B1 inhomogeneity correction of RARE MRI at low SNR: Quantitative in vivo 19 F MRI of mouse neuroinflammation with a cryogenically-cooled transceive surface radiofrequency probe.

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.

32-Channel self-grounded bow-tie transceiver array for cardiac MR at 7.0T.

PURPOSE: Design, implementation, evaluation, and application of a 32-channel Self-Grounded Bow-Tie (SGBT) transceiver array for cardiac MR (CMR) at 7.0T. METHODS: The array consists of 32 compact SGBT building blocks. Transmission field ( B1+ ) shimming and radiofrequency safety assessment were performed with numerical simulations and benchmarked against phantom experiments. In vivo B1+ efficiency mapping was conducted with actual flip angle imaging. The array's applicability for accelerated high spatial resolution 2D FLASH CINE imaging of the heart was examined in a volunteer study (n = 7). RESULTS: B1+ shimming provided a uniform field distribution suitable for female and male subjects. Phantom studies demonstrated an excellent agreement between simulated and measured B1+ efficiency maps (7% mean difference). The SGBT array afforded a spatial resolution of (0.8 × 0.8 × 2.5) mm3 for 2D CINE FLASH which is by a factor of 12 superior to standardized cardiovascular MR (CMR) protocols. The density of the SGBT array supports 1D acceleration of up to R = 4 (mean signal-to-noise ratio (whole heart) ≥ 16.7, mean contrast-to-noise ratio ≥ 13.5) without impairing image quality significantly. CONCLUSION: The compact SGBT building block facilitates a modular high-density array that supports accelerated and high spatial resolution CMR at 7.0T. The array provides a technological basis for future clinical assessment of parallel transmission techniques.

Wideband Self-Grounded Bow-Tie Antenna for Thermal MR.

The objective of this study was the design, implementation, evaluation and application of a compact wideband self-grounded bow-tie (SGBT) radiofrequency (RF) antenna building block that supports anatomical proton (1 H) MRI, fluorine (19 F) MRI, MR thermometry and broadband thermal intervention integrated in a whole-body 7.0 T system. Design considerations and optimizations were conducted with numerical electromagnetic field (EMF) simulations to facilitate a broadband thermal intervention frequency of the RF antenna building block. RF transmission (B1+ ) field efficiency and specific absorption rate (SAR) were obtained in a phantom, and the thigh of human voxel models (Ella, Duke) for 1 H and 19 F MRI at 7.0 T. B1+ efficiency simulations were validated with actual flip-angle imaging measurements. The feasibility of thermal intervention was examined by temperature simulations (f = 300, 400 and 500 MHz) in a phantom. The RF heating intervention (Pin = 100 W, t = 120 seconds) was validated experimentally using the proton resonance shift method and fiberoptic probes for temperature monitoring. The applicability of the SGBT RF antenna building block for in vivo 1 H and 19 F MRI was demonstrated for the thigh and forearm of a healthy volunteer. The SGBT RF antenna building block facilitated 19 F and 1 H MRI at 7.0 T as well as broadband thermal intervention (234-561 MHz). For the thigh of the human voxel models, a B1+ efficiency ≥11.8 µT/√kW was achieved at a depth of 50 mm. Temperature simulations and heating experiments in a phantom demonstrated a temperature increase ΔT >7 K at a depth of 10 mm. The compact SGBT antenna building block provides technology for the design of integrated high-density RF applicators and for the study of the role of temperature in (patho-) physiological processes by adding a thermal intervention dimension to an MRI device (Thermal MR).

Radiofrequency applicator concepts for thermal magnetic resonance of brain tumors at 297 MHz (7.0 Tesla).

