Frequency-specific SSFP for hyperpolarized C metabolic imaging at 14.1 T

Metabolic imaging of hyperpolarized [1-¹³C] pyruvate co-polarized with [¹³C]urea by dynamic nuclear polarization with rapid dissolution is a promising new method for assessing tumor metabolism and perfusion simultaneously in vivo. Novel pulse sequences are required to enable dynamic imaging of multiple ¹³C spectral lines with high spatiotemporal resolution. The goal of this study was to investigate a new frequency-specific approach for rapid metabolic imaging of multiple ¹³C resonances using the spectral selectivity of steady-state free precession pulse (SSFP) trains. Methods developed in simulations were implemented in a dynamic frequency-cycled balanced SSFP pulse sequence on a 14.1-T animal magnetic resonance imaging scanner. This acquisition was tested in thermal and hyperpolarized phantom imaging studies and in a transgenic mouse with prostate cancer.     

The First in Vivo Observation of C–N Coupling in Mammalian Brain

[5-¹³C,¹⁵N]Glutamine, with ¹J(¹³C–¹⁵N) of 16 Hz, was observed in vivo in the brain of spontaneously breathing rats by ¹³C MRS at 4.7 T. The brain [5-¹³C]glutamine peak consisted of the doublet from [5-¹³C,¹⁵N]glutamine and the center [5-¹³C,¹⁴N]glutamine peak, resulting in an apparent triplet with a separation of 8 Hz. The time course of formation of brain [5-¹³C,¹⁵N]glutamine was monitored in vivo with a time resolution of 20–35 min. This [5-¹³C,¹⁵N]glutamine was formed by glial uptake of released neurotransmitter [5-¹³C]glutamate and its reaction with ¹⁵NH₃ catalyzed by the glia-specific glutamine synthetase. The neurotransmitter glutamate C5 was selectively¹³C-enriched by intravenous [2,5-¹³C]glucose infusion to ¹³C-label whole-brain glutamate C5, followed by [¹²C]glucose infusion to chase ¹³C from the small and rapidly turning-over glial glutamate pool, leaving ¹³C mainly in the neurotransmitter [5-¹³C]glutamate pool, which is sequestered in vesicles until release. Hence, the observed [5-¹³C,¹⁵N]glutamine arises from a coupling between ¹³C of neuronal origin and ¹⁵N of glial origin. Measurement of the rate of brain [5-¹³C,¹⁵N]glutamine formation provides a novel noninvasive method of studying the kinetics of neurotransmitter uptake into glia in vivo, a process that is crucial for protecting the brain from glutamate excitotoxicity.     

In vivo measurement of normal rat intracellular pyruvate and lactate levels after injection of hyperpolarized [1-(13)C]alanine

Hyperpolarized technology utilizing dynamic nuclear polarization has enabled rapid and high-sensitivity measurements of ¹³C metabolism in vivo. The most commonly used in vivo agent for hyperpolarized ¹³C metabolic imaging thus far has been [1-¹³C]pyruvate. In preclinical studies, not only is its uptake detected, but also its intracellular enzymatic conversion to metabolic products including [1-¹³C]lactate and [1-¹³C]alanine. However, the ratio of ¹³C-lactate/¹³C-pyruvate measured in this data does not accurately reflect cellular values since much of the [1-¹³C]pyruvate is extracellular depending on timing, vascular properties, and extracellular space and monocarboxylate transporter activity. In order to measure the relative levels of intracellular pyruvate and lactate, in this project we hyperpolarized [1-¹³C]alanine and monitored the in vivo conversion to [1-¹³C]pyruvate and then the subsequent conversion to [1-¹³C]lactate. The intracellular lactate-to-pyruvate ratio of normal rat tissue measured with hyperpolarized [1-¹³C]alanine was 4.89±0.61 (mean±S.E.) as opposed to a ratio of 0.41±0.03 when hyperpolarized [1-¹³C]pyruvate was injected.     

