Magnetization Transfer Effects Research Articles

Pathological tissue changes in brain tumors affect the pH-sensitivity of the T1-corrected apparent exchange dependent relaxation (AREX) of the amide protons.

Measuring the intracellular pH (pHi) is of interest for brain tumor diagnostics. Common metrics of CEST imaging like the amide proton transfer-weighted (APTw) MTRasym are pHi sensitive and allow differentiating malignant tumor from healthy tissue. Yet, the image contrast also depends on additional magnetization transfer effects and T1. In contrast, the apparent exchange-dependent relaxation (AREX) provides a T1 corrected exchange rate of the amide protons. As AREX still depends on amide proton density, its pHi sensitivity remains ambiguous. Hence, we conducted this study to assess the influence of pathologic tissue changes on the pHi sensitivity of AREX in vivo. Patients with newly diagnosed intra-axial brain tumors were prospectively recruited and underwent conventional MRI, quantitative T1 relaxometry, APT-CEST and 31P-MRS on a 3T MRI scanner. Tumors were segmented into contrast-enhancing tumor (CE), surrounding T2 hyperintensity (T2-H) and contralateral normal appearing white matter (CNAWM). T1 mapping and APT-CEST metrics were correlated with 31P-MRS-derived pHi maps (Pearson's correlation). Without differentiating tissue subtypes, pHi did not only correlate significantly with MTRasym (r= 0.46) but also with T1 (r= 0.49). Conversely, AREX only correlated poorly with pHi (r= 0.17). Analyzing different tissue subtypes separately revealed a tissue dependency of the pHi sensitivity of AREX with a significant correlation (r= 0.6) in CNAWM and no correlation in T2-H or CE (r= -0.11/-0.24). CE showed significantly increased MTRasym, pHi, and T1 compared with CNAWM (p< 0.001). In our study, the pHi sensitivity of AREX was limited to CNAWM. The lack of sensitivity in CE and T2-H is probably attributable to altered amide and water proton concentrations in these tissues. Conversely, the correlation of pHi with MTRasym may be explained by the coincidental contrast increase through increased T1 and amide proton density. Therefore, limited structural deviations from CNAWM might be a perquisite for the use of CEST contrasts as pHi-marker.

Enhancing amide proton transfer imaging in ischemic stroke using a machine learning approach with partially synthetic data.

Amide proton transfer (APT) imaging, a technique sensitive to tissue pH, holds promise in the diagnosis of ischemic stroke. Achieving accurate and rapid APT imaging is crucial for this application. However, conventional APT quantification methods either lack accuracy or are time-consuming. Machine learning (ML) has recently been recognized as a potential solution to improve APT quantification. In this paper, we applied an ML model trained on a new type of partially synthetic data, along with an optimization approach utilizing recursive feature elimination, to predict APT imaging in an animal stroke model. This partially synthetic datum is not a simple blend of measured and simulated chemical exchange saturation transfer (CEST) signals. Rather, it integrates the underlying components including all CEST, direct water saturation, and magnetization transfer effects partly derived from measurements and simulations to reconstruct the CEST signals using an inverse summation relationship. Training with partially synthetic data requires less in vivo data compared to training entirely with fully synthetic or in vivo data, making it a more practical approach. Since this type of data closely resembles real tissue, it leads to more accurate predictions than ML models trained on fully synthetic data. Results indicate that an ML model trained on this partially synthetic data can successfully predict the APT effect with enhanced accuracy, providing significant contrast between stroke lesions and normal tissues, thus clearly delineating lesions. In contrast, conventional quantification methods such as the asymmetric analysis method, three-point method, and multiple-pool model Lorentzian fit showed inadequate accuracy in quantifying the APT effect. Moreover, ML methods trained using in vivo data and fully synthetic data exhibited poor predictive performance due to insufficient training data and inaccurate simulation pool settings or parameter ranges, respectively. Following optimization, only 13 frequency offsets were selected from the initial 69, resulting in significantly reduced scan time.

Parallel transmit hybrid pulse design for controlled on-resonance magnetization transfer in R1 mapping at 7T.

