title: Molecular imaging with engineered physiology.
abstract: In vivo imaging techniques are powerful tools for evaluating biological systems. Relating image signals to precise molecular phenomena can be challenging, however, due to limitations of the existing optical, magnetic and radioactive imaging probe mechanisms. Here we demonstrate a concept for molecular imaging which bypasses the need for conventional imaging agents by perturbing the endogenous multimodal contrast provided by the vasculature. Variants of the calcitonin gene-related peptide artificially activate vasodilation pathways in rat brain and induce contrast changes that are readily measured by optical and magnetic resonance imaging. CGRP-based agents induce effects at nanomolar concentrations in deep tissue and can be engineered into switchable analyte-dependent forms and genetically encoded reporters suitable for molecular imaging or cell tracking. Such artificially engineered physiological changes, therefore, provide a highly versatile means for sensitive analysis of molecular events in living organisms.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 16-561, Cambridge, Massachusetts 02139, USA.
authors.forename: Mitul
authors.initials: M
authors.lastname: Desai
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 16-561, Cambridge, Massachusetts 02139, USA.
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Slusarczyk
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 16-561, Cambridge, Massachusetts 02139, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Chapin
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 16-561, Cambridge, Massachusetts 02139, USA.
authors.forename: Mariya
authors.initials: M
authors.lastname: Barch
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 16-561, Cambridge, Massachusetts 02139, USA.|Department of Brain &Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 16-561, Cambridge, Massachusetts 02139, USA.|Department of Nuclear Science &Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 16-561, Cambridge, Massachusetts 02139, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Jasanoff
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D059906:Neuroimaging / Q000379:methods*; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015740:Calcitonin Gene-Related Peptide; D010100:Oxygen