Technical advances and clinical applications of quantitative myocardial blood flow imaging with cardiac MRI Bobak Heydari, Raymond Y. Kwong, Michael Jerosch-Herold PII: DOI: Reference:
S0033-0620(15)00012-2 doi: 10.1016/j.pcad.2015.02.003 YPCAD 646
To appear in:
Progress in Cardiovascular Diseases
Please cite this article as: Heydari Bobak, Kwong Raymond Y., Jerosch-Herold Michael, Technical advances and clinical applications of quantitative myocardial blood flow imaging with cardiac MRI, Progress in Cardiovascular Diseases (2015), doi: 10.1016/j.pcad.2015.02.003
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Technical advances and clinical applications of quantitative myocardial blood flow imaging with cardiac MRI
T
Bobak Heydari, MD, MPH, Raymond Y. Kwong, MD, MPH, Michael Jerosch-Herold, PhD
MA
NU
SC
RI P
Affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, 02215
AC
CE
PT
ED
Corresponding Author: Michael Jerosch-Herold, PhD Director of Medical Physics Brigham and Women's Hospital Associate Professor of Radiology Harvard Medical School Office: 617-525--8959 Email: [email protected]
Short title: Technical advances and clinical applications of quantitative myocardial blood flow imaging with cardiac MRI
ACCEPTED MANUSCRIPT 2
Abstract The recent FAME 2 study highlights the importance of myocardial ischemia
T
assessment, particularly in the post-COURAGE trial era of managing patients with
RI P
stable coronary artery disease. Qualitative assessment of myocardial ischemia by stress cardiovascular magnetic resonance imaging (CMR) has gained widespread
SC
clinical acceptance and utility. Despite the high diagnostic and prognostic performance of qualitative stress CMR, the ability to quantitatively assess
NU
myocardial perfusion reserve and absolute myocardial blood flow remains an important and ambitious goal for non-invasive imagers. Quantitative perfusion by
MA
stress CMR remains a research technique that has yielded progressively more encouraging results in more recent years. The ability to safely, rapidly, and precisely procure quantitative myocardial perfusion data would provide clinicians with a
ED
powerful tool that may substantially alter clinical practice and improve downstream patient outcomes and the cost effectiveness of healthcare delivery. This may also
PT
provide a surrogate endpoint for clinical trials, reducing study population sizes and costs through increased power. This review will cover emerging quantitative CMR
CE
techniques for myocardial perfusion assessment by CMR, including novel methods, such as 3-dimensional quantitative myocardial perfusion, and some of the
AC
challenges that remain before more widespread clinical adoption of these techniques may take place.
Key words: quantitative myocardial perfusion, cardiac magnetic resonance imaging, coronary artery disease, fractional flow reserve, myocardial flow reserve, ischemia, coronary flow reserve, myocardial infarction, perfusion
ACCEPTED MANUSCRIPT 3
List of Abbreviations coronary artery disease
CMR
cardiovascular magnetic resonance
CFR
coronary flow reserve
FFR
fractional flow reserve
LGE
late gadolinium enhancement
LV
left ventricular or left ventricle
MBF
myocardial blood flow
MI
myocardial infarction
MPI
myocardial perfusion imaging
MPR
myocardial perfusion reserve
MRI
magnetic resonance imaging
PCI
percutaneous coronary intervention
PET
positron emission tomography
QCA
quantitative coronary angiography
RI P SC
NU
MA
ED
PT
CE
AC
TPG
T
CAD
transmural perfusion gradients
ACCEPTED MANUSCRIPT 4
Introduction The landmark COURAGE trial1 highlighted the limitations of mechanical
T
revascularization for coronary artery disease (CAD) on the basis of anatomic
RI P
imaging alone. Because of the well-known limitations of assessing anatomical luminal stenosis, research in cardiac imaging has been directed at determining the
SC
functional impact of coronary stenoses to determine more precisely those lesions that may benefit from revascularization and reduce downstream adverse cardiac
NU
events. In particular, the recent FAME 2 trial reported a substantial reduction in the primary composite endpoint of death, nonfatal myocardial infarction (MI), or
MA
hospitalization for urgent revascularization using a fractional flow reserve (FFR)guided percutaneous coronary intervention (PCI) strategy.2 These results emphasize the importance of functional ischemic assessment guiding utilization of
ED
coronary revascularization in patients with CAD. The ability to objectively evaluate myocardial ischemic burden using non-invasive methods that are both highly
PT
precise and accurate, and potentially overcome some of the limitations of nuclear has improved.
