US 12,745,921 B2Granted

Manganese-enhanced magnetic resonance imaging

AssigneeIc Targets AS

InventorsJonny Østensen, Willy Eidsaunet

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Abstract

The present invention relates to manganese-enhanced MRI, more specifically to a method for determining a cardiomyocyte cellular manganese uptake rate of a subject, contrast agent comprising a manganese contrast agent, or a pharmaceutically acceptable salt thereof, for use in a method for in vivo diagnosis of heart disease in a subject, a computer-implemented method of determining a cardiomyocyte cellular manganese uptake rate in a subject, a data processing apparatus comprising means for carrying out said computer-implemented method, a computer program comprising instructions which, when the program is executed by a computer, cause the computer to carry out said computer-implemented method, and a computer-readable medium having stored thereon said computer program.

Claims17

Dependent claims

A method for determining a cardiomyocyte cellular manganese uptake rate of a subject, the method comprising the steps of:

i) performing, at a time point ti=0, a first longitudinal relaxation time measurement T1blood(0) of the blood of the subject, and performing, for a section of the heart of the subject, a first longitudinal relaxation time measurement T1myocardium(0) of the myocardium of the subject;
ii) administering to the subject a dose da of a contrast agent at a dosing rate of Da μmol/kg/min, wherein the contrast agent comprises a manganese contrast agent having a stability constant of 10-18, or a pharmaceutically acceptable salt thereof, and wherein the administration is completed at a time ta;
iii) performing, at one or more time points ti during the administration in step ii), 0-5 minutes before ta, measurements T1blood(ti) of the longitudinal relaxation time of the blood of the subject, and performing, for said section of the heart of the subject, at the same time points ti, measurements T1myocardium(ti) of the longitudinal relaxation time of the myocardium of the subject;
iv) performing, at one or more time points ti 0-60 minutes after ta, measurements T1blood(ti) of the longitudinal relaxation time of the blood of the subject and, for said section of the heart of the subject, at the same time points ti, measurements T1myocardium(ti) of the longitudinal relaxation time of the myocardium of the subject;
v) calculating the change in myocardial relaxation rate ΔR1myocard(ti) for each of the time points ti of steps i), iii) and iv) according to the formula
Δ
⁢
R
⁢
1
m
⁢
y
⁢
o
⁢
c
⁢
a
⁢
r
⁢
d
⁢
(
t
i
)
=
1
T
⁢
1
m
⁢
yocard
⁢
(
t
i
)
-
1
T
⁢
1
m
⁢
y
⁢
o
⁢
c
⁢
a
⁢
r
⁢
d
⁢
(
0
)
;
vi) obtaining a haematocrit value hct for the subject;
vii) calculating the change in plasma relaxation rate ΔR1plasma(ti) for each of the time points ti of steps i), iii) and iv) according to the formula
Δ
⁢
R
⁢
1
plasma
⁢
(
t
i
)
=
1
T
⁢
1
blood
⁢
(
t
i
)
-
1
T
⁢
1
blood
⁢
(
0
)
1
-
hct
;
viii) estimating the integrals
∫
0
t
i
Δ
⁢
R
⁢
1
plasma
⁢
(
t
)
⁢
dt
using each of the ΔR1plasma(ti) values of step vii);
ix) obtaining an estimate of an extracellular volume fraction (ECV) for said section of the heart of the subject;
x) defining an equation for a straight line y=A+Bx, wherein
y
=
ΔR1
⁢
myocardium
(
t
)
Δ
⁢
R
⁢
1
⁢
plasma
(
t
)
,
A=KECF*ECV, wherein KECF is a constant,
B
=
K
c
⁢
e
⁢
l
⁢
l
Δ
⁢
R
⁢
1
*
K
E
⁢
C
⁢
F
and
x
=
(
1
-
E
⁢
C
⁢
V
)
*
∫
0
t
Δ
⁢
R
⁢
1
⁢
plasma
(
t
)
⁢
dt
Δ
⁢
R
⁢
1
⁢
plasma
(
t
)
;
and
xi) estimating the slope B, and thus the cardiomyocyte cellular manganese uptake rate
K
c
⁢
e
⁢
l
⁢
l
M
⁢
n
*
K
E
⁢
C
⁢
F
=
B
,
by a linear regression method with forced intercept A=KECF*ECV.

