Real‐time MRI at a resolution of 20 ms

The desire to visualize noninvasively physiological processes at high temporal resolution has been a driving force for the development of MRI since its inception in 1973. In this article, we describe a unique method for real‐time MRI that reduces image acquisition times to only 20 ms. Although approaching the ultimate limit of MRI technology, the method yields high image quality in terms of spatial resolution, signal‐to‐noise ratio and the absence of artifacts. As proposed previously, a fast low‐angle shot (FLASH) gradient‐echo MRI technique (which allows for rapid and continuous image acquisitions) is combined with a radial encoding scheme (which offers motion robustness and moderate tolerance to data undersampling) and, most importantly, an iterative image reconstruction by regularized nonlinear inversion (which exploits the advantages of parallel imaging with multiple receiver coils). In this article, the extension of regularization and filtering to the temporal domain exploits consistencies in successive data acquisitions and thereby enhances the degree of radial undersampling in a hitherto unexpected manner by one order of magnitude. The results obtained for turbulent flow, human speech production and human heart function demonstrate considerable potential for real‐time MRI studies of dynamic processes in a wide range of scientific and clinical settings. Copyright © 2010 John Wiley & Sons, Ltd.     

Comparison of different compressed sensing algorithms for low SNR 19F MRI applications—Imaging of transplanted pancreatic islets and cells labeled with perfluorocarbons

Transplantation of pancreatic islets is a possible treatment option for patients suffering from Type I diabetes. In vivo imaging of transplanted islets is important for assessment of the transplantation site and islet distribution. Thanks to its high specificity, the absence of intrinsic background signal in tissue and its potential for quantification, ¹⁹F MRI is a promising technique for monitoring the fate of transplanted islets in vivo. In order to overcome the inherent low sensitivity of ¹⁹F MRI, leading to long acquisition times with low signal‐to‐noise ratio (SNR), compressed sensing (CS) techniques are a valuable option. We have validated and compared different CS algorithms for acceleration of ¹⁹F MRI acquisition in a low SNR regime using pancreatic islets labeled with perfluorocarbons both in vitro and in vivo. Using offline simulation on both in vitro and in vivo low SNR fully sampled ¹⁹F MRI datasets of labeled islets, we have shown that CS is effective in reducing the image acquisition time by a factor of three to four without seriously affecting SNR, regardless of the particular algorithms used in this study, with the exception of CoSaMP. Using CS, signals can be detected that might have been missed by conventional ¹⁹F MRI. Among different algorithms (SPARSEMRI, OMMP, IRWL1, Two‐level and CoSAMP), the two‐level l₁ method has shown the best performance if computational time is taken into account. We have demonstrated in this study that different existing CS algorithms can be used effectively for low SNR ¹⁹F MRI. An up to fourfold gain in SNR/scan time could be used either to reduce the scan time, which is beneficial for clinical and translational applications, or to increase the number of averages, to potentially detect otherwise undetected signal when compared with conventional ¹⁹F MRI acquisitions. Potential applications in the field of cell therapy have been demonstrated.     

A characterization of ABL‐101 as a potential tracer for clinical fluorine‐19 MRI

The two main challenges that prevent the translation of fluorine‐19 (¹⁹F) MRI for inflammation monitoring or cell tracking into clinical practice are (i) the relatively low signal‐to‐noise ratio generated by the injected perfluorocarbon (PFC), which necessitates long scan times, and (ii) the need for regulatory approval and a high biocompatibility of PFCs that are also suitable for MRI. ABL‐101, an emulsion of perfluoro(t‐butylcyclohexane), is a third‐generation PFC that is already used in clinical trials, but has not yet been used for ¹⁹F MRI. The objective of this study was therefore to assess the performance of ABL‐101 as a ¹⁹F MRI tracer. At magnetic field strengths of 3, 9.4 and 14.1 T, the CF₃ groups of ABL‐101 generated a large well‐separated singlet with T₂/T₁ ratios of >0.27, >0.14 and > 0.05, respectively. All relaxation times decreased with the increase in magnetic field strength. The detection limit of ABL‐101 in a 0.25 mm³ voxel at 3 T, 37°C and with a 3‐minute acquisition time was 7.21mM. After intravenous injection, the clearance half‐lives of the ABL‐101 ¹⁹F MR signal in mouse (n = 3) spleen and liver were 6.85 ± 0.45 and 3.20 ± 0.35 days, respectively. These results demonstrate that ABL‐101 has ¹⁹F MR characteristics that are similar to those of PFCs developed specifically for MRI, while it has clearance half‐lives similar to PFCs that have previously been used in large doses in non‐MRI clinical trials. Overall, ABL‐101 is thus a very promising candidate tracer for future clinical trials that use ¹⁹F MRI for cell tracking or the monitoring of inflammation.     

