Elevated phosphodiester and T2 levels can be measured in the absence of fat infiltration in Duchenne muscular dystrophy patients.

Quantitative MRI and MRS are increasingly important as non-invasive outcome measures in therapy development for Duchenne muscular dystrophy (DMD). Many studies have focussed on individual measures such as fat fraction and metabolite levels in relation to age and functionality, but much less attention has been given to how these indices relate to each other. Here, we assessed spatially resolved metabolic changes in leg muscles of DMD patients, and classified muscles according to the degree of fat replacement compared with healthy controls. Quantitative MRI (three-point Dixon and multi-spin echo without fat suppression and a tri-exponential fit) and 2D-CSI 31 P MRS scans were obtained from 18 DMD patients and 12 healthy controls using a 3 T and a 7 T MR scanner. Metabolite levels, T2 values and fat fraction were individually assessed for five lower leg muscles. In muscles with extensive fat replacement, phosphodiester over adenosine triphosphate (PDE/ATP), inorganic phosphate over phosphocreatine, intracellular tissue pH and T2 were significantly increased compared with healthy controls. In contrast, in muscles without extensive fat replacement, only PDE/ATP and T2 values were significantly elevated. Overall, our results show that PDE levels and T2 values increase prior to the occurrence of fat replacement and remain elevated in later stages of the disease. This suggests that these individual measures could not only function as early markers for muscle damage but also reflect potentially reversible pathology in the more advanced stages.

The technological future of 7 T MRI hardware.

In this article we present our projections of future hardware developments on 7 T human MRI systems. These include compact cryogen-light magnets, improved gradient performance, integrated RF-receive and direct current shimming coil arrays, new RF technology with adaptive impedance matching, patient-specific specific absorption rate estimation and monitoring, and increased integration of physiological monitoring systems. Copyright © 2015 John Wiley & Sons, Ltd.

Evaluation of skeletal muscle DTI in patients with duchenne muscular dystrophy.

Diffusion tensor imaging (DTI) is a popular method to assess differences in fiber organization in diseased and healthy muscle tissue. Previous work has shown that muscle DTI measurements depend on signal-to-noise ratio (SNR), %fat, and tissue T2. The goal of this study was to evaluate the potential biasing effects of these factors on skeletal muscle DTI data in patients with Duchenne Muscular Dystrophy (DMD). MR images were obtained of the right lower leg of 21 DMD patients and 12 healthy controls on a Philips 3T system. DTI measurements were combined with quantitative in-vivo measures of mean water T2, %fat and SNR to evaluate their effect on DTI parameter estimation. All outcome measures were determined within ROIs drawn for six lower leg muscles. Between group analysis, using all ROIs, revealed a significantly elevated FA in the GCL, SOL and PER muscles (p<0.05) and an increased mean diffusivity (p<0.05) and λ3 (p<0.05) in the TA muscle of DMD patients. In-vivo evaluation of the individual confounders showed behaviour in line with predictions from previous simulation work. To account for these confounders, subsequent analysis used only ROIs with SNR greater than 20. With this criterion we found significantly greater MD in the TA muscle of DMD patient (p<0.009) and λ3 in the TA and GCL muscles (p<0.001) of DMD patients, but no differences in FA. As both increased %fat and lower SNR are expected to reduce the apparent MD and λ3, these between-group differences are likely due to pathophysiology. However, the increased FA, observed when using all ROIs, likely reflects the effect of low SNR and %fat on the DTI parameter estimation. These findings suggest that measuring mean water T2, %fat and SNR is essential to ascribe changes in DTI measures to intrinsic diffusion changes or to confounding influences.

MR-monitored focused ultrasound using the acoustic-coupling water bath as an intrinsic high-mode dielectric resonator.

