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High-grade gliomas, the most common and aggressive primary brain tumors, are characterized by a complex tumor microenvironment (TME). Among the immune cells infiltrating the glioma TME, tumor-associated microglia and macrophages (TAMs) constitute the major compartment. In patients with gliomas, increased TAM abundance is associated with more aggressive disease. Alterations in TAM phenotypes and functions have been reported in preclinical models of multiple cancers during tumor development and after therapeutic interventions, including radiotherapy and molecular targeted therapies. These findings indicate that it is crucial to evaluate TAM abundance and dynamics over time. Current techniques to quantify TAMs in patients rely mainly on histological staining of tumor biopsies. Although informative, these techniques require an invasive procedure to harvest the tissue sample and typically only result in a snapshot of a small region at a single point in time. Fluorine isotope 19 MRI ( 19 F MRI) represents a powerful means to noninvasively and longitudinally monitor myeloid cells in pathological conditions by intravenously injecting perfluorocarbon-containing nanoparticles (PFC-NP). In this study, we demonstrated the feasibility and power of 19 F MRI in preclinical models of gliomagenesis, breast-to-brain metastasis, and breast cancer and showed that the major cellular source of 19 F signal consists of TAMs. Moreover, multispectral 19 F MRI with two different PFC-NP allowed us to identify spatially and temporally distinct TAM niches in radiotherapy-recurrent murine gliomas. Together, we have imaged TAMs noninvasively and longitudinally with integrated cellular, spatial, and temporal resolution, thus revealing important biological insights into the critical functions of TAMs, including in disease recurrence.

PURPOSE To implement, optimize, and characterize lipid-insensitive binomial off-resonant RF excitation (LIBRE) pulses for fat-suppressed fully self-gated free-running 5D cardiac MRI. METHODS Bloch equation simulations were used to optimize LIBRE parameter settings in non-interrupted bSSFP prior to in vitro validation. Thus, optimized LIBRE pulses were subsequently applied to free-running coronary MRA in 20 human adult subjects, where resulting images were quantitatively compared to those obtained with non-fat-suppressing excitation (SP), conventional 1-2-1 water excitation (WE), and a previously published interrupted free-running (IFR) sequence. SAR and scan times were recorded. Respiratory-and-cardiac-motion-resolved images were reconstructed with XD-GRASP, and contrast ratios, coronary artery detection rate, vessel length, and vessel sharpness were computed. RESULTS The numerically optimized LIBRE parameters were successfully validated in vitro. In vivo, LIBRE had the lowest SAR and a scan time that was similar to that of WE yet 18% shorter than that of IFR. LIBRE improved blood-fat contrast when compared to SP, WE, and IFR, vessel detection relative to SP and IFR, and vessel sharpness when compared to WE and IFR (for example, for the left main and anterior descending coronary artery, 51.5% ± 10.2% [LIBRE] versus 42.1% ± 6.8% [IFR]). Vessel length measurements remained unchanged for all investigated methods. CONCLUSION LIBRE enabled fully self-gated non-interrupted free-running 5D bSSFP imaging of the heart at 1.5T with suppressed fat signal. Measures of image quality, vessel conspicuity, and scan time compared favorably to those obtained with the more conventional non-interrupted WE and the previously published IFR, while SAR reduction offers added flexibility.

Fluorine-19 ( 19 F) magnetic resonance imaging (MRI) of injected perfluorocarbons (PFCs) can be used for the quantification and monitoring of inflammation in diseases such as atherosclerosis. To advance the translation of this technique to the clinical setting, we aimed to 1) demonstrate the feasibility of quantitative 19 F MRI in small inflammation foci on a clinical scanner, and 2) to characterize the PFC-incorporating leukocyte populations and plaques. To this end, thirteen atherosclerotic apolipoprotein-E-knockout mice received 2 × 200 µL PFC, and were scanned on a 3 T clinical MR system. 19 F MR signal was detected in the aortic arch and its branches in all mice, with a signal-to-noise ratio of 11.1 (interquartile range IQR = 9.5-13.1) and a PFC concentration of 1.15 mM (IQR = 0.79-1.28). Imaging flow cytometry was used on another ten animals and indicated that PFC-labeled leukocytes in the aortic arch and it branches were mainly dendritic cells, macrophages and neutrophils (ratio 9:1:1). Finally, immunohistochemistry analysis confirmed the presence of those cells in the plaques. We thus successfully used 19 F MRI for the noninvasive quantification of PFC in atherosclerotic plaque in mice on a clinical scanner, demonstrating the feasibility of detecting very small inflammation foci at 3 T, and advancing the translation of 19 F MRI to the human setting.