Purpose: Thermal intervention is a potent sensitizer of cells to chemo- and radiotherapy in cancer treatment. Glioblastoma multiforme (GBM) is a potential clinical target, given the cancer's aggressive nature and resistance to current treatment options. The annular phased array (APA) technique employing electromagnetic waves in the radiofrequency (RF) range allows for localized temperature increase in deep seated target volumes (TVs). Reports on clinical applications of the APA technique in the brain are still missing. Ultrahigh field magnetic resonance (MR) employs higher frequencies than conventional MR and has potential to provide focal temperature manipulation, high resolution imaging and noninvasive temperature monitoring using an integrated RF applicator (ThermalMR). This work examines the applicability of RF applicator concepts for ThermalMR of brain tumors at 297 MHz (7.0 Tesla).Methods: Electromagnetic field (EMF) simulations are performed for clinically realistic data based on GBM patients. Two algorithms are used for specific RF energy absorption rate based thermal intervention planning for small and large TVs in the brain, aiming at maximum RF power deposition or RF power uniformity in the TV for 10 RF applicator designs.Results: For both TVs , the power optimization outperformed the uniformity optimization. The best results for the small TV are obtained for the 16 element interleaved RF applicator using an elliptical antenna arrangement with water bolus. The two row elliptical RF applicator yielded the best result for the large TV.Discussion: This work investigates the capacity of ThermalMR to achieve targeted thermal interventions in model systems resembling human brain tissue and brain tumors.

Cardiorenal sodium MRI in small rodents using a quadrature birdcage volume resonator at 9.4 T.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Cardiorenal sodium MRI at 7.0 Tesla using a 4/4 channel 1 H/23 Na radiofrequency antenna array.

PURPOSE: Cardiorenal syndrome describes disorders of the heart and the kidneys in which a dysfunction of 1 organ induces a dysfunction in the other. This work describes the design, evaluation, and application of a 4/4-channel hydrogen-1/sodium (1 H/23 Na) RF array tailored for cardiorenal MRI at 7.0 Tesla (T) for a better physiometabolic understanding of cardiorenal syndrome. METHODS: The dual-frequency RF array is composed of a planar posterior section and a modestly curved anterior section, each section consisting of 2 loop elements tailored for 23 Na MR and 2 loopole-type elements customized for 1 H MR. Numerical electromagnetic field and specific absorption rate simulations were carried out. Transmission field ( B1+ ) uniformity was optimized and benchmarked against electromagnetic field simulations. An in vivo feasibility study was performed. RESULTS: The proposed array exhibits sufficient RF characteristics, B1+ homogeneity, and penetration depth to perform 23 Na MRI of the heart and kidney at 7.0 T. The mean B1+ field for sodium in the heart is 7.7 ± 0.8 µT/√kW and in the kidney is 6.9 ± 2.3 µT/√kW. The suitability of the RF array for 23 Na MRI was demonstrated in healthy subjects (acquisition time for 23 Na MRI: 18 min; nominal isotropic spatial resolution: 5 mm [kidney] and 6 mm [heart]). CONCLUSION: This work provides encouragement for further explorations into densely packed multichannel transceiver arrays tailored for 23 Na MRI of the heart and kidney. Equipped with this technology, the ability to probe sodium concentration in the heart and kidney in vivo using 23 Na MRI stands to make a critical contribution to deciphering the complex interactions between both organs.

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 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.

Millimeter spatial resolution in vivo sodium MRI of the human eye at 7 T using a dedicated radiofrequency transceiver array.

PURPOSE: The aim of this study was to achieve millimeter spatial resolution sodium in vivo MRI of the human eye at 7 T using a dedicated six-channel transceiver array. We present a detailed description of the radiofrequency coil design, along with electromagnetic field and specific absorption ratio simulations, data validation, and in vivo application. METHODS: Electromagnetic field and specific absorption ratio simulations were performed. Transmit field uniformity was optimized by using a multi-objective genetic algorithm. Transmit field mapping was conducted using a phase-sensitive method. An in vivo feasibility study was carried out with 3-dimensional density-adapted projection reconstruction imaging technique. RESULTS: Measured transmit field distribution agrees well with the one obtained from simulations. The specific absorption ratio simulations confirm that the radiofrequency coil is safe for clinical use. Our radiofrequency coil is light and conforms to an average human head. High spatial resolution (nominal 1.4 and 1.0 mm isotropic) sodium in vivo images of the human eye were acquired within scan times suitable for clinical applications (∼ 10 min). CONCLUSIONS: Three most important eye compartments in the context of sodium physiology were clearly delineated in all of the images: the vitreous humor, the aqueous humor, and the lens. Our results provide encouragement for further clinical studies. The implications for research into eye diseases including ocular melanoma, cataract, and glaucoma are discussed. Magn Reson Med 80:672-684, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

High peak and high average radiofrequency power transmit/receive switch for thermal magnetic resonance.