Wireless coils based on resonant and nonresonant coupled‐wire structure for small animal multinuclear imaging

Earlier work on RF metasurfaces for preclinical MRI has targeted applications such as whole‐body imaging and dual‐frequency coils. In these studies, a nonresonant loop was used to induce currents into a metasurface that was operated as a passive inductively powered resonator. However, as we show in this study, the strategy of using a resonant metasurface reduces the impact of the loop on the global performance of the assembled coil. To mitigate this deficiency, we developed a new approach that relies on the combination of a commercial surface coil and a coupled‐wire structure operated away from its resonance. This strategy enables the extension of the sensitive volume of the surface coil while maintaining its local high sensitivity without any hardware modification. A wireless coil based on a two parallel coupled‐wire structure was designed and electromagnetic field simulations were carried out with different levels of matching and coupling between both components of the coil. For experimental characterization, a prototype was built and tested at two frequencies, 300 MHz for ¹H and 282.6 MHz for ¹⁹F at 7 T. Phantom and in vivo MRI experiments were conducted in different configurations to study signal and noise figures of the structure. The results showed that the proposed strategy improves the overall sensitive volume while simultaneously maintaining a high signal‐to‐noise ratio (SNR). Metasurfaces based on coupled wires are therefore shown here as promising and versatile elements in the MRI RF chain, as they allow customized adjustment of the sensitive volume as a function of SNR yield. In addition, they can be easily adapted to different Larmor frequencies without loss of performance.     

Calibrationless multi-slice Cartesian MRI via orthogonally alternating phase encoding direction and joint low-rank tensor completion

We propose a multi-slice acquisition with orthogonally alternating phase encoding (PE) direction and subsequent joint calibrationless reconstruction for accelerated multiple individual 2D slices or multi-slice 2D Cartesian MRI. Specifically, multi-slice multi-channel data are first acquired with random or uniform PE undersampling while orthogonally alternating PE direction between adjacent slices. They are then jointly reconstructed through a recently developed low-rank multi-slice Hankel tensor completion (MS-HTC) approach. The proposed acquisition and reconstruction strategy was evaluated with human brain MR data. It effectively suppressed aliasing artifacts even at high acceleration factor, outperforming the existing MS-HTC approach, where PE direction is the same between adjacent slices. More importantly, the new strategy worked robustly with uniform undersampling or random undersampling without any consecutive central k-space lines. In summary, our proposed multi-slice MRI strategy exploits both coil sensitivity and image content similarities across adjacent slices. Orthogonally alternating PE direction among slices substantially facilitates the low-rank completion process and improves image reconstruction quality. This new strategy is applicable to uniform and random PE undersampling. It can be easily implemented in practice for Cartesian parallel imaging of multiple individual 2D slices without any coil sensitivity calibration.     

31P NMR relaxation of cortical bone mineral at multiple magnetic field strengths and levels of demineralization

Recent work has shown that solid‐state ¹H and ³¹P MRI can provide detailed insight into bone matrix and mineral properties, thereby potentially enabling differentiation of osteoporosis from osteomalacia. However, ³¹P MRI of bone mineral is hampered by unfavorable relaxation properties. Hence, accurate knowledge of these properties is critical to optimizing MRI of bone phosphorus. In this work, ³¹P MRI signal‐to‐noise ratio (SNR) was predicted on the basis of T₁ and T₂* (effective transverse relaxation time) measured in lamb bone at six field strengths (1.5–11.7 T) and subsequently verified by 3D ultra‐short echo‐time and zero echo‐time imaging. Further, T₁ was measured in deuterium‐exchanged bone and partially demineralized bone. ³¹P T₂* was found to decrease from 220.3 ± 4.3 µs to 98.0 ± 1.4 µs from 1.5 to 11.7 T, and T₁ to increase from 12.8 ± 0.5 s to 97.3 ± 6.4 s. Deuteron substitution of exchangeable water showed that 76% of the ³¹P longitudinal relaxation rate is due to ¹H–³¹P dipolar interactions. Lastly, hypomineralization was found to decrease T₁, which may have implications for ³¹P MRI based mineralization density quantification. Despite the steep decrease in the T₂*/T₁ ratio, SNR should increase with field strength as B₀^0.4 for sample‐dominated noise and as B₀^1.1 for coil‐dominated noise. This was confirmed by imaging experiments. Copyright © 2013 John Wiley & Sons, Ltd.     

