In vivo measurement of transverse relaxation time in the mouse brain at 17.6 T

Purpose: To establish regional T₁ and T₂ values of the healthy mouse brain at ultra‐high magnetic field strength of 17.6 T and to follow regional brain T₁ and T₂ changes with age. Methods: In vivo T₁ and T₂ values in the C57BL/6J mouse brain were followed with age using multislice‐multiecho sequence and multiple spin echo saturation recovery with variable repetition time sequence, respectively, at 9.4 and 17.6 T. Gadolinium‐tetra‐azacyclo‐dodecane‐tetra‐acetic acid phantoms were used to validate in vivo T₂ measurements. Student's t‐test was used to compare mean relaxation values. Results: A field‐dependent decrease in T₂ is shown and validated with phantom measurements. T₂ values at 17.6 T typically increased with age in multiple brain regions except in the hypothalamus and the caudate‐putamen, where a slight decrease was observed. Furthermore, T₁ values in various brain regions of young and old mice are presented at 17.6 T. A large gain in signal‐to‐noise ratio was observed at 17.6 T. Conclusions: This study establishes for the first time the normative T₁ and T₂ values at 17.6 T over different mouse brain regions with age. The estimates of in vivo T₁ and T₂ will be useful to optimize pulse sequences for optimal image contrast at 17.6 T and will serve as baseline values against which disease‐related relaxation changes can be assessed in mice. Magn Reson Med, 70:985–993, 2013. © 2012 Wiley Periodicals, Inc.     

Localized 7Li MR spectroscopy and spin relaxation in rat brain in vivo.

Localized 7Li MR point-resolved spectroscopy (PRESS) was developed as a technique to measure lithium (Li) concentration in rat brain in vivo. Localized 7Li spectra could be obtained at 4.7 T in a 0.7-ml voxel in rat brain over the entire therapeutic range of serum Li for humans. Localized 7Li spin-lattice (T1) and spin-spin (T2) relaxation times were measured. Measured intensities were corrected for spin relaxation effects and 7Li MR visibility in vivo. The average T1 was 3.3 +/- 0.9 sec, and the average T2 was 82 +/- 20 ms. Neither T1 nor T2 correlated with brain concentration. No statistically significant change was found in either T1 or T2 from approximately 7-17 days of Li dosing.     

Pseudo-continuous arterial spin labeling at very high magnetic field (11.75 T) for high-resolution mouse brain perfusion imaging

With the increasing number of transgenic mouse models of human brain diseases, there is a need for a sensitive method that allows assessing quantitative whole brain perfusion within a reasonable scan time. Arterial spin labeling (ASL), an MRI technique that permits the noninvasive quantification of cerebral blood flow, has been used to assess rodents brain perfusion. For mice, the reported experiments performed with continuous or pulsed ASL were challenged by poor multislice capability, limited sensitivity, or quantification issues. Here, the recently proposed pseudo-continuous ASL strategy, which has shown great promise for human studies, was investigated for mouse brain perfusion imaging at 11.75 T. Pseudo-continuous ASL was experimentally optimized and compared with a standard flow-sensitive alternating inversion recovery sequence for sensitivity, robustness, absolute quantification, and multislice imaging capability. A sensitivity gain up to 40% and clear advantages for multislice imaging are obtained with pseudo-continuous ASL.     

Magnetic field and tissue dependencies of human brain longitudinal 1H2O relaxation in vivo.

Brain water proton (1H2O) longitudinal relaxation time constants (T1) were obtained from three healthy individuals at magnetic field strengths (B0) of 0.2 Tesla (T), 1.0T, 1.5T, 4.0T, and 7.0T. A 5-mm midventricular axial slice was sampled using a modified Look-Locker technique with 1.5 mm in-plane resolution, and 32 time points post-adiabatic inversion. The results confirmed that for most brain tissues, T1 values increased by more than a factor of 3 between 0.2T and 7T, and over this range were well fitted by T1 (s)=0.583(B0)0.382, T1(s)=0.857(B0)0.376, and T1(s)=1.35(B0)0.340 for white matter (WM), internal GM, and blood 1H2O, respectively. The ventricular cerebrospinal fluid (CSF) 1H2O T1 value did not change with B0, and its average value (standard deviation (SD)) across subjects and magnetic fields was 4.3 (+/-0.2) s. The tissue 1/T1 values at each field were well correlated with the macromolecular mass fraction, and to a lesser extent tissue iron content. The field-dependent increases in 1H2O T1 values more than offset the well-known decrease in typical MRI contrast reagent (CR) relaxivity, and simulations predict that this leads to lower CR concentration detection thresholds with increased magnetic field.     

