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Purpose The linear change of the water proton resonance frequency shift (PRFS) with temperature is used to monitor temperature change based on the temporal difference of image phase. Here, the effect of motion-induced susceptibility artifacts on the phase difference was studied in the context of mild radio frequency hyperthermia in the pelvis. Methods First, the respiratory-induced field variations were disentangled from digestive gas motion in the pelvis. The projection onto dipole fields (PDF) as well as the Laplacian boundary value (LBV) algorithm were applied on the phase difference data to eliminate motion-induced susceptibility artifacts. Both background field removal (BFR) algorithms were studied using simulations of susceptibility artifacts, a phantom heating experiment, and volunteer and patient heating data. Results Respiratory-induced field variations were negligible in the presence of the filled water bolus. Even though LBV and PDF showed comparable results for most data, LBV seemed more robust in our data sets. Some data sets suggested that PDF tends to overestimate the background field, thus removing phase attributed to temperature. The BFR methods even corrected for susceptibility variations induced by a subvoxel displacement of the phantom. The method yielded successful artifact correction in 2 out of 4 patient treatment data sets during the entire treatment duration of mild RF heating of cervical cancer. The heating pattern corresponded well with temperature probe data. Conclusion The application of background field removal methods in PRFS-based MR thermometry has great potential in various heating applications and body regions to reduce motion-induced susceptibility artifacts that originate outside the region of interest, while conserving temperature-induced PRFS. In addition, BFR automatically removes up to a first-order spatial B0 drift.

Purpose To propose a phase error correction scheme for monopolar time-interleaved multi-echo gradient echo water–fat imaging that allows accurate and robust complex-based quantification of the proton density fat fraction (PDFF). Methods A three-step phase correction scheme is proposed to address a) a phase term induced by echo misalignments that can be measured with a reference scan using reversed readout polarity, b) a phase term induced by the concomitant gradient field that can be predicted from the gradient waveforms, and c) a phase offset between time-interleaved echo trains. Simulations were carried out to characterize the concomitant gradient field-induced PDFF bias and the performance estimating the phase offset between time-interleaved echo trains. Phantom experiments and in vivo liver and thigh imaging were performed to study the relevance of each of the three phase correction steps on PDFF accuracy and robustness. Results The simulation, phantom, and in vivo results showed in agreement with the theory an echo time-dependent PDFF bias introduced by the three phase error sources. The proposed phase correction scheme was found to provide accurate PDFF estimation independent of the employed echo time combination. Conclusion Complex-based time-interleaved water–fat imaging was found to give accurate and robust PDFF measurements after applying the proposed phase error correction scheme. Magn Reson Med 78:984–996, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Purpose To assess the ability of dynamic contrast-enhanced myocardial perfusion MRI to measure extracellular volume (ECV) and to investigate the possibility of estimating capillary transit time heterogeneity (CTH) in patients after myocardial infarction and successful revascularization. Methods Twenty-four perfusion data sets were acquired on a 3 Tesla positron emission tomography (PET)/MRI scanner. Three perfusion models of different complexity were implemented in a hierarchical fashion with an Akaike information criterion being used to determine the number of fit parameters supported by the data. Results were compared sector-wise to ECV from an equilibrium T1 mapping method (modified look-locker inversion recovery (MOLLI)). Results ECV derived from the perfusion analysis correlated well with equilibrium measurements (R² = 0.76). Estimation of CTH was supported in 16% of sectors (mostly remote). Inclusion of a nonzero CTH parameter usually led to lower estimates of first-pass extraction and slightly higher estimates of blood volume and flow. Estimation of the capillary permeability-surface area product was feasible in 81% of sectors. Conclusion Transit time heterogeneity has a measurable effect on the kinetic analysis of myocardial perfusion MRI data, and Gd-DTPA extravasation in the myocardium is usually not flow-limited in infarct-related pathology. Measurement of myocardial ECV using perfusion imaging could provide a scan-time efficient alternative to methods based on T1 mapping. Magn Reson Med 77:2320–2330, 2017. © 2016 International Society for Magnetic Resonance in Medicine

PURPOSE Because of the intrinsic low signal-to-noise ratio in diffusion-weighted imaging (DWI), magnitude processing often causes an overestimation of the signal's amplitude. This results in low-estimation accuracy of diffusion models and reduced contrast because of a superposition of the image signal and the noise floor. We adopt a new phase correction (PC) technique that yields real valued diffusion data while maintaining a Gaussian noise distribution. METHODS We conduct simulations of the noise propagation in the echo-planar imaging reconstruction chain to determine the spatial noise correlation in the image. Using the correlation pattern, optimized filter kernels are derived to estimate the true phase of the signal in each voxel. Furthermore, we adopt an outlier detection technique to replace the real value by the magnitude in case of substantial signal loss resulting from incorrect PC. RESULTS The benefits of our method are demonstrated on Monte Carlo simulations, DWI data acquired from healthy volunteer experiments, estimated parameters of the diffusion kurtosis imaging model, and the model-free diffusion spectrum imaging technique. The improved PC approach significantly reduces the noise bias and only slightly increases the sensitivity to local phase variations. CONCLUSION PC can enhance the usefulness of higher b-values, allowing deeper insights into tissue microstructure. Magn Reson Med 77:559-570, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Purpose Diffusional kurtosis imaging (DKI) is an approach to characterizing the non-Gaussian fraction of water diffusion in biological tissue. However, DKI is highly susceptible to the low signal-to-noise ratio of diffusion-weighted images, causing low precision and a significant bias due to Rician noise distribution. Here, we evaluate precision and bias using weighted linear least squares fitting of different acquisition schemes including several multishell schemes, a diffusion spectrum imaging (DSI) scheme, as well as a compressed sensing reconstruction of undersampled DSI scheme. Methods Monte Carlo simulations were performed to study the three-dimensional distribution of the apparent kurtosis coefficient (AKC). Experimental data were acquired from one healthy volunteer with multiple repetitions, using the same acquisition schemes as for the simulations. Results The angular distribution of the bias and precision were very inhomogeneous. While axial kurtosis was significantly overestimated, radial kurtosis was underestimated. The precision of radial kurtosis was up to 10-fold lower than axial kurtosis. Conclusion The noise bias behavior of DKI is highly complex and can cause overestimation as well as underestimation of the AKC even within one voxel. The acquisition scheme with three shells, suggested by Poot et al, provided overall the best performance. Magn Reson Med 76:1684–1696, 2016. © 2016 International Society for Magnetic Resonance in Medicine