The conventional set-up for MR-monitored focused ultrasound surgery includes a piezoelectric transducer and an acoustic-coupling water bath integrated into the MR patient table; a large surface RF coil is placed close to the patient or, alternatively, the body coil is used as the MR receiver. Potential disadvantages of this approach are that the body coil has low sensitivity because of its low filling factor and the local RF coil can interfere with and cause reflections of the ultrasound irradiation. In this article, a completely new approach is presented, in which an MR transmit/receive coil is not needed at all. Instead, the dimensions of the water bath are adjusted so that a high-order dielectric mode is excited, resulting in efficient MR excitation and reception at the transducer focal point. An example of monitoring ultrasound-mediated heating in a phantom is shown on a 7-T human system, although the new method can also be applied at lower fields.

Muscle MRS detects elevated PDE/ATP ratios prior to fatty infiltration in Becker muscular dystrophy.

Becker muscular dystrophy (BMD) is characterized by progressive muscle weakness. Muscles show structural changes (fatty infiltration, fibrosis) and metabolic changes, both of which can be assessed using MRI and MRS. It is unknown at what stage of the disease process metabolic changes arise and how this might vary for different metabolites. In this study we assessed metabolic changes in skeletal muscles of Becker patients, both with and without fatty infiltration, quantified via Dixon MRI and (31) P MRS. MRI and (31) P MRS scans were obtained from 25 Becker patients and 14 healthy controls using a 7 T MR scanner. Five lower-leg muscles were individually assessed for fat and muscle metabolite levels. In the peroneus, soleus and anterior tibialis muscles with non-increased fat levels, PDE/ATP ratios were higher (P < 0.02) compared with controls, whereas in all muscles with increased fat levels PDE/ATP ratios were higher compared with healthy controls (P ≤ 0.05). The Pi /ATP ratio in the peroneus muscles was higher in muscles with increased fat fractions (P = 0.005), and the PCr/ATP ratio was lower in the anterior tibialis muscles with increased fat fractions (P = 0.005). There were no other significant changes in metabolites, but an increase in tissue pH was found in all muscles of the total group of BMD patients in comparison with healthy controls (P < 0.05). These findings suggest that (31) P MRS can be used to detect early changes in individual muscles of BMD patients, which are present before the onset of fatty infiltration.

In vivo blood T(1) measurements at 1.5 T, 3 T, and 7 T.

The longitudinal relaxation time of blood is a crucial parameter for quantification of cerebral blood flow by arterial spin labeling and is one of the main determinants of the signal-to-noise ratio of the resulting perfusion maps. Whereas at low and medium magnetic field strengths (B0), its in vivo value is well established; at ultra-high field, this is still uncertain. In this study, longitudinal relaxation time of blood in the sagittal sinus was measured at 1.5 T, 3 T, and 7 T. A nonselective inversion pulse preceding a Look-Locker echo planar imaging sequence was performed to obtain the inversion recovery curve of venous blood. The results showed that longitudinal relaxation time of blood at 7 T was ∼ 2.1 s which translates to an anticipated 33% gain in the signal-to-noise ratio in arterial spin labeling experiments due to T1 relaxation alone compared with 3 T. In addition, the linear relationship between longitudinal relaxation time of blood and B0 was confirmed.

High-permittivity solid ceramic resonators for high-field human MRI.

The properties of a ceramic-based annular dielectric resonator designed for 7 T MRI have been examined. Electromagnetic simulations and experimentally determined modal frequencies agree to within ~1%. The dependence of the resonance frequency of the degenerate quadrature HEM11 modes on hole diameter and shield diameter was also investigated. The constructed coil, with a 2.5 cm diameter hole, had an unloaded Q value of 400, which was reduced to 150 when loaded with a human finger. Simulated and experimental B1(+) maps show a high degree of homogeneity with a sensitivity of ~11.5 µT/√W at the centre. A comparison with a loop gap resonator showed an approximately 25% higher sensitivity for the dielectric resonator. High-resolution images of the digital interphalangeal (DIP) and proximal interphalangeal (PIP) joints of volunteers were acquired in imaging times of less than 2 min. Finally, novel methods of double tuning such ceramic resonators to two relatively close frequencies, e.g. proton and fluorine, have been shown.

