Serial proton spectroscopy,magnetization transfer ratio and T 2 relaxation in pseudotumoral demyelinating lesions

In some rare cases, demyelinating plaques appear on contrast-enhanced T1-weighted images as pseudotumoral, cyst-like lesions (hypointense, ring enhancing). Serial proton MR spectroscopy, T2 relaxometry and magnetization transfer ratios (MTR) were performed on three pseudotumoral demyelinating lesions to obtain information about their pathological basis. Baseline and 1-month MTR and T2 values were similar to those of cerebrospinal fluid, while spectra showed lactate, lipids and choline. Three-month and 1 year exams showed recovery of MTR, T2 and N-acetylaspartate, approaching the contralateral values, while creatine and choline were normal or surpassed contralateral values. Lipids and lactate gradually disappeared. These results suggest that pseudotumoral, cyst-like, ring-enhancing lesions may be characterized by an accumulation of oedema in the extracellular space with an almost complete absence of cells. Reduction of the oedema allows restoration of the tissue to its original location, indicating that cellular destruction was less important than was expected after the first exam. Thus, the evolution of this kind of lesion should be kept in mind when considering lesion volume from T1-weighted images as a marker of disability or irreversible cellular destruction in MS.     

A combined analytical solution for chemical exchange saturation transfer and semi‐solid magnetization transfer

Off‐resonant RF irradiation in tissue indirectly lowers the water signal by saturation transfer processes: on the one hand, there are selective chemical exchange saturation transfer (CEST) effects originating from exchanging endogenous protons resonating a few parts per million from water; on the other hand, there is the broad semi‐solid magnetization transfer (MT) originating from immobile protons associated with the tissue matrix with kilohertz linewidths. Recently it was shown that endogenous CEST contrasts can be strongly affected by the MT background, so corrections are needed to derive accurate estimates of CEST effects. Herein we show that a full analytical solution of the underlying Bloch–McConnell equations for both MT and CEST provides insights into their interaction and suggests a simple means to isolate their effects. The presented analytical solution, based on the eigenspace solution of the Bloch–McConnell equations, extends previous treatments by allowing arbitrary lineshapes for the semi‐solid MT effects and simultaneously describing multiple CEST pools in the presence of a large MT pool for arbitrary irradiation. The structure of the model indicates that semi‐solid MT and CEST effects basically add up inversely in determining the steady‐state Z‐spectrum, as previously shown for direct saturation and CEST effects. Implications for existing previous CEST analyses in the presence of a semi‐solid MT are studied and discussed. It turns out that, to accurately quantify CEST contrast, a good reference Z‐value, the observed longitudinal relaxation rate of water, and the semi‐solid MT pool size fraction must all be known. Copyright © 2014 John Wiley & Sons, Ltd.     

Comparison of 31P saturation and inversion magnetization transfer in human liver and skeletal muscle using a clinical MR system and surface coils

³¹P MRS magnetization transfer (³¹P‐MT) experiments allow the estimation of exchange rates of biochemical reactions, such as the creatine kinase equilibrium and adenosine triphosphate (ATP) synthesis. Although various ³¹P‐MT methods have been successfully used on isolated organs or animals, their application on humans in clinical scanners poses specific challenges. This study compared two major ³¹P‐MT methods on a clinical MR system using heteronuclear surface coils. Although saturation transfer (ST) is the most commonly used ³¹P‐MT method, sequences such as inversion transfer (IT) with short pulses might be better suited for the specific hardware and software limitations of a clinical scanner. In addition, small NMR‐undetectable metabolite pools can transfer MT to NMR‐visible pools during long saturation pulses, which is prevented with short pulses. ³¹P‐MT sequences were adapted for limited pulse length, for heteronuclear transmit–receive surface coils with inhomogeneous B₁, for the need for volume selection and for the inherently low signal‐to‐noise ratio (SNR) on a clinical 3‐T MR system. The ST and IT sequences were applied to skeletal muscle and liver in 10 healthy volunteers. Monte‐Carlo simulations were used to evaluate the behavior of the IT measurements with increasing imperfections. In skeletal muscle of the thigh, ATP synthesis resulted in forward reaction constants (k) of 0.074 ±0.022 s^–1 (ST) and 0.137 ±0.042 s^–1 (IT), whereas the creatine kinase reaction yielded 0.459 ±0.089 s^–1 (IT). In the liver, ATP synthesis resulted in k = 0.267 ±0.106 s^–1 (ST), whereas the IT experiment yielded no consistent results. ST results were close to literature values; however, the IT results were either much larger than the corresponding ST values and/or were widely scattered. To summarize, ST and IT experiments can both be implemented on a clinical body scanner with heteronuclear transmit–receive surface coils; however, ST results are much more robust against experimental imperfections than the current implementation of IT. Copyright © 2014 John Wiley & Sons, Ltd.     