BACKGROUND Improved knee cartilage morphological delineation and T2 mapping precision necessitates isotropic 3D high-resolution and efficient fat suppression. PURPOSE To develop and assess an isotropic 3D lipid-insensitive T2 mapping technique of the knee for improved cartilage delineation and precise measurement of T2 relaxation times. STUDY TYPE Prospective. PHANTOM/SUBJECTS Phantoms (n = 6) used in this study were designed to mimic the T1 and T2 relaxation times of cartilage and fat. The study cohort comprised healthy volunteers (n = 7) for morphometry and T2 relaxation time measurements. FIELD STRENGTH/SEQUENCE A high-resolution isotropic 3D T2 mapping technique that uses sequential T2 -prepared segmented gradient-recalled echo (Iso3DGRE) images and lipid-insensitive binomial off-resonant radiofrequency (RF) excitation (LIBRE) at 3T. ASSESSMENT Numerical simulations and phantom experiments were performed to optimize the LIBRE pulse. Phantom studies were carried out to test the accuracy of the technique against reference standard spin-echo (SE) T2 mapping. Subsequently, T2 maps with and without LIBRE pulses were acquired in knees of healthy volunteers and the T2 relaxation time values in different cartilage compartments were compared. STATISTICAL TESTS A two-tailed paired Student's t-test was used to compare the average T2 values and the relative standard deviations (inverse measurement of the precision) obtained with and without LIBRE pulses. RESULTS A LIBRE pulse of 1 msec suppressed fat with an RF excitation frequency offset of 1560 Hz and optimal RF excitation angle of 35°. These results were corroborated by phantom and knee experiments. Robust and homogeneous fat suppression was obtained (a fat signal-to-noise ratio (SNR) decrease of 86.4 ± 2.4%). In phantoms, T2 values were found in good agreement when comparing LIBRE-Iso3DGRE with SE (slope 0.93 ± 0.04, intercept 0.11 ± 1.6 msec, R2 >0.99). In vivo, LIBRE excitation resulted in more precise T2 estimation (23.7 ± 7.4%) than normal excitation (30.5 ± 9.9%, P < 0.0001). DATA CONCLUSION Homogeneous LIBRE fat signal suppression was achieved with a total RF pulse duration of 1 msec, allowing for the removal of chemical shift artifacts and resulting in improved cartilage delineation and precise T2 values. LEVEL OF EVIDENCE 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1275-1284.

To develop high-spatial-resolution cardiac T 2 mapping that allows for a reduced acquisition time while maintaining its precision. We implemented and optimized a new golden-angle radial T 2 mapping technique named SKRATCH (Shared k-space Radial T 2 Characterization of the Heart) that shares k-space peripheries of T 2 -weighted images while preserving their contrasts. Six SKRATCH variants (gradient-recalled echo and balanced SSFP, free-breathing and breath-held, with and without a saturation preparation) were implemented, and their precision was compared with a navigator-gated reference technique in phantoms and 22 healthy volunteers at 3 T. The optimal breath-held SKRATCH technique was applied in a small cohort of patients with subacute myocardial infarction. The faster free-breathing SKRATCH technique reduced the acquisition time by 52.4%, while maintaining the precision and spatial resolution of the reference technique. Similarly, the most precise and robust breath-held SKRATCH technique demonstrated homogenous T 2 values that did not significantly differ from the navigator-gated reference (T 2 = 39.9 ± 3.4 ms versus 39.5 ± 3.4 ms, P > .20, respectively). All infarct patients demonstrated a large T 2 elevation in the ischemic regions of the myocardium. The optimized SKRATCH technique enabled the accelerated acquisition of high-spatial-resolution T 2 maps, was validated in healthy adult volunteers, and was successfully applied to a small initial group of patients.

