A noble cause
% C! ^/ r! E( m6 J5 N7 aHyperpolarized xenon can be used as an MRI temperature sensor, according to researchers in Germany and the US. Their new approach to MRI thermometry uses encaged xenon atoms and enables unprecedented accuracy of 0.1 degrees Celsius at low and ultralow sensor concentrations. The technique might be used in clinical diagnostics and therapy monitoring.
% }% l8 O; e6 n- SFranz Schilling, now at the Technical University of Munich, TU München, is lead author on a ChemPhysChem paper that outlines the benefits of the approach, which include non-invasiveness and the ability to obtain an image from any scan orientation with good spatial and temporal resolution. Co-authors include Krishnan Palaniappan, Sina Zapf, David Wemmer, Alexander Pines of the Lawrence Berkeley National Laboratory, Materials Sciences Division, Berkeley, California, USA, and Leif Schr?der.
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Various magnetic resonance parameters are temperature-sensitive, among them proton resonance frequency (PRF), diffusion coefficient or transverse and longitudinal relaxation times. As such these have been exploited in MRI thermometry. Unfortunately, the accuracy of these conventional techniques is somewhat limited. In contrast, encapsulated hyperpolarized xenon appears to have great promise for in vivo applications because it allows the mapping of absolute temperatures to be carried out.
2 r6 {% k( U1 r+ RObviously, protons are the most frequently imaged nucleus in MRI, but any nucleus with a net nuclear spin can be imaged, including xenon-129, although they require hyperpolarization in order to yield a strong enough signal under normal conditions. Now, Schilling and his colleagues have used spin exchange optical pumping, which increases the equilibrium net spin polarization of xenon-129 by three to four orders of magnitude. This, they explain, allows them to detect xenon at low concentrations as it interacts with molecules in a temperature dependent manner..
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To achieve their goal the team first had to trap xenon atoms in a cryptophane-A cage. A peptide component is used to make the sensor agent sufficiently soluble in water. Cryptophanes were discovered in the early 1980s by André Collet and Jacqueline Gabard when they used template-directed synthesis to produce the first cryptophane with its two cup-shaped units held together via peripheral units to from a closed cage. Making variations in the peripheral units has since allowed chemists to produce various cryptophanes with different symmetries, to alter the hydrophobic character of the interior, and of course, the overall size of the cryptophane cage.
2 ]) B, j9 Y4 M' u/ FSchilling and colleagues used the archetypal cryptophane to encapsulate xenon-129 and demonstrated that the magnetic resonance signal shifts is a linear fashion by 0.29 ppm per degree Celsius. This is a shift almost 30 times higher than seen with PRF, the current MRI thermometry method of choice. The team suggests that this new direct mapping concept can give MRI operators and researchers an absolute temperature with a previously unmatched precision of +/- 0.1 Celsius with a sensor concentration of just 150 micromolar.
0 o8 i- q; e0 _8 kThe direct measurement of temperature is, despite the advance, not always possible so the team has also demonstrated an indirect temperature detection technique using chemical exchange saturation transfer of hyperpolarized xenon. This technique, Hyper-CEST, was introduced previously by collaborator Schr?der, who is now at the Leibniz Institute for Molecular Pharmacology in Berlin. This technique makes possible to detect xenon sensors at an agent concentration as low as 10 nanomolar and was now combined with temperature sensing. 1 e6 H6 g$ B3 [$ _
"Thermometry based on hyperpolarized xenon sensors improves the accuracy of currently available MRI thermometry methods," the researchers conclude, "potentially it could give rise to biomedical applications of biosensors functionalized for binding to specific target molecules."
7 h V7 v& a" ^"The main idea for the xenon (bio)sensors is to establish a new type of functionalized contrast agent that can bind to specific disease markers on a molecular level. We hope that it will one day have medical applications that could also include monitoring of thermotherapy in cancer treatment or the detection of so-called hot arteriosclerotic plaques," Schr?der told SpectroscopyNOW. |