Real-time prediction of tissue fixation time
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Publication Number
US-12663401-B2
Publication Date
2026-06-23
Expiration Date
Abstract
The present disclosure provides systems and methods which facilitate the prediction of an estimated time in which one or more fluids will optimally be diffused into a biological specimen, e.g., a tissue sample derived from a human subject. In some embodiments, the present disclosure provides systems and methods which facilitate the prediction of an estimated time until a biological specimen will optimally be fixed with one or more fixatives. In other embodiments, the prediction of a future time at which the biological specimen will be optimally fixed is based on time-of-flight data acquired at a particular point in time during the fixation of the biological specimen that has been deemed sufficiently accurate to predict the time at which the biological specimen will be optimally diffused with fixative.
Core Innovation
The invention estimates a time in which a fluid will optimally be diffused into a biological specimen immersed in the fluid by using acoustic data acquired at one or more positions along the biological specimen. Time-of-flight (TOF) data is derived from the acquired acoustic data, where the derived TOF data comprises one or more computed TOF data points, one or more computed TOF curves, and/or one or more computed decay constants.
At least two confidence models are simultaneously computed based on the derived TOF data, with the at least two confidence models selected from a past confidence model, a present confidence model, and a future confidence model. A point in time is determined when the computed at least two confidence models each independently meet predetermined threshold criteria.
The time in which the fluid will optimally be diffused into the biological specimen is then estimated based on TOF data corresponding to the determined point in time when the computed at least two confidence models each independently met the predetermined threshold criteria. The disclosed approach further includes computing a past confidence model threshold using candidate decay constants compared to a calculated average decay constant within a predetermined threshold percentage value, and convergence testing is performed using candidate decay constants, an average decay constant, and a percent error comparison to a predetermined threshold percentage value.
Claims Coverage
The independent claims are directed to a method and to computer-implemented estimators that use acoustic TOF data with multiple confidence models (past/present/future) and predetermined threshold criteria to estimate an optimal fluid diffusion time. Across the independent claim set, the core inventive features total three main components: TOF derivation from acoustic data, simultaneous confidence-model threshold evaluation to select a time point, and past-model threshold satisfaction using candidate decay constants versus an average decay constant within a percentage threshold.
Acoustic TOF data derivation for fluid diffusion time estimation
Deriving time-of-flight (TOF) data from acquired acoustic data acquired at one or more positions along a biological specimen immersed in a fluid, wherein the derived TOF data comprises one or more computed TOF data points, one or more computed TOF curves, and/or one or more computed decay constants.
Simultaneous past/present/future confidence models with threshold-based time-point determination
Simultaneously computing at least two confidence models based on the derived TOF data, wherein the at least two confidence models are selected from a past confidence model, a present confidence model, and a future confidence model, and determining a point in time when the computed at least two confidence models each independently meet predetermined threshold criteria.
Optimal diffusion time estimation from TOF data at the threshold-satisfied point in time
Estimating the time in which the fluid will optimally be diffused into the biological specimen based on TOF data corresponding to the determined point in time when the computed at least two of confidence models each independently met the predetermined threshold criteria.
Past confidence model convergence using candidate decay constants versus an average decay constant within a percentage threshold
The computed past confidence model meets predetermined past confidence model threshold criteria when a predetermined number of retrieved computed candidate decay constants corresponding to a plurality of derived TOF data points are each determined to be within a predetermined threshold percentage value of a calculated average decay constant.
Taken together, the independent claim set covers estimating an optimal fluid diffusion time by deriving TOF data from acoustic measurements, simultaneously evaluating past/present/future confidence models against predetermined thresholds to select a time point, and estimating the diffusion completion time from TOF data at that point, with an additional quantitative refinement for the past confidence model based on candidate decay constants relative to a calculated average decay constant within a threshold percentage.
Stated Advantages
Provides real-time prediction of tissue/fluid diffusion time during fixation.
Provides prediction accuracy outcomes including convergence vs end time differences and narrow confidence intervals.
Provides proof-of-quality via biomarker staining outcomes with a dynamic fixation workflow while maintaining stain coverage/intensity comparable to longer controls.
Documented Applications
Fixation-related diffusion time prediction, including real-time prediction of tissue/fluid diffusion time during fixation and a dynamic fixation workflow for improving fixation timing.
Digital pathology and downstream immunohistochemistry (IHC) and immunohistochemistry/ISH staining workflows.
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