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.     

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.     

B0 dependence of the on-resonance longitudinal relaxation time in the rotating frame (T1rho) in protein phantoms and rat brain in vivo.

On-resonance longitudinal relaxation time in the rotating frame (T1rho) has been shown to provide unique information during the early minutes of acute stroke. In the present study, the contributions of the different relaxation mechanisms to on-resonance T1rho relaxation were assessed by determining relaxation rates (R1rho) in both protein phantoms and in rat brain at 2.35, 4.7, and 9.4 T. Similar to transverse relaxation rate (R2), R1rho increased substantially with increasing magnetic field strength (B0). The B0 dependence was more pronounced at weak spin-lock fields. In contrast to R1rho, longitudinal relaxation rate (R1) decreased as a function of increasing B0 field. The present data argue that dipole-dipole interaction forms only one pathway for T1rho relaxation and the contributions from other physicochemical factors need to be considered.     

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.     

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.     

Quantitative T1rho NMR spectroscopy of rat cerebral metabolites in vivo: effects of global ischemia.

The NMR relaxation times (T(1rho), T(2), and T(1)) of water, N-acetylaspartate (NAA), creatine (Cr), choline-containing compounds (Cho), and lactate (Lac) were quantified in rat brain at 4.7 T. In control animals, the cerebral T(1rho) figures, as determined with a spin-lock field of 1.0 G, were 575 +/- 30 ms, 380 +/- 19 ms, 705 +/- 53 ms, and 90 +/- 1 ms for NAA, Cr, Cho, and water, respectively. The T(1rho) figures were 62-103% longer than their respective T(2) values determined by a multiecho method. In global (ischemic) ischemia, T(1rho) of NAA declined by 34%, that of Cr and Cho did not change, and that of water increased by 10%. The T(1rho) of lactate in ischemic brain was 367 +/- 44 ms. Similar patterns of changes were observed in the multiecho T(2) of these cerebral metabolites. The T(1) of water and NAA changed in a fashion similar to that of T(1rho) and T(2). These results show differential responses in metabolite and water T(1rho) relaxation times following ischemia, and indicate that metabolite T(1rho) and T(2) relaxation times behave similarly in the ischemic brain. The contributions of dipolar and nondipolar effects on T(1rho) relaxation in vivo are discussed in this work.     

Quantitative T(1rho) and adiabatic Carr-Purcell T2 magnetic resonance imaging of human occipital lobe at 4 T.

The feasibility of performing quantitative T(1rho) MRI in human brain at 4 T is shown. T(1rho) values obtained from five volunteers were compared with T2 and adiabatic Carr-Purcell (CP) T2 values. Measured relaxation time constants increased in order from T2, CP-T2, T(1rho) both in white and gray matter, demonstrating differential sensitivities of these methods to dipolar interactions and/or proton exchange and diffusion in local microscopic field gradients, which are so-called dynamic averaging (DA) processes. In occipital lobe, all relaxation time constants were found to be higher in white matter than in gray matter, demonstrating contrast denoted as an "inverse transverse relaxation contrast." This contrast persisted despite changing the delay between refocusing pulses or changing the magnitude of the spin-lock field strength, which suggests that it does not originate from DA, as might be induced by the presence of Fe, but rather is related to dipolar interactions in the brain tissue.     

In vivo 1H2O T2+ measurement in the human occipital lobe at 4T and 7T by Carr-Purcell MRI: detection of microscopic susceptibility contrast.

A high-resolution spin-echo imaging method is presented (called CP-LASER) which exploits the spin refocusing capability of an adiabatic Carr-Purcell (CP) pulse sequence to measure apparent 1H2O transverse relaxation (T2+) and generate contrast based on microscopic tissue susceptibility. High-resolution CP-LASER images of the human occipital lobe were acquired at four different echo times from six subjects at 4T and eight subjects at 7T to investigate the effect of magnetic field strength (B(0)) and the CP interpulse time (tau(cp)) on T2+. Susceptibility contrast was identified and T2+ was quantified for long tau(cp) (>10 ms) and short tau(cp) (7 ms at 4T and 6 ms at 7T) in gray matter, white matter, and cerebral spinal fluid. The 1H2O relaxation rate constants (1/T2+) of gray and white matter each increased approximately linearly with field strength and T2+ was inversely related to tau(cp). The average T2+ value of gray matter was 19% and 9% smaller than that of white matter at 4T and 7T, respectively. These results are consistent with higher levels of compartmentalized ferritin and increased blood volume in gray matter compared to white matter in this region of the brain.     

Why does MTR change with neuronal depolarization?