CE
imaging, have garnered more attention recently as noninvasive imaging technology
AC
To date, numerous studies have demonstrated robust diagnostic and prognostic performance of qualitative stress myocardial perfusion imaging (MPI) by cardiac magnetic resonance imaging (CMR).3-6 Stress perfusion CMR has become a mainstream diagnostic tool in experienced centers, owing in particular to its safety, high spatial and temporal resolution, and freedom from technical limitations such as a use of ionizing radiation, soft tissue attenuation, and poor diagnostic imaging windows.7 Qualitative stress CMR has also proven cost-effectiveness, even amongst patients presenting acutely to the emergency department with chest pain, largely owing to superior downstream risk stratification and reclassification.8-11 Although early studies have suggested the potential for quantitative myocardial ischemia assessment using CMR, technical challenges and time consuming post-
ACCEPTED MANUSCRIPT 5
processing have limited greater generalizability of these CMR techniques. This review will discuss the potential clinical utility and technical advances of quantitative stress CMR perfusion imaging for the assessment of myocardial
AC
CE
PT
ED
MA
NU
SC
RI P
T
ischemia.
ACCEPTED MANUSCRIPT 6
Coronary Perfusion Changes in myocardial oxygen delivery are primarily regulated by increased 12
Epicardial stenosis, diffuse atherosclerotic disease, or small
RI P
arteriolar resistance.
T
coronary blood flow, which is foremost achieved by a reduction in small-vessel vessel disease and microcirculatory dysfunction may all contribute to impaired
SC
myocardial blood flow (MBF). Various quantitative measures have been derived (most of which are invasively assessed), such as: a) the coronary flow reserve (CFR),
NU
defined as the ratio of blood flow during maximal hyperemia divided by coronary blood flow at rest; b) myocardial perfusion reserve by CMR defined as the ratio of
MA
flows per unit volume of myocardium, and per unit of time for hyperemia and rest; c) FFR, defined as the ratio of pressure distal to a stenosis compared with pressure proximal to the same lesion (often using aortic pressure as a surrogate); and d)
ED
microcirculatory resistance index, quantified as distal coronary artery pressure divided by the inverse of hyperemic mean transit time (measured using a novel
PT
pressure/temperature tipped guidewire at the time of cardiac catheterization).13
CE
A severe epicardial stenosis may not cause significant ischemia due to the degree of compensatory coronary blood flow autoregulation. Conversely, significant ischemia
AC
may result from less severe epicardial stenosis due to downstream microvascular dysfunction or multiple intermediate stenoses in series, further highlighting the limitations of anatomic evaluation alone to evaluate myocardial perfusion.14 The myocardial perfusion reverse, unlike the CFR, directly measures myocardial perfusion, which includes the effects of the microcirculation downstream from an epicardial stenosis, and also accounts for any collateral supply. This may provide a more accurate measure of myocardial ischemia than invasively or non-invasively derived CFR.15 Increased Myocardial Workload
ACCEPTED MANUSCRIPT 7
Hyperemia to measure maximal MBF16 can be evaluated using exercise or pharmacological (dobutamine or vasodilator) stress CMR. Exercise is achieved through the use of a supine bicycle or non-ferromagnetic treadmill. At present,
T
since exercise testing inside a magnetic resonance imaging (MRI) room is not yet
RI P
widely available, an inotropic agent is often used as an alternative means to increase myocardial oxygen consumption and demand. Dobutamine, administered by with
standardized
protocol
(same
as
for
dobutamine
stress
SC
infusion
echocardiography) may also be used to induce hyperemia.17 For those patients
NU
unable to attain target heart rate, atropine may also be co-administered with the dobutamine infusion. One potential advantage of dobutamine is the ability to
MA
achieve a maximal hyperemic response irrespective of mechanical dysfunction.18 In practice dobutamine is not often used for CMR myocardial perfusion imaging, as the high heart rates during peak dobutamine infusion stage tend to cause a degradation
ED
of image quality, and limit coverage of the heart due to the competing requirement of maintaining appropriate temporal resolution. Furthermore, other vasodilating
PT
agents such as intravenous adenosine that induce predominantly hyperemia are safer in patients with CAD.
