Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading.

An extraordinary new technique using hyperpolarized (13)C-labeled pyruvate and taking advantage of increased glycolysis in cancer has the potential to improve the way magnetic resonance imaging is used for detection and characterization of prostate cancer. The aim of this study was to quantify, for the first time, differences in hyperpolarized [1-(13)C] pyruvate and its metabolic products between the various histologic grades of prostate cancer using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Fast spectroscopic imaging techniques were used to image lactate, alanine, and total hyperpolarized carbon (THC = lactate + pyruvate + alanine) from the entire abdomen of normal mice and TRAMP mice with low- and high-grade prostate tumors in 14 s. Within 1 week, the mice were dissected and the tumors were histologically analyzed. Hyperpolarized lactate SNR levels significantly increased (P < 0.05) with cancer development and progression (41 +/- 11, 74 +/- 17, and 154 +/- 24 in normal prostates, low-grade primary tumors, and high-grade primary tumors, respectively) and had a correlation coefficient of 0.95 with the histologic grade. In addition, there was minimal overlap in the lactate levels between the three groups with only one of the seven normal prostates overlapping with the low-grade primary tumors. The amount of THC, a possible measure of substrate uptake, and hyperpolarized alanine also increased with tumor grade but showed more overlap between the groups. In summary, elevated hyperpolarized lactate and potentially THC and alanine are noninvasive biomarkers of prostate cancer presence and histologic grade that could be used in future three-dimensional (13)C spectroscopic imaging studies of prostate cancer patients.

Hyperpolarized C-13 spectroscopic imaging of the TRAMP mouse at 3T-initial experience.

The transgenic adenocarcinoma of mouse prostate (TRAMP) mouse is a well-studied murine model of prostate cancer with histopathology and disease progression that mimic the human disease. To investigate differences in cellular bioenergetics between normal prostate epithelial cells and prostate tumor cells, in vivo MR spectroscopic (MRS) studies with non-proton nuclei, such as (13)C, in the TRAMP model would be extremely useful. The recent development of a method for retaining dynamic nuclear polarization (DNP) in solution permits high signal-to-noise ratio (SNR) (13)C MRI or MRSI data to be obtained following injection of a hyperpolarized (13)C agent. In this transgenic mouse study, this method was applied using a double spin-echo (DSE) pulse sequence with a small-tip-angle excitation RF pulse, hyperbolic-secant refocusing pulses, and a flyback echo-planar readout trajectory for fast (10-14 s) MRSI of (13)C pyruvate (pyr) and its metabolic products at 0.135 cm(3) nominal spatial resolution. Elevated (13)C lactate (lac) was observed in both primary and metastatic tumors, demonstrating the feasibility of studying cellular bioenergetics in vivo with DNP hyperpolarized (13)C MRSI.

Accurate flip-angle calibration for 13C MRI.

(13)C imaging and spectroscopy in the presence of injected labeled compounds can vastly extend the capability of MRI to perform metabolic imaging. The details of imaging in the presence of injected compounds, however, pose new technological challenges. Pulse sequences, in general, rely on precise flip-angle (FA) calibration to create high signal-to-noise ratio (SNR), artifact-free images. Signal quantification also requires precise knowledge of the excitation FA. In MRI scans that rely on signal acquisitions from injected compounds, however, such FA calibration is challenged by low natural-abundance (13)C signal levels before injection, and by time-varying signal following injection. A method to precisely set the FA at the (13)C frequency based on FA calibration at the (23)Na frequency is presented here. A practical implementation of a coil (a dual-tuned, (23)Na/(13)C low-pass birdcage coil) suitable for this calibration in vivo is also documented. Accurate FA calibration is demonstrated at the (13)C frequency for in vivo rat experiments using this approach.

Magnetic resonance imaging at 9.4 T as a tool for studying neural anatomy in non-vertebrates.

This report describes magnetic resonance imaging (MRI) methods we have developed at 9.4 T for observing internal organs and the nervous system of an invertebrate organism, the crayfish, Cherax destructor. We have compared results acquired using two different pulse sequences, and have tested manganese (Mn(2+)) as an agent to enhance contrast of neural tissues in this organism. These techniques serve as a foundation for further development of functional MRI and neural tract-tracing methods in non-vertebrate systems.