HYFI: Hybrid filling of the dead-time gap for faster zero echo time imaging.

The aim of this work was to improve the SNR efficiency of zero echo time (ZTE) MRI pulse sequences for faster imaging of short-T2 components at large dead-time gaps. ZTE MRI with hybrid filling (HYFI) is a strategy for retrieving inner k-space data missed during the dead-time gaps arising from radio-frequency excitation and switching in ZTE imaging. It performs hybrid filling of the inner k-space with a small single-point-imaging core surrounded by a stack of shells acquired on radial readouts in an onion-like fashion. The exposition of this concept is followed by translation into guidelines for parameter choice and implementation details. The imaging properties and performance of HYFI are studied in simulations as well as phantom, in vitro and in vivo imaging, with an emphasis on comparison with the pointwise encoding time reduction with radial acquisition (PETRA) technique. Simulations predict higher SNR efficiency for HYFI compared with PETRA at preserved image quality, with the advantage increasing with the size of the k-space gap. These results are confirmed by imaging experiments with gap sizes of 25 to 50 Nyquist dwells, in which scan times for similar image quality could be reduced by 25% to 60%. The HYFI technique provides both high SNR efficiency and image quality, thus outperforming previously known ZTE-based pulse sequences, in particular for large k-space gaps. Promising applications include direct imaging of ultrashort-T2 components, such as the myelin bilayer or collagen, T2 mapping of ultrafast relaxing signals, and ZTE imaging with reduced chemical shift artifacts.

High-resolution MRI of mummified tissues using advanced short-T2 methodology and hardware.

PURPOSE: Evolutionary medicine aims to study disease development from a long-term perspective, and through the analysis of mummified tissue, timescales of several thousand years are unlocked. Due to the status of mummies as ancient relics, noninvasive techniques are preferable, and, currently, CT imaging is the most widespread method. However, CT images lack soft-tissue contrast, making complementary MRI data desirable. Unfortunately, the dehydrated nature and short T2 times of mummified tissues render them practically invisible to standard MRI techniques. Specialized short-T2 approaches have therefore been used, but currently suffer severe resolution limitations. The purpose of the present study is to improve resolution in MRI of mummified tissues. METHODS: The zero-TE-based hybrid filling technique, together with a high-performance magnetic field gradient, was used to image three ancient Egyptian mummified human body parts: a hand, a foot, and a head. A similar pairing has already been shown to increase resolution and image quality in MRI of short-T2 tissues. RESULTS: MRI images of yet unparalleled image quality were obtained for all samples, reaching isotropic resolutions of 0.6 mm and SNR values above 100. The same general features as present in CT images were depicted but with different contrast, particularly for regions containing embalming substances. CONCLUSION: Mummy MRI is a potentially valuable tool for (paleo)pathological studies, as well as for investigations into ancient mummification processes. The results presented here show sufficient improvement in the depiction of mummified tissues to clear new paths for the exploration of this field.

Advances in MRI of the myelin bilayer.

Myelin plays a key role in the function of the central nervous system and is involved in many neurodegenerative diseases. Hence, depiction of myelin is desired for both research and diagnosis. However, MRI of the lipid bilayer constituting the myelin membrane is hampered by extremely rapid signal decay and cannot be accomplished with conventional sequences. Dedicated short-T2 techniques have therefore been employed, yet with extended sequence timings not well matched to the rapid transverse relaxation in the bilayer, which leads to signal loss and blurring. In the present work, capture and encoding of the ultra-short-T2 signals in the myelin bilayer is considerably improved by employing advanced short-T2 methodology and hardware, in particular a high-performance human-sized gradient insert. The approach is applied to tissue samples excised from porcine brain and in vivo in a human volunteer. It is found that the rapidly decaying non-aqueous components in the brain can indeed be depicted with MRI at useful resolution. As a considerable fraction of these signals is related to the myelin bilayer, the presented approach has strong potential to contribute to myelin research and diagnosis.

A transmit-receive array for brain imaging with a high-performance gradient insert.

