Measurement of arterial input function of <Superscript>17</Superscript>O water tracer in rat carotid artery by using a region-defined (REDE) implanted vascular RF coil

A method of determining arterial input function (AIF) by continuously detecting the ¹⁷O MR signal changes of ¹⁷O-labeled water tracer in the rat carotid artery using a region-defined (REDE) implanted vascular RF coil at 9.4 Tesla is reported. This coil has a compact physical size of 1 mm inner diameter, 3 mm outer diameter and 11 mm in length. It can be readily implanted into the rat neck and wrapped around the rat carotid artery for achieving adequate MR detection sensitivity for determining AIF with minimal surgical trauma. Water phantom and in vivo MR experiments were conducted for validating the coil's performance. A signal-to-noise ratio of ~20:1 was achieved for the ¹⁷O signal acquired from naturally abundant H₂ ¹⁷O in a small amount of blood (~7 μl) inside the rat carotid artery with an acquisition time of 11 s. The REDE RF coil design electromagnetically isolates the rat carotid artery from surrounding tissues and ensures that the MR signal detected by the RF coil is only attributable to the artery blood. It also minimizes the electromagnetic coupling between the implanted RF coil and a head surface coil tuned at the same operating frequency (two-coil configuration). This configuration allowed simultaneous measurements of dynamic changes of ¹⁷O MR signal of the H₂ ¹⁷O tracer in both rat carotid artery and brain. Compared to most contemporary MR approaches, the REDE implanted RF provides a simple, accurate, and promising solution for determination of AIF in small experimental animals.     

Dual resonant birdcage coils for1H detected13C microscopic imaging at 11.7 T

Liquid state, rotating frame cross polarisation experiments are very sensitive to RF field inhomogeneity. In this work, we present an easily fabricated, co-resident high- and low-pass linear birdcage resonator, optimised to perform liquid state rotating frame polarisation transfer at¹H and¹³C frequencies. Both the RF fields have been experimentally mapped, and used to validate the spatial signal dependence of a proton detected,¹³C image. The predicted performance was then confirmed using PRAWN-based, cyclic J-cross polarisation (CYCLCROP) imaging. A novel variant of a B₁-field mapping approach is also presented, using the signal enhancement of the CYCLCROP sequence to generate proton detected,¹³C field maps.     

Potential pitfall in the determination of free [Mg2+] by31P NMR when using the β/α-ATP peak height ratio method

Recently, Clarke et al., (Clarke K, Kashiwaya Y, King MT, Gates D, Keon CA, Cross HR, Radda GK, Veech RL. The β/α peak height ratio of ATP. A measure of free [Mg _free ²⁺ ] using³¹ P NMR, J. Biol. Chem. 1996;271:21142–21150.) reported a new method to noninvasively determine the concentration of intracellular free magnesium ([Mg _free ²⁺ ]) based on the measurement of the peak height ratioh _β/α of the β- and α-ATP signals in³¹P NMR spectra.h _β/α varies with Mg_free ²⁺], however, the study presented here shows thath _β/α also strongly depends on the homogeneity of the static magnetic field. For this reason, we performed at a magnetic field strength of 1.5 T³¹P NMR measurements of solutions that mimic intracellular medium. The magnetic field homogeneity was varied by changing the currents in the shim coils, and the effect onh _β/α is demonstrated with and without proton decoupling. In both cases,h _β/α strongly depends on the magnetic field homogeneity and can therefore lead to a pitfall in the determination of [Mg_free ²⁺].     

Assignment of the 2.03 ppm resonance in in vivo <Superscript>1</Superscript>H MRS of human brain tumour cystic fluid: contribution of macromolecules

MRI and MRS are established techniques for the evaluation of intracranial mass lesions and cysts. The 2.03 ppm signal recorded in their ¹H-MRS spectra is often assigned to NAA from outer volume contamination, although it has also been detected in non-infiltrating tumours and large cysts. We have investigated the molecular origin of this resonance in ten samples of cystic fluids from human brain tumours. The NMR detected content of the 2.03 ppm resonance in 136 ms echo time spectra, assuming an N- CH₃ origin, was 3.19 ± 1.01 mM. Only one third (34 ± 12%) of the N-acetyl containing compound (NAC) signal could be extracted by perchloric acid (PCA) indicating that most of it originated in a macromolecular PCA-insoluble component. Chemical analysis of the cyst fluids showed that sialic acid bound to macromolecules would account for 64.3% and hexuronic containing compounds for 29.2% of the NMR-detectable ex vivo signal, 93.4% of the signal at TE 136 ms. Lactate content measured by NMR (6.4 ± 4.4 mM) and the predominance of NAC originating in sialic acid point to a major origin from tumour rather than from plasma for this 2.03 ppm resonance.     