T1 and T2 relaxation, and magnetization transfer (MT) of the rat brain were measured during experimentally induced spreading depression (SD). All measured MR parameters changed during SD: T1 relaxation increased by approximately 13%, whereas the T2 increase was substantially larger (88%). MT results showed an MT ratio (MTR) decrease of 9%. The lack of change in the MT exchange rate indicated that the MT processes between water and macromolecular protons are not affected by neuronal depolarization. The observed decrease in MTR was only caused by changes in T1 and T2 relaxation.     

Exchange-influenced T2rho contrast in human brain images measured with adiabatic radio frequency pulses.

Transverse relaxation in the rotating frame (T(2rho)) is the dominant relaxation mechanism during an adiabatic Carr-Purcell (CP) spin-echo pulse sequence when no delays are used between pulses in the CP train. The exchange-induced and dipolar interaction contributions (T(2rho,ex) and T(2rho,dd)) depend on the modulation functions of the adiabatic pulses used. In this work adiabatic pulses having different modulation functions were utilized to generate T(2rho) contrast in images of the human occipital lobe at magnetic field of 4 T. T(2rho) time constants were measured using an adiabatic CP pulse sequence followed by an imaging readout. For these measurements, adiabatic full passage pulses of the hyperbolic secant HSn (n = 1 or 4) family having significantly different amplitude-and frequency-modulation functions were used with no time delays between pulses. A dynamic averaging (DA) mechanism (e.g., chemical exchange and diffusion in the locally different magnetic susceptibilities) alone was insufficient to fully describe differences in brain tissue water proton T(2rho) time constants. Measurements of the apparent relaxation time constants (T(2) (dagger)) of brain tissue water as a function of the time between centers of pulses (tau(cp)) at 4 and 7 T permitted separation of the DA contribution from that of dipolar relaxation. The methods presented assess T(2rho) relaxation influenced by DA in tissue and provide a means to generate T(2rho) contrast in MRI.     

Changes in the proton T2 relaxation times of cerebral water and metabolites during forebrain ischemia in rat at 9.4 T.

Proton T(2) relaxation times of cerebral water and metabolites were measured before, during, and after transient forebrain ischemia in rat at 9.4 T using localized proton magnetic resonance spectroscopy ((1)H-MRS) with Hahn echoes formed at different echo times (TEs). It was found that the T(2) values of water and N-acetyl aspartate (NAA) methyl, but not total creatine (tCr) methyl, decrease significantly (approximately 10%) during ischemia, and this T(2) reduction is reversed by reperfusion. The T(2) reduction observed for NAA was most likely caused by the extravascular component of the blood oxygenation level-dependent (BOLD) effect induced by a drastically increased deoxyhemoglobin content during ischemia. The absence of T(2) changes for tCr can probably be explained by the fact that the BOLD-related T(2) decrease was counterbalanced by the conversion of phosphocreatine (PCr) to creatine (Cr), which has a longer T(2) than PCr, during ischemia. The changes in T(2) should be taken into account for the quantification of metabolite concentrations during ischemia.     

T(1) relaxation in in vivo mouse brain at ultra-high field.

Accurate knowledge of relaxation times is imperative for adjustment of MRI parameters to obtain optimal signal-to-noise ratio (SNR) and contrast. As small animal MRI studies are extended to increasingly higher magnetic fields, these parameters must be assessed anew. The goal of this study was to obtain accurate spin-lattice (T(1)) relaxation times for the normal mouse brain at field strengths of 9.4 and 17.6 T. T(1) relaxation times were determined for cortex, corpus callosum, caudate putamen, hippocampus, periaqueductal gray, lateral ventricle, and cerebellum and varied from 1651 +/- 28 to 2449 +/- 150 ms at 9.4 T and 1824 +/- 101 to 2772 +/- 235 ms at 17.6 T. A field strength-dependent increase of T(1) relaxation times is shown. The SNR increase at 17.6 T is in good agreement with the expected SNR increase for a sample-dominated noise regime.     