In vivo blood T1 measurements at 1.5 T, 3 T,and 7 T

The longitudinal relaxation time of blood is a crucial parameter for quantification of cerebral blood flow by arterial spin labeling and is one of the main determinants of the signal‐to‐noise ratio of the resulting perfusion maps. Whereas at low and medium magnetic field strengths (B₀), its in vivo value is well established; at ultra‐high field, this is still uncertain. In this study, longitudinal relaxation time of blood in the sagittal sinus was measured at 1.5 T, 3 T, and 7 T. A nonselective inversion pulse preceding a Look‐Locker echo planar imaging sequence was performed to obtain the inversion recovery curve of venous blood. The results showed that longitudinal relaxation time of blood at 7 T was ～ 2.1 s which translates to an anticipated 33% gain in the signal‐to‐noise ratio in arterial spin labeling experiments due to T₁ relaxation alone compared with 3 T. In addition, the linear relationship between longitudinal relaxation time of blood and B₀ was confirmed. Magn Reson Med, 70:1082–1086, 2013. © 2012 Wiley Periodicals, Inc.     

High magnetic field water and metabolite proton T1 and T2 relaxation in rat brain in vivo.

Comprehensive and quantitative measurements of T1 and T2 relaxation times of water, metabolites, and macromolecules in rat brain under similar experimental conditions at three high magnetic field strengths (4.0 T, 9.4 T, and 11.7 T) are presented. Water relaxation showed a highly significant increase (T1) and decrease (T2) with increasing field strength for all nine analyzed brain structures. Similar but less pronounced effects were observed for all metabolites. Macromolecules displayed field-independent T2 relaxation and a strong increase of T1 with field strength. Among other features, these data show that while spectral resolution continues to increase with field strength, the absolute signal-to-noise ratio (SNR) in T1/T2-based anatomical MRI quickly levels off beyond approximately 7 T and may actually decrease at higher magnetic fields.     

The magnetic field dependence of water T1 in tissues

The magnetic field dependence of the composite (1)H(2)O nuclear magnetic resonance signal T(1) was measured for excised samples of rat liver, muscle, and kidney over the field range from 0.7 to 7 T (35-300 MHz) with a nuclear magnetic resonance spectrometer using sample-shuttle methods. Based on extensive measurements on simpler component systems, the magnetic field dependence of T(1) of all tissues studied are readily fitted at Larmor frequencies above 1 MHz with a simple relaxation equation consisting of three contributions: a power law, A*ω(-0.60) related to the interaction of water with long-lived-protein binding sites, a logarithmic term B*τ(d) *log(1+1/(ωτ(d))(2)) related to water diffusion at macromolecular interfacial regions, and a constant term associated with the high frequency limit of water-spin-lattice relaxation. The parameters A and B include the concentration and surface area dependences respectively. The logarithmic diffusion term becomes significant at high magnetic fields and is consistent with rapid translational dynamics at macromolecular surfaces. The data are fitted well with translational correlation times of approximately 15 ps for human brain white matter, but with a B value three times larger than gray matter tissues. This analysis suggests that the water-surface translational correlation time is approximately three times longer than in gray matter.     

Method to determine in vivo the relaxation time T1 of hyperpolarized xenon in rat brain.

