Publications by authors named "Kai Herz"

13 Publications

  • Page 1 of 1

Pulseq-CEST: Towards multi-site multi-vendor compatibility and reproducibility of CEST experiments using an open-source sequence standard.

Magn Reson Med 2021 Oct 7;86(4):1845-1858. Epub 2021 May 7.

Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany.

Purpose: As the field of CEST grows, various novel preparation periods using different parameters are being introduced. At the same time, large, multisite clinical studies require clearly defined protocols, especially across different vendors. Here, we propose a CEST definition standard using the open Pulseq format for a shareable, simple, and exact definition of CEST protocols.

Methods: We present the benefits of such a standard in three ways: (1) an open database on GitHub, where fully defined, human-readable CEST protocols can be shared; (2) an open-source Bloch-McConnell simulation to test and optimize CEST preparation periods in silico; and (3) a hybrid MR sequence that plays out the CEST preparation period and can be combined with any existing readout module.

Results: The exact definition of the CEST preparation period, in combination with the flexible simulation, leads to a good match between simulations and measurements. The standard allowed finding consensus on three amide proton transfer-weighted protocols that could be compared in healthy subjects and a tumor patient. In addition, we could show coherent multisite results for a sophisticated CEST method, highlighting the benefits regarding protocol sharing and reproducibility.

Conclusion: With Pulseq-CEST, we provide a straightforward approach to standardize, share, simulate, and measure different CEST preparation schemes, which are inherently completely defined.
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http://dx.doi.org/10.1002/mrm.28825DOI Listing
October 2021

Structure or Exchange? On the Feasibility of Chemical Exchange Detection with Balanced Steady-State Free Precession in Tissue - An In Vitro Study.

NMR Biomed 2020 03 13;33(3):e4200. Epub 2019 Dec 13.

High Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.

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 concentrations and tissue homogenates obtained from the brainstem of pig brains. The experimental results are compared to multi-pool Bloch-McConnell simulations. Additionally, the influence of white matter tract geometry is analyzed ex vivo in pig brain hemispheres measured at two different angles with respect to B . The detectable bSSFP profile asymmetry in glucose solutions with tissue-like relaxation times and white matter homogenates was consistent with Bloch-McConnell simulations but relatively small. In intact white matter tracts, the asymmetry was dominated by structural effects with a strong dependency on tract orientation relative to B . In tracts perpendicular to B , the asymmetry was ≈ 3-4 times higher than in the homogenates, thus barely affected by chemical exchange effects. In conclusion, chemical exchange-related bSSFP profile asymmetries are detectable in tissue homogenates, however, the observed asymmetry level is generally low and prone to confounding structural effects rendering in vivo chemical exchange detection with bSSFP challenging in the brain.
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http://dx.doi.org/10.1002/nbm.4200DOI Listing
March 2020

DeepCEST 3T: Robust MRI parameter determination and uncertainty quantification with neural networks-application to CEST imaging of the human brain at 3T.

Magn Reson Med 2020 07 10;84(1):450-466. Epub 2019 Dec 10.

Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.

Purpose: Calculation of sophisticated MR contrasts often requires complex mathematical modeling. Data evaluation is computationally expensive, vulnerable to artifacts, and often sensitive to fit algorithm parameters. In this work, we investigate whether neural networks can provide not only fast model fitting results, but also a quality metric for the predicted values, so called uncertainty quantification, investigated here in the context of multi-pool Lorentzian fitting of CEST MRI spectra at 3T.

Methods: A deep feed-forward neural network including a probabilistic output layer allowing for uncertainty quantification was set up to take uncorrected CEST-spectra as input and predict 3T Lorentzian parameters of a 4-pool model (water, semisolid MT, amide CEST, NOE CEST), including the B inhomogeneity. Networks were trained on data from 3 subjects with and without data augmentation, and applied to untrained data from 1 additional subject and 1 brain tumor patient. Comparison to conventional Lorentzian fitting was performed on different perturbations of input data.

Results: The deepCEST 3T networks provided fast and accurate predictions of all Lorentzian parameters and were robust to input perturbations because of noise or B artifacts. The uncertainty quantification detected fluctuations in input data by increase of the uncertainty intervals. The method generalized to unseen brain tumor patient CEST data.

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.
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http://dx.doi.org/10.1002/mrm.28117DOI Listing
July 2020

CEST MR-Fingerprinting: Practical considerations and insights for acquisition schedule design and improved reconstruction.

Magn Reson Med 2020 02 9;83(2):462-478. Epub 2019 Aug 9.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts.

Purpose: To understand the influence of various acquisition parameters on the ability of CEST MR-Fingerprinting (MRF) to discriminate different chemical exchange parameters and to provide tools for optimal acquisition schedule design and parameter map reconstruction.

