Eight-channel transceiver RF coil array tailored for (1)H/(19)F MR of the human knee and fluorinated drugs at 7.0 T

The purpose of this study was to evaluate the feasibility of an eight-channel dual-tuned transceiver surface RF coil array for combined (1) H/(19) F MR of the human knee at 7.0 T following application of (19) F-containing drugs. The (1) H/(19) F RF coil array includes a posterior module with two (1) H loop elements and two anterior modules, each consisting of one (1) H and two (19) F elements. The decoupling of neighbor elements is achieved by a shared capacitor. Electromagnetic field simulations were performed to afford uniform transmission fields and to be in accordance with RF safety guidelines. Localized (19) F MRS was conducted with 47 and 101 mmol/L of flufenamic acid (FA) - a (19) F-containing non-steroidal anti-inflammatory drug - to determine T1 and T2 and to study the (19) F signal-to-dose relationship. The suitability of the proposed approach for (1) H/(19) F MR was examined in healthy subjects. Reflection coefficients of each channel were less than -17 dB and coupling between channels was less than -11 dB. QL /QU was less than 0.5 for all elements. MRS results demonstrated signal stability with 1% variation. T1 and T2 relaxation times changed with concentration of FA: T1 /T2 = 673/31 ms at 101 mmol/L and T1 /T2 = 616/26 ms at 47 mmol/L. A uniform signal and contrast across the patella could be observed in proton imaging. The sensitivity of the RF coil enabled localization of FA ointment administrated to the knee with an in-plane spatial resolution of (1.5 × 1.5) mm(2) achieved in a total scan time of approximately three minutes, which is well suited for translational human studies. This study shows the feasibility of combined (1) H/(19) F MRI of the knee at 7.0 T and proposes T1 and T2 mapping methods for quantifying fluorinated drugs in vivo. Further technological developments are necessary to promote real-time bioavailability studies and quantification of (19) F-containing medicinal compounds in vivo

Solving the time- and frequency-multiplexed problem of constrained radiofrequency induced hyperthermia

Targeted radiofrequency (RF) heating induced hyperthermia has a wide range of applications, ranging from adjunct anti-cancer treatment to localized release of drugs. Focal RF heating is usually approached using time-consuming nonconvex optimization procedures or approximations, which significantly hampers its application. To address this limitation, this work presents an algorithm that recasts the problem as a semidefinite program and quickly solves it to global optimality, even for very large (human voxel) models. The target region and a desired RF power deposition pattern as well as constraints can be freely defined on a voxel level, and the optimum application RF frequencies and time-multiplexed RF excitations are automatically determined. 2D and 3D example applications conducted for test objects containing pure water (r(target) = 19 mm, frequency range: 500–2000 MHz) and for human brain models including brain tumors of various size (r(1) = 20 mm, r(2) = 30 mm, frequency range 100–1000 MHz) and locations (center, off-center, disjoint) demonstrate the applicability and capabilities of the proposed approach. Due to its high performance, the algorithm can solve typical clinical problems in a few seconds, making the presented approach ideally suited for interactive hyperthermia treatment planning, thermal dose and safety management, and the design, rapid evaluation, and comparison of RF applicator configurations

Fluorine-19 MRI at 21.1 T: enhanced spin-lattice relaxation of perfluoro-15-crown-5-ether and sensitivity as demonstrated in ex vivo murine neuroinflammation

OBJECTIVE: Fluorine MR would benefit greatly from enhancements in signal-to-noise ratio (SNR). This study examines the sensitivity gain of (19)F MR that can be practically achieved when moving from 9.4 to 21.1 T. MATERIALS AND METHODS: We studied perfluoro-15-crown-5-ether (PFCE) at both field strengths (B(0)), as a pure compound, in the form of nanoparticles (NP) as employed to study inflammation in vivo, as well as in inflamed tissue. Brains, lymph nodes (LNs) and spleens were obtained from mice with experimental autoimmune encephalomyelitis (EAE) that had been administered PFCE NPs. All samples were measured at both B(0) with 2D-RARE and 2D-FLASH using (19)F volume radiofrequency resonators together. T(1) and T(2) of PFCE were measured at both B(0) strengths. RESULTS: Compared to 9.4 T, an SNR gain of > 3 was observed for pure PFCE and > 2 for PFCE NPs at 21.1 T using 2D-FLASH. A dependency of (19)F T(1) and T(2) relaxation on B(0) was demonstrated. High spatially resolved (19)F MRI of EAE brains and LNs at 21.1 T revealed signals not seen at 9.4 T. DISCUSSION: Enhanced SNR and T(1) shortening indicate the potential benefit of in vivo (19)F MR at higher B(0) to study inflammatory processes with greater detail

