Blood flow estimates through replenishment curve fitting in ultrasound contrast imaging

• US 20060161062A1
• Filed: 12/12/2005
• Published: 07/20/2006
• Est. Priority Date: 06/12/2003
• Status: Active Grant

• Current Assignee: Bracco Suisse SA
• Original Assignee: Bracco Research SA
• Inventors: Frinking, Peter, Arditi, Marcel, Gori, Ilaria
• Granted Patent: US 8,491,482 B2
• Time in Patent Office: Days
• US Class Current: 600/443
• CPC Class Codes: A61B 8/06 Measuring blood flow measuring volume flow in general G01F, e.g. G01F1/66, G01F1/72; measuring speed of fluids in general G01P5/00
• CPC Class Codes: A61B 8/13 Tomography A61B8/10, A61B8/12 take precedence; tomography for radiation diagnosis A61B6/02
• CPC Class Codes: A61B 8/481 involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream analysis of echo signal exploiting properties of a contrast enhancer in devices for short-range imaging with acoustic waves G01S7/52039
• CPC Class Codes: A61K 49/223 Microbubbles, hollow microspheres, free gas bubbles, gas microspheres

Abstract

Method and system for non-invasive quantification of tissue perfusion obtainable by a destruction-reperfusion process that provide a signal representative of local agent concentration during reperfusion, by deriving at least one local tissue perfusion value. The system comprises means for adjusting or relating a function of time with S-shape characteristics to the signal proportional to the local agent concentration during reperfusion, and making a correspondence between at least one value of at least one parameter of the function with S-shape characteristics with at least one local tissue perfusion value (such as mean velocity, mean transit time, mean flow, perfusion volume) or attribute (such as the blood flow pattern, flow distribution variance or skewness).

Claims

1. A method of non-invasive quantification of perfusion in a tissue of a live subject, the method including the steps of:

providing a sequence of echo signals indicative of a replenishment of an imaging contrast agent in said tissue,

associating a parametric S-shape function of time with the echo signals, said S-shape function including an initial portion with a substantially constant initial value, a final portion with a substantially constant final value, and a central portion between the initial portion and the final portion wherein said S-shape function changes monotonically from the initial value to the final value; and

making a correspondence between at least one value of at least one parameter of said S-shape function and at least one local tissue perfusion value or attribute.

2. The method according to claim 1, wherein said contrast agent includes microvesicles having the capacity to reflect acoustic energy, said sequence of echo signals being obtainable by:

administering said contrast agent to the live subject;

applying an ultrasound pulse in an imaging plane of an ultrasound imaging apparatus, at an acoustic pressure sufficiently high to result in the destruction of a significant portion of the microvesicles present within that plane;

applying a sequence of further ultrasound pulses in said imaging plane, said further ultrasound pulses having an acoustic pressure sufficiently low to preserve a major portion of the microvesicles; and

repeating the step of applying the sequence of further ultrasound pulses at predetermined subsequent instants, and recording the echo signals originating from said plane by the further ultrasound pulses to monitor the replenishment of microvesicles within the imaging plane at said subsequent instants.

3. The method according to claim 1, further including the step, before associating the S-shape function, of:

processing said echo signals to make the echo signals proportional to a local concentration of the microvesicles thereby producing processed echo signals that are in proportion to a concentration of the contrast agent at any location within the imaging plane.

4. The method according to claim 3, wherein the echo signals are obtained as a two dimensional image associated to image elements proportional to an amplitude of said echo signal, and said processing includes linearization of said echo signals.

5. The method according to claim 3, wherein the echo signals have an amplitude proportional to an ultrasound echo amplitude and said processing includes linearization of said echo signals.

6. The method according to claim 5, wherein the echo signals are radio-frequency signals or demodulated radio-frequency signals.

7. The method according to claim 1, wherein the tissue perfusion value or attribute is estimated within a chosen area of interest.

8. The method according to claim 1, wherein the perfusion value or attribute is estimated within individual two-dimensional image elements and then displayed on a viewing monitor in the form of parametric images as pixel grayscale intensities or color rendering, where the pixel grayscale intensities or color rendering is coded according to the values of the individual locally-estimated parameters, or combinations thereof.

9. The method according to claim 1, wherein the perfusion value or attribute is estimated within groups of two-dimensional image elements, said groups being determined by a local imaging resolution in such a way that substantially one value only of each parameter is obtained for each group of image elements.

10. The method according to claim 1, wherein the perfusion value or attribute is estimated within groups of image elements, said groups of image elements having sizes that are substantially determined by a local speckle pattern of an echographic instrument of the ultrasound apparatus.

11. The method according to claim 10, wherein the sizes of said groups of image elements are determined from a two-dimensional spatial Fourier analysis of a local echographic image, and whose extents are inversely proportional to a maximum significant spatial frequencies present locally.

12. The method according to claim 1, wherein said correspondence is made with at least one perfusion value selected among the following:

mean transit time, mean velocity, mean flow and perfusion volume.

13. The method according to claim 1, wherein said correspondence is made with at least one perfusion attribute selected among the following:

blood flow pattern, flow distribution variance and flow skewness.

14. The method according to claim 1, wherein the perfusion value or attribute is estimated from a time lapse between the ultrasound pulse and an instant when the S-shape function reaches a value equivalent to a concentration of the contrast agent one half of the concentration present immediately before applying the ultrasound pulse.