Probing different perfluorocarbons for in vivo inflammation imaging by 19F MRI: image reconstruction,biological half‐lives and sensitivity

Inflammatory processes can reliably be assessed by ¹⁹F MRI using perfluorocarbons (PFCs), which is primarily based on the efficient uptake of emulsified PFCs by circulating cells of the monocyte–macrophage system and subsequent infiltration of the ¹⁹F‐labeled cells into affected tissue. An ideal candidate for the sensitive detection of fluorine‐loaded cells is the biochemically inert perfluoro‐15‐crown‐5 ether (PFCE), as it contains 20 magnetically equivalent ¹⁹F atoms. However, the biological half‐life of PFCE in the liver and spleen is extremely long, and so this substance is not suitable for future clinical applications. In the present study, we investigated alternative, nontoxic PFCs with predicted short biological half‐lives and high fluorine content: perfluorooctyl bromide (PFOB), perfluorodecalin (PFD) and trans‐bis‐perfluorobutyl ethylene (F‐44E). Despite the complex spectra of these compounds, we obtained artifact‐free images using sine‐squared acquisition‐weighted three‐dimensional chemical shift imaging and dedicated reconstruction accomplished with in‐house‐developed software. The signal‐to‐noise ratio of the images was maximized using a Nutall window with only moderate localization error. Using this approach, the retention times of the different PFCs in murine liver and spleen were determined at 9.4 T. The biological half‐lives were estimated to be 9 days (PFD), 12 days (PFOB) and 28 days (F‐44E), compared with more than 250 days for PFCE. In vivo sensitivity for inflammation imaging was assessed using an ear clip injury model. The alternative PFCs PFOB and F‐44E provided 37% and 43%, respectively, of the PFCE intensities, whereas PFD did not show any signal in the ear model. Thus, for in vivo monitoring of inflammatory processes, PFOB emerges as the most promising candidate for possible future translation of ¹⁹F MR inflammation imaging to human applications. Copyright © 2013 John Wiley & Sons, Ltd.     

Preclinical MR fingerprinting (MRF) at 7 T: effective quantitative imaging for rodent disease models

High‐field preclinical MRI scanners are now commonly used to quantitatively assess disease status and the efficacy of novel therapies in a wide variety of rodent models. Unfortunately, conventional MRI methods are highly susceptible to respiratory and cardiac motion artifacts resulting in potentially inaccurate and misleading data. We have developed an initial preclinical 7.0‐T MRI implementation of the highly novel MR fingerprinting (MRF) methodology which has been described previously for clinical imaging applications. The MRF technology combines a priori variation in the MRI acquisition parameters with dictionary‐based matching of acquired signal evolution profiles to simultaneously generate quantitative maps of T₁ and T₂ relaxation times and proton density. This preclinical MRF acquisition was constructed from a fast imaging with steady‐state free precession (FISP) MRI pulse sequence to acquire 600 MRF images with both evolving T₁ and T₂ weighting in approximately 30 min. This initial high‐field preclinical MRF investigation demonstrated reproducible and differentiated estimates of in vitro phantoms with different relaxation times. In vivo preclinical MRF results in mouse kidneys and brain tumor models demonstrated an inherent resistance to respiratory motion artifacts as well as sensitivity to known pathology. These results suggest that MRF methodology may offer the opportunity for the quantification of numerous MRI parameters for a wide variety of preclinical imaging applications. Copyright © 2015 John Wiley & Sons, Ltd.     

