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Purpose: To investigate the safety and value of hyperpolarized (HP) MRI of [1- 13 C]pyruvate in healthy volunteers using deuterium oxide (D 2 O) as a solvent., Methods: Healthy volunteers (n = 5), were injected with HP [1- 13 C]pyruvate dissolved in D 2 O and imaged with a metabolite-specific 3D dual-echo dynamic EPI sequence at 3T at one site (Site 1). Volunteers were monitored following the procedure to assess safety. Image characteristics, including SNR, were compared to data acquired in a separate cohort using water as a solvent (n = 5) at another site (Site 2). The apparent spin-lattice relaxation time (T 1 ) of [1- 13 C]pyruvate was determined both in vitro and in vivo from a mono-exponential fit to the image intensity at each time point of our dynamic data., Results: All volunteers completed the study safely and reported no adverse effects. The use of D 2 O increased the T 1 of [1- 13 C]pyruvate from 66.5 ± 1.6 s to 92.1 ± 5.1 s in vitro, which resulted in an increase in signal by a factor of 1.46 ± 0.03 at the time of injection (90 s after dissolution). The use of D 2 O also increased the apparent relaxation time of [1- 13 C]pyruvate by a factor of 1.4 ± 0.2 in vivo. After adjusting for inter-site SNR differences, the use of D 2 O was shown to increase image SNR by a factor of 2.6 ± 0.2 in humans., Conclusions: HP [1- 13 C]pyruvate in D 2 O is safe for human imaging and provides an increase in T 1 and SNR that may improve image quality., (© 2024 International Society for Magnetic Resonance in Medicine.)

Purpose: To develop a deep-learning model that leverages the spatial and temporal information from dynamic contrast-enhanced magnetic resonance (DCE MR) brain imaging in order to automatically estimate a vascular function (VF) for quantitative pharmacokinetic (PK) modeling., Methods: Patients with glioblastoma multiforme were scanned post-resection approximately every 2 months using a high spatial and temporal resolution DCE MR imaging sequence ( ≈ 5 s and ≈ 2 cm 3 ). A region over the transverse sinus was manually drawn in the dynamic T1-weighted images to provide a ground truth VF. The manual regions and their resulting VF curves were used to train a deep-learning model based on a 3D U-net architecture. The model concurrently utilized the spatial and temporal information in DCE MR images to predict the VF. In order to analyze the contribution of the spatial and temporal terms, different weighted combinations were examined. The manual and deep-learning predicted regions and VF curves were compared., Results: Forty-three patients were enrolled in this study and 155 DCE MR scans were processed. The 3D U-net was trained using a loss function that combined the spatial and temporal information with different weightings. The best VF curves were obtained when both spatial and temporal information were considered. The predicted VF curve was similar to the manual ground truth VF curves., Conclusion: The use of spatial and temporal information improved VF curve prediction relative to when only the spatial information is used. The method generalized well for unseen data and can be used to automatically estimate a VF curve suitable for quantitative PK modeling. This method allows for a more efficient clinical pipeline and may improve automation of permeability mapping., (© 2021 International Society for Magnetic Resonance in Medicine.)