Some groups have reported high diagnostic and
CE
prognostic utility when CMR myocardial perfusion is acquired during intermediate dobutamine stage to avoid the high heart rates that cause motion blurring and
AC
restrict cardiac coverage.18 Hyperemia may also be induced through use of a vasodilating agent, including adenosine (Adenoscan), dipyridamole (Persantine), and regadenoson (Lexiscan). These vasodilators are administered as an infusion, with the exception of regadenoson, which may be administered by bolus injection. Recently, Vasu and colleagues compared the vasodilator properties of these agents in 15 healthy normal volunteers.19 They reported that regadenoson produced higher MBF (3.58 ± 0.58 vs. 2.81 ± 0.67 vs. 2.78 ± 0.61 ml/min/g, p = 0.0009 and p = 0.0008 respectively) and myocardial perfusion reserve (MPR; 3.11 ± 0.63 vs 2.7 ± 0.61 vs. 2.61 ± 0.57, p = 0.02 and p = 0.04 respectively) during hyperemia than adenosine or dipyridamole. When normalized to heart rate, these differences persisted for
ACCEPTED MANUSCRIPT 8
dipyridamole, but not adenosine. Based on this dataset, the authors concluded that regadenoson and adenosine have similar vasodilator properties for quantitative stress CMR perfusion that were superior to dipyridamole. Overall, the use of these
T
agents to induce hyperemia for stress perfusion CMR assessment have been shown
RI P
to be extremely safe.20,21
SC
CMR Perfusion
Using CMR, MPI can be performed during either exercise, inotropic, or hyperemic
NU
stress (vasodilator agent). An extra-cellular MRI contrast agent, gadolinium, is bolus-injected during the stress state, which permits qualitative and quantitative
MA
assessment of maximal MBF using a rapid (e.g. 3-4 images per R-to-R interval), T1weighted pulse sequence for imaging during the first-pass of the contrast bolus. Gadolinium-based contrast agents (GBCAs) produce substantial shortening of T1 in
ED
blood and myocardium due to their relaxivity properties (high number of unpaired electrons). Gadolinium passage through the microcirculation leads to increased
PT
signal intensity by T1-weighted CMR imaging (e.g. the blood pool becomes “brighter”), whereas areas with reduced or absent perfusion will have reduced T1-
CE
shortening and appear hypo-intense compared to normally perfused myocardium. A detailed and comprehensive review of CMR acquisition methods for quantification
AC
of myocardial stress perfusion has recently been published.22 Semi-Quantitative Methods Semi-quantitative analysis of MPI may be performed by analyzing the change in myocardial signal intensity over time during the first pass to derive the rate of contrast enhancement in the myocardium, which is related to MBF, i.e. the rate at which blood-borne contrast enters a myocardial region (Figure 1). Deriving the maximum up-slope of the signal-intensity curves will provide the “signal up-slope” (which is often normalized to baseline signal intensity, because signal intensity has arbitrary units). The up-slope parameter may be visualized by a polar map to assess the relative variation of perfusion throughout the myocardium.23 This method has
ACCEPTED MANUSCRIPT 9
demonstrated high diagnostic accuracy in patients with suspected CAD.24 An arterial input function using the left ventricular (LV) cavity may be used as empirical correction to normalize the maximal upslope of the signal intensity for changes in
T
cardiac output from the various methods to induce or simulate stress. This
RI P
correction by the up-slope of the signal intensity in the blood pool is particularly relevant, when an up-slope parameter is used to derive a MPR index: here the up-
SC
slopes of the myocardial signal intensity curves alone would not account for the changed hemodynamics which alter the input function, even though the bolus
NU
injection rate may remain the same. These quantitative measures are dependent on an approximately linear relation between the concentration of the gadolinium
MA
contrast agent in the blood, and the measured signal intensity of contrast enhancement. This linear relation is typically maintained at lower doses of administered gadolinium. A dual bolus technique may be used for quantitative
ED
techniques with a low-dose initial contrast bolus for arterial input function calculation, followed by a higher-dose contrast bolus for measurement of
PT
myocardial enhancement.25 Although MPR may be estimated quite accurately with
CE
this method, absolute MBF requires fully quantitative assessment. Imbalances between subendocardial and subepicardial myocardial perfusion may
AC
