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Theranostic imaging methods could greatly enhance our understanding of the distribution of CNS-acting drugs in individual patients. Fluorine-19 magnetic resonance imaging ((19)F MRI) offers the opportunity to localize and quantify fluorinated drugs non-invasively, without modifications and without the application of ionizing or other harmful radiation. Here we investigated siponimod, a sphingosine 1-phosphate (S(1)P) receptor antagonist indicated for secondary progressive multiple sclerosis (SPMS), to determine the feasibility of in vivo (19)F MR imaging of a disease modifying drug. METHODS: The (19)F MR properties of siponimod were characterized using spectroscopic techniques. Four MRI methods were investigated to determine which was the most sensitive for (19)F MR imaging of siponimod under biological conditions. We subsequently administered siponimod orally to 6 mice and acquired (19)F MR spectra and images in vivo directly after administration, and in ex vivo tissues. RESULTS: The (19)F transverse relaxation time of siponimod was 381 ms when dissolved in dimethyl sulfoxide, and substantially reduced to 5 ms when combined with serum, and to 20 ms in ex vivo liver tissue. Ultrashort echo time (UTE) imaging was determined to be the most sensitive MRI technique for imaging siponimod in a biological context and was used to map the drug in vivo in the stomach and liver. Ex vivo images in the liver and brain showed an inhomogeneous distribution of siponimod in both organs. In the brain, siponimod accumulated predominantly in the cerebrum but not the cerebellum. No secondary (19)F signals were detected from metabolites. From a translational perspective, we found that acquisitions done on a 3.0 T clinical MR scanner were 2.75 times more sensitive than acquisitions performed on a preclinical 9.4 T MR setup when taking changes in brain size across species into consideration and using equivalent relative spatial resolution. CONCLUSION: Siponimod can be imaged non-invasively using (19)F UTE MRI in the form administered to MS patients, without modification. This study lays the groundwork for more extensive preclinical and clinical investigations. With the necessary technical development, (19)F MRI has the potential to become a powerful theranostic tool for studying the time-course and distribution of CNS-acting drugs within the brain, especially during pathology.

PURPOSE Low SNR in fluorine-19 (19 F) MRI benefits from cryogenically-cooled transceive surface RF probes (CRPs), but strong B1 inhomogeneities hinder quantification. Rapid acquisition with refocused echoes (RARE) is an SNR-efficient method for MRI of neuroinflammation with perfluorinated compounds but lacks an analytical signal intensity equation to retrospectively correct B1 inhomogeneity. Here, a workflow was proposed and validated to correct and quantify 19 F-MR signals from the inflamed mouse brain using a 19 F-CRP. METHODS In vivo 19 F-MR images were acquired in a neuroinflammation mouse model with a quadrature 19 F-CRP using an imaging setup including 3D-printed components to acquire co-localized anatomical and 19 F images. Model-based corrections were validated on a uniform 19 F phantom and in the neuroinflammatory model. Corrected 19 F-MR images were benchmarked against reference images and overlaid on in vivo 1 H-MR images. Computed concentration uncertainty maps using Monte Carlo simulations served as a measure of performance of the B1 corrections. RESULTS Our study reports on the first quantitative in vivo 19 F-MR images of an inflamed mouse brain using a 19 F-CRP, including in vivo T1 calculations for 19 F-nanoparticles during pathology and B1 corrections for 19 F-signal quantification. Model-based corrections markedly improved 19 F-signal quantification from errors > 50% to < 10% in a uniform phantom (p < 0.001). Concentration uncertainty maps ex vivo and in vivo yielded uncertainties that were generally < 25%. Monte Carlo simulations prescribed SNR ≥ 10.1 to reduce uncertainties < 10%, and SNR ≥ 4.25 to achieve uncertainties < 25%. CONCLUSION Our model-based correction method facilitated 19 F signal quantification in the inflamed mouse brain when using the SNR-boosting 19 F-CRP technology, paving the way for future low-SNR 19 F-MRI applications in vivo.

