Estimating and correcting for contrast agent extravasation in tissue perfusion imaging

• US 8,718,747 B2
• Filed: 04/18/2011
• Issued: 05/06/2014
• Est. Priority Date: 04/16/2010
• Status: Active Grant

• Current Assignee: Oslo Universitetssykehus Hf
• Original Assignee: Oslo Universitetssykehus Hf
• Inventors: Bjrnerud, Atle, Emblem, Kyrre Eeg
• Primary Examiner(s): Le, Long V.
• Assistant Examiner(s): EVOY, NICHOLAS LANE
• Application Number:
  US13/088,972
• Publication Number:
  US 20110257519A1
• Time in Patent Office: 1,114 Days
• Field of Search: 702/19, 600/420, 600/504, 600/410, 600/416, 382/128, 382/131, 424/9.3
• US Class Current: 600/431
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 6/481 involving the use of contrast agents
• CPC Class Codes: A61B 6/486 involving generating temporal series of image data
• CPC Class Codes: A61B 6/507 for determination of haemodynamic parameters, e.g. perfusion CT
• CPC Class Codes: A61B 6/5217 extracting a diagnostic or physiological parameter from medical diagnostic data
• CPC Class Codes: G01R 33/5601 involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
• CPC Class Codes: G01R 33/56366 Perfusion imaging
• CPC Class Codes: G06T 2207/10096 Dynamic contrast-enhanced magnetic resonance imaging [DCE-MRI]
• CPC Class Codes: G06T 2207/30016 Brain
• CPC Class Codes: G06T 7/0016 involving temporal comparison
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment

Abstract

The invention provides a method, an image analysis software product, and a system for medical imaging analysis for estimating contrast agent extravasation in contrast agent based perfusion imaging such as MRI dynamic contrast enhanced (DCE) imaging, and in particular correction, compensation, or visualization of extravascular leakage of contrast agent in tumors. According to the invention, the effect of extravasation is directly manifested in the tail part of an observed, apparent residue function, R′(t), obtained directly by de-convoluting the expression C(t)=R′(t)C_p′(t) with the arterial input function (AIF). A leakage rate or extravasation constant is determined directly from the tail part of the determined apparent residue function. The invention also relates to distinguishing between T₁-dominant and T₂*-dominant extravasation effects in perfusion imaging to from the sign of the tail part of the determined apparent residue function and to an automated method for DSC-MRI involving correction for contrast agent extravasation and partial volume effects.

Claims

1. A method for estimating contrast agent extravasation in contrast agent based perfusion imaging methods to be performed by an electronic processor, the method comprising:

accessing perfusion image data comprising a signal related to contrast agent concentration as a function of time in a voxel during the first and consecutive passages of the contrast agent through the vascular system;

representing the signal by a convolution, R_ps′

(t)C_p′

(t), of an apparent residue function, R_ps′

(t), and an estimated contrast agent concentration in plasma, C_p′

(t), and determining the apparent residue function R_ps′

(t) by deconvolution of the signal with C_p′

(t);

estimating a first leakage rate constant K_a from a tail part of the apparent residue function, where K_a is quantifying an apparent rate of contrast agent extravasation from plasma to extravascular, extracellular space (EES);

determining an extravasation corrected residue function, R_corr(t), from the apparent residue function R_ps′

(t) and the estimated K_a, wherein the extravasation corrected residue function, R_corr(t), is determined using at least one of the following algorithms;

R_corr(t)=R_ps′

(t)−

K_a

R_corr(t)=1/F(R_ps′

(t)−

K_a(1−

k_ept))

R_corr(t)=1/F(R_ps′

(t)−

K_α

e<sup>−

kept</sup>)

R_corr(t)=1/F(R_ps′

(t)−

mean[R_ps′

(t>

t_tp)]);

where F is the tissue flow and t_tp is an estimated start time of the tail part and where k_ep is a second leakage rate constant which is quantifying an apparent rate of contrast agent reflux from tissue back to blood.

5. A method according to claim 1, for estimating contrast agent extravasation in contrast agent based perfusion imaging methods to be performed by an electronic processor, the method comprising:

accessing perfusion image data comprising a signal related to contrast agent concentration as a function of time in a voxel during the first and consecutive passages of the contrast agent through the vascular system;

representing the signal by a convolution, R_ps′

(t)C_p′

(t), of an apparent residue function, R_ps′

(t), and an estimated contrast agent concentration in plasma, C_p′

(t), and determining the apparent residue function R_ps′

(t) by deconvolution of the signal with C_p′

(t);

estimating a first leakage rate constant K_a from a tail part of the apparent residue function, where K_a is quantifying an apparent rate of contrast agent extravasation from plasma to extravascular, extracellular space (EES); and

wherein the estimation comprises fitting an exponential or linear function involving K_a as a constant to at least the tail part of the apparent residue function.