Purpose We characterized the performance of a novel hyperpolarized perfusion marker, α-trideuteromethyl[15N]glutamine, for direct comparison with a 13C-based hyperpolarized perfusion marker, [13C, 15N2]urea. Methods A hardware platform and pulse sequence for in vivo 15N experiments were established. Hyperpolarized solutions of α-trideuteromethyl[15N]glutamine and [13C, 15N2]urea were injected into healthy male Lewis rats. Kidney slice images were acquired using a single-shot spiral readout. Both compounds were compared to determine in vivo signal lifetime and tracer distribution. Mass spectrometry was performed to evaluate excretion of the compound. Results Compared with 13C-labeled urea, a significantly increased signal lifetime was observed. While the urea signal was gone after 90 s, decay of the glutamine compound was sufficiently slow to obtain a quantifiable signal, even after 5 min. The glutamine derivative showed strong localization in the kidneys with little background signal. Effective T1 of α-trideuteromethyl[15N]glutamine was approximately eight-fold higher than that of urea. Mass spectrometry results confirmed rapid excretion within the time scale of the measurement. Conclusion Hyperpolarized α-trideuteromethyl[15N]glutamine is a highly promising candidate for renal studies because of its long signal lifetime, strong localization and rapid excretion. Magn Reson Med 76:1900–1904, 2016. © 2016 International Society for Magnetic Resonance in Medicine

Purpose To propose and optimize diffusion-weighted stimulated echo acquisition mode (DW-STEAM) for measuring fat unsaturation in the presence of a strong water signal by suppressing the water signal based on a shorter T2 and higher diffusivity of water relative to fat. Methods A parameter study for point-resolved spectroscopy (PRESS) and STEAM using oil phantoms was performed and correlated with gas chromatography (GC). Simulations of muscle tissue signal behavior using DW-STEAM and long–echo time (TE) PRESS and a parameter optimization for DW-STEAM were conducted. DW-STEAM and long-TE PRESS were applied in the gastrocnemius muscles of nine healthy subjects. Results STEAM with TE and mixing time (TM) up to 45 ms exhibited R2 correlations above 0.98 with GC and little T2-weighting and J-modulation for the quantified olefinic/methylene peak ratio. The optimal parameters for muscle tissue using DW-STEAM were b-value = 1800 s/mm2, TE = 33 ms, TM = 30 ms, and repetition time = 2300 ms. In vivo measured mean olefinic signal-to-noise ratios were 72 and 40, mean apparent olefinic water fractions were 0.19 and 0.11 for DW-STEAM and long-TE PRESS, respectively. Conclusion Optimized DW-STEAM MR spectroscopy is superior to long-TE PRESS for measuring fat unsaturation, if a strong water peak prevents the olefinic fat signal's quantification at shorter TEs and water's tissue specific ADC is substantially higher than fat. Magn Reson Med 75:32–41, 2016. © 2015 Wiley Periodicals, Inc.

The metabolism of acetate in the heart resembles fatty acid metabolism, which is altered in several diseases like ischemia, diabetes mellitus, and heart failure. A signal-to-noise ratio (SNR) optimized imaging framework for in vivo measurements of hyperpolarized [1-(13) C]acetate and its metabolic product [1-(13) C]acetylcarnitine (ALCAR) in rats at 3 Tesla (T) is presented in this work.A spectrospatial pulse was combined with IDEAL encoding to acquire well separated metabolic maps. The influence of dobutamine induced stress onto this metabolic system was investigated in spectra and in an imaging study.An increase of the ALCAR to acetate ratio with dobutamine induced stress was shown in slice selective spectra containing the rat hearts and skeletal muscles. Metabolic maps of acetate and ALCAR were acquired with an acceptable SNR. Quantification of the apparent conversion rate showed stable results in the heart in a time-window of 30 s. The effect of dobutamine on the signal intensities was shown to originatemainly from skeletal than cardiac muscles.The acetate activation was mapped with hyperpolarized [1-(13) C]acetate in a clinical 3T system. Quantitative measurement of the activity was possible in the heart, indicating that dobutamine induced stress does not improve the ALCAR SNR in the heart.

Purpose Because pH plays a crucial role in several diseases, it is desirable to measure pH in vivo noninvasively and in a spatially localized manner. Spatial maps of pH were quantified in vitro, with a focus on method-based errors, and applied in vivo. Methods In vitro and in vivo 13C mapping were performed for various flip angles for bicarbonate (BiC) and CO2 with spectral-spatial excitation and spiral readout in healthy Lewis rats in five slices. Acute subcutaneous sterile inflammation was induced with Concanavalin A in the right leg of Buffalo rats. pH and proton images were measured 2 h after induction. Results After optimizing the signal to noise ratio of the hyperpolarized 13C-bicarbonate, error estimation of the spectral-spatial excited spectrum reveals that the method covers the biologically relevant pH range of 6 to 8 with low pH error (< 0.2). Quantification of pH maps shows negligible impact of the residual bicarbonate signal. pH maps reflect the induction of acute metabolic alkalosis. Inflamed, infected regions exhibit lower pH. Conclusion Hyperpolarized 13C-bicarbonate pH mapping was shown to be sensitive in the biologically relevant pH range. The mapping of pH was applied to healthy in vivo organs and interpreted within inflammation and acute metabolic alkalosis models. Magn Reson Med 73:2274–2282, 2015. © 2014 Wiley Periodicals, Inc.