High-resolution MRI of uveal melanoma using a microcoil phased array at 7 T.

High-field MRI is a promising technique for the characterisation of ocular tumours, both in vivo and after enucleation. For in vivo imaging at 7 T, a dedicated three-element microcoil array was constructed as a high-sensitivity receive-only device. Using a dedicated blink/fixation protocol, high-resolution in vivo images could be acquired within 3 min in volunteers and patients with no requirement for post-acquisition image registration. Quantitative measures of axial length, aqueous depth and lens thickness in a healthy volunteer were found to agree well with standard ocular biometric techniques. In a patient with uveal melanoma, in vivo MRI gave excellent tumour/aqueous body contrast. Ex vivo imaging of the enucleated eye showed significant heterogeneity within the tumour.

Proton magnetic resonance spectroscopy shows lower intramyocellular lipid accumulation in middle-aged subjects predisposed to familial longevity.

Families predisposed to longevity show enhanced glucose tolerance and skeletal muscle insulin sensitivity compared with controls, independent of body composition and physical activity. Intramyocellular lipid (IMCL) accumulation in skeletal muscle has been associated with insulin resistance. Here, we assessed whether subjects enriched for familial longevity have lower IMCL levels. We determined IMCL levels in 48 subjects from the Leiden Longevity Study, comprising 24 offspring of nonagenarian siblings and 24 partners thereof as control subjects. IMCL levels were assessed noninvasively using short echo time proton magnetic resonance spectroscopy ((1)H-MRS) of the tibialis anterior muscle with a 7 Tesla human MR scanner. IMCL levels were calculated relative to the total creatine (tCr) CH3 signal. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). After correction for age, sex, BMI, and physical activity, offspring of long-lived nonagenarian siblings tended to show lower IMCL levels compared with controls (IMCL/tCr: 3.1 ± 0.5 vs. 4.5 ± 0.5, respectively, P = 0.051). In a pairwise comparison, this difference reached statistical significance (P = 0.038). We conclude that offspring of nonagenarian siblings predisposed to longevity show lower IMCL levels compared with environmentally matched control subjects. Future research should focus on assessing what mechanisms may explain the lower IMCL levels in familial longevity.

Simulations of high permittivity materials for 7 T neuroimaging and evaluation of a new barium titanate-based dielectric.

High permittivity "dielectric pads" have been shown to increase image quality at high magnetic fields in regions of low radiofrequency transmit efficiency. This article presents a series of electromagnetic simulations to determine the effects of pad size and geometry, relative permittivity value, as well as thickness on the transmit radiofrequency fields for neuroimaging at 7 T. For a 5-mm thick pad, there is virtually no effect on the transmit field for relative permittivity values lower than ∼90. Significant improvements are found for values between 90 and ∼180. If the relative permittivity is increased above ∼180 then areas of very low transmit efficiency are produced. For a 1-cm thick pad, the corresponding numbers are ∼60 and ∼120, respectively. Based upon the findings, a new material (barium titanate, relative permittivity ∼150) is used to produce thin (∼5 mm) dielectric pads which can easily be placed within a standard receive head array. Experimental measurements of transmit sensitivities, as well as acquisition of T(2) - and T 2*-weighted images show the promise of this approach.

Increasing signal homogeneity and image quality in abdominal imaging at 3 T with very high permittivity materials.

The appearance of severe signal drop-outs in abdominal imaging at 3 T arises primarily from areas of very low B1+ transmit field in the body, and is problematic in both obese as well as very thin subjects. In this study, we show how thin patient-friendly pads containing new high permittivity materials can be designed and optimized, and when placed around the subject increase substantially the B1+ uniformity and the image quality. Results from nine healthy volunteers show that inclusion of these dielectric pads results in statistically significant decreases in the coefficient of variance of the B1+ field, with stronger and more uniform fields being produced. In addition there are statistically significant decreases in time-averaged power required for scanning. These differences are present in both quadrature-mode operation (coefficient of variance decrease, P<0.0001, mean 25.4±10%: power decrease, P=0.005, mean 14±14%) and also for the RF-shimmed case (coefficient of variance decrease, P=0.01, mean 16±13%: power decrease, P=0.005, mean 22±11%) of a dual-transmit system.

