Radical-free hyperpolarized MRI using endogenously occurring pyruvate analogues and UV-induced nonpersistent radicals.

It was recently demonstrated that nonpersistent radicals can be generated in frozen solutions of metabolites such as pyruvate by irradiation with UV light, enabling radical-free dissolution dynamic nuclear polarization. Although pyruvate is endogenous, the presence of pyruvate may interfere with metabolic processes or the detection of pyruvate as a metabolic product, making it potentially unsuitable as a polarizing agent. Therefore, the aim of the current study was to characterize solutions containing endogenously occurring alternatives to pyruvate as UV-induced nonpersistent radical precursors for in vivo hyperpolarized MRI. The metabolites alpha-ketovalerate (αkV) and alpha-ketobutyrate (αkB) are analogues of pyruvate and were chosen as potential radical precursors. Sample formulations containing αkV and αkB were studied with UV-visible spectroscopy, irradiated with UV light, and their nonpersistent radical yields were quantified with electron spin resonance and compared with pyruvate. The addition of <sup>13</sup> C-labeled substrates to the sample matrix altered the radical yield of the precursors. Using αkB increased the <sup>13</sup> C-labeled glucose liquid-state polarization to 16.3% ± 1.3% compared with 13.3% ± 1.5% obtained with pyruvate, and 8.9% ± 2.1% with αkV. For [1- <sup>13</sup> C]butyric acid, polarization levels of 12.1% ± 1.1% for αkV, 12.9% ± 1.7% for αkB, 1.5% ± 0.2% for OX063 and 18.7% ± 0.7% for Finland trityl, were achieved. Hyperpolarized [1- <sup>13</sup> C]butyrate metabolism in the heart revealed label incorporation into [1- <sup>13</sup> C]acetylcarnitine, [1- <sup>13</sup> C]acetoacetate, [1- <sup>13</sup> C]butyrylcarnitine, [5- <sup>13</sup> C]glutamate and [5- <sup>13</sup> C]citrate. This study demonstrates the potential of αkV and αkB as endogenous polarizing agents for in vivo radical-free hyperpolarized MRI. UV-induced, nonpersistent radicals generated in endogenous metabolites enable high polarization without requiring radical filtration, thus simplifying the quality-control tests in clinical applications

Characterization of perfluorocarbon relaxation times and their influence on the optimization of fluorine-19 MRI at 3 tesla.

To characterize and optimize javax.xml.bind.JAXBElement@7524a985 F MRI for different perfluorocarbons (PFCs) at 3T and quantify the loss of acquisition efficiency as a function of different temperature and cellular conditions. The T javax.xml.bind.JAXBElement@1ef4ca84 and T javax.xml.bind.JAXBElement@295b7e6f relaxation times of the commonly used PFCs perfluoropolyether (PFPE), perfluoro-15-crown-5-ether (PFCE), and perfluorooctyl bromide (PFOB) were measured in phantoms and in several different conditions (cell types, presence of fixation agent, and temperatures). These relaxation times were used to optimize pulse sequences through numerical simulations. The acquisition efficiency in each cellular condition was then determined as the ratio of the signal after optimization with the reference relaxation times and after optimization with its proper relaxation times. Finally, PFC detection limits were determined. The loss of acquisition efficiency due to parameter settings optimized for the wrong temperature and cellular condition was limited to 13%. The detection limits of all PFCs were lower at 24 °C than at 37 °C and varied from 11.8 ± 3.0 mM for PFCE at 24 °C to 379.9 ± 51.8 mM for PFOB at 37 °C. Optimizing javax.xml.bind.JAXBElement@30187e57 F pulse sequences with a known phantom only leads to moderate loss in acquisition efficiency in cellular conditions that might be encountered in in vivo and in vitro experiments. Magn Reson Med 77:2263-2271, 2017. © 2016 International Society for Magnetic Resonance in Medicine

Motion-resolved fat-fraction mapping with whole-heart free-running multiecho GRE and pilot tone.