To design a preparation module for vessel signal suppression in MR neurography of the extremities, which causes minimal attenuation of nerve signal and is highly insensitive to eddy currents and motion.The orthogonally combined motion- and diffusion-sensitized driven equilibrium (OC-MDSDE) preparation was proposed, based on the improved motion- and diffusion-sensitized driven equilibrium methods (iMSDE and FC-DSDE, respectively), with specific gradient design and orientation. OC-MDSDE was desensitized against eddy currents using appropriately designed gradient prepulses. The motion sensitivity and vessel signal suppression capability of OC-MDSDE and its components were assessed in vivo in the knee using 3D turbo spin echo (TSE). Nerve-to-vessel signal ratios were measured for iMSDE and OC-MDSDE in 7 subjects.iMSDE was shown to be highly sensitive to motion with increasing flow sensitization. FC-DSDE showed robustness against motion, but resulted in strong nerve signal loss with diffusion gradients oriented parallel to the nerve. OC-MDSDE showed superior vessel suppression compared to iMSDE and FC-DSDE and maintained high nerve signal. Mean nerve-to-vessel signal ratios in 7 subjects were 0.40 ± 0.17 for iMSDE and 0.63 ± 0.37 for OC-MDSDE.OC-MDSDE combined with 3D TSE in the extremities allows high-near-isotropic-resolution imaging of peripheral nerves with reduced vessel contamination and high nerve signal. Magn Reson Med 79:407-415, 2018. © 2017 Wiley Periodicals, Inc.

To propose a phase error correction scheme for monopolar time-interleaved multi-echo gradient echo water-fat imaging that allows accurate and robust complex-based quantification of the proton density fat fraction (PDFF).A three-step phase correction scheme is proposed to address a) a phase term induced by echo misalignments that can be measured with a reference scan using reversed readout polarity, b) a phase term induced by the concomitant gradient field that can be predicted from the gradient waveforms, and c) a phase offset between time-interleaved echo trains. Simulations were carried out to characterize the concomitant gradient field-induced PDFF bias and the performance estimating the phase offset between time-interleaved echo trains. Phantom experiments and in vivo liver and thigh imaging were performed to study the relevance of each of the three phase correction steps on PDFF accuracy and robustness.The simulation, phantom, and in vivo results showed in agreement with the theory an echo time-dependent PDFF bias introduced by the three phase error sources. The proposed phase correction scheme was found to provide accurate PDFF estimation independent of the employed echo time combination.Complex-based time-interleaved water-fat imaging was found to give accurate and robust PDFF measurements after applying the proposed phase error correction scheme. Magn Reson Med 78:984-996, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

To assess the ability of dynamic contrast-enhanced myocardial perfusion MRI to measure extracellular volume (ECV) and to investigate the possibility of estimating capillary transit time heterogeneity (CTH) in patients after myocardial infarction and successful revascularization.Twenty-four perfusion data sets were acquired on a 3 Tesla positron emission tomography (PET)/MRI scanner. Three perfusion models of different complexity were implemented in a hierarchical fashion with an Akaike information criterion being used to determine the number of fit parameters supported by the data. Results were compared sector-wise to ECV from an equilibrium TECV derived from the perfusion analysis correlated well with equilibrium measurements (R² = 0.76). Estimation of CTH was supported in 16% of sectors (mostly remote). Inclusion of a nonzero CTH parameter usually led to lower estimates of first-pass extraction and slightly higher estimates of blood volume and flow. Estimation of the capillary permeability-surface area product was feasible in 81% of sectors.Transit time heterogeneity has a measurable effect on the kinetic analysis of myocardial perfusion MRI data, and Gd-DTPA extravasation in the myocardium is usually not flow-limited in infarct-related pathology. Measurement of myocardial ECV using perfusion imaging could provide a scan-time efficient alternative to methods based on T

Within the last decade hyperpolarized [1-13C] pyruvate chemical-shift imaging has demonstrated impressive potential for metabolic MR imaging for a wide range of applications in oncology, cardiology, and neurology. In this work, a highly efficient pulse sequence is described for time-resolved, multislice chemical shift imaging of the injected substrate and obtained downstream metabolites. Using spectral-spatial excitation in combination with single-shot spiral data acquisition, the overall encoding is evenly distributed between excitation and signal reception, allowing the encoding of one full two-dimensional metabolite image per excitation. The signal-to-noise ratio can be flexibly adjusted and optimized using lower flip angles for the pyruvate substrate and larger ones for the downstream metabolites. Selectively adjusting the excitation of the down-stream metabolites to 90° leads to a so-called "saturation-recovery" scheme with the detected signal content being determined by forward conversion of the available pyruvate. In case of repetitive excitations, the polarization is preserved using smaller flip angles for pyruvate. Metabolic exchange rates are determined spatially resolved from the metabolite images using a simplified two-site exchange model. This novel contrast is an important step toward more quantitative metabolic imaging. Goal of this work was to derive, analyze, and implement this "saturation-recovery metabolic exchange rate imaging" and demonstrate its capabilities in four rats bearing subcutaneous tumors.