Methods: Numerical simulations were conducted using a parallel computing implementation of the Bloch-McConnell equations, examining the effect of TR, TE, flip-angle, water and , saturation-pulse duration, power, and frequency on the discrimination ability of CEST-MRF. A modified Euclidean distance matching metric was evaluated and compared to traditional dot product matching. L-Arginine phantoms of various concentrations and pH were scanned at 4.7T and the results compared to numerical findings.

Results: Simulations for dot product matching demonstrated that the optimal flip-angle and saturation times are and 1100 ms, respectively. The optimal maximal saturation power was 3.4 μT for concentrated solutes with a slow exchange rate, and 5.2 μT for dilute solutes with medium-to-fast exchange rates. Using the Euclidean distance matching metric, much lower maximum saturation powers were required (1.6 and 2.4 μT, respectively), with a slightly longer saturation time (1500 ms) and flip-angle. For both matching metrics, the discrimination ability increased with the repetition time. The experimental results were in agreement with simulations, demonstrating that more than a 50% reduction in scan-time can be achieved by Euclidean distance-based matching.

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.
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http://dx.doi.org/10.1002/mrm.27937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190069PMC
February 2020

Adaptive denoising for chemical exchange saturation transfer MR imaging.

NMR Biomed 2019 11 30;32(11):e4133. Epub 2019 Jul 30.

Department of High-field Magnetic Resonance, Max-Planck-Institute for Biological Cybernetics, Tuebingen, Germany.

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.
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http://dx.doi.org/10.1002/nbm.4133DOI Listing
November 2019

Quantification of hydroxyl exchange of D-Glucose at physiological conditions for optimization of glucoCEST MRI at 3, 7 and 9.4 Tesla.

NMR Biomed 2019 09 17;32(9):e4113. Epub 2019 Jul 17.

High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.

Aims: To determine individual glucose hydroxyl exchange rates at physiological conditions and use this information for numerical optimization of glucoCEST/CESL preparation. To give guidelines for in vivo glucoCEST/CESL measurement parameters at clinical and ultra-high field strengths.

Methods: Five glucose solution samples at different pH values were measured at 14.1 T at various B power levels. Multi-B -Z-spectra Bloch-McConnell fits at physiological pH were further improved by the fitting of Z-spectra of five pH values simultaneously. The obtained exchange rates were used in a six-pool Bloch-McConnell simulation including a tissue-like water pool and semi-solid MT pool with different CEST and CESL presaturation pulse trains. In vivo glucose injection experiments were performed in a tumor mouse model at 7 T.

Results And Discussion: Glucose Z-spectra could be fitted with four exchanging pools at 0.66, 1.28, 2.08 and 2.88 ppm. Corresponding hydroxyl exchange rates could be determined at pH = 7.2, T = 37°C and 1X PBS. Simulation of saturation transfer for this glucose system in a gray matter-like and a tumor-like system revealed optimal pulses at different field strengths of 9.4, 7 and 3 T. Different existing sequences and approaches are simulated and discussed. The optima found could be experimentally verified in an animal model at 7 T.

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.
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http://dx.doi.org/10.1002/nbm.4113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771698PMC
September 2019

T1ρ-based dynamic glucose-enhanced (DGEρ) MRI at 3 T: method development and early clinical experience in the human brain.

Magn Reson Med 2019 11 23;82(5):1832-1847. Epub 2019 Jun 23.

Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.

Purpose: The aim of this study was to translate the T ρ-based dynamic glucose-enhanced (DGEρ) experiment from ultrahigh magnetic field strengths to a clinical field strength of 3 T. Although the protocol would seem to be as simple as gadolinium-enhanced imaging, several obstacles had to be addressed, including signal-to-noise ratio (SNR), robustness of contrast, and postprocessing, especially motion correction.

Methods: Spin-lock based presaturation and a 3D gradient-echo snapshot readout were optimized for 3 T with regard to robustness, chemical exchange saturation transfer effect strength, and SNR. Postprocessing steps, including dynamic B and motion correction, were analyzed and optimized in 7 healthy volunteers. The final protocol, including glucose injection, was applied to 3 glioblastoma patients.

Results: With appropriate postprocessing, motion-related artifacts could be drastically reduced, and an SNR of approximately 90 could be achieved for a single dynamic measurement. In 2 patients with blood-brain barrier breakdown, a significant glucose uptake could be observed with a DGEρ effect strength in the range of 0.4% of the water signal. Thorough analysis of possible residual motion revealed that the statistical evidence can decrease when tested against pseudo effects attributed to uncorrected motion.

