Hyperpolarized Experiments

Hyperpolarized ¹³Carbon

NMR is traditionally plagued by low signal to noise, and scientists typically pay millions of dollars for bigger magnets that increase signal by factors of two or less. But signal enhancements of 10,000X are possible, though only for short times, with cutting edge instrumentation that we have recently acquired. iMQC experiments will have unique advantages for these unusual experimental conditions.

While MRI can provide excellent soft tissue contrast, the inherently low signal upon which MRI is based limits its use to water protons. Hyperpolarization techniques have been developed which can increase the signal for short periods of time. These techniques allow for the imaging of nuclei which were previously very difficult to image.
The signal observed in magnetic resonance (MR) is based on the slight excess of spins in the lower energy state. This slight excess is given by the Boltzmann distribution: where E is the energy difference between the states, kB is the Boltzmann constant, and T is the temperature in Kelvin. The polarization (or net magnetization of a sample) is given by the net amount of spins in each energy state. The polarization of a sample increases with increasing magnetic field (as the energy gap between the two energy levels increases). Polarization can also be described for a spin ½ nucleus as: where γ is the gyromagnetic ration, h is Planck’s constant, and B₀ is the magnetic field. If you work through the numbers for a proton, this equation means that about one in a million nuclei are contributing to the observed MR signal.
In order to get increased signal, one can increase the magnetic field, or decrease the temperature. In order to achieve an increase in signal of 1000, one would need to cool the sample to 4.2K (liquid helium temperatures) and place it in a magnetic field of 20T. Fortunately, there are other ways to achieve large increases in signal, through the technique of hyperpolarization.
Hyperpolarization is a method that artificially and temporarily increases the polarization of a sample. There are 4 main techniques used to achieve a hyperpolarized state, but the most popular techniques used on ¹³C are DNP (dynamic nuclear polarization) and PHIP (Para-Hydrogen Induced Polarization).
The Hypersense system by Oxford instruments is the first commercially available DNP polarizer. DNP works by first cooling a sample doped with a small concentration of a paramagnetic trityl radical down to 1.4K and then bombarding it with microwaves which induce polarization in the sample. Once the desired level of polarization is achieved, the sample is rapidly dissolved and used.
Current work in the field of carbon imaging focuses on the unique properties that carbon offers. Since the natural abundance of the MR visible isotope of carbon (¹³C) is approximately 1% of all carbon, imaging natural abundance carbon is below the detection limits of most typical imaging systems. This low abundance of ¹³C also means that hyperpolarized images have almost no background signal, allowing for applications such as angiography, vascular imaging, catheter tracking, perfusion mapping, and metabolic imaging.

Angiography:

Several groups have explored the use of ¹³C hyperpolarized agents as a contrast medium for angiography. Below are two images of the cardiac and thoracic region acquired after the injection of a ¹³C hyperpolarized contrast agent taken by Jonas Svensson 1, Sven Månsson , Edvin Johansson , J. Stefan Petersson , Lars E. Olsson at Amersham Health R&D AB, GE Healthcare, Malmö, Sweden and Malmö University Hospital, Lund University, Malmö, Sweden. ¹³C imaging of pyruvate in the hind leg of a pig superimposed on an anatomical proton image done by Klaes Golman, René in ‘t Zandt, and Mikkel Thaning at Amersham Health R&D AB, GE Healthcare, Malmö, Sweden