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Purpose: Non-invasive measurement of cerebral venous oxygenation (Y v ) is of critical importance in brain diseases. The present work proposed a fast method to quantify regional Y v map for both large and small veins., Methods: A new sequence was developed, referred to as TRU-VERA (T 2 relaxation under velocity encoding and rapid acquisition, which isolates blood spins from static tissue with velocity-encoding preparation, modulates the T 2 weighting of venous signal with T 2 -preparation and utilizes a bSSFP readout to achieve fast acquisition with high resolution. The sequence was first optimized to achieve best sensitivity for both large and small veins, and then validated with TRUST (T 2 relaxation under spin tagging), TRUPC (T 2 relaxation under phase contrast), and accelerated TRUPC MRI. Regional difference of Y v was evaluated, and test-retest reproducibility was examined., Results: Optimal Venc was determined to be 3 cm/s, while recovery time and balanced SSFP flip angle within reasonable range had minimal effect on SNR efficiency. Venous T 2 measured with TRU-VERA was highly correlated with T 2 from TRUST (R 2  = 0.90), and a conversion equation was established for further calibration to Y v . TRU-VERA sequences showed consistent Y v estimation with TRUPC (R 2  = 0.64) and accelerated TRUPC (R 2  = 0.79). Coefficient of variation was 0.84% for large veins and 2.49% for small veins, suggesting an excellent test-retest reproducibility., Conclusion: The proposed TRU-VERA sequence is a promising method for vessel-specific oxygenation assessment., (© 2024 International Society for Magnetic Resonance in Medicine.)

Purpose: To develop a model-based deep neural network for high-quality image reconstruction of undersampled multi-coil CEST data., Theory and Methods: Inspired by the variational network (VN), the CEST image reconstruction equation is unrolled into a deep neural network (CEST-VN) with a k-space data-sharing block that takes advantage of the inherent redundancy in adjacent CEST frames and 3D spatial-frequential convolution kernels that exploit correlations in the x-ω domain. Additionally, a new pipeline based on multiple-pool Bloch-McConnell simulations is devised to synthesize multi-coil CEST data from publicly available anatomical MRI data. The proposed network is trained on simulated data with a CEST-specific loss function that jointly measures the structural and CEST contrast. The performance of CEST-VN was evaluated on four healthy volunteers and five brain tumor patients using retrospectively or prospectively undersampled data with various acceleration factors, and then compared with other conventional and state-of-the-art reconstruction methods., Results: The proposed CEST-VN method generated high-quality CEST source images and amide proton transfer-weighted maps in healthy and brain tumor subjects, consistently outperforming GRAPPA, blind compressed sensing, and the original VN. With the acceleration factors increasing from 3 to 6, CEST-VN with the same hyperparameters yielded similar and accurate reconstruction without apparent loss of details or increase of artifacts. The ablation studies confirmed the effectiveness of the CEST-specific loss function and data-sharing block used., Conclusions: The proposed CEST-VN method can offer high-quality CEST source images and amide proton transfer-weighted maps from highly undersampled multi-coil data by integrating the deep learning prior and multi-coil sensitivity encoding model., (© 2023 International Society for Magnetic Resonance in Medicine.)