High temporal resolution parametric MRI monitoring of the initial ischemia/reperfusion phase in experimental acute kidney injury

Ischemia/reperfusion (I/R) injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI). There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive parametric magnetic resonance imaging (MRI) may elucidate spatio-temporal pathophysiological changes in the kidney by monitoring the MR relaxation parameters T* and T, which are known to be sensitive to blood oxygenation. The aim of our study was to establish the technical feasibility of fast continuous T*/T mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of changes in all kidney regions during ischemia and early reperfusion. Significant changes in T* and T were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI

Performance of compressed sensing for fluorine-19 magnetic resonance imaging at low signal-to-noise ratio conditions

PURPOSE: To examine the performance of compressed sensing (CS) in reconstructing low signal-to-noise ratio (SNR) (19)F MR signals that are close to the detection threshold and originate from small signal sources with no a priori known location. METHODS: Regularization strength was adjusted automatically based on noise level. As performance metrics, root-mean-square deviations, true positive rates (TPRs), and false discovery rates were computed. CS and conventional reconstructions were compared at equal measurement time and evaluated in relation to high-SNR reference data. (19)F MR data were generated from a purpose-built phantom and benchmarked against simulations, as well as from the experimental autoimmune encephalomyelitis mouse model. We quantified the signal intensity bias and introduced an intensity calibration for in vivo data using high-SNR ex vivo data. RESULTS: Low-SNR (19)F MR data could be reliably reconstructed. Detection sensitivity was consistently improved and data fidelity was preserved for undersampling and averaging factors of α = 2 or = 3. Higher α led to signal blurring in the mouse model. The improved TPRs at α = 3 were comparable to a 2.5-fold increase in measurement time. Whereas CS resulted in a downward bias of the (19)F MR signal, Fourier reconstructions resulted in an unexpected upward bias of similar magnitude. The calibration corrected signal-intensity deviations for all reconstructions. CONCLUSION: CS is advantageous whenever image features are close to the detection threshold. It is a powerful tool, even for low-SNR data with sparsely distributed (19)F signals, to improve spatial and temporal resolution in (19)F MR applications

High spatial resolution and temporally resolved t(2) (*) mapping of normal human myocardium at 7.0 tesla: an ultrahigh field magnetic resonance feasibility study

Myocardial tissue characterization using T(2) (*) relaxation mapping techniques is an emerging application of (pre)clinical cardiovascular magnetic resonance imaging. The increase in microscopic susceptibility at higher magnetic field strengths renders myocardial T(2) (*) mapping at ultrahigh magnetic fields conceptually appealing. This work demonstrates the feasibility of myocardial T(2) (*) imaging at 7.0 T and examines the applicability of temporally-resolved and high spatial resolution myocardial T(2) (*) mapping. In phantom experiments single cardiac phase and dynamic (CINE) gradient echo imaging techniques provided similar T(2) (*) maps. In vivo studies showed that the peak-to-peak B(0) difference following volume selective shimming was reduced to approximately 80 Hz for the four chamber view and mid-ventricular short axis view of the heart and to 65 Hz for the left ventricle. No severe susceptibility artifacts were detected in the septum and in the lateral wall for T(2) (*) weighting ranging from TE = 2.04 ms to TE = 10.2 ms. For TE >7 ms, a susceptibility weighting induced signal void was observed within the anterior and inferior myocardial segments. The longest T(2) (*) values were found for anterior (T(2) (*) = 14.0 ms), anteroseptal (T(2) (*) = 17.2 ms) and inferoseptal (T(2) (*) = 16.5 ms) myocardial segments. Shorter T(2) (*) values were observed for inferior (T(2) (*) = 10.6 ms) and inferolateral (T(2) (*) = 11.4 ms) segments. A significant difference (p = 0.002) in T(2) (*) values was observed between end-diastole and end-systole with T(2) (*) changes of up to approximately 27% over the cardiac cycle which were pronounced in the septum. To conclude, these results underscore the challenges of myocardial T(2) (*) mapping at 7.0 T but demonstrate that these issues can be offset by using tailored shimming techniques and dedicated acquisition schemes

Visualizing brain inflammation with a shingled-leg radio-frequency head probe for (19)F/(1)H MRI