High‐field (11.75T) multimodal MR imaging of exercising hindlimb mouse muscles using a non‐invasive combined stimulation and force measurement device

We have designed and constructed an experimental set‐up allowing electrical stimulation of hindlimb mouse muscles and the corresponding force measurements at high‐field (11.75T). We performed high‐resolution multimodal MRI (including T₂‐weighted imaging, angiography and diffusion) and analysed the corresponding MRI changes in response to a stimulation protocol. Mice were tested twice over a 1‐week period to investigate the reliability of mechanical measurements and T₂ changes associated with the stimulation protocol. Additionally, angiographic images were obtained before and immediately after the stimulation protocol. Finally, multislice diffusion imaging was performed before, during and immediately after the stimulation session. Apparent diffusion coefficient (ADC) maps were calculated on the basis of diffusion weighted images (DWI). Both force production and T₂ values were highly reproducible as illustrated by the low coefficient of variation (<8%) and high intraclass correlation coefficient (≥0.75) values. Maximum intensity projection angiographic images clearly showed a strong vascular effect resulting from the stimulation protocol. Although a motion sensitive imaging sequence was used (echo planar imaging) and in spite of the strong muscle contractions, motion artifacts were minimal for DWI recorded under exercising conditions, thereby underlining the robustness of the measurements. Mean ADC values increased under exercising conditions and were higher during the recovery period as compared with the corresponding control values. The proposed experimental approach demonstrates accurate high‐field multimodal MRI muscle investigations at a preclinical level which is of interest for monitoring the severity and/or the progression of neuromuscular diseases but also for assessing the efficacy of potential therapeutic interventions. Copyright © 2014 John Wiley & Sons, Ltd.     

A radial sampling strategy for uniform k‐space coverage with retrospective respiratory gating in 3D ultrashort‐echo‐time lung imaging

The purpose of this work was to develop a 3D radial‐sampling strategy which maintains uniform k‐space sample density after retrospective respiratory gating, and demonstrate its feasibility in free‐breathing ultrashort‐echo‐time lung MRI. A multi‐shot, interleaved 3D radial sampling function was designed by segmenting a single‐shot trajectory of projection views such that each interleaf samples k‐space in an incoherent fashion. An optimal segmentation factor for the interleaved acquisition was derived based on an approximate model of respiratory patterns such that radial interleaves are evenly accepted during the retrospective gating. The optimality of the proposed sampling scheme was tested by numerical simulations and phantom experiments using human respiratory waveforms. Retrospectively, respiratory‐gated, free‐breathing lung MRI with the proposed sampling strategy was performed in healthy subjects. The simulation yielded the most uniform k‐space sample density with the optimal segmentation factor, as evidenced by the smallest standard deviation of the number of neighboring samples as well as minimal side‐lobe energy in the point spread function. The optimality of the proposed scheme was also confirmed by minimal image artifacts in phantom images. Human lung images showed that the proposed sampling scheme significantly reduced streak and ring artifacts compared with the conventional retrospective respiratory gating while suppressing motion‐related blurring compared with full sampling without respiratory gating. In conclusion, the proposed 3D radial‐sampling scheme can effectively suppress the image artifacts due to non‐uniform k‐space sample density in retrospectively respiratory‐gated lung MRI by uniformly distributing gated radial views across the k‐space. Copyright © 2016 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 ¹H/¹⁹F MR of the human knee at 7.0 T following application of ¹⁹F‐containing drugs. The ¹H/¹⁹F RF coil array includes a posterior module with two ¹H loop elements and two anterior modules, each consisting of one ¹H and two ¹⁹F 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 ¹⁹F MRS was conducted with 47 and 101 mmol/L of flufenamic acid (FA) – a ¹⁹F‐containing non‐steroidal anti‐inflammatory drug – to determine T₁ and T₂ and to study the ¹⁹F signal‐to‐dose relationship. The suitability of the proposed approach for ¹H/¹⁹F 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) mm² 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 ¹H/¹⁹F 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 ¹⁹F‐containing medicinal compounds in vivo. Copyright © 2015 John Wiley & Sons, Ltd.     

