Simulation of acquisition shifts in T2 weighted fluid-attenuated inversion recovery magnetic resonance images to stress test artificial intelligence segmentation networks.

Purpose: To provide a simulation framework for routine neuroimaging test data, which allows for "stress testing" of deep segmentation networks against acquisition shifts that commonly occur in clinical practice for T2 weighted (T2w) fluid-attenuated inversion recovery magnetic resonance imaging protocols. Approach: The approach simulates "acquisition shift derivatives" of MR images based on MR signal equations. Experiments comprise the validation of the simulated images by real MR scans and example stress tests on state-of-the-art multiple sclerosis lesion segmentation networks to explore a generic model function to describe the F1 score in dependence of the contrast-affecting sequence parameters echo time (TE) and inversion time (TI). Results: The differences between real and simulated images range up to 19% in gray and white matter for extreme parameter settings. For the segmentation networks under test, the F1 score dependency on TE and TI can be well described by quadratic model functions (R2>0.9). The coefficients of the model functions indicate that changes of TE have more influence on the model performance than TI. Conclusions: We show that these deviations are in the range of values as may be caused by erroneous or individual differences in relaxation times as described by literature. The coefficients of the F1 model function allow for a quantitative comparison of the influences of TE and TI. Limitations arise mainly from tissues with a low baseline signal (like cerebrospinal fluid) and when the protocol contains contrast-affecting measures that cannot be modeled due to missing information in the DICOM header.

3D whole heart k-space-based super-resolution cardiac T1 mapping using rotated stacks.

Objective. To provide three-dimensional (3D) whole-heart high-resolution isotropic cardiac T1 maps using a k-space-based through-plane super-resolution reconstruction (SRR) with rotated multi-slice stacks.Approach. Due to limited SNR and cardiac motion, often only 2D T1 maps with low through-plane resolution (4-8 mm) can be obtained. Previous approaches used SRR to calculate 3D high-resolution isotropic cardiac T1 maps. However, they were limited to the ventricles. The proposed approach acquires rotated stacks in long-axis orientation with high in-plane resolution but low through-plane resolution. This results in radially overlapping stacks from which high-resolution T1 maps of the whole heart are reconstructed using a k-space-based SRR framework considering the complete acquisition model. Cardiac and residual respiratory motion between different breath holds is estimated and incorporated into the reconstruction. The proposed approach was evaluated in simulations and phantom experiments and successfully applied to ten healthy subjects.Main results. 3D T1 maps of the whole heart were obtained in the same acquisition time as previous methods covering only the ventricles. T1 measurements were possible even for small structures, such as the atrial wall. The proposed approach provided accurate (P> 0.4;R2> 0.99) and precise T1 values (SD of 64.32 ± 22.77 ms in the proposed approach, 44.73 ± 31.9 ms in the reference). The edge sharpness of the T1 maps was increased by 6.20% and 4.73% in simulation and phantom experiments, respectively. Contrast-to-noise ratios between the septum and blood pool increased by 14.50% inin vivomeasurements with a k-space compared to an image-space-based SRR.Significance. The proposed approach provided whole-heart high-resolution 1.3 mm isotropic T1 maps in an overall acquisition time of approximately three minutes. Small structures, such as the atrial and right ventricular walls, could be visualized in the T1 maps.

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

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

Investigating the Role of Sulfate Groups for the Binding of Gd3+ Ions to Glycosaminoglycans with NMR Relaxometry.

Glycosaminoglycans (GAGs) are highly negatively charged macromolecules with a large cation binding capacity, but their interaction potential with exogeneous Gd3+ ions is under-investigated. These might be released from chelates used as Gadolinium-based contrast agents (GBCAs) for clinical MR imaging due to transmetallation with endogenous cations like Zn2+ . Recent studies have quantified how an endogenous GAG sequesters released Gd3+ ions and impacts the thermodynamic and kinetic stability of some GBCAs. In this study, we investigate and compare the chelation ability of two important GAGs (heparin and chondroitin sulfate), as well as the homopolysaccharides dextran and dextran sulfate that are used as models for alternative macromolecular chelators. Our combined approach of MRI-based relaxometry and isothermal titration calorimetry shows that the chelation process of Gd3+ into GAGs is not just a long-range electrostatic interaction as proposed for the Manning model, but presumably a site-specific binding. Furthermore, our results highlight the crucial role of sulfate groups in this process and indicate that the potential of a specific GAG to engage in this mechanism increases with its degree of sulfation. The transchelation of Gd3+ ions from GBCAs to sulfated GAGs should thus be considered as one possible explanation for the observed long-term deposition of Gd3+ in vivo and related observations of long-term signal enhancements on T1 -weighted MR images.

