U.S. patent application number 14/384636 was filed with the patent office on 2015-01-29 for mri display output reflecting contrast agent concentration as a function of time.
This patent application is currently assigned to HOLOGIC, INC.. The applicant listed for this patent is HOLOGIC, INC.. Invention is credited to Jiachao Liang, Jimmy R. Roehrig.
Application Number | 20150031983 14/384636 |
Document ID | / |
Family ID | 49161880 |
Filed Date | 2015-01-29 |
United States Patent
Application |
20150031983 |
Kind Code |
A1 |
Liang; Jiachao ; et
al. |
January 29, 2015 |
MRI DISPLAY OUTPUT REFLECTING CONTRAST AGENT CONCENTRATION AS A
FUNCTION OF TIME
Abstract
A magnetic resonant imaging (MRI) review workstation includes a
control processor, and a display integrated or otherwise
operatively coupled with the control processor, wherein the control
processor is configured to receive and analyze magnetic resonant
imaging information pertaining to an imaged volume of tissue, and
to cause to be displayed on the display output information that
reflects or is otherwise indicative of an absorption rate of a
contrast agent in the volume of tissue.
Inventors: |
Liang; Jiachao; (Palo Alto,
CA) ; Roehrig; Jimmy R.; (Aptos, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
HOLOGIC, INC. |
Marlborough |
MA |
US |
|
|
Assignee: |
HOLOGIC, INC.
Marlboro
MA
|
Family ID: |
49161880 |
Appl. No.: |
14/384636 |
Filed: |
March 15, 2013 |
PCT Filed: |
March 15, 2013 |
PCT NO: |
PCT/US13/32681 |
371 Date: |
September 11, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61611877 |
Mar 16, 2012 |
|
|
|
Current U.S.
Class: |
600/414 |
Current CPC
Class: |
G01R 33/50 20130101;
G01R 33/5601 20130101; A61B 5/055 20130101; A61B 5/742
20130101 |
Class at
Publication: |
600/414 |
International
Class: |
G01R 33/56 20060101
G01R033/56; G01R 33/50 20060101 G01R033/50; A61B 5/00 20060101
A61B005/00; A61B 5/055 20060101 A61B005/055 |
Claims
1. A magnetic resonant imaging (MRI) review workstation,
comprising: a control processor; and a display integrated or
otherwise operatively coupled with the control processor, wherein
the control processor is configured to receive and analyze magnetic
resonant imaging information pertaining to an imaged volume of
tissue, and to cause to be displayed on the display output
information that reflects or is otherwise indicative of an
absorption rate of a contrast agent in the volume of tissue,
wherein the displayed output information is derived from a signal
enhancement ratio for the tissue volume that has been normalized to
take into account an actual absorption rate of the contrast agent
in the tissue volume.
2. The MRI review workstation of claim 1, wherein the control
processor is configured to cause the output information to be
displayed during acquisition of the imaging information.
3. The MRI review workstation of claim 1, wherein the control
processor computes the normalized signal enhancement ratio for the
tissue volume as a function of time based, at least in part, upon a
pre-contrast relaxation value of the tissue volume.
4. The MRI review workstation of claim 3, wherein the pre-contrast
relaxation value of the tissue volume is a value obtained using a
reference tissue method, wherein the reference tissue is pectoral
muscle tissue or local fatty tissue, and the tissue volume is
breast tissue.
5. (canceled)
6. The MRI review workstation of claim 3, wherein the pre-contrast
relaxation value of the patient tissue volume is a value obtained
by direct measurement prior to introduction of the contrast agent
into the tissue volume.
7-8. (canceled)
9. The MRI review workstation of claim 1, wherein the control
processor computes the normalized signal enhancement ratio based,
at least in part, upon a pre-contrast relaxation value of the
tissue volume.
10-13. (canceled)
14. The MRI review workstation of claim 1, wherein the control
processor is configured to cause to be displayed an absolute value
of absorption of the contrast agent in the tissue volume.
15. The MRI review workstation of claim 1, wherein the output
information provides an indication of whether or not a wash out of
the contrast agent occurred in the tissue volume during acquisition
of the imaging information, regardless of a particular imaging
system or imaging protocol employed to acquire the imaging
information.
16. A system to facilitate a review and analysis of magnetic
resonant imaging information, comprising: at least one machine, the
at least one machine respectively including a processor
communicatively coupled to a storage device storing
computer-executable instructions, which instructions, when executed
by the processor, cause the processor to operate as: a record
module configured to acquire magnetic resonant imaging information
pertaining to a volume of tissue; and a processing module
configured to analyze magnetic resonant imaging information
pertaining to a volume of tissue received by the record module, and
to cause to be displayed on a display that is integrated or
otherwise operatively coupled with the control processor output
information that reflects or is otherwise indicative of an
absorption rate of a contrast agent in the volume of tissue,
wherein the displayed output information is derived from a signal
enhancement ratio for the tissue volume that has been normalized to
take into account an actual absorption rate of the contrast agent
in the tissue volume.
17. The system of claim 16, wherein the processing module is
configured to cause the output information to be displayed during
acquisition of the imaging information.
18. The system of claim 16, wherein the processing module is
configured to compute the signal enhancement ratio for the tissue
volume as a function of time based, at least in part, upon a
pre-contrast relaxation value of the tissue volume.