PURPOSE: To study the role of temperature in biological systems, diagnostic contrasts and thermal therapies, RF pulses for MR spin excitation can be deliberately used to apply a thermal stimulus. This application requires dedicated transmit/receive (Tx/Rx) switches that support high peak powers for MRI and high average powers for RF heating. To meet this goal, we propose a high-performance Tx/Rx switch based on positive-intrinsic-negative diodes and quarter-wavelength (λ/4) stubs. METHODS: The λ/4 stubs in the proposed Tx/Rx switch design route the transmitted RF signal directly to the RF coil/antenna without passing through any electronic components (e.g., positive-intrinsic-negative diodes). Bench measurements, MRI, MR thermometry, and RF heating experiments were performed at f = 297 MHz (B0 = 7 T) to examine the characteristics and applicability of the switch. RESULTS: The proposed design provided an isolation of -35.7dB/-41.5dB during transmission/reception. The insertion loss was -0.41dB/-0.27dB during transmission/reception. The switch supports high peak (3.9 kW) and high average (120 W) RF powers for MRI and RF heating at f = 297 MHz. High-resolution MRI of the wrist yielded image quality competitive with that obtained with a conventional Tx/Rx switch. Radiofrequency heating in phantom monitored by MR thermometry demonstrated the switch applicability for thermal modulation. Upon these findings, thermally activated release of a model drug attached to thermoresponsive polymers was demonstrated. CONCLUSION: The high-power Tx/Rx switch enables thermal MR applications at 7 T, contributing to the study of the role of temperature in biological systems and diseases. All design files of the switch will be made available open source at www.opensourceimaging.org.

Multiband diffusion-weighted MRI of the eye and orbit free of geometric distortions using a RARE-EPI hybrid.

Diffusion-weighted imaging (DWI) provides information on tissue microstructure. Single-shot echo planar imaging (EPI) is the most common technique for DWI applications in the brain, but is prone to geometric distortions and signal voids. Rapid acquisition with relaxation enhancement [RARE, also known as fast spin echo (FSE)] imaging presents a valuable alternative to DWI with high anatomical accuracy. This work proposes a multi-shot diffusion-weighted RARE-EPI hybrid pulse sequence, combining the anatomical integrity of RARE with the imaging speed and radiofrequency (RF) power deposition advantage of EPI. The anatomical integrity of RARE-EPI was demonstrated and quantified by center of gravity analysis for both morphological images and diffusion-weighted acquisitions in phantom and in vivo experiments at 3.0 T and 7.0 T. The results indicate that half of the RARE echoes in the echo train can be replaced by EPI echoes whilst maintaining anatomical accuracy. The reduced RF power deposition of RARE-EPI enabled multiband RF pulses facilitating simultaneous multi-slice imaging. This study shows that diffusion-weighted RARE-EPI has the capability to acquire high fidelity, distortion-free images of the eye and the orbit. It is shown that RARE-EPI maintains the immunity to B0 inhomogeneities reported for RARE imaging. This benefit can be exploited for the assessment of ocular masses and pathological changes of the eye and the orbit.

W(h)ither human cardiac and body magnetic resonance at ultrahigh fields? technical advances, practical considerations, applications, and clinical opportunities.

The objective of this study was to document and review advances and groundbreaking progress in cardiac and body MR at ultrahigh fields (UHF, B0 ≥ 7.0 T) with the goal to attract talent, clinical adopters, collaborations and resources to the biomedical and diagnostic imaging communities. This review surveys traits, advantages and challenges of cardiac and body MR at 7.0 T. The considerations run the gamut from technical advances to clinical opportunities. Key concepts, emerging technologies, practical considerations, frontier applications and future directions of UHF body and cardiac MR are provided. Examples of UHF cardiac and body imaging strategies are demonstrated. Their added value over the kindred counterparts at lower fields is explored along with an outline of research promises. The achievements of cardiac and body UHF-MR are powerful motivators and enablers, since extra speed, signal and imaging capabilities may be invested to overcome the fundamental constraints that continue to hamper traditional cardiac and body MR applications. If practical obstacles, concomitant physics effects and technical impediments can be overcome in equal measure, sophisticated cardiac and body UHF-MR will help to open the door to new MRI and MRS approaches for basic research and clinical science, with the lessons learned at 7.0 T being transferred into broad clinical use including diagnostics and therapy guiding at lower fields. Copyright © 2015 John Wiley & Sons, Ltd.

Eight-channel transceiver RF coil array tailored for ¹H/¹9F 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. Q(L)/Q(U) 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.