The magnetic polarization of the stable (129)Xe isotope may be enhanced dramatically by means of optical techniques and, in principle, hyperpolarized (129)Xe MRI should allow quantitative mapping of cerebral blood flow with better spatial resolution than scintigraphic techniques. A parameter necessary for this quantitation, and not previously known, is the longitudinal relaxation time (T(1) (tissue)) of (129)Xe in brain tissue in vivo: a method for determining this is reported. The time course of the MR signal in the brain during arterial injection of hyperpolarized (129)Xe in a lipid emulsion was analyzed using an extended two-compartment model. The model uses experimentally determined values of the RF flip angle and the T(1) of (129)Xe in the lipid emulsion. Measurements on rats, in vivo, at 2.35 T gave T(1) (tissue) = 3.6 +/- 2.1 sec (+/-SD, n = 6). This method enables quantitative mapping of cerebral blood flow.     

In vivo measurements of T1 relaxation times in mouse brain associated with different modes of systemic administration of manganese chloride

PURPOSE: To measure regional T1 and T2 values for normal C57Bl/6 mouse brain and changes in T1 after systemic administration of manganese chloride (MnCl2) at 9.4 T. MATERIALS AND METHODS: C57Bl/6 mice were anesthetized and baseline T1 and T2 measurements obtained prior to measurement of T1 after administration of MnCl2 at 9.4 T. MnCl2 was administered systemically either by the intravenous (IV), intraperitoneal (IP), or subcutaneous (SC) routes. T1 and T2 maps for each MRI transverse slice were generated using commercial software, and T1 and T2 values of white matter (WM), gray matter (GM), pituitary gland, and lateral ventricle were obtained. RESULTS: When compared with baseline values at low-field, significant lengthening of the T1 values was shown at 9.4 T, while no significant change was seen for T2 values. Significant T1 shortening of the normal mouse brain was observed following IV, IP, and SC administration of MnCl2, with IV and IP showing similar acute effects. Significant decreases in T1 values were seen for the pituitary gland and the ventricles 15 minutes after either IV or IP injection. GM showed greater uptake of the contrast agent than WM at 15 and 45 minutes after either IV or IP injections. Although both structures are within the blood-brain barrier (BBB), GM and WM revealed a steady decrease in T1 values at 24 and 72 hours after MnCl2 injection regardless of the route of administration. CONCLUSION: Systemic administration of MnCl2 by IV and IP routes induced similar time-course of T1 changes in different regions of the mouse brain. Acute effects of MnCl2 administration were mainly influenced by either the presence or absence of BBB. SC injection also provided significant T1 change at subacute stage after MnCl2 administration.     

Magnetic field dependence of proton spin-lattice relaxation times.

The magnetic field dependence of the water-proton spin-lattice relaxation rate (1/T(1)) in tissues results from magnetic coupling to the protons of the rotationally immobilized components of the tissue. As a consequence, the magnetic field dependence of the water-proton (1/T(1)) is a scaled report of the field dependence of the (1/T(1)) rate of the solid components of the tissue. The proton spin-lattice relaxation rate may be represented generally as a power law: 1/T(1)omega = A omega(-b), where b is usually found to be in the range of 0.5-0.8. We have shown that this power law may arise naturally from localized structural fluctuations along the backbone in biopolymers that modulate the proton dipole-dipole couplings. The protons in a protein form a spin communication network described by a fractal dimension that is less than the Euclidean dimension. The model proposed accounts quantitatively for the proton spin-lattice relaxation rates measured in immobilized protein systems at different water contents, and provides a fundamental basis for understanding the parametric dependence of proton spin-lattice relaxation rates in dynamically heterogeneous systems, such as tissues.     

1H metabolite relaxation times at 3.0 tesla: Measurements of T1 and T2 values in normal brain and determination of regional differences in transverse relaxation

PURPOSE: To measure 1H relaxation times of cerebral metabolites at 3 T and to investigate regional variations within the brain. MATERIALS AND METHODS: Investigations were performed on a 3.0-T clinical whole-body magnetic resonance (MR) system. T2 relaxation times of N-acetyl aspartate (NAA), total creatine (tCr), and choline compounds (Cho) were measured in six brain regions of 42 healthy subjects. T1 relaxation times of these metabolites and of myo-inositol (Ins) were determined in occipital white matter (WM), the frontal lobe, and the motor cortex of 10 subjects. RESULTS: T2 values of all metabolites were markedly reduced with respect to 1.5 T in all investigated regions. T2 of NAA was significantly (P < 0.001) shorter in the motor cortex (247 +/- 13 msec) than in occipital WM (301 +/- 18 msec). T2 of the tCr methyl resonance showed a corresponding yet less pronounced decrease (162 +/- 16 msec vs. 178 +/- 9 msec, P = 0.021). Even lower T2 values for all metabolites were measured in the basal ganglia. Metabolite T1 relaxation times at 3.0 T were not significantly different from the values at 1.5 T. CONCLUSION: Transverse relaxation times of the investigated cerebral metabolites exhibit an inverse proportionality to magnetic field strength, and especially T2 of NAA shows distinct regional variations at 3 T. These can be attributed to differences in relative WM/gray matter (GM) contents and to local paramagnetism.     