This work proposes a "hybrid" RF pulse design method for parallel transmit (pTx) systems to simultaneously control flip angle and root-mean-squared ( ). These pulses are generally only designed for flip angle, however, this can lead to uncontrolled , which then leads to variable magnetization transfer (MT) effects. We demonstrate the hybrid design approach for quantitative imaging where both flip angle and are important. A dual cost function optimization is performed containing the normalized mean squared errors of the flip angle and distributions weighted by a parameter . Simulations were conducted to study the behavior of both properties when simultaneously optimizing them. In vivo experiments on a 7T MRI system with an 8-channel pTx head coil were carried out to study the effect of the hybrid design approach on variable flip angle (= 1/T1) mapping. Simulations showed that both flip angle and can be homogenized simultaneously without detriment to either when compared to an individual optimization. By homogenizing flip angle and , maps were more uniform (coefficient of variation 6.6% vs. 13.0%) compared to those acquired with pulses that only homogenized flip angle. The proposed hybrid design homogenizes on-resonance MT effects while homogenizing the flip angle distribution, with only a small detriment in the latter compared to a pulse that just homogenizes flip angle. This improved mapping by controlling incidental MT effects, yielding more uniform maps.

Optimization of 1H-MRS methods for large-volume acquisition of low-concentration downfield resonances at 3 T and 7 T.

This goal of this study was to optimize spectrally selective 1H-MRS methods for large-volume acquisition of low-concentration metabolites with downfield resonances at 7 T and 3 T, with particular attention paid to detection of nicotinamide adenine dinucleotide (NAD+) and tryptophan. Spectrally selective excitation was used to avoid magnetization-transfer effects with water, and various sinc pulses were compared with a band-selective, uniform response, pure-phase (E-BURP) pulse. Localization using a single-slice selective pulse was compared with voxel-based localization that used three orthogonal refocusing pulses, and low bandwidth refocusing pulses were used to take advantage of the chemical shift displacement of water. A technique for water sideband removal was added, and a method of coil channel combination for large volumes was introduced. Proposed methods were compared qualitatively with previously reported techniques at 7 T. Sinc pulses resulted in reduced water signal excitation and improved spectral quality, with a symmetric, low bandwidth-time product pulse performing best. Single-slice localization allowed shorter TEs with large volumes, enhancing signal, whereas low-bandwidth slice-selective localization greatly reduced the observed water signal. Gradient cycling helped remove water sidebands, and frequency aligning and pruning individual channels narrowed spectral linewidths. High-quality brain spectra of NAD+ and tryptophan are shown in 4 subjects at 3 T. Improved spectral quality with higher downfield signal, shorter TE, lower nuisance signal, reduced artifacts, and narrower peaks was realized at 7 T. These methodological improvements allowed for previously unachievable detection of NAD+ and tryptophan in human brain at 3 T in under 5 min.

Ultra-low-field magnetization transfer imaging at 0.055T with low specific absorption rate.

To demonstrate magnetization transfer (MT) effects with low specific absorption rate (SAR) on ultra-low-field (ULF) MRI. MT imaging was implemented by using sinc-modulated RF pulse train (SPT) modules to provide bilateral off-resonance irradiation. They were incorporated into 3D gradient echo (GRE) and fast spin echo (FSE) protocols on a shielding-free 0.055T head scanner. MT effects were first verified using phantoms. Brain MT imaging was conducted in both healthy subjects and patients. MT effects were clearly observed in phantoms using six SPT modules with total flip angle 3600° at central primary saturation bands of approximate offset ±786 Hz, even in the presence of large relative B0 inhomogeneity. For brain, strong MT effects were observed in gray matter, white matter, and muscle in 3D GRE and FSE imaging using six and sixteen SPT modules with total flip angle 3600° and 9600°, respectively. Fat, cerebrospinal fluid, and blood exhibited relatively weak MT effects. MT preparation enhanced tissue contrasts in T2-weighted and FLAIR-like images, and improved brain lesion delineation. The estimated MT SAR was 0.0024 and 0.0008 W/kg for two protocols, respectively, which is far below the US Food and Drug Administration (FDA) limit of 3.0 W/kg. Robust MT effects can be readily obtained at ULF with extremely low SAR, despite poor relative B0 homogeneity in ppm. This unique advantage enables flexible MT pulse design and implementation on low-cost ULF MRI platforms to achieve strong MT effects in brain and beyond, potentially augmenting their clinical utility in the future.

Anisotropic longitudinal water proton relaxation in white matter investigated ex vivo in porcine spinal cord with sample rotation

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Fast magnetization transfer saturation imaging of the brain using MP2RAGE T1 mapping.