We characterized the performance of a novel hyperpolarized perfusion marker, α-trideuteromethyl[15N]glutamine, for direct comparison with a 13C-based hyperpolarized perfusion marker, [13C, 15N2]urea.A hardware platform and pulse sequence for in vivo 15N experiments were established. Hyperpolarized solutions of α-trideuteromethyl[15N]glutamine and [13C, 15N2]urea were injected into healthy male Lewis rats. Kidney slice images were acquired using a single-shot spiral readout. Both compounds were compared to determine in vivo signal lifetime and tracer distribution. Mass spectrometry was performed to evaluate excretion of the compound.Compared with 13C-labeled urea, a significantly increased signal lifetime was observed. While the urea signal was gone after 90 s, decay of the glutamine compound was sufficiently slow to obtain a quantifiable signal, even after 5 min. The glutamine derivative showed strong localization in the kidneys with little background signal. Effective T1 of α-trideuteromethyl[15N]glutamine was approximately eight-fold higher than that of urea. Mass spectrometry results confirmed rapid excretion within the time scale of the measurement.Hyperpolarized α-trideuteromethyl[15N]glutamine is a highly promising candidate for renal studies because of its long signal lifetime, strong localization and rapid excretion. Magn Reson Med 76:1900-1904, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Diffusional kurtosis imaging (DKI) is an approach to characterizing the non-Gaussian fraction of water diffusion in biological tissue. However, DKI is highly susceptible to the low signal-to-noise ratio of diffusion-weighted images, causing low precision and a significant bias due to Rician noise distribution. Here, we evaluate precision and bias using weighted linear least squares fitting of different acquisition schemes including several multishell schemes, a diffusion spectrum imaging (DSI) scheme, as well as a compressed sensing reconstruction of undersampled DSI scheme.Monte Carlo simulations were performed to study the three-dimensional distribution of the apparent kurtosis coefficient (AKC). Experimental data were acquired from one healthy volunteer with multiple repetitions, using the same acquisition schemes as for the simulations.The angular distribution of the bias and precision were very inhomogeneous. While axial kurtosis was significantly overestimated, radial kurtosis was underestimated. The precision of radial kurtosis was up to 10-fold lower than axial kurtosis.The noise bias behavior of DKI is highly complex and can cause overestimation as well as underestimation of the AKC even within one voxel. The acquisition scheme with three shells, suggested by Poot et al, provided overall the best performance. Magn Reson Med 76:1684-1696, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

This work presents a method that allows for the assessment of 3D murine myocardial motion in vivo at microscopic resolution. Phase-contrast (PC) magnetic resonance imaging (MRI) at 17.6 T was applied to map myocardial motion in healthy mice along three gradient directions. High-resolution velocity maps were acquired at three different levels in the murine myocardium with an in-plane resolution of 98 μm, a slice thickness of 0.6 mm, and a temporal resolution of 6 ms. The applied PC-MRI method was validated with phantom experiments that confirmed the correctness of the method with deviations of

Myocardial fiber structure can be determined with diffusion-weighted (DW) MRI as well as with high-resolution T*2 imaging. The purpose of the present study was twofold: to provide a more quantitative description of T*2-based myocardial fiber contrast, and to compare the T*2-based fiber structure with high-resolution (78 μm in-plane, 1-mm slice thickness) DW images of the isolated rat heart at 11.75 T. This study demonstrates that the static dephasing regime is responsible for visualization of myocardial microstructure, and that the dynamic dephasing regime can be neglected. In comparison with DW experiments, T*2 mapping and DW images yield almost equivalent information on myocardial fiber structure. Magn Reson Med 50:1144–1150, 2003. © 2003 Wiley-Liss, Inc.

The investigation of flow behavior in coronary arteries is of great importance for an understanding of heart failure and heart regulation mechanisms. The purpose of the present study was to demonstrate that flow velocity can be quantified in the coronary arteries of the isolated rat heart with high-resolution phase contrast MRI. A phase contrast cine-FLASH imaging sequence was used for flow quantification with an in-plane resolution of 70 microm and a slice thickness of 500 microm. With time-resolved measurements, coronary flow over the heart cycle was analyzed. Furthermore, the flow behavior in coronary stenosis was investigated and the degree of stenosis was quantified with MR phase contrast imaging. To achieve the required spatial resolution and a satisfactory signal-to-noise ratio, the experiments were performed at 11.75 T.

The analysis of myocardial microstructure in vivo is important for the determination of myocardial contractility and function. The purpose of the present study was to demonstrate that high-resolution T imaging has the potential to visualize the microstructure of beating, isolated rat hearts. To perform T imaging, a multiple gradient-echo sequence was implemented on an 11.75 Tesla microscopy system. An in-plane resolution of 78 μm and a slice thickness of 250 μm were achieved in 24 min. In comparison to histological sections, the T maps showed an excellent spatial correspondence to the myocardial fiber structure. To demonstrate the utility of this technique, morphologic alterations in myocardial microstructure were investigated in hearts with chronic myocardial infarction. Scar tissue and the extent of the infarcted region were clearly visualized and quantified using high-resolution T imaging. Magn Reson Med 49:371–375, 2003. © 2003 Wiley-Liss, Inc.

Myocardial motion of healthy mice and mice with myocardial infarction was assessed in vivo by phase contrast (PC) cine MRI. The imaging module was a segmented fast low angle shot (FLASH) sequence with velocity compensation in all three gradient directions. To accomplish additional motion encoding, the spin phase was prepared using bipolar gradient pulses, which resulted in a linear dependence between the voxel velocity and spin phase. This method provided accurate quantification of the velocity magnitude and direction of the murine myocardium at a spatial resolution of 234 μm and a temporal resolution of about 10 ms. The acquisition was EKG-gated and the mice were anesthetized by inhalation of 1.5–4.0 vol.% isoflurane at 1.5 l/min oxygen flow. To validate the MRI measurements, an experiment with a calibrated rotating phantom was performed. Deviations between MR velocity measurements and optical assessment by a light detector were lower than 1.6%. During our study, myocardial motion velocities between 0.4 cm/s and 1.7 cm/s were determined for the healthy murine myocardium across the heart cycle. Areas with myocardial infarction were clearly segmented and showed a motion velocity which was significantly reduced. In conclusion, the method is an accurate technique for the assessment of murine myocardial motion in vivo. Magn Reson Med 49:315–321, 2003. © 2003 Wiley-Liss, Inc.

