Oscillating gradient diffusion kurtosis imaging of normal and injured mouse brains

Recent advances in diffusion MRI employ multiple diffusion encoding schemes with varying diffusion direction, weighting, and diffusion time to investigate specific microstructural properties in biological tissues. In this study, we examined time‐dependent diffusion kurtosis contrast in adult mouse brains and in neonatal mouse brains after hypoxic–ischemic (HI) injury. In vivo diffusion kurtosis maps were acquired with a short diffusion time using an oscillating gradient spin echo (OGSE) sequence at 100 Hz and with a relatively long diffusion time (20 ms) using a pulsed gradient spin echo (PGSE) sequence. In the adult mouse brain, we found that the cortex and hippocampus showed larger differences between OGSE kurtosis and PGSE kurtosis than major white matter tracts. In neonatal mouse brains with unilateral HI injury, the OGSE kurtosis map overall provided stronger edema contrast than the PGSE kurtosis map, and the differences between OGSE and PGSE kurtosis measurements in the edema region reflected heterogeneity of injury. This is the first in vivo study that has demonstrated multi‐direction OGSE kurtosis contrasts in the mouse brain. Comparing PGSE and OGSE kurtosis measures may provide additional information on microstructural changes after ischemic stroke.     

Mapping the human brainstem: Brain nuclei and fiber tracts at 3 T and 7 T

Structural high‐resolution imaging of the brainstem can be of high importance in clinical practice. However, ultra‐high field magnetic resonance imaging (MRI) is still restricted in use due to limited availability. Therefore, quantitative MRI techniques (quantitative susceptibility mapping [QSM], relaxation measurements [ , R₁ ], diffusion tensor imaging [DTI]) and T₂ ‐ and proton density (PD)‐weighted imaging in the human brainstem at 3 T and 7 T are compared. Five healthy volunteers (mean age: 21.5 ± 1.9 years) were measured at 3 T and 7 T using multi‐echo gradient echo sequences for susceptibility mapping and relaxometry, magnetization‐prepared 2 rapid acquisition gradient echo sequences for R₁ relaxometry, turbo‐spin echo sequences for PD‐ and T₂ ‐weighted imaging and readout‐segmented echo planar sequences for DTI. Susceptibility maps were computed using Laplacian‐based phase unwrapping, V‐SHARP for background field removal and the streaking artifact reduction for QSM algorithm for dipole inversion. Contrast‐to‐noise ratios (CNRs) were determined at 3 T and 7 T in ten volumes of interest (VOIs). Data acquired at 7 T showed higher CNR. However, in four VOIs, lower CNR was observed for at 7 T. QSM was shown to be the contrast with which the highest number of structures could be identified. The depiction of very fine tracts such as the medial longitudinal fasciculus throughout the brainstem was only possible in susceptibility maps acquired at 7 T. DTI effectively showed the main tracts (crus cerebri, transverse pontine fibers, corticospinal tract, middle and superior cerebellar peduncle, pontocerebellar tract, and pyramid) at both field strengths. Assessing the brainstem with quantitative MRI methods such as QSM, , as well as PD‐ and T₂ ‐weighted imaging with great detail, is also possible at 3 T, especially when using susceptibility mapping calculated from a gradient echo sequence with a wide range of echo times from 10.5 to 52.5 ms. However, tracing smallest structures strongly benefits from imaging at ultra‐high field.     

31P magnetic resonance fingerprinting for rapid quantification of creatine kinase reaction rate in vivo