Retrospective image correction in the presence of nonlinear temporal magnetic field changes using multichannel navigator echoes.

Spatio-temporal magnetic field changes in the brain caused by breathing or body movements can lead to image artifacts. This is especially a problem in T(2)(*)-weighted sequences. With the acquisition of an extra echo (navigator), it is possible to measure the magnetic field change induced frequency offset for a given slice during image acquisition. However, substantial local variation across a slice can occur. This work describes an extension of the conventional navigator technique that improves the estimation of the magnetic field distribution in the brain during strong field fluctuations. This is done using the combination of signals from multiple coil elements, the coil sensitivity profiles, and frequency encoding: termed sensitivity-encoded navigator echoes. In vivo validation was performed in subjects who performed normal breathing, nose touching, and deep breathing during scanning. The sensitivity-encoded navigator technique leads to an error reduction in estimating the field distribution in the brain of 73% ± 16% compared with 56% ± 14% for conventional estimation. Image quality can be improved via incorporating this navigator information appropriately into the image reconstruction. When the sensitivity-encoded navigator technique was applied to a T(2)(*)-weighted sequence at 7 T, a ghosting reduction of 47% ± 13% was measured during nose touching experiments compared with no correction.

Deep learning-based single image super-resolution for low-field MR brain images.

Low-field MRI scanners are significantly less expensive than their high-field counterparts, which gives them the potential to make MRI technology more accessible all around the world. In general, images acquired using low-field MRI scanners tend to be of a relatively low resolution, as signal-to-noise ratios are lower. The aim of this work is to improve the resolution of these images. To this end, we present a deep learning-based approach to transform low-resolution low-field MR images into high-resolution ones. A convolutional neural network was trained to carry out single image super-resolution reconstruction using pairs of noisy low-resolution images and their noise-free high-resolution counterparts, which were obtained from the publicly available NYU fastMRI database. This network was subsequently applied to noisy images acquired using a low-field MRI scanner. The trained convolutional network yielded sharp super-resolution images in which most of the high-frequency components were recovered. In conclusion, we showed that a deep learning-based approach has great potential when it comes to increasing the resolution of low-field MR images.

Improvements in high-field localized MRS of the medial temporal lobe in humans using new deformable high-dielectric materials.

The intrinsic nonuniformities in the transmit radiofrequency field from standard quadrature volume resonators at high field are particularly problematic for localized MRS in areas such as the temporal lobe, where a low signal-to-noise ratio and poor metabolite quantification result from destructive B1⁺ field interference, in addition to line broadening and signal loss from strong susceptibility gradients. MRS of the temporal lobe has been performed in a number of neurodegenerative diseases at clinical fields, but a relatively low signal-to-noise ratio has prevented the reliable quantification of, for example, glutamate and glutamine, which are thought to play a key role in disease progression. Using a recently developed high-dielectric-constant material placed around the head, localized MRS of the medial temporal lobe using the stimulated echo acquisition mode sequence was acquired at 7 T. The presence of the material increased the signal-to-noise ratio of MRS by a factor of two without significantly reducing the sensitivity in other areas of the brain, as shown by the measured B1⁺ maps. An increase in the receive sensitivity B1⁻ was also measured close to the pads. The spectral linewidth of the unsuppressed water peak within the voxel of interest was reduced slightly by the introduction of the dielectric pads (although not to a statistically significant degree), a result confirmed by using a pad composed of lipid. Using LCmodel for quantitative analysis of metabolite concentrations, the increase in signal-to-noise ratio and the slight decrease in spectral linewidth contributed to statistically significant reductions in the Cramer-Rao lower bounds (CRLBs), also allowing the levels of glutamate and glutamine to be quantified with CRLBs below 20%.