Effects of formalin fixation and temperature on MR relaxation times in the human brain

Post‐mortem MRI of the brain is increasingly applied in neuroscience for a better understanding of the contrast mechanisms of disease induced tissue changes. However, the influence of chemical processes caused by formalin fixation and differences in temperature may hamper the comparability with results from in vivo MRI. In this study we investigated how formalin fixation and temperature affect T₁, T₂ and T₂* relaxation times of brain tissue. Fixation effects were examined with respect to changes in water content and crosslinking. Relaxometry was performed in brain slices from five deceased subjects at different temperatures. All measurements were repeated after 190 days of formaldehyde immersion. The water content of unfixed and fixed tissue was determined using the wet‐to‐dry ratio following drying. Protein weight was determined with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE). Fixation caused a strong decrease of all relaxation times, the strongest effect being seen on T₁, with a reduction of up to 76%. The temperature coefficient of T₁ was lower in the fixed than unfixed tissue, which was in contrast to T₂, where an increase of the temperature coefficient was observed following fixation. The reduction of the water content after fixation was in the range of 1–6% and thus not sufficient to explain the changes in relaxation time. Results from SDS‐PAGE indicated a strong increase of the protein size above 260 kDa in all brain structures examined. Our results suggest that crosslinking induced changes of the macromolecular matrix are responsible for T₁ shortening and a decreased temperature dependency. The relaxation times provided in this work should allow optimization of post‐mortem MRI protocols for the brain. Copyright © 2016 John Wiley & Sons, Ltd.     

Proton T2 relaxation of cerebral metabolites of normal human brain over large TE range

T2 of NAA, creatine and choline-containing compounds were measured in posterior frontal white matter and occipital grey matter in 10 healthy human volunteers. Decay curves comprised signals from eight TE times ranging from 30 to 800 ms with TR 2000 ms acquired with a PRESS sequence on a 1.5 T clinical scanner. Simulations were conducted to assess the precision of T2 estimates from decay curves comprising varying numbers and ranges of TE points. Mean and standard errors for T2s of NAA, creatine and choline-containing compounds were 300(8), 169(3) and 239(4) ms in posterior frontal white matter and 256(6), 159(8) and 249(8) ms in occipital grey matter. In vivo T2s found for choline and NAA were shorter than the T2s in the literature. The elevation of literature T2s is accounted for by the simulation results, which demonstrated that there is a bias towards lengthened T2s when T2 is measured with a maximum TE approximately T2. Concentration estimates are at risk of being underestimated if previously reported T2 corrections are used.     

Doubly selective multiple quantum chemical shift imaging and T1 relaxation time measurement of glutathione (GSH) in the human brain in vivo

Mapping of a major antioxidant, glutathione (GSH), was achieved in the human brain in vivo using a doubly‐selective multiple quantum filtering based chemical shift imaging (CSI) of GSH at 3 T. Both in vivo and phantom tests in CSI and single voxel measurements were consistent with excellent suppression of overlapping signals from creatine, γ‐Amino butyric acid (GABA) and macromolecules. GSH concentration in the fronto‐parietal region was 1.20 ± 0.16 µmol/g (mean ± SD, n = 7). The longitudinal relaxation time (T₁) of GSH in the human brain was 397 ± 44 ms (mean ± SD, n = 5), which was substantially shorter than that of other metabolites. This GSH‐CSI method permits us to address regional differences of GSH in the human brain under conditions where oxidative stress has been implicated, including multiple sclerosis, aging and neurodegenerative diseases. Copyright © 2012 John Wiley & Sons, Ltd.     