2. A method for estimating contrast agent extravasation in contrast agent based perfusion imaging methods to be performed by an electronic processor, the method comprising:

accessing perfusion image data comprising a signal related to contrast agent concentration as a function of time in a voxel during the first and consecutive passages of the contrast agent through the vascular system;

representing the signal by a convolution, R_ps′

(t)C_p′

(t), of an apparent residue function, R_ps′

(t), and an estimated contrast agent concentration in plasma, C_p′

(t), and determining the apparent residue function R_ps′

(t) by deconvolution of the signal with C_p′

(t);

estimating a first leakage rate constant K_a from a tail part of the apparent residue function, where K_a is quantifying an apparent rate of contrast agent extravasation from plasma to extravascular, extracellular space (EES),

wherein the tail part of the apparent residue function is determined by one or more of;

fitting a singly peaked, monotonously decreasing function, L(t), with zero asymptotes to a global maxima peak of the apparent residue function and defining the tail part of the apparent residue function as the part where the amplitude of the apparent residue function is consistently larger than the amplitude of L(t);

estimating the approximate mean transit time (MTT) from the perfusion image data, and from this estimate, estimating a time, t_fp, larger than MTT and using R′

(t) for t>

t_fp as the tail part of the apparent residue function;

finding the section of the apparent residue function following its peak amplitude with minimum relative variance (variance divided by mean value) over a predefined section length.

3. A method for estimating contrast agent extravasation in contrast agent based perfusion imaging methods to be performed by an electronic processor, the method comprising:

accessing perfusion image data comprising a signal related to contrast agent concentration as a function of time in a voxel during the first and consecutive passages of the contrast agent through the vascular system;

representing the signal by a convolution, R_ps′

(t)C_p′

(t), of an apparent residue function, R_ps′

(t), and an estimated contrast agent concentration in plasma, C_p′

(t), and determining the apparent residue function R_ps′

(t) by deconvolution of the signal with C_p′

(t);

estimating a first leakage rate constant K_a from a tail part of the apparent residue function, where K_a is quantifying an apparent rate of contrast agent extravasation from plasma to extravascular, extracellular space (EES); and

wherein K_a is estimated as being proportional to a mean value of the tail part of the apparent residue function.

4. A method for estimating contrast agent extravasation in contrast agent based perfusion imaging methods to be performed by an electronic processor, the method comprising:

accessing perfusion image data comprising a signal related to contrast agent concentration as a function of time in a voxel during the first and consecutive passages of the contrast agent through the vascular system;

representing the signal by a convolution, R_ps′

(t)C_ps′

(t), of an apparent residue function, R_ps′

(t), and an estimated contrast agent concentration in plasma, C_p′

(t), and determining the apparent residue function R_ps′

(t) by deconvolution of the signal with C_p′

(t);

estimating a first leakage rate constant K_a from a tail part of the apparent residue function, where K_a is quantifying an apparent rate of contrast agent extravasation from plasma to extravascular, extracellular space (EES); and

wherein K_a is estimated as being proportional to an asymptote of the apparent residue function.

6. A method for estimating contrast agent extravasation in contrast agent based perfusion imaging methods to be performed by an electronic processor, the method comprising:

accessing perfusion image data comprising a signal related to contrast agent concentration as a function of time in a voxel during the first and consecutive passages of the contrast agent through the vascular system;

representing the signal by a convolution, R_ps′

(t)C_p′

(t), of an apparent residue function, R_ps′

(t), and an estimated contrast agent concentration in plasma, C_p′

(t), and determining the apparent residue function R_ps′

(t) by deconvolution of the signal with C_p′

(t);

estimating a first leakage rate constant K_a from a tail part of the apparent residue function, where K_a is quantifying an apparent rate of contrast agent extravasation from plasma to extravascular, extracellular space (EES); and

wherein the estimation further comprises estimating a second leakage rate constant k_ep quantifying an apparent rate of contrast agent reflux EES back to plasma based on the tail part of the apparent residue function.

7. A method for estimating contrast agent extravasation in contrast agent based perfusion imaging methods to be performed by an electronic processor, the method comprising:

accessing perfusion image data comprising a signal related to contrast agent concentration as a function of time in a voxel during the first and consecutive passages of the contrast agent through the vascular system;

representing the signal by a convolution, R_ps′

(t)C_p′

(t), of an apparent residue function, R_ps′

(t), and an estimated contrast agent concentration in plasma, C_p′

(t), and determining the apparent residue function R_ps′

(t) by deconvolution of the signal with C_p′

(t);

estimating a first leakage rate constant K_a from a tail part of the apparent residue function, where K_a is quantifying an apparent rate of contrast agent extravasation from plasma to extravascular, extracellular space (EES); and

an automated segmentation of imaged tissue into a tumor region and white and/or grey matter, and wherein a mean value of K_a are estimated for the tumor region and for the white and/or grey matter.