also be evaluated using a semiquantitative analysis of transmural perfusion gradients (TPG).26 Chiribiri and colleagues evaluated TPG assessment by CMR in 67 patients with suspected myocardial ischemia and correlated again reference standard of FFR
S0033-0620(15)00012-2 doi: 10.1016/j.pcad.2015.02.003 YPCAD 646
To appear in:
Progress in Cardiovascular Diseases
Please cite this article as: Heydari Bobak, Kwong Raymond Y., Jerosch-Herold Michael, Technical advances and clinical applications of quantitative myocardial blood flow imaging with cardiac MRI, Progress in Cardiovascular Diseases (2015), doi: 10.1016/j.pcad.2015.02.003
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Technical advances and clinical applications of quantitative myocardial blood flow imaging with cardiac MRI
T
Bobak Heydari, MD, MPH, Raymond Y. Kwong, MD, MPH, Michael Jerosch-Herold, PhD
MA
NU
SC
RI P
Affiliation: Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, 02215
AC
CE
PT
ED
Corresponding Author: Michael Jerosch-Herold, PhD Director of Medical Physics Brigham and Women's Hospital Associate Professor of Radiology Harvard Medical School Office: 617-525--8959 Email: [email protected]
Short title: Technical advances and clinical applications of quantitative myocardial blood flow imaging with cardiac MRI
ACCEPTED MANUSCRIPT 2
Abstract The recent FAME 2 study highlights the importance of myocardial ischemia
T
assessment, particularly in the post-COURAGE trial era of managing patients with
RI P
stable coronary artery disease. Qualitative assessment of myocardial ischemia by stress cardiovascular magnetic resonance imaging (CMR) has gained widespread
SC
clinical acceptance and utility. Despite the high diagnostic and prognostic performance of qualitative stress CMR, the ability to quantitatively assess
NU
myocardial perfusion reserve and absolute myocardial blood flow remains an important and ambitious goal for non-invasive imagers. Quantitative perfusion by
MA
stress CMR remains a research technique that has yielded progressively more encouraging results in more recent years. The ability to safely, rapidly, and precisely procure quantitative myocardial perfusion data would provide clinicians with a
ED
powerful tool that may substantially alter clinical practice and improve downstream patient outcomes and the cost effectiveness of healthcare delivery. This may also
PT
provide a surrogate endpoint for clinical trials, reducing study population sizes and costs through increased power. This review will cover emerging quantitative CMR
CE
techniques for myocardial perfusion assessment by CMR, including novel methods, such as 3-dimensional quantitative myocardial perfusion, and some of the
AC
challenges that remain before more widespread clinical adoption of these techniques may take place.
Key words: quantitative myocardial perfusion, cardiac magnetic resonance imaging, coronary artery disease, fractional flow reserve, myocardial flow reserve, ischemia, coronary flow reserve, myocardial infarction, perfusion
ACCEPTED MANUSCRIPT 3
List of Abbreviations coronary artery disease
CMR
cardiovascular magnetic resonance
CFR
coronary flow reserve
FFR
fractional flow reserve
LGE
late gadolinium enhancement
LV
left ventricular or left ventricle
MBF
myocardial blood flow
MI
myocardial infarction
MPI
myocardial perfusion imaging
MPR
myocardial perfusion reserve
MRI
magnetic resonance imaging
PCI
percutaneous coronary intervention
PET
positron emission tomography
QCA
quantitative coronary angiography
RI P SC
NU
MA
ED
PT
CE
AC
TPG
T
CAD
transmural perfusion gradients
ACCEPTED MANUSCRIPT 4
Introduction The landmark COURAGE trial1 highlighted the limitations of mechanical
T
revascularization for coronary artery disease (CAD) on the basis of anatomic
RI P
imaging alone. Because of the well-known limitations of assessing anatomical luminal stenosis, research in cardiac imaging has been directed at determining the
SC
functional impact of coronary stenoses to determine more precisely those lesions that may benefit from revascularization and reduce downstream adverse cardiac
NU
events. In particular, the recent FAME 2 trial reported a substantial reduction in the primary composite endpoint of death, nonfatal myocardial infarction (MI), or
MA
hospitalization for urgent revascularization using a fractional flow reserve (FFR)guided percutaneous coronary intervention (PCI) strategy.2 These results emphasize the importance of functional ischemic assessment guiding utilization of
ED
coronary revascularization in patients with CAD. The ability to objectively evaluate myocardial ischemic burden using non-invasive methods that are both highly
PT
precise and accurate, and potentially overcome some of the limitations of nuclear has improved.