Quantitative ATP synthesis in human liver measured by localized 31P spectroscopy using the magnetization transfer experiment

The liver plays a central role in intermediate metabolism. Accumulation of liver fat (steatosis) predisposes to various liver diseases. Steatosis and abnormal muscle energy metabolism are found in insulin-resistant and type-2 diabetic states. To examine hepatic energy metabolism, we measured hepatocellular lipid content, using proton MRS, and rates of hepatic ATP synthesis in vivo, using the 31P magnetization transfer experiment. A suitable localization scheme was developed and applied to the measurements of longitudinal relaxation times (T1) in six healthy volunteers and the ATP-synthesis experiment in nine healthy volunteers. Liver 31P spectra were modelled and quantified successfully using a time domain fit and the AMARES (advanced method for accurate, robust and efficient spectral fitting of MRS data with use of prior knowledge) algorithm describing the essential components of the dataset. The measured T1 relaxation times are comparable to values reported previously at lower field strengths. All nine subjects in whom saturation transfer was measured had low hepatocellular lipid content (1.5 +/- 0.2% MR signal; mean +/- SEM). The exchange rate constant (k) obtained was 0.30 +/- 0.02 s(-1), and the rate of ATP synthesis was 29.5 +/- 1.8 mM/min. The measured rate of ATP synthesis is about three times higher than in human skeletal muscle and human visual cortex, but only about half of that measured in perfused rat liver. In conclusion, 31P MRS at 3 T provides sufficient sensitivity to detect magnetization transfer effects and can therefore be used to assess ATP synthesis in human liver.     

High‐resolution imaging of magnetisation transfer and nuclear Overhauser effect in the human visual cortex at 7 T

The aim of this study was to optimise a pulse sequence for high‐resolution imaging sensitive to the effects of conventional macromolecular magnetisation transfer (MT^m) and nuclear Overhauser enhancement (NOE), and to use it to investigate variations in these parameters across the cerebral cortex. A high‐spatial‐resolution magnetisation transfer‐prepared turbo field echo (MT‐TFE) sequence was designed to have high sensitivity to MT^m and NOE effects, whilst being robust to B₀ and B₁ inhomogeneities, and producing a good point spread function across the cortex. This was achieved by optimising the saturation and imaging components of the sequence using simulations based on the Bloch equations, including exchange and an image simulator. This was used to study variations in these parameters across the cortex. Using the sequence designed to be sensitive to NOE and MT^m, a variation in signals corresponding to a variation in MT^m and NOE across the cortex, consistent with a reduction in myelination from the white matter surface to the pial surface of the cortex, was observed. In regions in which the stria was visible on T₂*‐weighted images, it could also be detected in signals sensitive to MT^m and NOE. There was greater variation in signals sensitive to NOE, suggesting that the NOE signal is more sensitive to myelination. A sequence has been designed to image variations in MT^m and NOE at high spatial resolution and has been used to investigate variations in contrast in these parameters across the cortex. Copyright © 2013 John Wiley & Sons, Ltd.     

Noninvasive quantitative magnetization transfer MRI reveals tubulointerstitial fibrosis in murine kidney

