Overdiscrete echo-planar spectroscopic imaging with correlated higher-order phase correction.

PURPOSE: To introduce a robust methodology for fast 1 H MRSI of the brain at 3T with improved SNR and reduced phase-related artifacts. METHOD: An accelerated acquisition scheme using echo-planar spectroscopic imaging (EPSI) was combined with the overdiscrete reconstruction framework. This approach enables the interleaved acquisition of a water reference scan at each phase encoding step, maximizing its correlation with the water-suppressed measurement. Moreover, a generalized high-order phase correction was incorporated into the reconstruction pipeline. The spatial-temporal phase correction term was estimated from the reference scan and interpolated to high resolution using a polynomial basis. The method was implemented at 3T and validated with phantom and in vivo experiments. RESULTS: The methodology showed the elimination of spectral artifacts generated by phase disturbances and achieved mean SNR gains in vivo of 3.18 and 1.19 compared to standard reconstructions with corrections performed at nominal and high resolution, respectively. EPSI scans with interleaved water acquisition showed to be robust to system instabilities and potentially to patient motion. Moreover, phase distortions were effectively corrected in a single step, avoiding additional reference measurements and post-processing steps. CONCLUSION: The overdiscrete reconstruction framework with high-order phase correction allowed to effectively correct for distortions, related to B0 inhomogeneities, B0 drift, eddy currents, and system vibrations. Furthermore, the presented reconstruction method, combined with EPSI acquisitions, demonstrated improved measurement stability, substantial SNR enhancement, better spectral linewidth, and effective artifact removal.

Correction of motion-induced susceptibility artifacts and B0 drift during proton resonance frequency shift-based MR thermometry in the pelvis with background field removal methods.

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.

Accelerated multi-snapshot free-breathing B1+ mapping based on the dual refocusing echo acquisition mode technique (DREAM): An alternative to measure RF nonuniformity for cardiac MRI.

BACKGROUND: Field inhomogeneities in MRI caused by interactions between the radiofrequency field and the patient anatomy can lead to artifacts and contrast variations, consequently degrading the overall image quality and thereby compromising diagnostic value of the images. PURPOSE: To develop an efficient free-breathing and motion-robust B1+ mapping method that allows for the investigation of spatial homogeneity of the transmitted radiofrequency field in the myocardium at 3.0T. Three joint approaches are used to adapt the dual refocusing echo acquisition mode (DREAM) sequence for cardiac applications: (1) electrocardiograph triggering; (2) a multi-snapshot undersampling scheme, which relies on the Golden Ratio, to accelerate the acquisition; and (3) motion-compensation based on low-resolution images acquired in each snapshot. STUDY TYPE: Prospective. PHANTOM/SUBJECTS: Eurospin II T05 system, torso phantom, and five healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0T/DREAM. ASSESSMENT: The proposed method was compared with the Bloch-Siegert shift (BSS) method and validated against the standard DREAM sequence. Cardiac B1+ maps were obtained in free-breathing and breath-hold as a proof of concept of the in vivo performance of the proposed method. STATISTICAL TESTS: Mean and standard deviation (SD) values were analyzed for six standard regions of interest within the myocardium. Repeatability was assessed in terms of SD and coefficient of variation. RESULTS: Phantom results indicated low deviation from the BSS method (mean difference = 3%). Equivalent B1+ distributions for free-breathing and breath-hold in vivo experiments demonstrated the motion robustness of this method with good repeatability (SD < 0.05). The amount of B1+ variations was found to be 26% over the myocardium within a short axis slice. DATA CONCLUSION: The feasibility of a cardiac B1+ mapping method with high spatial resolution in a reduced scan time per trigger was demonstrated. The free-breathing characteristic could be beneficial to determine shim components for multi-channel systems, currently limited to two for a single breath-hold. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:499-507.

A phase-cycled temperature-sensitive fast spin echo sequence with conductivity bias correction for monitoring of mild RF hyperthermia with PRFS.

