Pitfalls and advantages of different strategies for the absolute quantification of N‐acetyl aspartate,creatine and choline in white and grey matter by 1H‐MRS

This study extensively investigates different strategies for the absolute quantitation of N‐acetyl aspartate, creatine and choline in white and grey matter by ¹H‐MRS at 1.5 T. The main focus of this study was to reliably estimate metabolite concentrations while reducing the scan time, which remains as one of the main problems in clinical MRS. Absolute quantitation was based on the water‐unsuppressed concentration as the internal standard. We compared strategies based on various experimental protocols and post‐processing strategies. Data were obtained from 30 control subjects using a PRESS sequence at several TE to estimate the transverse relaxation time, T₂, of the metabolites. Quantitation was performed with the algorithm QUEST using two different metabolite signal basis sets: a whole‐metabolite basis set (WhoM) and a basis set in which the singlet signals were split from the coupled signals (MSM). The basis sets were simulated in vivo for each TE used. Metabolites' T₂s were then determined by fitting the estimated signal amplitudes of the metabolites obtained at different TEs. Then the absolute concentrations (mM) of the metabolites were assessed for each subject using the estimated signal amplitudes and either the mean estimated relaxation times of all subjects (mean protocol, MP) or the T₂ estimated from the spectra derived from the same subject (individual protocol, IP). Results showed that MP represents a less time‐consuming alternative to IP in the quantitation of brain metabolites by ¹H‐MRS in both grey and white matter, with a comparable accuracy when performed by MSM. It was also shown that the acquisition time might be further reduced by using a variant of MP, although with reduced accuracy. In this variant, only one water‐suppressed and one water‐unsuppressed spectra were acquired, drastically reducing the duration of the entire MRS examination. However, statistical analysis highlights the reduced accuracy of MP when performed using WhoM, particularly at longer echo times. Copyright © 2009 John Wiley & Sons, Ltd.     

Can T1w/T2w ratio be used as a myelin‐specific measure in subcortical structures? Comparisons between FSE‐based T1w/T2w ratios,GRASE‐based T1w/T2w ratios and multi‐echo GRASE‐based myelin water fractions

Given the growing popularity of T₁‐weighted/T₂‐weighted (T₁w/T₂w) ratio measurements, the objective of the current study was to evaluate the concordance between T₁w/T₂w ratios obtained using conventional fast spin echo (FSE) versus combined gradient and spin echo (GRASE) sequences for T₂w image acquisition, and to compare the resulting T₁w/T₂w ratios with histologically validated myelin water fraction (MWF) measurements in several subcortical brain structures. In order to compare these measurements across a relatively wide range of myelin concentrations, whole‐brain T₁w magnetization prepared rapid acquisition gradient echo (MPRAGE), T₂w FSE and three‐dimensional multi‐echo GRASE data were acquired from 10 participants with multiple sclerosis at 3 T. Then, after high‐dimensional, non‐linear warping, region of interest (ROI) analyses were performed to compare T₁w/T₂w ratios and MWF estimates (across participants and brain regions) in 11 bilateral white matter (WM) and four bilateral subcortical grey matter (SGM) structures extracted from the JHU_MNI_SS ‘Eve’ atlas. Although the GRASE sequence systematically underestimated T₁w/T₂w values compared to the FSE sequence (revealed by Bland–Altman and mountain plots), linear regressions across participants and ROIs revealed consistently high correlations between the two methods (r² = 0.62 for all ROIs, r² = 0.62 for WM structures and r² = 0.73 for SGM structures). However, correlations between either FSE‐based or GRASE‐based T₁w/T₂w ratios and MWFs were extremely low in WM structures (FSE‐based, r² = 0.000020; GRASE‐based, r² = 0.0014), low across all ROIs (FSE‐based, r² = 0.053; GRASE‐based, r² = 0.029) and moderate in SGM structures (FSE‐based, r² = 0.20; GRASE‐based, r² = 0.17). Overall, our findings indicated a high degree of correlation (but not equivalence) between FSE‐based and GRASE‐based T₁w/T₂w ratios, and low correlations between T₁w/T₂w ratios and MWFs. This suggests that the two T₁w/T₂w ratio approaches measure similar facets of subcortical tissue microstructure, whereas T₁w/T₂w ratios and MWFs appear to be sensitized to different microstructural properties. On this basis, we conclude that multi‐echo GRASE sequences can be used in future studies to efficiently elucidate both general (T₁w/T₂w ratio) and myelin‐specific (MWF) tissue characteristics.     