Tissue hypoxia is an early key feature of acute kidney injury. Assessment of renal oxygenation using magnetic resonance imaging (MRI) markers TKS was determined from TUpon aortic occlusion KS decreased; this correlated with a decrease in TMonitoring KS allows physiological interpretation of acute renal oxygenation changes obtained by T

Thermal Magnetic Resonance (ThermalMR) is a theranostic concept that combines diagnostic magnetic resonance imaging (MRI) with targeted thermal therapy in the hyperthermia (HT) range using a radiofrequency (RF) applicator in an integrated system. ThermalMR adds a therapeutic dimension to a diagnostic MRI device. Focused, targeted RF heating of deep-seated brain tumors, accurate non-invasive temperature monitoring and high-resolution MRI are specific requirements of ThermalMR that can be addressed with novel concepts in RF applicator design. This work examines hybrid RF applicator arrays combining loop and self-grounded bow-tie (SGBT) dipole antennas for ThermalMR of brain tumors, at magnetic field strengths of 7.0 T, 9.4 T and 10.5 T. These high-density RF arrays improve the feasible transmission channel count, and provide additional degrees of freedom for RF shimming not afforded by using dipole antennas only, for superior thermal therapy and MRI diagnostics. These improvements are especially relevant for ThermalMR theranostics of deep-seated brain tumors because of the small surface area of the head. ThermalMR RF applicators with the hybrid loop+SGBT dipole design outperformed applicators using dipole-only and loop-only designs, with superior MRI performance and targeted RF heating. Array variants with a horse-shoe configuration covering an arc (270°) around the head avoiding the eyes performed better than designs with 360° coverage, with a 1.3 °C higher temperature rise inside the tumor while sparing healthy tissue. Our EMF and temperature simulations performed on a virtual patient with a clinically realistic intracranial tumor provide a technical foundation for implementation of advanced RF applicators tailored for ThermalMR theranostics of brain tumors.

PURPOSE: The use of surface radiofrequency (RF) coils is common practice to boost sensitivity in (pre)clinical MRI. The number of transceive surface RF coils is rapidly growing due to the surge in cryogenically cooled RF technology and ultrahigh‐field MRI. Consequently, there is an increasing need for effective correction of the excitation field (B(1)(+)) inhomogeneity inherent in these coils. Retrospective B(1) correction permits quantitative MRI, but this usually requires a pulse sequence‐specific analytical signal intensity (SI) equation. Such an equation is not available for fast spin‐echo (Rapid Acquisition with Relaxation Enhancement, RARE) MRI. Here we present, test, and validate retrospective B(1) correction methods for RARE. METHODS: We implemented the commonly used sensitivity correction and developed an empirical model‐based method and a hybrid combination of both. Tests and validations were performed with a cryogenically cooled RF probe and a single‐loop RF coil. Accuracy of SI quantification and T(1) contrast were evaluated after correction. RESULTS: The three described correction methods achieved dramatic improvements in B(1) homogeneity and significantly improved SI quantification and T(1) contrast, with mean SI errors reduced from >40% to >10% following correction in all cases. Upon correction, images of phantoms and mouse heads demonstrated homogeneity comparable to that of images acquired with a volume resonator. This was quantified by SI profile, SI ratio (error 80% in vivo and ex vivo compared to PIU > 87% with the reference RF coil). CONCLUSIONS: This work demonstrates the efficacy of three B(1) correction methods tailored for transceive surface RF probes and RARE MRI. The corrected images are suitable for quantification and show comparable results between the three methods, opening the way for T(1) measurements and X‐nuclei quantification using surface transceiver RF coils. This approach is applicable to other MR techniques for which no analytical SI exists.

Low SNR in fluorine-19 (In vivoOur study reports on the first quantitative in vivoOur model-based correction method facilitated

Kidney diseases constitute a major health challenge, which requires noninvasive imaging to complement conventional approaches to diagnosis and monitoring. Several renal pathologies are associated with changes in kidney size, offering an opportunity for magnetic resonance imaging (MRI) biomarkers of disease. This work uses dynamic MRI and an automated bean-shaped model (ABSM) for longitudinal quantification of pathophysiologically relevant changes in kidney size.A geometry-based ABSM was developed for kidney size measurements in rats using parametric MRI (TThe ABSM yielded renal size measurements with accuracy and precision equivalent to the manual segmentation, with70-fold time savings. The automated method could detect a ~7% reduction (aortic occlusion) and a ~5%, a ~2% and a ~6% increase in kidney size (venous occlusion, pelvis and intratubular pressure increase and injection of X-ray contrast medium, respectively). These measurements were not affected by reduced image quality following administration of ferumoxytol.Dynamic MRI in conjunction with renal segmentation using an ABSM supports longitudinal quantification of changes in kidney size in pathophysiologically relevant experimental setups mimicking realistic clinical scenarios. This can potentially be instrumental for developing MRI-based diagnostic tools for various kidney disorders and for gaining new insight into mechanisms of renal pathophysiology.

