Characterizing sources and targets of illumination in living tissue is challenging. MIT researchers show that spatial distributions of light in tissue can be mapped by using magnetic resonance imaging (MRI) in the presence of photosensitive nanoparticle probes. Each probe consists of a reservoir of paramagnetic molecules enclosed by a liposomal membrane incorporating photosensitive lipids. Incident light causes the photoisomerization of the lipids and alters hydrodynamic exchange across the membrane, thereby affecting longitudinal relaxation-weighted contrast in MRI. The researchers injected the nanoparticles into the brains of live rats and used MRI to map responses to illumination profiles characteristic of widely used applications of photostimulation, photometry and phototherapy. The responses deviated from simple photon propagation models and revealed signatures of light scattering and nonlinear responsiveness. Paramagnetic liposomal nanoparticles may enable MRI to map a broad range of optical phenomena in deep tissue and other opaque environments.
Principle of liposomal nanoparticle reporters
a, LisNRs are formulated by enclosing a high concentration of an MRI contrast agent such as gadoteridol (shown) in a liposomal membrane with regulable water permeability (orange). b, In their more permeable form, LisNRs support greater water exchange, leading to a higher effective relaxivity (r1eff) and greater T1w MRI signal. c, Two-compartment modelling enables estimation of r1eff as a function of permeability and liposomal diameter. All r1eff curves range from zero at low permeability to the r1 value of unencapsulated gadoteridol (r1in) at high permeability (dashed line). d, Liposomal membranes including unsaturated lipids such as POPC (bottom) display higher water permeability than membranes composed of fully saturated lipids such as DPPC (top). e, Experiments indicate the dynamic range of MRI signal differences for LisNR analogues formulated at 2.2 mM Gd3+ with increasing POPC concentrations (top), with corresponding underlying T1 relaxation rates (R1) graphed at the bottom. All lipid compositions also contain 5% DSPE-PEG. Error bars denote s.d. of 4 technical replicates.