Analysis of hyperpolarized dynamic C lactate imaging in a transgenic mouse model of prostate cancer

This study investigated the application of an acquisition that selectively excites the [1-¹³C]lactate resonance and allows dynamic tracking of the conversion of ¹³C-lactate from hyperpolarized ¹³C-pyruvate at a high spatial resolution. In order to characterize metabolic processes occurring in a mouse model of prostate cancer, 20 sequential 3D images of ¹³C-lactate were acquired 5 s apart using a pulse sequence that incorporated a spectral–spatial excitation pulse and a flyback echo-planar readout to track the time course of newly converted ¹³C-lactate after injection of prepolarized ¹³C-pyruvate. The maximum lactate signal (MLS), full-width half-maximum (FWHM), time to the peak ¹³C-lactate signal (TTP) and area under the dynamic curve were calculated from the dynamic images of 10 TRAMP mice and two wild-type controls. The regional variation in ¹³C-lactate associated with the injected pyruvate was demonstrated by the peak of the ¹³C-lactate signal occurring earlier in the kidney than in the tumor region. The intensity of the dynamic ¹³C-lactate curves also varied spatially within the tumor, illustrating the heterogeneity in metabolism that was most prominent in more advanced stages of disease development. The MLS was significantly higher in TRAMP mice that had advanced disease.     

Measuring the link between cardiac mechanical function and metabolism during hyperpolarized 13C-pyruvate magnetic resonance experiments

PurposeThe goal of this study was to develop a methodology to investigate the relationship between contractile function and hyperpolarized (HP) [1-¹³C]pyruvate metabolism in a small animal model. To achieve sufficient signal from HP ¹³C compounds, HP ¹³C MRS/MRSI has required relatively large infusion volumes relative to the total blood volume in small animal models, which may affect cardiac function.MethodsEight female Sprague Dawley rats were imaged on a 4.7T scanner with a dual tuned ¹H/¹³C volume coil. ECG and respiratory gated k-t spiral MRSI and an IDEAL based reconstruction to determine [1-¹³C]pyruvate metabolism in the myocardium. This was coupled with ¹H cine MRI to determine ventricular volumes and mechanical function pre- and post-infusion of [1-¹³C]pyruvate. For comparison to the [1-¹³C]pyruvate experiments, three female Sprague Dawley rats were imaged with ¹H cine MRI to determine myocardial function pre- and post-saline infusion.ResultsWe demonstrated significant changes in cardiac contractile function between pre- and post-infusion of [1-¹³C]pyruvate. Specifically, there was an increase in end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF). Additionally, the ventricular vascular coupling ratio (VVCR) showed an improvement after [1-¹³C]pyruvate infusion, indicating increased systolic performance due to an increased arterial load. There was a moderate to strong relationship between the downstream metabolic conversion of pyruvate to bicarbonate and a strong relationship between the conversion of pyruvate to lactate and the cardiac mechanical function response.ConclusionThe infusion of [1-¹³C]pyruvate resulted in demonstrable increases in contractile function which was related to pyruvate conversion to bicarbonate and lactate. The combined effects of the infusion volume and inotropic effects of pyruvate metabolism likely explains the augmentation in myocardial mechanical function seen in these experiments. Given the relationship between pyruvate metabolism and contractile function observed in this study, this methodological approach may be utilized to better understand cardiac metabolic and functional remodeling in heart disease.     

[13C]Aminopyrine and [13C]Caffeine Breath Test: Influence of Gender,Cigarette Smoking and Oral Contraceptives Intake

Abstract

The [¹³C]aminopyrine breath test ([¹³C]ABT) measures the global activity of cytochrome P450 in vivo and is a sensitive indicator of liver metabolic dysfunction. The present study aims to determine whether gender and cigarette smoking influence the results of [¹³C]ABT as well as to confirm the effect of oral contraceptive steroids (OCS) intake on this metabolic test. Hundred and ten healthy subjects, including men and women, smoker and non-smoker, women taking OCS or not, were phenotyped for CYP1A2 using the [¹³C]caffeine breath test and underwent a [¹³C]ABT. Both tests showed large inter-individual variations in accordance with that of CYP450 liver content. [¹³C]ABT was sensitive enough to point out a significant induction or inhibition related to cigarette smoking habits or OCS. The combined effect of smoking and OCS resulted in an overall unchanged metabolic activity. Consequently, the impact of the studied conditions on the [¹³C]ABT parameters must be considered by clinicians or clinical investigators.     