224 more elements

A computer-implemented method of determining a cardiomyocyte cellular manganese uptake rate in a subject, comprising:

i) receiving from a PACS system of an MRI instrument scan data from a first longitudinal relaxation time measurement T1blood(0) of blood of the subject and data from a first longitudinal relaxation time measurement T1myocardium(0) of the myocardium of the subject, performed for a section of the heart of the subject;
ii) receiving from the PACS system of the MRI instrument series of scan data from one or more measurements T1blood(ti) of the longitudinal relaxation time of the blood of the subject and one or more measurements T1myocardium(ti) of the longitudinal relaxation time of the myocardium of the subject, performed for said section of the heart of the subject, wherein the T1blood(ti) measurements and the T1myocardium(ti) measurements have been performed at one or more time points ti during administration to the subject of a dose da of a contrast agent at a dosing rate of Da μmol/kg/min, the contrast agent comprising a manganese contrast agent having a stability constant of 10-18, or a pharmaceutically acceptable salt thereof, the administration being completed at a time ta,
iii) receiving from the PACS system of the MRI instrument pulse sequence series data from one or more measurements T1blood(ti) of the longitudinal relaxation time of the blood of the subject and from one or more measurements T1myocardium(ti) of the longitudinal relaxation time of the myocardium of the subject, performed for said section of the heart of the subject, wherein the measurements have been performed at one or more time points ti up to 60 minutes after ta;
iv) calculating the change in myocardial relaxation rate ΔR1myocard(ti) for each of the time points ti of steps i), ii) and iii) according to the formula
Δ
⁢
R
⁢
1
m
⁢
y
⁢
o
⁢
c
⁢
a
⁢
r
⁢
d
⁢
(
t
i
)
=
1
T
⁢
1
m
⁢
y
⁢
o
⁢
card
⁡
(
t
i
)
-
1
T
⁢
1
m
⁢
y
⁢
o
⁢
c
⁢
a
⁢
r
⁢
d
⁢
(
0
)
;
v) receiving a haematocrit value, hct, for the subject;
vi) calculating the change in plasma relaxation rate ΔR1plasma(ti) for each of the time points ti of steps i), ii) and iii) according to the formula
Δ
⁢
R
⁢
1
plasma
⁢
(
t
i
)
=
1
T
⁢
1
blood
⁢
(
t
i
)
-
1
T
⁢
1
blood
⁢
(
0
)
1
-
hct
;
vii) estimating the integrals
∫
0
t
i
Δ
⁢
R
⁢
1
plasma
⁢
(
t
)
⁢
dt
using each ΔR1plasma(ti) value of step vi);
viii) receiving an estimate of an extracellular volume fraction (ECV) for said section of the heart of the subject;
ix) defining an equation for a straight line y=A+Bx, wherein
y
=
Δ
⁢
R
⁢
1
⁢
myocardium
(
t
)
Δ
⁢
R
⁢
1
⁢
plasma
(
t
)
,
A=KECF*ECV, wherein KECF is a constant,
B
=
K
cell
Δ
⁢
R
⁢
1
*
K
E
⁢
C
⁢
F
and
x
=
(
1
-
E
⁢
C
⁢
V
)
*
∫
0
t
ΔR1
⁢
plasma
(
t
)
⁢
dt
ΔR1
⁢
plasma
(
t
)
;
and
x) estimating the slope B, and thus the cardiomyocyte cellular manganese uptake rate
K
c
⁢
e
⁢
l
⁢
l
M
⁢
n
*
K
E
⁢
C
⁢
F
=
B
,
by a linear regression method with forced intercept A=KECF*ECV.