Comparison of T(1) and T(2) metabolite relaxation times in glioma and normal brain at 3T

PURPOSE: To measure T(1) and T(2) relaxation times of metabolites in glioma patients at 3T and to investigate how these values influence the observed metabolite levels. MATERIALS AND METHODS: A total of 23 patients with gliomas and 10 volunteers were studied with single-voxel two-dimensional (2D) J-resolved point-resolved spectral selection (PRESS) using a 3T MR scanner. Voxels were chosen in normal appearing white matter (WM) and in regions of tumor. The T(1) and T(2) of choline containing compounds (Cho), creatine (Cr), and N-acetyl aspartate (NAA) were estimated. RESULTS: Metabolite T(1) relaxation values in gliomas were not significantly different from values in normal WM. The T(2) of Cho and Cr were statistically significantly longer for grade 4 gliomas than for normal WM but the T(2) of NAA was similar. These differences were large enough to impact the corrections of metabolite levels for relaxation times with tumor grade in terms of metabolite ratios (P < 0.001). CONCLUSION: The differential increase in T(2) for Cho and Cr relative to NAA means that the ratios of Cho/NAA and Cr/NAA are higher in tumor at longer echo times (TEs) relative to values in normal appearing brain. Having this information may be useful in defining the acquisition parameters for optimizing contrast between tumor and normal tissue in MR spectroscopic imaging (MRSI) data, in which limited time is available and only one TE can be used.     

T1, T2 relaxation and magnetization transfer in tissue at 3T.

T1, T2, and magnetization transfer (MT) measurements were performed in vitro at 3 T and 37 degrees C on a variety of tissues: mouse liver, muscle, and heart; rat spinal cord and kidney; bovine optic nerve, cartilage, and white and gray matter; and human blood. The MR parameters were compared to those at 1.5 T. As expected, the T2 relaxation time constants and quantitative MT parameters (MT exchange rate, R, macromolecular pool fraction, M0B, and macromolecular T2 relaxation time, T2B) at 3 T were similar to those at 1.5 T. The T1 relaxation time values, however, for all measured tissues increased significantly with field strength. Consequently, the phenomenological MT parameter, magnetization transfer ratio, MTR, was lower by approximately 2 to 10%. Collectively, these results provide a useful reference for optimization of pulse sequence parameters for MRI at 3 T.     

Relaxation times of skeletal muscle metabolites at 7T

Purpose

To demonstrate the feasibility of quantitatively evaluating and measuring T₁ and T₂ relaxation times of human tibialis anterior (TA) muscles metabolites in vivo at 7T and to compare these results with those of 3T.

Materials and Methods

A model lipid phantom (corn oil) and healthy volunteers (n = 4, mean ± SD age 35.6 ± 5.6 years) were scanned on 3T and 7T whole‐body MR scanners. A voxel of 10 × 10 × 10 mm³ was positioned on the lipid phantom and right calf TA muscles using the single‐voxel stimulated echo acquisition mode (STEAM) pulse sequence. All magnetic resonance spectroscopy (MRS) data were processed with Java‐based Magnetic Resonance User Interface (JMRUI) using Hankel Lanczos Singular Value Decomposition (HLSVD) filtering to remove the residual water signal.

Results

T₁ shows a steady increase while T₂ shows a slight decrease with B₀ and the spectra show larger spectral resolution at 7T than at 3T in the lipid phantom. T₁ values of all the metabolites are higher, while T₂ values are slightly lower at 7T than those of 3T compared to reported results in TA. The maximum percentage of increase in T₁ is about ≈488%, the maximum percentage of decrease in T₂ is about ≈65%.

Conclusion

The preliminary results can potentially be used for calculating relaxation correction factors required for absolute quantitation of skeletal muscle metabolite concentrations and for further protocol and sequence optimization. J. Magn. Reson. Imaging 2009;29:1457–1464. © 2009 Wiley‐Liss, Inc.     

Rapid combined T1 and T2 mapping using gradient recalled acquisition in the steady state.

A novel, fully 3D, high-resolution T(1) and T(2) relaxation time mapping method is presented. The method is based on steady-state imaging with T(1) and T(2) information derived from either spoiling or fully refocusing the transverse magnetization following each excitation pulse. T(1) is extracted from a pair of spoiled gradient recalled echo (SPGR) images acquired at optimized flip angles. This T(1) information is combined with two refocused steady-state free precession (SSFP) images to determine T(2). T(1) and T(2) accuracy was evaluated against inversion recovery (IR) and spin-echo (SE) results, respectively. Error within the T(1) and T(2) maps, determined from both phantom and in vivo measurements, is approximately 7% for T(1) between 300 and 2000 ms and 7% for T(2) between 30 and 150 ms. The efficiency of the method, defined as the signal-to-noise ratio (SNR) of the final map per voxel volume per square root scan time, was evaluated against alternative mapping methods. With an efficiency of three times that of multipoint IR and three times that of multiecho SE, our combined approach represents the most efficient of those examined. Acquisition time for a whole brain T(1) map (25 x 25 x 10 cm) is less than 8 min with 1 mm(3) isotropic voxels. An additional 7 min is required for an identically sized T(2) map and postprocessing time is less than 1 min on a 1 GHz PIII PC. The method therefore permits real-time clinical acquisition and display of whole brain T(1) and T(2) maps for the first time.     