Simultaneous measurement of neuronal and glial metabolism in rat brain in vivo using co-infusion of [1,6-C2]glucose and [1,2-C2]acetate

In this work the feasibility of measuring neuronal-glial metabolism in rat brain in vivo using co-infusion of [1,6-¹³C₂]glucose and [1,2-¹³C₂]acetate was investigated. Time courses of ¹³C spectra were measured in vivo while infusing both ¹³C-labeled substrates simultaneously. Individual ¹³C isotopomers (singlets and multiplets observed in ¹³C spectra) were quantified automatically using LCModel. The distinct ¹³C spectral pattern observed in glutamate and glutamine directly reflected the fact that glucose was metabolized primarily in the neuronal compartment and acetate in the glial compartment. Time courses of concentration of singly and multiply-labeled isotopomers of glutamate and glutamine were obtained with a temporal resolution of 11 min. Although dynamic metabolic modeling of these ¹³C isotopomer data will require further work and is not reported here, we expect that these new data will allow more precise determination of metabolic rates as is currently possible when using either glucose or acetate as the sole ¹³C-labeled substrate.     

Towards an Inhalative 13C Breath Test Method

Abstract

Customary ¹³CO₂ breath tests—and also ¹⁵N urine tests—always start with an oral administration of a test substrate. The test person swallows a stable isotope labelled diagnostic agent. This technique has been used to study several pathophysiological changes in gastrointestinal organs. However, to study pathophysiological changes of the bronchial and lung epithelium, the inhalative administration of a stable isotope labelled agent appeared more suitable to us. [1-¹³C]Hexadecanol and [1-¹³C]glucose were chosen. Inhaled [1-¹³C]hexadecanol did not yield ¹³CO₂ in the exhaled air, but [1-¹³C]glucose did. To study the practicability of the [1-¹³C]glucose method and the reproducibility of the results, 18 inhalation tests were performed with healthy subjects. In 6 self-tests, the optimum inhalative dose of [¹³C]glucose was determined to be 205 mg. Using the APS aerosol provocation system with the nebulizer ‘Medic Aid’ (Erich Jaeger Würzburg), a 25% aqueous solution was inhaled. Then, breath samples were collected at 15 min. intervals and analysed for ¹³CO₂. 75–120min after the end of inhalation a well-reproducible maximum δ¹³C value of 6‰ over baseline (DOB) was detected for 12 healthy probands.

Speculating that the pulmonary resorption of the [¹³C]glucose is the rate-limiting step of elimination, decompensations in the epithelium ought to be reflected in changed [1-¹³C]glucose resorption rates and changed ¹³CO₂ output.

Therefore, we speculate that the inhalation of suitable ¹³C-labelled substrates will pave the way for a new group of ¹³CO₂ breath tests aiding investigations of specific pathophysiological changes in the pulmonary tract, such as inflammations of certain sections and decompensations of cell functions.     

Perfusion and diffusion sensitive C stimulated-echo MRSI for metabolic imaging of cancer

Metabolic imaging with hyperpolarized [1-¹³C]-pyruvate can rapidly probe tissue metabolic profiles in vivo and has been shown to provide cancer imaging biomarkers for tumor detection, progression, and response to therapy. This technique uses a bolus injection followed by imaging within 1–2 minutes. The observed metabolites include vascular components and their generation is also influenced by cellular transport. These factors complicate image interpretation, especially since [1-¹³C]lactate, a metabolic product that is a biomarker of cancer, is also produced by red blood cells. It would be valuable to understand the distribution of metabolites between the vasculature, interstitial space, and intracellular compartments. The purpose of this study was to better understand this compartmentalization by using a perfusion and diffusion-sensitive stimulated-echo acquisition mode (STEAM) MRSI acquisition method tailored to hyperpolarized substrates. Our results in mouse models showed that among metabolites, the injected substrate ¹³C-pyruvate had the largest vascular fraction overall while ¹³C-alanine had the smallest vascular fraction. We observed a larger vascular fraction of pyruvate and lactate in the kidneys and liver when compared to back muscle and prostate tumor tissue. Our data suggests that ¹³C-lactate in prostate tumor tissue voxels was the most abundant labeled metabolite intracellularly. This was shown in STEAM images that highlighted abnormal cancer cell metabolism and suppressed vascular ¹³C metabolite signals.     

Rapid sequential injections of hyperpolarized [1-C]pyruvate in vivo using a sub-kelvin,multi-sample DNP polarizer

The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of ¹³C metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1-¹³C]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5 min interval between injections of hyperpolarized [1-¹³C]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1 min after administration, and 6 min after administration. Dramatic increases in ¹³C-bicarbonate were detected just 1 min (as well as 6 min) after DCA administration.     