Rapid analytical CEST spectroscopy of competitive host-guest interactions using spatial parallelization with a combined approach of variable flip angle, keyhole and averaging (CAVKA).

A serious limitation of high resolution 129Xe chemical exchange saturation transfer (CEST) NMR spectroscopy for comparing competitive host-guest interactions from different samples is the long acquisition time due to step-wise encoding of the chemical shift dimension. A method of optimized use of 129Xe spin magnetization to enable the accelerated and simultaneous acquisition of CEST spectra from multiple samples or regions in a setup is described. The method is applied to investigate the host-guest system of commercially available cucurbit[7]uril (CB7) and xenon with competing guests: cis-1,4-bis(aminomethyl)cyclohexane, cadaverine, and putrescine. Interactions with the different guests prove that the observed CEST signal is from a CB6 impurity and that CB7 itself does not produce a CEST signal. Instead, rapid interactions between xenon and CB7 manifest in the spectrum as a broad saturation response that could be suppressed by cis-1,4-bis(aminomethyl)cyclohexane. This guest prevents interactions at the CB7 portals. The suggested method represents a type of spectroscopic imaging that is capable of capturing the exchange kinetics information of systems that otherwise suffer from shortened T2 times and yields multiple spectra for comparing exchange conditions with a reduction of >95% in acquisition time. The spectral quality is sufficient to perform quantitative analysis and quantifications relative to a CB6 standard as well as relative to a known blocker concentration (putrescine) that both reveal an unexpectedly high CB6 impurity of ca. 8%.

An NMR relaxometry approach for quantitative investigation of the transchelation of gadolinium ions from GBCAs to a competing macromolecular chelator.

Gadolinium-based contrast agents (GBCAs) have been used in clinical Magnetic Resonance Imaging (MRI) for more than 30 years. However, there is increasing evidence that their dissociation in vivo leads to long-term depositions of gadolinium ions in the human body. In vitro experiments provide critical insights into kinetics and thermodynamic equilibria of underlying processes, which give hints towards the in vivo situation. We developed a time-resolved MRI relaxometry-based approach that exploits distinct relaxivities of Gd3+ in different molecular environments. Its applicability to quantify the transmetallation of GBCAs, the binding of Gd3+ to competing chelators, and the combined transchelation process is demonstrated. Exemplarily, the approach is applied to investigate two representative GBCAs in the presence of Zn2+ and heparin, which is used as a model for a macromolecular and physiologically occurring chelator. Opposing indirect impacts of heparin on increasing the kinetic stability but reducing the thermodynamic stability of GBCAs are observed. The relaxivity of resulting Gd-heparin complexes is shown to be essentially increased compared to that of the parent GBCAs so that they might be one explanation for observed long-term MRI signal enhancement in vivo. In forthcoming studies, the presented method could help to identify the most potent Gd-complexing macromolecular species.

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

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.

A novel normalization for amide proton transfer CEST MRI to correct for fat signal-induced artifacts: application to human breast cancer imaging.

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.

Dynamic glucose-enhanced (DGE) MRI in the human brain at 7 T with reduced motion-induced artifacts based on quantitative R1ρ mapping.

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.

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. 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.

High Exchange Rate Complexes of 129 Xe with Water-Soluble Pillar[5]arenes for Adjustable Magnetization Transfer MRI.

Macrocyclic host structures for generating transiently bound 129 Xe have been used in various ultra-sensitive NMR and MRI applications for molecular sensing of biochemical analytes. They are based on hyperpolarized nuclei chemical exchange saturation transfer (Hyper-CEST). Here, we tested a set of water-soluble pillar[5]arenes with different counterions in order to compare their potential contrast agent abilities with that of cryptophane-A (CrA), the most widely used host for such purposes. The exchange of Xe with such compounds was found to be sensitive to the type of ions present in solution and can be used for switchable magnetization transfer (MT) contrast that arises from off-resonant pre-saturation. We demonstrate that the adjustable MT magnitude depends on the interplay of saturation parameters and found that the optimum MT contrast surpasses the CrA CEST performance at moderate saturation power. Since modification of such water-soluble pillar[5]arenes is straightforward, these compounds can be considered a promising platform for designing various sensors that may complement the field of Xe HyperCEST-based biosensing MRI.