Optimized truncation to integrate multi‐channel MRS data using rank‐R singular value decomposition

Multi‐channel phased receive arrays have been widely adopted for magnetic resonance imaging (MRI) and spectroscopy (MRS). An important step in the use of receive arrays for MRS is the combination of spectra collected from individual coil channels. The goal of this work was to implement an improved strategy termed OpTIMUS (i.e., op timized t runcation to i ntegrate m ulti‐channel MRS data u sing rank‐R s ingular value decomposition) for combining data from individual channels. OpTIMUS relies on spectral windowing coupled with a rank‐R decomposition to calculate the optimal coil channel weights. MRS data acquired from a brain spectroscopy phantom and 11 healthy volunteers were first processed using a whitening transformation to remove correlated noise. Whitened spectra were then iteratively windowed or truncated, followed by a rank‐R singular value decomposition (SVD) to empirically determine the coil channel weights. Spectra combined using the vendor‐supplied method, signal/noise² weighting, previously reported whitened SVD (rank‐1), and OpTIMUS were evaluated using the signal‐to‐noise ratio (SNR). Significant increases in SNR ranging from 6% to 33% (P ≤ 0.05) were observed for brain MRS data combined with OpTIMUS compared with the three other combination algorithms. The assumption that a rank‐1 SVD maximizes SNR was tested empirically, and a higher rank‐R decomposition, combined with spectral windowing prior to SVD, resulted in increased SNR.     

High‐temporospatial‐resolution dynamic contrast‐enhanced (DCE) wrist MRI with variable‐density pseudo‐random circular Cartesian undersampling (CIRCUS) acquisition: evaluation of perfusion in rheumatoid arthritis patients

This study is to evaluate highly accelerated three‐dimensional (3D) dynamic contrast‐enhanced (DCE) wrist MRI for assessment of perfusion in rheumatoid arthritis (RA) patients. A pseudo‐random variable‐density undersampling strategy, circular Cartesian undersampling (CIRCUS), was combined with k–t SPARSE‐SENSE reconstruction to achieve a highly accelerated 3D DCE wrist MRI. Two healthy volunteers and 10 RA patients were studied. Two patients were on methotrexate (MTX) only (Group I) and the other eight were treated with a combination therapy of MTX and anti‐tumor necrosis factor (TNF) therapy (Group II). Patients were scanned at baseline and 3 month follow‐up. DCE MR images were used to evaluate perfusion in synovitis and bone marrow edema pattern in the RA wrist joints. A series of perfusion parameters was derived and compared with clinical disease activity scores of 28 joints (DAS28). 3D DCE wrist MR images were obtained with a spatial resolution of 0.3 × 0.3 × 1.5 mm³ and temporal resolution of 5 s (with an acceleration factor of 20). The derived perfusion parameters, most notably transition time (dT) of synovitis, showed significant negative correlations with DAS28‐ESR (r = ?0.80, p < 0.05) and DAS28‐CRP (r = ?0.87, p < 0.05) at baseline and also correlated significantly with treatment responses evaluated by clinical score changes between baseline and 3 month follow‐up (with DAS28‐ESR r = ?0.79, p < 0.05, and DAS28‐CRP r = ?0.82, p < 0.05). Highly accelerated 3D DCE wrist MRI with improved temporospatial resolution has been achieved in RA patients and provides accurate assessment of neovascularization and perfusion in RA joints, showing promise as a potential tool for evaluating treatment responses. Copyright © 2015 John Wiley & Sons, Ltd.     

19 F MRSI of capecitabine in the liver at 7 T using broadband transmit–receive antennas and dual‐band RF pulses

Capecitabine (Cap) is an often prescribed chemotherapeutic agent, successfully used to cure some patients from cancer or reduce tumor burden for palliative care. However, the efficacy of the drug is limited, it is not known in advance who will respond to the drug and it can come with severe toxicity. ¹⁹ F Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Spectroscopic Imaging (MRSI) have been used to non‐invasively study Cap metabolism in vivo to find a marker for personalized treatment. In vivo detection, however, is hampered by low concentrations and the use of radiofrequency (RF) surface coils limiting spatial coverage. In this work, the use of a 7T MR system with radiative multi‐channel transmit–receive antennas was investigated with the aim of maximizing the sensitivity and spatial coverage of ¹⁹ F detection protocols. The antennas were broadband optimized to facilitate both the ¹H (298 MHz) and ¹⁹ F (280 MHz) frequencies for accurate shimming, imaging and signal combination. B₁⁺ simulations, phantom and noise measurements showed that more than 90% of the theoretical maximum sensitivity could be obtained when using B₁⁺ and B₁^? information provided at the ¹H frequency for the optimization of B₁⁺ and B₁^? at the ¹⁹ F frequency. Furthermore, to overcome the limits in maximum available RF power, whilst ensuring simultaneous excitation of all detectable conversion products of Cap, a dual‐band RF pulse was designed and evaluated. Finally, ¹⁹ F MRS(I) measurements were performed to detect ¹⁹ F metabolites in vitro and in vivo. In two patients, at 10 h (patient 1) and 1 h (patient 2) after Cap intake, ¹⁹ F metabolites were detected in the liver and the surrounding organs, illustrating the potential of the set‐up for in vivo detection of metabolic rates and drug distribution in the body. Copyright © 2015 John Wiley & Sons, Ltd.     