19. (canceled)
20. The MRI review workstation of claim 16, wherein the output
information provides an indication of whether or not a wash out of
the contrast agent occurred in the tissue volume during acquisition
of the imaging information, regardless of a particular imaging
system or imaging protocol employed to acquire the imaging
information.
21. A method for acquiring and evaluating magnetic resonant imaging
(MRI) information, comprising: acquiring MRI information of a
volume of tissue over a period of time; using a processor to
analyze the acquired MRI information; and displaying, on a display
integrated or otherwise operatively coupled with the processor,
output information that reflects or is otherwise indicative of an
absorption rate of a contrast agent in the volume of tissue during
the period of time, wherein the displayed output information is
derived from a signal enhancement ratio for the tissue volume that
has been normalized to take into account an actual absorption rate
of the contrast agent in the tissue volume.
22. The method of claim 21, comprising displaying the output
information on the display during acquisition of the imaging
information.
23. The method of claim 22, wherein the processor computes the
normalized signal enhancement ratio as a function of time based, at
least in part, upon a pre-contrast relaxation value of the tissue
volume.
24. The method of claim 23, wherein the pre-contrast relaxation
value of the tissue volume is a value obtained using a reference
tissue method, wherein the reference tissue is pectoral muscle
tissue or local fatty tissue, and the tissue volume is breast
tissue.
25. (canceled)
26. The method of claim 23, wherein the pre-contrast relaxation
value of the patient tissue volume is a value obtained by direct
measurement prior to introduction of the contrast agent into the
tissue volume.
27. The method of claim 23, wherein the pre-contrast relaxation
value of the tissue volume is based on a predetermined
approximation.
28-33. (canceled)
34. The method of claim 21, comprising displaying on the display an
absolute value of absorption of the contrast agent in the tissue
volume.
35. The method of claim 21, wherein the output information provides
an indication of whether or not a wash out of the contrast agent
occurred in the tissue volume during acquisition of the imaging
information, regardless of a particular imaging system or imaging
protocol employed to acquire the imaging information.
36. (canceled)
Description
RELATED APPLICATION DATA
[0001] The present application claims the benefit under 35 U.S.C.
.sctn.119 to U.S. Provisional Application No. 61/611,877, filed
Mar. 16, 2012, the contents of which are incorporated herein by
reference as though set forth in full.
FIELD OF THE INVENTION
[0002] The subject matter of the disclosed invention relates to the
acquisition and display of magnetic resonance imaging (MRI)
information, and more particularly, to a system and method for
analyzing MRI imaging information which computes and displays
output information that reflects or is otherwise indicative of an
absorption rate of a contrast agent in the volume of tissue.
CITED NON-PATENT PUBLICATIONS
[0003] The following non-patent publications are referenced in this
specification: [0004] 1. Jansen, Shimauchi, Zak, Fan, Wood,
Karczmar, Newstead. AJR 2009; 193:832-839, Kinetic Curves of
Malignant Lesions are Not Consistent Across MRI Systems: Need for
Improved Standardization of Breast Dynamic Contrast-Enhanced MRI
Acquisition [0005] 2. C K Kuhl, P M Mielcareck, S Klaschnik, C
Leutner, E Wardelmann, J Gieseke, H Schild, Radiology. 1999
211:101-110. Dynamic Breast MR Imaging: Are Signal Intensity Time
Course Data Useful for Differential Diagnosis of Enhancing Lesions?
[0006] 3. Haacke E M, Tkach J A. Fast MR imaging: techniques and
clinical applications. AJR Am J Roentgenol. 1990; 155(5):951-64.
[0007] 4. Frahm J, Haase A, Matthaei D. Rapid three-dimensional MR
imaging using the FLASH technique. J Comput Assist Tomogr. 1986;
10(2):363-8. [0008] 5. Tofts P S, Kermode A G. Measurement of the
blood-brain barrier permeability and leakage space using dynamic MR
imaging. 1. Fundamental concepts. MRM 1991; 17(2):357-67. [0009] 6.
Brix G, Semmler W, Port R, Schad L R, Layer G, Lorenz W J.
Pharmacokinetic parameters in CNS Gd-DTPA enhanced MR imaging. J
Comput Assist Tomogr. 1991; 15(4):621-8. [0010] 7. Rohrer M, Bauer
H, Mintorovitch J, Requardi M, Weinmann H J. Comparison of Magnetic
Properties of MRI Contrast Media Solutions at Different Magnetic
Field Strengths. Invest Radiol. 2005; 40(11):715-24. [0011] 8. C
Kuhl, Radiology. 2007 244:356-378. Dynamic Breast MR Imaging: Are
Signal Intensity Time Course Data Useful for Differential Diagnosis
of Enhancing Lesions? [0012] 9. Brix G, Kiessling F, Lucht R, Darai
S, Wasser K, Delorme S, Griebel J. Microcirculation and
Microvasculature in Breast Tumors: Pharmacokinetic Analysis of
Dynamic MR Image Series. Magn Reson Med. 2004; 52(2):420-9. [0013]
10. Slanisz G J, Odrobina E E, Pun J, Escaravage M, Graham S J,
Bronskill M J, Henkelman R M. T1, T2 relaxation and magnetization
transfer in tissue at 3T. Magn Reson Med. 2005; 54(3):507-12.