The purpose of this work was to develop a ³¹P spectroscopic magnetic resonance fingerprinting (MRF) method for fast quantification of the chemical exchange rate between phosphocreatine (PCr) and adenosine triphosphate (ATP) via creatine kinase (CK). A ³¹P MRF sequence (CK‐MRF) was developed to quantify the forward rate constant of ATP synthesis via CK ( ), the T ₁ relaxation time of PCr ( ), and the PCr‐to‐ATP concentration ratio ( . The CK‐MRF sequence used a balanced steady‐state free precession (bSSFP)‐type excitation with ramped flip angles and a unique saturation scheme sensitive to the exchange between PCr and γATP. Parameter estimation was accomplished by matching the acquired signals to a dictionary generated using the Bloch‐McConnell equation. Simulation studies were performed to examine the susceptibility of the CK‐MRF method to several potential error sources. The accuracy of nonlocalized CK‐MRF measurements before and after an ischemia–reperfusion (IR) protocol was compared with the magnetization transfer (MT‐MRS) method in rat hindlimb at 9.4 T (n  = 14). The reproducibility of CK‐MRF was also assessed by comparing CK‐MRF measurements with both MT‐MRS (n  = 17) and four angle saturation transfer (FAST) (n  = 7). Simulation results showed that CK‐MRF quantification of was robust, with less than 5% error in the presence of model inaccuracies including dictionary resolution, metabolite T ₂ values, inorganic phosphate metabolism, and B ₁ miscalibration. Estimation of by CK‐MRF (0.38 ± 0.02 s^?1 at baseline and 0.42 ± 0.03 s^?1 post‐IR) showed strong agreement with MT‐MRS (0.39 ± 0.03 s^?1 at baseline and 0.44 ± 0.04 s^?1 post‐IR). estimation was also similar between CK‐MRF and FAST (0.38 ± 0.02 s^?1 for CK‐MRF and 0.38 ± 0.11 s^?1 for FAST). The coefficient of variation from 20 s CK‐MRF quantification of was 42% of that by 150 s MT‐MRS acquisition and was 12% of that by 20 s FAST acquisition. This study demonstrates the potential of a ³¹P spectroscopic MRF framework for rapid, accurate and reproducible quantification of chemical exchange rate of CK in vivo .     

Demonstration and suppression of respiration‐related artifacts in Bloch–Siegert shift‐based B1+ maps of the human brain

Respiration‐induced movement of the chest wall and internal organs causes temporal B₀ variations extending throughout the brain. This study demonstrates that these variations can cause significant artifacts in maps obtained at 7 T with the Bloch–Siegert shift (BSS) mapping technique. To suppress these artifacts, a navigator correction scheme was proposed. Two sets of experiments were performed. In the first set of experiments, phase shifts induced by respiration‐related B₀ variations were assessed for five subjects at 7 T by using a gradient echo (GRE) sequence without phase‐encoding. In the second set of experiments, maps were acquired using a GRE‐based BSS pulse sequence with navigator echoes. For this set, the measurements were consecutively repeated 16 times for the same imaging slice. These measurements were averaged to obtain the reference map. Due to the periodicity of respiration‐related phase shifts, their effect on the reference map was assumed to be negligible through averaging. The individual maps of the 16 repetitions were calculated with and without using the proposed navigator scheme. These maps were compared with the reference map. The peak‐to‐peak value of respiration‐related phase shifts varied between subjects. Without navigator correction, the interquartile range of percentage error in varied between 4.0% and 8.3% among subjects. When the proposed navigator scheme was used, these numbers were reduced to 2.5% and 2.9%, indicating an improvement in the precision of GRE‐based BSS mapping at high magnetic fields.     

Measurement of distinctive features of cortical spreading depolarizations with different MRI contrasts

Growing clinical evidence suggests critical involvement of spreading depolarizations (SDs) in the pathophysiology of neurological disorders such as migraine and stroke. MRI provides powerful tools to detect and assess co‐occurring cerebral hemodynamic and cellular changes during SDs. This study reports the feasibility and advantages of two MRI scans, based on balanced steady‐state free precession (b‐SSFP) and diffusion‐weighted multi‐spin‐echo (DT2), heretofore unexplored for monitoring SDs. These were compared with gradient‐echo MRI. SDs were induced by KCl application in rat brain. Known for high SNR, the T₂‐ and T₁‐based b‐SSFP contrast was hypothesized to provide higher spatiotemporal specificity than ‐based gradient‐echo scanning. DT2 scanning was designed to provide simultaneous T₂ and apparent diffusion coefficient (ADC) measurements, thus enabling combined quantitative assessment of hemodynamic and cellular changes during SDs. Procedures were developed to automate identification of SD‐induced responses in all the scans. These responses were analyzed to determine detection sensitivity and temporal characteristics of signals from each scanning method. Cluster analysis was performed to elucidate unique temporal patterns for each contrast. All scans allowed detection of SD‐induced responses. b‐SSFP scans showed significantly larger relative intensity changes, narrower peak widths and greater spatial specificity compared with gradient‐echo MRI. SD‐induced effects on ADC, calculated from DT2 scans, showed the most pronounced signal changes, displaying about 20% decrease, as against 10–15% signal increases observed with b‐SSFP and gradient‐echo scanning. Cluster analysis revealed additional temporal sub‐patterns, such as an initial dip on gradient‐echo scans and temporally shifted T₂ and proton density changes in DT2 data. To summarize, b‐SSFP and DT2 scanning provide distinct information on SDs compared with gradient‐echo MRI. DT2 scanning, with its potential to simultaneously provide cellular and hemodynamic information, can offer unique information on the inter‐relationship between these processes in pathologic brain, which may improve monitoring of spreading depolarizations in (pre)clinical settings. Copyright © 2015 John Wiley & Sons, Ltd.     

