Molecular imaging with endogenous substances

Abstract

Dynamic nuclear polarization has enabled hyperpolarization of nuclei such as 13 C and 15 N in endogenous substances. The resulting high nuclear polarization makes it possible to perform subsecond 13 C MRI. By using the dynamic nuclear polarization hyperpolarization technique, 10% polarization was obtained in an aqueous solution of 100 mM 13 C-labeled urea, ready for injection. The in vivo T1 relaxation time of 13 C 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 highresolution (Ϸ1-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 [ 13 C]urea solution in a rat. The results show that it is possible to perform 13 C angiography with a signalto-noise ratio of Ϸ275 in Ϸ0.25 s. Perfusion studies with endogenous substances may allow higher spatial and͞or temporal resolution than is possible with current proton imaging techniques.T he diagnostic quality of magnetic resonance (MR) images depends on the signal-to-noise ratio (SNR) as well as the contrast-to-noise ratio (CNR). The SNR is a measure of what resolution and͞or scan time is needed to separate the NMR signal generated from a given region of interest from the background noise in the image. Every ͌ 2-fold improvement in SNR allows a doubling of the spatial resolution in one direction, and has a tremendous effect on the perceived image quality (1). The CNR is a measurement of how well a region of interest can be separated from surrounding regions, which in turn is the real measure of the clinical usefulness of an MR image. Above a given receiver frequency (when the dominating noise source is the subject to be imaged), the SNR will increase linearly with the main field (2). Consequently, the manufacturers of MRI scanners have directed considerable efforts toward the development of higher field instruments with the aim of improving the diagnostic quality of the images. In recent years, 3.0-T instruments have been introduced for clinical whole-body imaging (3).The use of dynamic nuclear polarization (DNP) techniques such as the Overhauser effect (4) has been suggested as an alternative to increase SNR without the need for high magnetic field strengths (5-7), and a signal enhancement factor of Ϸ60 has been achieved at a main field of 0.01 T (8). This enhancement is smaller than the theoretically expected factor of 329, which is based on dipolar interaction between the electron spins of the administered free radical and the 1 H nuclear spins. The main reason for this discrepancy is that the electron spin system cannot be fully saturated in vivo, because excessive radio frequency irradiation will lead to unacceptable heating of the subject. This problem can be circumvented by performing the polarization process outside the subject and the MR scanner. Nuclear polarizations close to 100% for protons and Ϸ50% for 13 C in various organic molecules have been reported when D...

Compressed sensing for resolution enhancement of hyperpolarized 13C flyback 3D-MRSI

“…With the development of techniques to maintain hyperpolarization of carbon-13 in liquid state [1], it has become possible to use 13 C substrates (tracers) for medical imaging [2]. More recent studies have used the metabolically active substrate [l- 13 C]pyruvate to examine its conversion to [l- 13 C]lactate, [l- 13 C]alanine, and 13 C-bicarbonate [3][4][5].…”

Feasibility of using hyperpolarized [1-13C]lactate as a substrate for in vivo metabolic 13C MRSI studies

“…This development has enabled in vivo 13 C MR studies at high signal to noise ratio (SNR) following injection of pre-polarized 13 C substrates (2). It has been shown by using [l-13 C]pyruvate as the substrate for hyperpolarized 13 C MRS/MRSI experiment, real time cellular metabolism can be studied in normal and diseased tissues in vivo (3)(4)(5).…”

In vivo single-shot 13C spectroscopic imaging of hyperpolarized metabolites by spatiotemporal encoding

“…Further developments are in progress to exploit additional benefits of spatiotemporal encoding, such as a built-in restricted FOV capability [24,26], multi-echo experiments and parallel imaging acquisition [34]. Representative metabolic images from a rat following injection of hyperpolarized [1][2][3][4][5][6][7][8][9][10][11][12][13] …”

“…Dissolution DNP has opened new horizons in dynamic metabolic imaging through 13 C spectral observations of hyperpolarized compounds in vivo [1][2]. DNP can result in signal enhancements >10,000 for 13 C; an unprecedented increase that is leading to new opportunities for imaging pathology and monitoring treatment [3][4][5][6][7].…”