Objective Fluorine MR would benefit greatly from enhancements in signal-to-noise ratio (SNR). This study examines the sensitivity gain of 19F 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 (B0), 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 B0 with 2D-RARE and 2D-FLASH using 19F volume radiofrequency resonators together. T1 and T2 of PFCE were measured at both B0 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 19F T1 and T2 relaxation on B0 was demonstrated. High spatially resolved 19F MRI of EAE brains and LNs at 21.1 T revealed signals not seen at 9.4 T. Discussion Enhanced SNR and T1 shortening indicate the potential benefit of in vivo 19F MR at higher B0 to study inflammatory processes with greater detail. Electronic supplementary material The online version of this article (10.1007/s10334-018-0710-z) contains supplementary material, which is available to authorized users.

The characteristic MRI features of multiple sclerosis (MS) lesions make it conceptually appealing to pursue parametric mapping techniques that support simultaneous generation of quantitative maps of 2 or more MR contrast mechanisms. We present a modular rapid acquisition with relaxation enhancement (RARE)-EPI hybrid that facilitates simultaneous TIn 2in1-RARE-EPI the first echoes in the echo train are acquired with a RARE module, later echoes are acquired with an EPI module. To define the fraction of echoes covered by the RARE and EPI module, an error analysis of TThere was a good agreement between TThis work demonstrates the feasibility of radially (under)sampled 2in1-RARE-EPI for simultaneous T

The overall goal of this article is to demonstrate a state-of-the-art ultrahigh field (UHF) magnetic resonance (MR) protocol of the brain at 7.0 Tesla in multiple sclerosis (MS) patients. MS is a chronic inflammatory, demyelinating, neurodegenerative disease that is characterized by white and gray matter lesions. Detection of spatially and temporally disseminated T2-hyperintense lesions by the use of MRI at 1.5 T and 3 T represents a crucial diagnostic tool in clinical practice to establish accurate diagnosis of MS based on the current version of the 2017 McDonald criteria. However, the differentiation of MS lesions from brain white matter lesions of other origins can sometimes be challenging due to their resembling morphology at lower magnetic field strengths (typically 3 T). Ultrahigh field MR (UHF-MR) benefits from increased signal-to-noise ratio and enhanced spatial resolution, both key to superior imaging for more accurate and definitive diagnoses of subtle lesions. Hence, MRI at 7.0 T has shown encouraging results to overcome the challenges of MS differential diagnosis by providing MS-specific neuroimaging markers (e.g., central vein sign, hypointense rim structures and differentiation of MS grey matter lesions). These markers and others can be identified by other MR contrasts other than T1 and T2 (T2*, phase, diffusion) and substantially improve the differentiation of MS lesions from those occurring in other neuroinflammatory conditions such as neuromyelitis optica and Susac syndrome. In this article, we describe our current technical approach to study cerebral white and grey matter lesions in MS patients at 7.0 T using different MR acquisition methods. The up-to-date protocol includes the preparation of the MR setup including the radio-frequency coils customized for UHF-MR, standardized screening, safety and interview procedures with MS patients, patient positioning in the MR scanner and acquisition of dedicated brain scans tailored for examining MS.