Purpose: The combined hyperpolarized (HP) 13 C pyruvate and urea MRI has provided a simultaneous assessment of glycolytic metabolism and tissue perfusion for improved cancer diagnosis and therapeutic evaluation in preclinical studies. This work aims to translate this dual-probe HP imaging technique to clinical research., Methods: A co-polarization system was developed where [1- 13 C]pyruvic acid (PA) and [ 13 C, 15 N 2 ]urea in water solution were homogeneously mixed and polarized on a 5T SPINlab system. Physical and chemical characterizations and toxicology studies of the combined probe were performed. Simultaneous metabolic and perfusion imaging was performed on a 3T clinical MR scanner by alternatively applying a multi-slice 2D spiral sequence for [1- 13 C]pyruvate and its downstream metabolites and a 3D balanced steady-state free precession (bSSFP) sequence for [ 13 C, 15 N 2 ]urea., Results: The combined PA/urea probe has a glass-formation ability similar to neat PA and can generate nearly 40% liquid-state 13 C polarization for both pyruvate and urea in 3-4 h. A standard operating procedure for routine on-site production was developed and validated to produce 40 mL injection product of approximately 150 mM pyruvate and 35 mM urea. The toxicology study demonstrated the safety profile of the combined probe. Dynamic metabolite-specific imaging of [1- 13 C]pyruvate, [1- 13 C]lactate, [1- 13 C]alanine, and [ 13 C, 15 N 2 ]urea was achieved with adequate spatial (2.6 mm × 2.6 mm) and temporal resolution (4.2 s), and urea images showed reduced off-resonance artifacts due to the J CN coupling., Conclusion: The reported technical development and translational studies will lead to the first-in-human dual-agent HP MRI study and mark the clinical translation of the first HP 13 C MRI probe after pyruvate., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To develop and evaluate an efficient precontrast T 1 mapping technique suitable for quantitative high-resolution whole-brain dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI)., Methods: Variable flip angle (VFA) T 1 mapping was considered that provides 1 × 1 × 2 mm 3 resolution to match a recent high-resolution whole-brain DCE-MRI protocol. Seven FAs were logarithmically spaced from 1.5° to 15°. T 1 and M 0 maps were estimated using model-based reconstruction. This approach was evaluated using an anatomically realistic brain tumor digital reference object (DRO) with noise-mimicking 3T neuroimaging and fully sampled data acquired from one healthy volunteer. Methods were also applied on fourfold prospectively undersampled VFA data from 13 patients with high-grade gliomas., Results: T 1 -mapping precision decreased with undersampling factor R, althoughwhereas bias remained small before a critical R. In the noiseless DRO, T 1 bias was <25 ms in white matter (WM) and <11 ms in brain tumor (BT). T 1 standard deviation (SD) was <119.5 ms in WM (coefficient of variation [COV] ~11.0%) and <253.2 ms in BT (COV ~12.7%). In the noisy DRO, T 1 bias was <50 ms in WM and <30 ms in BT. For R ≤ 10, T 1 SD was <107.1 ms in WM (COV ~9.9%) and <240.9 ms in BT (COV ~12.1%). In the healthy subject, T 1 bias was <30 ms for R ≤ 16. At R = 4, T 1 SD was 171.4 ms (COV ~13.0%). In the prospective brain tumor study, T 1 values were consistent with literature values in WM and BT., Conclusion: High-resolution whole-brain VFA T 1 mapping is feasible with sparse sampling, supporting its use for quantitative DCE-MRI., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To compare the silent rotating ultrafast imaging sequence (RUFIS) to a traditional Cartesian spoiled gradient-echo (SPGR) acquisition scheme for variable flip angle (VFA) T 1 mapping., Methods: A two-point VFA measurement was performed using RUFIS and Cartesian SPGR in a quantitative phantom and healthy volunteers. To correct for B 1 errors, a novel silent magnetization prepared B 1 map acquisition (SIMBA) was developed, which combined with RUFIS VFA allows for a completely silent T 1 mapping protocol., Results: The silent protocol was found to have comparable repeatability but higher reproducibility in vivo compared to the standard SPGR protocol, and showed no increase in acoustic noise levels above background noise levels compared to a 33 dBA increase for the SPGR acquisition., Conclusions: VFA T 1 mapping using RUFIS is a feasible alternative to SPGR, achieving silent T 1 mapping with comparable acquisition time., (© 2020 International Society for Magnetic Resonance in Medicine.)