The aim of this pilot study in humans was to investigate the effect of an intravascular contrast agent (CA) on relaxation rate in myocardium (R(1,myo)) in the steady state. The dependence of R(1,myo) on R(1,blood) was characterized and compared with a theoretical model which allowed determination of the intra- extracapillary water proton exchange frequency (f = 0.48 s(-1)) and the intracapillary blood volume (RBV = 12.9 %). A linear response range of DeltaR(1,myo) on DeltaR(1,blood) was estimated which in future studies will allow the determination of RBV with intravascular CA.

Peripheral nerve stimulation limits the use of whole-body gradient systems capable of slew rates > 80 T/m/s and gradient strengths > 25 mT/m. The stimulation threshold depends mainly on the amplitude of the induced electric field in the patient's body, and thus can be influenced by changing the total magnetic flux of the gradient coil. A gradient system was built which allows continuous variation of the field characteristics in order to permit the use of full gradient performance without stimulation (slew rate 190–210 T/m/s, Gmax 32–40 mT/m). The system consists of a modular six-channel gradient coil designed with a modified target field method, two three-channel amplifiers, and a six-channel gradient controller. It is demonstrated that two coils on one gradient axis can be driven by two amplifiers in parallel, without significant changes in image quality. Scaling of the field properties and stimulation threshold according to the current polarity and ratio of both coil sets was verified in both phantom and volunteer studies. Magn Reson Med 47:800–808, 2002. © 2002 Wiley-Liss, Inc.

MR-CAT (combined acquisition technique), a modular hybrid imaging concept, was introduced recently. In this article it is demonstrated that the CAT principles can be applied to form a versatile combination of spin and gradient echoes for abdominal imaging. This CAT approach, which essentially integrates RARE and EPI modules in a sequential fashion, was used to implement a set of segmented and single-shot RARE/EPI-CAT imaging techniques. CAT was used in in vivo studies to perform high-resolution abdominal imaging in five healthy subjects. The results demonstrate the feasibility of abdominal imaging using the proposed CAT approach and the potential of this technique to reduce imaging time while preserving image quality.

To propose and optimize diffusion-weighted stimulated echo acquisition mode (DW-STEAM) for measuring fat unsaturation in the presence of a strong water signal by suppressing the water signal based on a shorter T2 and higher diffusivity of water relative to fat.A parameter study for point-resolved spectroscopy (PRESS) and STEAM using oil phantoms was performed and correlated with gas chromatography (GC). Simulations of muscle tissue signal behavior using DW-STEAM and long-echo time (TE) PRESS and a parameter optimization for DW-STEAM were conducted. DW-STEAM and long-TE PRESS were applied in the gastrocnemius muscles of nine healthy subjects.STEAM with TE and mixing time (TM) up to 45 ms exhibited R(2) correlations above 0.98 with GC and little T2 -weighting and J-modulation for the quantified olefinic/methylene peak ratio. The optimal parameters for muscle tissue using DW-STEAM were b-value = 1800 s/mm(2), TE = 33 ms, TM = 30 ms, and repetition time = 2300 ms. In vivo measured mean olefinic signal-to-noise ratios were 72 and 40, mean apparent olefinic water fractions were 0.19 and 0.11 for DW-STEAM and long-TE PRESS, respectively.Optimized DW-STEAM MR spectroscopy is superior to long-TE PRESS for measuring fat unsaturation, if a strong water peak prevents the olefinic fat signal's quantification at shorter TEs and water's tissue specific ADC is substantially higher than fat.

Recently a self-calibrating SMASH technique, AUTO-SMASH, was described. This technique is based on PPA with RF coil arrays using auto-calibration signals. In AUTO-SMASH, important coil sensitivity information required for successful SMASH reconstruction is obtained during the actual scan using the correlation between undersampled SMASH signal data and additionally sampled calibration signals with appropriate offsets in k-space. However, AUTO-SMASH is susceptible to noise in the acquired data and to imperfect spatial harmonic generation in the underlying coil array. In this work, a new modified type of internal sensitivity calibration, VD-AUTO-SMASH, is proposed. This method uses a VD k-space sampling approach and shows the ability to improve the image quality without significantly increasing the total scan time. This new k-space adapted calibration approach is based on a k-space-dependent density function. In this scheme, fully sampled low-spatial frequency data are acquired up to a given cutoff-spatial frequency. Above this frequency, only sparse SMASH-type sampling is performed. On top of the VD approach, advanced fitting routines, which allow an improved extraction of coil-weighting factors in the presence of noise, are proposed. It is shown in simulations and in vivo cardiac images that the VD approach significantly increases the potential and flexibility of rapid imaging with AUTO-SMASH.

In this study the performance of FLASH imaging with selective inversion preparation for functional perfusion studies was investigated. In addition to the absolute quantification of perfusion by measurement of the longitudinal relaxation times with global (T1glob) and selective (T1sel) inversion, the measurement of absolute (BASE) and relative (FAIR) perfusion increases by subtraction of appropriately weighted images was also considered. The subject averages of absolute perfusion obtained by the quantitative method were 70.7 ± 4.0 ml/100g/min in gray matter, 10.2 ± 3.4 ml/100g/min in white matter, and 89.0 ± 3.1 ml/100g/min in visual cortex. These values, as well as the average increase of perfusion due to visual stimulation (44.4 ± 3.7 ml/100g/min), agree well with respective data reported by PET and other MRI studies. However, for individual subjects the standard deviations over single ROIs inside the visual cortex lay around 100% which prevented the detection of significant activation. BASE and FAIR, on the other hand, were able to detect significant activation in single subjects. The measured average perfusion increases were 51.7 ± 6.6 ml/100g/min and 56.5 ± 13.8%, respectively. Magn Reson Med 46:172–182, 2001. © 2001 Wiley-Liss, Inc.