OBJECTIVE: Mild hyperthermia (HT) treatments are generally monitored by phase-referenced proton resonance frequency shift calculations. A novel phase and thus temperature-sensitive fast spin echo (TFSE) sequence is introduced and compared to the double echo gradient echo (DEGRE) sequence. THEORY AND METHODS: For a proton resonance frequency shift (PRFS)-sensitive TFSE sequence, a phase cycling method is applied to separate even from odd echoes. This method compensates for conductivity change-induced bias in temperature mapping as does the DEGRE sequence. Both sequences were alternately applied during a phantom heating experiment using the clinical setup for deep radio frequency HT (RF-HT). The B0 drift-corrected temperature values in a region of interest around temperature probes are compared to the temperature probe data and further evaluated in Bland-Altman plots. The stability of both methods was also tested within the thighs of three volunteers at a constant temperature using the subcutaneous fat layer for B0-drift correction. RESULTS: During the phantom heating experiment, on average TFSE temperature maps achieved double temperature-to-noise ratio (TNR) efficiency in comparison with DEGRE temperature maps. In-vivo images of the thighs exhibit stable temperature readings of ± 1 °C over 25 min of scanning in three volunteers for both methods. On average, the TNR efficiency improved by around 25% for in vivo data. CONCLUSION: A novel TFSE method has been adapted to monitor temperature during mild HT.

Microfluidic-Based Synthesis of Magnetic Nanoparticles Coupled with Miniaturized NMR for Online Relaxation Studies.

Using compact desktop NMR systems for rapid characterization of relaxation properties directly after synthesis can expedite the development of functional magnetic nanoparticles. Therefore, an automated system that combines a miniaturized NMR relaxometer and a flow-based microreactor for online synthesis and characterization of magnetic iron oxide nanoparticles is constructed and tested. NMR relaxation properties are quantified online with a 0.5 T permanent magnet for measurement of transverse ( T2) and longitudinal ( T1) relaxation times. Nanoparticles with a primary particle size of about 25 nm are prepared by coprecipitation in a tape-based microreactor that utilizes 3D hydrodynamic flow focusing to avoid channel clogging. Cluster sizes are expeditiously optimized for maximum transverse relaxivity of 115.5 mM s-1. The compact process control system is an efficient tool that speeds up synthesis optimization and product characterization of magnetic nanoparticles for nanomedical, theranostic, and NMR-based biosensing applications.

Orthogonally combined motion- and diffusion-sensitized driven equilibrium (OC-MDSDE) preparation for vessel signal suppression in 3D turbo spin echo imaging of peripheral nerves in the extremities.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

High-resolution echo-planar spectroscopic imaging at ultra-high field.

MR spectroscopic imaging (MRSI) at ultra-high field (≥7 T) benefits from improved sensitivity that allows the detection of low-concentration metabolites in the brain. However, optimized acquisition techniques are required to overcome inherent limitations of MRSI at ultra-high field. This work describes an optimized method for fast high-resolution 1 H-MRSI of the brain at 7 T. The proposed acquisition sequence combines precise volume localization using semi-localization by adiabatic selective refocusing, fast spatial encoding using high-bandwidth symmetric echo-planar spectroscopic imaging (EPSI), and robust water suppression with variable power and optimized relaxation delays. This showed improved robustness to B0 and B1+ inhomogeneities, eddy currents, nuisance signal contamination and system instabilities. Furthermore, a method for correction of phase inconsistencies in symmetric EPSI enabled high-bandwidth measurements at 7 T. The proposed correction effectively removed spectral ghosting using a single-shot water reference scan. This framework was tested in healthy volunteers at 7 T and spectral quality was compared with lower-spatial-resolution scans, measured at 3 T using the same methodology. A gain in the signal-to-noise ratio (SNR) per unit volume and unit time of 1.57 was achieved, keeping acquisition time short (5 min) and the specific absorption rate within the permitted limits. This SNR enhancement obtained at ultra-high field enabled high-resolution (0.25-0.375 mL) metabolite mapping of the brain within a clinically feasible scan time. The correlation of the reconstructed maps with anatomical structures was observed, showing the diagnostic potential of the technique.

Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules.

pH is a tightly regulated physiological parameter that is often altered in diseased states like cancer. The development of biosensors that can be used to non-invasively image pH with hyperpolarized (HP) magnetic resonance spectroscopic imaging has therefore recently gained tremendous interest. However, most of the known HP-sensors have only individually and not comprehensively been analyzed for their biocompatibility, their pH sensitivity under physiological conditions, and the effects of chemical derivatization on their logarithmic acid dissociation constant (pKa). Proteinogenic amino acids are biocompatible, can be hyperpolarized and have at least two pH sensitive moieties. However, they do not exhibit a pH sensitivity in the physiologically relevant pH range. Here, we developed a systematic approach to tailor the pKa of molecules using modifications of carbon chain length and derivatization rendering these molecules interesting for pH biosensing. Notably, we identified several derivatives such as [1-13C]serine amide and [1-13C]-2,3-diaminopropionic acid as novel pH sensors. They bear several spin-1/2 nuclei (13C, 15N, 31P) with high sensitivity up to 4.8 ppm/pH and we show that 13C spins can be hyperpolarized with dissolution dynamic polarization (DNP). Our findings elucidate the molecular mechanisms of chemical shift pH sensors that might help to design tailored probes for specific pH in vivo imaging applications.