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 -ce tumor ring enhancement. However, effect sizes are small and careful clinical application is necessary.
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http://dx.doi.org/10.1002/mrm.27857DOI Listing
November 2019

Relaxation-compensated APT and rNOE CEST-MRI of human brain tumors at 3 T.

Magn Reson Med 2019 08 29;82(2):622-632. Epub 2019 Mar 29.

Division of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany.

Purpose: Relaxation-compensated CEST-MRI (i.e., the inverse metrics magnetization transfer ratio and apparent exchange-dependent relaxation) has already been shown to provide valuable information for brain tumor diagnosis at ultrahigh magnetic field strengths. This study aims at translating the established acquisition protocol at 7 T to a clinically relevant magnetic field strength of 3 T.

Methods: Protein model solutions were analyzed at multiple magnetic field strengths to assess the spectral widths of the amide proton transfer and relayed nuclear Overhauser effect (rNOE) signals at 3 T. This prior knowledge of the spectral range of CEST signals enabled a reliable and stable Lorentzian-fitting also at 3 T where distinct peaks are no longer resolved in the Z-spectrum. In comparison to the established acquisition protocol at 7 T, also the image readout was extended to three dimensions.

Results: The observed spectral range of CEST signals at 3 T was approximately ±15 ppm. Final relaxation-compensated amide proton transfer and relayed nuclear Overhauser effect contrasts were in line with previous results at 7 T. Examination of a patient with glioblastoma demonstrated the applicability of this acquisition protocol in a clinical setting.

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.
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http://dx.doi.org/10.1002/mrm.27751DOI Listing
August 2019

DeepCEST: 9.4 T Chemical exchange saturation transfer MRI contrast predicted from 3 T data - a proof of concept study.

Magn Reson Med 2019 06 25;81(6):3901-3914. Epub 2019 Feb 25.

High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.

Purpose: To determine the feasibility of employing the prior knowledge of well-separated chemical exchange saturation transfer (CEST) signals in the 9.4 T Z-spectrum to separate overlapping CEST signals acquired at 3 T, using a deep learning approach trained with 3 T and 9.4 T CEST spectral data from brains of the same subjects.

Methods: Highly spectrally resolved Z-spectra from the same volunteer were acquired by 3D-snapshot CEST MRI at 3 T and 9.4 T at low saturation power of B = 0.6 µT. The volume-registered 3 T Z-spectra-stack was then used as input data for a three layer deep neural network with the volume-registered 9.4 T fitted parameter stack as target data.

Results: An optimized neural net architecture could be found and verified in healthy volunteers. The gray-/white-matter contrast of the different CEST effects was predicted with only small deviations (Pearson R = 0.89). The 9.4 T prediction was less noisy compared to the directly measured CEST maps, although at the cost of slightly lower tissue contrast. Application to an unseen tumor patient measured at 3 T and 9.4 T revealed that tumorous tissue Z-spectra and corresponding hyper-/hypointensities of different CEST effects can also be predicted (Pearson R = 0.84).

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.
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http://dx.doi.org/10.1002/mrm.27690DOI Listing
June 2019

Possible artifacts in dynamic CEST MRI due to motion and field alterations.

J Magn Reson 2019 01 13;298:16-22. Epub 2018 Nov 13.

High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany; Department of Biomedical Magnetic Resonance, Eberhard-Karls University Tübingen, Tübingen, Germany.

Purpose: Dynamic CEST studies such as dynamic glucose enhanced imaging, have gained a lot of attention recently. The expected CEST effects after injection are rather small in tissue especially at clinical field strengths (0.5-2%). Small movements during the dynamic CEST measurement together with a subtraction-based evaluation can lead to pseudo CEST effects of the same order of magnitude. These artifacts are studied herein.

Methods: A brain tumor patient 3D-CEST baseline scan without glucose injection performed at 3 T is used to generate a virtual dynamic measurement introducing different kinds of simulated motion and B shifts.

Results: Minor motion (0.6 mm translations) and B artifacts (7 Hz shift) can lead to pseudo effects in the order of 1% in dynamic CEST imaging. Especially around tissue interfaces such as CSF borders or tumor affected areas, the pseudo effect patterns are non-intuitive and can be mistaken as dynamic agent uptake.

Conclusion: Correction or mitigation for small motions is crucial for dynamic CEST imaging, especially in subjects with lesions. Concomitant B alterations can as well induce pseudo CEST effects at 3 T.
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http://dx.doi.org/10.1016/j.jmr.2018.11.002DOI Listing
January 2019

3D gradient echo snapshot CEST MRI with low power saturation for human studies at 3T.

Magn Reson Med 2019 04 15;81(4):2412-2423. Epub 2018 Nov 15.

High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany.

