Fehler bei Datenbankabfrage (Menueeintraege ausgeben)

SELECT * FROM `ifn_menue` WHERE top = '' AND visible = '1' ORDER BY `pos` ASC\n

Fehler bei Datenbankabfrage (Menueeintraege ausgeben)

SELECT * FROM `ifn_menue` WHERE top = '' AND visible = '1' ORDER BY `pos` ASC\n

Fehler bei Datenbankabfrage (Menueeintraege ausgeben)

SELECT * FROM `ifn_menue` WHERE top = '' AND visible = '1' ORDER BY `pos` ASC\n
Methodological developments - Development of a new class of contrast agents using Para-Hydrogen Induced Polarization (PHIP) - Leibniz Institute for Neurobiology, Magdeburg
© 2000 - 2011 LIN - Leibniz Institut für Neurobiologie Magdeburg

LIN: Forschungsabteilungen > Akkustik, Lernen, Sprache > Unterpunkt Ebene 3 > Unterpunkt Ebene 4

Titel: LIN Layout

Home switch to german Print Search:
Facebook YouTube
Staff Links Sitemap

 Methodological developments

 Development of a new class of contrast agents using Para-Hydrogen Induced Polarization (PHIP)

Ute Bommerich, Jörg Stadler, Frank Angenstein

Although MRI is an indispensable and widely applied method in medical diagnosis and research this technique still suffers from a relative low sensitivity. This restriction is caused by the direct correlation of signal intensities to population differences of the involved spin states. This polarization of nuclear spins in a magnetic field at thermal equilibrium is determined by Boltzmann distribution which is affected by the magnetic field strength, temperature, and the gyromagnetic ratio of the observed nucleus. Even in high magnetic fields the polarization of proton spin levels, for example, is only about 10-5. A promising concept for sensitivity enhancement in NMR and MRI is to circumvent the described Boltzmann distribution by using hyperpolarization methods. These methods generate polarizations that overcome the just described population differences by selective population of special spin states.

One of these methods, called PHIP (ParaHydrogen Induced Polarization), has already been successfully applied in NMR spectroscopy since 1987. This technique increases the nuclear polarization by transfer of a special spin isomer of hydrogen on certain substrates by means of a chemical reaction. This spin isomer, namely parahydrogen, in which the magnetic moments of both nuclei in the molecule cancel because of their antiparallel orientation, can be transferred on unsaturated substrates via a homogeneous hydrogenation reaction using an appropriate catalyst.

The population of the resulting spin levels in the product molecule follows strict symmetry criteria. As a result only spin states with appropriate symmetry are occupied leading to an effective overpopulation of those levels as it is illustrated in the scheme below.

Because only the ab and ba states of the product system correlate with the nuclear spin function of parahydrogen, these states are overpopulated and give rise to strong characteristic antiphase signals.
Due to the significant deviation from Boltzmann statistics a signal enhancement of up to four orders of magnitude can be achieved.
This non-equilibrium spin order can also be converted to nuclear polarization of other nuclei in the same substrate like for example 13C or 19F. While this hyperpolarization can lead to strong signal enhancements for different nuclei, the generated substrates can be used as a new class of customized contrast agents to increase the sensitivity in MRI.
These hyperpolarized agents can be directly monitored because their functional principle is based on a signal enhancement of the agent itself and not on the directed influence on the signals related to the surrounding proton nuclei, as in the case of conventional contrast agents which operate by the paramagnetic properties of metals and their complexes.
One important focus of our investigations is the generation of physiologically compatible substrates showing 1H and 13C-hyperpolarization. For Protons the low sensitivity is partly compensated by a high spin density in biological tissues. Especially for MRI investigations on other nuclei, which can be found in drastically lower concentrations, this confinement becomes an interesting factor. Since the low natural abundance of 13C is far below the detection limit of typical imaging protocols, hyperpolarized 13C images are characterized by complete lack of background signal.
Not all structures qualify for this labelling procedure, so we concentrate our investigations on hyperpolarized drugs like inhalation narcotics, anti-epileptic drugs and brain metabolites. As a model compound for the interesting group of inhalation narcotics for example we use hyperpolarized diethyl ether which can be generated via hydrogenation of ethyl vinyl ether.

The above shown pictures illustrate the hyperpolarization effect of the just labelled substance (left picture) in comparison to the non-polarized form of the same substrate (right picture). The MR images of phantoms containing hyperpolarized diethyl ether were measured on a Bruker 4.7T BioSpec (200 MHz) small animal MR scanner using an optimized 2D gradient echo (FLASH) sequence.
Another very important aspect is the relaxation time of the nucleus that is detected. The labelled substrate can be monitored just as long as hyperpolarization persists which decays due to relaxation processes so that the time frame for the detection is limited.
Our investigations showed that the relaxation times of signals derived from hyperpolarized substrates can be extended significantly compared to the non-polarized forms.

last update: 2010-02-24 report a bug print this page