1H and 15N hyperpolarization using SABRE : : experimental approaches and hardware designs for continuous and batch hyperpolarization

Abstract: A) Hyperpolarization
This work is all about hyperpolarization (HP), which can be described as the magnetization of spins exceeding their thermal equilibrium magnetization levels. The range of
methods for reaching this goal is wide, this work is focused on chemically
induced hyperpolarization using parahydrogen. The HP of nuclear spins promises to
overcome MRI’s greatest impediment, its low polarization and thus low sensitivity. In
fact, 13C HP has been used successfully in metabolic MRI where it delivered significant
insights into cancer metabolism in vivo. Mostly, hyperpolarized small molecules in
solution are produced externally in a polarizer, followed by transfer, administration
and imaging in a conventional MR system at magnetic field strengths of 1.5 T or more.
From the moment of its production, HP decays with a characteristic time constant T1 that
depends on the magnetic field but rarely exceeds one minute. However, if the sample
is exposed to a magnetic field below a critical value, then rapid relaxation will occur
and the polarization is lost. Furthermore, during imaging, the transverse magnetization
decays according to T2 which is estimated to be of the order of 100 s to 0.1 s. Thus,
over time, polarization is lost to the in vivo measurement by readout, dilution, excretion
and relaxation. Despite these challenges, impressive results have been obtained with
respect to medical diagnostics in both mice and man through the injection of a single
bolus of hyperpolarized agent. Whilst pyruvate is receiving great attention, no other
agents have yet been injected into man as the regulatory approval process is difficult to
cross. Progress to bypass relaxation is however prospering with research into long-lived
magnetization of single nuclei like Lithium-64 or Silicon-295 and long-lived
quantum states of multi-atomic systems being particularly noteworthy. Recently,
a method to continuously hyperpolarize nuclear spins by means of parahydrogen (pH2)
and reversible exchange, Sabre, has emerged. It offers the potential of repolarizing spins continuously in the presence of pH2. Its biological applicability, though, is
limited because of the use of toxic methanol as the solvent as well as target molecules
with limited biocompatibility. In this work it is shown that more biologically relevant
agents can be hyperpolarized continuously in aqueous solution. However, as we
moved through experiments, it became clear that re-hyperpolarization in vivo would be
difficult if not impossible to achieve. Therefore, the next step was to instead generate
high batch magnetization (i.e. polarization above 1 % at concentrations in the high mmol/dm^3 range) instead of a lower, but renewable magnetization. This goal was aimed towards
the same parahydrogen based SABRE method, and, as an additional step, the focus
was shifted from 1H HP to X-nuclei, particularly 15N. The advantage here is that
relaxation times can be longer and there is no background signal from the usually widely
available water in biomedical application. This aim lead to the creation of new hardware
designs to optimize polarization parameters and thus increase magnetization to the
highest achievable levels.
B) Hardware
The hardware used in HP experiments is often costly and complex to use. Dynamic
nuclear polarization methods, for example, need high fields, low temperatures and
careful handling of the substrate after polarization to generate high polarizations.
Additionally, polarization times are long (with a few exceptions) often making long lead
times necessary. The hardware in this work was designed to be easily and cheaply
manufactured with ease of use and reproducibility in mind. Many aspects of hardware
design are covered: 3D-CAD design of the components, fluid path and flow design for
both gases and liquids, design of electronics for control of the setup and readout of
sensor data as well as construction of components of the NMR and MRI setup such as
coils for static magnetic field generation, radiofrequency-pulses and signal reception.
Manufacturing methods mostly used after manual constructions were milling, lathing
and 3D-printing. Using the equipment built in this work, high SABRE polarized samples
were produced and measured in commercially available small animal MRI. If biologically
relevant tracers are found, the setup can be used for generation of highly polarized
batches of sample that in-vivo will portray metabolic processes

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Universität Freiburg, Dissertation, 2020

Classification and Topics

• Keyword: Hyperpolarisierung ; NMR-Spektroskopie ; Kernspintomografie ; Spulensystem ; Fluidik ; Sensortechnik

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2020
• Creator: Rovedo, Philipp
• Contributor: Hennig, Jürgen ; Albert-Ludwigs-Universität Freiburg. Fakultät für Mathematik und Physik

Further information

• DOI: 10.6094/UNIFR/166207
• URN: urn:nbn:de:bsz:25-freidok-1662076
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 11:04 AM CEST