Age dependence of regional proton metabolites T2 relaxation times in the human brain at 3 T

Although recent studies indicate that use of a single global transverse relaxation time, T₂, per metabolite is sufficient for better than ±10% quantification precision at intermediate and short echo‐time spectroscopy in young adults, the age‐dependence of this finding is unknown. Consequently, the age effect on regional brain choline (Cho), creatine (Cr), and N‐acetylaspartate (NAA) T₂s was examined in four age groups using 3D (four slices, 80 voxels 1 cm³ each) proton MR spectroscopy in an optimized two‐point protocol. Metabolite T₂s were estimated in each voxel and in 10 gray and white matter (GM, WM) structures in 20 healthy subjects: four adolescents (13 ± 1 years old), eight young adults (26 ± 1); two middle‐aged (51 ± 6), and six elderly (74 ± 3). The results reveal that T₂s in GM (average ± standard error of the mean) of adolescents (NAA: 301 ± 30, Cr: 162 ± 7, Cho: 263 ± 7 ms), young adults (NAA: 269 ± 7, Cr: 156 ± 7, Cho: 226 ± 9 ms), and elderly (NAA: 259 ± 13, Cr: 154 ± 8, Cho: 229 ± 14 ms), were 30%, 16%, and 10% shorter than in WM, yielding mean global T₂s of NAA: 343, Cr: 172, and Cho: 248 ms. The elderly NAA, Cr, and Cho T₂s were 12%, 6%, and 10% shorter than the adolescents, a change of under 1 ms/year assuming a linear decline with age. Formulae for T₂ age‐correction for higher quantification precision are provided. Magn Reson Med 60:790–795, 2008. © 2008 Wiley‐Liss, Inc.     

Multicomponent T2 relaxation analysis in cartilage

MR techniques are sensitive to the early stages of osteoarthritis, characterized by disruption of collagen and loss of proteoglycan (PG), but are of limited specificity. Here, water compartments in normal and trypsin‐degraded bovine nasal cartilage were identified using a nonnegative least squares multiexponential analysis of T₂ relaxation. Three components were detected: T_2,1 = 2.3 ms, T_2,2 = 25.2 ms, and T_2,3 = 96.3 ms, with fractions w₁ = 6.2%, w₂ = 14.5%, and w₃ = 79.3%, respectively. Trypsinization resulted in increased (P < 0.01) values of T_2,2 = 64.2 ms and T_2,3 = 149.4 ms, supporting their assignment to water compartments that are bound and loosely associated with PG, respectively. The T₂ of the rapidly relaxing component was not altered by digestion, supporting assignment to relatively immobile collagen‐bound water. Relaxation data were simulated for a range of TE, number of echoes, and SNR to guide selection of acquisition parameters and assess the accuracy and precision of experimental results. Based on this, the expected experimental accuracy of measured T₂s and associated weights was within 2% and 4% respectively, with precision within 1% and 3%. These results demonstrate the potential of multiexponential T₂ analysis to increase the specificity of MR characterization of cartilage. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Proton T2 relaxation study of water, N-acetylaspartate, and creatine in human brain using Hahn and Carr-Purcell spin echoes at 4T and 7T.

Carr-Purcell and Hahn spin-echo (SE) measurements were used to estimate the apparent transverse relaxation time constant (T2) of water and metabolites in human brain at 4T and 7T. A significant reduction in the T2 values of proton resonances (water, N-acetylaspartate, and creatine/phosphocreatine) was observed with increasing magnetic field strength and was attributed mainly to increased dynamic dephasing due to increased local susceptibility gradients. At high field, signal loss resulting from T2 decay can be substantially reduced using a Carr-Purcell-type SE sequence.     