CE
imaging, have garnered more attention recently as noninvasive imaging technology
AC
To date, numerous studies have demonstrated robust diagnostic and prognostic performance of qualitative stress myocardial perfusion imaging (MPI) by cardiac magnetic resonance imaging (CMR).3-6 Stress perfusion CMR has become a mainstream diagnostic tool in experienced centers, owing in particular to its safety, high spatial and temporal resolution, and freedom from technical limitations such as a use of ionizing radiation, soft tissue attenuation, and poor diagnostic imaging windows.7 Qualitative stress CMR has also proven cost-effectiveness, even amongst patients presenting acutely to the emergency department with chest pain, largely owing to superior downstream risk stratification and reclassification.8-11 Although early studies have suggested the potential for quantitative myocardial ischemia assessment using CMR, technical challenges and time consuming post-
ACCEPTED MANUSCRIPT 5
processing have limited greater generalizability of these CMR techniques. This review will discuss the potential clinical utility and technical advances of quantitative stress CMR perfusion imaging for the assessment of myocardial
AC
CE
PT
ED
MA
NU
SC
RI P
T
ischemia.
ACCEPTED MANUSCRIPT 6
Coronary Perfusion Changes in myocardial oxygen delivery are primarily regulated by increased 12
Epicardial stenosis, diffuse atherosclerotic disease, or small
RI P
arteriolar resistance.
T
coronary blood flow, which is foremost achieved by a reduction in small-vessel vessel disease and microcirculatory dysfunction may all contribute to impaired
SC
myocardial blood flow (MBF). Various quantitative measures have been derived (most of which are invasively assessed), such as: a) the coronary flow reserve (CFR),
NU
defined as the ratio of blood flow during maximal hyperemia divided by coronary blood flow at rest; b) myocardial perfusion reserve by CMR defined as the ratio of
MA
flows per unit volume of myocardium, and per unit of time for hyperemia and rest; c) FFR, defined as the ratio of pressure distal to a stenosis compared with pressure proximal to the same lesion (often using aortic pressure as a surrogate); and d)
ED
microcirculatory resistance index, quantified as distal coronary artery pressure divided by the inverse of hyperemic mean transit time (measured using a novel
PT
pressure/temperature tipped guidewire at the time of cardiac catheterization).13
CE
A severe epicardial stenosis may not cause significant ischemia due to the degree of compensatory coronary blood flow autoregulation. Conversely, significant ischemia
AC
may result from less severe epicardial stenosis due to downstream microvascular dysfunction or multiple intermediate stenoses in series, further highlighting the limitations of anatomic evaluation alone to evaluate myocardial perfusion.14 The myocardial perfusion reverse, unlike the CFR, directly measures myocardial perfusion, which includes the effects of the microcirculation downstream from an epicardial stenosis, and also accounts for any collateral supply. This may provide a more accurate measure of myocardial ischemia than invasively or non-invasively derived CFR.15 Increased Myocardial Workload
ACCEPTED MANUSCRIPT 7
Hyperemia to measure maximal MBF16 can be evaluated using exercise or pharmacological (dobutamine or vasodilator) stress CMR. Exercise is achieved through the use of a supine bicycle or non-ferromagnetic treadmill. At present,
T
since exercise testing inside a magnetic resonance imaging (MRI) room is not yet
RI P
widely available, an inotropic agent is often used as an alternative means to increase myocardial oxygen consumption and demand. Dobutamine, administered by with
standardized
protocol
(same
as
for
dobutamine
stress
SC
infusion
echocardiography) may also be used to induce hyperemia.17 For those patients
NU
unable to attain target heart rate, atropine may also be co-administered with the dobutamine infusion. One potential advantage of dobutamine is the ability to
MA
achieve a maximal hyperemic response irrespective of mechanical dysfunction.18 In practice dobutamine is not often used for CMR myocardial perfusion imaging, as the high heart rates during peak dobutamine infusion stage tend to cause a degradation
ED
of image quality, and limit coverage of the heart due to the competing requirement of maintaining appropriate temporal resolution. Furthermore, other vasodilating
PT
agents such as intravenous adenosine that induce predominantly hyperemia are safer in patients with CAD.