To develop a free-running 3D radial whole-heart multiecho gradient echo (ME-GRE) framework for cardiac- and respiratory-motion-resolved fat fraction (FF) quantification. (N <sub>TE</sub> = 8) readouts optimized for water-fat separation and quantification were integrated within a continuous non-electrocardiogram-triggered free-breathing 3D radial GRE acquisition. Motion resolution was achieved with pilot tone (PT) navigation, and the extracted cardiac and respiratory signals were compared to those obtained with self-gating (SG). After extra-dimensional golden-angle radial sparse parallel-based image reconstruction, FF, R <sub>2</sub> *, and B <sub>0</sub> maps, as well as fat and water images were generated with a maximum-likelihood fitting algorithm. The framework was tested in a fat-water phantom and in 10 healthy volunteers at 1.5 T using N <sub>TE</sub> = 4 and N <sub>TE</sub> = 8 echoes. The separated images and maps were compared with a standard free-breathing electrocardiogram (ECG)-triggered acquisition. The method was validated in vivo, and physiological motion was resolved over all collected echoes. Across volunteers, PT provided respiratory and cardiac signals in agreement (r = 0.91 and r = 0.72) with SG of the first echo, and a higher correlation to the ECG (0.1% of missed triggers for PT vs. 5.9% for SG). The framework enabled pericardial fat imaging and quantification throughout the cardiac cycle, revealing a decrease in FF at end-systole by 11.4% ± 3.1% across volunteers (p < 0.0001). Motion-resolved end-diastolic 3D FF maps showed good correlation with ECG-triggered measurements (FF bias of -1.06%). A significant difference in free-running FF measured with N <sub>TE</sub> = 4 and N <sub>TE</sub> = 8 was found (p < 0.0001 in sub-cutaneous fat and p < 0.01 in pericardial fat). Free-running fat fraction mapping was validated at 1.5 T, enabling ME-GRE-based fat quantification with N <sub>TE</sub> = 8 echoes in 6:15 min

Probing cardiac metabolism by hyperpolarized 13C MR using an exclusively endogenous substrate mixture and photo-induced nonpersistent radicals.

To probe the cardiac metabolism of carbohydrates and short chain fatty acids simultaneously in vivo following the injection of a hyperpolarized <sup>13</sup> C-labeled substrate mixture prepared using photo-induced nonpersistent radicals. Droplets of mixed [1- <sup>13</sup> C]pyruvic and [1- <sup>13</sup> 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. Ultraviolet irradiation created nonpersistent radicals in a mixture containing <sup>13</sup> 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 <sup>13</sup> 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 <sup>13</sup> C signals from lactate, alanine, bicarbonate, and acetylcarnitine were detected following the metabolism of the injected substrate mixture. Copolarization of two different <sup>13</sup> 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 <sup>13</sup> C-substrates may simplify the translation to clinical use, as no radical filtration is required prior to injection

Tuning Properties of Iron Oxide Nanoparticles in Aqueous Synthesis without Ligands to Improve MRI Relaxivity and SAR.

Aqueous synthesis without ligands of iron oxide nanoparticles (IONPs) with exceptional properties still remains an open issue, because of the challenge to control simultaneously numerous properties of the IONPs in these rigorous settings. To solve this, it is necessary to correlate the synthesis process with their properties, but this correlation is until now not well understood. Here, we study and correlate the structure, crystallinity, morphology, as well as magnetic, relaxometric and heating properties of IONPs obtained for different durations of the hydrothermal treatment that correspond to the different growth stages of IONPs upon initial co-precipitation in aqueous environment without ligands. We find that their properties were different for IONPs with comparable diameters. Specifically, by controlling the growth of IONPs from primary to secondary particles firstly by colloidal and then also by magnetic interactions, we control their crystallinity from monocrystalline to polycrystalline IONPs, respectively. Surface energy minimization in the aqueous environment along with low temperature treatment is used to favor nearly defect-free IONPs featuring superior properties, such as high saturation magnetization, magnetic volume, surface crystallinity, the transversal magnetic resonance imaging (MRI) relaxivity (up to r₂ = 1189 mM(-1)·s(-1) and r₂/r₁ = 195) and specific absorption rate, SAR (up to 1225.1 W·gFe(-1))

Optimal Protocol for Contrast-enhanced Free-running 5D Whole-heart Coronary MR Angiography at 3T.

