Orally administered manganese with and without ascorbic acid as a liver-specific contrast agent and bowel marker for magnetic resonance imaging: phase I clinical trial assessing efficacy and safety.

Objectives: The objectives of this clinical trial of orally administered manganese in magnetic resonance imaging (MRI) of the liver were to assess signal enhancements in the liver with and without the addition of an uptake promoter, ascorbic acid, and to evaluate acute safety.

Materials And Methods: A total of 18 healthy adult males were enrolled in the present trial. Contrast medium: MnCl2, doses: 25, 50, and 100 micromoL/kg bw, respectively, and promoting agent: Ascorbic acid, doses: 50, 100, and 200 micromoL/kg bw, respectively, were used.

Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate.

As alterations in tissue pH underlie many pathological processes, the capability to image tissue pH in the clinic could offer new ways of detecting disease and response to treatment. Dynamic nuclear polarization is an emerging technique for substantially increasing the sensitivity of magnetic resonance imaging experiments. Here we show that tissue pH can be imaged in vivo from the ratio of the signal intensities of hyperpolarized bicarbonate (H(13)CO(3)(-)) and (13)CO(2) following intravenous injection of hyperpolarized H(13)CO(3)(-).

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.

Iodixanol 320 results in better renal tolerance and radiodensity than do gadolinium-based contrast media: arteriography in ischemic porcine kidneys.

Purpose: To prospectively compare nephrotoxicity and radiodensity of plasma hyperosmotic gadolinium chelates (attenuation-osmotic ratio of 1:1) with those of plasma iso-osmotic iodine-based contrast media (attenuation-osmotic ratio of 3:1 or 6:1) after renal arteriography in ischemic porcine kidneys.

Materials And Methods: The local animal care committee approved this study. The following contrast media were used: (a) iodixanol (150 mg of iodine per milliliter and 320 mg I/mL, 0.

Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy.

Measurements of early tumor responses to therapy have been shown, in some cases, to predict treatment outcome. We show in lymphoma-bearing mice injected intravenously with hyperpolarized [1-(13)C]pyruvate that the lactate dehydrogenase-catalyzed flux of (13)C label between the carboxyl groups of pyruvate and lactate in the tumor can be measured using (13)C magnetic resonance spectroscopy and spectroscopic imaging, and that this flux is inhibited within 24 h of chemotherapy. The reduction in the measured flux after drug treatment and the induction of tumor cell death can be explained by loss of the coenzyme NAD(H) and decreases in concentrations of lactate and enzyme in the tumors.

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.

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.

Metabolic imaging by hyperpolarized 13C magnetic resonance imaging for in vivo tumor diagnosis.

The "Warburg effect," an elevation in aerobic glycolysis, may be a fundamental property of cancer cells. For cancer diagnosis and treatment, it would be valuable if elevated glycolytic metabolism could be quantified in an image in animals and humans. The pyruvate molecule is at the metabolic crossroad for energy delivery inside the cell, and with a noninvasive measurement of the relative transformation of pyruvate into lactate and alanine within a biologically relevant time frame (seconds), it may be possible to quantify the glycolytic status of the cells.

Gadolinium contrast media are more nephrotoxic than iodine media. The importance of osmolality in direct renal artery injections.

A study was undertaken of the role of osmotoxicity in gadolinium (Gd) and iodine contrast media (CM) nephrotoxicity in ischemic porcine kidneys. Test solutions: mannitol iso-osmotic to 0.5 M: gadopentetate (1.

Real-time metabolic imaging.

The endogenous substance pyruvate is of major importance to maintain energy homeostasis in the cells and provides a window to several important metabolic processes essential to cell survival. Cell viability is therefore reflected in the metabolism of pyruvate. NMR spectroscopy has until now been the only noninvasive method to gain insight into the fate of pyruvate in the body, but the low NMR sensitivity even at high field strength has only allowed information about steady-state conditions.

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.

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.

3He MRI-based assessment of posture-dependent regional ventilation gradients in rats.

A recently developed method for quantitative assessment of regional lung ventilation was employed for the study of posture-dependent ventilation differences in rats. The measurement employed hyperpolarized (3)He MRI to detect the build-up of the signal intensity after increasing numbers of (3)He breaths, which allowed for computation of a regional ventilation parameter. A group of six anesthetized rats was studied in both supine and prone postures.