Excessive tissue scarring, or fibrosis, is a critical contributor to end stage renal disease, but current clinical tests are not sufficient for assessing renal fibrosis. Quantitative magnetization transfer (qMT) MRI provides indirect information about the macromolecular composition of tissues. We evaluated measurements of the pool size ratio (PSR, the ratio of immobilized macromolecular to free water protons) obtained by qMT as a biomarker of tubulointerstitial fibrosis in a well‐established murine model with progressive renal disease. MR images were acquired from 16‐week‐old fibrotic hHB‐EGF^Tg/Tg mice and normal wild‐type (WT) mice (N = 12) at 7 T. QMT parameters were derived using a two‐pool five‐parameter fitting model. A normal range of PSR values in the cortex and outer stripe of outer medulla (CR + OSOM) was determined by averaging across voxels within WT kidneys (mean ± 2SD). Regions in diseased mice whose PSR values exceeded the normal range above a threshold value (tPSR) were identified and measured. The spatial distribution of fibrosis was confirmed using picrosirius red stains. Compared with normal WT mice, scattered clusters of high PSR regions were observed in the OSOM of hHB‐EGF^Tg/Tg mouse kidneys. Moderate increases in mean PSR (mPSR) of CR + OSOM regions were observed across fibrotic kidneys. The abnormally high PSR regions (% area) detected by the tPSR were significantly increased in hHB‐EGF^Tg/Tg mice, and were highly correlated with regions of fibrosis detected by histological fibrosis indices measured from picrosirius red staining. Renal tubulointerstitial fibrosis in OSOM can thus be assessed by qMT MRI using an appropriate analysis of PSR. This technique may be used as an imaging biomarker for chronic kidney diseases.     

Magnetization transfer studies of the fast and slow tissue water diffusion components in the human brain

Magnetization transfer (MT) properties of the fast and slow diffusion components recently observed in the human brain were assessed experimentally. One set of experiments, performed at 1.5 T in healthy volunteers, was designed to determine whether the amplitudes of fast and slow diffusion components, differentiated on the basis of biexponential fits to signal decays over a wide range of b-factors, demonstrated a different or similar magnetization transfer ratio (MTR). Another set of experiments, performed at 3 T in healthy volunteers, was designed to determine whether MTRs differed when measured from high signal-to-noise images acquired with b-factor weightings of 350 vs 3500 s/mm2. The 3 T studies included measurements of MTR as a function of off-resonance frequency for the MT pulse at both low and high b-factors. The primary conclusion drawn from all the studies is that there appears to be no significant difference between the magnetization transfer properties of the fast and slow tissue water diffusion components. The conclusions do not lend support to a direct interpretation of the 'components' of the biexponential diffusion decay in terms of the 'compartments' associated with intra- and extracellular water.     

T2 measurement of J-coupled metabolites in the human brain at 3T

Proton T₂ relaxation times of metabolites in the human brain were measured using point resolved spectroscopy at 3T in vivo. Four echo times (54, 112, 246 and 374 ms) were selected from numerical and phantom analyses for effective detection of the glutamate multiplet at ~ 2.35 ppm. In vivo data were obtained from medial and left occipital cortices of five healthy volunteers. The cortices contained predominantly gray and white matter, respectively. Spectra were analyzed with LCModel software using volume‐localized calculated spectra of brain metabolites. The estimate of the signal strength vs. TE was fitted to a monoexponential function for estimation of apparent T₂ (T₂^?). T₂^? was estimated to be similar between the brain regions for creatine, choline, glutamate and myo‐inositol, but significantly different for N‐acetylaspartate singlet and multiplet. T₂^?s of glutamate and myo‐inositol were measured as 181 ± 16 and 197 ± 14 ms (mean ± SD, N = 5) for medial occipital cortices, and 180 ± 12 and 196 ± 17 ms for left occipital cortices, respectively. Copyright © 2011 John Wiley & Sons, Ltd.     

Accuracy in the quantification of chemical exchange saturation transfer (CEST) and relayed nuclear Overhauser enhancement (rNOE) saturation transfer effects

Accurate quantification of chemical exchange saturation transfer (CEST) effects, including dipole–dipole mediated relayed nuclear Overhauser enhancement (rNOE) saturation transfer, is important for applications and studies of molecular concentration and transfer rate (and thereby pH or temperature). Although several quantification methods, such as Lorentzian difference (LD) analysis, multiple‐pool Lorentzian fits, and the three‐point method, have been extensively used in several preclinical and clinical applications, the accuracy of these methods has not been evaluated. Here we simulated multiple‐pool Z spectra containing the pools that contribute to the main CEST and rNOE saturation transfer signals in the brain, numerically fit them using the different methods, and then compared their derived CEST metrics with the known solute concentrations and exchange rates. Our results show that the LD analysis overestimates contributions from amide proton transfer (APT) and intermediate exchanging amine protons; the three‐point method significantly underestimates both APT and rNOE saturation transfer at ?3.5 ppm (NOE(?3.5)). The multiple‐pool Lorentzian fit is more accurate than the other two methods, but only at lower irradiation powers (≤1 μT at 9.4 T) within the range of our simulations. At higher irradiation powers, this method is also inaccurate because of the presence of a fast exchanging CEST signal that has a non‐Lorentzian lineshape. Quantitative parameters derived from in vivo images of rodent brain tumor obtained using an irradiation power of 1 μT were also compared. Our results demonstrate that all three quantification methods show similar contrasts between tumor and contralateral normal tissue for both APT and the NOE(?3.5). However, the quantified values of the three methods are significantly different. Our work provides insight into the fitting accuracy obtainable in a complex tissue model and provides guidelines for evaluating other newly developed quantification methods.     