Assessing the predictability of IDH mutation and MGMT methylation status in glioma patients using relaxation-compensated multipool CEST MRI at 7.0 T.

Background: Early identification of prognostic superior characteristics in glioma patients such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH mutation status, MGMT promoter methylation, and differentiation of low-grade versus high-grade glioma (LGG vs HGG) in newly diagnosed patients employing relaxation-compensated multipool chemical exchange saturation transfer (CEST) MRI at 7.0 Tesla. Methods: Thirty-one patients with newly diagnosed glioma were included in this prospective study. CEST MRI was performed at a 7T whole-body scanner. Nuclear Overhauser effect (NOE) and isolated amide proton transfer (APT; downfield NOE-suppressed APT = dns-APT) CEST signals (mean value and 90th signal percentile) were quantitatively investigated in the whole tumor area with regard to predictability of IDH mutation, MGMT promoter methylation status, and differentiation of LGG versus HGG. Statistics were performed using receiver operating characteristic (ROC) and area under the curve (AUC) analysis. Results were compared with advanced MRI methods (apparent diffusion coefficient and relative cerebral blood volume ROC/AUC analysis) obtained at 3T. Results: dns-APT CEST yielded highest AUCs in IDH mutation status prediction (dns-APTmean = 91.84%, P < 0.01; dns-APT90 = 97.96%, P < 0.001). Furthermore, dns-APT metrics enabled significant differentiation of LGG versus HGG (AUC: dns-APTmean = 0.78, P < 0.05; dns-APT90 = 0.83, P < 0.05). There was no significant difference regarding MGMT promoter methylation status at any contrast (P > 0.05). 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 procedure. For this purpose, the approach of chemical exchange saturation transfer (CEST) was extended to a radiofrequency (RF) irradiation scheme at two different frequency offsets (dualCEST). Using protein model solutions, it was demonstrated that the dualCEST technique allows the calculation of an image contrast which is exclusively sensitive to changes in concentration, molecular size and the folding state of mobile proteins. With respect to application in humans, dualCEST overcomes the selectivity limitations at relatively low magnetic field strengths, and thus enables examinations on clinical MR scanners. The feasibility of dualCEST examinations in humans was verified by a proof-of-principle examination of a brain tumor patient at 3 T. With its specificity for the mobile fraction of the proteome, its comparable sensitivity to conventional water proton MRI and its applicability to clinical MR scanners, this technique represents a further step towards the non-invasive imaging of proteomic changes in humans.

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 with a 7.0-T whole-body unit with a temporal resolution of approximately 7 seconds, yielding the time-resolved DGE contrast. T1ρ-weighted DGE MR imaging was performed with injection of 100 mL of 20% d-glucose via the cubital vein. Glucose enhancement, given by the relative signal intensity change at T1ρ-weighted MR imaging (DGEρ), was quantitatively investigated in brain gray matter versus white matter of healthy volunteers and in tumor tissue versus normal-appearing white matter of patients with glioblastoma. The median signal intensities of the assessed brain regions were compared by using the Wilcoxon rank-sum test. Results In healthy volunteers, the median signal intensity in basal ganglia gray matter (DGEρ = 4.59%) was significantly increased compared with that in white matter tissue (DGEρ = 0.65%) (P = .028). In patients, the median signal intensity in the glucose-enhanced tumor region as displayed on T1ρ-weighted DGE images (DGEρ = 2.02%) was significantly higher than that in contralateral normal-appearing white matter (DGEρ = 0.08%) (P < .0001). Conclusion T1ρ-weighted DGE MR imaging in healthy volunteers and patients with newly diagnosed, untreated glioblastoma enabled visualization of brain glucose physiology and pathophysiologically increased glucose uptake and may have the potential to provide information about glucose metabolism in tumor tissue. © RSNA, 2017 Online supplemental material is available for this article.

