Τετάρτη 25 Ιανουαρίου 2012

Real Time Molecular imaging using hyperpolarized 13C and 3He

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.g. 13C and 15N, and their molecular distribution in vivo can be visualized in a clinically relevant time window. This article reviews different hyperpolarization techniques and some of the many application areas.








As an example, experiments are presented where hyperpolarized 13C nuclei have been injected into rabbits, followed by rapid 13C MRI with high spatial resolution (scan time <1 s and 1.0 mm in-plane resolution). The high degree of polarization thus enabled mapping of the molecular distribution within various organs, a few seconds after injection. The hyperpolarized 13C MRI technique allows a selective identification of the molecules that give rise to the MR signal, offering direct molecular imaging.
Two noble gases, the stable spin ½ isotopes 3He and 129Xe, can be polarized by optical pumping. Nuclear polarizations up to 80% are achieved with the existing techniques and laser sources. This corresponds to a huge polarization enhancement or «hyperpolarization », 105 above the thermal polarizations obtained in standard magnetic resonance imaging (MRI) magnets.  These hyperpolarized gases (HPG) can be used as sources of nuclear magnetic resonance (NMR) signals with excellent signal/noise ratios (SNR) and interesting specific properties. A great variety of applications can be found in a broad range of disciplines : material sciences (surfaces, porous media), chemistry, biology, medicine... Among the potential clinical applications,  the opportunity to image the air spaces of human lungs has immediately risen a considerable interest. Current conventional (proton-based) MRI cannot image these hollow spaces. Even the surrounding lung tissues cannot be satisfactorily imaged. HPG appear as promising tools for non-invasive investigation of human lung ventilation, giving access to static imaging during breathhold, dynamics of inspiration/expiration and functional imaging. The impact on the understanding of lung physiology and function, in healthy or diseased state is being evaluated and assessed.
   Current research program are focused on the production and use HP 3He gas for NMR and MRI purposes, especially for lung ventilation studies in humans.



Hyperpolarized MRI differs from conventional MRI, in the sense that any magnetization used up by the imaging process cannot be recovered. The obvious drawback is that the imaging protocol gets restricted , and the time window for imaging is limited. Typically, several images with high temporal resolution are needed to study the distribution of a contrast agent. In this study, only one image was acquired for each injection. A technique to preserve the magnetization between subsequent images has been presented , but was not available on the scanner used in this study.
The introduction of an injectable, hyperpolarized 13C substance opens a new field of MRI. With the coil and the receiver system of the scanner tuned to the resonance frequency of the hyperpolarized nucleus, only signals from the injected substance will be detected. The signal strength is a linear function of the concentration and the polarization level of the nucleus in question. This is not the case for a conventional contrast agent (e.g. Gd-chelates and other paramagnetic molecules/particles) that operates by altering the relaxation times of water protons in surrounding tissues. When irradiated with a radiofrequency wave, the injected 13C nuclei emits a radiofrequency signal, contrary to the tracer substance used in PET or SPECT imaging, which emits γ-rays. More information can be obtained from an NMR-active nucleus, since its resonance frequency is a function of its chemical and physiological environment (e.g. chemical shielding, viscosity and mobility). Thereby, it is possible to separate the signals from 13C nuclei within different molecules. This feature is exploited in the field of analytical NMR spectroscopy and in vivo MR spectroscopy. While PET and SPECT are only capable of mapping the distribution of the nuclei, regardless if they are still contained within the injected molecules or not, NMR is capable of distinguishing signals from the tracer nuclei (e.g. 13C) present in different molecules. This specificity on a molecular level is the basis for the clinical use of MR spectroscopy. Due to SNR limitations, this has been restricted to protons, 19F and 31P, and to the use of large image voxels (∼1 cm3). The hyperpolarization procedure used in the present work overcomes these restrictions, but still retains the specificity of the NMR technique, and thus makes it possible to perform direct molecular imaging. Consequently, distribution patterns may be mapped by injection and imaging of several hyperpolarized 13C molecules simultaneously, delivering valuable information about membrane structure and permeability.

1 ) http://medgadget.com/archives/2006/10/hyperpolarized.html
2) http://xenon.unh.edu/
3) http://ultra.bu.edu/projects.asp?project=mri
4) http://adsabs.harvard.edu/abs/2001PhDT........10V
5) https://www.spl.harvard.edu/pages/projects/HypX/currentresult0.html
6) http://ipn2.epfl.ch/LPMN/sdnpi/research_aboutDNP.html
7) http://www.europhysicsnews.com/full/25/article9/article9.html
8) http://www.ep1.ruhr-uni-bochum.de/~dagmar/ardenkjaer.pdf

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