PASADENA hyperpolarization of 13C biomolecules: equipment design and installation

Object  The PASADENA method has achieved hyperpolarization of 16–20% (exceeding 40,000-fold signal enhancement at 4.7 T), in liquid samples of biological molecules relevant to in vivo MRI and MRS. However, there exists no commercial apparatus to perform this experiment conveniently and reproducibly on the routine basis necessary for translation of PASADENA to questions of biomedical importance. The present paper describes equipment designed for rapid production of six to eight liquid samples per hour with high reproducibility of hyperpolarization. Materials and methods  Drawing on an earlier, but unpublished, prototype, we provide diagrams of a delivery circuit, a laminar-flow reaction chamber within a low field NMR contained in a compact, movable housing. Assembly instructions are provided from which a computer driven, semi-automated PASADENA polarizer can be constructed. Results  Together with an available parahydrogen generator, the polarizer, which can be operated by a single investigator, completes one cycle of hyperpolarization each 52 s. Evidence of efficacy is presented. In contrast to competing, commercially available devices for dynamic nuclear polarization which characteristically require 90 min per cycle, PASADENA provides a low-cost alternative for high throughput. Conclusions  This equipment is suited to investigators who have an established small animal NMR and wish to explore the potential of heteronuclear (¹³ C and ¹⁵ N) MRI, MRS, which harnesses the enormous sensitivity gain offered by hyperpolarization.     

Transmit/receive headcoil for optimal <Superscript>1</Superscript>H MR spectroscopy of the brain in paediatric patients at 3 T

¹H magnetic resonance (MR) spectroscopy is a useful tool to obtain metabolic information from the brain in paediatric patients. To detect signals of metabolites at low concentrations or from small volumes, the signal-to-noise ratio (SNR) has to be optimized. The SNR can be increased by going to higher field strengths. However, this leads to higher spectral bandwidths, which increases the chemical shift artefact. Here we present a transmit/receive headcoil which is adapted to the dimensions of the paediatric head and enables PRESS localization with high radio-frequency (RF) bandwidths that minimize the chemical shift displacement to only 5%. In addition, since the pulse lengths are shorter with higher RF bandwidths, the echo time can be reduced to 10 ms improving SNR as well.Parts of this work have been presented at the European Society for Magnetic Resonance in Medicine and Biology in Rotterdam in 2003     

Experimental31p nmr study of the influence of ionic strength on the apparent dissociation constant of mgatp

The classical method for³¹P NMR determination of intracellular free magnesium concentration ([Mg _free ²⁺ ]) requires an accurate knowledge of the apparent dissociation constant (K _D ) of MgATP. There is a large difference between the previously determined values ofK _D . Although the value of 50 µM, determined by a³¹P NMR method, is now largely accepted, a value of 86 µM has more recently been measured with a fitting method derived from the original one, and with a different ionic strength. The purpose of our study was to assess if the cause of the difference between these two previously reportedK _D values was due to the measuring method or to the ionic strength value used.Working at pH=7.2,T=37°C, and [KCl]=0.25 M, we performedK _D measurements with the original³¹P NMR method and with the fitting method. The results (67±13 µM and 61±20 µM, respectively) were not significantly different. Then, with the first method, we measured K_D at [KCl]=0.12 M and found a value of 19±5 µM. We conclude that the main cause of difference between theK _D values measured by³¹P NMR reside in the disparity of ionic strength values used for their measurement. OurK _D measurements at [KCl]=0.25 and 0.12 M demonstrate the importance of the ionic strength value used for imitating the intracellular medium on the absolute value of ([Mg _free ²⁺ ]) measured by³¹P NMR spectroscopy.Address for correspondence: Université Catholique de Louvain, Unité CPMC, Bâtiment Lavoisier, Place Louis Pasteur n°1, B-1348 Louvain-la-Neuve, Belgium. Additional reprints of this chapter may be obtained from the Reprints Department, Chapman & Hall, One Penn Plaza, New York, NY 10119.     