PURPOSE: The aim of this work was to provide parallel imaging capability for the human head in a gradient insert of 33-cm inner diameter within the related constraints of space, encoding ambiguity, and eddy current immunity. METHODS: Eddy current behavior of the 8-channel transmit-receive array coil was investigated via heating and field deviation measurements. RF performance was evaluated using S-parameters, noise statistics, B1 maps, and g-factor maps. In vivo images of a human head and knee were acquired with Cartesian readout and TE below 0.45 ms. RESULTS: Under intense gradient use, the shield was heated up to 55°C and other coil structures to 40°C. After standard preemphasis calibration, eddy current-related field distortions caused by the developed RF coil were smaller than for a commercial receive-only coil. In the ambiguous regions of the gradient, B1+ is 20 dB lower than in the center of the FOV. Coupling between elements is below -15 dB, and noise correlation is less than 0.31 when the coil is loaded with a head. Power efficiency was 0.52 ± 0.02 µT/√W, and the SD of the flip angle was below 10% in central slices of the brain. 2D, up to fourfold acceleration causes less than 30% noise amplification. The RF coil can be used during full gradient performance. CONCLUSION: Based on the described features, the presented coil enables parallel imaging in the high-performance gradient insert.

High-resolution short-T2 MRI using a high-performance gradient.

PURPOSE: To achieve high resolution in imaging of short-T2 materials and tissues by using a high-performance human-sized gradient insert with strength up to 200 mT/m and 100% duty cycle. METHODS: Dedicated short-T2 methodology and hardware are used, such as the pointwise encoding time reduction with radial acquisition (PETRA) technique with modulated excitation pulses, optimized radio-frequency hardware, and a high-performance gradient insert. A theoretical analysis of actual spatial resolution and SNR is provided to support the choice of scan parameters and interpretation of the results. Imaging is performed in resolution phantoms, animal specimen, and human volunteers at both conventional and maximum available gradient strengths and compared using image subtraction. RESULTS: Calculations suggest that increasing gradient strength beyond conventional values considerably improves both actual resolution and SNR efficiency in short-T2 imaging. Resolution improvements are confirmed in all investigated samples, in particular 2 mm slots were resolved in a hard-plastic plate with T2 ≈ 10 µs and in vivo musculoskeletal images were acquired at isotropic 200 µm resolution. Expected improvements in signal yield are realized in fine structures benefitting from high resolution but to less extent in regions of low contrast where decay-related blurring leads to signal overlap between neighboring locations. CONCLUSION: Strong gradients with high duty cycle enable short-T2 imaging at unprecedentedly high resolution, holding the potential for improving MRI of, eg, bone, tendon, lung, or teeth. Moreover, it allows direct access of tissues with T2 of tens of microseconds such as myelin or collagen.

Long-T2 -suppressed zero echo time imaging with weighted echo subtraction and gradient error correction.

PURPOSE: To perform direct, selective MRI of short-T2 tissues using zero echo time (ZTE) imaging with weighted echo subtraction (WSUB). METHODS: Radial imaging was performed at 7T, acquiring both ZTE and gradient echo (GRE) signals created by bipolar gradients. Long-T2 suppression was achieved by weighted subtraction of ZTE and GRE images. Special attention was given to imperfections of gradient dynamics, to which radial GRE imaging is particularly susceptible. To compensate for gradient errors, matching of gradient history was combined with data correction based on trajectory measurement. The proposed approach was first validated in phantom experiments and then demonstrated in musculoskeletal (MSK) imaging. RESULTS: Trajectory analysis and phantom imaging demonstrated that gradient imperfections were successfully addressed. Gradient history matching enabled consistency between antiparallel projections as required for deriving zeroth-order eddy current dynamics. Trajectory measurement provided individual echo times per projection that showed considerable variation between gradient directions. In in vivo imaging of knee, ankle, and tibia, the proposed approach enabled high-resolution 3D depiction of bone, tendons, and ligaments. Distinct contrast of these structures indicates excellent selectivity of long-T2 suppression. Clarity of depiction also confirmed sufficient SNR of short-T2 tissues, achieved by high baseline sensitivity at 7T combined with high SNR efficiency of ZTE acquisition. CONCLUSION: Weighted subtraction of ZTE and GRE data reconciles robust long-T2 suppression with fastest k-space coverage and high SNR efficiency. This approach enables high-resolution imaging with excellent selectivity to short-T2 tissues, which are of major interest in MSK and neuroimaging applications.

A high-performance gradient insert for rapid and short-T2 imaging at full duty cycle.