Fluorine-19 MRI shows great promise for a wide range of applications including renal imaging, yet the typically low signal-to-noise ratios and sparse signal distribution necessitate a thorough data preparation.This chapter describes a general data preparation workflow for fluorine MRI experiments. The main processing steps are: (1) estimation of noise level, (2) correction of noise-induced bias and (3) background subtraction. The protocol is supplemented by an example script and toolbox available online.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

Here we describe a simple and inexpensive protocol for preparing ex vivo rodent phantoms for use in MR imaging studies. The experimental animals are perfused and fixed with formaldehyde, and then wrapped with gauze and sealed with liquid latex. This yields a phantom that preserves all organs in situ, and which avoids the need to keep fixed animals and organs in containers that have dimensions very different from living animals. This is especially important for loading in MR detectors, and specifically the RF coils, they are usually used with. The phantom can be safely stored and conveniently reused, and can provide MR scientists with a realistic phantom with which to establish protocols in preparation for preclinical in vivo studies—for renal, brain, and body imaging. The phantom also serves as an ideal teaching tool, for trainees learning how to perform preclinical MRI investigations of the kidney and other target organs, while avoiding the need for handling living animals, and reducing the total number of animals required.This protocol chapter is part of the PARENCHIMA initiative “MRI Biomarkers for CKD” (CA16103), a community-driven Action of the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.

Renal MRI holds incredible promise for making a quantum leap in improving diagnosis and care of patients with a multitude of diseases, by moving beyond the limitations and restrictions of current routine clinical practice. Clinical and preclinical renal MRI is advancing with ever increasing rapidity, and yet, aside from a few examples of renal MRI in routine use, it is still not good enough. Several roadblocks are still delaying the pace of progress, particularly inefficient education of renal MR researchers, and lack of harmonization of approaches that limits the sharing of results among multiple research groups.Here we aim to address these limitations for preclinical renal MRI (predominantly in small animals), by providing a comprehensive collection of more than 40 publications that will serve as a foundational resource for preclinical renal MRI studies. This includes chapters describing the fundamental principles underlying a variety of renal MRI methods, step-by-step protocols for executing renal MRI studies, and detailed guides for data analysis. This collection will serve as a crucial part of a roadmap toward conducting renal MRI studies in a robust and reproducible way, that will promote the standardization and sharing of data.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.

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Kidney-associated pathologies would greatly benefit from noninvasive and robust methods that can objectively quantify changes in renal function. In the past years there has been a growing incentive to develop new applications for fluorine (19F) MRI in biomedical research to study functional changes during disease states. 19F MRI represents an instrumental tool for the quantification of exogenous 19F substances in vivo. One of the major benefits of 19F MRI is that fluorine in its organic form is absent in eukaryotic cells. Therefore, the introduction of exogenous 19F signals in vivo will yield background-free images, thus providing highly selective detection with absolute specificity in vivo. Here we introduce the concept of 19F MRI, describe existing challenges, especially those pertaining to signal sensitivity, and give an overview of preclinical applications to illustrate the utility and applicability of this technique for measuring renal function in animal models.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Inflammation is one underlying contributing factor in the pathology of acute and chronic kidney disorders. Phagocytes such as monocytes, neutrophils and dendritic cells are considered to play a deleterious role in the progression of kidney disease but may also contribute to organ homeostasis. The kidney is a target of life-threatening autoimmune disorders such as the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). Neutrophils and monocytes express ANCA antigens and play an important role in the pathogenesis of AAV. Noninvasive in vivo methods that can quantify the distribution of inflammatory cells in the kidney as well as other organs in vivo would be vital to identify the causality and significance of inflammation during disease progression. Here we describe an noninvasive technique to study renal inflammation in rodents in vivo using fluorine (19F) MRI. In this protocol we chose a murine ANCA-AAV model of renal inflammation and made use of nanoparticles prepared from perfluoro-5-crown-15-ether (PFCE) for renal 19F MRI.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis.

The use of surface radiofrequency (RF) coils is common practice to boost sensitivity in (pre)clinical MRI. The number of transceive surface RF coils is rapidly growing due to the surge in cryogenically cooled RF technology and ultrahigh-field MRI. Consequently, there is an increasing need for effective correction of the excitation field (We implemented the commonly used sensitivity correction and developed an empirical model-based method and a hybrid combination of both. Tests and validations were performed with a cryogenically cooled RF probe and a single-loop RF coil. Accuracy of SI quantification and TThe three described correction methods achieved dramatic improvements in BThis work demonstrates the efficacy of three B