Quantification of glutamate and glutamine using constant‐time point‐resolved spectroscopy at 3 T

Separate quantification of glutamate (Glu) and glutamine (Gln) using conventional MRS on clinical scanners is challenging. In previous work, constant‐time point‐resolved spectroscopy (CT‐PRESS) was optimized at 3 T to detect Glu, but did not resolve Gln. To quantify Glu and Gln, a time‐domain basis set was constructed taking into account metabolite T₂ relaxation times and dephasing from B₀ inhomogeneity. Metabolite concentrations were estimated by fitting the basis one‐dimensional CT‐PRESS diagonal magnitude spectra to the measured spectrum. This method was first validated using seven custom‐built phantoms containing variable metabolite concentrations, and then applied to in vivo data acquired in rats exposed to vaporized ethanol and controls. Separate metabolite quantification revealed increased Gln after 16 weeks and increased Glu after 24 weeks of vaporized ethanol exposure in ethanol‐treated compared with control rats. Without separate quantification, the signal from the combined resonances of Glu and Gln (Glx) showed an increase at both 16 and 24 weeks in ethanol‐exposed rats, precluding the determination of the independent and differential contribution of each metabolite at each time. Copyright © 2012 John Wiley & Sons, Ltd.     

Optimized MEGA‐SPECIAL for in vivo glutamine detection in the rat brain at 14.1 T

Glutamine has multiple roles in brain metabolism and its concentration can be altered in various pathological conditions. An accurate knowledge of its concentration is therefore highly desirable to monitor and study several brain disorders in vivo. However, in recent years, several MRS studies have reported conflicting glutamine concentrations in the human brain. A recent hypothesis for explaining these discrepancies is that a short T₂ component of the glutamine signal may impact on its quantification at long echo times. The present study therefore aimed to investigate the impact of acquisition parameters on the quantified glutamine concentration using two different acquisition techniques, SPECIAL at ultra‐short echo time and MEGA‐SPECIAL at moderate echo time. For this purpose, MEGA‐SPECIAL was optimized for the first time for glutamine detection. Based on the very good agreement of the glutamine concentration obtained between the two measurements, it was concluded that no impact of a short T₂ component of the glutamine signal was detected. Copyright © 2014 John Wiley & Sons, Ltd.     

Inversion recovery ultrashort echo time imaging of ultrashort T2 tissue components in ovine brain at 3 T: a sequential D2O exchange study

Inversion recovery ultrashort echo time (IR‐UTE) imaging holds the potential to directly characterize MR signals from ultrashort T₂ tissue components (STCs), such as collagen in cartilage and myelin in brain. The application of IR‐UTE for myelin imaging has been challenging because of the high water content in brain and the possibility that the ultrashort T₂* signals are contaminated by water protons, including those associated with myelin sheaths. This study investigated such a possibility in an ovine brain D₂O exchange model and explored the potential of IR‐UTE imaging for the quantification of ultrashort T₂* signals in both white and gray matter at 3 T. Six specimens were examined before and after sequential immersion in 99.9% D₂O. Long T₂ MR signals were measured using a clinical proton density‐weighted fast spin echo (PD‐FSE) sequence. IR‐UTE images were first acquired with different inversion times to determine the optimal inversion time to null the long T₂ signals (TI_null). Then, at this TI_null, images with echo times (TEs) of 0.01–4 ms were acquired to measure the T₂* values of STCs. The PD‐FSE signal dropped to near zero after 24 h of immersion in D₂O. A wide range of TI_null values were used at different time points (240–330 ms for white matter and 320–350 ms for gray matter at TR = 1000 ms) because the T₁ values of the long T₂ tissue components changed significantly. The T₂* values of STCs were 200–300 μs in both white and gray matter (comparable with the values obtained from myelin powder and its mixture with D₂O or H₂O), and showed minimal changes after sequential immersion. The ultrashort T₂* signals seen on IR‐UTE images are unlikely to be from water protons as they are exchangeable with deuterons in D₂O. The source is more likely to be myelin itself in white matter, and might also be associated with other membranous structures in gray matter.     