Magnetization transfer saturation (MTsat) mapping is commonly used to examine the macromolecular content of brain tissue. This study compared variable flip angle (VFA) T1 mapping against compressed-sensing MP2RAGE (csMP2RAGE) T1 mapping for accelerating MTsat imaging. VFA, MP2RAGE, and csMP2RAGE were compared against inversion-recovery T1 in an aqueous phantom at 3 T. The same 1-mm VFA, MP2RAGE, and csMP2RAGE protocols were acquired in 4 healthy subjects to compare T1 and MTsat. Bloch-McConnell simulations were used to investigate differences between the phantom and in vivo T1 results. Ten healthy controls were imaged twice with the csMP2RAGE MTsat protocol to quantify repeatability. The MP2RAGE and csMP2RAGE protocols were 13.7% and 32.4% faster than the VFA protocol, respectively. At these scan times, all approaches provided strong repeatability and accurate T1 times (< 5% difference) in the phantom, but T1 accuracy was more impacted by T2 for VFA than for MP2RAGE. In vivo, VFA estimated longer T1 times than MP2RAGE and csMP2RAGE. Simulations suggest that the differences in the T1 measured using VFA, MP2RAGE, and inversion recovery could be explained by the magnetization-transfer effects. In the test-retest experiment, we found that the csMP2RAGE has a minimum detectable change of 2.3% for T1 mapping and 7.8% for MTsat imaging. We demonstrated that MP2RAGE can be used in place of VFA T1 mapping in an MTsat protocol. Furthermore, a shorter scan time and high repeatability can be achieved using the csMP2RAGE sequence.

Robust T2 estimation with balanced steady state free precession.

To develop a novel signal representation for balanced steady state free precession (bSSFP) displaying its T2 independence on B1 and on magnetization transfer (MT) effects. A signal model for bSSFP is developed that shows only an explicit dependence (up to a scaling factor) on E2 (and, therefore, T2) and a novel parameter c (with implicit dependence on the flip angle and E1). Moreover, it is shown that MT effects, entering the bSSFP signal via a binary spin bath model, can be captured by a redefinition of T1 and, therefore, leading to modification of E1, resulting in the same signal model. Various sets of phase-cycled bSSFP brain scans (different flip angles, different TR, different RF pulse durations, and different number of phase cycles) were recorded at 3 T. The parameters T2 (E2) and c were estimated using a variable projection (VARPRO) method and Monte-Carlo simulations were performed to assess T2 estimation precision. Initial experiments confirmed the expected independence of T2 on various protocol settings, such as TR, the flip angle, B1 field inhomogeneity, and the RF pulse duration. Any variation (within the explored range) appears to directly affect the estimation of the parameter c only-in agreement with theory. BSSFP theory predicts an extraordinary feature that all MT and B1-related variational aspects do not enter T2 estimation, making it a potentially robust methodology for T2 quantification, pending validation against existing standards.

A rapid method for phosphocreatine-weighted imaging in muscle using double saturation power-chemical exchange saturation transfer.

Monitoring the variation in phosphocreatine (PCr) levels following exercise provides valuable insights into muscle function. Chemical exchange saturation transfer (CEST) has emerged as a sensitive method with which to measure PCr levels in muscle, surpassing conventional MR spectroscopy. However, existing approaches for quantifying PCr CEST signals rely on time-consuming fitting methods that require the acquisition of the entire or a section of the CEST Z-spectrum. Additionally, traditional fitting methods often necessitate clear CEST peaks, which may be challenging to obtain at low magnetic fields. This paper evaluated the application of a new model-free method using double saturation power (DSP), termed DSP-CEST, to estimate the PCr CEST signal in muscle. The DSP-CEST method requires the acquisition of only two or a few CEST signals at the PCr frequency offset with two different saturation powers, enabling rapid dynamic imaging. Additionally, the DSP-CEST approach inherently eliminates confounding signals, offering enhanced robustness compared with fitting methods. Furthermore, DSP-CEST does not demand clear CEST peaks, making it suitable for low-field applications. We evaluated the capability of DSP-CEST to enhance the specificity of PCr CEST imaging through simulations and experiments on muscle tissue phantoms at 4.7 T. Furthermore, we applied DSP-CEST to animal leg muscle both before and after euthanasia and observed successful reduction of confounding signals. The DSP-CEST signal still has contaminations from a residual magnetization transfer (MT) effect and an aromatic nuclear Overhauser enhancement effect, and thus only provides a PCr-weighted imaging. The residual MT effect can be reduced by a subtraction of DSP-CEST signals at 2.6 and 5 ppm. Results show that the residual MT-corrected DSP-CEST signal at 2.6 ppm has significant variation in postmortem tissues. By contrast, both the CEST signal at 2.6 ppm and a conventional Lorentzian difference analysis of CEST signal at 2.6 ppm demonstrate no significant variation in postmortem tissues.