PATENT REFERENCES
[0014] Reference is further made to U.S. Pat. Nos. 7,693,320,
7,949,164 and U.S. Pat. No. 8,175,366, to Hadassa Degani et al.,
which disclose and describe methods and systems for reviewing and
analyzing MRI imaging information related to the systems and
methods disclosed and described herein, and the contents of which
are hereby incorporated by reference as if fully set forth
herein.
BACKGROUND
[0015] MRI imaging is well-known for medical applications, in which
three dimensional (i.e., volumetric) imaging information of a
patient's body region is acquired for diagnostic purposes. The MRI
information may be acquired at a single point in time, or may be
acquired at multiple points in time ("dynamic imaging"), in order
to study the time progression of dynamic processes, such as the
movement of blood.
[0016] There are a number of parameters that influence the strength
of the signal obtained from an MRI scanner, and the appearance of
the acquired image. Some of these parameters are controlled by the
operator of the scanner, such as the repetition time TR, the echo
time TE, and the flip angle .alpha.. Other parameters are
characteristics of the tissue being studied, such as the relaxation
times T1 and T2. In principle, the unambiguous interpretation of an
image involves only the observation and determination of the tissue
dependent parameters, such as T1 and T2. In practice, however,
these parameters are at least partially obscured by differing
selections of TR and TE. Thus, it would be desirable to disentangle
the effects of user-selected scanner parameters from the
tissue-dependent imaging parameters.
[0017] Commercially available computer-controlled workstations
employ a number of common types of displays to communicate useful
information to a radiologist or technician (together hereinafter
referred to "medical professional"). For example, MRI displays for
the study of breast tissue, e.g., to identify the presence and
location of cancer lesions, are well-known. Such MRI displays for
breast tissue typically display images showing various
two-dimensional slices taken through one or both breasts, and
provide the medical professional with the ability to scroll through
the respective tissue image slices using a common device, such as
mouse. This scrolling enables the medical professional or other
reviewer to readily view different slices, eventually covering the
entire breast region.
[0018] Also, the medical professional or other reviewer may employ
the MRI scanner to acquire volumetric image information of the
breast/breasts using different MRI parameters to emphasize
different physiological information. For example, "T2 weighted"
images may be acquired with one set of acquisition parameters, and
would show different information from "T1 weighted" images acquired
with different scanner parameters. In addition, a set of images may
be acquired before the administration of a contrast agent, and
thereafter for several time periods after the contrast agent has
entered the blood stream. The MRI workstation can be configured to
display a selection of all of these image types, arranged in some
order on a flat screen display. This arrangement of these multiple
images is called the "hanging protocol," and is usually set up by
the manufacturer according to the preferences of the particular
reviewer.
[0019] In addition to the different acquired images described
above, a flat panel display is typically provided for showing
certain computed information, such as "maximum intensity
projections" ("MIPs"), 3-D volume renderings, and a graph
displaying signal intensity as a function of time, such as that
shown in the screen capture displayed in FIG. 1. In particular, the
"signal intensity" curves that appear in FIG. 1 depict the
grey-level or pixel value at the user-selected voxel (y-axis) at
each point in time (x-axis) in which the scanner acquired a time
series of volumes. The first time point is taken before the
introduction (e.g., by injection) of contrast agent into the
patient's vasculature, and the subsequent time points after
introduction of the contrast agent, typically spaced by
approximately one minute per time point. Thus, each of the depicted
signal intensity curves in FIG. 1 show a positive slope after the
first time point, representing a "signal enhancement" taking place,
which is due to the immediate increase in amount of contrast agent
in the tissue volume being observed following introduction into the
vasculature.
[0020] Of particular interest is the "shape" of the respective
curve after the initial rapid enhancement. By "shape" is meant
whether the slope of curve after the "knee" is positive, flat, or
negative. The criterion generally accepted by the medical imaging
community is that a slope less than +-10% is considered "flat" or
"plateau", and beyond 10% either sustained enhancement or
"washout." In particular, the shape of the curve is assumed to be
indicative of different physiological conditions, and is often
classified into three "Types," i.e., Type I, Type II or Type III,
as shown in FIG. 2 (reproduced from Kuhl et al 2), with Type I
associated with benign tissue (sub-types "Ia" and "Ib" are depicted
in FIG. 2), Type II "suggestive of malignancy" (but often
equivocal), and Type III associated with malignant lesions. With
this in mind, in the screen capture shown in FIG. 1, curve 20 shows
sustained enhancement; curve 22 shows Type I or rapid initial and
sustained enhancement, curve 24 shows Type II or plateau behavior,
and curve 26, indicating the most suspicious lesions, shows Type
III or rapid initial enhancement with washout.
[0021] Notably, the manner in which the time progression of the
signal intensity is displayed in FIG. 1 and FIG. 2 gives the
reviewer the impression that the signal is, at least in some way,
proportional to the amount of contrast agent in the tissue volume
being studied. However, this is not necessarily the case.