Triple‐echo steady‐state T2 relaxometry of the human brain at high to ultra‐high fields

Quantitative MRI techniques, such as T₂ relaxometry, have demonstrated the potential to detect changes in the tissue microstructure of the human brain with higher specificity to the underlying pathology than in conventional morphological imaging. At high to ultra‐high field strengths, quantitative MR‐based tissue characterization benefits from the higher signal‐to‐noise ratio traded for either improved resolution or reduced scan time, but is impaired by severe static (B₀) and transmit (B₁) field heterogeneities. The objective of this study was to derive a robust relaxometry technique for fast T₂ mapping of the human brain at high to ultra‐high fields, which is highly insensitive to B₀ and B₁ field variations. The proposed method relies on a recently presented three‐dimensional (3D) triple‐echo steady‐state (TESS) imaging approach that has proven to be suitable for fast intrinsically B₁‐insensitive T₂ relaxometry of rigid targets. In this work, 3D TESS imaging is adapted for rapid high‐ to ultra‐high‐field two‐dimensional (2D) acquisitions. The achieved short scan times of 2D TESS measurements reduce motion sensitivity and make TESS‐based T₂ quantification feasible in the brain. After validation in vitro and in vivo at 3 T, T₂ maps of the human brain were obtained at 7 and 9.4 T. Excellent agreement between TESS‐based T₂ measurements and reference single‐echo spin‐echo data was found in vitro and in vivo at 3 T, and T₂ relaxometry based on TESS imaging was proven to be feasible and reliable in the human brain at 7 and 9.4 T. Although prominent B₀ and B₁ field variations occur at ultra‐high fields, the T₂ maps obtained show no B₀‐ or B₁‐related degradations. In conclusion, as a result of the observed robustness, TESS T₂ may emerge as a valuable measure for the early diagnosis and progression monitoring of brain diseases in high‐resolution 2D acquisitions at high to ultra‐high fields. Copyright © 2014 John Wiley & Sons, Ltd.     

Measurement of regional variation of GABA in the human brain by optimized point‐resolved spectroscopy at 7 T in vivo

The ¹H resonances of γ‐aminobutyric acid (GABA) in the human brain in vivo are extensively overlapped with the neighboring abundant resonances of other metabolites and remain indiscernible in short‐TE MRS at 7 T. Here we report that the GABA resonance at 2.28 ppm can be fully resolved by means of echo time optimization of a point‐resolved spectroscopy (PRESS) scheme. Following numerical simulations and phantom validation, the subecho times of PRESS were optimized at (TE, TE₂) = (31, 61) ms for detection of GABA, glutamate (Glu), glutamine (Gln), and glutathione (GSH). The in vivo feasibility of the method was tested in several brain regions in nine healthy subjects. Spectra were acquired from the medial prefrontal, left frontal, medial occipital, and left occipital brain and analyzed with LCModel. Following the gray and white matter (GM and WM) segmentation of T₁‐weighted images, linear regression of metabolite estimates was performed against the fractional GM contents. The GABA concentration was estimated to be about seven times higher in GM than in WM. GABA was overall higher in frontal than in occipital brain. Glu was about twice as high in GM as in WM in both frontal and occipital brain. Gln was significantly different between frontal GM and WM while being similar between occipital GM and WM. GSH did not show significant dependence on tissue content. The signals from N‐acetylaspartylglutamate were clearly resolved, giving the concentration more than 10 times higher in WM than in GM. Our data indicate that the PRESS TE = 92 ms method provides an effective means for measuring GABA and several challenging J‐coupled spin metabolites in human brain at 7 T. Copyright © 2014 John Wiley & Sons, Ltd.     