Correlation of hyperpolarized 13C‐MRI data with tissue extract measurements

Hyperpolarized (HP) MRI provides the means to monitor lactate metabolism noninvasively in tumours. Since ‐lactate signal levels obtained from HP imaging depend on multiple factors, such as the rate of substrate delivery via the vasculature, the expression level of monocarboxylate transporters (MCTs) and lactate dehydrogenase (LDH), and the local lactate pool size, the interpretation of HP metabolic images remains challenging. In this study, ex vivo tissue extract measurements (i.e., NMR isotopomer analysis, western blot analysis) derived from an MDA‐MB‐231 xenograft model in nude rats were used to test for correlations between the in vivo data and the ex vivo measures. The lactate‐to‐pyruvate ratio from HP MRI was strongly correlated with [1‐ ]lactate concentration measured from the extracts using NMR (R = 0.69, p 0.05), as well as negatively correlated with tumour wet weight (R =  0.60, p 0.05). In this tumour model, both MCT1 and MCT4 expressions were positively correlated with wet weight ( = 0.78 and 0.93, respectively, p 0.01). Lactate pool size and the lactate‐to‐pyruvate ratio were not significantly correlated.     

High angular resolution diffusion imaging with stimulated echoes: compensation and correction in experiment design and analysis

Stimulated echo acquisition mode (STEAM) diffusion MRI can be advantageous over pulsed‐gradient spin‐echo (PGSE) for diffusion times that are long compared with T₂. It therefore has potential for biomedical diffusion imaging applications at 7T and above where T₂ is short. However, gradient pulses other than the diffusion gradients in the STEAM sequence contribute much greater diffusion weighting than in PGSE and lead to a disrupted experimental design. Here, we introduce a simple compensation to the STEAM acquisition that avoids the orientational bias and disrupted experiment design that these gradient pulses can otherwise produce. The compensation is simple to implement by adjusting the gradient vectors in the diffusion pulses of the STEAM sequence, so that the net effective gradient vector including contributions from diffusion and other gradient pulses is as the experiment intends. High angular resolution diffusion imaging (HARDI) data were acquired with and without the proposed compensation. The data were processed to derive standard diffusion tensor imaging (DTI) maps, which highlight the need for the compensation. Ignoring the other gradient pulses, a bias in DTI parameters from STEAM acquisition is found, due both to confounds in the analysis and the experiment design. Retrospectively correcting the analysis with a calculation of the full B matrix can partly correct for these confounds, but an acquisition that is compensated as proposed is needed to remove the effect entirely. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

An in vivo study of the orientation‐dependent and independent components of transverse relaxation rates in white matter

Diffusion‐weighted imaging (DWI) provides information that allows the estimation of white‐matter (WM) fibre orientation and distribution, but it does not provide information about myelin density, fibre concentration or fibre size within each voxel. On the other hand, quantitative relaxation contrasts (like the apparent transverse relaxation, ) offer iron and myelin‐related contrast, but their dependence on the orientation of microstructure with respect to the applied magnetic field, B₀, is often neglected. The aim of this work was to combine the fibre orientation information retrieved from the DWI acquisition and the sensitivity to microstructural information from quantitative relaxation parameters. The in vivo measured quantitative transverse relaxation maps (R₂ and ) were decomposed into their orientation‐dependent and independent components, using the DWI fibre orientation information as prior knowledge. The analysis focused on major WM fibre bundles such as the forceps major (FMj), forceps minor (FMn), cingulum (CG) and corticospinal tracts (CST). The orientation‐dependent R₂ parameters, despite their small size (0–1.5 Hz), showed higher variability across different fibre populations, while those derived from , although larger (3.1–4.5 Hz), were mostly bundle‐independent. With this article, we have, for the first time, attempted the in vivo characterization of the orientation‐(in)dependent components of the transverse relaxation rates and demonstrated that the orientation of WM fibres influences both R₂ and contrasts.     