Real valued diffusion-weighted imaging using decorrelated phase filtering.

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.

Measurement of extracellular volume and transit time heterogeneity using contrast-enhanced myocardial perfusion MRI in patients after acute myocardial infarction.

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.

Correction of phase errors in quantitative water-fat imaging using a monopolar time-interleaved multi-echo gradient echo sequence.

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.

T2 mapping with magnetization-prepared 3D TSE based on a modified BIR-4 T2 preparation.

The purpose of this work was to investigate the performance of the modified BIR-4 T2 preparation for T2 mapping and propose a method to remove T2 quantification errors in the presence of large B1 and B0 offsets. The theoretical investigation of the magnetization evolution during the T2 preparation in the presence of B1 and B0 offsets showed deviations from a mono-exponential T2 decay (two parameter fit). A three parameter fit was used to improve T2 accuracy. Furthermore, a two parameter fit with an additional saturation preparation scan was proposed to improve T2 accuracy and precision. These three fitting methods were compared based on simulations, phantom measurements and an in vivo healthy volunteer study of the neck musculature using a 3D TSE readout. The results based upon the pure two parameter fit overestimated T2 in regions with high B0 offsets (up to 40% in phantoms). The three parameter fit T2 values were robust to B0 offsets but with higher standard deviation (up to 40% in simulations). The two parameter fit with the saturation preparation yielded high robustness towards B0 offsets with a noise performance comparable to that of the two parameter fit. In the volunteer study the T2 values obtained by the pure two parameter fit showed a dependence on the field inhomogeneities, whereas the T2 values from the proposed fitting approach were shown to be insensitive to B0 offsets. The proposed method enabled accurate and precise T2 mapping in the presence of large B1 and B0 offsets.

Deuteration of Hyperpolarized 13 C-Labeled Zymonic Acid Enables Sensitivity-Enhanced Dynamic MRI of pH.

Aberrant pH is characteristic of many pathologies such as ischemia, inflammation or cancer. Therefore, a non-invasive and spatially resolved pH determination is valuable for disease diagnosis, characterization of response to treatment and the design of pH-sensitive drug-delivery systems. We recently introduced hyperpolarized [1,5-13 C2 ]zymonic acid (ZA) as a novel MRI probe of extracellular pH utilizing dissolution dynamic polarization (DNP) for a more than 10000-fold signal enhancement of the MRI signal. Here we present a strategy to enhance the sensitivity of this approach by deuteration of ZA yielding [1,5-13 C2 , 3,6,6,6-D4 ]zymonic acid (ZAd ), which prolongs the liquid state spin lattice relaxation time (T1 ) by up to 39 % in vitro. Measurements with ZA and ZAd on subcutaneous MAT B III adenocarcinoma in rats show that deuteration increases the signal-to-noise ratio (SNR) by up to 46 % in vivo. Furthermore, we demonstrate a proof of concept for real-time imaging of dynamic pH changes in vitro using ZAd , potentially allowing for the characterization of rapid acidification/basification processes in vivo.

α-trideuteromethyl[15N]glutamine: A long-lived hyperpolarized perfusion marker.

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.

Diffusion-weighted stimulated echo acquisition mode (DW-STEAM) MR spectroscopy to measure fat unsaturation in regions with low proton-density fat fraction.

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 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. 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.

Bias and precision analysis of diffusional kurtosis imaging for different acquisition schemes.

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.

Probing lactate secretion in tumours with hyperpolarised NMR.