15. The method according to claim 14 when dependent on claim 2, wherein said perfusion value is a mean local blood velocity which is expressed as the ratio between one-half a thickness of a slice where the microvesicles are destroyed and a time to half-maximum concentration.

16. The method according to claim 15, wherein the thickness of the slice where the microvesicles are destroyed is approximated by the value of a width, in a direction perpendicular to the imaging plane, of the applied ultrasound pulse.

17. The method according to claim 1, wherein the ultrasound contrast agent is suitable to be administered intravenously as a continuous infusion.

18. The method according to claim 1, wherein the ultrasound contrast agent is administered intravenously as a bolus in such a way as to provide a period of several seconds with a local agent concentration supply of essentially constant value to the imaged area until the local concentration reaches at least one-half the concentration existing immediately prior to applying the ultrasound pulse.

19. The method according to claim 1, wherein the S-shape function is a cumulative normal probability distribution function, a sigmoid function or a polynomial approximation of a cumulative normal probability distribution function.

20. The method according to claim 19, wherein the S-shape function is a parametric expression including limited expansion of a polynomial form or a parametric expression of a cumulative lognormal probability distribution function.

21. The method according to claim 19, wherein the S-shape function is a parametric expression of a sum or integral of cumulative normal probability distribution functions, weighted by a lognormal probability distribution of flow velocities or transit times, the S-shape function having best-fit parameter values that represent physical quantities of organ perfusion.

22. The method according to claim 1, wherein the echo signals are processed through a smoothing function before associating the S-shape function.

23. The method according to claim 1, wherein said echo signals are analyzed by a wavelet decomposition method to estimate a distribution of contributions at different flow transit times or velocities.

24. The method according to claim 23, wherein the echo signal proportional to local concentration is differentiated twice before being analyzed by the wavelet decomposition method.

25. The method according to claim 24, wherein a mother wavelet used for the decomposition is the second time derivative of a cumulative normal distribution function used to describe the S-shape function for a single flow value.

26. The method according to claim 1, wherein the echo signals are analyzed to estimate a distribution of contributions at different flow transit times or velocities, the analysis including the steps of:

selecting a first set of flow transit times or velocities; and

making a first estimate by a best fit of a linear combination of a plurality of S-shaped functions with the echo signals.

27. The method according to claim 26 wherein said first set of flow transit times or velocities is obtained from a linear combination of from 4 to 16 S-shape functions.

28. The method according to claim 26, wherein the analysis further includes the step of:

making a second estimate to define a second set of flow transit times or velocities, using said first estimate as a basis for defining said second set.

29. The method according to claim 28 wherein said second set of flow transit times or velocities is obtained from a linear combination of from 8 to 64 S-shape functions.

30. The method according to claim 28 wherein the second estimate is used to provide an initial set of values for making a third estimate.

31. The method according to claim 28 wherein the second estimate is made using cubic spline extrapolation.

32. The method according to claim 28 wherein the third estimate is made using a neural network analysis.

33. The method according to claim 32, wherein the neural network is defined by a plurality of weights for the flow transit times or velocities and a plurality of bias values for the weighted flow transit times or velocities, the third estimate including:

iteratively adjusting the bias values and the weights, and

periodically resetting the bias values and each negative weight to zero.

34. The method according to claim 33, wherein the step of resetting is performed with a periodicity equal to a number of iterations between 10 and 200.

35. The method of claim 26 wherein the first estimate is made using at most 8 S-shaped functions.

36. The method of claim 35 wherein the second estimate is made using a set of at least 16 flow transit times or velocities.

37. A computer program including program code means directly loadable into a working memory of a data processing system for performing the method of claim 1 when the program is run on the system.

38. A program product including a computer readable medium embodying the computer program of claim 37.

39. A system of non-invasive quantification of perfusion in a tissue of a live subject, the system including means for providing a sequence of echo signals indicative of a replenishment of an imaging contrast agent in said tissue, means for associating a parametric S-shape function of time with the echo signals, said S-shape function including an initial portion with a substantially constant initial value, a final portion with a substantially constant final value, and a central portion between the initial portion and the final portion wherein said S-shape function changes monotonically from the initial value to the final value;

and means for making a correspondence between at least one value of at least one parameter of said S-shape function and at least one local tissue perfusion value or attribute.

40. The system according to claim 39, wherein said contrast agent includes microvesicles having the capacity to reflect acoustic energy, the means for providing the sequence of echo signals including means for applying an ultrasound pulse in an imaging plane of an ultrasound imaging apparatus, at an acoustic pressure sufficiently high to result in the destruction of a significant portion of the microvesicles present within that plane, means for applying a sequence of further ultrasound pulses in said imaging plane, said further ultrasound pulses having an acoustic pressure sufficiently low to preserve a major portion of the microvesicles, and means for recording the echo signals originating from said plane by the further ultrasound pulses at predetermined subsequence instants to monitor the replenishment of microvesicles within the imaging plane at said subsequent instants.

41. The system according to claim 39, further including means for processing said echo signals, before associating the S-shape function, to make the echo signals proportional to a local concentration of the microvesicles thereby producing processed echo signals that are in proportion to a concentration of the contrast agent at any location within the imaging plane.

42. An apparatus for use in the system of claim 39, the apparatus including means for inputting said echo signals, said means for associating the parametric S-shape function of time with the echo signals, and said means for making the correspondence.