Myelin bilayer mapping in the human brain in vivo.

PURPOSE: To quantitatively map the myelin lipid-protein bilayer in the live human brain. METHODS: This goal was pursued by integrating a multi-TE acquisition approach targeting ultrashort T2 signals with voxel-wise fitting to a three-component signal model. Imaging was performed at 3 T in two healthy volunteers using high-performance RF and gradient hardware and the HYFI sequence. The design of a suitable imaging protocol faced substantial constraints concerning SNR, imaging volume, scan time, and RF power deposition. Model fitting to data acquired using the proposed protocol was made feasible through simulation-based optimization, and filtering was used to condition noise presentation and overall depiction fidelity. RESULTS: A multi-TE protocol (11 TEs of 20-780 µs) for in vivo brain imaging was developed in adherence with applicable safety regulations and practical scan time limits. Data acquired using this protocol produced accurate model fitting results, validating the suitability of the protocol for this purpose. Structured, grainy texture of myelin bilayer maps was observed and determined to be a manifestation of correlated image noise resulting from the employed acquisition strategy. Map quality was significantly improved by filtering to uniformize the k-space noise distribution and simultaneously extending the k-space support. The final myelin bilayer maps provided selective depiction of myelin, reconciling competitive resolution (1.4 mm) with adequate SNR and benign noise texture. CONCLUSION: Using the proposed technique, quantitative maps of the myelin bilayer can be obtained in vivo. These maps offer unique information content with potential applications in basic research, diagnosis, disease monitoring, and drug development.

Mapping the myelin bilayer with short-T2 MRI: Methods validation and reference data for healthy human brain.

PURPOSE: To explore the properties of short-T2 signals in human brain, investigate the impact of various experimental procedures on these properties and evaluate the performance of three-component analysis. METHODS: Eight samples of non-pathological human brain tissue were subjected to different combinations of experimental procedures including D2 O exchange and frozen storage. Short-T2 imaging techniques were employed to acquire multi-TE (33-2067 µs) data, to which a three-component complex model was fitted in two steps to recover the properties of the underlying signal components and produce amplitude maps of each component. For validation of the component amplitude maps, the samples underwent immunohistochemical myelin staining. RESULTS: The signal component representing the myelin bilayer exhibited super-exponential decay with T2,min of 5.48 µs and a chemical shift of 1.07 ppm, and its amplitude could be successfully mapped in both white and gray matter in all samples. These myelin maps corresponded well to myelin-stained tissue sections. Gray matter signals exhibited somewhat different components than white matter signals, but both tissue types were well represented by the signal model. Frozen tissue storage did not alter the signal components but influenced component amplitudes. D2 O exchange was necessary to characterize the non-aqueous signal components, but component amplitude mapping could be reliably performed also in the presence of H2 O signals. CONCLUSIONS: The myelin mapping approach explored here produced reasonable and stable results for all samples. The extensive tissue and methodological investigations performed in this work form a basis for signal interpretation in future studies both ex vivo and in vivo.

Pulse encoding for ZTE imaging: RF excitation without dead-time penalty.

PURPOSE: To overcome limitations in the duration of RF excitation in zero-TE (ZTE) MRI by exploiting intrinsic encoding properties of RF pulses to retrieve data missed during the dead time caused by the pulse. METHODS: An enhanced ZTE signal model was developed using multiple RF pulses, which enables accessing information hidden in the pulse-induced dead time via encoding intrinsically applied by the RF pulses. Such ZTE with pulse encoding was implemented by acquisition of two ZTE data sets using excitation with similar frequency-swept pulses differing only by a small off-resonance in their center frequency. In this way, the minimum scan time is doubled but each acquisition contributes equally to the SNR, as with ordinary averaging. The method was demonstrated on long-T2 and short-T2 phantoms as well as in in vivo experiments. RESULTS: ZTE with pulse encoding provided good image quality at unprecedented dead-time gaps, demonstrated here up to 6 Nyquist dwells. In head imaging, the ability to use longer excitation pulses led to approximately 2-fold improvements in SNR efficiency as compared with conventional ZTE and allowed the creation of T1 contrast. CONCLUSION: Exploiting intrinsic encoding properties of RF pulses in a new signal model enables algebraic reconstruction of ZTE data sets with large dead-time gaps. This permits larger flip angles, which can be used to achieve enhanced T1 contrast and significant improvements in SNR efficiency in case the Ernst angle can be better approached, thus broadening the range of application of ZTE MRI.

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.

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.

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.

Minimizing the echo time in diffusion imaging using spiral readouts and a head gradient system.

