High Resolution Multiplexed Fluorescence Tomography
Small animal Fluorescence Tomography has emerged as powerful biomedical research tool since it allows three-dimensional imaging of molecularly-targeted fluorescent probes and red-shifted fluorescent proteins in unperturbed environments in vivo. Despite significant advances in instrumentation and image reconstruction algorithms in recent years, Fluorescence tomographic imaging technology remains far from optimized. Two critical limitations are the relatively poor image Resolution (limited to 1 or 2 mm) due to the High degree of light scatter in biological tissues, and an inability to perform High-throughput imaging of many fluorescent targets simultaneously (i.e. “multiplexing”), largely due to the spectral overlap of common fluorophores, long data acquisition times and tissue autoFluorescence. In this project, we will develop a Highly novel Fluorescence tomographic scanner that will address these critical limitations using a number of unique design elements including; i) High- speed time-gated photon counting detection of the earliest-transmitted and therefore least scattered photons through animals, thereby allowing imaging Resolution approaching 250 5m without loss of sensitivity or accuracy, ii) fast acquisition of both hyperspectral and Fluorescence lifetime data in about 1 minute per axial slice, allowing robust de-mixing of at least five concurrent fluorophores and rejection of tissue autoFluorescence, iii) a High speed, pulsed supercontinuum light source for excitation of virtually any fluorophore in the red and near-infrared region. The system will image mice in sequential axial slices over 360 degrees in an instrument configuration analogous to X-ray Computed Tomography. We will demonstrate that the scanner is capable of High-Resolution Multiplexed imaging, first in complex fluorescent optical phantoms with simulated background autoFluorescence, and secondly in nude mice with multiply-labeled human glioma (Gli-36 and GBM8) tumor xenografts. We anticipate that the system will have applications in many areas of biomedical research including studying disease development and response to novel therapeutics non- invasively in live animals.
Northeastern University’s College of Engineering is home to numerous federally-funded research centers and an array of leading-edge projects and initiatives that advance discovery and new knowledge in health, sustainability, and security.