PURPOSE: The goal of this study was to devise a gradient system for MRI in humans that reconciles cutting-edge gradient strength with rapid switching and brings up the duty cycle to 100% at full continuous amplitude. Aiming to advance neuroimaging and short-T2 techniques, the hardware design focused on the head and the extremities as target anatomies. METHODS: A boundary element method with minimization of power dissipation and stored magnetic energy was used to design anatomy-targeted gradient coils with maximally relaxed geometry constraints. The design relies on hollow conductors for high-performance cooling and split coils to enable dual-mode gradient amplifier operation. With this approach, strength and slew rate specifications of either 100 mT/m with 1200 mT/m/ms or 200 mT/m with 600 mT/m/ms were reached at 100% duty cycle, assuming a standard gradient amplifier and cooling unit. RESULTS: After manufacturing, the specified values for maximum gradient strength, maximum switching rate, and field geometry were verified experimentally. In temperature measurements, maximum local values of 63°C were observed, confirming that the device can be operated continuously at full amplitude. Testing for peripheral nerve stimulation showed nearly unrestricted applicability in humans at full gradient performance. In measurements of acoustic noise, a maximum average sound pressure level of 132 dB(A) was determined. In vivo capability was demonstrated by head and knee imaging. Full gradient performance was employed with echo planar and zero echo time readouts. CONCLUSION: Combining extreme gradient strength and switching speed without duty cycle limitations, the described system offers unprecedented options for rapid and short-T2 imaging. Magn Reson Med 79:3256-3266, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

A virtually 1H-free birdcage coil for zero echo time MRI without background signal.

PURPOSE: MRI of tissues with rapid transverse relaxation can be performed efficiently using the zero echo time (ZTE) technique. At high bandwidths leading to large relative initial radiofrequency (RF) dead times, the method becomes increasingly sensitive to artifacts related to signal stemming from outside the field of view, particularly from the RF coils. Therefore, in this work, a birdcage coil was designed that is virtually free of 1H signal. METHODS: A transmit-receive birdcage RF coil for MRI of joints at 7T was designed by rigorously avoiding materials containing 1H nuclei, by using purely mechanical connections without glue, and by spoiling of unwanted signal by application of ferromagnetic materials. The coil was tested for residual 1H signal using ZTE phantom and in vivo joint imaging. RESULTS: In standard ZTE imaging, no 1H signal was detected above noise level. Only at extreme averaging, residual signal was observed close to conductors associated with 1H-containing molecules at adjacent glass surfaces. Phantom images with dead times up to 3.8 Nyquist dwells were obtained with only negligible background artifacts. Furthermore, high-quality ZTE images of human joints were acquired. CONCLUSION: A virtually 1H-free birdcage coil is presented, thus enabling in vivo ZTE MRI practically free of background signal, even at high bandwidths. Magn Reson Med 78:399-407, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

(39) K and (23) Na relaxation times and MRI of rat head at 21.1 T.

At ultrahigh magnetic field strengths (B0 ≥ 7.0 T), potassium ((39) K) MRI might evolve into an interesting tool for biomedical research. However, (39) K MRI is still challenging because of the low NMR sensitivity and short relaxation times. In this work, we demonstrated the feasibility of (39) K MRI at 21.1 T, determined in vivo relaxation times of the rat head at 21.1 T, and compared (39) K and sodium ((23) Na) relaxation times of model solutions containing different agarose gel concentrations at 7.0 and 21.1 T. (39) K relaxation times were markedly shorter than those of (23) Na. Compared with the lower field strength, (39) K relaxation times were up to 1.9- (T1 ), 1.4- (T2S ) and 1.9-fold (T2L ) longer at 21.1 T. The increase in the (23) Na relaxation times was less pronounced (up to 1.2-fold). Mono-exponential fits of the (39) K longitudinal relaxation time at 21.1 T revealed T1 = 14.2 ± 0.1 ms for the healthy rat head. The (39) K transverse relaxation times were 1.8 ± 0.2 ms and 14.3 ± 0.3 ms for the short (T2S ) and long (T2L ) components, respectively. (23) Na relaxation times were markedly longer (T1 = 41.6 ± 0.4 ms; T2S = 4.9 ± 0.2 ms; T2L = 33.2 ± 0.2 ms). (39) K MRI of the healthy rat head could be performed with a nominal spatial resolution of 1 × 1 × 1 mm(3) within an acquisition time of 75 min. The increase in the relaxation times with magnetic field strength is beneficial for (23) Na and (39) K MRI at ultrahigh magnetic field strength. Our results demonstrate that (39) K MRI at 21.1 T enables acceptable image quality for preclinical research. Copyright © 2016 John Wiley & Sons, Ltd.

Blood Glucose Homeostasis in the Course of Partial Pancreatectomy--Evidence for Surgically Reversible Diabetes Induced by Cholestasis.