Effects of magnetization and heat transfer on electrically conducting magnetohydrodynamics flow with mixed convection flow over porous duct

The effects of magnetic field and heat transfer problem on incompressible magnetohydrodynamics (MHD) mixed unsteady convective flow of an electrically conducting viscous fluid in a duct filled with a porous medium are investigated. The fluid flow is subjected to an applied uniform magnetic field vertical to the duct and uniform free stream of constant velocity and temperature. The system of nonlinear differential equations governing flow and heat transfer phenomena are derived and reduced into a set of ordinary differential equations using the auxiliary variable method. The reduced equations are solved numerically using Runge-Kutta method associated with slip boundary conditions. The graphical results for velocity, temperature and heat transfer rate are obtained using MATLAB software. It is observed that the velocity profiles increase with an increase of similarity parameter (fI) while temperature gradient decreases rapidly with an increase of similarity parameter (θI) for different values of Grosh number, Magnetization and Prandtl number respectively.

Fast and robust pulsed chemical exchange saturation transfer (CEST) MRI using a quasi-steady-state (QUASS) algorithm at 3 T

Chemical exchange saturation transfer (CEST) has emerged as a powerful technique to image dilute labile protons. However, its measurement depends on the RF saturation duration (Tsat) and relaxation delay (Trec). Although the recently developed quasi-steady-state (QUASS) solution can reconstruct equilibrium CEST effects under continuous-wave RF saturation, it does not apply to pulsed-CEST MRI on clinical scanners with restricted hardware or specific absorption rate limits. This study proposed a QUASS algorithm for pulsed-CEST MRI and evaluated its performance in muscle CEST measurement. An approximated expression of a steady-state pulsed-CEST signal was incorporated in the off-resonance spin-lock model, from which the QUASS pulsed-CEST effect was derived. Numerical simulation, creatine phantom, and healthy volunteer scans were conducted at 3 T. The CEST effect was quantified with asymmetry analysis in the simulation and phantom experiments. CEST effects of creatine, amide proton transfer, phosphocreatine, and combined magnetization transfer and nuclear Overhauser effects were isolated from a multi-pool Lorentzian model in muscles. Apparent and QUASS CEST measurements were compared under different Tsat/Trec and duty cycles. Paired Student's t-test was employed with P < 0.05 as statistically significant. The simulation, phantom, and human studies showed the strong impact of Tsat/Trec on apparent CEST measurements, which were significantly smaller than the corresponding QUASS CEST measures, especially under short Tsat/Trec times. In comparison, the QUASS algorithm mitigates such impact and enables accurate CEST measurements under short Tsat/Trec times. In conclusion, the QUASS algorithm can accelerate robust pulsed-CEST MRI, promising the efficient detection and evaluation of muscle diseases in clinical settings.

B1 inhomogeneity-corrected T1 mapping and quantitative magnetization transfer imaging via simultaneously estimating Bloch-Siegert shift and magnetization transfereffects.

To introduce a method of inducing Bloch-Siegert shift and magnetization Transfer Simultaneously (BTS) and demonstrate its utilization for measuring binary spin-bath model parameters free pool spin-lattice relaxation ( ), macromolecular fraction ( ), magnetization exchange rate ( ) and local transmit field ( ). Bloch-Siegert shift and magnetization transfer is simultaneously induced through the application of off-resonance irradiation in between excitation and acquisition of an RF-spoiled gradient-echo scheme. Applying the binary spin-bath model, an analytical signal equation is derived and verified through Bloch simulations. Monte Carlo simulations were performed to analyze the method's performance. The estimation of the binary spin-bath parameters with compensation was further investigated through experiments, both ex vivo and in vivo. Comparing BTS with existing methods, simulations showed that existing methods can significantly bias estimation when not accounting for transmit heterogeneity and MT effects that are present. Phantom experiments further showed that the degree of this bias increases with increasing macromolecular proton fraction. Multi-parameter fit results from an in vivo brain study generated values in agreement with previous literature. Based on these studies, we confirmed that BTS is a robust method for estimating the binary spin-bath parameters in macromolecule-rich environments, even in the presence of inhomogeneity. A method of estimating Bloch-Siegert shift and magnetization transfer effect has been developed and validated. Both simulations and experiments confirmed that BTS can estimate spin-bath parameters ( , , ) that are free from bias.