Furthermore, based on the way the signal intensity is displayed in
these figures, the reviewer may mistakenly assume that the signal
is linearly proportional to the amount of contrast agent. Again,
this is not necessarily the case. Instead, as will be explained in
detail herein, such linearity is actually a necessary condition for
the assignment of a Type I to III to a volume of tissue to be
independent of MRI scanner acquisition parameters, particularly TR,
TE, and flip angle .alpha.. Without such a linear relationship, a
portion of tissue that appears as Type 1 or Type III, may change to
Type II simply by being scanned with different acquisition
parameters.
SUMMARY OF THE DISCLOSED INVENTIONS
[0022] In accordance with one aspect of the disclosed inventions, a
magnetic resonant imaging (MRI) review workstation comprises a
control processor, and a display integrated or otherwise
operatively coupled with the control processor, wherein the control
processor is configured to receive and analyze magnetic resonant
imaging information pertaining to an imaged volume of tissue, and
to cause to be displayed on the display output information that
reflects or is otherwise indicative of an absorption rate of a
contrast agent in the volume of tissue. In accordance with an
object of the disclosed inventions, the output information provides
an accurate indication of whether or not a wash out of the contrast
agent occurred in the tissue volume during acquisition of the
imaging information, regardless of a particular imaging system or
imaging protocol employed to acquire the imaging information.
[0023] By way of example, the control processor may be configured
to cause to be displayed a graphical representation of a
concentration of the contrast agent in the tissue volume as a
function of time during acquisition of the imaging information. By
way of another example, the control processor may be configured to
cause to be displayed a graphical representation of a signal
intensity ratio in the tissue volume as a function of time, wherein
the signal intensity ratio is normalized to take into account an
actual absorption rate of the contrast agent in the tissue volume,
wherein the control processor computes the normalized signal
intensity ratio based, at least in part, upon a pre-contrast
relaxation value of the tissue volume. In either case, the contrast
agent concentration as a function of time may be computed by the
control processor based, at least in part, upon a pre-contrast
relaxation value of the tissue volume, and wherein the pre-contrast
relaxation value of the tissue volume may be obtained using (i) a
reference tissue method, (ii) direct measurement, or (iii a
predetermined approximation. In one embodiment in which a reference
tissue method is employed, the volume of tissue is breast tissue,
and the reference tissue is pectoral muscle tissue or local fatty
tissue. In various embodiments, the output information may
comprise, or the control processor may be configured to
additionally cause to be displayed, an absolute value of absorption
of the contrast agent in the tissue volume. In accordance with
another aspect of the disclosed inventions, a system is provided to
facilitate a review and analysis of magnetic resonant imaging
information, wherein the system comprises at least one machine, the
at least one machine respectively including a processor
communicatively coupled to a storage device storing
computer-executable instructions, which instructions, when executed
by the processor, cause the processor to operate as: (i) a record
module configured to acquire magnetic resonant imaging information
pertaining to a volume of tissue; and (ii) a processing module
configured to analyze magnetic resonant imaging information
pertaining to a volume of tissue received by the record module, and
to cause to be displayed on a display that is integrated or
otherwise operatively coupled with the control processor output
information that reflects or is otherwise indicative of an
absorption rate of a contrast agent in the volume of tissue. Again,
the output information preferably provides an indication of whether
or not a wash out of the contrast agent occurred in the tissue
volume during acquisition of the imaging information.
[0024] By way of one example, the processing module may be
configured to cause to be displayed on the display a graphical
representation of a concentration of the contrast agent in the
tissue volume as a function of time during acquisition of the
imaging information, wherein the contrast agent concentration as a
function of time is computed based, at least in part, upon a
pre-contrast relaxation value of the tissue volume. By way of
another example, the processing module may be configured to cause
to be displayed on the display a graphical representation of a
signal intensity ratio in the tissue volume as a function of time,
wherein the signal intensity ratio is normalized to take into
account an actual absorption rate of the contrast agent in the
tissue volume, regardless of a particular imaging system or imaging
protocol employed to acquire the imaging information.
[0025] In accordance with still another aspect of the disclosed
inventions, a method is provided for acquiring and evaluating
magnetic resonant imaging (MRI) information, wherein the method
includes the steps or acts of (i) acquiring MRI information of a
volume of tissue over a period of time; (ii) using a processor to
analyze the acquired MRI information; and (iii) displaying, on a
display integrated or otherwise operatively coupled with the
processor, information that reflects or is otherwise indicative of
an absorption rate of a contrast agent in the volume of tissue
during the period of time. In accordance with an object of the
disclosed inventions, the output information preferably provides an
indication of whether or not a wash out of the contrast agent
occurred in the tissue volume during acquisition of the imaging
information.
[0026] In one embodiment, the method includes the step or act of
displaying on the display a graphical representation of a
concentration of the contrast agent in the tissue volume as a
function of time during acquisition of the imaging information,
wherein the contrast agent concentration is computed as a function
of time based, at least in part, upon a pre-contrast relaxation
value of the tissue volume. In another embodiment, the method
includes the step or act of displaying on the display a graphical
representation of a signal intensity ratio in the tissue volume as
a function of time, wherein the signal intensity ratio is
normalized to take into account an actual absorption rate of the
contrast agent in the tissue volume, regardless of a particular
imaging system or imaging protocol employed to acquire the imaging
information. In either case, the contrast agent concentration as a
function of time may be computed by the control processor based, at
least in part, upon a pre-contrast relaxation value of the tissue
volume, and wherein the pre-contrast relaxation value of the tissue
volume may be obtained using (i) a reference tissue method, (ii)
direct measurement, or (iii a predetermined approximation. In one
embodiment in which a reference tissue method is employed, the
volume of tissue is breast tissue, and the reference tissue is
pectoral muscle tissue or local fatty tissue.