Purpose: Measuring lipid composition provides more information than just total lipid content. Hence, the non-invasive measurement of unsaturated lipid protons with both high efficiency and precision is of pressing need. This study was to optimize echo time (TE) for the best resolving of J-difference editing of unsaturated lipid resonances., Methods: The TE dependence of J-difference-edited (JDE) MRS was verified in the density-matrix simulation, soybean oil phantom, in-vivo experiments of white adipose tissue (WAT), and skeletal muscles using single-voxel MEGA-PRESS sequence at 3T. The peak SNRs and Cramér-Rao lower bounds (CRLBs) acquired at the proposed TE of 45 ms and previously published TE of 70 ms were compared (eight pairs) in WAT, extramyocelluar lipids (EMCLs), and intramyocellular lipids (IMCLs). The lipid composition in skeletal muscles was compared between healthy males (n = 7) and females (n = 7)., Results: The optimal TE was suggested as 45 ms. Compared to 70 ms, the mean signal gains at TE of 45 ms were 151% in WAT, 168% in EMCL, 204% in IMCL for allylic resonance, and 52% in EMCL for diallylic resonance. CRLBs were significantly reduced at TE of 45 ms in WAT, EMCL, IMCL for allylic resonance and in EMCL for diallylic resonance. With TE of 45 ms, significant gender differences were found in the lipid composition in EMCL pools, while no difference in IMCL pools., Conclusion: The JDE-MRS protocol with TE of 45 ms allows improved quantification of unsaturated lipid resonances in vivo and future lipid metabolism investigations., (© 2023 International Society for Magnetic Resonance in Medicine.)

Purpose: 3D pulse sequences enable high-resolution acquisition with a high SNR and ideal slice profiles, which, however, is particularly difficult for diffusion MRI (dMRI) due to the additional phase errors from diffusion encoding., Methods: We proposed a twin navigator-based 3D diffusion-weighted gradient spin-echo (GRASE) sequence to correct the phase errors between shots and between odd and even spin echoes for human whole-brain acquisition. We then compared the SNR of 3D GRASE and 2D simultaneous multi-slice EPI within the same acquisition time. We further tested the performance of 2D versus 3D acquisition at equivalent SNR on fiber tracking and microstructural mapping, using the diffusion tensor and high-order fiber orientation density-based metrics., Results: The proposed twin navigator approach removed multi-shot phase errors to some extent in the whole brain dMRI, and the 2D navigator performed better than the 1D navigator. Comparisons of SNR between the 2D simultaneous multi-slice EPI and 3D GRASE sequences demonstrated that the SNR of the GRASE sequence was 1.4-1.5-fold higher than the EPI sequence at an equivalent scan time. More importantly, we found a significantly higher fiber cross-section in the cerebrospinal tract, as well as richer subcortical fibers (U-fibers) using the 3D GRASE sequence compared to 2D EPI., Conclusion: The twin navigator-based 3D diffusion-weighted-GRASE sequence minimized the multishot phase error and effectively improved the SNR for whole-brain dMRI acquisition. We found differences in fiber tracking and microstructural mapping between 2D and 3D acquisitions, possibly due to the different slice profiles., (© 2023 International Society for Magnetic Resonance in Medicine.)

Purpose: To propose a novel Numerical fitting method of the Extrapolated semisolid Magnetization transfer Reference (NEMR) signal for quantifying the CEST effect., Theory and Methods: Modified two-pool Bloch-McConnell equations were used to numerically fit the magnetization transfer (MT) and direct water saturation (DS) signals at far off-resonance frequencies, which was subsequently extrapolated into the frequency range of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) pools. Then the subtraction of the fitted two-pool z-spectrum and the experimentally acquired z-spectrum yielded APT # and NOE # signals mostly free of MT and DS contamination. Several strategies were used to accelerate the NEMR fitting. Furthermore, the proposed NEMR method was compared with the conventional extrapolated semisolid magnetization transfer reference (EMR) and magnetization transfer ratio asymmetry (MTR asym ) methods in simulations and stroke patients., Results: The combination of RF downsampling, MT lineshape look-up table, and conversion of MATLAB code to C code accelerated the NEMR fitting by over 2700-fold. Monte-Carlo simulations showed that NEMR had higher accuracy than EMR and eliminated the requirement of the steady-state condition. In ischemic stroke patients, the NEMR maps at 1 μT removed hypointense artifacts seen on EMR and MTR asym images, and better depicted stroke lesions than EMR. For NEMR, NOE # yielded significantly (p < 0.05) stronger signal contrast between stroke and normal tissues than APT # at 1 μT., Conclusion: The proposed NEMR method is suitable for arbitrary saturation settings and can remove MT and DS contamination from the CEST signal for improved detection of ischemic stroke., (© 2023 International Society for Magnetic Resonance in Medicine.)