Purpose: To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized 13 C-labeled substrate mixture prepared using photo-induced nonpersistent radicals., Methods: Droplets of mixed [1- 13 C]pyruvic and [1- 13 C]butyric acids were frozen into glassy beads in liquid nitrogen. Ethanol addition was investigated as a means to increase the polarization level. The beads were irradiated with ultraviolet light and the radical concentration was measured by ESR spectroscopy. Following dynamic nuclear polarization in a 7T polarizer, the beads were dissolved, and the radical-free hyperpolarized solution was rapidly transferred into an injection pump located inside a 9.4T scanner. The hyperpolarized solution was injected in healthy rats to measure cardiac metabolism in vivo., Results: Ultraviolet irradiation created nonpersistent radicals in a mixture containing 13 C-labeled pyruvic and butyric acids, and enabled the hyperpolarization of both substrates by dynamic nuclear polarization. Ethanol addition increased the radical concentration from 16 to 26 mM. Liquid-state 13 C polarization was 3% inside the pump at the time of injection, and increased to 5% by addition of ethanol to the substrate mixture prior to ultraviolet irradiation. In the rat heart, the in vivo 13 C signals from lactate, alanine, bicarbonate, and acetylcarnitine were detected following the metabolism of the injected substrate mixture., Conclusion: Copolarization of two different 13 C-labeled substrates and the detection of their myocardial metabolism in vivo was achieved without using persistent radicals. The absence of radicals in the solution containing the hyperpolarized 13 C-substrates may simplify the translation to clinical use, as no radical filtration is required prior to injection., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: To develop a fast 2D method for MRI near metal with reduced B 0 in-plane and through-slice artifacts., Methods: Multi-spectral imaging (MSI) approaches reduce artifacts in MR images near metal, but require 3D imaging of multiple excited volumes regardless of imaging geometry or artifact severity. The proposed 2D MSI method rapidly excites a limited slice and spectral region using gradient reversal between excitation and refocusing pulses, then uses standard 2D imaging, with the process repeating to cover multiple spectral offsets that are combined as in other MSI techniques. 2D MSI was implemented in a spin-echo-train sequence and validated in phantoms and in vivo by comparing it with standard spin-echo imaging and existing MSI techniques., Results: 2D MSI images for each spatial-spectral region follow isocontours of the dipole-like B 0 field variation, and thus frequency variation, near metal devices. Artifact correction in phantoms and human subjects with metal is comparable to 3D MSI methods, and superior to standard spin-echo techniques. Scan times are reduced compared with 3D MSI methods in cases where a limited number of slices are needed, though signal-to-noise ratio is also reduced as expected., Conclusion: 2D MSI offers a fast and flexible alternative to 3D MSI for artifact reduction near metal. Magn Reson Med 79:968-973, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: To develop a gradient pre-emphasis scheme that prospectively counteracts the effects of the first-order concomitant fields for any arbitrary gradient waveform played on asymmetric gradient systems, and to demonstrate the effectiveness of this approach using a real-time implementation on a compact gradient system., Methods: After reviewing the first-order concomitant fields that are present on asymmetric gradients, we developed a generalized gradient pre-emphasis model assuming arbitrary gradient waveforms to counteract their effects. A numerically straightforward, easily implemented approximate solution to this pre-emphasis problem was derived that was compatible with the current hardware infrastructure of conventional MRI scanners for eddy current compensation. The proposed method was implemented on the gradient driver subsystem, and its real-time use was tested using a series of phantom and in vivo data acquired from two-dimensional Cartesian phase-difference, echo-planar imaging, and spiral acquisitions., Results: The phantom and in vivo results demonstrated that unless accounted for, first-order concomitant fields introduce considerable phase estimation error into the measured data and result in images with spatially dependent blurring/distortion. The resulting artifacts were effectively prevented using the proposed gradient pre-emphasis., Conclusion: We have developed an efficient and effective gradient pre-emphasis framework to counteract the effects of first-order concomitant fields of asymmetric gradient systems. Magn Reson Med 77:2250-2262, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: A chemical shift separation technique for hyperpolarized (13) C metabolic imaging with high spatial and temporal resolution was developed. Specifically, a fast three-dimensional pulse sequence and a reconstruction method were implemented to acquire signals from multiple (13) C species simultaneously with subsequent separation into individual images., Theory and Methods: A stack of flyback echo-planar imaging readouts and a set of multiband excitation radiofrequency pulses were designed to spatially modulate aliasing patterns of the acquired metabolite images, which translated the chemical shift separation problem into parallel imaging reconstruction problem. An eight-channel coil array was used for data acquisition and a parallel imaging method based on nonlinear inversion was developed to separate the aliased images., Results: Simultaneous acquisitions of pyruvate and lactate in a phantom study and in vivo rat experiments were performed. The results demonstrated successful separation of the metabolite distributions into individual images having high spatial resolution., Conclusion: This method demonstrated the ability to provide accelerated metabolite imaging in hyperpolarized (13) C MR using multichannel coils, tailored readout, and specialized RF pulses., (© 2014 Wiley Periodicals, Inc.)

Purpose: We propose the use of a retrospectively gated cine fast spin echo (FSE) sequence for characterization of carotid artery dynamics. The aim of this study was to compare cine FSE measures of carotid dynamics with measures obtained on prospectively gated FSE images., Methods: The common carotid arteries in 10 volunteers were imaged using two temporally resolved sequences: (i) cine FSE and (ii) prospectively gated FSE. Three raters manually traced a common carotid artery area for all cardiac phases on both sequences. Measured areas and systolic-diastolic area changes were calculated and compared. Inter- and intra-rater reliability were assessed for both sequences., Results: No significant difference between cine FSE and prospectively gated FSE areas were observed (P = 0.36). Both sequences produced repeatable cross-sectional area measurements: inter-rater intraclass correlation coefficient (ICC) = 0.88 on cine FSE images and 0.87 on prospectively gated FSE images. Minimum detectable difference (MDD) in systolic-diastolic area was 4.9 mm(2) with cine FSE and 6.4 mm(2) with prospectively gated FSE., Conclusion: This cine FSE method produced repeatable dynamic carotid artery measurements with less artifact and greater temporal efficiency compared with prospectively gated FSE., (© 2014 Wiley Periodicals, Inc.)

