Hyperpolarized MR Imaging: Neurologic Applications of Hyperpolarized Metabolism

Abstract

SUMMARY:Hyperpolarization is the general term for a method of enhancing the spin-polarization difference of populations of nuclei in a magnetic field. No less than 5 distinct techniques (dynamic nuclear polarization [DNP]; parahydrogen-induced polarizationϪparahydrogen and synthesis allow dramatically enhanced nuclear alignment [PHIP-PASADENA]; xenon/helium polarization transfer; Brute Force; 1 H hyperpolarized water) are currently under exhaustive investigation as means of amplifying the intrinsically (a few parts per million) weak signal intensity used in conventional MR neuroimaging and spectroscopy. HD-MR imaging in vivo is a metabolic imaging tool causing much of the interest in HD-MR imaging. The most successful to date has been DNP, in which carbon-13 ( 13 C) pyruvic acid has shown many. PHIP-PASADENA with 13 C succinate has shown HD-MR metabolism in vivo in tumorbearing mice of several types, entering the KrebsϪtricarboxylic acid cycle for ultrafast detection with 13 C MR imaging, MR spectroscopy, and chemical shift imaging. We will discuss 5 promising preclinical studies:13 C succinate PHIP in brain tumor; 13 C ethylpyruvate DNP and 13 C acetate; DNP in rodent brain;13 C succinate PHIP versus gadolinium imaging of stroke; and 1 H hyperpolarized imaging. Recent developments in clinical 13 C neurospectroscopy encourage us to overcome the remaining barriers to clinical HD-MR imaging.T he symposium 1 dealt with the topic of novel contrast agents "that enhance your image." If the definition of contrast is the addition of any new dimension, then a reasonable theme for this review-which asks whether hyperpolarized (HD)-MR imaging and spectroscopy of the brain are both feasible and contributory-would be to discuss the novel contrast that is enhanced by chemistry. Chemical ContrastMore than 80 brain metabolites can be distinguished and displayed (as a spectrum) by using MR spectroscopy. However, a quick glance at the metabolic diagram provided as a guide to the human single-voxel proton brain examination (the conventional and automated PROBE/SV; GE Healthcare, Milwaukee, Wisconsin) shows that we do not directly observe any metabolites of the KrebsϪtricarboxylic acid (TCA-the centerpiece of cerebral mitochondrial energy metabolism) cycle and do not draw any conclusions about it or several other important aspects of brain chemistry, except by inference. Under special circumstances, the TCA cycle intermediates do appear in a human brain spectrum. As an example, succinate, at an estimated concentration of 25 mmol/L, appears at a chemical shift of 2.42 ppm. The concentration has been estimated on the basis of the reference creatine (Cr) peak at 3.02 ppm, which is generally present at a 10-mmol/L concentration (an "amount" of succinate, for the 8-cm 3 result, equivalent to 200 mol). For future reference, for the proton spectrum, 4 minutes' accumulation detected 200 mol of succinate, approximately 50 mol/min. Spatial ContrastChemical shift imaging, so-called because multiple spectra are acquired during a single MR spec...

Magnetic resonance imaging with hyperpolarized agents: methods and applications

“…An excellent review of the H 2 isomers and their role in PHIP is given by Duckett and Wood [18]. Several molecules have been successfully polarized using this method, most notably [1- 13 C] succinate [19, 20]. Polarizations up to 50% have been achieved with PHIP [4, 19, 21, 22].…”

Tumor imaging using hyperpolarized 13C magnetic resonance spectroscopy

“…Contrast this with an anabolic substrate such as choline, which would be very interesting to study in cancer because there is often upregulation of choline metabolism in tumors. Although 15 N-labeled choline has a very long T 1 ($4 min) and has been successfully hyperpolarized [the polarization being detected either directly (24) or indirectly via J-coupled protons (25)], there is as yet no evidence that its cellular uptake and subsequent phosphorylation to phosphocholine is sufficiently rapid to allow detection within the lifetime of the polarization. Some of the promising DNP substrates for oncological imaging are described below and summarized in Table 1; several of these demonstrate significant metabolism in vivo and enable fundamental biological processes to be probed.…”

“…There have been a number of recent review articles and book chapters on this subject (12)(13)(14)(15)(16)(17), and therefore, the purpose of this brief review is to: highlight those DNP substrates that have shown the greatest promise for oncological applications in vivo; summarize the biochemical mechanisms responsible for label transfer from pyruvate to other metabolites in tumors; and finally provide an overview of the main challenges in label detection and imaging and how these may be addressed. those used in anabolism (to make cell structures) because in general, catabolism is faster than anabolism.…”

Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

“…38 Recent advances in hyperpolarisation, such as MRS using dynamic nuclear polarisation (DNP-MR), based on the differences in the fraction of nuclei in different energy states, is used for studying key tumour-related metabolic intermediates and direct tracking of drugs. 39,40 Hyperpolarised imaging is also used for analysing lipid metabolism, and preliminary preclinical studies in a prostate cancer model have shown the potential of hyperpolarised 13 C MRS in clinical practice. 39e41 PASADENA effect (parahydrogen and synthesis allow dramatically enhanced nuclear alignment) is the most widely used hyperpolarisation technique for MRI and NMR spectroscopybased metabolism imaging and has the advantages of being inexpensive, portable, and easy for routine biomedical/ clinical applications.…”

“…42 These techniques are based on the principle of polarisation of molecules containing 13 C and 15 N to detect metabolic activity in individual, enzymecatalysed reactions, and have implications for biological characterisation of tumour tissue. 39,40,42 Another recently developed MRI technique includes chemical-exchange saturation transfer (CEST), an endogenous contrast enhancement imaging technique, which enables indirect detection of metabolites with exchangeable protons. 43 One of the most studied CEST-based imaging is glucoCEST.…”