Purpose: To correct the temporal B 0 drift in chemical exchange saturation transfer (CEST) imaging in real-time with extra free-induction-decay (FID) readout., Theory and Methods: The frequency stabilization module of the recently proposed frequency-stabilized CEST (FS-CEST) sequence was further simplified by replacing the original three k-space lines of gradient-echo (GRE) readout with a single k-space line of FID readout. The B 0 drift was quantified using the phase difference between the odd and even parts of the FID signal in the frequency stabilization module and then used to update the B 0 frequency in the succeeding modules. The proposed FS-CEST sequence with FID readout (FID FS-CEST) was validated in phantoms and 16 human subjects on cross-vendor scanners., Results: In the Siemens experiments, the FID FS-CEST sequence successfully corrected the user-induced B 0 drift, generating consistent amide proton transfer-weighted (APTw) images and magnetization transfer ratio asymmetry (MTR asym ) spectra with those from the non-frequency-stabilized CEST (NFS-CEST) sequence without B 0 drift. In the Philips experiments, the FID FS-CEST sequence produced more stable APTw images and MTR asym spectra than the NFS-CEST sequence in the presence of practical B 0 drift. Quantitatively, the SD of the APTw signal values in the deep gray matter from 15 subjects was 0.26% for the FID FS-CEST sequence compared to 1.03% for the NFS-CEST sequences, with the fluctuations reduced by nearly three-quarters., Conclusions: The proposed FS-CEST sequence with FID readout can effectively correct the temporal B 0 drift on cross-vendor scanners., (© 2020 International Society for Magnetic Resonance in Medicine.)

Purpose: Oscillating gradient (OG) enables the access of short diffusion times for time-dependent diffusion MRI (dMRI); however, it poses several technical challenges for clinical use. This study proposes a 3D oscillating gradient-prepared gradient spin-echo (OGprep-GRASE) sequence to improve SNR and shorten acquisition time for OG dMRI on clinical scanners., Methods: The 3D OGprep-GRASE sequence consisted of global saturation, diffusion encoding, fat saturation, and GRASE readout modules. Multiplexed sensitivity-encoding reconstruction was used to correct the phase errors between multiple shots. We compared the scan time and SNR of the proposed sequence and the conventional 2D-EPI sequence for OG dMRI at 30-90-mm slice coverage. We also examined the time-dependent diffusivity changes with OG dMRI acquired at frequencies of 50 Hz and 25 Hz and pulsed-gradient dMRI at diffusion times of 30 ms and 60 ms., Results: The OGprep-GRASE sequence reduced the scan time by a factor of 1.38, and increased the SNR by 1.74-2.27 times compared with 2D EPI for relatively thick slice coverage (60-90 mm). The SNR gain led to improved diffusion-tensor reconstruction in the multishot protocols. Image distortion in 2D-EPI images was also reduced in GRASE images. Diffusivity measurements from the pulsed-gradient dMRI and OG dMRI showed clear diffusion-time dependency in the white matter and gray matter of the human brain, using both the GRASE and EPI sequences., Conclusion: The 3D OGprep-GRASE sequence improved scan time and SNR and reduced image distortion compared with the 2D multislice acquisition for OG dMRI on a 3T clinical system, which may facilitate the clinical translation of time-dependent dMRI., (© 2020 International Society for Magnetic Resonance in Medicine.)

