In vivo cardiac 1H-MRS in the mouse.

The mouse is the predominant animal model to study the effect of gene manipulations. Imaging techniques to define functional effects on the heart caused by genomic alterations are becoming increasingly routine in mice, yet methods for in vivo investigation of metabolic phenotypes in the mouse heart are lacking. In this work, cardiac 1H-MRS was developed and applied in mouse hearts in vivo using a single-voxel technique (PRESS). In normal C57Bl/6J mice, stability and reproducibility achieved by dedicated cardiac and respiratory gating was demonstrated by measuring amplitude and zero-order phase changes of the unsuppressed water signal. Various cardiac metabolites, such as creatine, taurine, carnitine, or intramyocardial lipids were successfully detected and quantified relative to the total water content in voxels as small as 2 microl, positioned in the interventricular septum. The method was applied to a murine model of guanidinoacetate N-methyltransferase (GAMT) deficiency, which is characterized by substantially decreased myocardial creatine levels. Creatine deficiency was confirmed noninvasively in myocardium of anesthetized GAMT-/- mice. This is the first study to report the application of cardiac 1H-MRS in mice in vivo.     

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.     

Measuring the longitudinal relaxation time of GABA in vivo at 3 tesla

Purpose:

To measure the in vivo longitudinal relaxation time T1 of GABA at 3 Tesla (T).

Materials and Methods:

J‐difference edited single‐voxel MR spectroscopy was used to isolate γ‐aminobutyric acid (GABA) signals. An increased echo time (80 ms) acquisition was used, accommodating the longer, more selective editing pulses required for symmetric editing‐based suppression of co‐edited macromolecular signal. Acquiring edited GABA measurements at a range of relaxation times in 10 healthy participants, a saturation‐recovery equation was used to model the integrated data.

Results:

The longitudinal relaxation time of GABA was measured as T_1,GABA = 1.31 ± 0.16 s.

Conclusion:

The method described has been successfully applied to measure the T1 of GABA in vivo at 3T. J. Magn. Reson. Imaging 2013;37:999–1003. © 2012 Wiley Periodicals, Inc.     

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.     

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.     

Human brain-structure resolved T(2) relaxation times of proton metabolites at 3 Tesla.

The transverse relaxation times, T(2), of N-acetylaspartate (NAA), total choline (Cho), and creatine (Cr) obtained at 3T in several human brain regions of eight healthy volunteers are reported. They were obtained simultaneously in 320 voxels with three-dimensional (3D) proton MR spectroscopy ((1)H-MRS) at 1 cm(3) spatial resolution. A two-point protocol, optimized for the least error per given time by adjusting both the echo delay (TE(i)) and number of averages, N(i), at each point, was used. Eight healthy subjects (four males and four females, age = 26 +/- 2 years) underwent the hour-long procedure of four 15-min, 3D acquisitions (TE(1) = 35 ms, N(1) = 1; and TE(2) = 285 ms, N(2) = 3). The results reveal that across all subjects the NAA and Cr T(2)s in gray matter (GM) structures (226 +/- 17 and 137 +/- 12 ms, respectively) were 13-17% shorter than the corresponding T(2)s in white matter (WM; 264 +/- 10 and 155 +/- 7 ms, respectively). The T(2)s of Cho did not differ between GM and WM (207 +/- 17 and 202 +/- 8, respectively). For the purpose of metabolic quantification, these values justify to within +/-10% the previous use of one T(2) per metabolite for 1) the entire brain and 2) all subjects. These T(2) values (which to our knowledge were obtained for the first time at this field, spatial resolution, coverage, and precision) are essential for reliable absolute metabolic quantification.     

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.     

Determining the effect of water temperature on the T1 and T2 relaxation times of the lung tissue at 9.4 T MRI: A drowning mouse model

Japanese individuals have a unique culture of soaking in a bathtub, and forensic pathologists have experienced fatal cases due to drowning. However, T1 and T2 relaxation times of a drowning lung are poorly documented.In the present study, we investigated the relationship between drowning water temperature and T1 and T2 relaxation times of drowning lung tissues at 9.4 T MRI (Bruker, BioSpec94/20USR). The mice used as animal drowning models were directly submerged in freshwater. Water temperature was set to 8 °C–10 °C (cold), 20 °C–22 °C (normal), 30 °C, and 45 °C. The regions of interest (ROIs) on the axial section of the third slice were set at the central and peripheral areas of each—the left and the right—lung. T1 relaxation times measured immediately after death differed by the presence or absence of soaking water, except in case of cold water temperature. In the drowning groups, T1 relaxation time showed a linear dependency on water temperature. By contrast, T2 relaxation time was almost constant regardless of the presence of drowning under the same temperature condition; when compared in the lung areas of the same individuals, the times were uniformly reduced in drowning models. To minimize the effects of hypostasis and decomposition, we performed measurements immediately after death and were able to determine the noticeable difference in drowning water temperature. These results may be useful for qualitative assessments of a drowning lung and may serve as a basis when imaging the human body during forensic autopsy cases.     

