation-compensated CEST-MRI of the human brain at 7T: Unbiased insight into NOE and amide signal changes in human glioblastoma
  Endogenous chemical exchange saturation transfer (CEST) effects of protons resonating near to water protons are always diluted by competing effects such as direct water saturation and semi-solid magnetization transfer (MT). This leads to unwanted T2 and MT signal contributions that contaminate the observed CEST signal. Furthermore, all CEST effects appear to be scaled by the T1 relaxation time of the mediating water pool. As MT, T1 and T2 are also altered in tumor regions, a recently published...
• A combined analytical solution for chemical exchange saturation transfer and semi-solid magnetization transfer
  Off-resonant RF irradiation in tissue indirectly lowers the water signal by saturation transfer processes: on the one hand, there are selective chemical exchange saturation transfer (CEST) effects originating from exchanging endogenous protons resonating a few parts per million from water; on the other hand, there is the broad semi-solid magnetization transfer (MT) originating from immobile protons associated with the tissue matrix with kilohertz linewidths. Recently it was shown that endogenous...
• Imaging of amide proton transfer and nuclear Overhauser enhancement in ischemic stroke with corrections for competing effects
  Chemical exchange saturation transfer (CEST) potentially provides the ability to detect small solute pools through indirect measurements of attenuated water signals. However, CEST effects may be diluted by various competing effects, such as non-specific magnetization transfer (MT) and asymmetric MT effects, water longitudinal relaxation (T1 ) and direct water saturation (radiofrequency spillover). In the current study, CEST images were acquired in rats following ischemic stroke and analyzed by...
• Towards quantification of pulsed spinlock and CEST at clinical MR scanners: an analytical interleaved saturation-relaxation (ISAR) approach
  Off-resonant spinlock (SL) enables an NMR imaging technique that can detect dilute metabolites similar to chemical exchange saturation transfer. However, in clinical MR scanners, RF pulse widths are restricted due to recommended specific absorption rate limits. Therefore, trains of short RF pulses that provide effective saturation during the required irradiation period are commonly employed. Quantitative evaluation of spectra obtained by pulsed saturation schemes is harder to achieve, since the...
• Nuclear overhauser enhancement mediated chemical exchange saturation transfer imaging at 7 Tesla in glioblastoma patients
  CONCLUSION: NOE mediated CEST Imaging at 7 T provides additional information on the structure of peritumoral hyperintensities in glioblastoma and displays isolated high intensity regions within the CE-T1 tumor that cannot be acquired on CE-T1 or T2-weighted images. Further research is needed to determine the origin of NOE mediated CEST and possible clinical applications such as therapy assessment or biopsy planning.
• Ultrafast CEST imaging
  We describe a new MR imaging method for the rapid characterization or screening of chemical exchange saturation transfer (CEST) contrast agents. It is based on encoding the chemical shift dimension with an additional gradient as proposed in previous ultrafast CEST spectroscopy approaches, but extends these with imaging capabilities. This allows us to investigate multiple compounds simultaneously with an arbitrary sample tube arrangement. The technique requires a fast multislice readout to ensure...
• Characterization of creatine guanidinium proton exchange by water-exchange (WEX) spectroscopy for absolute-pH CEST imaging in vitro
  Chemical exchange saturation transfer (CEST) enables indirect detection of small metabolites in tissue by MR imaging. To optimize and interpret creatine-CEST imaging we characterized the dependence of the exchange-rate constant k(sw) of creatine guanidinium protons in aqueous creatine solutions as a function of pH and temperature T in vitro. Model solutions in the low pH range (pH = 5-6.4) were measured by means of water-exchange (WEX)-filtered ¹H NMR spectroscopy on a 3 T whole-body MR...