<Superscript>1</Superscript>H NMR relaxation times of skeletal muscle metabolites at 3 T

This study reports proton relaxation times of water and metabolites in soleus and tibialis anterior muscles of young healthy volunteers at 3 T. The results are in agreement with data reported for 1.5 and 4 T, showing a steady increase of spin-lattice relaxation times of water, creatine and lipids with B₀ and no effect of B₀ on spin–spin relaxation. Comparison between muscles revealed a longer spin–spin relaxation time of water in soleus than in tibialis anterior muscle (31±1 ms vs. 28±1 ms, p<0.05). These data can be applied to relaxation correction for the absolute quantification of skeletal muscle metabolite concentrations and further sequence optimization.     

Quality assurance of PASADENA hyperpolarization for 13C biomolecules

Object  Define MR quality assurance procedures for maximal PASADENA hyperpolarization of a biological ¹³C molecular imaging reagent. Materials and methods  An automated PASADENA polarizer and a parahydrogen generator were installed. ¹³C enriched hydroxyethyl acrylate, 1-¹³C, 2,3,3-d₃ (HEA), was converted to hyperpolarized hydroxyethyl propionate, 1-¹³C, 2,3,3-d₃ (HEP) and fumaric acid, 1-¹³C, 2,3-d₂ (FUM) to hyperpolarized succinic acid, 1-¹³C, 2,3-d₂ (SUC), by reaction with parahydrogen and norbornadiene rhodium catalyst. Incremental optimization of successive steps in PASADENA was implemented. MR spectra and in vivo images of hyperpolarized ¹³C imaging agents were acquired at 1.5 and 4.7 T. Results  Application of quality assurance (QA) criteria resulted in incremental optimization of the individual steps in PASADENA implementation. Optimal hyperpolarization of HEP of P = 20% was achieved by calibration of the NMR unit of the polarizer (B ₀ field strength ± 0.002 mT). Mean hyperpolarization of SUC, P = [15.3 ± 1.9]% (N = 16) in D ₂O, and P = [12.8 ± 3.1]% (N = 12) in H ₂O, was achieved every 5–8 min (range 13–20%). An in vivo ¹³C succinate image of a rat was produced. Conclusion  PASADENA spin hyperpolarization of SUC to 15.3% in average was demonstrated (37,400 fold signal enhancement at 4.7 T). The biological fate of ¹³C succinate, a normally occurring cellular intermediate, might be monitored with enhanced sensitivity.     

Ultra-fast three dimensional imaging of hyperpolarized 13C in vivo

Objective: PASADENA, a chemical method of enhancing nuclear spin polarization has demonstrated ¹³C polarizations of order unity for the nascent products of molecular addition by parahydrogen. The extreme brevity of signal enhancement obtained by hyperpolarization requires improved ¹³C MR in vivo imaging techniques for their optimum utility. Materials and Methods: ¹³C imaging sequences, including ¹³C 3D FIESTA, were compiled for a GE LX 1.5 T clinical MR scanner. Two water soluble ¹³C imaging agents were hyperpolarized utilizing parahydrogen and an automated polarizer. ¹³C polarization was quantified in flow phantoms and in rats with jugular vein catheters. Results: Fast 3D FIESTA ¹³C MR imaging technique acquired sequential 3D images (3.66 s/acquisition) with superior SNR. Hyperpolarized ¹³C solutions and vascular phantoms achieved a maximum signal of 26,624±593. In vivo ¹³C MR images of the cardiopulmonary circulation showed maximum ¹³C signal of 2,402±158. ¹³C images acquired within 3.66 s showed signal enhancement over 10,000 compared to equilibrium polarization. Conclusion: 3D-FIESTA was effective for sub-second in vivo imaging of hyperpolarized ¹³C reagents produced in a custom-built parahydrogen polarizer. Application to ¹³C hyperpolarized by parahydrogen is demonstrated in vitro and in vivo     

31P MR spectroscopy and in vitro markers of oxidative capacity in type 2 diabetes patients