Development of high resolution 3D hyperpolarized carbon-13 MR molecular imaging techniques

The goal of this project was to develop and apply techniques for T₂ mapping and 3D high resolution (1.5 mm isotropic; 0.003 cm³) ¹³C imaging of hyperpolarized (HP) probes [1-¹³C]lactate, [1-¹³C]pyruvate, [2-¹³C]pyruvate, and [¹³C,¹⁵N₂]urea in vivo. A specialized 2D bSSFP sequence was implemented on a clinical 3T scanner and used to obtain the first high resolution T₂ maps of these different hyperpolarized compounds in both rats and tumor-bearing mice. These maps were first used to optimize timings for highest SNR for single time-point 3D bSSFP acquisitions with a 1.5 mm isotropic spatial resolution of normal rats. This 3D acquisition approach was extended to serial dynamic imaging with 2-fold compressed sensing acceleration without changing spatial resolution. The T₂ mapping experiments yielded measurements of T₂ values of > 1 s for all compounds within rat kidneys/vasculature and TRAMP tumors, except for [2-¹³C]pyruvate which was ~ 730 ms and ~ 320 ms, respectively. The high resolution 3D imaging enabled visualization the biodistribution of [1-¹³C]lactate, [1-¹³C]pyruvate, and [2-¹³C]pyruvate within different kidney compartments as well as in the vasculature. While the mouse anatomy is smaller, the resolution was also sufficient to image the distribution of all compounds within kidney, vasculature, and tumor. The development of the specialized 3D sequence with compressed sensing provided improved structural and functional assessments at a high (0.003 cm³) spatial and 2 s temporal resolution in vivo utilizing HP ¹³C substrates by exploiting their long T₂ values. This 1.5 mm isotropic resolution is comparable to ¹H imaging and application of this approach could be extended to future studies of uptake, metabolism, and perfusion in cancer and other disease models and may ultimately be of value for clinical imaging.     

Use of hyperpolarized [1-C]pyruvate and [2-C]pyruvate to probe the effects of the anticancer agent dichloroacetate on mitochondrial metabolism in vivo in the normal rat

Development of hyperpolarized technology utilizing dynamic nuclear polarization has enabled the measurement of ¹³C metabolism in vivo at very high signal-to-noise ratio (SNR). In vivo mitochondrial metabolism can, in principle, be monitored with pyruvate, which is catalyzed to acetyl-CoA via pyruvate dehydrogenase (PDH). The purpose of this work was to determine whether the compound sodium dichloroacetate (DCA) could aid the study of mitochondrial metabolism with hyperpolarized pyruvate. DCA stimulates PDH by inhibiting its inhibitor, pyruvate dehydrogenase kinase. In this work, hyperpolarized [1-¹³C]pyruvate and [2-¹³C]pyruvate were used to probe mitochondrial metabolism in normal rats. Increased conversion to bicarbonate (+ 181±69%, P=.025) was measured when [1-¹³C]pyruvate was injected after DCA administration, and increased glutamate (+ 74±23%, P=.004), acetoacetate (+ 504±281%, P=.009) and acetylcarnitine (+ 377±157%, P=.003) were detected when [2-¹³C]pyruvate was used.     

In vivo C magnetic resonance spectroscopy of a human brain tumor after application of C-1-enriched glucose

Objectives

As a unique tool to assess metabolic fluxes noninvasively, ¹³C magnetic resonance spectroscopy (MRS) could help to characterize and understand malignancy in human tumors. However, its low sensitivity has hampered applications in patients. The aim of this study was to demonstrate that with sensitivity-optimized localized ¹³C MRS and intravenous infusion of [1-¹³C]glucose under euglycemia, it is possible to assess the dynamic conversion of glucose into its metabolic products in vivo in human glioma tissue.

Materials and Methods

Measurements were done at 3 T with a broadband single RF channel and a quadrature ¹³C surface coil inserted in a ¹H volume coil. A ¹H/¹³C polarization transfer sequence was applied, modified for localized acquisition, alternatively in two (50 ml) voxels, one encompassing the tumor and the other normal brain tissue.

Results

After about 20 min of [1-¹³C]glucose infusion, a [3-¹³C]lactate signal appeared among several resonances of metabolic products of glucose in MR spectra of the tumor voxel. The resonance of [3-¹³C]lactate was absent in MR spectra from contralateral tissue. In addition, the intensity of [1-¹³C]glucose signals in the tumor area was about 50% higher than that in normal tissue, likely reflecting more glucose in extracellular space due to a defective blood–brain barrier. The signal intensity for metabolites produced in or via the tricarboxylic acid (TCA) cycle was lower in the tumor than in the contralateral area, albeit that the ratios of isotopomer signals were comparable.