PURPOSE: Diffusion weighted imaging (DWI) is commonly limited by low signal-to-noise ratio (SNR) as well as motion artifacts. To address this limitation, a method that allows to maximize the achievable signal yield and increase the resolution in motion robust single-shot DWI is presented. METHODS: DWI was performed on a 3T scanner equipped with a recently developed gradient insert (gradient strength: 200 mT/m, slew rate: 600 T/m/s). To further shorten the echo time, Stejskal-Tanner diffusion encoding with a single-shot spiral readout was implemented. To allow non-Cartesian image reconstruction using such strong and fast gradients, the characterization of eddy current and concomitant field effects was performed based on field-camera measurements. RESULTS: An echo time of only 19 ms was achieved for a b-factor of 1000 s/mm2 . An in-plane resolution of 0.68 mm was encoded by a single-shot spiral readout of 40.5 ms using 3-fold undersampling. The resulting images did not suffer from off-resonance artifacts and T 2 ∗ blurring that are common to single-shot images acquired with regular gradient systems. CONCLUSION: Spiral diffusion imaging using a head gradient system, together with an accurate characterization of the encoding process allows for a substantial reduction of the echo time, and improves the achievable resolution in motion-insensitive single-shot DWI.

Echo-planar imaging of the human head with 100 mT/m gradients and high-order modeling of eddy current fields.

PURPOSE: To demonstrate the utility of a high-performance gradient insert for ultrafast MRI of the human head. METHODS: EPI was used for the first time with a readout gradient amplitude of 100 mT/m, 1200 T/m/s slew rate, and nearly 1 MHz signal bandwidth for human head scanning. To avoid artefacts due to eddy currents, the magnetic field was dynamically monitored with NMR probes at multiple points, modeled by solid harmonics up to fifth order, and included in the image reconstruction. An approximation of a negligible intra-echo effect of the eddy currents was made to accelerate the high-order reconstruction. The field monitoring-based approach was compared with a recently proposed phase error estimation from separate reconstructions of even and odd echoes. RESULTS: Images obtained with the gradient insert have significantly lower distortions than it is the case with the whole body 30 mT/m, 200 T/m/s gradients of the same system. However, eddy currents of high spatial order must be properly characterized and corrected for in order to avoid a persistent 2D Nyquist ghost. Multi-position monitoring proves to be a robust method to measure the eddy currents and allows higher undersampling rates than the image-based approach. The proposed approximation of the eddy currents effect allows a significant acceleration of the high-order reconstruction by a separate processing of each spatial dimension. CONCLUSION: Strong gradients with adequate switching rates are highly beneficial for the quality of EPI provided that robust measures are taken to include the contribution of eddy currents to the image encoding.

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.

Filling the dead-time gap in zero echo time MRI: Principles compared.

PURPOSE: MRI of tissues with short coherence lifetimes T2 or T2* can be performed efficiently using zero echo time (ZTE) techniques such as algebraic ZTE, pointwise encoding time reduction with radial acquisition (PETRA), and water- and fat-suppressed proton projection MRI (WASPI). They share the principal challenge of recovering data in central k-space missed due to an initial radiofrequency dead time. The purpose of this study was to compare the three techniques directly, with a particular focus on their behavior in the presence of ultra-short-lived spins. METHODS: The most direct comparison was enabled by aligning acquisition and reconstruction strategies of the three techniques. Image quality and short- T2* performance were investigated using point spread functions, 3D simulations, and imaging of phantom and bone samples with short (<1 ms) and ultra-short (<100 µs) T2*. RESULTS: Algebraic ZTE offers favorable properties but is limited to k-space gaps up to approximately three Nyquist dwells. At larger gaps, PETRA enables robust imaging with little compromise in image quality, whereas WASPI may be prone to artifacts from ultra-short T2* species. CONCLUSION: For small k-space gaps (<4 dwells) and T2* much larger than the dead time, all techniques enable artifact-free short- T2* MRI. However, if these requirements are not fulfilled careful consideration is needed and PETRA will generally achieve better image quality. Magn Reson Med 79:2036-2045, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

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.

Separation of collagen-bound and porous bone-water longitudinal relaxation in mice using a segmented inversion recovery zero-echo-time sequence.