13. An automated method for DSC-MRI comprising the following to be performed by an electronic processor for at least each slice in acquired image data:

automatic detection of an arterial input function (AIF);

estimating a first leakage rate constant K_a quantifying an apparent rate of contrast agent extravasation and a partial volume correction factor, f_pv, according to claim 7.

8. A method for estimating contrast agent extravasation in contrast agent based perfusion imaging methods to be performed by an electronic processor, the method comprising:

accessing perfusion image data comprising a signal related to contrast agent concentration as a function of time in a voxel during the first and consecutive passages of the contrast agent through the vascular system;

representing the signal by a convolution, R′

(t)C_p′

(t), of an apparent residue function, R_ps′

(t), and an estimated contrast agent concentration in plasma, C_p′

(t), and determining the apparent residue function R_ps′

(t) by deconvolution of the signal with C_p′

(t);

estimating a first leakage rate constant K_a from a tail part of the apparent residue function, where K_a is quantifying an apparent rate of contrast agent extravasation from plasma to extravascular, extracellular space (EES); and

wherein K_a is allowed to take both positive and negative values, and wherein the method further comprises separating between T₁- and T₂*-dominant leakage by determining the sign of K_a, so that negative K_a values reflect T₁-dominant leakage effects and positive K_a values reflect T₂*-dominant leakage effects.

9. A method for estimating contrast agent extravasation in contrast agent based perfusion imaging methods to be performed by an electronic processor, the method comprising:

accessing perfusion image data comprising a signal related to contrast agent concentration as a function of time in a voxel during the first and consecutive passages of the contrast agent through the vascular system;

representing the signal by a convolution, R_ps′

(t)C_p′

(t), of an apparent residue function, R_ps′

(t), and an estimated contrast agent concentration in plasma, C_p′

(t), and determining the apparent residue function R_ps′

(t) by deconvolution of the signal with C_p′

(t);

estimating a first leakage rate constant K_a from a tail part of the apparent residue function, where K_a is quantifying an apparent rate of contrast agent extravasation from plasma to extravascular, extracellular space (EES); and

wherein the apparent residue function, R_ps′

(t), is estimated as;

10. A method for estimating contrast agent extravasation in contrast agent based perfusion imaging methods to be performed by an electronic processor, the method comprising:

accessing perfusion image data comprising a signal related to contrast agent concentration as a function of time in a voxel during the first and consecutive passages of the contrast agent through the vascular system;

representing the signal by a convolution, R_ps′

(t)C_p′

(t), of an apparent residue function, R_ps′

(t), and an estimated contrast agent concentration in plasma, C_p′

(t), and determining the apparent residue function R_ps′

(t) by deconvolution of the signal with C_p′

(t);

estimating a first leakage rate constant K_a from a tail part of the apparent residue function, where K_a is quantifying an apparent rate of contrast agent extravasation from plasma to extravascular, extracellular space (EES); and

wherein the apparent residue function, R_ps′

(t), is estimated as;

11. A method for estimating contrast agent extravasation in contrast agent based perfusion imaging methods to be performed by an electronic processor, the method comprising:

accessing perfusion image data comprising a signal related to contrast agent concentration as a function of time in a voxel during the first and consecutive passages of the contrast agent through the vascular system;

representing the signal by a convolution, R_ps′

(t)C_p′

(t), of an apparent residue function, R_ps′

(t), and an estimated contrast agent concentration in plasma, C_p′

(t), and determining the apparent residue function R_ps′

(t) by deconvolution of the signal with C_p′

(t);

estimating a first leakage rate constant K_a from a tail part of the apparent residue function, where K_a is quantifying an apparent rate of contrast agent extravasation from plasma to extravascular, extracellular space (EES); and

estimating a factor to be used in correction of partial volume (PV) effects in contrast agent based perfusion MR or CT images to be performed by an electronic processor, the method comprising determining a PV correction factor, f_pv, as a ratio between parts of the signal following the first passage of the contrast agent from one or more voxels comprising arterial blood and one or more voxels filled with venous blood, respectively.

12. A method of distinguishing between T₁-dominant and T₂*-dominant extravasation effects in perfusion imaging to be performed by an electronic processor, the method comprising:

accessing perfusion image data comprising a signal related to contrast agent concentration as a function of time in a voxel during the first and consecutive passages of the contrast agent through the vascular system;

representing the signal by a convolution, R_ps′

(t)C_p′

(t), of an apparent residue function, R_ps′

(t), and an estimated contrast agent concentration in plasma, C_p′

(t), and determining the apparent residue function R_ps′

(t) for each voxel by deconvolution of the signal with C_p′

(t);

determining a sign of the tail part of the apparent residue function; and

generating an image of a parameter reflecting the determined sign and magnitude.