A rapid inversion technique for the measurement of longitudinal relaxation times of brain metabolites: application to lactate in high‐grade gliomas at 3 T

The aim of this study was to develop a time‐efficient inversion technique to measure the T₁ relaxation time of the methyl group of lactate (Lac) in the presence of contaminating lipids and to measure T₁ at 3 T in a cohort of primary high‐grade gliomas. Three numerically optimized inversion times (TIs) were chosen to minimize the expected error in T₁ estimates for a given input total scan duration (set to be 30 min). A two‐cycle spectral editing scheme was used to suppress contaminating lipids. The T₁ values were then estimated from least‐squares fitting of signal measurements versus TI. Lac T₁ was estimated as 2000 ± 280 ms. After correcting for T₁ (and T₂ from literature values), the mean absolute Lac concentration was estimated as 4.3 ± 2.6 mm . The technique developed agrees with the results obtained by standard inversion recovery and can be used to provide rapid T₁ estimates of other spectral components as required. Lac T₁ exhibits similar variations to other major metabolites observable by MRS in high‐grade gliomas. The T₁ estimate provided here will be useful for future MRS studies wishing to report relaxation‐corrected estimates of Lac concentration as an objective tumor biomarker. Copyright © 2016 John Wiley & Sons, Ltd.     

Global brain metabolic quantification with whole‐head proton MRS at 3 T

Total N‐acetyl‐aspartate + N‐acetyl‐aspartate–glutamate (NAA), total creatine (Cr) and total choline (Cho) proton MRS (¹H–MRS) signals are often used as surrogate markers in diffuse neurological pathologies, but spatial coverage of this methodology is limited to 1%–65% of the brain. Here we wish to demonstrate that non‐localized, whole‐head (WH) ¹H–MRS captures just the brain's contribution to the Cho and Cr signals, ignoring all other compartments. Towards this end, 27 young healthy adults (18 men, 9 women), 29.9 ± 8.5 years old, were recruited and underwent T₁‐weighted MRI for tissue segmentation, non‐localizing, approximately 3 min WH ¹H–MRS (T_E/T_R/T_I = 5/10 1 /940 ms) and 30 min ¹H–MR spectroscopic imaging (MRSI) (T_E/T_R = 35/2100 ms) in a 360 cm³ volume of interest (VOI) at the brain's center. The VOI absolute NAA, Cr and Cho concentrations, 7.7 ± 0.5, 5.5 ± 0.4 and 1.3 ± 0.2 mM, were all within 10% of the WH: 8.6 ± 1.1, 6.0 ± 1.0 and 1.3 ± 0.2 mM. The mean NAA/Cr and NAA/Cho ratios in the WH were only slightly higher than the “brain‐only” VOI: 1.5 versus 1.4 (7%) and 6.6 versus 5.9 (11%); Cho/Cr were not different. The brain/WH volume ratio was 0.31 ± 0.03 (brain ≈ 30% of WH volume). Air‐tissue susceptibility‐driven local magnetic field changes going from the brain outwards showed sharp gradients of more than 100 Hz/cm (1 ppm/cm), explaining the skull's Cr and Cho signal losses through resonance shifts, line broadening and destructive interference. The similarity of non‐localized WH and localized VOI NAA, Cr and Cho concentrations and their ratios suggests that their signals originate predominantly from the brain. Therefore, the fast, comprehensive WH‐¹H‐MRS method may facilitate quantification of these metabolites, which are common surrogate markers in neurological disorders.     

In vivo T2 relaxation time measurement with echo‐time averaging

The accuracy of metabolite concentrations measured using in vivo proton (¹H) MRS is enhanced following correction for spin–spin (T₂) relaxation effects. In addition, metabolite proton T₂ relaxation times provide unique information regarding cellular environment and molecular mobility. Echo‐time (TE) averaging ¹H MRS involves the collection and averaging of multiple TE steps, which greatly simplifies resulting spectra due to the attenuation of spin‐coupled and macromolecule resonances. Given the simplified spectral appearance and inherent metabolite T₂ relaxation information, the aim of the present proof‐of‐concept study was to develop a novel data processing scheme to estimate metabolite T₂ relaxation times from TE‐averaged ¹H MRS data. Spectral simulations are used to validate the proposed TE‐averaging methods for estimating methyl proton T₂ relaxation times for N‐acetyl aspartate, total creatine, and choline‐containing compounds. The utility of the technique and its reproducibility are demonstrated using data obtained in vivo from the posterior‐occipital cortex of 10 healthy control subjects. Compared with standard methods, distinct advantages of this approach include built‐in macromolecule resonance attenuation, in vivo T₂ estimates closer to reported values when maximum TE ≈ T₂, and the potential for T₂ calculation of metabolite resonances otherwise inseparable in standard ¹H MRS spectra recorded in vivo. Copyright © 2014 John Wiley & Sons, Ltd.     