217 more elements

A method for in vivo diagnosis of heart failure or heart disease in a subject, comprising:

i) performing, at a time point ti=0, a first longitudinal relaxation time measurement T1blood(0) of the blood of the subject, and performing, for a section of the heart of the subject, a first longitudinal relaxation time measurement T1myocardium(0) of the myocardium of the subject;
ii) administering to the subject a dose da of a contrast agent at a dosing rate of Da μmol/kg/min, wherein the contrast agent comprises a manganese contrast agent having a stability constant of 10-18, or a pharmaceutically acceptable salt thereof, and wherein the administration is completed at a time ta;
iii) performing, at one or more time points ti during the administration in step ii), 0-5 minutes before ta, measurements T1blood(ti) of the longitudinal relaxation time of the blood of the subject, and performing, for said section of the heart of the subject, at the same time points ti, measurements T1myocardium(ti) of the longitudinal relaxation time of the myocardium of the subject;
iv) performing, at one or more time points ti 0-60 minutes after ta, measurements T1blood(ti) of the longitudinal relaxation time of the blood of the subject and, for said section of the heart of the subject, at the same time points ti, measurements T1myocardium(ti) of the longitudinal relaxation time of the myocardium of the subject;
v) calculating the change in myocardial relaxation rate ΔR1myocard(ti) for each of the time points ti of steps i), iii) and iv) according to the formula
Δ
⁢
R
⁢
1
m
⁢
y
⁢
o
⁢
c
⁢
a
⁢
r
⁢
d
⁢
(
t
i
)
=
1
T
⁢
1
m
⁢
y
⁢
o
⁢
card
⁡
(
t
i
)
-
1
T
⁢
1
m
⁢
y
⁢
o
⁢
c
⁢
a
⁢
r
⁢
d
⁢
(
0
)
;
vi) obtaining a haematocrit value hct for the subject;
vii) calculating the change in plasma relaxation rate ΔR1plasma(ti) for each of the time points ti of steps i), iii) and iv) according to the formula
Δ
⁢
R
⁢
1
plasma
⁢
(
t
i
)
=
1
T
⁢
1
blood
⁢
(
t
i
)
-
1
T
⁢
1
blood
⁢
(
0
)
1
-
hct
;
viii) estimating the integrals
∫
0
t
i
Δ
⁢
R
⁢
1
plasma
⁢
(
t
)
⁢
dt
using each of the ΔR1plasma(ti) values of step vii);
ix) obtaining an estimate of an extracellular volume fraction (ECV) for said section of the heart of the subject;
x) defining an equation for a straight line y=A+Bx, wherein
y
=
Δ
⁢
R
⁢
1
⁢
myocardium
(
t
)
Δ
⁢
R
⁢
1
⁢
plasma
(
t
)
,
A=KECF*ECV, wherein KECF is a constant,
B
=
K
c
⁢
e
⁢
l
⁢
l
Δ
⁢
R
⁢
1
*
K
E
⁢
C
⁢
F
and
x
=
(
1
-
E
⁢
C
⁢
V
)
*
∫
0
t
ΔR1
⁢
plasma
(
t
)
⁢
dt
ΔR1
⁢
plasma
(
t
)
;
and
xi) estimating the slope B, and thus the cardiomyocyte cellular manganese uptake rate
K
c
⁢
e
⁢
l
⁢
l
M
⁢
n
*
K
E
⁢
C
⁢
F
=
B
,
by a linear regression method with forced intercept A=KECF*ECV;
and
xii) comparing the
K
c
⁢
e
⁢
l
⁢
l
M
⁢
n
value to one or more reference values for the relaxivity change in order to diagnose a heart disease in the subject.

238 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/566,924Filed 3 Jun 2022
Priority: NO 202107347 Jun 2021
Published: US 2024/0277246 A122 Aug 2024
Granted: 29 Sep 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification12 codes

A61B 5/055
Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves:…
A61B 5/0044
Adapted for image acquisition of a particular organ or body part: for the heart
A61B 5/14535
Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g.…: for…
A61B 5/4866
Other medical applications: evaluating metabolism