Original contributions
Quantitative myocardial distribution volume from dynamic contrast-enhanced MRI

https://doi.org/10.1016/j.mri.2007.10.003Get rights and content

Abstract

The objective of this study was to investigate if dynamic contrast-enhanced magnetic resonance imaging (MRI) can be used to quantitate the distribution volume (ve) in regions of normal and infarcted myocardium. ve reflects the volume of the extracellular, extravascular space within the myocardial tissue. In regions of the heart where an infarct has occurred, the loss of viable cardiac cells results in an elevated ve compared to normal regions. A quantitative estimate of the magnitude and spatial distribution of ve is significant because it may provide information complementary to delayed enhancement MRI alone.

Using a hybrid gradient echo–echoplanar imaging pulse sequence on a 1.5T MRI scanner, 12 normal subjects and four infarct patients were imaged dynamically, during the injection of a contrast agent, to measure the regional blood and tissue enhancement in the left ventricular (LV) myocardium. Seven of the normal subjects and all of the infarct patients were also imaged at steady-state contrast enhancement to estimate the steady-state ratio of contrast agent in the tissue and blood (Ct/Cb) — a validated measure of ve. Normal and infarct regions of the LV were manually selected, and the blood and tissue enhancement curves were fit to a compartment model to estimate ve. Also, the effect of the vascular blood signal on estimates of ve was evaluated using simulations and in the dynamic and steady-state studies.

Aggregate estimates of ve were 23.6±6.3% in normal myocardium and 45.7±3.4% in regions of infarct. These results were not significantly different from the reference standards of Ct/Cb (22.9±6.8% and 42.6±6.3%, P=.073). From the dynamic contrast-enhanced studies, approximately 1 min of scan time was necessary to estimate ve in the normal myocardium to within 10% of the steady-state estimate. In regions of infarct, up to 3 min of dynamic data were required to estimate ve to within 10% of the steady-state ve value.

By measuring the kinetics of blood and tissue enhancement in the myocardium during an extended dynamic contrast enhanced MRI study, ve may be estimated using compartment modeling.

Introduction

Delayed enhancement (DE) magnetic resonance imaging (MRI) is a widely used and powerful clinical tool for the detection of myocardial infarct. Typically, a paramagnetic contrast agent is injected into a patient to temporarily distribute in the extracellular, extravascular space (ve) in the myocardium. In regions of the heart where an infarct has occurred, the loss of viable cardiac cells results in an increased ve where the contrast agent can accumulate. This increase in contrast agent shortens the T1 of the tissue, making regions of scar tissue visible when an inversion recovery sequence set to null the normal myocardium is used [1]. DE MRI has become the gold standard for noninvasively identifying the presence and extent of myocardial scarring [2], [3], [4]. DE MRI can also discriminate small regions of subendocardial infarct from viable tissue and has shown promise for reproducible sizing of infarcts and viability assessment in serial studies [5], [6].

In effect, ve directly reflects how much of an image region is composed of extracellular, extravascular space. The remaining fraction of the image region consists of viable cells and vasculature. A quantitative estimate of the magnitude and spatial distribution of ve may provide a complementary measure of the severity and characteristics of infarcts compared to DE imaging alone. Furthermore, the accurate estimation of regional ve maps of the heart may provide a means to track changes in the degree of myocardial scarring in follow-up studies.

The “steady-state” (Ct/Cb) tissue enhancement method is one validated means of quantitating ve in the myocardium [7]. To estimate ve using this method, a slow infusion or a bolus injection [7], [8], [9], [10] of contrast agent is given and allowed to reach a near-equilibrium state of contrast agent transfer into and out of the tissue. At equilibrium, the ratio of the concentration of contrast agent in the vasculature to the concentration of contrast agent in the extracellular, extravascular space constitutes the partition coefficient [11]. When the partition coefficient is scaled to account for the blood hematocrit, then the steady-state ratio of contrast agent in the tissue and blood, Ct/Cb, directly reflects the myocardial distribution volume, ve [10], [12], [13]. Here, Ct is the concentration of contrast agent in the tissue and Cb is the concentration of contrast agent in the blood. The bolus and slow infusion methods require nearly 10 min and 20 min [7], [9], [10], respectively, for the flow of contrast agent into and out of the myocardium to reach a steady-state condition.

We hypothesize that a relatively short dynamic contrast-enhanced MRI scan can also quantitate ve in the myocardium. With this proposed method, the kinetics of myocardial blood and tissue enhancement are imaged dynamically for 1–5 min after a bolus injection of contrast agent. The enhancement of the myocardium is assumed to increase and decrease according to a physiologically derived compartmental model [14], [15]. ve is then estimated from the kinetics of tissue enhancement in the myocardium, according to the representative model. While ve values from dynamic contrast-enhanced scans have been reported [12], [16], [17], [18], [19], they have not been validated, and the one study that included infarct regions [19] reported a decrease in ve with infarction, contrary to expectations.

Section snippets

Methods

Simulation and patient studies were performed in order to evaluate the accuracy of estimating ve from dynamic contrast-enhanced perfusion data. The simulation studies were used to investigate how imaging time and the inclusion of a vascular blood signal (Vb) in the kinetic and Ct/Cb models would affect ve estimates in a typical case. Preliminary patient studies were also performed to determine the minimum imaging time necessary to fully capture the delayed kinetics of tissue and blood

Simulation results

In simulation studies of normal and infarct tissue enhancement, the effects of imaging time on the kinetic model estimates of ve were evaluated. Fig. 2 shows simulated blood and tissue enhancement curves that were extended to a steady-state enhancement of 15 min. Approximately 30 s of the noise-free simulated kinetic tissue and blood enhancement data was required after contrast agent injection to estimate normal values of ve to within 5% of the true 900-s steady-state value. For the infarct

Discussion

The primary finding of this study is that estimates of myocardial ve can be quantified from dynamic contrast-enhanced perfusion MRI, using compartment models. One minute of dynamic tissue enhancement data is necessary to estimate ve in normal regions of the myocardium and three min of tissue enhancement data is necessary to estimate ve in regions of infarct. While only 1 min of dynamic enhancement data were sufficient to estimate infarct ve to within 5% of the steady-state ve value in one

Conclusion

This study has demonstrated that dynamic contrast-enhanced imaging can be used to accurately quantitate ve in normal and scarred myocardium. The estimates of ve and Ct/Cb are not significantly different (P=.073) in human and simulation studies, when 3 min of postinjection dynamic contrast-enhanced data are acquired in regions of infarct. One minute of dynamic contrast-enhanced data may be sufficient to estimate ve if the patient has no myocardial scarring. To ensure that ve and Ct/Cb estimates

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      This could therefore be a useful tool to shorten CMR exams and to personalize them to each patient's requirements. The acquisition duration of at least 2 min is enough to guarantee an estimation error of Ve inferior to 5% in healthy myocardium, but could lead to slightly more imprecision in the infarcted area, as demonstrated by Pack et al. [18]. In the same study, they also shown an increase of such error if the acquisition duration is below this limit.

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    This work was supported by NIH R01 EB00177 and the Ben B. and Iris M. Margolis Foundation.

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