Regional neurochemical profiles in the human brain measured by 1H MRS at 7 T using local B1 shimming

Increased sensitivity and chemical shift dispersion at ultra‐high magnetic fields enable the precise quantification of an extended range of brain metabolites from ¹H MRS. However, all previous neurochemical profiling studies using single‐voxel MRS at 7 T have been limited to data acquired from the occipital lobe with half‐volume coils. The challenges of ¹H MRS of the human brain at 7 T include short T₂ and complex B₁ distribution that imposes limitations on the maximum achievable B₁ strength. In this study, the feasibility of acquiring and quantifying short‐echo (TE = 8 ms), single‐voxel ¹H MR spectra from multiple brain regions was demonstrated by utilizing a 16‐channel transceiver array coil with 16 independent transmit channels, allowing local transmit B₁ (B₁⁺) shimming. Spectra were acquired from volumes of interest of 1–8 mL in brain regions that are of interest for various neurological disorders: frontal white matter, posterior cingulate, putamen, substantia nigra, pons and cerebellar vermis. Local B₁⁺ shimming substantially increased the transmit efficiency, especially in the peripheral and ventral brain regions. By optimizing a STEAM sequence for utilization with a 16‐channel coil, artifact‐free spectra were acquired with a small chemical shift displacement error (<5% /ppm/direction) from all regions. The high signal‐to‐noise ratio enabled the quantification of neurochemical profiles consisting of at least nine metabolites, including γ‐aminobutyric acid, glutamate and glutathione, in all brain regions. Significant differences in neurochemical profiles were observed between brain regions. For example, γ‐aminobutyric acid levels were highest in the substantia nigra, total creatine was highest in the cerebellar vermis and total choline was highest in the pons, consistent with the known biochemistry of these regions. These findings demonstrate that single‐voxel ¹H MRS at ultra‐high field can reliably detect region‐specific neurochemical patterns in the human brain, and has the potential to objectively detect alterations in neurochemical profiles associated with neurological diseases. Copyright © 2011 John Wiley & Sons, Ltd.     

The age dependence of T2 relaxation times of N‐acetyl aspartate,creatine and choline in the human brain at 3 and 4T

Knowledge of the T₂ age dependence is of importance for MRS clinical studies involving subject groups with a wide age range. A number of studies have focused on the age dependence of T₂ values in the human brain, with rather conflicting results. The aim of this study was to analyze the age dependence of T₂ values of N‐acetyl aspartate (NAA), creatine (Cr) and choline (Cho) in the human brain using data acquired at 3T and 4T and to assess the influence of the macromolecule (MM) baseline handling on the obtained results. Two distinct groups of young and elderly controls have been measured at 3T (T_E = 30–540 ms, 9 young and 11 elderly subjects) and 4T (T_E = 10–180 ms, 18 young and 14 elderly subjects) using single‐voxel spectroscopy. In addition, MM spectra were measured from two subjects using the inversion‐recovery technique at 4T. All spectra were processed with LCModel using basis sets with different MM signals (measured or simulated) and also with MM signals included for a different T_E range. Individual estimated T₂ values were statistically analyzed using the R programming language for the age dependence of T₂ values as well as the influence of the MM baseline handling. A significant decrease of T₂ values of NAA and Cr in elderly subjects compared with young subjects was confirmed. The same trend was observed for Cho. Significantly higher T₂ values calculated using the measured MM baseline for all studied metabolites at 4T were observed for both young and elderly subjects. To conclude, while the handling of MM and lipid signals may have a significant effect on estimated T₂ values, we confirmed the age dependence of T₂ values of NAA and Cr and the same trend for Cho in the human brain. Copyright © 2016 John Wiley & Sons, Ltd.     