Magnetic resonance imaging (MRI) provides the opportunity of tracking cells in vivo. Major challenges in dissecting cells from the recipient tissue and signal sensitivity constraints albeit exist. In this study, we aimed to tackle these limitations in order to study inflammation in autoimmune encephalomyelitis. We constructed a very small dual-tunable radio frequency (RF) birdcage probe tailored for (19)F (fluorine) and (1)H (proton) MR mouse neuroimaging. The novel design eliminated the need for extra electrical components on the probe structure and afforded a uniform -field as well as good SNR. We employed fluorescently-tagged (19)F nanoparticles and could study the dynamics of inflammatory cells between CNS and lymphatic system during development of encephalomyelitis, even within regions of the brain that are otherwise not easily visualized by conventional probes. (19)F/(1)H MR Neuroimaging will allow us to study the nature of immune cell infiltration during brain inflammation over an extensive period of time

Enhanced fluorine-19 MRI sensitivity using a cryogenic radiofrequency probe: technical developments and ex vivo demonstration in a mouse model of neuroinflammation

Neuroinflammation can be monitored using fluorine-19 ((19)F)-containing nanoparticles and (19)F MRI. Previously we studied neuroinflammation in experimental autoimmune encephalomyelitis (EAE) using room temperature (RT) (19)F radiofrequency (RF) coils and low spatial resolution (19)F MRI to overcome constraints in signal-to-noise ratio (SNR). This yielded an approximate localization of inflammatory lesions. Here we used a new (19)F transceive cryogenic quadrature RF probe ((19) F-CRP) that provides the SNR necessary to acquire superior spatially-resolved (19)F MRI. First we characterized the signal-transmission profile of the (19) F-CRP. The (19) F-CRP was then benchmarked against a RT (19)F/(1)H RF coil. For SNR comparison we used reference compounds including (19)F-nanoparticles and ex vivo brains from EAE mice administered with (19)F-nanoparticles. The transmit/receive profile of the (19) F-CRP diminished with increasing distance from the surface. This was counterbalanced by a substantial SNR gain compared to the RT coil. Intraparenchymal inflammation in the ex vivo EAE brains was more sharply defined when using 150 μm isotropic resolution with the (19) F-CRP, and reflected the known distribution of EAE histopathology. At this spatial resolution, most (19)F signals were undetectable using the RT coil. The (19) F-CRP is a valuable tool that will allow us to study neuroinflammation with greater detail in future in vivo studies

Probing renal blood volume with magnetic resonance imaging

Damage to the kidney substantially reduces life expectancy. Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. In vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) is sensitive to changes in the effective transversal relaxation time (T(2)*) in vivo, is non-invasive and indicative of renal tissue oxygenation. However, the renal T(2)* to tissue pO(2) relationship is not governed exclusively by renal blood oxygenation, but is affected by physiological confounders with alterations in renal blood volume fraction (BVf) being of particular relevance. To decipher this interference probing renal BVf is essential for the pursuit of renal MR oximetry. Superparamagnetic iron oxide nanoparticle (USPIO) preparations can be used as MRI visible blood pool markers for detailing alterations in BVf. This review promotes the opportunities of MRI based assessment of renal BVf. Following an outline on the specifics of renal oxygenation and perfusion, changes in renal BVf upon interventions and their potential impact on renal T(2)* are discussed. We also describe the basic principles of renal BVf assessment using ferumoxytol enhanced MRI in the equilibrium concentration regime. We demonstrate that ferumoxytol does not alter control of renal haemodynamics and oxygenation. Preclinical applications of ferumoxytol enhanced renal MRI as well as considerations for its clinical implementation for examining renal BVf changes are provided alongside practical considerations. Finally, we explore the future directions of MRI based assessment of renal BVf

ERK1 as a therapeutic target for dendritic cell vaccination against high-grade gliomas

Glioma regression requires the recruitment of potent anti-tumor immune cells into the tumor microenvironment. Dendritic cells (DCs) play a role in immune responses to these tumors. The fact that DC vaccines do not effectively combat high-grade gliomas, however, suggests that DCs need to be genetically modified especially to promote their migration to tumor relevant sites. Previously, we identified extracellular signal-regulated kinase (ERK1) as a regulator of DC immunogenicity and brain autoimmunity. In the present study, we made use of modern magnetic resonance methods to study the role of ERK1 in regulating DC migration and tumor progression in a model of high-grade glioma. We found that ERK1-deficient mice are more resistant to the development of gliomas, and tumor growth in these mice is accompanied by a higher infiltration of leukocytes. ERK1-deficient DCs exhibit an increase in migration that is associated with sustained Cdc42 activation and increased expression of actin-associated cytoskeleton-organizing proteins. We also demonstrated that ERK1 deletion potentiates DC vaccination and provides a survival advantage in high-grade gliomas. Considering the therapeutic significance of these results, we propose ERK1-deleted DC vaccines as an additional means of eradicating resilient tumor cells and preventing tumor recurrence