BOLD background gradient contributions in diffusion‐weighted fMRI—comparison of spin‐echo and twice‐refocused spin‐echo sequences

The interaction (‘cross terms’) between diffusion‐weighting gradients and susceptibility‐induced background gradient fields around vessels has an impact on apparent diffusion coefficient (ADC) measurements and diffusion‐weighted functional magnetic resonance imaging (DFMRI) experiments. Monte‐Carlo (MC) simulations numerically integrating the Bloch equations for a large number of random walks in a vascular model were used to investigate to what extent such interactions would influence the extravascular signal change as well as the ADC change observed in DFMRI experiments. The vascular model consists of a set of independent, randomly oriented, infinite cylinders whose internal magnetic susceptibility varies as the state changes between rest and activation. In such a network, the cross terms result in the observation of a functional increase in ADC accompanied by a descending percent signal change with increasing diffusion weighting. It is shown that the twice‐refocused spin‐echo sequence permits sufficient yet not total suppression of such effects compared to the standard Stejskal‐Tanner spin‐echo diffusion weighting under experimentally relevant conditions. Copyright © 2010 John Wiley & Sons, Ltd.     

High‐resolution in vivo MR‐STAT using a matrix‐free and parallelized reconstruction algorithm

MR‐STAT is a recently proposed framework that allows the reconstruction of multiple quantitative parameter maps from a single short scan by performing spatial localisation and parameter estimation on the time‐domain data simultaneously, without relying on the fast Fourier transform (FFT). To do this at high resolution, specialized algorithms are required to solve the underlying large‐scale nonlinear optimisation problem. We propose a matrix‐free and parallelized inexact Gauss–Newton based reconstruction algorithm for this purpose. The proposed algorithm is implemented on a high‐performance computing cluster and is demonstrated to be able to generate high‐resolution (1 mm 1 mm in‐plane resolution) quantitative parameter maps in simulation, phantom, and in vivo brain experiments. Reconstructed and values for the gel phantoms are in agreement with results from gold standard measurements and, for the in vivo experiments, the quantitative values show good agreement with literature values. In all experiments, short pulse sequences with robust Cartesian sampling are used, for which MR fingerprinting reconstructions are shown to fail.     

Exercising calf muscle changes correlate with pH,PCr recovery and maximum oxidative phosphorylation

Skeletal muscle metabolism is impaired in disorders like diabetes mellitus or peripheral vascular disease. The skeletal muscle echo planar imaging (EPI) signal (S_EPI) and its relation to energy metabolism are still debated. Localised 31P MRS and S_EPI data from gastrocnemius medialis of 19 healthy subjects were combined in one scanning session to study direct relationships between phosphocreatine (PCr), pH kinetics and parameters of time courses. Dynamic spectroscopy (semi‐LASER) and EPI were performed immediately before, during and after 5 min of plantar flexions. Data were acquired in a 7 T MR scanner equipped with a custom‐built ergometer and a dedicated ³¹P/¹H radio frequency (RF) coil array. Using a form‐fitted multi‐channel ³¹P/¹H coil array resulted in high signal‐to‐noise ratio (SNR). PCr and pH in the gastrocnemius medialis muscle were quantified from each ³¹P spectrum, acquired every 6 s. During exercise, S_EPI(t) was found to be a linear function of tissue pH(t) (cross‐correlation r = –0.85 ± 0.07). Strong Pearson's correlations were observed between post exercise time‐to‐peak (TTP) of S_EPI and (a) the time constant of PCr recovery τ_{PCr recovery} (r = 0.89, p < 10^{? 6}), (b) maximum oxidative phosphorylation using the linear model, Q_{max, lin} (r = 0.65, p = 0.002), the adenosine‐diphosphate‐driven model, Q_max,ADP (r = 0.73, p = 0.0002) and (c) end exercise pH (r = 0.60, p = 0.005). Based on combined accurately localised 31P MRS and weighted MRI, both with high temporal resolution, strong correlations of the skeletal muscle S_EPI during exercise and tissue pH time courses and of post exercise S_EPI and parameters of energy metabolism were observed. In conclusion, a tight coupling between skeletal muscle metabolic activity and tissue signal weighting, probably induced by osmotically driven water shift, exists and can be measured non‐invasively, using NMR at 7 T. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

Diffusion‐prepared stimulated‐echo turbo spin echo (DPsti‐TSE): An eddy current‐insensitive sequence for three‐dimensional high‐resolution and undistorted diffusion‐weighted imaging

