Fast metabolite mapping in the pig heart after injection of hyperpolarized 13C-pyruvate with low-flip angle balanced steady-state free precession imaging.

The conversion of hyperpolarized (13)C pyruvate to metabolic products in the Krebs cycle provides valuable information about the metabolic status and the viability of the myocardium. Therefore, imaging methods must be able to spectrally discriminate different (13)C metabolites. However, the requirement for spectral selectivity conflicts with the demands for rapid image acquisition and high spatial resolution in cardiac imaging. In this work, the feasibility of a balanced steady state free precession sequence with low flip angles was investigated in the pig heart after injection of hyperpolarized (13)C(1)-pyruvate. Using cardiac gating, it was possible to acquire (13)C-bicarbonate images within a single heartbeat (acquisition time 150 ms) without destroying the substrate signal from the hyperpolarized pyruvate. Therefore, the technique may be useful in dynamic studies of cardiac metabolism.

Hyperpolarized molecules in solution.

Hyperpolarization is a technique to enhance the nuclear polarization and thereby increase the available signal in magnetic resonance (MR). This chapter provides an introduction to the concept of hyperpolarization as well as an overview of dynamic nuclear polarization (DNP) and para-hydrogen induced polarization (PHIP), two methods used to generate hyperpolarized molecules in aqueous solution.

Applications of hyperpolarized agents in solutions.

This chapter provides an overview of pulse sequences adapted to hyperpolarized MR imaging. Applications of hyperpolarized agents in aqueous solution are reviewed. Vascular (e.g., angiography, perfusion, and catheter tracking) as well as metabolic (e.g., oncology, cardiology, neurology, and pH mapping) applications are covered. Due to the rapid development of new applications for hyperpolarized agents, a review format has been used for this chapter instead of a strict protocol/procedure structure.

Fast multiecho balanced SSFP metabolite mapping of (1)H and hyperpolarized (13)C compounds.

OBJECT: To investigate the feasibility of multiecho balanced steady-state free precession (bSSFP)-based fast chemical shift mapping hyperpolarized (13)C metabolites. The overall goal was to reduce total imaging time and to increase spatial resolution compared to common chemical shift imaging (CSI). MATERIALS AND METHODS: A multiecho bSSFP sequence in combination with an iterative reconstruction algorithm was implemented. (1)H experiments were performed on phantoms and on a human volunteer in order to investigate the feasibility of the method on a system with metabolite maps that are known beforehand. (13)C experiments were performed in vivo on pigs, where CSI images were acquired also for comparison. RESULTS: Chemical shift images of three and four distinct (1)H resonance frequencies as well as chemical shift images of up to five hyperpolarized (13)C metabolites were successfully obtained. CONCLUSION: Fast metabolite mapping based on multiecho balanced SSFP in combination with an iterative reconstruction approach could successfully separate several (1)H resonances and hyperpolarized (13)C metabolites.

Cardiac metabolism measured noninvasively by hyperpolarized 13C MRI.

Pyruvate is included in the energy production of the heart muscle and is metabolized into lactate, alanine, and CO(2) in equilibrium with HCO(3) (-). The aim of this study was to evaluate the feasibility of using (13)C hyperpolarization enhanced MRI to monitor pyruvate metabolism in the heart during an ischemic episode. The left circumflex artery of pigs (4 months, male, 29-34 kg) was occluded for 15 or 45 min followed by 2 hr of reperfusion. Pigs were examined by (13)C chemical shift imaging following intravenous injection of 1-(13)C pyruvate. (13)C chemical shift MR imaging was used in order to visualize the local concentrations of the metabolites. After a 15-min occlusion (no infarct) the bicarbonate signal level in the affected area was reduced (25-44%) compared with the normal myocardium. Alanine signal level was normal. After a 45-min occlusion (infarction) the bicarbonate signal was almost absent (0.2-11%) and the alanine signal was reduced (27-51%). Due to image-folding artifacts the data obtained for lactate were inconclusive. These studies demonstrate that cardiac metabolic imaging with hyperpolarized 1-(13)C-pyruvate is feasible. The changes in concentrations of the metabolites within a minute after injection can be detected and metabolic maps constructed.

