Who: Prof. Peter Caravan, Institute for Innovation in Imaging (i3), Massachusetts General Hospital and Harvard Medical School, USA
When: October 14, 2020 at 11:30 am
Where: Zoom. Request the link by email.
Magnetic Resonance Imaging (MRI) is a mainstay of diagnostic radiology. Exquisite 3D anatomical images and functional measures of perfusion, tissue permeability, and heart motion are routinely used in the clinic for disease diagnosis, treatment planning, or follow up. Additional information can be obtained by administering a paramagnetic or superparamagnetic compound to alter the local tissue relaxation properties and create image contrast. Specific molecular readouts can be obtained by targeting the paramagnetic probe molecule to a specific pathology. Another approach is to exploit the presence of enzymes like myeloperoxidase (MPO), over expressed in inflammation, to chemically transform the molecular probe and in turn alter the MRI signal. In this lecture I will describe our efforts in the design, characterization, and application of molecular MR probes. I will start with the development of a Mn(II)-based general purpose contrast agent, and then describe our efforts in imaging inflammation and in particular MPO activity. One approach relies on oxidation of high spin Fe(II), which is a poor MR relaxation agent, to high spin Fe(III) which is a potent relaxation agent. The other is to oxidize the ligand in a Gd(III) complex to create products which have slower rotational dynamics and more efficient relaxation properties. Finally, I will describe our efforts in targeting allysine, an aldehyde-containing amino acid formed during tissue fibrogenesis and applications in imaging fibroproliferative diseases like idiopathic pulmonary fibrosis (IPF), chronic liver disease, and chronic kidney disease.
Peter Caravan is the Director of the Institute for Innovation in Imaging (i3) at Massachusetts General Hospital and Professor of Radiology at Harvard Medical School. He leads a multidisciplinary and translational molecular imaging lab focused on the invention of novel molecular probes and their broad applications in cardiovascular, pulmonary, renal, and hepatic diseases as well as in cancers. His research spans novel chemistry technologies to advanced MRI and PET imaging in animal models through to applications in patient populations. Originally from Bay Roberts, Newfoundland, Dr. Caravan received his BSc (Hons) from Acadia University followed by a PhD in Inorganic Chemistry from the University of British Columbia under the mentorship of Prof. Chris Orvig. Following a NSERC post-doctoral fellowship with Prof. André Merbach at the Université de Lausanne, he worked in industry developing targeted MR probes. He joined the faculty of Harvard Medical School in 2007 and has been a continuously funded NIH researcher ever since.