Intravital mesoscopic fluorescence molecular tomography allows non-invasive in vivo monitoring and quantification of breast cancer growth dynamics

摘要

a Extraction of tumor cells from the donor animal and the implantation into the receiving animal. b Schematic of longitudinal imaging of a single animal. Different time points refer to different stages of tumor development: tumor growth (Doxycycline administration: DoXON) and tumor regression (DoXOFF). c Principle of IFT method: (i) focused laser beam excites fluorescence inside the sample volume by raster scanning while a detector array simultaneously images the scanned area. For each scan location, multiple-scattered emission light is collected by the detector array (sCMOS camera). (ii) After a full scan of the sample, each detector yields an image, with all detector images together constituting the raw data (measurement). (iii) A GPU-accelerated Monte-Carlo algorithm simulates the optical propagation of scattered light inside the sample volume. (iv) The raw data and model matrix are fed into a reconstruction algorithm, to extract the 3D distribution of the fluorescence emission. d A CAD representation of the IFT imaging setup. An excitation laser (e) enters the system through a standard filter cube (FC). The laser is raster scanned by a 2D galvanometric mirror (GM) and imaged onto the sample by a scanning lens (SL). The emitted fluorescence light is de-scanned, separated from the excitation light by the FC, and imaged onto the camera (C) by an imaging lens (IL). For in vivo experiments we use an anesthesia system (AS) for narcosis and monitoring of physiological parameters while the region of interest is stabilized with a custom, non-invasive imaging window (NIVOW – zoom-in). e Mouse skin position as a function of time as measured by OCT, showing tissue motion along z and x axes without (left) and with (right) NIVOW.