RSC Liversidge Award lecture: New Directions in Chemistry and Physics Improve Modern Molecular Imaging

Molecular imaging-the use of chemical signatures to image function instead of merely structure-promises to enable a new generation of clinical modalities that can revolutionize both diagnosis and treatment. I will focus on two specific modalities-magnetic resonance and optical imaging-and discuss how a close coupling between basic physics on the one hand, and focused clinical questions on the other hand, enable new and important applications. In magnetic resonance, new “hyperpolarization” technologies have improved clinical MRI; but the existing technology is expensive and complex, and short spin relaxation times (< 1 min) greatly limit the generality. We have used fundamental spin physics (well understood in the 1950s, but ignored since then) to generate long-lived hyperpolarized spin agents (minutes to hours); and we have developed a new organometallic catalytic approach to make in-magnet hyperpolarization practical. In optics, our lab developed femtosecond pulse shaping two decades ago; today we know that the "killer application" is to access intrinsic nonlinear signatures that were not previously observable in tissue, such as excited state absorption, ground state depletion, and cross phase modulation. Applications to imaging hemoglobins and melanins in tissue to detect and assess cancer will be highlighted. Finally, I will also present closely related work on nonlinear imaging of historical pigments to infer the artist’s original colors and intent.