[0027] In various embodiments, the method may further comprise the
step or act of introducing by injection or other means a contrast
agent into the tissue volume.
[0028] These and other aspects and embodiments of the disclosed
inventions are described in more detail below, in conjunction with
the accompanying figures.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] FIG. 1 is a captured MRI workstation display screenshot of a
graph depicting relative signal intensity as a function of
time.
[0030] FIG. 2 is a graph reproduced from Kuhl et al 2, depicting
exemplary signal intensity curves types I, II and III.
[0031] FIG. 3 is a table showing the MRI systems and imaging
protocols used in the Jansen et al. study.
[0032] FIGS. 4A-4C are respective pie charts illustrating a
proportion of cases in data sets exhibiting Types I, II and III
curves for the respective different imaging systems used in the
Jansen et al. study.
[0033] FIG. 5A depicts signal enhancement as a function of
concentration for different values of T.sub.10, and FIG. 5B depicts
the signal enhancement ratio versus contrast agent concentration,
respectively, from the 3 systems in Newstead et al with T.sub.10
selected at 1200 ms.
[0034] FIG. 6 is a graph depicting a first, hypothetical
concentration curve exhibiting high initial uptake followed by
rapid washout or type II, and a second, signal enhancement curve
derived therefrom exhibiting high initial uptake followed by a
plateau or Type II.
[0035] FIG. 7 is a pie chart in which the data depicted in FIG. 4C
is corrected to accurately represent the distribution of curve
types which is differentiated by washout ratio from peak
enhancement.
[0036] FIGS. 8A and 8B are graphs depicting T.sub.10 estimation
using the Reference Tissue method.
[0037] FIG. 9 is a graphical depiction of example signal
enhancement ratio curves being "normalized" based on actual
contrast agent absorption.
[0038] FIG. 10 is a flow diagram depicting an MRI imaging
acquisition and analysis method carried out according to one
embodiment of the invention.
DETAILED DESCRIPTION OF THE DISCLOSED INVENTIONS
[0039] In describing the depicted embodiments of the disclosed
inventions illustrated in the accompanying figures, specific
terminology is employed for the sake of clarity and ease of
description. However, the disclosure of this patent specification
is not intended to be limited to the specific terminology so
selected, and it is to be understood that each specific element
includes all technical equivalents that operate in a similar
manner. It is to be further understood that the various elements
and/or features of different illustrative embodiments may be
combined with each other and/or substituted for each other wherever
possible within the scope of this disclosure and the appended
claims.
[0040] In contrast to the prior art display modalities, a new
display provided in accordance with one aspect of the disclosed
inventions plots a concentration of contrast agent as a function of
time, making the indirect connection between signal and
concentration irrelevant. As explained herein, the concentration
may be computed from the known physics of the MRI acquisition and
the known acquisition parameters. Embodiments of the display are to
be used with (as part of) an MRI display workstation, in which the
time plot of contrast agent concentration may supplement or replace
the presently used signal intensity plot depicted in FIG. 1, in
order to more provide more accurate information to the medical
professional for evaluating patient MRI information.
[0041] The difficulties resulting from the non-linear relationship
between the signal and the concentration of contrast agent are
demonstrated in Jansen et al [1], which describes a study performed
of 601 patients, including 497 malignant and 185 benign lesions
viewed on three different scanner/protocol combinations. The three
data sets produced were called "System 1-3" by the authors, each
group indicating which of the three scanner/protocol combinations
was used for each individual case. The table shown in FIG. 3
summarizes the MRI systems and Protocols used in the study. The
present inventors believe the parameters most responsible for
differences are shown in the TR/TE row and the Flip angle. The
finding of this study was that only 47% of Invasive ductal
carcinoma (IDC) lesions imaged with System 3 exhibited washout type
curves, compared with 75% and 74% of those imaged with System 1 and
System, 2. These differences are shown graphically in the pie
charts of FIGS. 4A-4C, in which:
[0042] FIG. 4A depicts the respective proportion of data sets
exhibiting Type III washout (40a), Type II plateau (44a), and Type
I persistent (42a) for System 1;
[0043] FIG. 4B depicts the respective proportion of data sets
exhibiting Type III washout (40b), Type II plateau (44b), and Type
I persistent (42b) for System 2; and
[0044] FIG. 4A depicts the respective proportion of data sets
exhibiting Type III washout (40c), Type II plateau (44c), and Type
I persistent (42c) for System 3.
[0045] It is believed that many if not most medical professional
base their diagnosis of the malignancy of a lesion largely on which
of these curve types is characteristic of its time curve, with Type
III being most indicative of cancer, Type I indicative of benign
tissue, and Type II either suggestive or ambiguous. There is an
intuitive explanation of why a malignant lesion would be expected
to have a Type III curve having to do with the vascularity of
lesions and vessel permeability. Breast cancer has increased
vascularity with an increased permeability leading to an early
uptake and early washout behavior, i.e., Type III. However, the
results of the Jansen et al study, as summarized in the pie charts
in FIGS. 4A-C, suggest that cases may be placed into different
types or classifications, due of differences in scanner/protocol
parameters used in the signal acquisition, not only because of
underlying likelihood of malignancy. This would appear to be a very
serious disadvantage of the present method of analyzing kinetic
behavior.