PURPOSE: Cortical bone mechanical properties are related to the collagen-bound water (CBW) and pore water (PW) components of cortical bone. The study evaluates the feasibility of zero-echo-time imaging in mice in vivo for longitudinal relaxation time (T1) measurements in cortical bone and separation of CBW and PW components. METHODS: Zero-echo-time data were acquired at 4.7 Tesla in six mice with 14 different inversion times (0-2,600 ms). Region-of-interest analysis was performed at level of femur diaphysis. The T1 of cortical bone and of CBW (T1cbw) and PW (T1pw) as well as the CBW fraction (cbwf) was computed using a mono-exponential and a bi-exponential fitting approach, respectively. The sum of the squared residuals (Res) to the fit was provided for both approaches. RESULTS: For the mono-exponential model, mean T1 ± standard deviation (SD) was 1,057 ± 160 ms. The bi-exponential approach provided a reliable separation of two different bone-water components, with a mean T1cbw of 213 ± 95 ms, T1pw of 2,152 ± 894 ms, and cbwf of 7.4 ± 2.7 %. Lower Res was obtained with bi-exponential approach (P < 0.001), and Res mean values ± SD were 0.016 ± 0.007 (bi-exponential) and 0.033 ± 0.016 (mono-exponential). CONCLUSION: Zero-echo-time imaging allows for longitudinal relaxation measurements of cortical bone in vivo in mice models, with a reliable separation of PW and CBW components using a bi-exponential curve fitting approach. Magn Reson Med 77:1909-1915, 2017. © 2016 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.

Correction of parallel transmission using concurrent RF and gradient field monitoring.

OBJECTIVES: The accuracy and precision of the parallel RF excitations are highly dependent on the spatial and temporal fidelity of the magnetic fields involved in spin excitation. The consistency between the nominal and effective fields is typically limited by the imperfections of the employed hardware existing both in the gradient system and the RF chain. In this work, we experimentally presented highly improved spatially tailored parallel excitations by turning the native hardware accuracy challenge into a measurement and control problem using an advanced field camera technology to fully correct parallel RF transmission experiment. MATERIALS AND METHODS: An array of NMR field probes is used to measure the multiple channel RF pulses and gradient waveforms recording the high power RF pulses simultaneously with low frequency gradient fields on equal time basis. The recorded waveforms were integrated in RF pulse design for gradient trajectory correction, time imperfection compensation and introduction of iterative RF pre-emphasis. RESULTS: Superior excitation accuracy was achieved. Two major applications were presented at 7 Tesla including multi-dimensional tailored RF pulses for spatially selective excitation and slice-selective spoke pulses for [Formula: see text] mitigation. CONCLUSION: Comprehensive field monitoring is a highly effective means of correcting for the field deviations during parallel transmit pulse design.

In vivo magnetization transfer imaging of the lung using a zero echo time sequence at 4.7 Tesla in mice: Initial experience.

PURPOSE: The aim of the present study was to assess the feasibility of magnetization transfer-prepared zero echo time (ZTE) imaging of the lung in vivo at high field strength [4.7 Tesla) T] in mice. METHODS: Eighteen C57BL/10 mice underwent MRI examinations in a 4.7T MR-scanner. A three-dimensional ZTE sequence was applied for lung imaging combined with a Gaussian MT-prepulse, which was followed by a train of 100 ZTE imaging readouts. Degree of MT was assessed by calculation of the magnetization transfer ratio (MTR). Direct saturation was estimated using Bloch equation simulations based on T1 measurements. The line-width of pulmonary tissue was estimated using T2* measurements. RESULTS: Experimental MTR-values of nonpulmonary tissues obtained with ZTE exhibited the characteristics known from conventional MT-sequences (skeletal muscle and liver: high values; fatty tissue: low values). Lung tissue demonstrated MTR-values in between fatty tissue and liver tissue. Direct saturation could be estimated by the Bloch simulation; however, an adequate approximation was only possible for T2 values nearly in the range of parenchymal organs. CONCLUSION: Pulmonary MT measurements at high field strength using the proposed MT-ZTE sequence is feasible; however, estimation of direct saturation remains challenging. Magn Reson Med 76:156-162, 2016. © 2015 Wiley Periodicals, Inc.

Separation of collagen-bound and porous bone water transverse relaxation in mice: proposal of a multi-step approach.