In this study a novel partially parallel acquisition method is presented, which can be used to accelerate image acquisition using an RF coil array for spatial encoding. In this technique, Parallel Imaging with Localized Sensitivities (PILS), it is assumed that the individual coils in the array have localized sensitivity patterns, in that their sensitivity is restricted to a finite region of space. Within the PILS model, a detailed, highly accurate RF field map is not needed prior to reconstruction. In PILS, each coil in the array is fully characterized by only two parameters: the center of coil's sensitive region in the FOV and the width of the sensitive region around this center. In this study, it is demonstrated that the incorporation of these coil parameters into a localized Fourier transform allows reconstruction of full FOV images in each of the component coils from data sets acquired with a reduced number of phase encoding steps compared to conventional imaging techniques. After the introduction of the PILS technique, primary focus is given to issues related to the practical implementation of PILS, including coil parameter determination and the SNR and artifact power in the resulting images. Finally, in vivo PILS images are shown which demonstrate the utility of the technique.

Measurement of regional blood volume (RBV) in the myocardium in vivo is important for the assessment of tissue viability and function. The method in this work is based on the acquisition of a T(1) map before and after intravascular contrast agent application. It is known that this method is influenced by perfusion that causes an overestimation of RBV values. In order to solve this problem, the new method is proposed which acquires T(1) maps with slice selective inversion pulses. Due to blood flow nonexcited spins enter the detection slice, which leads to an acceleration of the relaxation time. A model that divides tissue into two compartments is adapted to slice selective inversion in order to derive a simple expression for perfusion-corrected RBV. The aim of the study is to demonstrate the feasibility and accuracy of this technique for quantification of RBV in rat myocardium in vivo. RBV maps were obtained for five rats, and the reproducibility was determined by repeating the experiment several times. A mean RBV value of 12.8 +/- 0.7% (v/v) over all animals was obtained in the myocardium. The results were compared with RBV maps obtained with perfusion-sensitive RBV imaging in the same five rats and with first-pass RBV studies. In order to demonstrate the strength of the new method the vasodilator adenosine was administered and alterations in microcirculation were imaged. Magn Reson Med 42:500-506, 1999.

The purpose of this work was to develop high-resolution cardiac magnetic resonance imaging techniques for the in vivo mouse model for quantification of myocardial function and mass. Eight male mice were investigated on a 7-Tesla MRI scanner. High-quality images in multiple short axis slices (in-plane resolution 117 microm2, slice thickness 1 mm) were acquired with an ECG-gated cine sequence. Left ventricular end-diastolic and end-systolic volumes and mass were calculated from segmented slice volumes. There was precise agreement of left ventricular mass determined ex vivo and by MRI. Intraobserver (5%) and interobserver (5%) variability of in vivo MR measurements were low.

The purpose of this study was to measure the spatially varying 31P MR signals in global and regional ischemic injury in the isolated, perfused rat heart. Chronic myocardial infarcts were induced by occluding the left anterior descending coronary artery eight weeks before the MR examination. The effects of acute global low-flow ischemia were observed by reducing the perfusate flow. Chemical shift imaging (CSI) with three spatial dimensions was used to obtain 31P spectra in 54-microl voxels. Multislice 1H imaging with magnetization transfer contrast enhancement provided anatomical information. In normal hearts (n = 8), a homogeneous distribution of high-energy phosphate metabolites (HEP) was found. In chronic myocardial infarction (n = 6), scar tissue contained negligible amounts of HEP, but their distribution in residual myocardium was uniform. The size of the infarcted area could be measured from the metabolic images; the correlation of infarct sizes determined by histology and 31P MR CSI was excellent (P < 0.006). In global low-flow ischemia (n = 8), changes of HEP showed substantial regional heterogeneity. Three-dimensional 31P MR CSI should yield new insights into the regionally distinct metabolic consequences of various forms of myocardial injury.

A radial BURST approach combining BURST excitations with projection reconstruction (PR) gradients for excitation and acquisition is introduced. With the application of PR gradients during excitation, the applied RF energy is distributed more homogeneously across the sample than in the initial BURST approach. Computer simulations of the radial BURST excitation scheme are presented and experimentally verified. Actual radial BURST implementation acquiring a 64 x 64 radial BURST image in 45 ms is reported. Extensions of the radial BURST imaging technique placing a magnetization preparation experiment in front of the whole imaging sequence are also described. Furthermore, the feasibility of combining radial BURST with a multishot approach is demonstrated.

A technique for noninvasive quantitative magnetic resonance imaging of perfusion is presented. It relies on using endogenous water as a freely diffusible tracer. Tissue water proton spins are magnetically labeled by slice-selective inversion, and longitudinal relaxation within the slice is detected using a fast gradient echo magnetic resonance imaging technique. Due to blood flow, nonexcited spins are washed into the slice resulting in an acceleration of the longitudinal relaxation process. Incorporating this phenomenon into the Bloch equation yields an expression that allows quantification of perfusion on the basis of a slice-selective and a nonselective inversion recovery experiment. Based on this technique, quantitative parameter maps of the regional cerebral blood flow (rCBF) were obtained from eight rats. Evaluation of regions of interest within the cerebral hemispheres yielded an average rCBF value of 104 ± 21 ml/min/100 g, which increased to 219 ± 30 ml/min/100 g during hypercapnia. The measured rCBF values are in good agreement with previously reported literature values.

In cancer research, tumor spheroids are a well established system to study tumor metabolism resembling the situation in vivo more closely cell monolayers. Spherical aggregates of malignant melanoma cells (MV3) and their invasion into rat brain aggregates have been investigated by quantitative NMR microscopy. Relaxation times (T1, T2) and diffusion parameter images were acquired with an in-plane resolution of 14 x 14 microns2. The authors were able to demonstrate that the morphology of the spheroids can be visualized on these NMR maps. The contrast was mainly manifested in relaxation maps, where average relaxation times T1 = 1.94 +/- 0.17 s and T2 = 42.8 +/- 6.3 ms were obtained for proliferating cells, and T1 = 2.49 +/- 0.31 s and T2 = 104.3 +/- 29.4 ms for the necrobiotic center. The mean diffusion coefficients were 0.59 +/- 0.12 micron2/ms and 0.85 +/- 0.14 micron2/ms, respectively. The authors could follow the dynamic process of tumor cell invasion in the investigated co-culture system. Knowledge about tumor cell migration and tumor cell invasion is essential for the understanding of cancer and its therapy. Quantitative NMR microscopy can study this dynamic process noninvasively and therefore may help to assess the influence of therapy on the micromilieu of these spheroids.