[0046] The present inventors believe this problem occurs as a
result of the non-linear relationship between the MRI signal and
the contrast agent concentration, in particular, in a signal of the
type shown in FIG. 1, and not the concentration being observed and
classified into Types I-III. In the spoiled gradient echo sequence,
the standard method used in dynamic breast MRI, the signal
intensity can be expressed as a function of tissue and acquisition
parameters by equation 1 [3,4]:
S ( t ) = PD .times. sin .alpha. .times. 1 - exp - ( - TR / T 1 ) 1
- cos .alpha.exp ( - TR / T 1 ) ( 1 ) ##EQU00001##
where P is the proton density, D is the scanner gain, .alpha. is
the flip angle, and T1 is the tissue relaxation time, a
characteristic of the tissue being examined.
[0047] The tissue relaxation time T.sub.1 is related to the
pre-contrast relaxation time T.sub.10 and the local tissue
relaxation rate R.sub.1. This is assumed to be in a linear fashion
as shown in equation 2 [5,6]:
1 T 1 = 1 T 0 + R 1 CA C ( t ) ( 2 ) ##EQU00002##
where R.sub.1CA is treated as a known constant, uniquely determined
by the choice of contrast agent [Rohrer et al 7].
[0048] Introducing equation 2 into equation 1, the relative signal
enhancement is given by equation 3:
E ( t ) = S ( t ) - S ( 0 ) S ( 0 ) = [ 1 - exp ( - TR / T 10 ) cos
.alpha. ] ( 1 - exp { - TR { 1 / T 10 + R 1 C t ( t ) } } ) ( 1 -
exp { - TR [ 1 / T 10 + R 1 C t ( t 0 ) ] } cos .alpha. ) [ 1 - exp
( - TR / T 10 ) ] ( 3 ) ##EQU00003##
[0049] Relative signal enhancement allows the proton density to
cancel out. This is the fundamental relationship between signal
intensity E(t) and contrast agent concentration C(t), and it
depends on many parameters that change between protocols, such as
TR and flip angle .alpha., and on parameters that depend on the
tissue T.sub.10. Specifically, this demonstrates a highly
non-linear relationship between S(t) and C(t), meaning that the
shape of the C(t) curve will not in general be preserved when
transformed to S(t).
[0050] By way of demonstrative example, FIG. 5A depicts signal
enhancement as a function of concentration for different values of
T.sub.10, and FIG. 5B depicts the signal enhancement ratio versus
contrast agent concentration from the 3 systems in Newstead et al
with T.sub.10 selected at 1200 ms. One skilled in the art will be
able to observe the non-linearity of the curves in FIG. 5A. In
particular, the curve for System 3 even shows saturation at
approximately 200%, i.e., the concentration can increase greatly
without a significant increase in signal.
[0051] A hypothetical case demonstrates how a concentration curve
with the suspicious time dependence of Type III can be turned into
the ambivalent signal curve of Type II by this non-linear
transformation. Curve 62 in FIG. 6 shows the hypothetical
concentration curve exhibiting high initial uptake followed by
rapid washout. The y-axis for concentration is shown at left and is
in units of mmol/liter. Curve 60 shows the signal enhancement
derived from this with the transformation shown in FIG. 6. The
y-axis is on the right is in units of %. The peak concentration
point occurring near time point 3 is depressed relative to later
points due to the saturation of the concentration--signal curve.
This tends to make a "peaking" distribution (Type III), flatter, or
more like Type II. Clearly, in this case, shown in FIG. 6, the
signal enhancement exhibits plateau behavior in spite of a clear
Type III behavior of the concentration.
[0052] Similarly, a continuously increasing concentration of the
Type I curve type can artificially plateau because of the
saturation of the Signal/Concentration curve, and become a Type II
signal curve. In retrospect it is believed that the intuitive
expectation of the curve types is actually an expectation of the
curve shape for concentration enhancement, which is generally
assumed to be equivalent to the curve shape for signal enhancement,
but this would only be true if the transformation from the former
to the later were linear, which it is not.
[0053] Notably, the present inventors used the average peak signal
enhancement ratio of malignant cancers in the UC data, and
converted the ratio into contrast agent concentration to simulate
the change in the pie chart shown in FIG. 4C. This is depicted in
FIG. 7, which shows much closer agreement to System 1 and System 2,
consistent with the proposition by the present inventors that the
non-linear transformation from concentration to signal is
responsible for the different proportions shown in FIG. 4C. Thus,
one advantage of proving a display of kinetic information in the
form of Contrast as a function of time, rather than signal versus
time, is that contrast is the quantity that is directly related to
the physiology of the lesion, independent of scanner parameters
such as TR and TE and flip angle .alpha., and thus avoids the
adverse effects caused by non-linearity.
[0054] Having described and explained the advantage of displaying
C(t) versus time over the traditional S(t) display, we now discuss
in detail how the concentration can be obtained from the known
physics of the MRI acquisition process and the known acquisition
parameters.