CEST2022 - mapping multi-pool CEST signal changes in an animal model of brain tumor with quasi-steady-state reconstruction-empowered CEST quantification

Chemical exchange saturated transfer (CEST) MRI has biomarker potential to assess tissue microenvironment in brain tumors. Multi-pool Lorentzian or spinlock models provides useful insights into the CEST contrast mechanism. However, T1 contribution to the complex overlapping effects of brain tumors is difficult under the non-equilibrium state. Therefore, this study evaluated T1 contributions on multi-pool parameters with quasi-steady-state (QUASS) algorithm reconstructed equilibrium data. MRI scans were performed in rat brain tumor models, including relaxation, diffusion, and CEST imaging. A pixel-wise seven-pool spinlock-model was employed to fit QUASS reconstructed CEST Z-spectra and evaluated the magnetization transfer (MT), amide, amine, guanidyl, and nuclear-overhauled effect (NOE) signals in tumor and normal tissues. In addition, T1 was estimated from the spinlock-model fitting and compared with measured T1. We observed tumor had a statistically significant increase in the amide signal (p < 0.001) and decreases in the MT and NOE signals (p < 0.001). On the other hand, the differences in amine and guanidyl between the tumor and contralateral normal regions were not statistically significant. The differences between measured and estimated T1 values were 8% in the normal tissue and 4% in the tumor. Furthermore, the isolated MT signal strongly correlated with R1 (r = 0.96, P < 0.001). In summary, we successfully unraveled multi-factorial effects in the CEST signal using spinlock-model fitting and QUASS method and demonstrated the effect of T1 relaxation on MT and NOE.

Isolation of amide proton transfer effect and relayed nuclear Overhauser enhancement effect at -3.5ppm using CEST with double saturation powers.

Quantifications of amide proton transfer (APT) and nuclear Overhauser enhancement (rNOE(-3.5)) mediated saturation transfer with high specificity are challenging because their signals measured in a Z-spectrum are overlapped with confounding signals from direct water saturation (DS), semi-solid magnetization transfer (MT), and CEST of fast-exchange pools. In this study, based on two canonical CEST acquisitions with double saturation powers (DSP), a new data-postprocessing method is proposed to specifically quantify the effects of APT and rNOE. For CEST imaging with relatively low saturation powers ( ), both the fast-exchange CEST effect and the semi-solid MT effect roughly depend on , whereas the slow-exchange APT/rNOE(-3.5) effect do not, which is exploited to isolate a part of the APT and rNOE effects from the confounding signals in this study. After a mathematical derivation for the establishment of the proposed method, numerical simulations based on Bloch equations are then performed to demonstrate its specificity to detections of the APT and rNOE effects. Finally, an in vivo validation of the proposed method is conducted using an animal tumor model at a 4.7 T MRI scanner. The simulations show that DSP-CEST can quantify the effects of APT and rNOE and substantially eliminate the confounding signals. The in vivo experiments demonstrate that the proposed DSP-CEST method is feasible for the imaging of tumors. The data-postprocessing method proposed in this study can quantify the APT and rNOE effects with considerably increased specificities and a reduced cost of imaging time.

Quantitative MRI by nonlinear inversion of the Bloch equations

Development of a generic model-based reconstruction framework for multiparametric quantitative MRI that can be used with data from different pulse sequences. Generic nonlinear model-based reconstruction for quantitative MRI estimates parametric maps directly from the acquired k-space by numerical optimization. This requires numerically accurate and efficient methods to solve the Bloch equations and their partial derivatives. In this work, we combine direct sensitivity analysis and pre-computed state-transition matrices into a generic framework for calibrationless model-based reconstruction that can be applied to different pulse sequences. As a proof-of-concept, the method is implemented and validated for quantitative and mapping with single-shot inversion-recovery (IR) FLASH and IR bSSFP sequences in simulations, phantoms, and the human brain. The direct sensitivity analysis enables a highly accurate and numerically stable calculation of the derivatives. The state-transition matrices efficiently exploit repeating patterns in pulse sequences, speeding up the calculation by a factor of 10 for the examples considered in this work, while preserving the accuracy of native ordinary differential equations solvers. The generic model-based method reproduces quantitative results of previous model-based reconstructions based on the known analytical solutions for radial IR FLASH. For IR bSFFP it produces accurate and maps for the National Insitute of Standards and Technology (NIST) phantom in numerical simulations and experiments. Feasibility is also shown for human brain, although results are affected by magnetization transfer effects. By developing efficient tools for numerical optimizations using the Bloch equations as forward model, this work enables generic model-based reconstruction for quantitative MRI.