A comparison of somatic relaxation and EEG activity in classical progressive relaxation and transcendental meditation

Oxygen consumption, electroencephalogram (EEG), and four other measures of somatic relaxation were monitored in groups of long-term practitioners of classical Jacobson's progressive relaxation (PR) and Transcendental Meditation (TM) and also in a group of novice PR trainees. All subjects (1) practiced relaxation or meditation (treatment), (2) sat with eyes closed (EC control), and (3) read from a travel book during two identical sessions on different days. EEG findings indicated that all three groups remained primarily awake during treatment and EC control and that several subjects in each group displayed rare theta (5–7 Hz) waveforms. All three groups demonstrated similar decrements in somatic activity during treatment and EC control which were generally of small magnitude (e.g., 2–5% in oxygen consumption). These results supported the relaxation response model for state changes in somatic relaxation for techniques practiced under low levels of stress but not the claim that the relaxation response produced a hypometabolic state. Despite similar state effects, the long-term PR group manifested lower levels of somatic activity across all conditions compared to both novice PR and long-term TM groups. We concluded that PR causes a generalized trait of somatic relaxation which is manifested in a variety of settings and situations. Two likely explanations for this trait were discussed: (1) PR practitioners are taught to generalize relaxation to daily activities, and/or (2) according to a multiprocess model, PR is a somatic technique, which should produce greater somatic relaxation than does TM, a cognitive technique. Further research is required to elucidate these possibilities.Portions of the data presented here have been previously presented at the Eighth and Ninth Annual Conferences of the Biofeedback Society of America, held, respectively, in Orlando, Florida, in 1977, and Albuquerque, New Mexico, in 1978.     

31P‐MRS of healthy human brain: ATP synthesis,metabolite concentrations,pH, and T1 relaxation times

The conventional method for measuring brain ATP synthesis is ³¹P saturation transfer (ST), a technique typically dependent on prolonged pre‐saturation with γ‐ATP. In this study, ATP synthesis rate in resting human brain is evaluated using EBIT (exchange kinetics by band inversion transfer), a technique based on slow recovery of γ‐ATP magnetization in the absence of B₁ field following co‐inversion of PCr and ATP resonances with a short adiabatic pulse. The unidirectional rate constant for the P_i → γ‐ATP reaction is 0.21 ± 0.04 s^?1 and the ATP synthesis rate is 9.9 ± 2.1 mmol min^?1 kg^?1 in human brain (n = 12 subjects), consistent with the results by ST. Therefore, EBIT could be a useful alternative to ST in studying brain energy metabolism in normal physiology and under pathological conditions. In addition to ATP synthesis, all detectable ³¹P signals are analyzed to determine the brain concentration of phosphorus metabolites, including UDPG at around 10 ppm, a previously reported resonance in liver tissues and now confirmed in human brain. Inversion recovery measurements indicate that UDPG, like its diphosphate analogue NAD, has apparent T₁ shorter than that of monophosphates (P_i, PMEs, and PDEs) but longer than that of triphosphate ATP, highlighting the significance of the ³¹P–³¹P dipolar mechanism in T₁ relaxation of polyphosphates. Another interesting finding is the observation of approximately 40% shorter T₁ for intracellular P_i relative to extracellular P_i, attributed to the modulation by the intracellular phosphoryl exchange reaction P_i ? γ‐ATP. The sufficiently separated intra‐ and extracellular P_i signals also permit the distinction of pH between intra‐ and extracellular environments (pH 7.0 versus pH 7.4). In summary, quantitative ³¹P MRS in combination with ATP synthesis, pH, and T₁ relaxation measurements may offer a promising tool to detect biochemical alterations at early stages of brain dysfunctions and diseases. Copyright © 2015 John Wiley & Sons, Ltd.     