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 potentially the metabolism of tumors. As an important step to fulfill the clinical needs for practicability, reproducibility and imaging speed we present here a robust and quantitative T1ρ-weighted technique for dynamic glucose enhanced MRI (DGE-MRI) with a temporal resolution of less than 7 seconds. Applied to a brain tumor patient, the new technique provided a distinct DGE contrast between tumor and healthy brain tissue and showed the detailed dynamics of the glucose enhancement after intravenous injection. Development of this fast and quantitative DGE-MRI technique allows for a more detailed analysis of DGE correlations in the future and potentially enables non-invasive diagnosis, staging and monitoring of tumor response to therapy.

Simultaneous mapping of water shift and B1 (WASABI)-Application to field-Inhomogeneity correction of CEST MRI data.

PURPOSE: Together with the development of MRI contrasts that are inherently small in their magnitude, increased magnetic field accuracy is also required. Hence, mapping of the static magnetic field (B0 ) and the excitation field (B1 ) is not only important to feedback shim algorithms, but also for postprocess contrast-correction procedures. METHODS: A novel field-inhomogeneity mapping method is presented that allows simultaneous mapping of the water shift and B1 (WASABI) using an off-resonant rectangular preparation pulse. The induced Rabi oscillations lead to a sinc-like spectrum in the frequency-offset dimension and allow for determination of B0 by its symmetry axis and of B1 by its oscillation frequency. RESULTS: Stability of the WASABI method with regard to the influences of T1 , T2 , magnetization transfer, and repetition time was investigated and its convergence interval was verified. B0 and B1 maps obtained simultaneously by means of WASABI in the human brain at 3 T and 7 T can compete well with maps obtained by standard methods. Finally, the method was applied successfully for B0 and B1 correction of chemical exchange saturation transfer MRI (CEST-MRI) data of the human brain. CONCLUSION: The proposed WASABI method yields a novel simultaneous B0 and B1 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.

Adiabatically prepared spin-lock approach for T1ρ-based dynamic glucose enhanced MRI at ultrahigh fields.

PURPOSE: Chemical exchange sensitive spin-lock and related techniques allow to observe the uptake of administered D-glucose in vivo. The exchange-weighting increases with the magnetic field strength, but inhomogeneities in the radiofrequency (RF) field at ultrahigh field whole-body scanners lead to artifacts in conventional spin-lock experiments. Thus, our aim was the development of an adiabatically prepared T1ρ -based imaging sequence applicable to studies of glucose metabolism in tumor patients at ultrahigh field strengths. METHODS: An adiabatically prepared on-resonant spin-lock approach was realized at a 7 Tesla whole-body scanner and compared with conventional spin-lock. The insensitivity to RF field inhomogeneities as well as the chemical exchange sensitivity of the approach was investigated in simulations, model solutions and in the human brain. RESULTS: The suggested spin-lock approach was shown to be feasible for in vivo application at ultrahigh field whole-body scanners and showed substantially improved image quality compared with conventional spin-lock. The sensitivity of the presented method to glucose was verified in model solutions and a glucose contrast was observed in a glioblastoma patient after intravenous administration of glucose solution. CONCLUSION: An adiabatically prepared spin-lock preparation was presented that enables a homogeneous and chemical exchange sensitive T1ρ -based imaging at ultra-high field whole-body scanners, e.g., for T1ρ -based dynamic glucose enhanced MRI. Magn Reson Med 78:215-225, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

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 CEST contrasts can be strongly affected by the MT background, so corrections are needed to derive accurate estimates of CEST effects. Herein we show that a full analytical solution of the underlying Bloch-McConnell equations for both MT and CEST provides insights into their interaction and suggests a simple means to isolate their effects. The presented analytical solution, based on the eigenspace solution of the Bloch-McConnell equations, extends previous treatments by allowing arbitrary lineshapes for the semi-solid MT effects and simultaneously describing multiple CEST pools in the presence of a large MT pool for arbitrary irradiation. The structure of the model indicates that semi-solid MT and CEST effects basically add up inversely in determining the steady-state Z-spectrum, as previously shown for direct saturation and CEST effects. Implications for existing previous CEST analyses in the presence of a semi-solid MT are studied and discussed. It turns out that, to accurately quantify CEST contrast, a good reference Z-value, the observed longitudinal relaxation rate of water, and the semi-solid MT pool size fraction must all be known.