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Yves De Deene Homepage: Hyperpolarized MRI

Hyperpolarized MRI

Introduction

Nuclear magnetic resonance imaging (MRI) is one of the most versatile and helpful medical imaging modalities that is routinely used in clinical diagnostics and physiological research. However, because it relies on the nuclear magnetization of protons in body water, which can only be achieved at very low levels using magnetic fields at physiological temperatures, it has inherently low detection sensitivity. This may seem surprising, given the high soft-tissue contrast and high image quality of conventional clinical MR images but this is because body tissue contains a large abundance of hydrogen protons. However, the thermal nuclear magnetic polarization of hydrogen protons is insufficient to use MRI in low density tissue (such as the lungs), for in vivo MR spectroscopy of metabolites that occur in concentrations of less than 10 millimolar (10 mM) or for molecular imaging.

SensitivityResolution

Figure 1 - Major medical imaging modalities arranged by their sensitivity and spatial resolution. The sensitivity of MRI can be drastically improved by use of hyperpolarization.

 

Hyperpolarization principle

Thermal nuclear magnetic polarization is a quantum stochastic phenomenon that can be described by the Boltzmann statistics for fermions. At a magnetic field strength of 3 Tesla, the population difference in the energy eigenstates is only 1 at 100,000. It is this difference that is responsible for the resulting nuclear net magnetization. However, using hyperpolarization it is possible to occupy the lowest energy eigenstate almost completely, hence an increase in sensitivity with 4 to 5 orders of magnitude.

HyperpolPrinciple

Figure 2 - Principle of hyperpolarization. In conventional MRI, only 1/100,000 of the nuclear magnetic spin dipoles contributes to the signal as described by Boltzmann statistics. By use of hyperpolarization, this fraction can be increased with a factor of 104 - 105.

 

Hyperpolarization techniques

Several methods can be used to achieve hyperpolarization: (1) With the so-called 'Brute Force method', the sample is cooled to down to almost absolute zero. It is apparent from the Boltzmann equation (see figure 2), that the lower energy eigenstate becomes more and more populated by cooling down. When the substance of interest is subsequently heated up rapidly, the population difference can be sustained for a reasonable long time as long as the T1 relaxation time is relatively long. (2) Similar polarization levels can be achieved at higher temperatures by use of Dynamic Nuclear Polarization (DNP). In DNP, the substance is mixed with trityl radicals and ESR excitation of the trityl radical electrons is achieved by use of microwaves. The (higher) electron magnetization of the electrons is than exchanged with the nuclear spins yielding high polarization levels. (3) Parahydrogen Induced Polarization (PHIP): Dihydrogen gas (H2) occurs in two isomeric forms: parahydrogen, with its two proton spins aligned antiparallel and orthohydrogen, with its two proton spins aligned parallel. At room temperature, the fractions are respectively 1:3 for parahydrogen:orthohydrogen, which corresponds with the degeneracy of the spin states. This fraction is significantly altered at lower temperatures. At 77 K, the fraction becomes 1:1 and at 30 K, 95% of the hydrogen gas is in the para-state. If the hydrogen gas reacts with another molecule (hydrogenation), the spin order is preserved and can be transferred onto another nucleus on the molecule by field-cycling. (4) Gas atoms can be hyperpolarized using a technique of Spin Exchange Optical Pumping (SEOP). In SEOP, a mixture of Rubidium vapour and a noble gas with odd numbers of nucleons (protons or neutrons) is brought in a glass cell. The glass cell is mounted in a magnetic field to cause Zeeman splitting of the energy eigenstate levels of the Rubidium electrons and of the nuclei of the gas atoms. One of the Rubidium electron eigenstates is populated through optical pumping with a strong circularly polarized laser beam. As the Rubidium atoms collide with the gas molecules, they will transfer magnetic moment onto the noble gas nuclei, yielding high levels of nuclear magnetization.

 

Hyperpolarized gas MRI

Our research group is constructing a hyperpolarized gas generator for 129Xe MRI.

Hyperpolarizer

Figure 3 - Benchtop hyperpolarized gas generator for 129Xe MRI. A 30 Watt laser beam is linear polarized using a beam splitter and converted into circular polarized light by use of lambda/4-waveplates. The glass cell is heated to approximately 130 oC and a magnetic field of 5 mT is produced. Solenoid coils are able to excite the spin system and capture the NMR signal.