Design, implementation, evaluation and application of a quadrature birdcage radiofrequency (RF) resonator tailored for renal and cardiac sodium (23Na) magnetic resonance imaging (MRI) in rats at 9.4 T. A low pass birdcage resonator (16 rungs, din = 62 mm) was developed. The transmission field (B1+) was examined with EMF simulations. The scattering parameter (S-parameter) and the quality factor (Q-factor) were measured. For experimental validation B1+-field maps were acquired with the double-angle method. In vivo sodium imaging of the heart (spatial resolution: (1 × 1 × 5) mm3) and kidney (spatial resolution: (1 × 1 × 10) mm3) was performed with a FLASH technique. The RF resonator exhibits RF characteristics, transmission field homogeneity and penetration that afford 23Na MR in vivo imaging of the kidney and heart at 9.4 T. For the renal cortex and medulla a SNRs of 8 and 13 were obtained and a SNRs of 14 and 15 were observed for the left and right ventricle. These initial results obtained in vivo in rats using the quadrature birdcage volume RF resonator for 23Na MRI permit dedicated studies on experimental models of cardiac and renal diseases, which would contribute to translational research of the cardiorenal syndrome.

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 (T2 *) in vivo, and is non-invasive and indicative of renal tissue oxygenation. However, the renal T2 * to tissue pO2 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 T2 * are discussed. We also describe the basic principles of renal BVf assessment using ferumoxytol-enhanced MRI in the equilibrium concentration regimen. 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.

Diffusion-weighted magnetic resonance imaging (DWI) is a non-invasive imaging technique sensitive to tissue water movement. By enabling a discrimination between tissue properties without the need of contrast agent administration, DWI is invaluable for probing tissue microstructure in kidney diseases. DWI studies commonly make use of single-shot Echo-Planar Imaging (ss-EPI) techniques that are prone to suffering from geometric distortion. The goal of the present study was to develop a robust DWI technique tailored for preclinical magnetic resonance imaging (MRI) studies that is free of distortion and sensitive to detect microstructural changes. Since fast spin-echo imaging techniques are less susceptible to B0 inhomogeneity related image distortions, we introduced a diffusion sensitization to a split-echo Rapid Acquisition with Relaxation Enhancement (RARE) technique for high field preclinical DWI at 9.4 T. Validation studies in standard liquids provided diffusion coefficients consistent with reported values from the literature. Split-echo RARE outperformed conventional ss-EPI, with ss-EPI showing a 3.5-times larger border displacement (2.60 vs. 0.75) and a 60% higher intra-subject variability (cortex = 74%, outer medulla = 62% and inner medulla = 44%). The anatomical integrity provided by the split-echo RARE DWI technique is an essential component of parametric imaging on the way towards robust renal tissue characterization, especially during kidney disease.

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This study examines the influence of the environmental factor temperature on theStudies on PFCE, isoflurane, teriflunomide, and flupentixol showed a relationship between temperature and their physicochemical characteristics, namely, chemical shift, TThe impact of temperature on the

The integrity of the blood-brain barrier (BBB) can be noninvasively monitored by magnetic resonance imaging (MRI). Conventional MR contrast agents (CAs) containing gadolinium are used in association with MRI in routine clinical practice to detect and quantify BBB leakage. Under normal circumstances CAs do not cross the intact BBB. However due to their small size they extravasate from the blood into the brain tissue even when the BBB is partially compromised. Here we describe an MR method based on T

The integrity of the blood-brain barrier (BBB) can be noninvasively monitored by magnetic resonance imaging (MRI). Conventional MR contrast agents (CAs) containing gadolinium are used in association with MRI in routine clinical practice to detect and quantify BBB leakage. Under normal circumstances CAs do not cross the intact BBB. However due to their small size they extravasate from the blood into the brain tissue even when the BBB is partially compromised. Here we describe an MR method based on T1-weighted images taken prior to and after CA injection. This MR method is useful for investigating BBB permeability in in vivo mouse models and can be easily applied in a number of experimental disease conditions including neuroinflammation disorders, or to assess (un)wanted drug effects.