In this study, we present a new three‐dimensional (3D), diffusion‐prepared turbo spin echo sequence based on a stimulated‐echo read‐out (DPsti‐TSE) enabling high‐resolution and undistorted diffusion‐weighted imaging (DWI). A dephasing gradient in the diffusion preparation module and rephasing gradients in the turbo spin echo module create stimulated echoes, which prevent signal loss caused by eddy currents. Near to perfect agreement of apparent diffusion coefficient (ADC) values between DPsti‐TSE and diffusion‐weighted echo planar imaging (DW‐EPI) was demonstrated in both phantom transient signal experiments and phantom imaging experiments. High‐resolution and undistorted DPsti‐TSE was demonstrated in vivo in prostate and carotid vessel wall. 3D whole‐prostate DWI was achieved with four b values in only 6 min. Undistorted ADC maps of the prostate peripheral zone were obtained at low and high imaging resolutions with no change in mean ADC values [(1.60 ± 0.10) × 10^?3 versus (1.60 ± 0.02) × 10^?3 mm²/s]. High‐resolution 3D DWI of the carotid vessel wall was achieved in 12 min, with consistent ADC values [(1.40 ± 0.23) × 10^?3 mm²/s] across different subjects, as well as slice locations through the imaging volume. This study shows that DPsti‐TSE can serve as a robust 3D diffusion‐weighted sequence and is an attractive alternative to the traditional two‐dimensional DW‐EPI approaches.     

Diffusion of hyperpolarized 13C‐metabolites in tumor cell spheroids using real‐time NMR spectroscopy

The detection of tumors noninvasively, the characterization of their progression by defined markers and the monitoring of response to treatment are goals of medical imaging techniques. In this article, a method which measures the apparent diffusion coefficients (ADCs) of metabolites using hyperpolarized ¹³C diffusion‐weighted spectroscopy is presented. A pulse sequence based on the pulsed gradient spin echo (PGSE) was developed that encodes both kinetics and diffusion information. In experiments with MCF‐7 human breast cancer cells, we detected an ADC of intracellularly produced lactate of 1.06 ± 0.15 µm²/ms, which is about one‐half of the value measured with pyruvate in extracellular culture medium. When monitoring tumor cell spheroids during progressive membrane permeabilization with Triton X‐100, the ratio of lactate ADC to pyruvate ADC increases as the fraction of dead cells increases. Therefore, ¹³C ADC detection can yield sensitive information on changes in membrane permeability and subsequent cell death. Our results suggest that both metabolic label exchange and ¹³C ADCs can be acquired simultaneously, and may potentially serve as noninvasive biomarkers for pathological changes in tumor cells. Copyright © 2012 John Wiley & Sons, Ltd.     

Towards higher sensitivity and stability of axon diameter estimation with diffusion‐weighted MRI

Diffusion‐weighted MRI is an important tool for in vivo and non‐invasive axon morphometry. The ActiveAx technique utilises an optimised acquisition protocol to infer orientationally invariant indices of axon diameter and density by fitting a model of white matter to the acquired data. In this study, we investigated the factors that influence the sensitivity to small‐diameter axons, namely the gradient strength of the acquisition protocol and the model fitting routine. Diffusion‐weighted ex. vivo images of the mouse brain were acquired using 16.4‐T MRI with high (G_max of 300 mT/m) and ultra‐high (G_max of 1350 mT/m) gradient strength acquisitions. The estimated axon diameter indices of the mid‐sagittal corpus callosum were validated using electron microscopy. In addition, a dictionary‐based fitting routine was employed and evaluated. Axon diameter indices were closer to electron microscopy measures when higher gradient strengths were employed. Despite the improvement, estimated axon diameter indices (a lower bound of ~ 1.8 μm) remained higher than the measurements obtained using electron microscopy (~1.2 μm). We further observed that limitations of pulsed gradient spin echo (PGSE) acquisition sequences and axonal dispersion could also influence the sensitivity with which axon diameter indices could be estimated. Our results highlight the influence of acquisition protocol, tissue model and model fitting, in addition to gradient strength, on advanced microstructural diffusion‐weighted imaging techniques. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

Proton change of parotid glands after gustatory stimulation examined by magnetic resonance imaging