Conclusion

With an improved ¹³C MRS approach, the uptake of glucose and its conversion into metabolites such as lactate can be monitored noninvasively in vivo in human brain tumors. This opens the way to assessing metabolic activity in human tumor tissue.     

In Vivo3D LocalizedC Spectroscopy Using Modified INEPT and DEPT

The 3D localized¹³C spectroscopy methods LINEPT and LODEPT, which are modifications of INEPT and DEPT, are proposed. As long as a¹³C inversion pulse (180-degree pulse) is applied at 1/(4J) before the proton echo time in LINEPT and a¹³C excitation pulse (90-degree pulse) is applied at 1/(2J) before the proton echo time in LODEPT, the proton echo time can be set to any value longer than 1/(2J) in LINEPT and longer than 1/Jin LODEPT. As a result, the proton and the¹³C pulses can be applied separately and these proton pulses can be made slice-selective pulses. These localization features of LINEPT and LODEPT were evaluated using a phantom consisting of a cylinder filled with ethanol placed inside another cylinder filled with oil, and localized ethanol spectra could be obtained.In vivo3D localized¹³C spectra from the brain of a monkey could be obtained using decoupled LINEPT, and glutamate C-4 appeared directly after the administration of glucose C-1, followed by the appearance of glutamate C-2, C-3 and glutamine C-2, C-3, C-4.     

Comparison of two dosage regimens of the substrate for the [13C]methacetin breath test

The [¹³C]methacetin breath test ([¹³C]MBT) – a valuable non-invasive tool dedicated to the assessment of the liver metabolic capacity – still needs standardisation. The aim of this study was to check whether currently used dosage regimens of [¹³C]methacetin provide concordant [¹³C]MBT results in subjects with an atypical body constitution. Healthy volunteers: low body mass<55 kg (eight women), and high body mass>95 kg (eight large body frame men) were recruited. They underwent [¹³C]MBT on separate days, taking in random order [¹³C]methacetin: a fixed 75 mg dose (FX75), or a 1 mg kg^?1 body mass-adjusted dose (BMAD). Samples of expiratory air for ¹³CO₂ measurement were collected over 3 h. The maximum momentary ¹³C elimination in breath air occurred earlier and was higher following BMAD than with FX75 in the low body mass females (T _max 14.6±1.0 min vs. 22.1±2.4 min, p=0.019; D _max 41.9±2.9 % dose h^?1 vs. 36.6±3.6 % dose h^?1, p=0.071). In the high body mass men, T _max remained unchanged, whereas D _max was slightly higher with BMAD compared to FX75 (21.5±3.2 min vs. 23.0±3.0 min; 38.5±2.9 % dose h^?1 vs. 32.3±2.5 % dose h^?1). It is concluded that in subjects with a body constitution outside the general population average, the dosage of the substrate may affect some results of the [¹³C]MBT. The dosage-related differences appear, however, to be insignificant if the result of the [¹³C]MBT is reported as a cumulative ¹³C recovery in breath air.     

The feasibility of assessing branched-chain amino acid metabolism in cellular models of prostate cancer with hyperpolarized [1-C]-ketoisocaproate

Recent advancements in the field of hyperpolarized ¹³C magnetic resonance spectroscopy (MRS) have yielded powerful techniques capable of real-time analysis of metabolic pathways. These non-invasive methods have increasingly shown application in impacting disease diagnosis and have further been employed in mechanistic studies of disease onset and progression. Our goals were to investigate branched-chain aminotransferase (BCAT) activity in prostate cancer with a novel molecular probe, hyperpolarized [1-¹³C]-2-ketoisocaproate ([1-¹³C]-KIC), and explore the potential of branched-chain amino acid (BCAA) metabolism to serve as a biomarker. Using traditional spectrophotometric assays, BCAT enzymatic activities were determined in vitro for various sources of prostate cancer (human, transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse and human cell lines). These preliminary studies indicated that low levels of BCAT activity were present in all models of prostate cancer but enzymatic levels are altered significantly in prostate cancer relative to healthy tissue. The MR spectroscopic studies were conducted with two cellular models (PC-3 and DU-145) that exhibited levels of BCAA metabolism comparable to the human disease state. Hyperpolarized [1-¹³C]-KIC was administered to prostate cancer cell lines, and the conversion of [1-¹³C]-KIC to the metabolic product, [1-¹³C]-leucine ([1-¹³C]-Leu), could be monitored via hyperpolarized ¹³C MRS.     