Passive catheter tracking during interventional MRI using hyperpolarized 13C.

Interventional procedures in MRI can be performed preclinically using active or passive catheter-tracking methods. A novel passive nonproton technique is suggested that uses a catheter filled with a hyperpolarized (13)C contrast agent. A prototype three-lumen catheter was built with two closed lumens containing a flowing hyperpolarized (13)C contrast agent. Entire-length (13)C catheter projection visualization could be performed in vivo with a catheter SNR of approximately 80, one dual projection frame per approximately 700 ms, and an in-plane resolution of 2 x 2 mm(2) while traveling through the aorta of a pig. The traveling path of the (13)C catheter was visualized after back-projection catheter reconstruction and after image fusion with an anatomical offline proton road map. Catheter length visualization was aided by an oblique planar visualization mode. The high catheter signal demonstrated, together with the entire catheter length visualization and high surrounding soft-tissue contrast, warrants further development into a real-time technique.

Hyperpolarized 13C MRI of the pulmonary vasculature and parenchyma.

The study of lung perfusion in normal and diseased subjects is of great interest to physiologists and physicians. In this work we demonstrate the application of a liquid-phase hyperpolarized (HP) carbon-13 ((13)C) tracer to magnetic resonance imaging (MRI) of the pulmonary vasculature and pulmonary perfusion in a porcine model. Our results show that high spatial and temporal resolution images of pulmonary perfusion can be obtained with this contrast technique. Traditionally, pulmonary perfusion measurement techniques have been challenging because of insufficient signal for quantitative functional assessments. The use of polarized (13)C in MRI overcomes this limitation and may lead to a viable clinical method for studying the pulmonary vasculature and perfusion.

Fast chemical shift mapping with multiecho balanced SSFP.

OBJECT: A method is proposed that provides spectroscopic images with high spatial resolution and moderate spectral resolution at very short total data acquisition times. MATERIALS AND METHODS: Balanced steady-state free precession (bSSFP, TrueFISP, FIESTA, b-FFE) is combined with a multiecho readout gradient and frequency-sensitive reconstruction such as Fourier reconstruction known from echo-planar spectroscopic imaging (EPSI) or matrix inversion. Balanced SSFP imaging requires short repetition times to minimize banding artefacts, thereby restricting the achievable frequency resolution. RESULTS: Two-dimensional (2D) high-resolution spectroscopic images were produced of three 1H resonances (water, acetone and fat) on phantoms and water/fat separation in vivo within 1-2 s. Additionally, fast 31P spectroscopic images were acquired from a phantom consisting of two resonances within 195 ms. CONCLUSION: Frequency-sensitive reconstruction of multiecho bSSFP data can provide spectroscopic images with high spatial and temporal resolution while the frequency resolution is moderate at around 100 Hz. The method can also separate more than three resonances, allowing for hetero-nuclei metabolite mapping, for example 13C and 31P.

MR coronary angiography in pigs with intraarterial injections of a hyperpolarized 13C substance.

A new diagnostic application of a water-soluble contrast medium (CM) based on the hyperpolarization of a 13C substance is introduced. The degree of polarization achieved is >30%, which is about a factor of 10(5) higher than the thermal equilibrium polarization level at 1.5 T. Imaging of hyperpolarized (HP) CM during a cardiac interventional MRI procedure was studied. Catheters were positioned in the left and right coronary arteries of pigs. A coil tuned to 13C was used for nonproton imaging. The HP-13C CM ( approximately 5 ml, 0.5 M, approximately 30% polarization) was injected during projection imaging using a fully balanced steady-state free precession (SSFP) pulse sequence with and without cardiac gating. The contrast agent-filled catheter was clearly visible during the procedure. The coronary arteries were well depicted and the signal-to-noise ratios (SNRs) were in the range of 10-40. The use of HP-13C CM may provide a new diagnostic procedure for interventional MRI.

13C imaging-a new diagnostic platform.