The aim of this study was to investigate proton changes of the parotid gland after gustatory stimulation by semi‐quantitative parameters and an empirical mathematical model (EMM) using high‐temporal‐resolution, double‐echo, echo‐planar imaging (EPI). Approved by a local institutional review board, this study examined 20 parotid glands from 10 healthy volunteers (male:female = 6: 4; age ± standard deviation =35.1 ± 14.1 years) with written informed consent obtained. All participants underwent 1.5‐T, double‐echo EPI with gustatory stimulation. Semi‐quantitative parameters, including maximal drop ratio (MDR), time to peak (TTP), drop slope (DS), recovery slope (RS) and recovery ratio (RR), were calculated. The effect of temporal resolution on parotid functional parameters was evaluated. An EMM comprising an output function ( ) and an input function ( ) was also applied to fit all dynamic curves. Kruskal–Wallis test, Wilcoxon test, linear regression analysis and goodness of fit were used for statistical analysis. p < 0.05 was considered to be statistically significant. The signal intensity dropped significantly after gustatory stimulation on the proton density (PD) image (p < 0.01). MDR was 8.26% in the PD image. MDR and RR were negatively associated with time interval, whereas DS and TTP were significantly positively associated with time interval (all p < 0.05). EMM parametric values derived from PD–time curves of parotid glands were 12.04 ± 6.81%, 6.43 ± 4.23 min^–1, 88.73 ± 6.18%, 8.41 ± 4.86 min^–1 and 1.09 ± 1.35 for A_o, k_o, B, A_in and k_in, respectively. Semi‐quantitative functional parameters and EMM parameters using high‐temporal‐resolution, double‐echo EPI allow the quantification of parotid proton changes after gustatory stimulation.     

Measurement of brain lactate during visual stimulation using a long TE semi‐LASER sequence at 7 T

Estimation of metabolic changes during neuronal activation represents a challenge for in vivo MRS, especially for metabolites with low concentration and signal overlap, such as lactate. In this work, we aimed to evaluate the feasibility of detecting lactate during brain activation using a long (144 ms) semi‐LASER sequence at 7 T. spectra were acquired on healthy volunteers ( ) during a paradigm with 15 min of visual stimulation. Outer‐volume signals were further attenuated by the use of saturation slabs, and macromolecular signals in the vicinity of the inverted lactate peak were individually fitted with simulated Lorentzian peaks. All spectra were free of artefacts and highly reproducible across subjects. Lactate was accurately quantified with an average Cramér‐Rao lower bound of 8%. Statistically significant ( , one‐tailed ‐test) increases in lactate ( 10%) and glutamate ( 3%) levels during stimulation were detected in the visual cortex. Lactate and glutamate changes were consistent with previous measurements. We demonstrated that quantification of a clear and non‐contaminated lactate peak obtained with a long TE sequence has the potential of improving the accuracy of functional MRS studies targeting non‐oxidative reaction pathways.     

Continuous‐wave saturation considerations for efficient xenon depolarization

The combination of hyperpolarized Xe with chemical exchange saturation transfer (Hyper‐CEST) is a powerful NMR technique to detect highly dilute concentrations of Xe binding sites using RF saturation pulses. Crucially, that combination of saturation pulse strength and duration that generates the maximal Hyper‐CEST effect is a priori unknown. In contrast to CEST in proton MRI, where the system reaches a steady‐state for long saturation times, Hyper‐CEST has an optimal saturation time, i.e. saturating for shorter or longer reduces the Hyper‐CEST effect. Here, we derive expressions for this optimal saturation pulse length. We also found that a pulse strength, B₁, corresponding to five times the Xe exchange rate, k_BA (i.e. B₁ = 5 k_BA/γ with the gyromagnetic ratio of ¹²⁹Xe, γ), generates directly and without further optimization 96 % of the maximal Hyper‐CEST contrast while preserving spectral selectivity. As a measure that optimizes the amplitude and the width of the Hyper‐CEST response simultaneously, we found an optimal saturation pulse strength corresponding to times the Xe exchange rate, i.e. . When extremely low host concentration is detected, then the expression for the optimum saturation time simplifies as it approaches the longitudinal relaxation time of free Xe. Copyright © 2015 John Wiley & Sons, Ltd.     