Sodium MRI of the human heart at 7.0 T: preliminary results.

The objective of this work was to examine the feasibility of three-dimensional (3D) and whole heart coverage (23)Na cardiac MRI at 7.0 T including single-cardiac-phase and cinematic (cine) regimes. A four-channel transceiver RF coil array tailored for (23)Na MRI of the heart at 7.0 T (f = 78.5 MHz) is proposed. An integrated bow-tie antenna building block is used for (1)H MR to support shimming, localization and planning in a clinical workflow. Signal absorption rate simulations and assessment of RF power deposition were performed to meet the RF safety requirements. (23) Na cardiac MR was conducted in an in vivo feasibility study. 3D gradient echo (GRE) imaging in conjunction with Cartesian phase encoding (total acquisition time T(AQ) = 6 min 16 s) and whole heart coverage imaging employing a density-adapted 3D radial acquisition technique (T(AQ) = 18 min 20 s) were used. For 3D GRE-based (23)Na MRI, acquisition of standard views of the heart using a nominal in-plane resolution of (5.0 × 5.0) mm(2) and a slice thickness of 15 mm were feasible. For whole heart coverage 3D density-adapted radial (23)Na acquisitions a nominal isotropic spatial resolution of 6 mm was accomplished. This improvement versus 3D conventional GRE acquisitions reduced partial volume effects along the slice direction and enabled retrospective image reconstruction of standard or arbitrary views of the heart. Sodium cine imaging capabilities were achieved with the proposed RF coil configuration in conjunction with 3D radial acquisitions and cardiac gating. Cardiac-gated reconstruction provided an enhancement in blood-myocardium contrast of 20% versus the same data reconstructed without cardiac gating. The proposed transceiver array enables (23)Na MR of the human heart at 7.0 T within clinical acceptable scan times. This capability is in positive alignment with the needs of explorations that are designed to examine the potential of (23)Na MRI for the assessment of cardiovascular and metabolic diseases.

Cerebral blood volume estimation by ferumoxytol-enhanced steady-state MRI at 9.4 T reveals microvascular impact of α1 -adrenergic receptor antibodies.

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 9.4 T, 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 ferumoxytol-enhanced MRI at 9.4 T, and further underlines the significance of this antibody in brain diseases involving vasculature impairments, such as dementia.

Imaging of magnetic microfield distortions allows sensitive single-cell detection.

Cell tracking with magnetic resonance imaging (MRI) is mostly performed using superparamagnetic iron oxide (SPIO) nanoparticle-labeled cells. However, negative contrast in T2*-weighted imaging is inherently problematic as a homogeneous background signal is required to visualize the negative signal. In a magnetic field, SPIO-labeled cells develop their own magnetization, distorting the main field. We show here a method to visualize these distortions and use them to identify single cells with increased sensitivity and certainty compared to T2* images. We labeled HeLa cells with SPIOs, suspended labeled cells in agarose to make phantoms, and performed high-resolution gradient-echo MRI. Phase images were processed to enhance the visibility of single cells. To quantify SPIO content, we generated a map of frequency differences. MRI of cell phantoms showed that single cells could be detected at concentrations ranging from 200 to 10,000 cells mL(-1). Postprocessing of the magnetic resonance phase images reveals characteristic microfield distortions, increasing dramatically the sensitivity of cell recognition, compared to unprocessed T2* images. Calculating frequency shifts and comparing microfield distortions to simulations permit estimation of the nanoparticle load of single cells. We expect the ability to detect and quantify the iron load of single cells to prove useful in studies of cell trafficking, especially in rare cell populations.

GDNF mediates glioblastoma-induced microglia attraction but not astrogliosis.