Non-contrast estimate of blood-brain barrier permeability in humans using arterial spin labeling and magnetization transfer at 7T.

Blood-brain barrier (BBB) dysfunction is associated with a number of central nervous system diseases. This study demonstrates the application of a novel noninvasive technique to measure the BBB permeability in the human brain at 7T. The technique exploits the fact that, when tissue macromolecules are saturated by off-resonance RF pulse, the intravascular and the extravascular (tissue) water experience different magnetization transfer effects. This principle was combined with arterial spin labeling to distinguish between the intravascular and the tissue water, and was used to calculate perfusion, water extraction fraction (E), and BBB permeability surface area product for water (PS). Simultaneous coregistered magnetization transfer ratio maps were also generated that can provide valuable additional information. Eighteen healthy volunteers (seven females), age = 27 ± 11 years and weight = 65 ± 9kg, participated in the study. Average perfusion was 67 ± 5 and 29 ± 4ml/100 g/min (p< 0.05); and E was 0.921 ± 0.025 and 0.962 ± 0.015 (p < 0.05) in the gray matter (GM) and the white matter (WM), respectively. PS was higher in the GM (171 ± 20 ml/100 g/min) compared with the WM (95 ± 18 ml/100 g/min) (p < 0.05). The parameters exhibited good reliability with test re-test experiments. The sensitivity of this technique was demonstrated by 200 mg caffeine intake, which resulted in a decrease in the resting PS by ~31%.

Generalization of quasi-steady-state reconstruction to CEST MRI with two-tiered RF saturation and gradient-echo readout-Synergistic nuclear Overhauser enhancement contribution to brain tumor amide proton transfer-weighted MRI.

While amide proton transfer-weighted (APTw) MRI has been adopted in tumor imaging, there are concurrent APT, magnetization transfer, and nuclear Overhauser enhancement changes. Also, the APTw image is confounded by relaxation changes, particularly when the relaxation delay and saturation time are not sufficiently long. Our study aimed to extend a quasi-steady-state (QUASS) solution to determine the contribution of the multipool CEST signals to the observed tumor APTw contrast. Our study derived the QUASS solution for a multislice CEST-MRI sequence with an interleaved RF saturation and gradient-echo readout between signal averaging. Multiparametric MRI scans were obtained in rat brain tumor models, including T1 , T2 , diffusion, and CEST scans. Finally, we performed spinlock model-based multipool fitting to determine multiple concurrent CEST signal changes in the tumor. The QUASS APTw MRI showed small but significant differences in normal and tumor tissues and their contrast from the acquired asymmetry calculation. The spinlock model-based fitting showed significant differences in semisolid magnetization transfer, amide, and nuclear Overhauser enhancement effects between the apparent and QUASS CEST MRI. In addition, we determined that the tumor APTw contrast is due to synergistic APT increase (+3.5ppm) and NOE decrease (-3.5ppm), with their relative contribution being about one third and two thirds under a moderate B1 of 0.75 μT at 4.7 T. Our study generalized QUASS analysis to gradient-echo image readout and quantified the underlying tumor CEST signal changes, providing an improved elucidation of the commonly used APTw MRI.

A comparative study of quantitative metrics in chemical exchange saturation transfer imaging for grading gliomas in adults