Characterization of displacement forces and image artifacts in the presence of passive medical implants in low-field (<100 mT) permanent magnet-based MRI systems, and comparisons with clinical MRI systems.

PURPOSE: To investigate the displacement forces and image artifacts associated with passive medical implants for recently-developed low-field (<100 mT) MRI systems, and to compare these with values from higher field strengths used for clinical diagnosis. METHODS: Setups were constructed to measure displacement forces in a permanent magnet-based Halbach array used for in vivo MRI at 50 mT, and results compared with measurements at 7 T. Image artifacts were assessed using turbo (fast) spin echo imaging sequences for four different passive medical implants: a septal occluder, iliac stent, pedicle screw and (ferromagnetic) endoscopic clip. Comparisons were made with artifacts produced at 1.5, 3 and 7 T. Finally, specific absorption rate (SAR) simulations were performed to determine under what operating conditions the limits might be approached at low-field. RESULTS: Displacement forces at 50 mT on all but the ferromagnetic implant were between 1 and 10 mN. Image artifacts at 50 mT were much less than at clinical field strengths for all passive devices, and with the exception of the ferromagnetic clip. SAR simulations show that very long echo train (>128) turbo spin echo sequences can be run with short inter-pulse times (5-10 ms) within SAR limits. CONCLUSIONS: This work presents the first evaluation of the effects of passive implants at field strengths less than 100 mT in terms of displacement forces, image artifacts and SAR. The results support previous claims that such systems can be used safely and usefully in challenging enviroments such as the intensive care unit.

Performance of the Emprint and Amica Microwave Ablation Systems in ex vivo Porcine Livers: Sphericity and Reproducibility Versus Size.

PURPOSE: To investigate the performance of two microwave ablation (MWA) systems regarding ablation volume, ablation shape and variability. MATERIALS AND METHODS: In this ex vivo study, the Emprint and Amica MWA systems were used to ablate porcine livers at 4 different settings of time and power (3 and 5 minutes at 60 and 80 Watt). In total, 48 ablations were analysed for ablation size and shape using Vitrea Advanced Visualization software after acquisition of a 7T MRI scan. RESULTS: Emprint ablations were smaller (11,1 vs. 21,1 mL p < 0.001), more spherical (sphericity index of 0.89 vs. 0.59 p < 0.001) and showed less variability than Amica ablations. In both systems, longer ablation time and higher power resulted in significantly larger ablation volumes. CONCLUSION: Emprint ablations were more spherical, and the results showed a lower variability than those of Amica ablations. This comes at the price of smaller ablation volumes.

Origin and reduction of motion and f0 artifacts in high resolution T2*-weighted magnetic resonance imaging: application in Alzheimer's disease patients.

The altered iron concentration in many neurodegenerative diseases such as Alzheimer's disease (AD) has led to the development of MRI sequences that are sensitive to the accompanying changes in the transverse relaxation rate. Heavily T(2)*-weighted imaging sequences at high magnetic field strength (7T and above), in particular, show potential for detecting small changes in iron concentration. However, these sequences require a long echo time in combination with a long scanning time for high resolution and are therefore prone to image artifacts caused by physiological fluctuations, patient motion or system instabilities. Many groups have found that the high image quality that was obtained using high resolution T(2)*-weighted sequences at 7T in healthy volunteers, could not be obtained in AD patients. In this study the source of the image artifacts was investigated in phantom and in healthy volunteer experiments by incorporating movement parameters and resonance frequency (f0) variations which were measured in AD patients. It was found that image degradation caused by typical f0 variations was a factor-of-four times larger than artifacts caused by movement characteristic of AD patients in the scanner. In addition to respiratory induced f0 variations, large jumps in the f0 were observed in AD patients. By implementing a navigator echo technique to correct for f0 variations, the image quality of high resolution T(2)*-weighted images increased considerably. This technique was successfully applied in five AD patients and in five subjective memory complainers. Visual scoring showed improvements in image quality in 9 out of 10 subjects. Ghosting levels were reduced by 24+/-13%.