[0055] The physics of the acquisition, given in Equation 4,
repeated here:
E ( t ) = S ( t ) - S ( 0 ) S ( 0 ) = [ 1 - exp ( - TR / T 10 ) cos
.alpha. ] ( 1 - exp { - TR { 1 / T 10 + R 1 C t ( t ) } } ) ( 1 -
exp { - TR [ 1 / T 10 + R 1 C t ( t 0 ) ] } cos .alpha. ) [ 1 - exp
( - TR / T 10 ) ] - 1 ( 4 ) ##EQU00004##
[0056] This well-known equation, sometimes called the "FLASH"
equation, is correct for the spoiled gradient echo sequence, which
is the most commonly used sequence for breast MRI [8]. Other
sequences, such as "TURBO FLASH", although rarely used in breast
MRI applications, will have other known equations relating Signal
E(t) to Concentration C(t). In this equation, the repetition time
TR and flip angle .alpha. are parameters set by the operator of the
scanner. R.sub.1 is the rate constant, measured in other
experiments to be 4.3 to 6.7 L/mml s, depending on the type of
Gadolineum Chelate used [7]. The remaining parameter in this
equation is T.sub.10, the pre-contrast value of tissue T.sub.1.
Although "textbook" values for T.sub.10 may be taken from published
measurements of "typical tissue," these numbers can have
significant errors when applied to different individuals, and do
not adequately take into account the variability observed in an
actual tissue lesion.
[0057] Alternative methods of measuring the T.sub.10 value at each
voxel of the imaged volume from the individual patient include T1
mapping, which requires at least one, and preferably two extra
volume acquisitions prior to injection of CA, each acquisition
using a different flip angle .alpha.. This method can be understood
by considering the signal equations for the commonly used scanner
sequences used in breast imaging (SPGR, FFE, or FLASH). In these
sequences a series of low flip angle RF pulses are used within a
short TR period. The signal from an FFE sequence with flip angle
.alpha. across the whole slice is given by equation 5:
.rho. ( a ) = .rho. 0 1 - - TR / T 1 1 - cos .times. a .times. - TR
/ T 1 sin a ( 5 ) ##EQU00005##
[0058] A computationally simple method for estimating T1 can be
obtained by manipulating equation 4 and rearranging into the form
shown below in equation 6.
.rho. ( a ) sin ( a ) = - TR / T 1 .rho. ( a ) tan ( a ) + .rho. 0
( 1 - - TR / T 1 ) ( 6 ) ##EQU00006##
[0059] Note that a plot of .rho./(sin .alpha. vs .rho./tan .alpha.)
at different values of flip angle forms a straight line with slope
a=exp(-TR/T1). T1 can therefore be obtained as:
T1=-TR/ln(a) (7)
[0060] To obtain the slope then requires at least two sequences
with different flip angles, or, for better accuracy, three flip
sequences with different flip angles. T1 mapping therefore requires
extra volume acquisitions, each one adding approximately a minute
to the total patient procedure. It may happen that this extra
scanning time is prohibitively expensive for many medical
facilities, and for this reason the present inventors prefer a
further alternative approach using reference tissue instead of
textbook values or T1 mapping. In particular assuming, as in
conventional DCE-MRI protocols, the use of short TR and small flip
angle, the relative signal S(0)/S.sub.ref(0) (as opposed to the
absolute signal S(0) of a lesion) is relatively insensitive to the
actual protocol adjustment of MRI system. In this case the
following linear relation can be used to estimate the pre-contrast
relaxation T.sub.10.
S ( 0 ) S ref ( 0 ) = 1 - exp ( - TR / T 10 ref ) cos .alpha. ( 1 -
exp ( - TR / T 10 ) ) [ 1 - exp ( - TR / T 10 ) cos .alpha. ] ( 1 -
exp ( - TR / T 10 ref ) ) .apprxeq. T 10 ref T 10 ( 8 )
##EQU00007##
where S.sub.ref(0) is the signal intensity of muscle tissue prior
to contrast agent injection and T.sub.10ref is a T.sub.1 relaxation
time of muscle tissue before contrast agent injection. S(0) and
T.sub.10 are the signal and T.sub.10 value respectively of the
tissue of interest.
[0061] As depicted in FIGS. 8A and 8B, by assuming the measured
value for breast pectoral muscle of the T.sub.1 relaxation time of
607 ms [9], the T.sub.10 estimated from equation 4 using a standard
DCE-MRI protocol (TR/TE:5.2/2.5 ms, FA:10 as recommended by the
QIBA panel) results in less than 0.3% error in a range from 400 ms
to 2000 ms of true T.sub.10 values. The graph of FIG. 8B shows the
maximum error occurring at very large values of T1, but with most
of the T1 range with a much smaller error. Brix's [9] study also
confirms the viability of using the relative signal ratio
(S(0)/S.sub.fat(0)) to estimate the lesion T1 relaxation value.