PurposeTo evaluate the performance of different chemical exchange saturation transfer (CEST) metrics for grading gliomas with semiautomatically defined regions of interest (ROIs). MethodsThirty-eight adult subjects were included, including 23 high-grade gliomas and 15 low-grade gliomas confirmed by histopathology. The B0-corrected CEST z-spectra were first calculated with magnetization transfer ratio asymmetry (MTRasym) analysis at frequency offsets of 3.5, 3, 2.5, 2, 1.5, and 1 ppm to obtain the fit-free metrics and subsequently fitted with three Lorentzian functions denoting direct water saturation (DS), amide proton transfer (APT), and combined semisolid magnetization transfer and nuclear Overhauser enhancement (MT & NOE) effects to derive the fit-based metrics. Wilcoxon rank-sum test was performed to determine if a statistically significant difference was present in the CEST metrics between low- and high-grade gliomas. Receiver operating characteristic (ROC) curves were used to evaluate the differentiation of CEST metrics between low- and high-grade gliomas. Pearson correlation coefficients were employed to evaluate the correlations of CEST metrics. ResultsFor the fit-free metrics, the highest areas under the curve (AUCs) of 0.85, 0.88, and 0.88, corresponding to MTRasym, MTRnormref (normalization by the reference scan), and MTRRex (subtraction of inverse z-spectra), respectively, were obtained at 3 ppm across various frequency offsets. In addition, the AUCs generated from the fit-based metrics (0.88–0.90) were higher than those generated from the fit-free metrics at 3 ppm. ConclusionThe results of this preliminary study indicate that fit-free CEST metrics at 3 ppm are superior to the other frequency offsets for grading human brain gliomas. The fit-based metrics manifested improved differentiation between low- and high-grade gliomas compared to the fit-free CEST metrics.

Sandwich spatial saturation for neuromelanin-sensitive MRI: Development and multi-center trial

Neuromelanin (NM)-sensitive MRI using a magnetization transfer (MT)-prepared T1-weighted sequence has been suggested as a tool to visualize NM contents in the brain. In this study, a new NM-sensitive imaging method, sandwichNM, is proposed by utilizing the incidental MT effects of spatial saturation RF pulses in order to generate consistent high-quality NM images using product sequences. The spatial saturation pulses are located both superior and inferior to the imaging volume, increasing MT weighting while avoiding asymmetric MT effects. When the parameters of the spatial saturation were optimized, sandwichNM reported a higher NM contrast ratio than those of conventional NM-sensitive imaging methods with matched parameters for comparability with sandwichNM (SandwichNM: 23.6 ± 5.4%; MT-prepared TSE: 20.6 ± 7.4%; MT-prepared GRE: 17.4 ± 6.0%). In a multi-vendor experiment, the sandwichNM images displayed higher means and lower standard deviations of the NM contrast ratio across subjects in all three vendors (SandwichNM vs. MT-prepared GRE; Vendor A: 28.4 ± 1.5% vs. 24.4 ± 2.8%; Vendor B: 27.2 ± 1.0% vs. 13.3 ± 1.3%; Vendor C: 27.3 ± 0.7% vs. 20.1 ± 0.9%). For each subject, the standard deviations of the NM contrast ratio across the vendors were substantially lower in SandwichNM (SandwichNM vs. MT-prepared GRE; subject 1: 1.5% vs. 8.1%, subject 2: 1.1 % vs. 5.1%, subject 3: 0.9% vs. 4.0%, subject 4: 1.1% vs. 5.3%), demonstrating consistent contrasts across the vendors. The proposed method utilizes product sequences, requiring no alteration of a sequence and, therefore, may have a wide practical utility in exploring the NM imaging.

Average saturation efficiency filter ASEF-CEST MRI of stroke rodents.

The average saturation efficiency filter (ASEF) is a novel method of improving the specificity of CEST; however, there is a mismatch between the magnetization transfer (MT) effect under high-duty cycle and low-duty cycle pulse trains. We explore measures of mitigation and the sensitivity and potential of ASEF imaging in phantoms and stroke rats. Simulation and nicotinamide phantoms in denatured protein were used to investigate the effect of different average saturation powers and MT pool parameters on matching coefficients used for correction as well as the ASEF ratio signal and baseline. Then, in vivo studies were performed in stroke rodents to further investigate the sensitivity and fidelity of ASEF ratio spectra. Simulation and studies of nicotinamide phantoms show that the matching coefficient needed to correct the baseline MT mismatch is strongly dependent on the average saturation power. In vivo studies in stroke rodents show that the matching coefficient required to correct the baseline MT mismatch is different for normal versus ischemic tissue. Thus, a baseline correction was performed to further suppress the residue MT mismatch. After correction of the mismatch, ASEF ratio achieved comparable contrast at 3.6ppm between normal and ischemic tissue when compared to the apparent amide proton transfer (APT*) approach. Moreover, contrasts for 2.0 and 2.6ppm were also ascertainable from the same spectra. ASEF can improve the CEST signal specificity of slow exchange labile protons such as amide and guanidyl, with small loss to sensitivity. It has strong potential in the CEST imaging of various diseases.