Purpose: To achieve fast whole-brain chemical exchange saturation transfer (CEST) imaging with negligible susceptibility artifact., Methods: An optimized turbo spin echo readout module, also known as sampling perfection with application optimized contrasts by using different flip angle evolutions (SPACE), was deployed in the CEST sequence. The SPACE-CEST sequence was tested in a phantom, 6 healthy volunteers, and 3 brain tumor patients on a 3T human scanner. A dual-echo gradient echo sequence was used for B 0 inhomogeneity mapping. In addition, the proposed SPACE-CEST sequence was compared with the widely used turbo spin echo-CEST sequence for amide proton transfer-weighted (APTw) images., Results: The SPACE-CEST sequence generated highly consistent APTw maps to those of the turbo spin echo-CEST sequence in the phantom. In healthy volunteers, the SPACE-CEST sequence yielded whole-brain 2.8-mm isotropic APTw source images within 5 minutes, with no discernible susceptibility artifact. As for the B 0 maps in the whole brain, its mean, median, and standard deviation B 0 offset values were 5.0 Hz, 5.6 Hz, and 16 Hz, respectively. Regarding the APTw map throughout the whole brain, its mean, median, and standard deviation values were 0.78%, 0.56%, and 1.74%, respectively. The SPACE-CEST sequence was also successfully applied to a postsurgery brain tumor patient, suggesting no disease progression. In addition, on the newly diagnosed brain tumor patients, the SPACE-CEST and turbo spin echo-CEST sequences yielded essentially identical APTw values., Conclusion: The proposed SPACE-CEST technique can rapidly generate whole-brain CEST source images with negligible susceptibility artifact., (© 2020 International Society for Magnetic Resonance in Medicine.)

Purpose: The purpose of this study is to introduce a novel design method of a shim coil array specifically optimized for whole brain shimming and to compare the performance of the resulting coils to conventional spherical harmonic shimming., Methods: The proposed design approach is based on the stream function method and singular value decomposition. Eighty-four field maps from 12 volunteers measured in seven different head positions were used during the design process. The cross validation technique was applied to find an optimal number of coil elements in the array. Additional 42 field maps from 6 further volunteers were used for an independent validation. A bootstrapping technique was used to estimate the required population size to achieve a stable coil design., Results: Shimming using 12 and 24 coil elements outperforms fourth- and fifth-order spherical harmonic shimming for all measured field maps, respectively. Coil elements show novel coil layouts compared to the conventional spherical harmonic coils and existing multi-coils. Both leave-one-out and independent validation demonstrate the generalization ability of the designed arrays. The bootstrapping analysis predicts that field maps from approximately 140 subjects need to be acquired to arrive at a stable design., Conclusions: The results demonstrate the validity of the proposed method to design a shim coil array matched to the human brain anatomy, which naturally satisfies the laws of electrodynamics. The design method may also be applied to develop new shim coil arrays matched to other human organs., (© 2019 International Society for Magnetic Resonance in Medicine.)