Comparison of T1 relaxation times of the neurochemical profile in rat brain at 9.4 tesla and 14.1 tesla

Knowledge of T₁ relaxation times can be important for accurate relative and absolute quantification of brain metabolites, for sensitivity optimizations, for characterizing molecular dynamics, and for studying changes induced by various pathological conditions. ¹H T₁ relaxation times of a series of brain metabolites, including J‐coupled ones, were determined using a progressive saturation (PS) technique that was validated with an adiabatic inversion‐recovery (IR) method. The ¹H T₁ relaxation times of 16 functional groups of the neurochemical profile were measured at 14.1T and 9.4T. Overall, the T₁ relaxation times found at 14.1T were, within the experimental error, identical to those at 9.4T. The T₁s of some coupled spin resonances of the neurochemical profile were measured for the first time (e.g., those of γ‐aminobutyrate [GABA], aspartate [Asp], alanine [Ala], phosphoethanolamine [PE], glutathione [GSH], N‐acetylaspartylglutamate [NAAG], and glutamine [Gln]). Our results suggest that T₁ does not increase substantially beyond 9.4T. Furthermore, the similarity of T₁ among the metabolites (～1.5 s) suggests that T₁ relaxation time corrections for metabolite quantification are likely to be similar when using rapid pulsing conditions. We therefore conclude that the putative T₁ increase of metabolites has a minimal impact on sensitivity when increasing B₀ beyond 9.4T. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart.

A novel pulse sequence scheme is presented that allows the measurement and mapping of myocardial T1 in vivo on a 1.5 Tesla MR system within a single breath-hold. Two major modifications of conventional Look-Locker (LL) imaging are introduced: 1) selective data acquisition, and 2) merging of data from multiple LL experiments into one data set. Each modified LL inversion recovery (MOLLI) study consisted of three successive LL inversion recovery (IR) experiments with different inversion times. We acquired images in late diastole using a single-shot steady-state free-precession (SSFP) technique, combined with sensitivity encoding to achieve a data acquisition window of < 200 ms duration. We calculated T1 using signal intensities from regions of interest and pixel by pixel. T1 accuracy at different heart rates derived from simulated ECG signals was tested in phantoms. T1 estimates showed small systematic error for T1 values from 191 to 1196 ms. In vivo T1 mapping was performed in two healthy volunteers and in one patient with acute myocardial infarction before and after administration of Gd-DTPA. T1 values for myocardium and noncardiac structures were in good agreement with values available from the literature. The region of infarction was clearly visualized. MOLLI provides high-resolution T1 maps of human myocardium in native and post-contrast situations within a single breath-hold.     

Highly resolved in vivo 1H NMR spectroscopy of the mouse brain at 9.4 T.

An efficient shim system and an optimized localization sequence were used to measure in vivo 1H NMR spectra from cerebral cortex, hippocampus, striatum, and cerebellum of C57BL/6 mice at 9.4 T. The combination of automatic first- and second-order shimming (FASTMAP) with strong custom-designed second-order shim coils (shim strength up to 0.04 mT/cm2) was crucial to achieve high spectral resolution (water line width of 11-14 Hz). Requirements for second-order shim strengths to compensate field inhomogeneities in the mouse brain at 9.4 T were assessed. The achieved spectral quality (resolution, S/N, water suppression, localization performance) allowed reliable quantification of 16 brain metabolites (LCModel analysis) from 5-10-microL brain volumes. Significant regional differences (up to 2-fold, P < 0.05) were found for all quantified metabolites but Asp, Glc, and Gln. In contrast, 1H NMR spectra measured from the striatum of C57BL/6, CBA, and CBA/BL6 mice revealed only small (<13%, P < 0.05) interstrain differences in Gln, Glu, Ins, Lac, NAAG, and PE. It is concluded that 1H NMR spectroscopy at 9.4 T can provide precise biochemical information from distinct regions of the mouse brain noninvasively that can be used for monitoring of disease progression and treatment as well as phenotyping in transgenic mice models.