[0062] Two uncertainties in this method might include B1
inhomogeneity and what literature value of T.sub.10 of normal
pectoral muscle [9] tissue is used. The present inventors believe
the former is not a concern and that the Reference Tissue method is
robust to B1 inhomogeneity error because of the low flip angle used
in the DCE-MRI protocol for breast. For example, using the same
imaging protocol as in FIG. 8, but with a large B1 inhomogeneity
that results in a 50% change in the signal still yields less than
3% of error in the T.sub.10 estimation. Thus, while obtaining the
pre-contrast value T.sub.10 using the above-described "Reference
Tissue" method can result in a possible error due an erroneous
literature value of T.sub.10, such error (especially if pectoral
muscle is chosen as the reference tissue), should not substantially
impact on the accuracy of the estimated and displayed contrast
agent in the patient tissue volume as a function of time.
Proposed MRI Review Workstation
[0063] In view of the foregoing, the present invention provides an
improved MRI review workstation display, in which output
information is displayed in conjunction with the patient imaging
data that reflects or is otherwise indicative of an absorption rate
of a contrast agent in the volume of tissue. While the form and
content of the output information may vary depending on the
particular system display design and reviewer preferences, what is
important is that the displayed output information provides an
accurate indication of whether or not a "wash out" of the contrast
agent occurred in the tissue volume during acquisition of the
imaging information, regardless of a particular imaging system or
imaging protocol employed to acquire the imaging information.
[0064] By way of non-limiting example, the output information may
be a graphical representation of a concentration of the contrast
agent in the tissue volume as a function of time during acquisition
of the imaging information. Alternatively and/or additionally, the
output information may be a graphical representation of a signal
intensity ratio in the tissue volume as a function of time, wherein
the signal intensity ratio is normalized to take into account an
actual absorption rate of the contrast agent in the tissue volume.
These options are shown in FIG. 9, which demonstrates how the
imaging data reflected in what appear to be disparate signal
enhancement ratio curves (A) and (B) obtained for the same tissue
volume using different MRI systems into and/or imaging protocols
can instead be reflected (i.e., converted) into the absorption rate
curve (C), which in turn can be converted back to a signal
enhancement ratio curve (D) that has been "normalized" so that the
displayed curve accurately reflects the tissue volume image data
notwithstanding the differences in the imaging system and/or
protocol used to acquire the imaging data.
[0065] Thus, as is depicted in FIG. 9, the MRI review workstation
controller (aka "control processor") of embodiments of the present
invention is preferably programmed to compute the so-called
normalized signal intensity ratio based, at least in part, upon a
pre-contrast relaxation value of the tissue volume. Also,
regardless of the particular form of the displayed output
information, the contrast agent concentration as a function of time
is preferably computed by the workstation control processor based,
at least in part, upon a pre-contrast relaxation value of the
tissue volume. As explained above, the pre-contrast relaxation
value of the tissue volume may be obtained using any of (i) a
Reference Tissue method, (ii) direct measurement, or (iii a
predetermined approximation. In an embodiment in which the tissue
volume being imaged is breast tissue, a Reference Tissue method is
preferably employed, wherein the reference tissue is pectoral
muscle tissue or local fatty tissue. It may also be desired to have
the output information comprise), or otherwise include, an absolute
value of absorption of the contrast agent in the tissue volume.
[0066] With reference to FIG. 10, in accordance with still another
aspect of the disclosed inventions, a method is provided for
acquiring and evaluating magnetic resonant imaging (MRI)
information of a volume of tissue, such as but not limited to
breast tissue. The method 100 includes, at step 102, obtaining a
pre-contrast relaxation value for the tissue volume. This can be
accomplished by any one of alternative steps 104, using a reference
tissue method, 106, directly measuring the relaxation value prior
to introducing the contrast agent, or 108, using a predetermined
approximation for the respective tissue volume.
[0067] Thereafter, at step 110, the contrast agent is introduced
into the subject's vasculature, e.g., by injection or other means.
Then, at step 112, MRI imaging information of the tissue volume is
acquired over the requisite time period. At step 114, the imaging
information is analyzed/evaluated, i.e., by the review workstation
processor, and at step 116, the workstation displays on a display
integrated or otherwise operatively coupled with the workstation,
output information that reflects or is otherwise indicative of an
absorption rate of a contrast agent in the volume of tissue during
the period of time, wherein the output information provides an
indication of whether or not a wash out of the contrast agent
occurred in the tissue volume during acquisition of the imaging
information. As discussed above, the contrast agent concentration
is computed as a function of time based, at least in part, upon a
pre-contrast relaxation value of the tissue volume. As also
discussed above, the output information may include displaying a
graphical representation of a signal intensity ratio in the tissue
volume as a function of time, wherein, as indicated at step 118 in
FIG. 10, the signal intensity ratio is normalized to take into
account an actual absorption rate of the contrast agent in the
tissue volume.
[0068] Having described exemplary embodiments, it can be
appreciated that the examples described above and depicted in the
accompanying figures are only illustrative, and that other
embodiments and examples also are encompassed within the scope of
the appended claims. For example, while the flow diagrams provided
in the accompanying figures are illustrative of exemplary steps;
the overall image merge process may be achieved in a variety of
manners using other data merge methods known in the art. The system
block diagrams are similarly representative only, illustrating
functional delineations that are not to be viewed as limiting
requirements of the disclosed inventions. Thus the above specific
embodiments are illustrative, and many variations can be introduced
on these embodiments without departing from the scope of the
appended claims.
* * * * *