Most tumours exhibit a high rate of glycolysis and predominantly produce energy by lactic acid fermentation. To maintain energy production and prevent toxicity, the lactate generated needs to be rapidly transported out of the cell. This is achieved by monocarboxylate transporters (MCTs), which therefore play an essential role in cancer metabolism and development. In vivo experiments were performed on eight male Fisher F344 rats bearing a subcutaneous mammary carcinoma after injection of hyperpolarised [1-(13) C]pyruvate. A Gd(III)DO3A complex that binds to pyruvate and its metabolites was used to efficiently destroy the extracellular magnetisation after hyperpolarised lactate had been formed. Moreover, a pulse sequence including a frequency-selective saturation pulse was designed so that the pyruvate magnetisation could be destroyed to exclude effects arising from further conversion. Given this preparation, metabolite transport out of the cell manifested as additional decay and apparent cell membrane transporter rates could thus be obtained using a reference measurement without a relaxation agent. In addition to slice-selective spectra, spatially resolved maps of apparent membrane transporter activity were acquired using a single-shot spiral gradient readout. A considerable increase in decay rate was detected for lactate, indicating rapid transport out of the cell. The alanine signal was unaltered, which corresponds to a slower efflux rate. This technique could allow for better understanding of tumour metabolism and progression, and enable treatment response measurements for MCT-targeted cancer therapies. Moreover, it provides vital insights into the signal kinetics of hyperpolarised [1-(13) C]pyruvate examinations. Copyright © 2016 John Wiley & Sons, Ltd.

Multiparametric human hepatocellular carcinoma characterization and therapy response evaluation by hyperpolarized (13) C MRSI.

Individual tumor characterization and treatment response monitoring based on current medical imaging methods remain challenging. This work investigates hyperpolarized (13) C compounds in an orthotopic rat hepatocellular carcinoma (HCC) model system before and after transcatheter arterial embolization (TAE). HCC ranks amongst the top six most common cancer types in humans and accounts for one-third of cancer-related deaths worldwide. Early therapy response monitoring could aid in the development of personalized therapy approaches and novel therapeutic concepts. Measurements with selectively (13) C-labeled and hyperpolarized urea, pyruvate and fumarate were performed in tumor-bearing rats before and after TAE. Two-dimensional, slice-selective MRSI was used to obtain spatially resolved maps of tumor perfusion, cell energy metabolic conversion rates and necrosis, which were additionally correlated with immunohistochemistry. All three injected compounds, taken together with their respective metabolites, exhibited similar signal distributions. TAE induced a decrease in blood flow into the tumor and thus a decrease in tumor to muscle and tumor to liver ratios of urea, pyruvate and its metabolites, alanine and lactate, whereas conversion rates remained stable or increased on TAE in tumor, muscle and liver tissue. Conversion from fumarate to malate successfully indicated individual levels of necrosis, and global malate signals after TAE suggested the washout of fumarase or malate itself on necrosis. This study presents a combination of three (13) C compounds as novel candidate biomarkers for a comprehensive characterization of genetically and molecularly diverse HCC using hyperpolarized MRSI, enabling the simultaneous detection of differences in tumor perfusion, metabolism and necrosis. If, as in this study, bolus dynamics are not required and qualitative perfusion information is sufficient, the desired information could be extracted from hyperpolarized fumarate and pyruvate alone, acquired at higher fields with better spectral separation. Copyright © 2016 John Wiley & Sons, Ltd.

Imaging of the lumbar plexus: Optimized refocusing flip angle train design for 3D TSE.

PURPOSE: To study the effects of refocusing angle modulation with 3D turbo spin echo (TSE) on signal and sharpness of small oblique nerves embedded in muscle and suppressed fat in the lumbar plexus. MATERIALS AND METHODS: Flip angle trains were generated with extended phase graphs (EPG) for a sequence parameter subspace. Signal loss and width broadening were simulated for a single-pixel nerve embedded in muscle and suppressed fat to prescribe a flip angle modulation that gives the best compromise between signal and sharpness of small nerves. Two flip angle trains were defined based on the simulations of small embedded nerves: design denoted A, predicting maximum global signal, and design denoted B, predicting maximum signal for minimum width broadening. In vivo data of the lumbar plexus in 10 healthy volunteers was acquired at 3.0T with 3D TSE employing flip angle trains A and B. Quantitative and qualitative analyses of the acquired data were made to assess changes in width and signal intensity. RESULTS: Changing flip angle modulation from A to B resulted in: 1) average signal losses of 23% in (larger) L5 nerves and 9% in (smaller) L3 nerves; 2) average width reductions of 4% in L5 nerves and of 16% in L3 nerves; and 3) statistically significant sharpness improvement (P = 0.005) in L3 nerves. CONCLUSION: An optimized flip angle train in 3D TSE imaging of the lumbar plexus considering geometry-specific blurring effects from both the nerve and the surrounding tissue can improve the delineation of small nerves.