  The inherently low signal-to-noise ratio of NMR and MRI is now being
addressed by hyperpolarization methods. For example, iridium-based catalysts
that reversibly bind both parahydrogen and ligands in solution can
hyperpolarize protons (SABRE) or heteronuclei (X-SABRE) on a wide variety of
ligands, using a complex interplay of spin dynamics and chemical exchange
processes, with common signal enhancements between $10^3-10^4$. This does not
approach obvious theoretical limits, and further enhancement would be valuable
in many applications (such as imaging mM concentration species in vivo). Most
SABRE/X-SABRE implementations require far lower fields (${\mu}T-mT$) than
standard magnetic resonance (>1T), and this gives an additional degree of
freedom: the ability to fully modulate fields in three dimensions. However,
this has been underexplored because the standard simplifying theoretical
assumptions in magnetic resonance need to be revisited. Here we take a
different approach, an evolutionary strategy algorithm for numerical
optimization, Multi-Axis Computer-aided HEteronuclear Transfer Enhancement for
SABRE (MACHETE-SABRE). We find nonintuitive but highly efficient multi-axial
pulse sequences which experimentally can produce a 10-fold improvement in
polarization over continuous excitation. This approach optimizes polarization
differently than traditional methods, thus gaining extra efficiency.