BACKGROUND AND AIM: Partial pancreatic resection is accompanied not only by a reduction in the islet cell mass but also by a variety of other factors that are likely to interfere with glucose metabolism. The aim of this work was to characterize the patient dynamics of blood glucose homeostasis during the course of partial pancreatic resection and to specify the associated clinico-pathological variables. METHODS: In total, 84 individuals undergoing elective partial pancreatic resection were consecutively recruited into this observational trial. The individuals were assigned based on their fasting glucose or oral glucose tolerance testing results into one of the following groups: (I) deteriorated, (II) stable or (III) improved glucose homeostasis three months after surgery. Co-variables associated with blood glucose dynamics were identified. RESULTS: Of the 84 participants, 25 (30%) displayed a normal oGTT, 17 (20%) showed impaired glucose tolerance, and 10 (12%) exhibited pathological glucose tolerance. Elevated fasting glucose was present in 32 (38%) individuals before partial pancreatic resection. Three months after partial pancreatic resection, 14 (17%) patients deteriorated, 16 (19%) improved, and 54 (64%) retained stable glucose homeostasis. Stability and improvement was associated with tumor resection and postoperative normalization of recently diagnosed glucose dysregulation, preoperatively elevated tumor markers and markers for common bile duct obstruction, acute pancreatitis and liver cell damage. Improvement was linked to preoperatively elevated insulin resistance, which normalized after resection and was accompanied by a decrease in fasting- and glucose-stimulated insulin secretion. CONCLUSIONS: Surgically reversible blood glucose dysregulation diagnosed concomitantly with a (peri-) pancreatic tumor appears secondary to compromised liver function due to tumor compression of the common bile duct and the subsequent increase in insulin resistance. It can be categorized as "cholestasis-induced diabetes" and thereby distinguished from other forms of hyperglycemic disorders.

In vivo 39K MR imaging of human muscle and brain.

PURPOSE: To implement potassium 39 ((39)K) magnetic resonance (MR) imaging with a 7-T MR imaging system and to evaluate its feasibility for in vivo imaging of human muscle and brain. MATERIALS AND METHODS: Three healthy volunteers were examined with approval of the ethical review board of Heidelberg University. Written informed consent was obtained from all volunteers. Because the available 7-T MR imaging system did not support (39)K, a frequency conversion scheme was developed and connected to the imaging unit. The standard X-nucleus frequency of lithium 7 (115 MHz) was converted to the frequency of (39)K at 7 T (14 MHz). Relaxation times of healthy thigh muscle and brain tissue were estimated by using multiple-echo and inversion-recovery sequences. Data analysis was conducted with a nonlinear least squares curve fitting tool. In vivo (39)K MR imaging of healthy human thigh muscle and brain was performed. RESULTS: With use of the custom-built frequency conversion scheme, (39)K MR imaging is feasible with a commercially available 7-T MR imaging system. Nominal spatial resolutions of 8 × 8 × 16 mm(3) and 9.5 × 9.5 × 9.5 mm(3) were achieved for human thigh muscle and brain, respectively. Acquisition time was 30 minutes for both muscle and brain tissue. The measured potassium concentration (uncorrected for fat fraction) of thigh muscle tissue (112-124 mmol/L) lies within the expected range. CONCLUSION: In vivo (39)K MR imaging in humans can be performed in clinically feasible measurement times (approximately 30 minutes) with voxel sizes of approximately 1 mL.

Sulfated hyaluronan derivatives reduce the proliferation rate of primary rat calvarial osteoblasts.

Glycosaminoglycans (GAG) and proteoglycans, which are components of the extracellular bone matrix, are also localized in and at the membrane of osteoblasts and in the pericellular matrix. Due to their interaction with several growth factors, water and cations these molecules play an important role in regulating proliferation and differentiation of osteoblasts and bone development. The aim of this study was to assess in vitro the effects of two chemically sulfated hyaluronan (HyaS) derivatives on the proliferation of rat calvarial osteoblasts and to compare with those of native hyaluronan (Hya) and natural sulfated GAG such as chondroitin-4-sulfate (C4S), chondroitin-6-sulfate (C6S), dermatan sulfate (DS) and heparan sulfate (HS). Moderately and highly sulfated HyaS derivatives caused a time-dependent reduction of osteoblast proliferation. The anti-proliferative effect of HyaS was accompanied by a cell cycle arrest in the G1 phase, but was not associated with cell death. Whereas non-sulfated high molecular weight (HMW)- and low molecular weight (LMW)-Hya as well as C4S, C6S, DS and HS showed no effect on the cell proliferation.