B(1) inhomogeneity correction of RARE MRI with transceive surface radiofrequency probes

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

Magnetic resonance elastography reveals altered brain viscoelasticity in experimental autoimmune encephalomyelitis

Cerebral magnetic resonance elastography (MRE) measures the viscoelastic properties of brain tissues in vivo. It was recently shown that brain viscoelasticity is reduced in patients with multiple sclerosis (MS), highlighting the potential of cerebral MRE to detect tissue pathology during neuroinflammation. To further investigate the relationship between inflammation and brain viscoelasticity, we applied MRE to a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). EAE was induced and monitored by MRE in a 7-tesla animal MRI scanner over 4 weeks. At the peak of the disease (day 14 after immunization), we detected a significant decrease in both the storage modulus (G') and the loss modulus (G″), indicating that both the elasticity and the viscosity of the brain are reduced during acute inflammation. Interestingly, these parameters normalized at a later time point (day 28) corresponding to the clinical recovery phase. Consistent with this, we observed a clear correlation between viscoelastic tissue alteration and the magnitude of perivascular T cell infiltration at both day 14 and day 28. Hence, acute neuroinflammation is associated with reduced mechanical cohesion of brain tissues. Moreover, the reduction of brain viscoelasticity appears to be a reversible process, which is restored when inflammation resolves. For the first time, our study has demonstrated the applicability of cerebral MRE in EAE, and showed that this novel imaging technology is highly sensitive to early tissue alterations resulting from the inflammatory processes. Thus, MRE may serve to monitor early stages of perivascular immune infiltration during neuroinflammation

Monitoring kidney size to interpret MRI-based assessment of renal oxygenation in acute pathophysiological scenarios

AIM: Tissue hypoxia is an early key feature of acute kidney injury. Assessment of renal oxygenation using magnetic resonance imaging (MRI) markers T(2) and T(2) * enables insights into renal pathophysiology. This assessment can be confounded by changes in the blood and tubular volume fractions, occurring upon pathological insults. These changes are mirrored by changes in kidney size (KS). Here we used dynamic MRI to monitor KS for physiological interpretation of T(2) * and T(2) changes in acute pathophysiological scenarios. METHODS: KS was determined from T(2) *,T(2) mapping in rats. Six interventions which acutely alter renal tissue oxygenation were performed directly within the scanner, including interventions which change the blood and/or tubular volume. A biophysical model was used to estimate changes in O(2) saturation of haemoglobin from changes in T(2) * and KS. RESULTS: Upon aortic occlusion KS decreased; this correlated with a decrease in T(2) *,T (2). Upon renal vein occlusion KS increased; this negatively correlated with a decrease in T(2) *,T(2). Upon simultaneous occlusion of both vessels KS remained unchanged; there was no correlation with decreased T(2)*,T(2). Hypoxaemia induced mild reductions in KS and T(2) *,T . Administration of an X-ray contrast medium induced sustained KS increase, with an initial increase in T(2) *,T(2) followed by a decrease. Furosemide caused T(2) *,T(2) elevation and a minor increase in KS. Model calculations yielded physiologically plausible calibration ratios for T(2) *. CONCLUSION: Monitoring KS allows physiological interpretation of acute renal oxygenation changes obtained by T(2) *,T(2) . KS monitoring should accompany MRI-oximetry, for new insights into renal pathophysiology and swift translation into human studies

Preparation of ex vivo rodent phantoms for developing, testing, and training MR imaging of the kidney and other organs

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

Accelerated simultaneous T2 and T2* mapping of multiple sclerosis lesions using compressed sensing reconstruction of radial RARE-EPI MRI

(1) BACKGROUND: Radial RARE-EPI MRI facilitates simultaneous T2 and T2* mapping (2in1-RARE-EPI). With modest undersampling (R = 2), the speed gain of 2in1-RARE-EPI relative to Multi-Spin-Echo and Multi-Gradient-Recalled-Echo references is limited. Further reduction in scan time is crucial for clinical studies investigating T2 and T2* as imaging biomarkers. We demonstrate the feasibility of further acceleration, utilizing compressed sensing (CS) reconstruction of highly undersampled 2in1-RARE-EPI. (2) METHODS: Two-fold radially-undersampled 2in1-RARE-EPI data from phantoms, healthy volunteers (n = 3), and multiple sclerosis patients (n = 4) were used as references, and undersampled (Rextra = 1–12, effective undersampling Reff = 2–24). For each echo time, images were reconstructed using CS-reconstruction. For T2 (RARE module) and T2* mapping (EPI module), a linear least-square fit was applied to the images. T2 and T2* from CS-reconstruction of undersampled data were benchmarked against values from CS-reconstruction of the reference data. (3) RESULTS: We demonstrate accelerated simultaneous T2 and T2* mapping using undersampled 2in1-RARE-EPI with CS-reconstruction is feasible. For Rextra = 6 (TA = 01:39 min), the overall MAPE was ≤8% (T2*) and ≤4% (T2); for Rextra = 12 (TA = 01:06 min), the overall MAPE was <13% (T2*) and <5% (T2). (4) CONCLUSION: Substantial reductions in scan time are achievable for simultaneous T2 and T2* mapping of the brain using highly undersampled 2in1-RARE-EPI with CS-reconstruction

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

High fidelity 3D magnetic stray field mapping of smartphones to address safety considerations with active implantable electronic medical devices

Case reports indicate that magnets in smartphones could be a source of electromagnetic interference (EMI) for active implantable medical devices (AIMD), which could lead to device malfunction, compromising patient safety. Recognizing this challenge, we implemented a high-fidelity 3D magnetic field mapping (spatial resolution 1 mm) setup using a three-axis Hall probe and teslameter, controlled by a robot (COSI Measure). With this setup, we examined the stray magnetic field of an iPhone 13 Pro, iPhone 12, and MagSafe charger to identify sources of magnetic fields for the accurate risk assessment of potential interferences with AIMDs. Our measurements revealed that the stray fields of the annular array of magnets, the wide-angle camera, and the speaker of the smartphones exceeded the 1 mT limit defined by ISO 14117:2019. Our data-driven safety recommendation is that an iPhone 13 Pro should be kept at least 25 mm away from an AIMD to protect it from unwanted EMI interactions. Our study addresses safety concerns due to potential device–device interactions between smartphones and AIMDs and will help to define data-driven safety guidelines. We encourage vendors of electronic consumer products (ECP) to provide information on the magnetic fields of their products and advocate for the inclusion of smartphones in the risk assessment of EMI with AIMDs

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 ((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

B(1) 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 (19F) MRI benefits from cryogenically-cooled transceive surface RF probes (CRPs), but strong B(1) 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 B(1) 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 B(1) 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 T(1) calculations for (19)F-nanoparticles during pathology and B(1) 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

Reliable kidney size determination by magnetic resonance imaging in pathophysiological settings

AIM: Kidney diseases constitute a major health challenge, which requires non-invasive 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. METHODS: A geometry-based ABSM was developed for kidney size measurements in rats using parametric MRI (T(2), T(2)* mapping). The ABSM approach was applied to longitudinal renal size quantification using occlusion of the (i) suprarenal aorta or (ii) the renal vein, (iii) increase in renal pelvis and intratubular pressure, and (iv) injection of an X-ray contrast medium into the thoracic aorta to induce pathophysiologically relevant changes in kidney size. RESULTS: The ABSM yielded renal size measurements with accuracy and precision equivalent to the manual segmentation, with >70-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. CONCLUSION: 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