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Proceedings Paper

Dynamic subnanosecond time-of-flight detection for ultra-precise diffusion monitoring and optimization of biomarker preservation
Author(s): Daniel R. Bauer; Benjamin Stevens; Jefferson Taft; David Chafin; Vinnie Petre; Abbey P. Theiss; Michael Otter
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Paper Abstract

Recently, it has been demonstrated that the preservation of cancer biomarkers, such as phosphorylated protein epitopes, in formalin-fixed paraffin-embedded tissue is highly dependent on the localized concentration of the crosslinking agent. This study details a real-time diffusion monitoring system based on the acoustic time-of-flight (TOF) between pairs of 4 MHz focused transducers. Diffusion affects TOF because of the distinct acoustic velocities of formalin and interstitial fluid. Tissue is placed between the transducers and vertically translated to obtain TOF values at multiple locations with a spatial resolution of approximately 1 mm. Imaging is repeated for several hours until osmotic equilibrium is reached. A post-processing technique, analogous to digital acoustic interferometry, enables detection of subnanosecond TOF differences. Reference subtraction is used to compensate for environmental effects. Diffusion measurements with TOF monitoring ex vivo human tonsil tissue are well-correlated with a single exponential curve (R2>0.98) with a magnitude of up to 50 ns, depending on the tissue size (2-6 mm). The average exponential decay constant of 2 and 6 mm diameter samples are 20 and 315 minutes, respectively, although times varied significantly throughout the tissue (σmax=174 min). This technique can precisely monitor diffusion progression and could be used to mitigate effects from tissue heterogeneity and intersample variability, enabling improved preservation of cancer biomarkers distinctly sensitive to degradation during preanalytical tissue processing.

Paper Details

Date Published: 20 March 2014
PDF: 10 pages
Proc. SPIE 9040, Medical Imaging 2014: Ultrasonic Imaging and Tomography, 90400B (20 March 2014); doi: 10.1117/12.2043972
Show Author Affiliations
Daniel R. Bauer, Ventana Medical Systems, Inc. (United States)
Benjamin Stevens, Ventana Medical Systems, Inc. (United States)
Jefferson Taft, Ventana Medical Systems, Inc. (United States)
David Chafin, Ventana Medical Systems, Inc. (United States)
Vinnie Petre, Ventana Medical Systems, Inc. (United States)
Abbey P. Theiss, Ventana Medical Systems, Inc. (United States)
Michael Otter, Ventana Medical Systems, Inc. (United States)

Published in SPIE Proceedings Vol. 9040:
Medical Imaging 2014: Ultrasonic Imaging and Tomography
Johan G. Bosch; Marvin M. Doyley, Editor(s)

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