Saturation transfer in human red blood cells with normal and unstable hemoglobin

Saturation transfer phenomena from irradiated protein protons to observed water protons in packed human red blood cells (RBCs) with normal or unstable hemoglobin (Hb), i.e. Hb Yokohama and Hb Koeln, were studied using intermolecular cross-relaxation rates [CR; 1/T(IS)(H(2)O)], action spectra [[1-(I(infinity)/I(0))] vs f(2) (ppm), where I(0) and I(infinity) are the longitudinal magnetization of observed water protons before and after long-time f(2)-irradiation, respectively], CR spectra [CR vs f(2) (ppm)] and CR ratio vs f(2) (ppm) with f(2)-irradiation from -100 to 100 ppm at gammaH(2)/2pi of 69 or 250 Hz. RBCs (Hb Yokohama) exhibited many large Heinz bodies and strongly impaired filterability, while RBCs (Hb Koeln) showed few microscopically typical Heinz bodies and virtually normal filterability. However, increases in CR values for RBCs (Hb Koeln) and RBCs (Hb Yokohama), monitored by f(2)-irradiation below approximately -6 and above approximately 14 ppm, clearly indicated marked increases in association or aggregation of unstable Hb in RBCs compared with those in normal RBCs. CR values, monitored between approximately 0 and approximately 10 ppm, were related to not only association or aggregation of unstable Hb but also amounts of water in RBCs. Aggregation or association of unstable Hb exhibited greater effects on CR values compared with those of methemoglobin formation.     

Proton T1 relaxation times of cerebral metabolites differ within and between regions of normal human brain

Saturation recovery spectra (STEAM) were acquired at 1.5 T with 7 TRs ranging from 530 to 5000 ms and a constant TE of 30 ms in voxels (7.2 ml) located in occipital grey, parietal white and frontal white matter (10 subjects each location). Spectra were also acquired at 7, 21 and 37 degrees C from separate 100 mm solutions of inositol (Ins), choline-containing compounds (Cho), N-acetyl-aspartate (NAA) and creatine. Simulations of T(1) fits with 2, 3 and 7 TRs demonstrated that at typical SNR there is potential for both inaccurate and biased results. In vivo, different metabolites had significantly different T(1)s within the same brain volume. The same order from shortest to longest T(1) (Ins, Cho, NAA, creatine) was found for all three brain regions. The order (Ins, NAA, creatine, Cho) was found in the metabolite solutions and was consistent with a simple model in which T(1) is inversely proportional to molecular weight. For all individual metabolites, T(1) increased from occipital grey to parietal white to frontal white matter. This study demonstrates that, in spectra acquired with TR near 1 s, T(1) weightings are substantially different for metabolites within a single tissue and also for the same metabolites in different tissues.     

Endothelium dependence of prostanoid-induced relaxation in human hand veins

The endothelium dependence of prostanoid-induced relaxation was examined in human isolated hand veins precontracted by endothelin. Indomethacin (10^-6 mol l^-1) and the thromboxane A₂-receptor antagonist BM 13.505 (10^-6 mol l^-1) were present throughout. The endothelium was removed by insufflating carbogen through the vessel lumen. Prostaglandin (PG) F_2α, PGE₁ PGE₂, and prostacyclin (PGI₂) elicited concentration-dependent relaxant effects. Removal of the endothelium reduced the relaxation induced by PGE_2α and PGE₂, but not that elicited by PGE₁ and PGI₂. The order of potency was PGE₂? PGE₁? PGI₂? PGF_2α regardless of the presence or absence of endothelium. The relaxation elicited by an acidified solution of NaNO₂ (generating nitric oxide) was almost identical in intact and endothelium-denuded vein segments. The results are compatible with the existence of two prostanoid receptor populations mediating relaxation: (1) one located on the smooth muscle cells and; (2) another present on the endothelium or possibly on the smooth muscle and modulated by the endothelium. The latter receptor appears to be activated by PGF_2α and PGE₂, but not by PGE₁ and PGI₂.     