PURPOSE 1) To implement a higher-resolution isotropic 3D T2 mapping technique that uses sequential T2 -prepared segmented gradient-recalled echo (Iso3DGRE) images for knee cartilage evaluation, and 2) to validate it both in vitro and in vivo in healthy volunteers and patients with knee osteoarthritis. MATERIALS AND METHODS The Iso3DGRE sequence with an isotropic 0.6 mm spatial resolution was developed on a clinical 3T MR scanner. Numerical simulations were performed to optimize the pulse sequence parameters. A phantom study was performed to validate the T2 estimation accuracy. The repeatability of the sequence was assessed in healthy volunteers (n = 7). T2 values were compared with those from a clinical standard 2D multislice multiecho (MSME) T2 mapping sequence in knees of healthy volunteers (n = 13) and in patients with knee osteoarthritis (OA, n = 5). RESULTS The numerical simulations resulted in 100 excitations per segment and an optimal radiofrequency (RF) excitation angle of 15°. The phantom study demonstrated a good correlation of the technique with the reference standard (slope 0.9 ± 0.05, intercept 0.2 ± 1.7 msec, R2 ≥ 0.99). Repeated measurements of cartilage T2 values in healthy volunteers showed a coefficient of variation of 5.6%. Both Iso3DGRE and MSME techniques found significantly higher cartilage T2 values (P < 0.03) in OA patients. Iso3DGRE precision was equal to that of the MSME T2 mapping in healthy volunteers, and significantly higher in OA (P = 0.01). CONCLUSION This study successfully demonstrated that high-resolution isotropic 3D T2 mapping for knee cartilage characterization is feasible, accurate, repeatable, and precise. The technique allows for multiplanar reformatting and thus T2 quantification in any plane of interest. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:362-371.

The two main challenges that prevent the translation of fluorine-19 ( 19 F) MRI for inflammation monitoring or cell tracking into clinical practice are (i) the relatively low signal-to-noise ratio generated by the injected perfluorocarbon (PFC), which necessitates long scan times, and (ii) the need for regulatory approval and a high biocompatibility of PFCs that are also suitable for MRI. ABL-101, an emulsion of perfluoro(t-butylcyclohexane), is a third-generation PFC that is already used in clinical trials, but has not yet been used for 19 F MRI. The objective of this study was therefore to assess the performance of ABL-101 as a 19 F MRI tracer. At magnetic field strengths of 3, 9.4 and 14.1 T, the CF 3 groups of ABL-101 generated a large well-separated singlet with T 2 /T 1 ratios of >0.27, >0.14 and > 0.05, respectively. All relaxation times decreased with the increase in magnetic field strength. The detection limit of ABL-101 in a 0.25 mm 3 voxel at 3 T, 37°C and with a 3-minute acquisition time was 7.21mM. After intravenous injection, the clearance half-lives of the ABL-101 19 F MR signal in mouse (n = 3) spleen and liver were 6.85 ± 0.45 and 3.20 ± 0.35 days, respectively. These results demonstrate that ABL-101 has 19 F MR characteristics that are similar to those of PFCs developed specifically for MRI, while it has clearance half-lives similar to PFCs that have previously been used in large doses in non-MRI clinical trials. Overall, ABL-101 is thus a very promising candidate tracer for future clinical trials that use 19 F MRI for cell tracking or the monitoring of inflammation.

Fluorine-19 (19 F) MRI of injected perfluorocarbon emulsions (PFCs) allows for the non-invasive quantification of inflammation and cell tracking, but suffers from a low signal-to-noise ratio and extended scan time. To address this limitation, we tested the hypotheses that a 19 F MRI pulse sequence that combines a specific undersampling regime with signal averaging has both increased sensitivity and robustness against motion artifacts compared with a non-averaged fully sampled pulse sequence, when both datasets are reconstructed with compressed sensing. As a proof of principle, numerical simulations and phantom experiments were performed on selected variable ranges to characterize the point spread function of undersampling patterns, as well as the vulnerability to noise of undersampling and reconstruction parameters with paired numbers of x signal averages and acceleration factor x (NAx-AFx). The numerical simulations demonstrated that a probability density function that uses 25% of the samples to fully sample the k-space central area allowed for an optimal balance between limited blurring and artifact incoherence. At all investigated noise levels, the Dice similarity coefficient (DSC) strongly depended on the regularization parameters and acceleration factor. In phantoms, the motion robustness of an NA8-AF8 undersampling pattern versus NA1-AF1 was evaluated with simulated and real motion patterns. Differences were assessed with the DSC, which was consistently higher for the NA8-AF8 compared with the NA1-AF1 strategy, for both simulated and real cyclic motion patterns (P < 0.001). Both strategies were validated in vivo in mice (n = 2) injected with perfluoropolyether. Here, the images displayed a sharper delineation of the liver with the NA8-AF8 strategy than with the NA1-AF1 strategy. In conclusion, we validated the hypotheses that in 19 F MRI the combination of undersampling and averaging improves both the sensitivity and the robustness against motion artifacts.