A number of techniques that recently have been used for fast NMR-imaging are based on a hybrid sequence of echo planar imaging (EPI) and FLASH imaging: after each NMR excitation several k-space lines are measured. The complete k-space is covered by performance of several excitations. It has been observed that there is usually an optimal hybrid sequence that maximizes the signal-to-noise ratio. In this work, a method is presented that allows a determination of the optimal sequence as a function of the relaxation times T1 and T2*.

Within the last decade hyperpolarized [1-13C] pyruvate chemical-shift imaging has demonstrated impressive potential for metabolic MR imaging for a wide range of applications in oncology, cardiology, and neurology. In this work, a highly efficient pulse sequence is described for time-resolved, multislice chemical shift imaging of the injected substrate and obtained downstream metabolites. Using spectral-spatial excitation in combination with single-shot spiral data acquisition, the overall encoding is evenly distributed between excitation and signal reception, allowing the encoding of one full two-dimensional metabolite image per excitation. The signal-to-noise ratio can be flexibly adjusted and optimized using lower flip angles for the pyruvate substrate and larger ones for the downstream metabolites. Selectively adjusting the excitation of the down-stream metabolites to 90° leads to a so-called "saturation-recovery" scheme with the detected signal content being determined by forward conversion of the available pyruvate. In case of repetitive excitations, the polarization is preserved using smaller flip angles for pyruvate. Metabolic exchange rates are determined spatially resolved from the metabolite images using a simplified two-site exchange model. This novel contrast is an important step toward more quantitative metabolic imaging. Goal of this work was to derive, analyze, and implement this "saturation-recovery metabolic exchange rate imaging" and demonstrate its capabilities in four rats bearing subcutaneous tumors.

Metabolic imaging with hyperpolarized [1-(13)C]pyruvate offers the unique opportunity for a minimally invasive detection of cellular metabolism. Efficient and robust acquisition and reconstruction techniques are required for capturing the wealth of information present for the limited duration of the hyperpolarized state (~1 min). In this study, the Dixon/IDEAL type of water-fat separation is expanded toward spectroscopic imaging of [1-(13) C]pyruvate and its down-stream metabolites. For this purpose, the spectral-spatial encoding is based on single-shot spiral image encoding and echo-time shifting in between excitations for the chemical-shift encoding. In addition, also a free-induction decay spectrum is acquired and the obtained chemical-shift prior knowledge is efficiently used in the reconstruction. The spectral-spatial reconstruction problem is found to efficiently separate into a chemical-shift inversion followed by a spatial reconstruction. The method is successfully demonstrated for dynamic, multislice [1-(13)C]pyruvate metabolic MR imaging in phantom and in vivo rat experiments.

We describe the speeding up of snapshot FLASH MRI by placing a slice selection experiment before the whole imaging sequence. In conventional snapshot FLASH slice selection is made in every projection, thus consuming a great deal of experimental time. This problem can be overcome by applying only one slice-selective procedure before starting the imaging. The idea is to make a selective saturation of the outer volume and to interrogate the unaffected slice by a train of rapid, hard, low-angle pulses. By this new method the measuring times of snapshot FLASH can be further reduced. © 1992 Academic Press, Inc.

An intuitive approach is presented for assessment of the TrueFISP signal behavior in the transient phase and the steady state, based on geometrical considerations in combination with the Bloch equations. Short formulations are derived for the zenith and phase angle determining the direction of the magnetization vector for which a smooth monoexponential decay is obtained even at considerable off-resonance frequencies, thus compactly defining the target of various preparation schemes proposed in literature. A pictorial explanation is provided to illustrate how the interplay between RF excitation and relaxation governs the TrueFISP transient phase and steady state. Closed form expressions are developed that describe the signal evolution, accounting for the influence of T1, T2, flip angle, and resonance frequency offset in agreement with recently published studies. These results are obtained directly from basic assumptions, without the need for abstract mathematical treatment or further approximations. The validity of the conceptual framework and the analytical description is verified by simulations based on the Bloch equations as well as with MR phantom experiments. The theory may be used for contrast calculations and has the potential to facilitate improved parameter quantification with magnetization prepared TrueFISP experiments accounting for off-resonance effects. Magn Reson Med, 2006. © 2005 Wiley-Liss, Inc.

The absolute perfusion and the intracapillary or regional blood volume (RBV) in murine myocardium were assessed in vivo by spin labeling magnetic resonance imaging. Pixel-based perfusion and RBV maps were calculated at a pixel resolution of 469 × 469 μm and a slice thickness of 2 mm. The T1 imaging module was a segmented inversion recovery snapshot fast low angle shot sequence with velocity compensation in all three gradient directions. The group average myocardial perfusion at baseline was determined to be 701 ± 53 mL (100 g · min)−1 for anesthesia with isoflurane (N = 11) at a mean heart rate (HR) of 455 ± 10 beats per minute (bpm). This value is in good agreement with perfusion values determined by invasive microspheres examinations. For i.v. administration of the anesthetic Propofol, the baseline perfusion decreased to 383 ± 40 mL (100 g · min)−1 (N = 17, P < 0.05 versus. isoflurane) at a mean heart rate of 261 ± 13 bpm (P < 0.05 versus isoflurane). In addition, six mice with myocardial infarction were studied under isoflurane anesthesia (HR 397 ± 7 bpm). The perfusion maps showed a clear decrease of the perfusion in the infarcted area. The perfusion in the remote myocardium decreased significantly to 476 ± 81 mL (100 g · min)−1 (P < 0.05 versus sham). Regarding the regional blood volume, a mean value of 11.8 ± 0.8 vol % was determined for healthy murine myocardium under anesthesia with Propofol (N = 4, HR 233 ± 17 bpm). In total, the presented techniques provide noninvasive in vivo assessment of the perfusion and the regional blood volume in the murine myocardium for the first time and seem to be promising tools for the characterization of mouse models in cardiovascular research. Magn Reson Med 53:584–592, 2005. © 2005 Wiley-Liss, Inc.