In vivo 31P MRS detection of an alkaline inorganic phosphate pool with short T1 in human resting skeletal muscle.

Non-invasive determination of mitochondrial content is an important objective in clinical and sports medicine. 31P MRS approaches to obtain information on this parameter at low field strength typically require in-magnet exercise. Direct observation of the intra-mitochondrial inorganic phosphate (Pi) pool in resting muscle would constitute an alternative, simpler method. In this study, we exploited the higher spectral resolution and signal-to-noise at 7T to investigate the MR visibility of this metabolite pool. 31P in vivo MR spectra of the resting soleus (SOL) muscle were obtained with 1H MR image-guided surface coil localization (six volunteers) and of the SOL and tibialis anterior (TA) muscle using 2D CSI (five volunteers). A resonance at a frequency 0.38 ppm downfield from the cytosolic Pi resonance (Pi(1); pH 7.0 ± 0.04) was reproducibly detected in the SOL muscle in all subjects and conditionally attributed to the intra-mitochondrial Pi pool (Pi(2); pH 7.3 ± 0.07). In the SOL muscle, the Pi(2)/Pi(1) ratio was 1.6 times higher compared to the TA muscle in the same individual. Localized 3D CSI results showed that the Pi(2) peak was present in voxels well away from blood vessels. Determination of the T1 of the two Pi pools in a single individual using adiabatic excitation of the spectral region around 5 ppm yielded estimates of 4.3 ± 0.4 s vs 1.4 ± 0.5 s for Pi(1) and Pi(2), respectively. Together, these results suggest that the intra-mitochondrial Pi pool in resting human skeletal muscle may be visible with 31P MRS at high field.

Three-dimensional MRI in a homogenous 27 cm diameter bore Halbach array magnet.

Modern clinical MRI systems utilise very high magnetic fields strengths to produce high resolution images of the human body. The high up-front and maintenance cost of these systems means that much of the world lacks access to this technology. In this paper we propose a low cost, head-only, homogenous Halbach magnet array with the potential for paediatric neuroimaging in low-resource settings. The homogeneity of the Halbach array is improved by allowing the diameter of the Halbach array to vary along its length, and also adding smaller internal shim magnets. The constructed magnet has a bore diameter of 27 cm, mean B0 field strength of 50.4 mT and a homogeneity of 2400 ppm over a 20 cm diameter spherical volume. The level of homogeneity of the system means that coil-based gradients can be used for spatial encoding which greatly increases the flexibility in image acquisition. 3D images of a "brain phantom" were acquired over a 22 × 22 × 22 cm field of view with a 3.5 mm isotropic resolution using a spin-echo sequence. Future development of a low-cost gradient amplifier and an open-source spectrometer has the potential of offering a fully open-source, low-cost MRI system for paediatric neuroimaging in low-resource settings.

High-Permittivity Pad Design for Dielectric Shimming in Magnetic Resonance Imaging Using Projection-Based Model Reduction and a Nonlinear Optimization Scheme.

Inhomogeneities in the transmit radio frequency magnetic field ( ) reduce the quality of magnetic resonance (MR) images. This quality can be improved by using high-permittivity pads that tailor the fields. The design of an optimal pad is application-specific and not straightforward and would therefore benefit from a systematic optimization approach. In this paper, we propose such a method to efficiently design dielectric pads. To this end, a projection-based model order reduction technique is used that significantly decreases the dimension of the design problem. Subsequently, the resulting reduced-order model is incorporated in an optimization method in which a desired field in a region of interest can be set. The method is validated by designing a pad for imaging the cerebellum at 7 T. The optimal pad that is found is used in an MR measurement to demonstrate its effectiveness in improving the image quality.