The evolution of magnetic resonance imaging (MRI) has been astounding since the early 1980s, and a broad range of applications has emerged. To date, clinical imaging of nuclei other than protons has been precluded for reasons of sensitivity. However, with the recent development of hyperpolarization techniques, the signal from a given number of nuclei can be increased as much as 100,000 times, sufficient to enable imaging of nonproton nuclei. Technically, imaging of hyperpolarized nuclei offers several unique properties, such as complete lack of background signal and possibility for local and permanent destruction of the signal by means of radio frequency (RF) pulses. These properties allow for improved as well as new techniques within several application areas. Diagnostically, the injected compounds can visualize information about flow, perfusion, excretory function, and metabolic status. In this review article, we explain the concept of hyperpolarization and the techniques to hyperpolarize 13C. An overview of results obtained within angiography, perfusion, and catheter tracking is given, together with a discussion of the particular advantages and limitations. Finally, possible future directions of hyperpolarized 13C MRI are pointed out.

Molecular imaging with endogenous substances.

Dynamic nuclear polarization has enabled hyperpolarization of nuclei such as 13C and 15N in endogenous substances. The resulting high nuclear polarization makes it possible to perform subsecond 13C MRI. By using the dynamic nuclear polarization hyperpolarization technique, 10% polarization was obtained in an aqueous solution of 100 mM 13C-labeled urea, ready for injection. The in vivo T1 relaxation time of 13C in the urea solution was determined to 20 +/- 2 s. Due to the long relaxation time, it is possible to use the hyperpolarized substance for medical imaging. A series of high-resolution ( approximately 1-mm) magnetic resonance images were acquired, each with a scan time of 240 ms, 0-5 s after an i.v. injection of the hyperpolarized aqueous [13C]urea solution in a rat. The results show that it is possible to perform 13C angiography with a signal-to-noise ratio of approximately 275 in approximately 0.25 s. Perfusion studies with endogenous substances may allow higher spatial and/or temporal resolution than is possible with current proton imaging techniques.

Hyperpolarized 13C MR angiography using trueFISP.

A (13)C-enriched water-soluble compound (bis-1,1-(hydroxymethyl)-1-(13)C-cyclopropane-D(8)), with a (13)C-concentration of approximately 200 mM, was hyperpolarized to approximately 15% using dynamic nuclear polarization, and then used as a contrast medium (CM) for contrast-enhanced magnetic resonance angiography (CE-MRA). The long relaxation times (in vitro: T(1) approximately 82 s, T(2) approximately 18 s; in vivo: T(1) approximately 38 s, T(2) approximately 1.3 s) are ideal for steady-state free precession (SSFP) imaging with a true fast imaging and steady precession (trueFISP) pulse sequence. It was shown both theoretically and experimentally that the optimal flip angle was 180 degrees. CE-MRA was performed in four anesthetized live rats after intravenous injection of 3 ml CM. The angiograms covered the thoracic/abdominal region in two of the animals, and the head-neck region in the other two. Fifteen consecutive images were acquired in each experiment, with a flip-back pulse at the end of each image acquisition. In the angiograms, the vena cava (SNR approximately 240), aorta, renal arteries, carotid arteries (SNR approximately 75), jugular veins, and several other vessels were visible. The SNR in the cardiac region was 500. Magnetization was preserved from one image acquisition to the next using the flip-back technique (SNR(cardiac) approximately 10 in the 15th image).

Quantitative measurement of regional lung ventilation using 3He MRI.

A new strategy for a quantitative measurement of regional pulmonary ventilation using hyperpolarized helium-3 (3He) MRI has been developed. The method employs the build-up of the signal intensity after a variable number of (3)He breaths. A mathematical model of the signal dynamics is presented, from which the local ventilation, defined as the fraction of gas exchanged per breath within a given volume, is calculated. The model was used to create ventilation maps of coronal slices of guinea pig lungs. Ventilation values very close to 1 were found in the trachea and the major airways. In the lung parenchyma, regions adjacent to the hilum showed values of 0.6-0.8, whereas 0.2-0.4 was measured in peripheral regions. Monte Carlo simulations were used to investigate the accuracy of the method and its limitations. The simulations revealed that, at presently attainable signal-to-noise ratios, the ventilation parameter can be determined with a relative uncertainty of <5% over a wide range of values.