The post-genomic promise of a plethora of new therapeutic drugs has remained largely unfulfilled because of two principal bottlenecks: insufficient high-throughput drug toxicity assays, and acceptable in vitro surrogates to in vivo testing. In this paper, we report coherence-domain functional imaging of bulk tissue response to drug toxicity using cellular motility as both a contrast agent for imaging and as a biomarker for metabolic activity. Osteogenic sarcoma tumor spheroids treated with sodium azide exhibit a rapid onset of increased cellular motility, followed by cellular exhaustion. This behavior correlates with the known biological progression of azide poisoning. These specific findings for azide poisoning are relevant in general because of the common action of many drug candidates on the same oxidative phosphorylation pathways affected by azide. Furthermore, azide poisoning is generally representative of hypoxia, including ischemic hypoxia, which is the most common cause of tissue damage in disease and trauma. The OCI motility mapping technique could therefore introduce a new and general approach to the study of toxicity and pathology in vitro.

Date Published: 20 February 2006
PDF: 8 pages
Proc. SPIE 6079, Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedicine X, 60790K (20 February 2006); doi: 10.1117/12.646582

Published in SPIE Proceedings Vol. 6079:
Coherence Domain Optical Methods and Optical Coherence Tomography in Biomedicine X
Valery V. Tuchin; Joseph A. Izatt; James G. Fujimoto, Editor(s)