Quantification of 1H–MRS signals based on sparse metabolite profiles in the time‐frequency domain

MRS is an analytical approach used for both quantitative and qualitative analysis of human body metabolites. The accurate and robust quantification capability of proton MRS (¹H–MRS) enables the accurate estimation of living tissue metabolite concentrations. However, such methods can be efficiently employed for quantification of metabolite concentrations only if the overlapping nature of metabolites, existing static field inhomogeneity and low signal‐to‐noise ratio (SNR) are taken into consideration. Representation of ¹H–MRS signals in the time‐frequency domain enables us to handle the baseline and noise better. This is possible because the MRS signal of each metabolite is sparsely represented, with only a few peaks, in the frequency domain, but still along with specific time‐domain features such as distinct decay constant associated with T ₂ relaxation rate. The baseline, however, has a smooth behavior in the frequency domain. In this study, we proposed a quantification method using continuous wavelet transformation of ¹H–MRS signals in combination with sparse representation of features in the time‐frequency domain. Estimation of the sparse representations of MR spectra is performed according to the dictionaries constructed from metabolite profiles. Results on simulated and phantom data show that the proposed method is able to quantify the concentration of metabolites in ¹H–MRS signals with high accuracy and robustness. This is achieved for both low SNR (5 dB) and low signal‐to‐baseline ratio (?5 dB) regimes.     

Non‐water‐suppressed short‐echo‐time magnetic resonance spectroscopic imaging using a concentric ring k‐space trajectory

Water‐suppressed MRS acquisition techniques have been the standard MRS approach used in research and for clinical scanning to date. The acquisition of a non‐water‐suppressed MRS spectrum is used for artefact correction, reconstruction of phased‐array coil data and metabolite quantification. Here, a two‐scan metabolite‐cycling magnetic resonance spectroscopic imaging (MRSI) scheme that does not use water suppression is demonstrated and evaluated. Specifically, the feasibility of acquiring and quantifying short‐echo (T_E = 14 ms), two‐dimensional stimulated echo acquisition mode (STEAM) MRSI spectra in the motor cortex is demonstrated on a 3 T MRI system. The increase in measurement time from the metabolite‐cycling is counterbalanced by a time‐efficient concentric ring k‐space trajectory. To validate the technique, water‐suppressed MRSI acquisitions were also performed for comparison. The proposed non‐water‐suppressed metabolite‐cycling MRSI technique was tested for detection and correction of resonance frequency drifts due to subject motion and/or hardware instability, and the feasibility of high‐resolution metabolic mapping over a whole brain slice was assessed. Our results show that the metabolite spectra and estimated concentrations are in agreement between non‐water‐suppressed and water‐suppressed techniques. The achieved spectral quality, signal‐to‐noise ratio (SNR) > 20 and linewidth <7 Hz allowed reliable metabolic mapping of five major brain metabolites in the motor cortex with an in‐plane resolution of 10 × 10 mm² in 8 min and with a Cramér‐Rao lower bound of less than 20% using LCModel analysis. In addition, the high SNR of the water peak of the non‐water‐suppressed technique enabled voxel‐wise single‐scan frequency, phase and eddy current correction. These findings demonstrate that our non‐water‐suppressed metabolite‐cycling MRSI technique can perform robustly on 3 T MRI systems and within a clinically feasible acquisition time.     

Spectral fitting using basis set modified by measured B0 field distribution

This study sought to demonstrate and evaluate a novel spectral fitting method to improve quantification accuracy in the presence of large magnetic field distortion, especially with high fields. MRS experiments were performed using a point‐resolved spectroscopy (PRESS)‐type sequence at 7 T. A double‐echo gradient echo (GRE) sequence was used to acquire B₀ maps following MRS experiments. The basis set was modified based on the measured B₀ distribution within the MRS voxel. Quantification results were obtained after fitting the measured MRS data using the modified basis set. The proposed method was validated using numerical Monte Carlo simulations, phantom measurements, and comparison of occipital lobe MRS measurements under homogeneous and inhomogeneous magnetic field conditions. In vivo results acquired from voxels placed in thalamus and prefrontal cortex regions close to the frontal sinus agreed well with published values. Instead of noise‐amplifying complex division, the proposed method treats field variations as part of the signal model, thereby avoiding inherent statistical bias associated with regularization. Simulations and experiments showed that the proposed approach reliably quantified results in the presence of relatively large magnetic field distortion. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.     

