Dynamic subnanosecond time-of-flight detection for ultra-precise diffusion monitoring and optimization of biomarker preservation

Daniel R. Bauer; Benjamin Stevens; Jefferson Taft; David Chafin; Vinnie Petre; Abbey P. Theiss; Michael Otter

doi:10.1117/12.2043972

20 March 2014 Dynamic subnanosecond time-of-flight detection for ultra-precise diffusion monitoring and optimization of biomarker preservation

Daniel R. Bauer, Benjamin Stevens, Jefferson Taft, David Chafin, Vinnie Petre, Abbey P. Theiss, Michael Otter

Author Affiliations +

Proceedings Volume 9040, Medical Imaging 2014: Ultrasonic Imaging and Tomography; 90400B (2014) https://doi.org/10.1117/12.2043972
Event: SPIE Medical Imaging, 2014, San Diego, California, United States

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 (σ_max=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.

Citation Download Citation

Daniel R. Bauer, Benjamin Stevens, Jefferson Taft, David Chafin, Vinnie Petre, Abbey P. Theiss, and Michael Otter "Dynamic subnanosecond time-of-flight detection for ultra-precise diffusion monitoring and optimization of biomarker preservation", Proc. SPIE 9040, Medical Imaging 2014: Ultrasonic Imaging and Tomography, 90400B (20 March 2014); https://doi.org/10.1117/12.2043972

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