Background: Skeletal muscle mitochondrial function in type 2 diabetes (T2D) is currently being studied intensively. In vivo ³¹P magnetic resonance spectroscopy (³¹P MRS) is a noninvasive tool used to measure mitochondrial respiratory function (MIFU) in skeletal muscle tissue. However, microvascular co-morbidity in long-standing T2D can interfere with the ³¹P MRS methodology. Aim: To compare ³¹P MRS-derived parameters describing in vivo MIFU with an in vitro assessment of muscle respiratory capacity and muscle fiber-type composition in T2D patients. Methods: ³¹P MRS was applied in long-standing, insulin-treated T2D patients. ³¹P MRS markers of MIFU were measured in the M. vastus lateralis. Muscle biopsy samples were collected from the same muscle and analyzed for succinate dehydrogenase activity (SDH) and fiber-type distribution. Results: Several ³¹P MRS parameters of MIFU showed moderate to good correlations with the percentage of type I fibers and type I fiber-specific SDH activity (Pearson’s R between 0.70 and 0.75). In vivo and in vitro parameters of local mitochondrial respiration also correlated well with whole-body fitness levels (VO _2peak) in these patients (Pearson’s R between 0.62 and 0.90). Conclusion: Good correlations exist between in vivo and in vitro measurements of MIFU in long-standing insulin-treated T2D subjects, which are qualitatively and quantitatively consistent with previous results measured in healthy subjects. This justifies the use of ³¹P MRS to measure MIFU in relation to T2D.     

Temperature dependence photo-luminescence of Nd<Superscript>3+</Superscript> doped PLZT ceramic

Temperature dependence of photo-luminescence for Nd³⁺ doped PLZT(9/65/35) was measured across its structural phase transition temperature. The absorption corresponding to ⁴ I _9/2 → ⁴ F _5/2, ² H _9/2 energy level near 808 nm was used for exciting the sample. The major emission bands at 0.9, 1.06, and 1.34 μm were observed. No shift in the peak position of these emission bands was observed across the diffused structural transition with increase in temperature. However, a 10% increase in FWHM was observed. The absence of any discernible peak shift is attributed to the shielding of the intra-configurational 4f-4f transitions, in trivalent Nd³⁺ ions, by external 5 s and 5d orbitals. The red shifted phonon side bands appeared with increase in temperature.     

Magnetic resonance spectroscopy data analysis: time or frequency domain?

Comparisons of time and frequency domain methods are presented forin vitro ¹H andin vivo ³¹P magnetic resonance spectroscopy (MRS) data. Many distortions in the MR spectrum, introduced by applying the Fourier transform to a nonideal free-induction decay (FID), can be handled more elegantly in the time domain, where operations are carried out directly on the measured signal. It was found that if the measured signal is well conditioned—high signal-to-noise ratio (S/N), no truncation, no baseline problems—then both time and frequency domain methods give the same results within the error limits. However, distortions in the measured signal make analysis by time domain methods preferable over frequency domain methods. In all applications, the use of prior knowledge appeared to play an important role.     

Time-domain quantitation of <Superscript>1</Superscript>H short echo-time signals: background accommodation

Quantitation of ¹H short echo-time signals is often hampered by a background signal originating mainly from macromolecules and lipids. While the model function of the metabolite signal is known, that of the macromolecules is only partially known. We present time-domain semi-parametric estimation approaches based on the QUEST quantitation algorithm (QUantitation based on QUantum ESTimation) and encompassing Cramér–Rao bounds that handle the influence of nuisance parameters related to the background. Three novel methods for background accommodation are presented. They are based on the fast decay of the background signal in the time domain. After automatic estimation, the background signal can be automatically (1) subtracted from the raw data, (2) included in the basis set as multiple components, or (3) included in the basis set as a single entity. The performances of these methods combined with QUEST are evaluated through extensive Monte Carlo studies. They are compared in terms of bias–variance trade-off. Because error bars on the amplitudes are of paramount importance for diagnostic reliability, Cramér–Rao bounds accounting for the uncertainty caused by the background are proposed. Quantitation with QUEST of in vivo short echo-time ¹H human brain with estimation of the background is demonstrated.     