Molecular imaging using hyperpolarized 13C.

MRI provides unsurpassed soft tissue contrast, but the inherent low sensitivity of this modality has limited the clinical use to imaging of water protons. With hyperpolarization techniques, the signal from a given number of nuclear spins can be raised more than 100 000 times. The strong signal enhancement enables imaging of nuclei other than protons, e.

Perfusion assessment with bolus differentiation: a technique applicable to hyperpolarized tracers.

A new technique for assessing tissue blood flow using hyperpolarized tracers, based on the fact that the magnetization of a hyperpolarized substance can be destroyed permanently, is described. Assessments of blood flow with this technique are inherently insensitive to arterial delay and dispersion, and allow for quantification of the transit time and dispersion in the arteries that supply the investigated tissue. Renal cortical blood flow was studied in six rabbits using a 13C-labeled compound (2-hydroxyethylacrylate) that was polarized by the parahydrogen-induced polarization (PHIP) technique.

Cerebral perfusion assessment by bolus tracking using hyperpolarized 13C.

Cerebral perfusion was assessed with 13C MRI in a rat model after intravenous injections of the 13C-labeled compound bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-D8 in aqueous solutions hyperpolarized by dynamic nuclear polarization (DNP). Since the tracer acted as a direct signal source, several of the problems associated with techniques based on traditional dynamic susceptibility contrast (DSC) MRI contrast agents were avoided. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were calculated.

Characterization of diffusing capacity and perfusion of the rat lung in a lipopolysaccaride disease model using hyperpolarized 129Xe.

The ability to quantify pulmonary diffusing capacity and perfusion using dynamic hyperpolarized (129)Xe NMR spectroscopy is demonstrated. A model of alveolar gas exchange was developed, which, in conjunction with (129)Xe NMR, enables quantification of average alveolar wall thickness, pulmonary perfusion, capillary diffusion length, and mean transit time. The technique was employed to compare a group of naïve rats (n = 10) with a group of rats with acute inflammatory lung injury (n = 10), caused by instillation of lipopolysaccaride (LPS).

Increase of signal-to-noise of more than 10,000 times in liquid state NMR.

Extract: Two major applications exist for Nuclear Magnetic Resonance (NMR): spectroscopy and imaging. NMR spectroscopy has gained acceptance as one of the major analytical techniques, due to the detailed information that can be obtained about molecular structure, dynamics and intra- and inter-molecular interactions. Magnetic resonance imaging (MRI) is a non-invasive technique with superior soft tissue contrast and broad diagnostic value.

Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR.

A method for obtaining strongly polarized nuclear spins in solution has been developed. The method uses low temperature, high magnetic field, and dynamic nuclear polarization (DNP) to strongly polarize nuclear spins in the solid state. The solid sample is subsequently dissolved rapidly in a suitable solvent to create a solution of molecules with hyperpolarized nuclear spins.

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.

Gradient echo imaging of flowing hyperpolarized nuclei: theory and phantom studies on 129Xe dissolved in ethanol.

The influence of flip angle and flow velocity on the signal intensity achieved when imaging a hyperpolarized substance with a spoiled gradient echo sequence was investigated. The study was performed both theoretically and experimentally using hyperpolarized xenon dissolved in ethanol. Analytical expressions regarding the optimal flip angle with respect to signal and the corresponding signal level are presented and comparisons with thermally polarized substances are made.

Echo-planar MR imaging of dissolved hyperpolarized 129Xe.

Purpose: The feasibility of hyperpolarized 129Xe for fast MR angiography (MRA) was evaluated using the echo-planar imaging (EPI) technique.

Material And Methods: Hyperpolarized Xe gas was dissolved in ethanol, a carrier agent with high solubility for Xe (Ostwald solubility coefficient 2.5) and long relaxation times.

A study of the use of Overhauser enhancement to assist with needle and catheter placement during interventional MRI.

The practicability of using Overhauser enhancement of saline in interventional MRI was investigated. Saline was used as a means of marking the path taken by a fluid-filled cavity, similar to that formed by a needle, catheter, or cannula during interventional MRI procedures. A prototype device was designed and constructed for saturation and propulsion of 0.