High-grade gliomas are the most common primary brain tumors. Their malignancy is promoted by the complex crosstalk between different cell types in the central nervous system. Microglia/brain macrophages infiltrate high-grade gliomas and contribute to their progression. To identify factors that mediate the attraction of microglia/macrophages to malignant brain tumors, we established a glioma cell encapsulation model that was applied in vivo. Mouse GL261 glioma cell line and human high-grade glioma cells were seeded into hollow fibers (HF) that allow the passage of soluble molecules but not cells. The glioma cell containing HF were implanted into one brain hemisphere and simultaneously HF with non-transformed fibroblasts (controls) were introduced into the contralateral hemisphere. Implanted mouse and human glioma- but not fibroblast-containing HF attracted microglia and up-regulated immunoreactivity for GFAP, which is a marker of astrogliosis. In this study, we identified GDNF as an important factor for microglial attraction: (1) GL261 and human glioma cells secret GDNF, (2) reduced GDNF production by siRNA in GL261 in mouse glioma cells diminished attraction of microglia, (3) over-expression of GDNF in fibroblasts promoted microglia attraction in our HF assay. In vitro migration assays also showed that GDNF is a strong chemoattractant for microglia. While GDNF release from human or mouse glioma had a profound effect on microglial attraction, the glioma-induced astrogliosis was not affected. Finally, we could show that injection of GL261 mouse glioma cells with GDNF knockdown by shRNA into mouse brains resulted in reduced tumor expansion and improved survival as compared to injection of control cells.

MRI of Implantation Sites Using Parallel Transmission of an Optimized Radiofrequency Excitation Vector.

Postoperative care of orthopedic implants is aided by imaging to assess the healing process and the implant status. MRI of implantation sites might be compromised by radiofrequency (RF) heating and RF transmission field (B1+) inhomogeneities induced by electrically conducting implants. This study examines the applicability of safe and B1+-distortion-free MRI of implantation sites using optimized parallel RF field transmission (pTx) based on a multi-objective genetic algorithm (GA). Electromagnetic field simulations were performed for eight eight-channel RF array configurations (f = 297.2 MHz), and the most efficient array was manufactured for phantom experiments at 7.0 T. Circular polarization (CP) and orthogonal projection (OP) algorithms were applied for benchmarking the GA-based shimming. B1+ mapping and MR thermometry and imaging were performed using phantoms mimicking muscle containing conductive implants. The local SAR10g of the entire phantom in GA was 12% and 43.8% less than the CP and OP, respectively. Experimental temperature mapping using the CP yielded ΔT = 2.5-3.0 K, whereas the GA induced no extra heating. GA-based shimming eliminated B1+ artefacts at implantation sites and enabled uniform gradient-echo MRI. To conclude, parallel RF transmission with GA-based excitation vectors provides a technical foundation en route to safe and B1+-distortion-free MRI of implantation sites.

First in vivo fluorine-19 magnetic resonance imaging of the multiple sclerosis drug siponimod.

Theranostic imaging methods could greatly enhance our understanding of the distribution of CNS-acting drugs in individual patients. Fluorine-19 magnetic resonance imaging (19F 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 (S1P) receptor antagonist indicated for secondary progressive multiple sclerosis (SPMS), to determine the feasibility of in vivo 19F MR imaging of a disease modifying drug. Methods: The 19F MR properties of siponimod were characterized using spectroscopic techniques. Four MRI methods were investigated to determine which was the most sensitive for 19F MR imaging of siponimod under biological conditions. We subsequently administered siponimod orally to 6 mice and acquired 19F MR spectra and images in vivo directly after administration, and in ex vivo tissues. Results: The 19F 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 19F 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 19F 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, 19F 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.

Design and application of a four-channel transmit/receive surface coil for functional cardiac imaging at 7T.

PURPOSE: To design and evaluate a four-channel cardiac transceiver coil array for functional cardiac imaging at 7T. MATERIALS AND METHODS: A four-element cardiac transceiver surface coil array was developed with two rectangular loops mounted on an anterior former and two rectangular loops on a posterior former. specific absorption rate (SAR) simulations were performed and a B 1+ calibration method was applied prior to obtain 2D FLASH CINE (mSENSE, R = 2) images from nine healthy volunteers with a spatial resolution of up to 1 × 1 × 2.5 mm(3). RESULTS: Tuning and matching was found to be better than 10 dB for all subjects. The decoupling (S(21)) was measured to be >18 dB between neighboring loops, >20 dB for opposite loops, and >30 dB for other loop combinations. SAR values were well within the limits provided by the IEC. Imaging provided clinically acceptable signal homogeneity with an excellent blood-myocardium contrast applying the B 1+ calibration approach. CONCLUSION: A four-channel cardiac transceiver coil array for 7T was built, allowing for cardiac imaging with clinically acceptable signal homogeneity and an excellent blood-myocardium contrast. Minor anatomic structures, such as pericardium, mitral, and tricuspid valves and their apparatus, as well as trabeculae, were accurately delineated.

Functional Imaging Using Fluorine (19F) MR Methods: Basic Concepts.

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.