299th LG : Dr. Mohammed Qutaish's presentation

Friday, January 13, 2017 - 12:00
Dr. Mohammed Qutaish's presentation
The goal of this work is to create a platform methodology consisting of cryo-imaging experimental methods and specialized image analysis software to provide unique 3D, quantitative characterization of tumor models, including spread via dispersal and metastasis, and assessment of imaging agent targeting to dispersed tumor cell and metastatic tumor. Analyses used microscopic, 3D cryo-imaging which has the sensitivity to detect fluorescently labeled single cells over large volumes of tissues. Specifically, tumor cell dispersal in Glioblastoma multioforme (GBM) and micrometastases in breast cancer mouse models were detected, quantified, and visualized. Targeting of the fluorescently labeled SBK2 peptide to GBM dispersing cells, and CREKA peptide multiplexed Gd-MR probe to breast cancer metastases, were analyzed. For GBM tumor cell dispersal analyses in cryo-images, algorithms were developed to detect blood vessels, dispersing tumor cells, white matter tract and main tumor mass, as well as measure cell dispersal distance. Multiple GBM cell lines were characterized to find those that showed high dispersive patterns similar to the human disease. Software was created to assess how far from the main tumor mass, SBK2 efficiently labeled dispersing cells. Results showed that LN-229 and CNS-1 cell lines are highly dispersive, and cells mainly dispersed along blood vessels and white matter tract. Dispersal distance was as far as 562μm in LN-229 and >3mm in CNS-1. Fluorescently labeled SBK2 peptide labeled more than 99% of dispersing cells, and as far as 3.5 mm. For breast cancer metastasis analyses, software was created to quantify number and size of metastases using cryo-imaging volumes. Multimodality 3D deformable image registration was employed to register MRI and cryo-imaging volume. This enabled the validation of CREKA peptide targeting in MRI using the high resolution cryo volumes, and provided information about limitation and efficiency of the developed MRI agent. The 4T1 cell line was used to create a metastatic breast cancer model. Results showed an average of 156 metastases in cryo-volumes ranging in size of 0.1–8mm in diameter. Metastases were mainly found in lungs, liver, bones and adrenal gland. Rose criterion showed >73% of micrometastases in lungs were labeled by the MRI CREKA. Results were shown visually and quantitatively.