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Journal of Medical Imaging • Open Access

Active monitoring of formaldehyde diffusion into histological tissues with digital acoustic interferometry
Author(s): Daniel R. Bauer; Benjamin Stevens; David Chafin; Abbey P. Theiss; Michael Otter

Paper Abstract

The preservation of certain labile cancer biomarkers with formaldehyde-based fixatives can be considerably affected by preanalytical factors such as quality of fixation. Currently, there are no technologies capable of quantifying a fixative’s concentration or the formation of cross-links in tissue specimens. This work examined the ability to detect formalin diffusion into a histological specimen in real time. As formaldehyde passively diffused into tissue, an ultrasound time-of-flight (TOF) shift of several nanoseconds was generated due to the distinct sound velocities of formalin and exchangeable fluid within the tissue. This signal was resolved with a developed digital acoustic interferometry algorithm, which compared the phase differential between signals and computed the absolute TOF with subnanosecond precision. The TOF was measured repeatedly across the tissue sample for several hours until diffusive equilibrium was realized. The change in TOF from 6-mm thick ex vivo human tonsil fit a single-exponential decay (R2adj≥0.98) with rate constants that varied drastically spatially between 2 and 10 h (σ=2.9  h) due to substantial heterogeneity. This technology may prove essential to personalized cancer diagnostics by documenting and tracking biospecimen preanalytical fixation, guaranteeing their suitability for diagnostic assays, and speeding the workflow in clinical histopathology laboratories.

Paper Details

Date Published: 8 February 2016
PDF: 9 pages
J. Med. Img. 3(1) 017002 doi: 10.1117/1.JMI.3.1.017002
Published in: Journal of Medical Imaging Volume 3, Issue 1
Show Author Affiliations
Daniel R. Bauer, Ventana Medical Systems, Inc. (United States)
Benjamin Stevens, Ventana Medical Systems, Inc. (United States)
David Chafin, Ventana Medical Systems, Inc. (United States)
Abbey P. Theiss, Ventana Medical Systems, Inc. (United States)
Michael Otter, Ventana Medical Systems, Inc. (United States)


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