A model‐based reconstruction for undersampled radial spin‐echo DTI with variational penalties on the diffusion tensor

Radial spin‐echo diffusion imaging allows motion‐robust imaging of tissues with very low T₂ values like articular cartilage with high spatial resolution and signal‐to‐noise ratio (SNR). However, in vivo measurements are challenging, due to the significantly slower data acquisition speed of spin‐echo sequences and the less efficient k‐space coverage of radial sampling, which raises the demand for accelerated protocols by means of undersampling. This work introduces a new reconstruction approach for undersampled diffusion‐tensor imaging (DTI). A model‐based reconstruction implicitly exploits redundancies in the diffusion‐weighted images by reducing the number of unknowns in the optimization problem and compressed sensing is performed directly in the target quantitative domain by imposing a total variation (TV) constraint on the elements of the diffusion tensor. Experiments were performed for an anisotropic phantom and the knee and brain of healthy volunteers (three and two volunteers, respectively). Evaluation of the new approach was conducted by comparing the results with reconstructions performed with gridding, combined parallel imaging and compressed sensing and a recently proposed model‐based approach. The experiments demonstrated improvements in terms of reduction of noise and streaking artifacts in the quantitative parameter maps, as well as a reduction of angular dispersion of the primary eigenvector when using the proposed method, without introducing systematic errors into the maps. This may enable an essential reduction of the acquisition time in radial spin‐echo diffusion‐tensor imaging without degrading parameter quantification and/or SNR. Copyright © 2015 John Wiley & Sons, Ltd.     

Effect of verapamil on restoration of cardiac performance in raised [K+]0 by adrenergic stimulation in the rabbit

Modulation of the L-type calcium channel by catecholamines improves action potential parameters in single ventricular myocytes depolarized by high [K⁺]₀ Tyrode. Whether this modulation is important in offsetting the negative effects of hyperkalaemia in the whole heart is not known. We tested the effects of the calcium channel antagonist, verapamil, on restoration of cardiac performance by adrenergic stimulation in high [K⁺]₀ in anaesthetized rabbits and isolated perfused working rabbit hearts. Raised [K⁺]₀ decreased SBP, LVP and LVdP/dt_maxin vivo ([K⁺]_a 8.6 ± 0.2 mM; n= 10) and aortic flow (AF) in the isolated heart (8 mM [K⁺]₀ Tyrode; n= 25). However, the negative effects of raised [K⁺]_a were offset by isoprenaline (Iso, 1 μg kg^-1 min^-1 i.v.) in vivo and by noradrenaline (NA, 80 nM) in the isolated heart. Verapamil (0.15 mg kg^-1 iv.; 15 nM isolated heart) markedly potentiated the negative inotropic effects of raised [K⁺]_n in both preparations. Verapamil attenuated the effect of isoprenaline in vivo but in the isolated heart, the protective effect of NA in 8 mM [K⁺] Tyrode (AF 97 ± 10 mL min¹ in 8 mM [K⁺]₀ compared with AF 141 ± 8.5 mL min^-1 in 8 mM [K⁺]₀+ NA) was offset by the drug (90±8mL min^-1 in 8 mM [K⁺]₀+ NA + V). Furthermore, verapamil abolished aortic flow in 8 mM [K⁺]₀ alone. These findings suggest that the heart may be critically dependent on modulation of intracellular calcium in order to tolerate concentrations of K⁴ similar to those seen during a short burst of intensive exercise ([K⁺]_a 8.6 mM).     

Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes

U2AF1 mutations (U2AF1MT) occur commonly in myelodysplastic syndromes (MDS) without ring sideroblasts. The aim of this study was to investigate the clinical and biological implications of different U2AF1 mutation types in MDS. We performed targeted gene sequencing in a cohort of 511 MDS patients. Eighty‐six patients (17%) were found to have U2AF1MT, which occurred more common in younger patients (P = .001) and represented ancestral lesions in a substantial proportion (71%) of cases. ASXL1MT and isolated +8 were significantly enriched in U2AF1MT‐positive cases, whereas TP53MT, SF3B1MT, and complex karyotypes were inversely associated with U2AF1MT. U2AF^S34 subjects were enriched for isolated +8 and were inversely associated with complex karyotypes. U2AF1MT was significantly associated with anemia, thrombocytopenia, and poor survival in both lower‐risk and higher‐risk MDS. U2AF1^S34 subjects had more frequently platelet levels of <50 × 10⁹/L (P = .043) and U2AF1^Q157/U2AF1^R156 subjects had more frequently hemoglobin concentrations at <80 g/L (P = .008) and more often overt fibrosis (P = .049). In conclusion, our study indicates that U2AF1MT is one of the earliest genetic events in MDS patients and that different types of U2AF1MT have distinct clinical and biological characteristics.     

Fractional ventilation mapping using inert fluorinated gas MRI in rat models of inflammation and fibrosis

The purpose of this study was to extend established methods for fractional ventilation mapping using ¹⁹F MRI of inert fluorinated gases to rat models of pulmonary inflammation and fibrosis. In this study, five rats were instilled with lipopolysaccharide (LPS) in the lungs two days prior to imaging, six rats were instilled with bleomycin in the lungs two weeks prior to imaging and an additional four rats were used as controls. ¹⁹F MR lung imaging was performed at 3 T with rats continuously breathing a mixture of sulfur hexafluoride and O₂. Fractional ventilation maps were obtained using a wash‐out approach, by switching the breathing mixture to pure O₂, and acquiring images following each successive wash‐out breath. The mean fractional ventilation (r) was 0.29 ± 0.05 for control rats, 0.23 ± 0.10 for LPS‐instilled rats and 0.19 ± 0.03 for bleomycin‐instilled rats. Bleomycin‐instilled rats had a significantly decreased mean r value compared with controls (P = 0.010). Although LPS‐instilled rats had a slightly reduced mean r value, this trend was not statistically significant (P = 0.556). Fractional ventilation gradients were calculated in the anterior/posterior (A/P) direction, and the mean A/P gradient was ?0.005 ± 0.008 cm^?1 for control rats, 0.013 ± 0.005 cm^?1 for LPS‐instilled rats and 0.009 ± 0.018 cm^?1 for bleomycin‐instilled rats. Fractional ventilation gradients were significantly different for control rats compared with LPS‐instilled rats only (P = 0.016). The ventilation gradients calculated from control rats showed the expected gravitational relationship, while ventilation gradients calculated from LPS‐ and bleomycin‐instilled rats showed the opposite trend. Histology confirmed that LPS‐instilled rats had a significantly elevated alveolar wall thickness, while bleomycin‐instilled rats showed signs of substantial fibrosis. Overall, ¹⁹F MRI may be able to detect the effects of pulmonary inflammation and fibrosis using a simple and inexpensive imaging approach that can potentially be translated to humans. Copyright © 2016 John Wiley & Sons, Ltd.     

Reconciling PC‐MRI and CFD: An in‐vitro study

Several well‐resolved 4D Flow MRI acquisitions of an idealized rigid flow phantom featuring an aneurysm, a curved channel as well as a bifurcation were performed under pulsatile regime. The resulting hemodynamics were processed to remove MRI artifacts. Subsequently, they were compared with CFD predictions computed on the same flow domain, using an in‐house high‐order low dissipative flow solver. Results show that reaching a good agreement is not straightforward but requires proper treatments of both techniques. Several sources of discrepancies are highlighted and their impact on the final correlation evaluated. While a very poor correlation (r² = 0.63) is found in the entire domain between raw MRI and CFD data, correlation as high as r² = 0.97 is found when artifacts are removed by post‐processing the MR data and down sampling the CFD results to match the MRI spatial and temporal resolutions. This work demonstrates that, in a well‐controlled environment, both PC‐MRI and CFD might bring reliable and correlated flow quantities when a proper methodology to reduce the errors is followed.     

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 (¹H) MRI, fluorine (¹⁹F) 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 ¹H and ¹⁹F 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 (P_in = 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 ¹H and ¹⁹F MRI was demonstrated for the thigh and forearm of a healthy volunteer. The SGBT RF antenna building block facilitated ¹⁹F and ¹H 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).