Purpose: The inhomogeneity of flip angle distribution is a major challenge impeding the application of high-field MRI. We report a method combining spatially selective excitation using generalized spatial encoding magnetic fields (SAGS) with radiofrequency (RF) shimming to achieve homogeneous excitation. This method can be an alternative approach to address the challenge of B1+ inhomogeneity using nonlinear gradients., Methods: We proposed a two-step algorithm that jointly optimizes the combination of nonlinear spatial encoding magnetic fields and the combination of multiple RF transmitter coils and then optimizes the locations, RF amplitudes, and phases of the spokes., Results: Our results show that jointly designed SAGS and RF shimming can provide a more homogeneous flip angle distribution than using SAGS or RF shimming alone. Compared with RF shimming alone, our approach can reduce the relative standard deviation of flip angle by 56% and 52% using phantom and human head data, respectively., Conclusion: The jointly designed SAGS and RF shimming method can be used to achieve homogeneous flip angle distributions when fully parallel RF transmission is not available. Magn Reson Med 78:577-587, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: To develop a method of achieving large field of view (FOV) imaging with a smaller amount of data in ultra-low-field (ULF) MRI., Theory: In rotary scanning acquisition (RSA), data from the imaging object is acquired at multiple angles by rotating the object or the scanner. RSA is similar to radial-trajectory acquisition but simplifies the measurement and image reconstruction when concomitant fields are nonnegligible., Methods: RSA was implemented to achieve large FOV with only three localized superconductive quantum interference device (SQUID) sensors at the ULF-MRI field of 50 μT., Results: Simulations suggest benefits of RSA, including reduced concomitant field artifacts, large FOV imaging, and SNR improvement. Experimental data demonstrate the feasibility of reconstructing large FOV images using only three SQUID sensors with 33% of the amount of data collected using a Cartesian trajectory., Conclusion: RSA can be useful in low-field, low-weight, or portable MRI to generate large FOV images with only a few sensors. Magn Reson Med 75:2255-2264, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Purpose: High-field magnetic resonance imaging (MRI) has the challenge of inhomogeneous B(1)(+), and consequently inhomogeneous flip angle distribution, which causes spatially dependent contrast and makes clinical diagnosis difficult., Method: We propose a two-step pulse design procedure in which (1) a combination of linear and nonlinear spatial encoding magnetic fields (SEMs) is used to remap the B(1)(+) map in order to reduce the dimensionality of the problem, (2) the locations, amplitudes, and phases of spoke pulses are estimated in one dimension. The advantage of this B(1)(+) remapping is that when the isointensity contours of a linear combination of SEMs are similar to the isointensity contours of B(1)(+), a simple pulse sequence design using time-varying SEMs can achieve a homogenous flip-angle distribution efficiently., Results: We demonstrate that spatially selective radiofrequency (RF) excitation with generalized SEMs (SAGS) using both linear and quadratic SEMs in a multi-spoke k-space trajectory can mitigate the B(1)(+) inhomogeneity at 7T efficiently. Numerical simulations based on experimental data suggest that, compared with other methods, SAGS provide a formulation allowing multiple-pulse design, a similar average flip-angle distribution with less RF power, and/or a more homogeneous flip-angle distribution., Conclusion: Without using multiple RF coils for parallel transmission, SAGS can be used to mitigate the B(1)(+) inhomogeneity in high-field MRI experiments., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: For ultra-low-field MRI, the spatial-encoding magnetic fields generated by gradient coils can have strong concomitant fields leading to prominent image distortion. Additionally, using superconducting magnet to pre-polarize magnetization can improve the signal-to-noise ratio of ultra-low-field MRI. Yet the spatially inhomogeneous remanence field due to the permanently trapped flux inside a superconducting pre-polarizing coil modulates magnetization and causes further image distortion., Method: We propose a two-stage frequency-space (f-x) formulation to accurately describe the dynamics of spatially-encoded magnetization under the influence of concomitant and remanence fields, which allows for correcting image distortion due to concomitant and remanence fields., Results: Our method is computationally efficient as it uses a combination of the fast Fourier transform algorithm and a linear equation solver. With sufficiently dense discretization in solving the linear equation, the performance of this f-x method was found to be stable among different choices of the regularization parameter and the regularization matrix., Conclusion: We present this method together with numerical simulations and experimental data to demonstrate how concomitant and remanence field artifacts in ultra-low-field MRI can be corrected efficiently., (Copyright © 2013 Wiley Periodicals, Inc.)

In ultra-low-field magnetic resonance imaging, arrays of up to hundreds of highly sensitive superconducting quantum interference devices (SQUIDs) can be used to detect the weak magnetic fields emitted by the precessing magnetization. Here, we investigate the noise amplification in sensitivity-encoded ultra-low-field MRI at various acceleration rates using a SQUID array consisting of 102 magnetometers, 102 gradiometers, or 306 magnetometers and gradiometers, to cover the whole head. Our results suggest that SQUID arrays consisting of 102 magnetometers and 102 gradiometers are similar in g-factor distribution. A SQUID array of 306 sensors (102 magnetometers and 204 gradiometers) only marginally improves the g-factor. Corroborating with previous studies, the g-factor in 2D sensitivity-encoded ultra-low-field MRI with 9 to 16-fold 2D accelerations using the SQUID array studied here may be acceptable., (© 2012 Wiley Periodicals, Inc.)