T1rho relaxation mapping in human osteoarthritis (OA) cartilage: comparison of T1rho with T2

PURPOSE: To quantify the spin-lattice relaxation time in the rotating frame (T1rho) in various clinical grades of human osteoarthritis (OA) cartilage specimens obtained from total knee replacement surgery, and to correlate the T1rho with OA disease progression and compare it with the transverse relaxation time (T2). MATERIALS AND METHODS: Human cartilage specimens were obtained from consenting patients (N = 8) who underwent total replacement of the knee joint at the Pennsylvania Hospital, Philadelphia, PA, USA. T2- and T1rho-weighted images were obtained on a 4.0 Tesla whole-body GE Signa scanner (GEMS, Milwaukee, WI, USA). A 7-cm diameter transmit/receive quadrature birdcage coil tuned to 170 MHz was employed. RESULTS: All of the surgical knee replacement OA cartilage specimens showed elevated relaxation times (T2 and T1rho) compared to healthy cartilage tissue. In various grades of OA specimens, the T1rho relaxation times varied from 62 +/- 5 msec to 100 +/- 8 msec (mean +/- SEM) depending on the degree of cartilage degeneration. However, T2 relaxation times varied only from 32 +/- 2 msec to 45 +/- 4 msec (mean +/- SEM) on the same cartilage specimens. The increase in T2 and T1rho in various clinical grades of OA specimens were approximately 5-50% and 30-120%, respectively, compared to healthy specimens. The degenerative status of the cartilage specimens was also confirmed by histological evaluation. CONCLUSION: Preliminary results from a limited number of knee specimens (N = 8) suggest that T1rho relaxation mapping is a sensitive noninvasive marker for quantitatively predicting and monitoring the status of macromolecules in early OA. Furthermore, T1rho has a higher dynamic range (>100%) for detecting early pathology compared to T2. This higher dynamic range can be exploited to measure even small macromolecular changes with greater accuracy compared to T2. Because of these advantages, T1rho relaxation mapping may be useful for evaluating early OA therapy.     

Investigation of apparent diffusion constant as an indicator of early degenerative disease in articular cartilage

PURPOSE: To investigate the apparent diffusion constant (ADC) as a prospective magnetic resonance imaging (MRI) marker of early degeneration in articular cartilage. MATERIALS AND METHODS: Early degenerative changes were studied using in vitro MRI on cartilage-bone specimens excised from human femoral condyles. The loss of proteoglycans developed in vivo due to a degenerative process was compared with a gadolinium diethylenetriamine pentaacetate anion (Gd-DTPA(2-)) enhanced decrease of T(1) relaxation times, and with an increase of ADCs and T(2) relaxation times. RESULTS: Contrast enhanced T(1) values decreased and the diffusion constants increased in cartilage regions with depleted proteoglycans. The relative changes in diffusion constants were smaller than those of Gd-DTPA(2-) enhanced T(1), and in some proteoglycan-depleted regions no changes in the diffusion constants were detected. T(2) relaxation times showed considerable spatial variability that did not correlate with proteoglycan concentration. CONCLUSION: In contrast to Gd-DTPA(2-) enhanced T(1), which reflects changes in chemical composition, diffusion constants may reflect structural degradation of the cartilage matrix.     

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.     

Nonexponential T2* decay in white matter

Visualizing myelin in human brain may help the study of diseases such as multiple sclerosis. Previous studies based on T₁ and T₂ relaxation contrast have suggested the presence of a distinct water pool that may report directly on local myelin content. Recent work indicates that T₂* contrast may offer particular advantages over T₁ and T₂ contrast, especially at high field. However, the complex mechanism underlying T₂* relaxation may render interpretation difficult. To address this issue, T₂* relaxation behavior in human brain was studied at 3 and 7 T. Multiple gradient echoes covering most of the decay curve were analyzed for deviations from mono‐exponential behavior. The data confirm the previous finding of a distinct rapidly relaxing signal component (T₂* ～ 6 ms), tentatively attributed to myelin water. However, in extension to previous findings, this rapidly relaxing component displayed a substantial resonance frequency shift, reaching 36 Hz in the corpus callosum at 7 T. The component's fractional amplitude and frequency shift appeared to depend on both field strength and fiber orientation, consistent with a mechanism originating from magnetic susceptibility effects. The findings suggest that T₂* contrast at high field may be uniquely sensitive to tissue myelin content and that proper interpretation will require modeling of susceptibility‐induced resonance frequency shifts. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.