Some groups have reported high diagnostic and
CE
prognostic utility when CMR myocardial perfusion is acquired during intermediate dobutamine stage to avoid the high heart rates that cause motion blurring and
AC
restrict cardiac coverage.18 Hyperemia may also be induced through use of a vasodilating agent, including adenosine (Adenoscan), dipyridamole (Persantine), and regadenoson (Lexiscan). These vasodilators are administered as an infusion, with the exception of regadenoson, which may be administered by bolus injection. Recently, Vasu and colleagues compared the vasodilator properties of these agents in 15 healthy normal volunteers.19 They reported that regadenoson produced higher MBF (3.58 ± 0.58 vs. 2.81 ± 0.67 vs. 2.78 ± 0.61 ml/min/g, p = 0.0009 and p = 0.0008 respectively) and myocardial perfusion reserve (MPR; 3.11 ± 0.63 vs 2.7 ± 0.61 vs. 2.61 ± 0.57, p = 0.02 and p = 0.04 respectively) during hyperemia than adenosine or dipyridamole. When normalized to heart rate, these differences persisted for
ACCEPTED MANUSCRIPT 8
dipyridamole, but not adenosine. Based on this dataset, the authors concluded that regadenoson and adenosine have similar vasodilator properties for quantitative stress CMR perfusion that were superior to dipyridamole. Overall, the use of these
T
agents to induce hyperemia for stress perfusion CMR assessment have been shown
RI P
to be extremely safe.20,21
SC
CMR Perfusion
Using CMR, MPI can be performed during either exercise, inotropic, or hyperemic
NU
stress (vasodilator agent). An extra-cellular MRI contrast agent, gadolinium, is bolus-injected during the stress state, which permits qualitative and quantitative
MA
assessment of maximal MBF using a rapid (e.g. 3-4 images per R-to-R interval), T1weighted pulse sequence for imaging during the first-pass of the contrast bolus. Gadolinium-based contrast agents (GBCAs) produce substantial shortening of T1 in
ED
blood and myocardium due to their relaxivity properties (high number of unpaired electrons). Gadolinium passage through the microcirculation leads to increased
PT
signal intensity by T1-weighted CMR imaging (e.g. the blood pool becomes “brighter”), whereas areas with reduced or absent perfusion will have reduced T1-
CE
shortening and appear hypo-intense compared to normally perfused myocardium. A detailed and comprehensive review of CMR acquisition methods for quantification
AC
of myocardial stress perfusion has recently been published.22 Semi-Quantitative Methods Semi-quantitative analysis of MPI may be performed by analyzing the change in myocardial signal intensity over time during the first pass to derive the rate of contrast enhancement in the myocardium, which is related to MBF, i.e. the rate at which blood-borne contrast enters a myocardial region (Figure 1). Deriving the maximum up-slope of the signal-intensity curves will provide the “signal up-slope” (which is often normalized to baseline signal intensity, because signal intensity has arbitrary units). The up-slope parameter may be visualized by a polar map to assess the relative variation of perfusion throughout the myocardium.23 This method has
ACCEPTED MANUSCRIPT 9
demonstrated high diagnostic accuracy in patients with suspected CAD.24 An arterial input function using the left ventricular (LV) cavity may be used as empirical correction to normalize the maximal upslope of the signal intensity for changes in
T
cardiac output from the various methods to induce or simulate stress. This
RI P
correction by the up-slope of the signal intensity in the blood pool is particularly relevant, when an up-slope parameter is used to derive a MPR index: here the up-
SC
slopes of the myocardial signal intensity curves alone would not account for the changed hemodynamics which alter the input function, even though the bolus
NU
injection rate may remain the same. These quantitative measures are dependent on an approximately linear relation between the concentration of the gadolinium
MA
contrast agent in the blood, and the measured signal intensity of contrast enhancement. This linear relation is typically maintained at lower doses of administered gadolinium. A dual bolus technique may be used for quantitative
ED
techniques with a low-dose initial contrast bolus for arterial input function calculation, followed by a higher-dose contrast bolus for measurement of
PT
myocardial enhancement.25 Although MPR may be estimated quite accurately with
CE
this method, absolute MBF requires fully quantitative assessment. Imbalances between subendocardial and subepicardial myocardial perfusion may
AC
also be evaluated using a semiquantitative analysis of transmural perfusion gradients (TPG).26 Chiribiri and colleagues evaluated TPG assessment by CMR in 67 patients with suspected myocardial ischemia and correlated again reference standard of FFR