Diagnosis of early-stage acute kidney injury (AKI) will benefit from a timely identification of local tissue hypoxia. Renal tissue hypoxia is an early feature in AKI pathophysiology, and renal oxygenation is increasingly being assessed through T(2)*-weighted magnetic resonance imaging (MRI). However, changes in renal blood volume fraction (BVf) confound renal T(2)*. The aim of this study was to assess the feasibility of intravascular contrast-enhanced MRI for monitoring renal BVf during physiological interventions that are concomitant with variations in BVf and to explore the possibility of correcting renal T(2)* for BVf variations. A dose-dependent study of the contrast agent ferumoxytol was performed in rats. BVf was monitored throughout short-term occlusion of the renal vein, which is known to markedly change renal blood partial pressure of O(2) and BVf. BVf calculated from MRI measurements was used to estimate oxygen saturation of hemoglobin (SO(2)). BVf and SO(2) were benchmarked against cortical data derived from near-infrared spectroscopy. As estimated from magnetic resonance parametric maps of T(2) and T(2)*, BVf was shown to increase, whereas SO(2) was shown to decline during venous occlusion (VO). This observation could be quantitatively reproduced in test-retest scenarios. Changes in BVf and SO(2) were in good agreement with data obtained from near-infrared spectroscopy. Our findings provide motivation to advance multiparametric MRI for studying AKIs, with the ultimate goal of translating MRI-based renal BVf mapping into clinical practice en route noninvasive renal magnetic resonance oximetry as a method of assessing AKI and progression to chronic damage.

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.

Labeling cells for non-invasive tracking in vivo using magnetic resonance imaging (MRI) is an emerging hot topic garnering ever increasing attention, yet it is fraught with numerous methodological challenges, which merit careful attention. Several of the current procedures used to label cells for tracking by MRI take advantage of the intrinsic phagocytic nature of cells to engulf nanoparticles, though cells with low intrinsic phagocytic capacity are also commonly studied. Before we take the next steps towards administering such cells in vivo, it is essential to understand how the nanolabel is recognized, internalized, trafficked and distributed within the specific host cell. This is even more critical when contemplating labeling of cells that may ultimately be applied in vivo to patients in a therapeutic context.

Neuroinflammation can be monitored using fluorine-19 (19F)-containing nanoparticles and 19F MRI. Previously we studied neuroinflammation in experimental autoimmune encephalomyelitis (EAE) using room temperature (RT) 19F radiofrequency (RF) coils and low spatial resolution 19F MRI to overcome constraints in signal-to-noise ratio (SNR). This yielded an approximate localization of inflammatory lesions. Here we used a new 19F transceive cryogenic quadrature RF probe ( 19 F-CRP) that provides the SNR necessary to acquire superior spatially-resolved 19F MRI. First we characterized the signal-transmission profile of the 19 F-CRP. The 19 F-CRP was then benchmarked against a RT 19F/1H RF coil. For SNR comparison we used reference compounds including 19F-nanoparticles and ex vivo brains from EAE mice administered with 19F-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 19F 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.

Our recent studies demonstrated that electrostatically stabilized very small superparamagnetic iron oxide particles (VSOPs) are promising MRI probes for detecting various pathological aspects of autoimmunity in the central nervous system (CNS). However, investigation of the precise tissue and cellular distribution of VSOP has been technically limited due to the need to use iron detection methods for VSOP visualization. Therefore, we assessed here the utility of europium (Eu)-doped VSOP as an MRI tool for in vivo investigations in the animal model experimental autoimmune encephalomyelitis (EAE), and as a tool to investigate histopathological processes in the CNS using fluorescence microscopy. We demonstrated that Eu-VSOP display the same properties as VSOP in terms of revealing inflammation-mediated changes by binding to brain endothelium in vitro, and in terms of visualizing brain lesions in EAE in vivo. MRI examinations with Eu-VSOP confirm that at peak disease particles accumulated inside the choroid plexus, and in cerebellar and meningeal lesions. Importantly, Eu-VSOP-based MRI showed for the first time in a longitudinal setup that particles were absent from the choroid plexus in mice during remission of EAE, but accumulated again during subsequent relapse. Within the choroid plexus, Eu-VSOP were associated both with monocytes/macrophages present in the plexus stroma, and associated with epithelial cells. Using Eu-VSOP, we demonstrated for the first time the involvement of the choroid plexus in relapses. Thus, Eu-VSOP have the potential to reveal various aspects of choroid plexus involvement in neuroinflammation, including monocyte recruitment from the blood and alterations of the choroid plexus epithelium.