PURPOSE To characterize and optimize 19 F MRI for different perfluorocarbons (PFCs) at 3T and quantify the loss of acquisition efficiency as a function of different temperature and cellular conditions. METHODS The T1 and T2 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. RESULTS 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. CONCLUSION Optimizing 19 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.

To implement a fluorine-19 ( 19 F) chemical shift encoding (CSE) approach for the sensitive imaging of molecules with multi-resonance spectra to remove their chemical shift displacement (CSD) artifacts, and to characterize its sensitivity versus established pulse sequences. The feasibility of CSE spoiled gradient echo (GRE) and balanced steady-state free precession (bSSFP) was first demonstrated in a phantom study. The dependence of the sensitivity of CSE-bSSFP on several pulse sequence parameters was then established, after which the occurrence of out-of-plane excitation was assessed for 2D and 3D techniques. Next, the sensitivity (in mm -3 s -0.5 ) of both CSE techniques was compared to bSSFP ultrashort echo time (bSSFP-UTE) imaging and multi-chemical-shift-selective turbo spin echo (MCSS-TSE) in a second phantom study. Finally, the sensitivity of the CSE-bSSFP, bSSFP-UTE, and MCSS-TSE pulse sequences was compared in a preliminary in vivo mouse study. Both CSE approaches were successfully implemented and resulted in negligible residual CSD artifacts, while large-volume 3D acquisitions should be considered to reduce problems related to out-of-plane excitation. CSE-bSSFP was shown to have a higher sensitivity than the bSSFP-UTE and MCSS-TSE pulse sequences (15.8 ± 1.3 vs. 11.7 ± 1.0 vs. 13.3 ± 0.9 mm -3 s -0.5 , respectively, P < 0.001), whereas CSE-GRE technique had a lower sensitivity (4.8 ± 1.1 mm -3 s -0.5 ). CSE 19 F MR imaging enables the unambiguous visualization of compounds with complex spectra, and provides high sensitivity both in vitro and in vivo. Magn Reson Med 79:2724-2730, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

To develop high-spatial-resolution cardiac TSix SKRATCH variants (gradient-recalled echo and balanced SSFP, free-breathing and breath-held, with and without a saturation preparation) were implemented, and their precision was compared with a navigator-gated reference technique in phantoms and 22 healthy volunteers at 3 T. The optimal breath-held SKRATCH technique was applied in a small cohort of patients with subacute myocardial infarction.The faster free-breathing SKRATCH technique reduced the acquisition time by 52.4%, while maintaining the precision and spatial resolution of the reference technique. Similarly, the most precise and robust breath-held SKRATCH technique demonstrated homogenous TThe optimized SKRATCH technique enabled the accelerated acquisition of high-spatial-resolution T

1) To implement a higher-resolution isotropic 3D TThe Iso3DGRE sequence with an isotropic 0.6 mm spatial resolution was developed on a clinical 3T MR scanner. Numerical simulations were performed to optimize the pulse sequence parameters. A phantom study was performed to validate the TThe numerical simulations resulted in 100 excitations per segment and an optimal radiofrequency (RF) excitation angle of 15°. The phantom study demonstrated a good correlation of the technique with the reference standard (slope 0.9 ± 0.05, intercept 0.2 ± 1.7 msec, RThis study successfully demonstrated that high-resolution isotropic 3D T1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:362-371.

Previous studies identified the train compartment as the place where people can experience the highest exposure levels to electromagnetic fields in the radiofrequency range. Thus, in this study, a possible scenario of a train compartment has been reproduced and characterized, both numerically and experimentally, in order to assess the individual exposure. A very good agreement between the electric field values measured and simulated has been found. Results indicate that the individual exposure may increase, depending on the number of active cell phones, the coverage condition, and the position inside the compartment, while remaining well below the limits imposed by the international regulations.

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.