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.     

Quantitative assessment of myocardial T2 relaxation times in cardiac amyloidosis

Purpose

To evaluate cardiac MRI (CMR) in the diagnosis of cardiac amyloidosis by comparing the T2 relaxation times of left ventricular myocardium in a pilot patient group to a normal range established in healthy controls.

Materials and Methods

Forty‐nine patients with suspected amyloidosis‐related cardiomyopathy underwent comprehensive CMR examination, which included assessment of myocardial T2 relaxation times, ventricular function, resting myocardial perfusion, and late gadolinium enhancement (LGE) imaging. T2‐weighted basal, mid, and apical left ventricular slices were acquired in each patient using a multislice T2 magnetization preparation spiral sequence. Slice averaged T2 relaxation times were subsequently calculated offline and compared to the previously established normal range.

Results

Twelve of the 49 patients were confirmed to have cardiac amyloidosis by biopsy. There was no difference in mean T2 relaxation times between the amyloid cases and normal controls (51.3 ± 8.1 vs. 52.1 ± 3.1 msec, P = 0.63). Eleven of the 12 amyloid patients had abnormal findings by CMR, eight having LGE involving either ventricles or atria and four demonstrating resting subendocardial perfusion defects.

Conclusion

CMR is a potentially valuable tool in the diagnosis of cardiac amyloidosis. However, calculation of myocardial T2 relaxation times does not appear useful in distinguishing areas of amyloid deposition from normal myocardium. J. Magn. Reson. Imaging 2009. © 2009 Wiley‐Liss, Inc.     

Proton T1 relaxation times of metabolites in human occipital white and gray matter at 7 T

Proton T₁ relaxation times of metabolites in the human brain have not previously been published at 7 T. In this study, T₁ values of CH₃ and CH₂ group of N‐acetylaspartate and total creatine as well as nine other brain metabolites were measured in occipital white matter and gray matter at 7 T using an inversion‐recovery technique combined with a newly implemented semi‐adiabatic spin‐echo full‐intensity acquired localized spectroscopy sequence (echo time = 12 ms). The mean T₁ values of metabolites in occipital white matter and gray matter ranged from 0.9 to 2.2 s. Among them, the T₁ of glutathione, scyllo‐inositol, taurine, phosphorylethanolamine, and N‐acetylaspartylglutamate were determined for the first time in the human brain. Significant differences in T₁ between white matter and gray matter were found for water (?28%), total choline (?14%), N‐acetylaspartylglutamate (?29%), N‐acetylaspartate (+4%), and glutamate (+8%). An increasing trend in T₁ was observed when compared with previously reported values of N‐acetylaspartate (CH₃), total creatine (CH₃), and total choline at 3 T. However, for N‐acetylaspartate (CH₃), total creatine, and total choline, no substantial differences compared to previously reported values at 9.4 T were discernible. The T₁ values reported here will be useful for the quantification of metabolites and signal‐to‐noise optimization in human brain at 7 T. Magn Reson Med 69:931–936, 2013. © 2012 Wiley Periodicals, Inc.     

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.     

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.     

Effect of J-coupling on lipid composition determination with localized proton magnetic resonance spectroscopy at 9.4 T

Purpose:

To demonstrate, at 9.4 T, that J‐coupling interactions exhibited by lipid protons affects lipid composition determination with a point resolved spectroscopy (PRESS) sequence.

Materials and Methods:

Experiments were conducted on four oils (almond, corn, sesame, and sunflower), on visceral adipose tissue of a euthanized mouse, and on pure linoleic acid at 9.4 T. The 2.1, 2.3, and 2.8 ppm resonances were measured at multiple echo times (TEs) by a standard PRESS sequence and by a PRESS sequence consisting of narrow‐bandwidth refocusing pulses designed to rewind the J‐coupling evolution of the target peak protons in the voxel of interest. T₂ corrections were performed on both groups of data for the three peaks and lipid compositions for the oils and for the mouse tissue were determined. Lipid compositions were also calculated from a short‐TE standard PRESS spectrum.

Results:

A chemical analysis of the samples was not performed; however, the oil compositions calculated from resonance peaks acquired with the PRESS sequence designed to minimize J‐coupling effects, following T₂ relaxation correction, closely agreed with values in the literature, which was not the case for all of the compositions determined from the regular PRESS spectra.

Conclusion:

The presented work brings to attention the significance of J‐coupling effects when calculating lipid compositions from localized proton spectra. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.