Purpose: For clinical implementation, a chemical exchange saturation transfer (CEST) imaging sequence must be fast, with high signal-to-noise ratio (SNR), 3D coverage, and produce robust contrast. However, spectrally selective CEST contrast requires dense sampling of the Z-spectrum, which increases scan duration. This article proposes a compromise: using a 3D snapshot gradient echo (GRE) readout with optimized CEST presaturation, sampling, and postprocessing, highly resolved Z-spectroscopy at 3T is made possible with 3D coverage at almost no extra time cost.

Methods: A 3D snapshot CEST sequence was optimized for low-power CEST MRI at 3T. Pulsed saturation was optimized for saturation power and saturation duration. Spectral sampling and postprocessing (B correction, denoising) was optimized for spectrally selective Lorentzian CEST effect extraction. Reproducibility was demonstrated in 3 healthy volunteers and feasibility was shown in 1 tumor patient.

Results: Low-power saturation was achieved by a train of 80 pulses of duration t  = 20 ms (total saturation time t = 3.2 seconds at 50% duty cycle) with B = 0.6 μT at 54 irradiation frequency offsets. With the 3D snapshot CEST sequence, a 180 × 220 × 54 mm field of view was acquired in 7 seconds per offset. Spectrally selective CEST effects at +3.5 and -3.5 ppm were quantified using multi-Lorentzian fitting. Reproducibility was high with an intersubject coefficient of variation below 10% in CEST contrasts. Amide and nuclear overhauser effect CEST effects showed similar correlations in tumor and necrosis as show in previous ultra-high field work.

Conclusion: A sophisticated CEST tool ready for clinical application was developed and tested for feasibility.
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http://dx.doi.org/10.1002/mrm.27569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718050PMC
April 2019

CEST imaging at 9.4 T using adjusted adiabatic spin-lock pulses for on- and off-resonant T1⍴-dominated Z-spectrum acquisition.

Magn Reson Med 2019 01 8;81(1):275-290. Epub 2018 Sep 8.

Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany.

Purpose: The CEST experiment, with its correlation to rare proton species that are in exchange with the water pool, is very similar to the off-resonant water spin-lock (SL) experiment. In particular, low-power SL Z-spectrum acquisition allows insight into T and exchange effects with decreased direct water saturation. Because the available SL methods either require high B power or are instable in the presence of strong B and B inhomogeneity present at ultra-high fields, the goal of this study was to find a robust adiabatic SL pulse for on- and off-resonant application in the human brain at 9.4 T.

Methods: A series of Bloch simulations were used to find optimal pulse shape parameters of an adjusted hyperbolic secant pulse applicable in the low power regime typically used for exchange-weighted SL experiments. The optimized pulse was implemented and tested in phantom and in vivo experiments on a 9.4 T human scanner for on- and off-resonant T - and Z-spectrum measurements.

Results: The simulation yielded a feasible pulse shape, which yielded robust images, less sensitivity to B and B inhomogeneity compared with previous SL approaches and less direct water saturation, as well as a higher chemical exchange weighting compared with conventional CEST approaches.

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.
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http://dx.doi.org/10.1002/mrm.27380DOI Listing
January 2019

Chemical exchange saturation transfer MRI contrast in the human brain at 9.4 T.

Neuroimage 2018 10 15;179:144-155. Epub 2018 Jun 15.

High-field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany; Department of Biomedical Magnetic Resonance, Eberhard-Karls University Tübingen, Tübingen, Germany.

Purpose: The high chemical shift separation at 9.4 T allows for selective saturation of proton pools in exchange with water protons. For the first time, highly selective and comprehensive chemical exchange saturation transfer (CEST) experiments were performed in the human brain at 9.4 T. This work provides insight into CEST signals in the human brain in comparison with existing animal studies, as well as with CEST effects in vivo at lower field strengths.

Methods: A novel snapshot-CEST method for human brain scans at 9.4 T was optimized and employed for highly-spectrally-resolved (95 offsets) CEST measurements in healthy subjects and one brain tumor patient. Reproducibility and stability between scans was verified in grey and white matter after B, B, and motion correction of the acquired 3D CEST volumes. Two-step Lorentzian fitting was used to further improve separation of spectrally discernible signals to create known and novel CEST contrast maps at 9.4 T.

Results: At a saturation power of B = 0.5 μT most selective CEST effects could be obtained in the human brain with high inter-scan reproducibility. While contrast behavior of previously measured signals at lower field, namely amide-, guanidyl- and NOE-CEST effects, could be reproduced, novel signals at 2.7 ppm, and -1.6 ppm could be verified in healthy subjects and in a brain tumor patient for the first time.

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.
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http://dx.doi.org/10.1016/j.neuroimage.2018.06.026DOI Listing
October 2018
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