A multi‐compartmental SE‐BOLD interpretation for stimulus‐related signal changes in diffusion‐weighted functional MRI

A new interpretation is proposed for stimulus‐induced signal changes in diffusion‐weighted functional MRI. T₂‐weighted spin‐echo echo‐planar images were acquired at different diffusion‐weightings while visual stimulation was presented to human volunteers. The amplitudes of the positive stimulus‐correlated response and post‐stimulus undershoot (PSU) in the functional time‐courses were found to follow different trends as a function of b‐value. Data were analysed using a three‐compartment signal model, with one compartment being purely vascular and the other two dominated by fast‐ and slow‐diffusing molecules in the brain tissue. The diffusion coefficients of the tissue were assumed to be constant throughout the experiments. It is shown that the stimulus‐induced signal changes can be decomposed into independent contributions originating from each of the three compartments. After decomposition, the fast‐diffusion phase displays a substantial PSU, while the slow‐diffusion phase demonstrates a highly reproducible and stimulus‐correlated time‐course with minimal undershoot. The decomposed responses are interpreted in terms of the spin‐echo blood oxygenation level dependent (SE‐BOLD) effect, and it is proposed that the signal produced by fast‐ and slow‐diffusing molecules reflect a sensitivity to susceptibility changes in arteriole/venule‐ and capillary‐sized vessels, respectively. This interpretation suggests that diffusion‐weighted SE‐BOLD imaging may provide subtle information about the haemodynamic and neuronal responses. Copyright © 2009 John Wiley & Sons, Ltd.     

Relaxation‐compensated CEST‐MRI at 7 T for mapping of creatine content and pH – preliminary application in human muscle tissue in vivo

The small biomolecule creatine is involved in energy metabolism. Mapping of the total creatine (mostly PCr and Cr) in vivo has been done with chemical shift imaging. Chemical exchange saturation transfer (CEST) allows an alternative detection of creatine via water MRI. Living tissue exhibits CEST effects from different small metabolites, including creatine, with four exchanging protons of its guanidinium group resonating about 2 ppm from the water peak and hence contributing to the amine proton CEST peak. The intermediate exchange rate (≈ 1000 Hz) of the guanidinium protons requires high RF saturation amplitude B₁. However, strong B₁ fields also label semi‐solid magnetization transfer (MT) effects originating from immobile protons with broad linewidths (~kHz) in the tissue. Recently, it was shown that endogenous CEST contrasts are strongly affected by the MT background as well as by T₁ relaxation of the water protons. We show that this influence can be corrected in the acquired CEST data by an inverse metric that yields the apparent exchange‐dependent relaxation (AREX). AREX has some useful linearity features that enable preparation of both concentration, and – by using the AREX‐ratio of two RF irradiation amplitudes B₁ – purely exchange‐rate‐weighted CEST contrasts. These two methods could be verified in phantom experiments with different concentration and pH values, but also varying water relaxation properties. Finally, results from a preliminary application to in vivo CEST imaging data of the human calf muscle before and after exercise are presented. The creatine concentration increases during exercise as expected and as confirmed by ³¹P NMR spectroscopic imaging. However, the estimated concentrations obtained by our method were higher than the literature values: to . The CEST‐based pH method shows a pH decrease during exercise, whereas a slight increase was observed by ³¹P NMR spectroscopy. Copyright © 2015 John Wiley & Sons, Ltd.     

DTI of human skeletal muscle: the effects of diffusion encoding parameters,signal‐to‐noise ratio and T2 on tensor indices and fiber tracts

In this study, we have performed simulations to address the effects of diffusion encoding parameters, signal‐to‐noise ratio (SNR) and T₂ on skeletal muscle diffusion tensor indices and fiber tracts. Where appropriate, simulations were corroborated and validated by in vivo diffusion tensor imaging (DTI) of human skeletal muscle. Specifically, we have addressed: (i) the accuracy and precision of the diffusion parameters and eigenvectors at different SNR levels; (ii) the effects of the diffusion gradient direction encoding scheme; (iii) the optimal b value for diffusion tensor estimation; (iv) the effects of changes in skeletal muscle T₂; and, finally, the influence of SNR on fiber tractography and derived (v) fiber lengths, (vi) pennation angles and (vii) fiber curvatures. We conclude that accurate DTI of skeletal muscle requires an SNR of at least 25, a b value of between 400 and 500 s/mm², and data acquired with at least 12 diffusion gradient directions homogeneously distributed on half a sphere. Furthermore, for DTI studies focusing on skeletal muscle injury or pathology, apparent changes in the diffusion parameters need to be interpreted with great care in view of the confounding effects of T₂, particularly for moderate to low SNR values. Copyright © 2013 John Wiley & Sons, Ltd.