Free-running 5D whole-heart coronary MR angiography (MRA) is gaining in popularity because it reduces scanning complexity by removing the need for specific slice orientations, respiratory gating, or cardiac triggering. At 3T, a gradient echo (GRE) sequence is preferred in combination with contrast injection. However, neither the injection scheme of the gadolinium (Gd) contrast medium, the choice of the RF excitation angle, nor the dedicated image reconstruction parameters have been established for 3T GRE free-running 5D whole-heart coronary MRA. In this study, a Gd injection scheme, RF excitation angles of lipid-insensitive binominal off-resonance RF excitation (LIBRE) pulse for valid fat suppression and continuous data acquisition, and compressed-sensing reconstruction regularization parameters were optimized for contrast-enhanced free-running 5D whole-heart coronary MRA using a GRE sequence at 3T. Using this optimized protocol, contrast-enhanced free-running 5D whole-heart coronary MRA using a GRE sequence is feasible with good image quality at 3T

Natively fat-suppressed 5D whole-heart MRI with a radial free-running fast-interrupted steady-state (FISS) sequence at 1.5T and 3T.

To implement, optimize, and test fast interrupted steady-state (FISS) for natively fat-suppressed free-running 5D whole-heart MRI at 1.5 tesla (T) and 3T. FISS was implemented for fully self-gated free-running cardiac- and respiratory-motion-resolved radial imaging of the heart at 1.5T and 3T. Numerical simulations and phantom scans were performed to compare fat suppression characteristics and to determine parameter ranges (number of readouts [NR] per FISS module and TR) for effective fat suppression. Subsequently, free-running FISS data were collected in 10 healthy volunteers and images were reconstructed with compressed sensing. All acquisitions were compared with a continuous balanced steady-state free precession version of the same sequence, and both fat suppression and scan times were analyzed. Simulations demonstrate a variable width and location of suppression bands in FISS that were dependent on TR and NR. For a fat suppression bandwidth of 100 Hz and NR ≤ 8, simulations demonstrated that a TR between 2.2 ms and 3.0 ms is required at 1.5T, whereas a range of 3.0 ms to 3.5 ms applies at 3T. Fat signal increases with NR. These findings were corroborated in phantom experiments. In volunteers, fat SNR was significantly decreased using FISS compared with balanced steady-state free precession (P < 0.05) at both field strengths. After protocol optimization, high-resolution (1.1 mm <sup>3</sup> ) 5D whole-heart free-running FISS can be performed with effective fat suppression in under 8 min at 1.5T and 3T at a modest scan time increase compared to balanced steady-state free precession. An optimal FISS parameter range was determined enabling natively fat-suppressed 5D whole-heart free-running MRI with a single continuous scan at 1.5T and 3T, demonstrating potential for cardiac imaging and noncontrast angiography

Patient respiratory-triggered quantitative T₂ mapping in the pancreas.

Long acquisition times and motion sensitivity limit T <sub>2</sub> mapping in the abdomen. Accelerated mapping at 3 T may allow for quantitative assessment of diffuse pancreatic disease in patients during free-breathing. To test the feasibility of respiratory-triggered quantitative T <sub>2</sub> analysis in the pancreas and correlate T <sub>2</sub> -values with age, body mass index, pancreatic location, main pancreatic duct dilatation, and underlying pathology. Retrospective single-center pilot study. Eighty-eight adults. Ten-fold accelerated multiecho-spin-echo 3 T MRI sequence to quantify T <sub>2</sub> at 3 T. Two radiologists independently delineated three regions of interest inside the pancreatic head, body, and tail for each acquisition. Means and standard deviations for T <sub>2</sub> values in these regions were determined. T <sub>2</sub> -value variation with demographic data, intraparenchymal location, pancreatic duct dilation, and underlying pancreatic disease was assessed. Interreader reliability was determined by calculating the interclass coefficient (ICCs). T <sub>2</sub> values were compared for different pancreatic locations by analysis of variance (ANOVA). Interpatient associations between T <sub>2</sub> values and demographical, clinical, and radiological data were calculated (ANOVA). The accelerated T <sub>2</sub> mapping sequence was successfully performed in all participants (mean acquisition time, 2:48 ± 0:43 min). Low T <sub>2</sub> value variability was observed across all patients (intersubject) (head: 60.2 ± 8.3 msec, body: 63.9 ± 11.5 msec, tail: 66.8 ± 16.4 msec). Interreader agreement was good (ICC, 0.82, 95% confidence interval: 0.77-0.86). T <sub>2</sub> -values differed significantly depending on age (P < 0.001), location (P < 0.001), main pancreatic duct dilatation (P < 0.001), and diffuse pancreatic disease (P < 0.03). The feasibility of accelerated T <sub>2</sub> mapping at 3 T in moving abdominal organs was demonstrated in the pancreas, since T <sub>2</sub> values were stable and reproducible. In the pancreatic parenchyma, T <sub>2</sub> -values were significantly dependent on demographic and clinical parameters. 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:410-416

A robust broadband fat-suppressing phaser T₂ -preparation module for cardiac magnetic resonance imaging at 3T.