Q‐ball imaging with PROPELLER EPI acquisition

Q‐ball imaging (QBI) is an imaging technique that is capable of resolving intravoxel fiber crossings; however, the signal readout based on echo‐planar imaging (EPI) introduces geometric distortions in the presence of susceptibility gradients. This study proposes an imaging technique that reduces susceptibility distortions in QBI by short‐axis PROPELLER EPI acquisition. Conventional QBI and PROPELLER QBI data were acquired from two 3T MR scans of the brains of five healthy subjects. Prior to the PROPELLER reconstruction, residual distortions in single‐blade low‐resolution b0 and diffusion‐weighted images (DWIs) were minimized by linear affine and nonlinear diffeomorphic demon registrations. Subsequently, the PROPELLER keyhole reconstruction was applied to the corrected DWIs to obtain high‐resolution PROPELLER DWIs. The generalized fractional anisotropy and orientation distribution function maps contained fewer distortions in PROPELLER QBI than in conventional QBI, and the fiber tracts more closely matched the brain anatomy depicted by turbo spin‐echo (TSE) T₂‐weighted imaging (T2WI). Furthermore, for fixed T_E, PROPELLER QBI enabled a shorter scan time than conventional QBI. We conclude that PROPELLER QBI can reduce susceptibility distortions without lengthening the acquisition time and is suitable for tracing neuronal fiber tracts in the human brain. Copyright © 2013 John Wiley & Sons, Ltd.     

Decreased water T2 in fatty infiltrated skeletal muscles of patients with neuromuscular diseases

Quantitative imaging techniques are emerging in the field of magnetic resonance imaging of neuromuscular diseases (NMD). T₂ of water (T_2w) is considered an important imaging marker to assess acute and chronic alterations of the muscle fibers, being generally interpreted as an indicator for “disease activity” in the muscle tissue. To validate the accuracy and robustness of quantitative imaging methods, ¹H magnetic resonance spectroscopy (MRS) can be used as a gold standard. The purpose of the present work was to investigate T_2w of remaining muscle tissue in regions of higher proton density fat fraction (PDFF) in 40 patients with defined NMD using multi‐TE single‐voxel ¹H MRS. Patients underwent MR measurements on a 3 T system to perform a multi‐TE single‐voxel stimulated echo acquisition method (STEAM) MRS (TE = 11/15/20/25(/35) ms) in regions of healthy, edematous and fatty thigh muscle tissue. Muscle regions for MRS were selected based on T₂‐weighted water and fat images of a two‐echo 2D Dixon TSE. MRS results were confined to regions with qualitatively defined remaining muscle tissue without edema and high fat content, based on visual grading of the imaging data. The results showed decreased T_2w values with increasing PDFF with R² = 0.45 (p < 10^?3) (linear fit) and with R² = 0.51 (exponential fit). The observed dependence of T_2w on PDFF should be considered when using T_2w as a marker in NMD imaging and when performing single‐voxel MRS for T_2w in regions enclosing edematous, nonedematous and fatty infiltrated muscle tissue.     

Three‐dimensional whole‐brain perfusion quantification using pseudo‐continuous arterial spin labeling MRI at multiple post‐labeling delays: accounting for both arterial transit time and impulse response function

Measurement of the cerebral blood flow (CBF) with whole‐brain coverage is challenging in terms of both acquisition and quantitative analysis. In order to fit arterial spin labeling‐based perfusion kinetic curves, an empirical three‐parameter model which characterizes the effective impulse response function (IRF) is introduced, which allows the determination of CBF, the arterial transit time (ATT) and T_1,eff. The accuracy and precision of the proposed model were compared with those of more complicated models with four or five parameters through Monte Carlo simulations. Pseudo‐continuous arterial spin labeling images were acquired on a clinical 3‐T scanner in 10 normal volunteers using a three‐dimensional multi‐shot gradient and spin echo scheme at multiple post‐labeling delays to sample the kinetic curves. Voxel‐wise fitting was performed using the three‐parameter model and other models that contain two, four or five unknown parameters. For the two‐parameter model, T_1,eff values close to tissue and blood were assumed separately. Standard statistical analysis was conducted to compare these fitting models in various brain regions. The fitted results indicated that: (i) the estimated CBF values using the two‐parameter model show appreciable dependence on the assumed T_1,eff values; (ii) the proposed three‐parameter model achieves the optimal balance between the goodness of fit and model complexity when compared among the models with explicit IRF fitting; (iii) both the two‐parameter model using fixed blood T₁ values for T_1,eff and the three‐parameter model provide reasonable fitting results. Using the proposed three‐parameter model, the estimated CBF (46 ± 14 mL/100 g/min) and ATT (1.4 ± 0.3 s) values averaged from different brain regions are close to the literature reports; the estimated T_1,eff values (1.9 ± 0.4 s) are higher than the tissue T₁ values, possibly reflecting a contribution from the microvascular arterial blood compartment.     