The separation and quantification of collagen-bound water (CBW) and pore water (PW) components of the cortical bone signal are important because of their different contribution to bone mechanical properties. Ultrashort TE (UTE) imaging can be used to exploit the transverse relaxation from CBW and PW, allowing their quantification. We tested, for the first time, the feasibility of UTE measurements in mice for the separation and quantification of the transverse relaxation of CBW and PW in vivo using three different approaches for T2 * determination. UTE sequences were acquired at 4.7 T in six mice with 10 different TEs (50-5000 µs). The transverse relaxation time T2 * of CBW (T2 *cbw ) and PW (T2 *pw ) and the CBW fraction (bwf) were computed using a mono-exponential (i), a standard bi-exponential (ii) and a new multi-step bi-exponential (iii) approach. Regions of interest were drawn at multiple levels of the femur and vertebral body cortical bone for each mouse. The sum of the normalized squared residuals (Res) and the homogeneity of variance were tested to compare the different methods. In the femur, approach (i) yielded mean T2 * ± standard deviation (SD) of 657 ± 234 µs. With approach (ii), T2 *cbw , T2 *pw and bwf were 464 ± 153 µs, 15 777 ± 10 864 µs and 57.6 ± 9.9%, respectively. For approach (iii), T2 *cbw , T2 *pw and bwf were 387 ± 108 µs, 7534 ± 2765 µs and 42.5 ± 6.2%, respectively. Similar values were obtained from vertebral bodies. Res with approach (ii) was lower than with the two other approaches (p < 0.007), but T2 *pw and bwf variance was lower with approach (iii) than with approach (ii) (p < 0.048). We demonstrated that the separation and quantification of cortical bone water components with UTE sequences is feasible in vivo in mouse models. The direct bi-exponential approach exhibited the best approximation to the measured signal curve with the lowest residuals; however, the newly proposed multi-step algorithm resulted in substantially lower variability of the computed parameters. Copyright © 2016 John Wiley & Sons, Ltd.

Magnetization transfer as a potential tool for the early detection of acute graft rejection after lung transplantation in mice.

PURPOSE: To investigate the value of magnetization transfer (MT) measurements for assessment of acute rejection (AR) in a murine lung transplantation model. MATERIALS AND METHODS: Thirty mice including 15 C57BL/10 mice serving as donors and 15 C57BL/6 mice as recipients were examined in this study. MT imaging datasets were acquired on a 4.7 Tesla small animal MR scanner using a three-dimensional zero echo time sequence with a Gaussian-shaped MT prepulse with 1000° or 3000° flip angle and systematic variation of off-resonance frequencies between 1000 and 15,000 Hz. After image acquisition, the images were qualitatively assessed, magnetization transfer ratio (MTR) values were calculated and lungs were taken for histologic examination including staining with hematoxylin/eosin, Masson's trichrome (collagen), and α-smooth muscle (fibroproliferative tissue) staining. RESULTS: Lung transplantation was successfully performed in all 15 mice. All animals showed AR characterized by the presence of interstitial mononuclear cell infiltrates. There were significant differences of MTR in lungs with and without AR (P = 0.007). With a flip angle of 1000°, the largest differences between the MTR of healthy lungs and lungs with AR were observed for an off-resonance frequency of 10,000 Hz (difference MTR 1.80%) and 15,000 Hz (1.91%) and with a flip angle of 3000° at off-resonance frequencies of 6000 Hz (1.37%) and 8000 Hz (1.70%). CONCLUSION: MT measurements may provide a tool for the quantitative assessment of AR. J. Magn. Reson. Imaging 2016;44:1091-1098.

Ultra-short echo-time magnetic resonance imaging distinguishes ischemia/reperfusion injury from acute rejection in a mouse lung transplantation model.

To investigate whether lung tissue characterization by ultra-short echo-time (UTE) magnetic resonance imaging (MRI) allows ischemia/reperfusion injury to be distinguished from acute rejection in a mouse lung transplantation model. After orthotopic lung transplantation with 6 mice receiving syngeneic (C57Bl/6) lung transplants and 6 mice receiving allogeneic (BALB/c) transplants, they underwent postoperative imaging using three-dimensional UTE-MRI (echo times TE = 50-5000 µs) and conventional T2-weighted fast spin-echo imaging. Quantitative T2* values of lung transplant parenchyma and spin density (SD) were compared by region-of-interest analysis. All samples underwent histological and immunohistochemical workup. In the allogeneic group, alveolar infiltration resulting from acute organ rejection was visualized in the UTE sequences. This was reflected by the quantitative measurements of SD and T2* values with higher values in the allogeneic group compared with the syngeneic group and nontransplanted lung at the first time point (24 h postoperative: Tx allogeneic group SD: 2133.9 ± 516; Tx syngeneic group SD: 1648.61 ± 271; P = 0.004; Tx allogeneic group T2*: 1710.16 ± 644 µs, Tx syngeneic group T2*: 577.16 ± 263 µs; P = <0.001). Changes caused by acute rejection after lung transplantation can be visualized and characterized using a UTE sequence due to different relaxation properties compared with both syngeneic lung transplants and normal lung tissue.