Purpose: The proposed method is aimed at reducing eddy current (EC) induced distortion in diffusion weighted echo planar imaging, without the need to perform further image coregistration between diffusion weighted and T2 images. These ECs typically have significant high order spatial components that cannot be compensated by preemphasis., Theory and Methods: High order ECs are first calibrated at the system level in a protocol independent fashion. The resulting amplitudes and time constants of high order ECs can then be used to calculate imaging protocol specific corrections. A combined prospective and retrospective approach is proposed to apply correction during data acquisition and image reconstruction., Results: Various phantom, brain, body, and whole body diffusion weighted images with and without the proposed method are acquired. Significantly reduced image distortion and misregistration are consistently seen in images with the proposed method compared with images without., Conclusion: The proposed method is a powerful (e.g., effective at 48 cm field of view and 30 cm slice coverage) and flexible (e.g., compatible with other image enhancements and arbitrary scan plane) technique to correct high order ECs induced distortion and misregistration for various diffusion weighted echo planar imaging applications, without the need for further image post processing, protocol dependent prescan, or sacrifice in signal-to-noise ratio., (Copyright © 2013 Wiley Periodicals, Inc.)

Conventional 1D, spatially nonselective fat saturation can generate uncrushed fat signals in areas far outside the imaging slice where crushers are weak because of reduced gradient linearity. These fat signals can corrupt in-slice water signal, and in functional MRI, they can manifest themselves as artifacts such as clouds in image background or localized signal fluctuation over time. In this article, a spectral-spatial radiofrequency pulse is proposed to replace the conventional, spatially nonselective fat saturation pulse. The advantage of the proposed method is that fat protons far outside the image slice would not be excited because of the spatial selectivity, thereby removing the root cause of the fat aliasing artifacts. The proposed method also preserves thin slice capability, pulse duration, and fat suppression performance of the conventional method. Bloch simulation and human volunteer results show that the method is effective in reducing the fat aliasing artifacts seen in functional MRI., (Copyright © 2012 Wiley Periodicals, Inc.)

Nyquist ghost artifacts are a serious issue in echo planar imaging. These artifacts primarily originate from phase difference between even and odd echo images and can be removed or reduced using phase correction methods. The commonly used 1D phase correction can only correct phase difference along readout axis. 2D correction is, therefore, necessary when phase difference presents along both readout and phase encoding axes. However, existing 2D methods have several unaddressed issues that affect their practicality. These issues include uncharacterized noise behavior, image artifact due to unoptimized phase estimation, Gibbs ringing artifact when directly applying to partial k(y) data, and most seriously a new image artifact under tight field-of-view (i.e., field-of-view slightly smaller than object size). All these issues are addressed in this article. Specifically, theoretical analysis of noise amplification and effect of phase estimation error is provided, and tradeoff between noise and ghost is studied. A new 2D phase correction method with improved polynomial fitting, joint homodyne processing and phase correction, compatibility with tight field-of-view is then proposed. Various results show that the proposed method can robustly generate images free of Nyquist ghosts and other image artifacts even in oblique scans or when cross-term eddy current terms are significant., (Copyright © 2010 Wiley-Liss, Inc.)

(13)C imaging and spectroscopy in the presence of injected labeled compounds can vastly extend the capability of MRI to perform metabolic imaging. The details of imaging in the presence of injected compounds, however, pose new technological challenges. Pulse sequences, in general, rely on precise flip-angle (FA) calibration to create high signal-to-noise ratio (SNR), artifact-free images. Signal quantification also requires precise knowledge of the excitation FA. In MRI scans that rely on signal acquisitions from injected compounds, however, such FA calibration is challenged by low natural-abundance (13)C signal levels before injection, and by time-varying signal following injection. A method to precisely set the FA at the (13)C frequency based on FA calibration at the (23)Na frequency is presented here. A practical implementation of a coil (a dual-tuned, (23)Na/(13)C low-pass birdcage coil) suitable for this calibration in vivo is also documented. Accurate FA calibration is demonstrated at the (13)C frequency for in vivo rat experiments using this approach., ((c) 2007 Wiley-Liss, Inc.)