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 minutes of tissue enhancement data is necessary to estimate ve in regions of infarct. While only one minute of dynamic enhancement data was sufficient to estimate infarct ve to within 5% of the steady-state ve value in one infarct patient, the other patients required up to three minutes to be within 5% of the steady-state ve estimate. A larger population is needed to determine if there is a correlation between patient characteristics or the types of infarcts imaged and the amount of imaging time required to measure the steady-state ve value in regions of infarct.
The estimates of ve
and Ct/Cb are not significantly different (p=0.073) in viable and scarred myocardium when the vascular blood signal, Vb, is included in both the kinetic and steady-state models. One limitation of the study is that when computing ve
and Ct/Cb, the vascular blood volume was assumed to be a constant Vb=0.04, which was the mean model estimate of Vb from all of the dynamic contrast-enhanced perfusion studies. While this value of Vb is comparable to values found by another group using MRI (18
), it is lower than estimates of Vb found by some histopathological estimates (30
), and it may be possible that within a region of myocardium the fraction of tissue comprised of blood vasculature may not be spatially uniform.
In this study, estimates of ve
and Ct/Cb are both approximately 23±6% in normal myocardium and approximately 45±6% in infarcted myocardium. These results parallel the findings from numerous studies that have measured ve
in normal and infarcted myocardium, although there are some discrepancies. summarizes these previous findings from other groups. Specifically, the estimates of ve
from this study are similar to ve
results from autoradiographic imaging and histological sectioning techniques (29
) and are comparable to ve
estimates from the steady-state Ct/Cb method, using regional changes in signal enhancement (7
measurements from histological studies range from 19%–30% depending on the method of chemical fixation and histological analysis. ve
estimates from the Ct/Cb studies range from 16%–26% in normal myocardium and from 36%–48% in infarcted myocardium. Differences may vary according to whether the ve
of acute or chronic infarct was measured or whether Vb was accounted for in the Ct/Cb model. In the current study, only stable chronic infarcts were imaged and Vb was included in the calculation of Ct/Cb.
Estimates of normal ve
from several kinetic modeling studies are slightly lower than the results presented here, ranging from 10%–20% in the normal myocardium (12
), and are generally lower than histology and Ct/Cb measurements. It is hypothesized that the difference in these results may be from the techniques used to convert the measured MR signal to contrast agent concentration, or because dynamic contrast-enhanced data was acquired for too short a time to accurately measure the delayed kinetics of tissue enhancement. Differences may also be due to the exclusion of the vascular blood signal in the compartmental models.
In two studies using inversion recovery sequences and T1-mapping to estimate Ct/Cb, ve
results are higher than histological findings and the results of the current study. One author suggests that the elevation in ve
estimates may be due to partial volume effects of mixed blood-myocardium voxels that resulted from the limited spatial resolution of the imaging sequence (11
) (although other studies report similar spatial resolutions and different estimates of ve
). Another author suggests the elevated measurements may be due to long-standing severe heart failure with LV remodeling in their patient population (9
). The exclusion of Vb in these Ct/Cb models may also have elevated the estimates of ve
. From Eq. (2)
, it is clear that the inclusion of Vb in the steady-state model can only reduce the estimates of Ct/Cb from the steady-state images. Similarly, from Eq. (1)
, the inclusion of Vb in the compartmental model can only reduce ve
Of the studies in that included patients with infarct, all but one reported an increase in ve
in regions of myocardial scarring. It is hypothesized that in regions of the heart where an infarct has occurred, the loss of viable cardiac cells results in an increased distribution volume. Furthermore, (29
) reports that ve
increases with increased time of coronary artery occlusion and that ve
is greater in the core of an infarct than in the peripheral infarct regions. This finding suggests that there may be a range of ve
values within an infarct that vary according to the severity of cellular damage in the region. Thus the one study that reported a decrease in ve
in regions of infarct (19
) is difficult to rationalize. The reduction in ve
may be due to the short time duration of the dynamic contrast-enhanced perfusion scan or the no-reflow phenomenon (19
Sources of inaccuracy of the ve
estimates in this study include the low SNR of the dynamic contrast-enhanced images, and missed images during the dynamic scans due to poor ECG gating in some subjects. Gating inaccuracies were minimized by using the acquisition time of each image to correct for non-uniform or spurious time sampling errors in the model fitting algorithm (28
). Another source of error in the estimates is patient motion during the scan (respiratory or otherwise), which can corrupt the images with out-of-plane motion and make the image segmentation process and model curve-fitting less accurate.
Accurately measuring ve
may provide complementary information to DE imaging to objectively measure the spatial distribution or severity of scarring in infarct patients. Another practical advantage of including quantitative perfusion imaging in a DE study is that the ve
images are intrinsically registered to the perfusion images for direct comparison or subsequent analysis. This may better allow for classifying perfusion as being within-infarct or peri-infarct ischemia. Alternatively, ve
could be used to improve the specificity of perfusion imaging in the same way DE imaging has been used (33
), but with better registration that matches cardiac phase and heart rate. This could better discriminate between ischemia and artifacts.