title: Precision Medicine Starts With Preanalytics: Real-Time Assessment of Tissue Fixation Quality by Ultrasound Time-of-Flight Analysis.
abstract: Personalized medicine promises diagnosis and treatment of disease at the individual level and relies heavily on clinical specimen integrity and diagnostic assay quality. Preanalytics, the collection and handling steps of a clinical specimen before immunohistochemistry or other clinical assay, are critically important to enable the correct diagnosis of disease. However, the effects of preanalytics are often overlooked due to a lack of standardization and limited assessment tools to quantify their variation. Here, we report a novel real-time ultrasound time-of-flight instrument that is capable of monitoring and imaging the critical step in formalin fixation, diffusion of the fixative into tissue, which provides a quantifiable quality metric for tissue fixation in the clinical laboratory ensuring consistent downstream molecular assay results. We analyzed hundreds of tissue specimens from 34 distinct human tissue types and 12 clinically relevant diseased tissues for diffusion and fixation metrics. Our measurements can be converted into tissue diffusivity constants that correlate with the apparent diffusion constant calculated using magnetic resonance imaging (R=0.83), despite the differences in the approaches, indicating that our approach is biophysically plausible. Using data collected from time-of-flight analysis of many tissues, we have therefore developed a novel rapid fixation program that could ensure high-quality downstream assay results for a broad range of human tissue types.
authors.affiliation: *Department of Laboratory Medicine, University of Washington, Seattle, WA †Ventana Medical Systems Inc., Tucson, AZ.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Lerch
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Bauer
authors.forename: David
authors.initials: D
authors.lastname: Chafin
authors.forename: Abbey
authors.initials: A
authors.lastname: Theiss
authors.forename: Michael
authors.initials: M
authors.lastname: Otter
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Baird
mesh_terms: D006801:Humans; D007150:Immunohistochemistry; D057285:Precision Medicine; D016707:Tissue Fixation / Q000379:methods*; D014465:Ultrasonics