Obtaining true diffusivity constant

Patent metadata

Field	Value
Publication number	US-10620037-B2
Application number	US-201715624644-A
Country	US
Kind code	B2
Filing date	Jun 15, 2017
Priority date	Dec 17, 2014
Publication date	Apr 14, 2020
Grant date	Apr 14, 2020

Abstract

The subject disclosure presents systems and computer-implemented methods for calculating the diffusivity constant of a sample using acoustic time-of-flight (TOF) based information correlated with a diffusion model to reconstruct a sample's diffusivity coefficient. Operations disclosed herein such as acoustically determining the phase differential accumulated through passive fluid exchange (i.e. diffusion) based on the geometry of the tissue sample, modeling the impact of the diffusion on the TOF, and using a post-processing algorithm to correlate the results to determine the diffusivity constant, are enabled by monitoring the changes in the speed of sound caused by penetration of fixative such as formalin into several tissue samples. A tissue preparation system may be adapted to monitor said diffusion of a tissue sample and determine an optimal processing workflow.

First claim

The invention claimed is:

1. A method for determining a true diffusivity constant of a porous material comprising:
computing a set of experimental time-of-flights (TOFs) from measured acoustic data of acoustic waves, the acoustic waves having been detected by an acoustic monitoring device and having traveled through the porous material, each experimental TOF of the computed set of experimental TOFs indicating the TOF of acoustic waves that traveled through a candidate diffusivity point of the porous material at a respective one of a plurality of time points;
setting a range of candidate diffusivity constants for the porous material;
for each of the candidate diffusivity constants, simulating a spatial dependence concentration model of an expected concentration of a reagent within the porous material for the plurality of time points and for the candidate diffusivity point, the expected concentration of the reagent being a function of time, space and said candidate diffusivity constant;
using the simulated spatial dependence concentration model for computing a spatial dependence TOF model for the porous material, the TOF model assigning, to the candidate diffusivity point for each of the plurality of time points and for each of the candidate diffusivity constants, a respectively modeled TOF; and
determining an error function for the candidate diffusivity point for each of the plurality of time points and for each of the candidate diffusivity constants, the error function being indicative of a distance between each of the modeled TOFs assigned to said candidate diffusivity point from a corresponding experimental TOF, the experimental TOF having been measured by the acoustic monitoring device at the same time point as used for modeling its corresponding modeled TOF;
determining a minimum error function based on the determined error function for the candidate diffusivity point for each of the plurality of time points and for each of the candidate diffusivity constants;
calculating the true diffusivity constant for the porous material based on the determined minimum error function,

wherein the computation of the spatial dependence TOF model comprising:
selecting a first one of the candidate diffusivity constants;
calculating an expected reagent concentration (c reagent ) at each of the candidate diffusivity points in the porous material for each of the plurality of time points in dependence of the selected candidate diffusivity constant;
calculating an integrated reagent concentration (c detected ) for each of the plurality of time points and for each of the candidate diffusivity constants by integrating the expected reagent concentration (c reagent ) calculated for said time point and said candidate diffusivity constant over a radius of the porous material;
converting the integrated reagent concentration to the respective modeled TOF of the spatial dependence TOF model by computing a linear combination of a speed of the acoustic waves in the porous material prior to diffusion with the reagent and the speed of the acoustic waves in the reagent being free of the porous material; and
selecting a next one of the candidate diffusivity constants and repeating this step and the three previous steps for the next selected candidate diffusivity constant until a termination criterion is reached.

2. The method of claim 1 , wherein computing the spatial dependence TOF model comprises determining each of the modeled TOFs by solving a heat equation for the porous material.

3. The method of claim 1 , wherein the acoustic data comprises:
velocity of the acoustic waves in the porous material prior to diffusion with the reagent; and/or
the experimental TOFs of the acoustic waves through the porous material at the plurality of time points during diffusion of the reagent into the porous material; and/or experimental phase shift data for computing the experimental TOFs from the experimental phase shift data;
velocity of the acoustic waves in the reagent being free of the porous material; and/or
a thickness of the porous material.

4. The method of claim 1 , wherein the speed of the acoustic waves in the reagent being free of the porous material is calculated by transmitting an ultrasonic wave between an ultrasonic transmitter and an ultrasonic receiver through the fluid, calculating the TOF between the ultrasonic transmitter and the ultrasonic receiver, and calculating the speed of the acoustic wave of the reagent according to the following formula:

r
fluid

=

d
t

wherein r fluid is the speed of sound in the reagent, d is a distance between the ultrasonic transmitter and the ultrasonic receiver, and t is the TOF between the transmitter and receiver.

5. The method of claim 1 , wherein the speed of the acoustic waves in the undiffused porous material (r orig ) are determined according to the following formula:

1

r
orig

=

1

r
fluid

+

Δ
⁢

⁢
t

d
mat

wherein Δt is a difference in TOF between waves passing through the reagent and the porous material and waves passing through the reagent only, and d mat is a thickness of the porous material.

6. The method of claim 1 , wherein the spatial dependence concentration model is configured to calculate the expected concentration of the reagent at the candidate diffusivity point by using a heat equation, the heat equation being descriptive of the distribution of heat in a given region of an object having a same 3D shape as the porous material over time.

7. The method of claim 6 , wherein the porous material is cylindrical and the heat equation is specified by the following formula:

c
fluid

⁡

(

t
,
D
,
x

)

=

c
max

⁡

(

1
-

2
⁢

∑

n
=
1

∞

⁢

⁢

Assignees

• Ventana Med Syst Inc

Inventors

• Bauer Daniel
• Otter Michael
• Stevens Benjamin

Classifications

• G01N29/07

  by measuring propagation velocity or propagation time of acoustic waves · CPC title

• A61B8/4483

  characterised by features of the ultrasound transducer · CPC title

• G01N29/4472

  Mathematical theories or simulation · CPC title

• G01N2291/02475

  Tissue characterisation · CPC title

• A61N2007/0039

  using microbubbles · CPC title