Measurements of the transverse relaxation time T2 are usually conducted with the Carr Purcell Meiboom Gill (CPMG) pulse sequence, which causes T2-weighted magnetization. Diffusion effects are a common source of error in measurements of this kind, because the incoherent motion of spins in external magnetic field gradients distorts T2 weighting of the transverse magnetization. As a result, inaccurate T2-values are obtained. In this work, we present a method which completely compensates for the effect of diffusion.

Myocardial fiber structure can be determined with diffusion-weighted (DW) MRI as well as with high-resolution T*(2) imaging. The purpose of the present study was twofold: to provide a more quantitative description of T*(2)-based myocardial fiber contrast, and to compare the T*(2)-based fiber structure with high-resolution (78 microm in-plane, 1-mm slice thickness) DW images of the isolated rat heart at 11.75 T. This study demonstrates that the static dephasing regime is responsible for visualization of myocardial microstructure, and that the dynamic dephasing regime can be neglected. In comparison with DW experiments, T*(2) mapping and DW images yield almost equivalent information on myocardial fiber structure.

The investigation of flow behavior in coronary arteries is of great importance for an understanding of heart failure and heart regulation mechanisms. The purpose of the present study was to demonstrate that flow velocity can be quantified in the coronary arteries of the isolated rat heart with high-resolution phase contrast MRI. A phase contrast cine-FLASH imaging sequence was used for flow quantification with an in-plane resolution of 70 microm and a slice thickness of 500 microm. With time-resolved measurements, coronary flow over the heart cycle was analyzed. Furthermore, the flow behavior in coronary stenosis was investigated and the degree of stenosis was quantified with MR phase contrast imaging. To achieve the required spatial resolution and a satisfactory signal-to-noise ratio, the experiments were performed at 11.75 T.

Genetically engineered mouse models provide enormous potential for investigation of the underlying mechanisms of atherosclerotic disease, but noninvasive imaging methods for analysis of atherosclerosis in mice are currently limited. This study aimed to demonstrate the feasibility of MRI to noninvasively visualize atherosclerotic plaques in the thoracic aorta in mice deficient in apolipoprotein-E, who develop atherosclerotic lesions similar to those observed in humans. To freeze motion, MR data acquisition was both ECG- and respiratory-gated. T(1)-weighted MR images were acquired with TR/TE approximately 1000/10 ms. Spatial image resolution was 49 x 98 x 300 micro m(3). MRI revealed a detailed view of the lumen and the vessel wall of the entire thoracic aorta. Comparison of MRI with corresponding cross-sectional histopathology showed excellent agreement of aortic vessel wall area (r = 0.97). Hence, noninvasive MRI should allow new insights into the mechanisms involved in progression and regression of atherosclerotic disease.

The analysis of myocardial microstructure in vivo is important for the determination of myocardial contractility and function. The purpose of the present study was to demonstrate that high-resolution T*2 imaging has the potential to visualize the microstructure of beating, isolated rat hearts. To perform T*2 imaging, a multiple gradient-echo sequence was implemented on an 11.75 Tesla microscopy system. An in-plane resolution of 78 microm and a slice thickness of 250 microm were achieved in 24 min. In comparison to histological sections, the T*2 maps showed an excellent spatial correspondence to the myocardial fiber structure. To demonstrate the utility of this technique, morphologic alterations in myocardial microstructure were investigated in hearts with chronic myocardial infarction. Scar tissue and the extent of the infarcted region were clearly visualized and quantified using high-resolution T*2 imaging.

In this study, a novel partially parallel acquisition (PPA) method is presented which can be used to accelerate image acquisition using an RF coil array for spatial encoding. This technique, GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) is an extension of both the PILS and VD-AUTO-SMASH reconstruction techniques. As in those previous methods, a detailed, highly accurate RF field map is not needed prior to reconstruction in GRAPPA. This information is obtained from several k-space lines which are acquired in addition to the normal image acquisition. As in PILS, the GRAPPA reconstruction algorithm provides unaliased images from each component coil prior to image combination. This results in even higher SNR and better image quality since the steps of image reconstruction and image combination are performed in separate steps. After introducing the GRAPPA technique, primary focus is given to issues related to the practical implementation of GRAPPA, including the reconstruction algorithm as well as analysis of SNR in the resulting images. Finally, in vivo GRAPPA images are shown which demonstrate the utility of the technique.

Semipermeable hydrogels formed with a biocompatible alginate solution and Ba(2+) ions protect encapsulated cells and tissues from a foreign immune system. For the viability and metabolic activity of the encapsulated materials, a sufficient oxygen supply inside the capsules is necessary. Quantitative (19)F-MRI was performed on perfluorocarbon-loaded alginate capsules implanted into the peritoneal cavity, the musculus quadriceps femoris, and beneath the kidney capsule of rats, in order to determine in vivo the partial oxygen pressure (pO(2)) inside the capsules at these implantation sites. The temporal behavior of the pO(2) values was observed for at least 3 months. The most stable values over time were observed in the kidney, where inter-rat pO(2) differences were considerable. In the muscle, the values were very high directly after implantation and decreased to nearly zero after 2 weeks. In the peritoneal cavity, values changed randomly over a wide range between different rats and over time. Magn Reson Med 42:1039-1047, 1999.