Kinetics of PCr to ATP and β-ATP to β-ADP phosphoryl conversion are modified in working rat skeletal muscle after training

Kinetics of phosphoryl transfers from PCr to γ-ATP and from β-ATP to β-ADP were measured by magnetization transfer in an in vivo³¹P NMR experiment in working rat skeletal hind leg muscles. Two groups were examined. One group was submitted to a 6-week training program of treadmill running. The other group was composed of sedentary animals. Metabolic oxidative capacity and mechanical performance were improved greatly by training as shown previously. Phosphoryl transfer of PCr→γ-ATP or β-ATP→β-ADP total fluxes were identical in resting trained and untrained muscles. Under stimulation, the flux of creatine kinase transfer was significantly inhibited by 23% compared with resting level in untrained muscles; by contrast, it was not inhibited and maintained at the high resting level in trained muscles. Thus physiological changes probably linked to a decrease of the production of anions, which could inhibit creatine kinase, were able to maintain creatine kinase flux. The flux of β-ATP to β-ADP transfer were enhanced largely in working muscles from 1.4±0.8 and 2±0.8 at rest to 4±1.6 and 6.6±2.7 mM s⁻¹ for untrained and trained muscles respectively; the effect was more pronounced in trained than in untrained muscles. These results showed an acceleration of phosphoryl turnover in working muscles after training, which could contribute to improve oxidative and mechanical performances. Such kinetic measurements of phosphoryl conversion may provide information on ATP turnover in pathophysiologic situations where ADP accumulates because of impaired ATP synthesis (mitochondrial myopathies, lower perfusion level).     

<Superscript>1</Superscript>H MR spectroscopy as a diagnostic tool for cerebral creatine deficiency

Objective  Total creatine (tCr) constitutes one of the most prominent signals in human brain MR spectra. A significant decrease in the tCr signal indicates a severe disorder of creatine metabolism. We describe the potential of ¹H MR spectroscopy in differential diagnosis of creatine transporter (SLC6A8) deficiency syndrome. Materials and methods  Two siblings, a 7-year-old female presenting with mild psychomotor delay, and a 5-year-old male with severe psychomotor retardation, epilepsy and autistic spectrum of problems including speech delay, underwent MR examination because of suspected creatine deficiency. After the MRI examination, ¹H MR spectroscopy using the CSI technique was performed. Results  Metabolic images of N-acetylaspartate, tCr and choline concentrations showed a very low tCr signal in the male, which was approximately three times lower than in his sister (male/female/controls: tCr = 1.6/4.6/7.5 mM). Despite creatine supplementation, no improvement in clinical status and tCr concentration in the MR spectra of the male was observed and diagnosis of SLC6A8 deficiency was proposed. Sequence analysis of the SLC6A8 gene revealed a novel pathogenic frameshift mutation c.219delC; p.Asn74ThrfsX23, hemizygous in the male and heterozygous in the female. Conclusions  The diagnosis of X-linked mental retardation caused by the SLC6A8 deficiency can be independently established by ¹H MR spectroscopy.     

ECG-gated <Superscript>23</Superscript>Na-MRI of the human heart using a 3D-radial projection technique with ultra-short echo times

Pathological changes in tissue often manifest themselves in an altered sodium gradient between intra- and extracellular space due to a malfunctioning Na⁺–K⁺ pump, resulting in an increase in total sodium concentration in ischaemic regions. Therefore, ²³Na-MRI has the potential to non-invasively differentiate viable from non-viable tissue by detecting concentration changes of intra- and extracellular sodium. As the in vivo sodium signal shows a bi-exponential T₂ decay, with a short component of less than 1 ms, the accurate quantification of the total sodium content requires imaging techniques with ultra-short echo times (TE) below 0.5 ms. A 3D-radial projection technique has been developed which allows the acquisition of ECG-triggered sodium images of the human heart with a TE of 0.4 ms. With this pulse sequence ²³Na-MRI volunteer measurements of the head or the heart were performed in less than 18 min on a 1.5-T clinical scanner with an isotropic resolution of 10 mm³. The signal to noise ratio of the radial projection technique is twofold higher than that of a Cartesian gradient echo pulse sequence (TE = 3.2 ms). Radial ²³Na-MRI provides a tool for clinical studies, aiming at the differentiation of viable and non-viable tissue.     