White matter microstructure and longitudinal relaxation time anisotropy in human brain at 3 and 7 T

A high degree of structural order by white matter (WM) fibre tracts creates a physicochemical environment where water relaxations are rendered anisotropic. Recently, angularly dependent longitudinal relaxation has been reported in human WM. We have characterised interrelationships between T1 relaxation and diffusion MRI microstructural indices at 3 and 7 T. Eleven volunteers consented to participate in the study. Multishell diffusion MR images were acquired with b-values of 0/1500/3000 and 0/1000/2000 s/mm² at 1.5 and 1.05 mm³ isotropic resolutions at 3 and 7 T, respectively. DTIFIT was used to compute DTI indices; the fibre-to-field angle (θ_FB) maps were obtained using the principal eigenvector images. The orientations and volume fractions of multiple fibre populations were estimated using BedpostX in FSL, and the orientation dispersion index (ODI) was estimated using the NODDI protocol. MP2RAGE was used to acquire images for T1 maps at 1.0 and 0.9 mm³ isotropic resolutions at 3 and 7 T, respectively. At 3 T, T1 as a function of θ_FB in WM with high fractional anisotropy and one-fibre orientation volume fraction or low ODI shows a broad peak centred at 50^o, but a flat baseline at 0^o and 90^o. The broad peak amounted up to 7% of the mean T1. At 7 T, the broad peak appeared at 40^o and T1 in fibres running parallel to B0 was longer by up to 75 ms (8.3% of the mean T1) than in those perpendicular to the field. The peak at 40^o was approximately 5% of mean T1 (i.e., proportionally smaller than that at 54^o at 3 T). The data demonstrate T1 anisotropy in WM with high microstructural order at both fields. The angular patterns are indicative of the B0-dependency of T1 anisotropy. Thus myelinated WM fibres influence T1 contrast both by acting as a T1 contrast agent and rendering T1 dependent on fibre orientation with B0.     

Errors in 1H‐MRS estimates of brain metabolite concentrations caused by failing to take into account tissue‐specific signal relaxation

Accurate measurement of brain metabolite concentrations with proton magnetic resonance spectroscopy (¹H‐MRS) can be problematic because of large voxels with mixed tissue composition, requiring adjustment for differing relaxation rates in each tissue if absolute concentration estimates are desired. Adjusting for tissue‐specific metabolite signal relaxation, however, also requires a knowledge of the relative concentrations of the metabolite in gray (GM) and white (WM) matter, which are not known a priori. Expressions for the estimation of the molality and molarity of brain metabolites with ¹H‐MRS are extended to account for tissue‐specific relaxation of the metabolite signals and examined under different assumptions with simulated and real data. Although the modified equations have two unknowns, and hence are unsolvable explicitly, they are nonetheless useful for the estimation of the effect of tissue‐specific metabolite relaxation rates on concentration estimates under a range of assumptions and experimental parameters using simulated and real data. In simulated data using reported GM and WM T₁ and T₂ times for N‐acetylaspartate (NAA) at 3 T and a hypothetical GM/WM NAA ratio, errors of 6.5–7.8% in concentrations resulted when TR = 1.5 s and TE = 0.144 s, but were reduced to less than 0.5% when TR = 6 s and TE = 0.006 s. In real data obtained at TR/TE = 1.5 s/0.04 s, the difference in the results (4%) was similar to that obtained with simulated data when assuming tissue‐specific relaxation times rather than GM–WM‐averaged times. Using the expressions introduced in this article, these results can be extrapolated to any metabolite or set of assumptions regarding tissue‐specific relaxation. Furthermore, although serving to bound the problem, this work underscores the challenge of correcting for relaxation effects, given that relaxation times are generally not known and impractical to measure in most studies. To minimize such effects, the data should be acquired with pulse sequence parameters that minimize the effect of signal relaxation.