Liver function assessment with three 13C breath tests by two-point measurements

In this study, we performed three breath tests – l-[1-¹³C ]phenylalanine breath test (PBT), l-[1-¹³C ] methionine breath test, and [¹³C]methacetin breath test (MethaBT) – in patients with chronic liver disease to determine the optimal timing of expired air collection for diagnosing chronic liver disease and evaluating the grade of fibrosis. The subjects were 61 adults with normal livers, 98 chronic hepatitis patients, and 91 liver cirrhosis patients. We investigated the relationships of breath test results with routine biochemical tests and the Child–Pugh score, as well as the diagnostic capacities of the breath tests for liver dysfunction/cirrhosis and grade of liver fibrosis. For the diagnosis of liver cirrhosis and correlations with liver fibrosis, the accuracy of the PBT at 30 min (PBT30) was similar to that of the MethaBT at 15 min (Metha15). For liver function assessment by two-point measurement with ¹³C breath tests, we recommend the PBT30 and the Metha15.     

One- and two-dimensional C–H/N–H dipolar correlation experiments under fast magic-angle spinning for determining the peptide dihedral angle φ

A recently proposed ¹³C–¹H recoupling sequence operative under fast magic-angle spinning (MAS) [K. Takegoshi, T. Terao, Solid State Nucl. Magn. Reson. 13 (1999) 203–212.] is applied to observe ¹³C–¹H and ¹⁵N–¹H dipolar powder patterns in the ¹H–¹⁵N–¹³C–¹H system of a peptide bond. Both patterns are correlated by ¹⁵N-to-¹³C cross polarization to observe one- or two-dimensional (1D or 2D) correlation spectra, which can be simulated by using a simple analytical expression to determine the H–N–C–H dihedral angle. The 1D and 2D experiments were applied to N-acetyl[1,2-¹³C,¹⁵N] -valine, and the peptide φ angle was determined with high precision by the 2D experiment to be ±155.0°±1.2°. The positive one is in good agreement with the X-ray value of 154°±5°. The 1D experiment provided the value of φ=±156.0°±0.8°.     

Hyperpolarized 13C MRS Cardiac Metabolism Studies in Pigs: Comparison Between Surface and Volume Radiofrequency Coils

Cardiac metabolism assessment with hyperpolarized ¹³C magnetic resonance spectroscopy in pig models requires the design of dedicated coils capable of providing large field of view with high signal-to-noise ratio (SNR) data. This work presents a comparison between a commercial ¹³C quadrature birdcage coil and a homebuilt ¹³C circular coil both designed for hyperpolarized studies of pig heart with a clinical 3T scanner. In particular, the simulation of the two coils is described by developing an SNR model for coil performance prediction and comparison. While coil resistances were calculated from Ohm’s law, the magnetic field patterns and sample-induced resistances were calculated using a numerical finite-difference time-domain algorithm. After the numerical simulation of both coils, the results are presented as SNR-versus-depth profiles using experimental SNR extracted from the [1-¹³C]acetate phantom chemical shift image and with a comparison of metabolic maps acquired by hyperpolarized [1-¹³C]pyruvate injected in a pig. The accuracy of the developed SNR models was demonstrated by good agreement between the theoretical and experimental coil SNR-versus-depth profiles.     

Zur Herstellung von 14C- und 3H-markiertem Guajakolglycerinäther und dessen Metabolismus im Tierkörper

Für die Herstellung von Guajakol-[1,3-¹⁴C]glycerinäther, [7-¹⁴C]Guajakolgylycerinäther und ³H-Guajakolglycerinäther werden Synthesevorschriften angegeben. Der Metbolismus wird mit Hilfe der ¹³C- oder ³H-markierten Verbindung im Tierexperiment verfolgt. Dabei kann nachgewiesen werden, daβ Guajakolglycerinä;ther hauptsächlich in nicht veränderter Form durch Urin und Galle wieder ausgeschieden wird. Nur in Spuren werden als Metaboliten Brenzkatechin und Guajakol gefunden.