Improved resolution of glutamate,glutamine and γ‐aminobutyric acid with optimized point‐resolved spectroscopy sequence timings for their simultaneous quantification at 9.4 T

Glutamine (Gln), glutamate (Glu) and γ‐aminobutyric acid (GABA) are relevant brain metabolites that can be measured with magnetic resonance spectroscopy (MRS). This work optimizes the point‐resolved spectroscopy (PRESS) sequence echo times, TE₁ and TE₂, for improved simultaneous quantification of the three metabolites at 9.4 T. Quantification was based on the proton resonances of Gln, Glu and GABA at ≈2.45, ≈2.35 and ≈2.28 ppm, respectively. Glu exhibits overlap with both Gln and GABA; in addition, the Gln peak is contaminated by signal from the strongly coupled protons of N‐acetylaspartate (NAA), which resonate at about 2.49 ppm. J‐coupling evolution of the protons was characterized numerically and verified experimentally. A {TE₁, TE₂} combination of {106 ms, 16 ms} minimized the NAA signal in the Gln spectral region, whilst retaining Gln, Glu and GABA peaks. The efficacy of the technique was verified on phantom solutions and on rat brain in vivo. LCModel was employed to analyze the in vivo spectra. The average T₂‐corrected Gln, Glu and GABA concentrations were found to be 3.39, 11.43 and 2.20 mM, respectively, assuming a total creatine concentration of 8.5 mM. LCModel Cramér–Rao lower bounds (CRLBs) for Gln, Glu and GABA were in the ranges 14–17%, 4–6% and 16–19%, respectively. The optimal TE resulted in concentrations for Gln and GABA that agreed more closely with literature concentrations compared with concentrations obtained from short‐TE spectra acquired with a {TE₁, TE₂} combination of {12 ms, 9 ms}. LCModel estimations were also evaluated with short‐TE PRESS and with the optimized long TE of {106 ms, 16 ms}, using phantom solutions of known metabolite concentrations. It was shown that concentrations estimated with LCModel can be inaccurate when combined with short‐TE PRESS, where there is peak overlap, even when low (<20%) CRLBs are reported.     

Refined modelling of the short‐T2 signal component and ensuing detection of glutamate and glutamine in short‐TE,localised, 1H MR spectra of human glioma measured at 3 T

Short‐TE ¹H MRS has great potential for brain cancer diagnostics. A major difficulty in the analysis of the spectra is the contribution from short‐T₂ signal components, mainly coming from mobile lipids. This complicates the accurate estimation of the spectral parameters of the resonance lines from metabolites, so that a qualitative to semi‐quantitative interpretation of the spectra dominates in practice. One solution to overcome this difficulty is to measure and estimate the short‐T₂ signal component and to subtract it from the total signal, thus leaving only the metabolite signals. The technique works well when applied to spectra obtained from healthy individuals, but requires some optimisation during data acquisition. In the clinical setting, time constraints hardly allow this. Here, we propose an iterative estimation of the short‐T₂ signal component, acquired in a single acquisition after measurement of the full spectrum. The method is based on QUEST (quantitation based on quantum estimation) and allows the refinement of the estimate of the short‐T₂ signal component after measurement. Thus, acquisition protocols used on healthy volunteers can also be used on patients without further optimisation. The aim is to improve metabolite detection and, ultimately, to enable the estimation of the glutamine and glutamate signals distinctly. These two metabolites are of great interest in the characterisation of brain cancer, gliomas in particular. When applied to spectra from healthy volunteers, the new algorithm yields similar results to QUEST and direct subtraction of the short‐T₂ signal component. With patients, up to 12 metabolites and, at least, seven can be quantified in each individual brain tumour spectrum, depending on the metabolic state of the tumour. The refinement of the short‐T₂ signal component significantly improves the fitting procedure and produces a separate short‐T₂ signal component that can be used for the analysis of mobile lipid resonances. Thus, in brain tumour spectra, distinct estimates of signals from glutamate and glutamine are possible. Copyright © 2016 John Wiley & Sons, Ltd.