Hyperpolarisation

Our research in to hyperpolarisation methodology is focused on two main topics: hyperpolarisation physics and pulse sequence development.

On

Overview

Our research in to hyperpolarisation methodology is focused on two main topics:

Hyperpolarisation physics:
- Polarised noble gases: design and construction of spin-exchange optical pumping polarisers, using optimised physics and engineering parameters to provide maximum polarisation of hyperpolarised noble gases for clinical lung MRI.
- Dynamic Nuclear Polarisation: hyperpolarisation of isotopically labelled molecules for the tracking of in vivo metabolism. Images or spectra are rapidly acquired to observe the conversion of a tracer molecule to its metabolic products. Applications include preclinical oncology and cellular metabolism.
Pulse sequence development:
- Design and optimisation of MR pulse sequences for rapid, high sensitivity functional lung and metabolic imaging.

Hyperpolarisation of noble gases: spin-exchange optical pumping

The working principle behind the hyperpolarisation of noble gases is simple: a hyperpolariser transforms select inert gases, e.g. ³He and ¹²⁹Xe, into a hyperpolarised state with circularly polarised laser light. This process, known as spin-exchange optical pumping (SEOP), leaves the gases chemically the same, while physically their nuclei are left magnetically aligned (hyperpolarised). This hyperpolarisation process makes it possible to produce high-resolution magnetic resonance (MR) images of ³He and ¹²⁹Xe (see figure below), which would be impossible under normal circumstances owing to the density of these gases being ~4 orders of magnitude lower than the density of tissues normally visualised on a conventional ¹H MRI scan.

Diagram of the physics of Spin Exchange Optical Pumping — Cartoon of the 129Xe-Rb spin-exchange optical pumping process. Left circularly polarised light (+hbar) polarises the Rb valence electrons and the energy is transferred via the Fermi contact interaction to polarise 129Xe nuclei.

While the basic principle of SEOP is simple, the underlying physical mechanisms governing the hyperpolarisation process are strongly coupled. This makes the optimisation of hyperpolarised gas generation a challenging, multi-parameter problem. Much of our research in the hyperpolarisation lab is dedicated to better understanding of the physics of SEOP for clinical-scale production (2–4 litres of xenon gas per hour) of polarised ¹²⁹Xe, as well as developing experiments and theoretical models to resolve the widely-reported discrepancy between theoretical and experimental polariser performance.

Hyperpolarised 129Xe images in healthy and COPD lungs, and the brain and kidneys — Left: 3D MRI of hyperpolarised 129Xe in healthy human lungs; middle: images acquired from the lungs of a patient with COPD; right: 2D MR images of 129Xe dissolved in the brain and kidneys.

Dynamic Nuclear Polarisation

Dynamic Nuclear Polarisation (DNP) is method for detecting and imaging cellular metabolism. DNP is versatile in that it can be applied to a range of atoms, particularly spin ½ nuclei, e.g. ¹³C and ¹⁵N. Similar to SEOP in noble gas hyperpolarisation, DNP uses the spin polarisation of electrons at ultra-low temperature, 1—2 K. Through microwave irradiation, the electron polarisation is transferred to a target molecule. This boosts the MR signal of the target molecule by 3—4 orders of magnitude. The sample is then rapidly returned to room temperature, where its signal can be monitored over time.

Hyperpolarisation of 13C — Preparation of hyperpolarised material. Target molecule is mixed with a source of electrons and cooled in liquid 4He. Microwave irradiation in a magnetic field allows the molecule's signal to build up. The sample is returned to room temperature for use.

Its main application is in understanding metabolism of different organs, tissue or cells. The hyperpolarised molecule is administered to these, where it is metabolised to form daughter metabolic products that exhibit distinct NMR resonances, and can therefore be detected separately.

Kinetics of 13C pyruvate to lactate conversion — Rapid sequential acquisition of MR spectra shows the time evolution of peaks representing hyperpolarised pyruvate and its metabolic products, lactate & bicarbonate (left). The size of the peaks can be fitted to model metabolic conversion rates (right).

One of the mainstay applications of the technique is hyperpolarised pyruvate. This molecule is important in detecting the relative importance of glycolytic metabolism (lactate) and oxidative phosphorylation (bicarbonate). High levels of lactate are a marker of cancer, and when combined with imaging DNP can detect tumour cells and their response to response to treatment. The technique has been applied to other target organs, including the heart, kidney and brain.

DNP is a complimentary technique that works in conjunction with an MRI scanner. The HyperSense instrument is state of the art; with fully automated sample handling to maximise both the available signal and the range of metabolically active molecules that can be observed.

MRI Pulse Sequence Development

The magnetisation of hyperpolarised nuclei decays over time, and through excitation by radiofrequency pulses, and is non-renewable; this behaviour is in stark contrast to conventional ¹H MRI. In addition, as respiratory motion can severely corrupt MR images, it is beneficial to acquire hyperpolarised gas MRI during a short breath-hold after inhalation.

The design and optimisation of rapid MR pulse sequences for lung imaging with hyperpolarised gases is thus crucial to obtain high quality images and maximise the functional information attainable within a single breath-hold, and the lifetime of the polarisation.

Our group have established expertise in:

Acceleration techniques, including random undersampling of k-space and compressed sensing reconstruction, and parallel imaging
Non Cartesian sampling of k-space (e.g. with radial or spiral trajectories)
Balanced steady state free precession sequences
Methods for simultaneous imaging of multiple nuclei during a single breath-hold (¹H, ³He, ¹²⁹Xe)
Pulse programming for GE Healthcare (EPIC), Philips (PPE) and Bruker MR systems