Effects of Al<Superscript>3+</Superscript> substitution on the luminescence properties of LuNbO<Subscript>4</Subscript> doped with Eu<Superscript>3+</Superscript> and Tb<Superscript>3+</Superscript> ions

The effect of Al³⁺ substitution on the enhancement of the luminescence of Lu_1–xAl_xNbO₄:Eu³⁺ and Lu_1–xAl_xNbO₄:Tb³⁺ was investigated. X-ray diffraction patterns confirmed that the Eu³⁺, Tb³⁺, and Al³⁺ ions were fully incorporated into the Lu³⁺ sites. In the case of Lu_1–xAl_xNbO₄:Eu³⁺, the predominant red emission (614 nm) was assigned to the ⁵D₀?→?⁷F₂ transition of Eu³⁺ and for x?=?0–0.05, its intensity increased up to ~125 and 108% under 395 nm (⁷F₀ → ⁵L₆) and a charge transfer band excitation, respectively. For Lu_1–xAl_xNbO₄:Tb³⁺, the strongest emission band peaking at 551 nm was attained in the green region among multiple emission bands corresponding to the ⁵D₄?→?⁷F_J transitions of Tb³⁺. Increasing the x values from 0 to 0.05 increased the green emission significantly by ~137%. These phenomena were explained by the local structural distortions and crystal field asymmetry surrounding Eu³⁺ and Tb³⁺, which were attributed to a large difference in the ionic radii of Al³⁺ and Lu³⁺.     

The magnitude of signal errors introduced by ISIS in quantitative31P MRS

It is well known that the quality of a quantitative³¹P MRS measurement relies largely on the performance of the volume selection method, and that image selected in vivo spectroscopy (ISIS) suffers from contaminating signal caused mostly by Tl smearing. However, these signal errors and their magnitude are seldom addressed in clinical studies. The aim of this study was therefore to investigate the magnitude of signal errors in³¹P MRS when using ISIS. The results from the measurements with a homogeneous head phantom are as follows: at low TR/T1 ratios the contamination increases rapidly, especially for small (< 27 cm³) VOI sizes; at TR/T1 = 1, the signal from a 27 cm³ VOI was 20% too high, and from an 8 cm³ VOI 150% too high. The signal obtained from different VOI positions varied between 80 and 127%. The signal varied linearly with the³¹P concentration in the object. However, a too high signal was obtained when the concentration was lower in the region of interest (inner container) than in the rest of the phantom. The agreement between the simulations and measurements shows that the results of this study are generally applicable to the measurement geometry and the ISIS experiment order rather than being specific for the MR system studied. The errors obtained both experimentally and in computer simulations are too large to be ignored in clinical studies using the ISIS pulse sequence.     

Na<Superscript>+</Superscript>-fast ionic conducting glass-ceramics of silicophosphates

The Na⁺-fast ionic conducting glass-ceramics with Na₅YSi₄O₁₂ (N5)-type structure were successfully synthesized using the composition formula of Na_3+3x-y R_1-x P _y Si_3-y O₉ for a variety of rare earth ions, R, under the appropriate composition parameters. In the crystallization of N5-type glass-ceramics, its relatives (Na₃YSi₃O₉ (N3)- and Na₉YSi₆O₁₈ (N9)-type glass-ceramics) structurally belonging to the family of Na_24−3x Y _x Si₁₂O₃₆ were found to crystallize as the precursor phase at low temperatures. In order to produce N5 single phase glass-ceramics, the concentration of both phosphorus and rare earth was found important. The meaning of the composition was evaluated by thermodynamic and kinetic studies on the phase transformation of metastable N3 or N9 phases to stable N5 phase with Na⁺-fast ionic conductivity. The possible combinations of x and y became more limited for the crystallization of the fast ionic conducting phase as the ionic radius of R increased, while the Na⁺ conduction properties were more enhanced in the glass-ceramics of larger R. These results are discussed in view of the structure and the conduction mechanism. Also studied were the microstructural effects on the conduction properties, which were dependent upon the heating conditions of crystallization. These effects were understood in relation to the grain boundary conduction properties as well as the transmission electron microstructural morphology of grain boundaries.