Cerebrovascular abnormality is frequently accompanied by cognitive dysfunctions, such as dementia. Antibodies against the α1-adrenoceptor (α1-AR) can be found in patients with Alzheimer’s disease with cerebrovascular disease, and have been shown to affect the larger vessels of the brain in rodents. However, the impact of α1-AR antibodies on the cerebral vasculature remains unclear. In the present study, we established a neuroimaging method to measure the relative cerebral blood volume (rCBV) in small rodents with the ultimate goal to detect changes in blood vessel density and/or vessel size induced by α1-AR antibodies. For this purpose, mapping of R2* and R2 was performed using MRI at 9.4T, before and after the injection of intravascular iron oxide particles (ferumoxytol). The change in the transverse relaxation rates (ΔR2*, ΔR2) showed a significant rCBV decrease in the cerebrum, cortex and hippocampus of rats (except hippocampal ΔR2), which was more pronounced for ΔR2* than for ΔR2. Immunohistological analyses confirmed that the α1-AR antibody induced blood vessel deficiencies. Our findings support the hypothesis that α1-AR antibodies lead to cerebral vessel damage throughout the brain, which can be monitored by MRI-derived rCBV, a non-invasive neuroimaging method. This demonstrates the value of rCBV estimation by ferumoxytolenhanced MRI at 9.4T, and further underlines the significance of this antibody in brain diseases involving vasculature impairments, such as dementia. Copyright © 2014 John Wiley & Sons, Ltd. Additional supporting information may be found in the online version of this article at the publisher’s web site.

OBJECTIVES: This study was designed to examine the feasibility of ophthalmic magnetic resonance imaging (MRI) at 7.0 T using a local 6-channel transmit/receive radiofrequency (RF) coil array in healthy volunteers and patients with intraocular masses. MATERIALS AND METHODS: A novel 6-element transceiver RF coil array that makes uses of loop elements and that is customized for eye imaging at 7.0 T is proposed. Considerations influencing the RF coil design and the characteristics of the proposed RF coil array are presented. Numerical electromagnetic field simulations were conducted to enhance the RF coil characteristics. Specific absorption rate simulations and a thorough assessment of RF power deposition were performed to meet the safety requirements. Phantom experiments were carried out to validate the electromagnetic field simulations and to assess the real performance of the proposed transceiver array. Certified approval for clinical studies was provided by a local notified body before the in vivo studies. The suitability of the RF coil to image the human eye, optical nerve, and orbit was examined in an in vivo feasibility study including (a) 3-dimensional (3D) gradient echo (GRE) imaging, (b) inversion recovery 3D GRE imaging, and (c) 2D T2-weighted fast spin-echo imaging. For this purpose, healthy adult volunteers (n = 17; mean age, 34 +- 11 years) and patients with intraocular masses (uveal melanoma, n = 5; mean age, 57 +- 6 years) were investigated. RESULTS: All subjects tolerated all examinations well with no relevant adverse events. The 6-channel coil array supports high-resolution 3D GRE imaging with a spatial resolution as good as 0.2 × 0.2 × 1.0 mm, which facilitates the depiction of anatomical details of the eye. Rather, uniform signal intensity across the eye was found. A mean signal-to-noise ratio of approximately 35 was found for the lens, whereas the vitreous humor showed a signal-to-noise ratio of approximately 30. The lens-vitreous humor contrast-to-noise ratio was 8, which allows good differentiation between the lens and the vitreous compartment. Inversion recovery prepared 3D GRE imaging using a spatial resolution of 0.4 × 0.4 × 1.0 mm was found to be feasible. T2-weighted 2D fast spin-echo imaging with the proposed RF coil afforded a spatial resolution of 0.25 × 0.25 × 0.7 mm. CONCLUSIONS: This work provides valuable information on the feasibility of ophthalmic MRI at 7.0 T using a dedicated 6-channel transceiver coil array that supports the acquisition of high-contrast, high-spatial resolution images in healthy volunteers and patients with intraocular masses. The results underscore the challenges of ocular imaging at 7.0 T and demonstrate that these issues can be offset by using tailored RF coil hardware. The benefits of such improvements would be in positive alignment with explorations that are designed to examine the potential of MRI for the assessment of spatial arrangements of the eye segments and their masses with the ultimate goal to provide imaging means for guiding treatment decisions in ophthalmological diseases.