Designing a new T <sub>2</sub> -preparation (T <sub>2</sub> -Prep) module to simultaneously provide robust fat suppression and efficient T <sub>2</sub> preparation without requiring an additional fat-suppression module for T <sub>2</sub> -weighted imaging at 3T. The tip-down radiofrequency (RF) pulse of an adiabatic T <sub>2</sub> -Prep module was replaced by a custom-designed RF-excitation pulse that induces a phase difference between water and fat, resulting in a simultaneous T <sub>2</sub> preparation of water signals and the suppression of fat signals at the end of the module (a phaser adiabatic T <sub>2</sub> -Prep). Numerical simulations and in vitro and in vivo electrocardiogram (ECG)-triggered navigator-gated acquisitions of the human heart were performed. Blood, myocardium, and fat signal-to-noise ratios and right coronary artery vessel sharpness were compared against previously published adiabatic T <sub>2</sub> -Prep approaches. Numerical simulations predicted an increased fat-suppression bandwidth and decreased sensitivity to transmit magnetic field inhomogeneities using the proposed approach while preserving the water T <sub>2</sub> -Prep capabilities. This was confirmed by the tissue signals acquired in the phantom and the in vivo images, which show similar blood and myocardium signal-to-noise ratio, contrast-to-noise ratio, and significantly reduced fat signal-to-noise ratio compared with the other methods. As a result, the right coronary artery conspicuity was significantly increased. A novel fat-suppressing T <sub>2</sub> -Prep method was developed and implemented that showed robust fat suppression and increased vessel sharpness compared with conventional techniques while preserving its T <sub>2</sub> -Prep capabilities

Noncontrast free-breathing respiratory self-navigated coronary artery cardiovascular magnetic resonance angiography at 3 T using lipid insensitive binomial off-resonant excitation (LIBRE).

Robust and homogeneous lipid suppression is mandatory for coronary artery cardiovascular magnetic resonance (CMR) imaging since the coronary arteries are commonly embedded in epicardial fat. However, effective large volume lipid suppression becomes more challenging when performing radial whole-heart coronary artery CMR for respiratory self-navigation and the problem may even be exacerbated at increasing magnetic field strengths. Incomplete fat suppression not only hinders a correct visualization of the coronary vessels and generates image artifacts, but may also affect advanced motion correction methods. The aim of this study was to evaluate a recently reported lipid insensitive CMR method when applied to a noncontrast self-navigated coronary artery CMR acquisitions at 3 T, and to compare it to more conventional fat suppression techniques. Lipid insensitive binomial off resonant excitation (LIBRE) radiofrequency excitation pulses were included into a self-navigated 3D radial GRE coronary artery CMR sequence at 3 T. LIBRE was compared against a conventional CHESS fat saturation (FS) and a binomial 1-180°-1 water excitation (WE) pulse. First, fat suppression of all techniques was numerically characterized using Matlab and experimentally validated in phantoms and in legs of human volunteers. Subsequently, free-breathing self-navigated coronary artery CMR was performed using the LIBRE pulse as well as FS and WE in ten healthy subjects. Myocardial, arterial and chest fat signal-to-noise ratios (SNR), as well as coronary vessel conspicuity were quantitatively compared among those scans. The results obtained in the simulations were confirmed by the experimental validations as LIBRE enabled near complete fat suppression for 3D radial imaging in vitro and in vivo. For self-navigated whole-heart coronary artery CMR at 3 T, fat SNR was significantly attenuated using LIBRE compared with conventional FS. LIBRE increased the right coronary artery (RCA) vessel sharpness significantly (37 ± 9% (LIBRE) vs. 29 ± 8% (FS) and 30 ± 8% (WE), both p < 0.05) and led to a significant increase in the measured RCA vessel length to (83 ± 31 mm (LIBRE) vs. 56 ± 12 mm (FS) and 59 ± 27 (WE) p < 0.05). Applied to a respiratory self-navigated noncontrast 3D radial whole-heart sequence, LIBRE enables robust large volume fat suppression and significantly improves coronary artery image quality at 3 T compared to the use of conventional FS and WE